Critical Care
The Southwest Journal of Pulmonary and Critical Care publishes articles directed to those who treat patients in the ICU, CCU and SICU including chest physicians, surgeons, pediatricians, pharmacists/pharmacologists, anesthesiologists, critical care nurses, and other healthcare professionals. Manuscripts may be either basic or clinical original investigations or review articles. Potential authors of review articles are encouraged to contact the editors before submission, however, unsolicited review articles will be considered.
July 2020 Critical Care Case of the Month: Not the Pearl You Were Looking For...
Yuet-Ming Chan MD1
David C. Miller MD2
Farshad Shirazi MD3
Janet Campion MD2
1Department of Medicine, 2Pulmonary, Allergy, Critical Care and Sleep Medicine and 3Arizona Poison and Drug Information Center
University of Arizona School of Medicine
Tucson, AZ USA
History of Present Illness
A 75-year-old man presented with unsteady gait, difficulty concentrating and abdominal pain with loose stools. One day prior to admission, he experienced waxing and waning nausea, cramping abdominal pain, one episode of emesis and loose stools. He described acute gait disorder related to difficulty with balance. Due to concern for dehydration, he drank 10-12 cans of carbonated water without further emesis. He also experienced vague and alternating sensations of feeling “hot” in half of his body and “cold” in the other half of his body. Forty-eight hours prior to presentation, he had just returned from a five-day trip to New Orleans.
PMH, SH, and FH
The patient has hypertension and hyperlipidemia that is well-controlled. Regular medicines include losartan, diltiazem, HCTZ and simvastatin. He is a professor of medicine. He had distant tobacco use with a 10 pk-yr history. He denies recreational drug use. He endorsed drinking one glass of wine per day during his recent trip. He had eaten oysters and redfin fish during his trip.
Physical Examination
- Afebrile, HR=38, RR=12, BP=134/72, O2 sat=95% on RA
- In general, patient was slightly argumentative and in obvious distress due to abdominal pain. HEENT - nonicteric, pupils reactive, moist oral mucosa
- Neck - No elevated JVP, LAD or thyromegaly
- CV - Bradycardic, regular, no murmur
- Pulmonary - Clear to auscultation all lung fields
- Abdomen - Soft with diffuse tenderness to palpation, bowel sounds present, no HSM or mass
- Lower extremities - Cool to the touch without cyanosis, intact and symmetric distal pulses
- Neuro – Cranial nerves intact, no focal motor or sensory deficits, oriented but with difficulty concentrating on thoughts, poor short-term recall, no obvious visual or auditory hallucinations.
Laboratory
Initial laboratory testing was notable for hyponatremia of 126, otherwise a metabolic panel, complete blood count, troponin, urinalysis, urine drug screen and thyroid stimulating hormone were unremarkable. EKG showed sinus bradycardia without ischemic changes. An abdominal flat plate (KUB) showed a nonspecific bowel gas pattern without evidence of obstruction. Chest x-ray was negative for acute cardiopulmonary abnormality.
He was given 1 liter of normal saline with improvement of sodium to 131, but his pulse remained low at 36. He also developed worsening nausea and mentation, was incoherent at times, and began telling staff that “I’m going to die.”
For the initial presentation of nausea, vomiting, bradycardia, hyponatremia, mental status changes, what is your leading diagnosis?
- Acute porphyria
- Excessive water intake
- Neurotoxic shellfish poisoning
- Recreational drug use
- Small cell lung cancer
Cite as: Chan Y-M, Miller DC, Shirazi F, Campion J. July 2020 critical care case of the month: not the pearl you were looking for. Southwest J Pulm Crit Care. 2020;21(1):1-8. doi: https://doi.org/10.13175/swjpcc002-20 PDF
Choosing Among Unproven Therapies for the Treatment of Life-Threatening COVID-19 Infection: A Clinician’s Opinion from the Bedside
Robert A. Raschke, MD
HonorHealth Scottsdale Osborn Medical Center
Scottsdale, AZ USA
We are clearly in unprecedented times. As clinicians watch patients die from COVID-19 infection in the ICU, many feel they cannot wait for clinical trials to prove that various proposed therapies are efficacious. Treatments for which any rationale suggest the possibility of benefit are being administered to patients and the literature abounds with reports of case series or poorly-designed observational trials in which small numbers of patients seem to have favorable outcomes when given these unproven therapies (1). In many cases, these reports are made globally available via social networking without the benefit of peer-review or are being published despite severe methodological flaws that would not have been acceptable prior to the COVID-19 outbreak.
Standard therapy for COVID-19 has recently been published by the Surviving Sepsis Campaign, which have taken a conservative, evidence-based approach (2). But many clinicians are not able to maintain such equipoise in the face of catastrophe. Therefore, I propose an approach to consideration of bedside implementation of unproven therapies for life-threatening COVID-19 for comment and criticism. None of the therapies discussed below have even marginally-acceptable empirical evidence of clinical benefit in patients with COVID-19, so let us put critical appraisal of the literature aside for the moment, and accept that we cannot evaluate these therapies using the normal rules of evidence-based practice (3), application of which would exclude all from further consideration were this any other disease than COVID-19.
I will focus on four unproven therapies that are currently being given to patients with COVID-19 infection: hydroxychloroquine (4), tissue plasminogen activator (tPA) and heparin for presumed pulmonary microthrombosis (5), immunosuppressive treatment of “cytokine storm” (6), and transfusion of convalescent serum (7).
I based my opinions on these four unproven therapies on the following principles:
- COVID-19 is a viral pneumonia. Although it may prove to have some distinctive features, it is likely to be similar to other viral pneumonias (such as SARS CoV-1, MERS, and H1N1 influenza) in terms of its clinical manifestations and response to therapy. We are more likely to gain helpful insights by looking at previous clinical data related to viral pneumonia than to data regarding various noninfectious entities such as high-altitude pulmonary edema or pulmonary venous occlusive disease, as some authors have suggested. COVID-19 viral pneumonia is unlikely, a priori, to respond to therapies that have never shown clinical benefit in the treatment of other viruses, particularly viral pneumonias.
- Demonstration of in-vitro activity rarely translates into clinical efficacy (8,9). In-vitro activity should be a basis for clinical trials, not bedside implementation.
- If unproven therapies are to be given, their safety must be an important consideration. First do no harm.
- We should be willing to apply any treatment recommendation we make for patients to ourselves or beloved family members.
Based on these principles, I propose the following:
Hydroxychloroquine. The non-specific anti-viral properties of chloroquine and hydroxychloroquine were demonstrated in cell cultures 40 years ago. Although active in vitro against Dengue, HIV, Ebola, Influenza and other viruses, this has never convincingly translated into clinical effectiveness (9). A large cohort study focusing on prevention of influenza pneumonia included over 4000 patients receiving HCQ, and showed that they had an increased risk of hospitalization for pneumonia compared to controls (10). Given this long track record, it seems unlikely that HCQ will suddenly be found to have clinical anti-viral benefit in 2020. When it is nevertheless given, care should be exercised to monitor QTc, especially if used in conjunction with other QTc-prolonging drugs like azithromycin and/or in patients with cardiomyopathy.
tPA and heparin. A high incidence of venous thromboembolism has been observed in some cohorts of COVID-19 patients, as has previously been described in patients with H1N1 pneumonia (11). Standard thromboprophylaxis should be employed and venous thromboembolism should be diagnosed and treated in patients with COVID-19 infection. However, some clinicians are administering tPA and therapeutic-dose heparin to patients with COVID-19 and elevated D-dimer in the absence of documented DVT or PE, based on the theory that these patients have microvascular thrombosis requiring treatment. Several large multicenter RCTs examined the use of human activated protein C (Xigris®) to prevent/treat microvascular thrombosis in patients with severe sepsis and convincingly demonstrated no clinical benefit (12). There is no other infectious disease for which the use of tPA or treatment-dose heparin has been proven to be clinically beneficial in the absence of standard indications related to documented venous thromboembolism. Lytic/antithrombotic therapy has a relatively high potential for causing life-threatening hemorrhage. In my opinion, it should not be employed without support from well-designed clinical trials.
Cytokine Storm or HLH. The terms cytokine storm and hemophagocytic lymphohistiocytosis (HLH) have been used to describe similar (perhaps identical) maladaptive immune responses to viral infections. HLH has been well-described in H1N1 pneumonia, SARS-CoV-1 and MERS. There is a rich history of (mostly) observational clinical research supporting the use of immunosuppressive therapies including steroids, anakinra and tocilizumab to treat HLH secondary to viral infection (13). Although immunosuppression can be associated with life-threatening secondary opportunistic infections, treating secondary HLH in selected patients is an approach with a long track record and could be considered standard therapy in Covid19 patients fulfilling HLH diagnostic criteria.
Convalescent Serum. The use of convalescent serum is supported by low-quality observational data going back over 100 years. Although never proven effective in well-designed clinical trials, prior reports in patients with Spanish influenza, SARS-CoV-1 and H1N1 all suggest potentially significant reductions in mortality with acceptable safety (14-16). This therapy is more difficult to operationalize, requiring (expedited) FDA approval, collection, processing and testing of neutralizing antibody titers by a licensed blood bank (17), however based on the principles outlined above, its benefit/harm ratio seems to support its use as an investigational therapy in patients with life-threatening COVID-19.
References
- Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer 2014;110:551-5. [CrossRef] [PubMed]
- Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Mar 27. [Epub ahead of print]. [CrossRef] [PubMed]
- Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA. 1993 Dec 1;270(21):2598-601. [CrossRef] [PubMed]
- Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. [CrossRef] [PubMed]
- Wang J., Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tpa) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020 (in press). [CrossRef] [PubMed]
- Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-4.[CrossRef] [PubMed]
- Duan K, Liu B, Cesheng L, Zhang H, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 6. pii: 202004168. [CrossRef] [PubMed]
- Seyhan, A.A. Lost in translation: the valley of death across preclinical and clinical divide - identification of problems and overcoming obstacles. Transl Med Commun. 2019;4:18. [CrossRef]
- Dyall J, Gross R, Kindrachuk J, et al. Middle east respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs. 2017;77:1935-66. [CrossRef] [PubMed]
- Vanasse A, Courteau J, Chiu Y, Cantin A, Leduc R. Hydroxychloroquine: an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population. MedRxIv .April 10, 2020. [CrossRef]
- Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD. Pandemic H1N1 influenza infection and vascular thrombosis.Clin Infect Dis. 2011 Jan 15;52(2):e14-7.
- Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. [CrossRef] [PubMed]
- Yildiz H, Van Den Neste E, Defour JP, Danse E, Yombi JC. Adult haemophagocytic lymphohistiocytosis: a review. QJM. 2020 Jan 14. [Epub ahead of print] [CrossRef] [PubMed]
- Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for spanish influenza pneumonia: a future H5N1 treatment?. Ann Intern Med. 2006;145:599-609. [CrossRef] [PubMed]
- Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. [CrossRef] [PubMed]
- Yeh KM, Chiueh TS, Siu LK, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. [CrossRef] [PubMed]
- US Food & Drug Administration. Recommendations for Investigational COVID-19 Convalescent Plasma. April 8, 2020. Available at:https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma (accessed 4/10/20).
Cite as: Raschke RA. Choosing among unproven therapies for the treatment of life-threatening covid-19 infection: a clinician’s opinion from the beside. Southwest J Pulm Crit Care. 2020;20(4):131-4. doi: https://doi.org/10.13175/swjpcc026-20 PDF
April 2020 Critical Care Case of the Month: Another Emerging Cause for Infiltrative Lung Abnormalities
Henry W. Luedy, MD1
Sandra L. Till, DO2
Robert A. Raschke, MD1
1HonorHealth Scottsdale Osborn Medical Center
2Banner University Medical Center-Phoenix
Phoenix, AZ USA
Editor’s Note: the following case presentation represents a compilation of several patients.
History of Present Illness
The patient is a 27-year-old man who presented to the Emergency Department in late February 2020 with fever, cough, and green sputum production. He was recently in Hawaii where he meant his Asian girlfriend and was “partying hard”. He was intoxicated and had recent nausea and vomiting.
PMH, SH and FH
No significant PMH or FH. He does admit to smoking, marijuana use, THC use, and vaping.
Physical Examination
- Vital Signs: BP 111/54 (BP Location: Right arm) | Pulse 74 | Temp 98.7 °F (37.1 °C) (Oral) | Resp 18 | Ht 5' 11" (1.803 m) | Wt 72.6 kg (160 lb) | SpO2 99% | BMI 22.32 kg/m²
- General: Awake, alert, interactive, no acute distress
- HEENT: Anicteric, moist mucosa, trachea midline
- CV: RRR
- Lungs: bilateral lower lobe rhonchi, no wheezing, symmetric expansion
- Abdomen: Soft, non-tender, non-distended, positive bowel sounds
- Extremities: no Lower extremity edema, no clubbing, no cyanosis
- Neuro: No focal deficits, moves all extremities.
- Psych: Appropriate
Which of the following are appropriate at this time? (Click on the correct answer to be directed to the second of six pages.)
Cite as: Luedy HW, Till SL, Raschke RA. April 2020 critical care case of the month: another emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(4):119-23. doi: https://doi.org/10.13175/swjpcc018-20 PDF
Further COVID-19 Infection Control and Management Recommendations for the ICU
Robert A. Raschke MD
HonorHealth Osborne Medical Center
Scottsdale, AZ USA
An ad hoc committee of intensivists from the Phoenix area has been meeting via Zoom. They are sharing some of their thoughts and recommendations. Like the previous ICU recommendations published in SWJPCC (1), these are not necessarily evidence-based but based on recent experience and published experience with previous coronavirus outbreaks such as SARS. They are meant to supplement CDC recommendations, not to conflict or restate them.
Infection control outside the rooms of suspected/confirmed COVID-19 patients.
- All healthcare workers should be allowed to exercise droplet precautions at all times while at work.
- All staff should wear a single surgical mask per day to see all non-COVID patients and for rounds. The mask mitigates droplet spread bidirectionally between patients and HCWs and also helps prevent inadvertent touching of the nose and mouth.
- Treat all code patients with airborne / standard / contact precautions
- Use MDIs in preference to SVNs (as long as MDIs hold out)
- Reduce unnecessary staff and visitor traffic in all patient rooms. Avoid duplication of effort, repeated chest examinations with a stethoscope, in the same day by various doctors and nurses, are unlikely to benefit the care of most patients. Don’t enter the patient’s room without a specific purpose and try to perform multiple required tasks with each room entry.
- Hand washing before/after: doorknobs, eating, using a computer, phones, googles.
- Phones – use your own cellphone rather than shared landlines. Use speaker phone so you don’t have to touch your face.
- Consolidate computer use temporally and geographically. Clean your entire workstation (keyboard, mouse, surrounding desktop) before and after each use.
- Keep track of and clean any object on your person that might be contaminated with fomites. This includes any medical instruments that you touch will your gloved hands while seeing patients (stethoscope, pen light, googles, etc). Leave these at work.
- When walking down hallways, don’t touch things.
Patients under investigation or with known COVID-19.
- Avoid use of high-flow nasal cannula (HFNC) or BiPAP. This in opposition to surviving sepsis campaign recommendations, but data from SARS-CoV-1 show that non-invasive ventilation was associated with increased risk of infection of health care workers (2).
- Use metered dose inhalers (MDIs) instead of small volume nebulizers (SVNs).
- Use N95 or PAPR during aerosol-producing procedures such as obtaining nasopharyngeal swab for SARS-CoV-2 RT-PCR, HFNC, BiPAP, bronchoscopy, intubation, breaking ventilator circuit for any reason, extubation, tracheostomy.
- Consider early intubation. Prepare the bag mask with a high-efficiency particulate air (HEPA) filter and attempt rapid sequence intubation with fiberoptic laryngoscope.
- If available, powered air-purifying respirators (PAPR) using P100 HEPA filters (filter >99.97% of 0.3 um particles) should be considered over N-95 (filter 95% of 5 um particles) masks during this high risk procedure based on prior reports of SARS CoV-1 transmission to health care workers (HCW) wearing N95 masks PAPR protects the entire head and neck of the HCW, but requires additional training on donning/duffing.
- If unable to wear PAPR, we recommend N95 masks, gowns and gloves, with googles instead of open face shielded masks. Aerosolized particles are more likely to pass around shields into eyes during these high-risk procedures. Also recommend hats and foot protection.
- The smallest number of personnel required to safely perform the intubation should be present in the room. Fiberoptic laryngoscopy may be preferred over direct laryngoscopy to reduce exposure to aerosolized particles.
- Once intubated:
- Be sure all connections in the ventilator circuit are tight and do not break the circuit casually.
- Place HEPA filter on exhalational limb of ventilator.
- Obtain bronchial secretions using closed-circuit suction device
Code blue patients.
- Use the same precautions as for COVID-19 patients in all patients for whom a code is called.
- We recommend aerosol, contact and standard precautions and eye protection for all code team members for all codes - regardless of whether COVID-19 is suspected. There is no time in a code to determine the likelihood the patient has COVID-19, and bag-masking and intubation will aerosolize the patient’s respiratory secretions.
- A HEPA filter should be placed between the patient and the bag mask to reduce aerosolization of viral particles into the atmosphere.
Diagnosis of COVID-19.
The sensitivity of RT-PCR for COVID-19 is currently uncertain, but preliminary data suggests it may only be in the range of 70% for nasopharyngeal swabs and respiratory secretions. Bronchoscopy with bronchoalveolar lavage may have sensitivity about 90%, but likely poses a risk to HCWs. This poses difficulty in ruling-out COVID-19. Bayesian logic dictates that the pre-test probability of disease influences interpretation of test results.
During active epidemic in Wuhan, the prevalence of COVID-19 among patients admitted with suspicion of having viral pneumonia was 60% (3). Assuming sensitivities by RT-PCR for NP swab of 70%, respiratory secretions 70%, and BAL 90%, and specificity >95%, the false negative rate for a single NP swab used to rule out COVID-19 is 31.6% - that is, 31.6% of patients taken out of isolation based on the negative NP swab result would actually be infected with COVID-19. If a second test, for instance respiratory secretions or another NP swab were performed on all patients whose first test was negative, the false negative rate for the series of tests is 8.8% - likely still not good enough to rule a patient out with confidence. If the second test was a BAL, the false negative rate for the series is 3.5%.
In patients with high pre-test probability of COVID-19, a negative NP swab PCR cannot be safely relied-upon to rule out COVID-19. We recommend bronchial secretions be sent for PCR (in addition to NP swab) in all suspected patients who are intubated. A negative CT scan reduces the probability that a hospitalized patient has COVID-19, but will uncommonly be “negative” in hospitalized patients in whom the diagnosis is considered.
Infection control at home during a surge.
- Clothes: don’t wear jewelry/watches. Wear hospital-laundered scrubs at work, or take off your work clothes when you get home and throw them in wash machine. Leave your work shoes in your car.
- Work equipment: Leave stethoscope, pen, googles and other work-related equipment in a locker at work. Wash your hands and ID badge just before getting in your car to leave the hospital. Leave your ID badge in your car while away from work. Don’t bring your personal computer into work unless absolutely necessary.
- Food: Put a Purell dispenser in front of the refrigerator. Stay out of the kitchen. If have your food prepared for you. Eat on paper plates and then throw them out yourself.
- Use separate bathroom and sleeping quarters if available.
References
- Raschke RA, Till SL, Luedy HW. COVID-19 prevention and control recommendations for the ICU. Southwest J Pulm Crit Care. 2020;20(3):95-7. [CrossRef]
- Cheng VC, Chan JF, To KK, Yuen KY. Clinical management and infection control of SARS: lessons learned. Antiviral Res. 2013 Nov;100(2):407-19. [CrossRef] [PubMed]
- Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020 Mar 11. [Epub ahead of print] [CrossRef] [PubMed]
Cite as: Raschke RA. Further COVID-19 infection control and management recommendations for the ICU. Southwest J Pulm Crit Care. 2020;20(3):100-2. doi: https://doi.org/10.13175/swjpcc020-20 PDF
COVID-19 Prevention and Control Recommendations for the ICU
Robert A. Raschke, MD1
Sandra L. Till, DO2
Henry W. Luedy, MD1
1HonorHealth Scottsdale Osborn Medical Center
2Banner University Medical Center-Phoenix
Phoenix, AZ USA
Editor’s Note: We are planning on presenting a case of COVID-19 from Osborn as our case of the month for April. The authors felt we should publish preliminary recommendations now early in the COVID-19 pandemic. The recommendations are not necessarily evidence-based but are based on recent experience and published experience with previous coronavirus outbreaks such as SARS.
Background:
- COVID-19 is likely somewhat more infectious than influenza (R value in 2-3 range), and can be transmitted by asymptomatic/presymptomatic persons.
- COVID-19 is already in the community and likely being spread from person to person, Therefore, not all COVID-19 patients will present with a recognized exposure history. Furthermore, fever and pneumonia are not universally present.
- As of this writing, >3,300 healthcare workers have been confirmed infected globally with 6 deaths.
- Testing is currently extremely limited in the US with only a minority of potential cases having been tested at this time. This will likely improve over the next few days to weeks. True incidence likely much higher than reported rates of “confirmed COVID-19”.
- About 15% of patients with confirmed COVID-19 have severe disease and 5% require ICU level care. Mortality rates of approximately 1-2% may be confounded by undertesting, but is currently more than 10 times higher than that of influenza (approx. mortality of 0.05-0.1%) (1).
Infectious disease control issues in the ICU. We recommend droplet, contact and standard precautions when seeing any patient presenting with symptoms of acute upper or lower respiratory tract infection of unknown etiology, regardless whether they meet full CDC criteria for COVID-19 testing.
Studies during the SARS epidemic showed that intubation, bag-mask ventilation, non-invasive ventilation and tracheostomy procedures were all associated with increased transmission of SARS to healthcare workers (2).
Code arrest. We recommend aerosol, contact and standard precautions and eye protection for all code team members for all codes - regardless of whether COVID-19 is suspected. There is no time in a code to determine the likelihood of the patient having COVID-19, and bag-masking and intubation will aerosolize the patient’s respiratory secretions. A HEPA filter should be placed between the patient and the bag mask to reduce aerosolization of viral particles into the atmosphere.
Elective or semi-elective endotracheal intubation of patients with possible or confirmed COVID-19. If available, powered air-purifying respirators (PAPR) using P100 HEPA filters (filter >99.97% of 0.3 um particles) should be considered over N-95 (filter 95% of 5 um particles) masks during this high-risk procedure based on prior reports of SARS CoV-1 transmission to healthcare workers wearing N95 masks (3). PAPR protects the entire head and neck of the HCW, but requires additional training on donning/duffing.
If unable to wear PAPR, we recommend N95 masks, gowns and gloves, with googles instead of open face shielded masks. Aerosolized particles are more likely to pass around shields into eyes during these high-risk procedures. We also recommend hats and foot protection.
The smallest number of personal required to safely perform the intubation should be present in the room. Fiberoptic laryngoscopy may be preferred over direct laryngoscopy to reduce exposure to aerosolized particles. Once intubated, a HEPA filter should be placed on the exhalational limb of the ventilator.
Non-invasive ventilation and high-flow nasal oxygen. Non-invasive ventilation and high-flow nasal oxygen likely increase the infectivity of COVID-19 by aerosolizing the patient’s respiratory secretions. Consideration should be given to early intubation in patients under investigation or confirmed for COVID-19 (4).
Visitors should not be allowed inside the rooms of such patients except under extreme circumstances and with one-on-one supervision to assure proper use of PPE and handwashing.
Furthermore, we think it is prudent to employ PPE in the rooms of all patients receiving these therapies, since patients with COVID-19 may present atypically (as in the Osborn case). The doors of their rooms should be kept closed, unnecessary traffic in the room reduced, and droplet contact and standard PPE considered, even in patients in whom COVID-19 is not suspected. (This approach has the downside of consuming PPE that might later be in short supply, but has the upside of preserving healthcare workers who also might later be in short supply).
References
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. [Epub ahead of print]. [CrossRef] [PubMed]
- Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One. 2012;7(4):e35797. [CrossRef] [PubMed]
- Cheng VC, Chan JF, To KK, Yuen KY. Clinical management and infection control of SARS: lessons learned. Antiviral Res. 2013 Nov;100(2):407-19. [CrossRef] [PubMed]
- Zuo MZ, Huang YG, Ma WH, Xue ZG, Zhang JQ, Gong YH, Che L; Chinese Society of Anesthesiology Task Force on Airway Management. Expert recommendations for tracheal intubation in critically ill patients with noval [sic] coronavirus disease 2019. Chin Med Sci J. 2020 Feb 27. [CrossRef] [PubMed]
Cite as: Raschke RA, Till SL, Luedy HW. COVID-19 prevention and control recommendations for the ICU. Southwest J Pulm Crit Care. 2020;20(3):95-7. doi: https://doi.org/10.13175/swjpcc017-20 PDF
Loperamide Abuse: A Case Report and Brief Review
Jaclyn Leong DO1
Kava Afu MS-32
Ella Starobinska MD1
Michael Insel MD3
1Department of Internal Medicine, 2University of Arizona College of Medicine, and 3Department of Pulmonary and Critical Care
Banner University Medical Center
Tucson, AZ USA
Case Presentation
A 29-year-old man with unspecified mood disorder, childhood attention deficit hyperactivity disorder, and 2 prior suicide attempts with zolpidem and methadone presented with altered mental status as a transfer from an outside hospital. The patient was found in his truck outside of a grocery store by a bystander who contacted emergency medical services. At the time, he was noted to have seizure-like activity. He had an empty shopping bag in his possession with 14 empty loperamide (Imodium®) bottles, each were supposed to contain 24 tablets. The patient was taken to the nearest medical facility where he was found to be in status epilepticus. After no response to 4 mg intravenous (IV) lorazepam, he was then intubated for airway protection. Propofol infusion was started and a loading dose of levetiracetam 1600 mg IV was administered. Despite medical management, he continued to show evidence of seizure-like activity. Due to the lack of a neurology service at the hospital, the patient was transferred to our academic medical center.
On arrival, patient was intubated, sedated and hemodynamically stable. Sedation was paused to allow a thorough neurologic examination, at which time, he became agitated and was not redirectable. However, he did not exhibit seizure activity. Toxicology service was consulted for suspected loperamide overdose.
Laboratory workup revealed white blood cell count 16,600 µL with neutrophilic predominance (4000-11000), glucose 205 (70- 106 mg/dL), lactic acid of 10 (0.5- 1.7 mmol/L), creatinine kinase 164 (35- 232 IU/L), creatinine 1.39 ( 0.60- 1.50 mg/dL), EGFR 79 (Normal Low >=60). Tylenol and salicylate levels were undetectable. Urine drug screen was negative. Computer tomography (CT) of the head showed no acute intracranial process. CT abdomen/pelvis showed bibasilar airspace consolidations concerning for aspiration pneumonia. Echo revealed left ventricular ejection fraction of 38% with a large-sized apical, septal, anteroseptal, anterior, inferior, posterior, and lateral wall motion abnormality with hypokinesis to akinesis of the segments.
Electrocardiograms (ECG) initially showed QTc and QRS prolongation of 571 ms and 160 ms, respectively. During the initial 24-hours at our hospital, serial EKGs were performed to monitor QTc. Additionally, patient was treated empirically for aspiration pneumonia with ampicillin/sulbactam.
On day two of his hospitalization, his ECG revealed sinus rhythm, with first-degree AV block and QT prolongation greater than 700 ms. Subsequently, torsades de pointes developed, progressing into ventricular tachycardia storm. Several ampules of bicarbonate were administered, and the patient was cardioverted. Dobutamine and magnesium infusions were started and a temporary transvenous pacer was placed with overdrive pacing initiated at 110 bpm. Over the next 24 hours, magnesium and dobutamine were discontinued. The transvenous pacer was removed on hospital day 4 after the patient demonstrated a native rhythm with normal QRS and QT intervals. Levetiracetam was also discontinued, per neurology recommendations. The patient was safely extubated on hospital day 5. He was subsequently evaluated by the psychiatry service who scheduled close follow up after discharge.
Discussion
Loperamide is a nonprescription drug used most commonly to control acute, nonspecific diarrhea, as well as chronic diarrhea associated with inflammatory bowel disease. It acts on mu-opioid receptors in the myenteric plexus to reduce peristaltic activity, thus lengthening bowel transit time and lowering volume and frequency of bowel movements (1). In contrast to other opioid receptor agonists, loperamide has poor absorption from the gastrointestinal tract and limited ability to cross the blood-brain barrier (1,2). Consequently, the drug was deemed low risk for physical dependence and abuse and since 1982 has been sold over-the-counter (OTC) (3).
Despite this labeling, there is an increasing number of reports documenting cases of loperamide misuse and abuse (3). It has only recently been discovered that loperamide is being ingested at supratherapeutic doses (>16 mg/day) for its euphoric effects or for the relief of opioid withdrawal symptoms (3,4). In 2013, online reports of recreational loperamide use at doses of 70-100mg began circulating (3). In the following three years, a 71% increase of loperamide-associated presentations to drug and poison control agencies was reported (3,6).
As a result, the cardiotoxic effects of this drug have come to light, particularly QT-prolongation and QRS- widening (3). At supratherapeutic plasma concentrations, loperamide causes a blockade of the human ether-a-go-go-related gene (hERG) cardiac potassium channel with high affinity, delaying repolarization of the cardiac myocytes and affecting QT-interval and QRS complex (5). Life-threatening dysrhythmias ensue, accounting for the increasing rate of deaths associated with loperamide overdose and toxicity (3). Reports of loperamide-associated cardiac toxicity have increased greatly in number over the past few years and include: at least 21 individual published case reports of loperamide cardiotoxicity, including one published in SWJPCC (3,7); 48 cases of serious loperamide-associated cardiac events, identified in the FDA Adverse Event Reporting System database; and 22 cases of patients found dead with elevated plasma concentrations of loperamide (3).
Loperamide is just one of an increasing number of OTC drugs with potential abuse because of the stimulant or sedative effects. Other OTC drugs commonly known for abuse are dextromethorphan, pseudoephedrine, phenylephrine, diphenhydramine and oxybutynin especially among teenagers, however, loperamide is a less commonly known drug for its opioid abuse. It is important for physicians to be aware of this increasing risk of abuse and significant life-threatening cardiotoxic effects.
References
- Killinger JM, Weintraub HS, Fuller BL. Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride. J Clin Pharmacol. 1979;19:211-8. [CrossRef] [PubMed]
- Regnard C, Twycross R, Mihalyo M, et al. Loperamide. J Pain Symptom Manage. 2011;42:319-23.[CrossRef] [PubMed]
- Wu PE, Juurlink DN. Clinical review: Loperamide toxicity. Annals of Emergency Med. 2017;70:245-52. [CrossRef] [PubMed]
- Daniulaityte R, Carlson R, Falck R, et al. "I just wanted to tell you that loperamide will work": a web-based study of extra-medical use of loperamide. Drug Alcohol Depend. 2013;130:241-4. [CrossRef] [PubMed]
- Salama A, Levin Y, Jha P, et al. Ventricular fibrillation due to overdose of loperamide, the "poor man's methadone." J Community Hosp Intern Med Perspect. 2017;7(4):222-6. [CrossRef] [PubMed]
- Stanciu CN, Gnanasegaram SA. Loperamide, the "Poor Man's Methadone": Brief review. Journal of Psychoactive Drugs. 2017;49:18-21. [CrossRef] [PubMed]
- Watkins SA, Smelski G, French RNE, Insel M, Campion J. January 2019 critical care case of the month: A 32-year-old woman with cardiac arrest. Southwest J Pulm Crit Care. 2019;18(1):1-7. [CrossRef]
Cite as: Leong J, Afu K, Starobinska E, Insel M. Loperamide abuse: a case report and brief review. Southwest J Pulm Crit Care. 2020;20(2):73-5. doi: https://doi.org/10.13175/swjpcc007-20 PDF
Single-Use Telescopic Bougie: Case Series
Evan Denis Schmitz MD
La Jolla, CA USA
Abstract
AIRODTM is a single-use telescopic bougie that is small enough to fit into a pocket. AIRODTM is sterile and can be expanded in hast when needed, saving precious seconds, while attempting to intubate a patient. The non-malleable bougie is able to overcome the compressive force of the oropharyngeal tissue improving the view of the vocal cords and facilitating advancement of an endotracheal tube into the trachea along with a laryngoscope. This series reports four cases of successful first pass intubation with the AIRODTM.
Introduction
There are approximately 50 million intubations performed a year with 1/3 of those occurring in the USA. A multicenter registry of ED intubations, reporting data from 2002-2012, found that approximately 12% of intubations resulted in adverse intubation-related events such as death (1). In order to reduce the likelihood of adverse events it is imperative that the first attempt at endotracheal intubation is successful (2). Despite increasing adoption of expensive video laryngoscopy first-attempt intubation success rates are only 85% (1). The BEAM trial reported a 96% success rate in first-attempt intubation of a difficult airway with a bougie vs only 82% with endotracheal tube + stylet (3).
AIRODTM was designed to aid in the advancement of an endotracheal tube past the vocal cords with the use of a laryngoscope (Figure 1).
Figure 1. Single-Use Telescopic Bougie in the closed (A) and extended (B) position with an endotracheal tube loaded at the distal end.
AIRODTM can also improve the view of the vocal cords during intubation by displacing oropharyngeal tissue. The following case series demonstrates the usefulness of the AIRODTM: each of the 4 intubations were successful on the first attempt and facilitated by the single-use telescopic bougie without causing any trauma. All intubations were performed by the author.
Case 1
A 70-year-old woman with severe COPD not on home oxygen presented with an oxygen saturation of 70%. She was found to have multi-lobar pneumonia predominately in the right upper and middle lobes. Despite bilevel positive airway pressure (BiPAP) therapy her hypoxia worsened, and she required intubation. Inspection of her oropharynx prior to intubation revealed very prominent 1st incisors as well as canines that were eroded at the roots left worse than right. Multiple black, necrotic molars were noted, right worse than left, with a putrid odor. Her oxygen saturation, despite being on 15L nasal cannula, hovered in the low 90s. In anticipation of a difficult airway the AIRODTM was prepared by extended the rods and ensuring the rods were in the locked position. A Miller 4 blade was gently inserted past the teeth and into the oropharynx. A grade 2 view (larynx plus the posterior surface of epiglottis) was obtained. This was immediately followed by gentle insertion of the AIRODTM which was advanced just distal to the vocal cords. An 8.0 endotracheal tube was advanced down the AIRODTM by the respiratory therapist while the AIRODTM was held in position. As the endotracheal tube was advanced into the oropharynx, hand position was changed from holding the AIRODTM to holding the tip of the endotracheal tube while the respiratory therapist held the distal end of the AIRODTM. The endotracheal tube was then advanced past the vocal cords and into the trachea while the respiratory therapist removed the AIRODTM with ease. No complications occurred. No trauma occurred to the oropharynx, vocal cords or trachea. The patient was successful ventilated and oxygen saturations improved to high 90s.
Case 2
A61-year-old man with severe schizophrenia and acute delirium had a PaO2 of 61 mmHg despite BiPAP 14/6 on 90% fio2 with a minute ventilation of 18 L/min from multi-lobar pneumonia. A Miller 4 blade was gently inserted past the teeth and into the oropharynx. A grade 1 view (whole vocal cords seen; the epiglottis is not seen at all) was obtained. The AIRODTM was gently advanced 2 cm past the vocal cords followed by an assistant advancing a 7.5 endotracheal tube down the AIRODTM until grasped, then the endotracheal tube was slid into the trachea while the assistant held the distal end of the AIRODTM. The AIRODTM was then removed intact with no evidence of airway trauma.
Case 3
A 54-year-old man with severe coronary artery disease on aspirin and Plavix with a history of a seizure disorder associated with alcohol withdrawal became unresponsive and a code blue was called. He was found to be apneic with oxygen saturation in the 50s. He was stimulated by the hospitalist and woke up. He was transferred to the ICU where he became completely unresponsive again and became apneic. He was immediately ventilated with a bag-valve mask and oxygenation improved to 100%. He then bolted up out of bed and became very combative. Propofol was given and he was laid supine and ventilated with a bag-valve mask. Inspection of his oropharynx revealed a very large tongue, some missing and multiple sharp teeth with mouth opening of only 2 fingerbreadths. There was blood and emesis in his oropharynx that was suctioned. A Miller 4 blade was inserted into the oropharynx but only a grade 4 view (the anterior tip of the epiglottis is seen and encroaching on the view of vocal cords obstructing <50% of view) could be obtained. The AIRODTM was inserted into the oropharynx in the fully extended and locked position and the proximal tip was used to gently lift the epiglottis exposing the vocal cords and improving the view to a grade 2. AIRODTM was advanced 2 cm past the vocal cords and an assistant advanced an 8.0 endotracheal tube down the AIRODTM until it was grasped, and the endotracheal tube was advanced successfully past the vocal cords while the assistant held the distal end of the AIRODTM. The AIRODTM was removed intact without any oropharyngeal or vocal cord trauma.
Case 4
A 48-year-old obese who was an alcoholic and a smoker was critically ill with an admission albumin of 0.9 and lactic acid of 9 with multiorgan system failure from an intra-abdominal abscess with septic shock on 15 mcg/min of epinephrine and 25 mcg/min of Levophed. He was obtunded and in acute respiratory failure. The AIRODTM was pre-loaded with an 8.0 endotracheal tube onto the distal end of the AIRODTM prior to providing sedation with Etomidate and bag-valve mask ventilation in anticipation of a difficult airway: full beard, mouth opening 2 cm, large tongue, collapse of the walls of the oropharynx as well as false cords. Using a Miller 4 blade a grade 2 view was obtained and the AIRODTM was advanced 1 cm past the vocal cords followed by the endotracheal tube while an assistant held the distal end. There was no significant desaturation or trauma to the vocal cords or oropharynx. Pre-loading the AIRODTM with the endotracheal tube improved the speed and autonomy of the intubation.
Discussion
AIRODTM is a single-use telescopic endotracheal intubation bougie. It is rigid, made of stainless steel and sterilized. It telescopes to two feet and has a specialized 20-degree angled tip. Once expanded it locks so it cannot be retracted. An endotracheal tube 7.0 or greater can be advanced over the telescoping bougie for smooth placement in the adult trachea.
AIRODTM is non-malleable and can gently displace oropharyngeal tissue, it does not sag and pull like plastic bougies, the unique locking mechanism prevents collapse and the square handle improves dexterity as well as spatial awareness of the proximal tip.
AIRODTM telescopes open allowing for storage in small spaces such as a pocket or a crash cart without damaging its integrity like so many bougies that are ruined when bent for storage. Because of its small size, it can be stored in a myriad of places and easily accessed by emergency personnel in the field, emergency department, intensive care unit and operating room.
AIRODTM can be used with multiple different varieties of laryngoscopes. My preference is a Miller 4 laryngoscope because of the ability to lift the epiglottis and visualize the vocal cords especially in patients with a large tongue, limited mouth opening and decreased neck mobility. The AIRODTM can be slid along the length of the laryngoscope blade if needed to overcome the force of oropharyngeal tissue. Once the AIRODTM is advanced a few centimeters past the vocal cords the rigidity of the AIRODTM allows advancement of the endotracheal tube with ease because it can withstand the forces applied by the oropharyngeal tissue without significant bending. I have also used a Macintosh laryngoscope with the AIRODTM which allows for displacement of the tongue and oropharyngeal tissue but placement into the vallecula above the epiglottis can limit exposure to the vocal cords. The AIRODTM can overcome the limitation of the Macintosh laryngoscope by directly lifting the epiglottis, exposing the vocal cords then the AIRODTM can be gently slid along the posterior surface of the epiglottis past the vocal cords followed by advancement of an endotracheal tube for successful intubation. Because the AIRODTM is made of steel, similar to the Gliderite stylet used with the Glidescope as well as laryngoscopes and rigid bronchoscopes, it is possible that if used incorrectly trauma to the oropharynx as well as the trachea may occur, and caution is advised.
The cost of the AIRODTM is similar to the Glidescope’s disposable covers that are used with each intubation. Because of the loss of direct sight and acute angles involved in the process of advancing an introducer during intubation with the Glidescope I do not recommend using the AIRODTM with the Glidescope. The AIRODTM was designed only to be used with adults.
Conclusion
AIRODTM is a sterile single-use telescopic bougie that is used along with a laryngoscope when performing endotracheal intubation. Because of its small size it is easily stored in a pocket, helicopter, ambulance, crash cart, operating room, emergency department, intubation box and in the intensive care unit. Its rigidity helps displace oropharyngeal tissue improving the view of the vocal cords and it facilitates advancement of an endotracheal tube. It can also be used in the closed position as a stylet making it an ideal instrument for first-attempt intubation along with a laryngoscope.
Conflict of Interest Disclosures
The author Evan Denis Schmitz, MD is the inventor of the AIRODTM.
References
- Brown CA 3rd, Bair AE, Pallin DJ, Walls RM; NEAR III Investigators. Techniques, success, and adverse events of emergency department adult intubations. Ann Emerg Med. 2015 Apr;65(4):363-70. [CrossRef] [PubMed]
- Sakles JC, Chiu S, Mosier J, Walker C, Stolz U. The importance of first pass success when performing orotracheal intubation in the emergency department. Acad Emerg Med. 2013 Jan;20(1):71-8. [CrossRef] [PubMed]
- Driver BE, Prekker ME, Klein LR, Reardon RF, Miner JR, Fagerstrom ET, Cleghorn MR, McGill JW, Cole JB. Effect of use of a bougie vs endotracheal tube and stylet on first-attempt intubation success among patients with difficult airways undergoing emergency intubation: a randomized clinical trial. JAMA. 2018 Jun 5;319(21):2179-89. [CrossRef] [PubMed]
Cite as: Schmitz ED. Single-use telescopic bougie: case series. Southwest J Pulm Crit Care. 2020;20(2):64-8. doi: https://doi.org/10.13175/swjpcc005-20 PDF
Editor's Note: On April 19, 2020 Dr. Schmitz has submitted a video showing a 6 second intubation using the AIROD and a mannequin which is below.
Safety and Efficacy of Lung Recruitment Maneuvers in Pediatric Post-Operative Cardiac Patients
Renee L. Devor MD1,2
Harjot K. Bassi MD3
Paul Kang MPH4
Tiffany Morandi MD2
Kristi Richardson RT5
John J. Nigro MD2,6
Christine Tenaglia RT5
Chasity Wellnitz RN, BSN, MPH6
Brigham C. Willis MD1,2,7
1Division of Cardiac Critical Care, Phoenix Children’s Hospital, Phoenix, Arizona
2Department of Child Health, University of Arizona College of Medicine, Phoenix, Arizona
3Division of Critical Care, Phoenix Children’s Hospital, Phoenix, Arizona
4Department of Epidemiology and Biostatistics, University of Arizona College of Medicine, Phoenix, Arizona
5Department of Respiratory Therapy, Phoenix Children’s Hospital, Phoenix, Arizona
6Division of Cardiology, Phoenix Children’s Hospital, Phoenix, Arizona
7Department of Pediatrics, Creighton University School of Medicine, Phoenix, Arizona
Abstract
Background: Recruitment maneuvers are a dynamic process of transient increases in transpulmonary pressure intended to open unstable airless alveoli. Due to concerns regarding the hemodynamic consequences of recruitment maneuvers in children with heart disease, these maneuvers have not been widely utilized in this population. The objective of this study was to demonstrate the safety and efficacy of lung recruitment maneuvers in post-operative pediatric cardiac patients. We hypothesized that multiple recruitment maneuvers are physiologically beneficial and hemodynamically tolerated in children with congenital cardiac disease.
Methods: Retrospective chart review was conducted of post-operative cardiac surgical subjects who received recruitment maneuvers, as well as a matched control group who did not, at a Cardiac ICU in a quaternary care free-standing children’s hospital. Repetitive lung recruitment maneuvers using incremental positive end-expiratory pressure were performed. Hemodynamic and respiratory physiologic variables were recorded.
Results: Sixty-one post-operative cardiac subjects had a total of 435 lung recruitment maneuvers. Assessment of hemodynamic tolerability demonstrated no change in MAP, HR, or CVP during or after the maneuvers. There was a 28% increase in dynamic compliance following recruitment maneuvers (p <0.01, 95% CI). Specific outcomes in the 59 matched control subjects demonstrated no significant difference in length of mechanical ventilation (p = 0.26), length of hospital stay (p = 0.28), mortality (p = 0.58) or difference in occurrence of pneumothorax (p = 0.26).
Conclusions: Post-operative pediatric cardiac surgical subjects tolerated repeated lung recruitment maneuvers without significant hemodynamic changes. The maneuvers successfully improved dynamic compliance without any adverse effects.
Introduction
Mechanical ventilation is a common therapy used for pediatric patients in the intensive care unit and is frequently used for children with congenital cardiac disease following surgical repair. However, it is well known that mechanical ventilation can induce lung injury or worsen preexisting lung disease (1-3). In patients with congenital cardiac disease, it is crucial to protect the lung from injury and optimize ventilation and oxygenation due to their underlying hemodynamic and physiologic fragility (4, 5). Post-operatively, several factors including general anesthesia, cardiopulmonary bypass, atelectasis, and hypoxemia can contribute to lung dysfunction, which may lead to prolonged mechanical ventilation (6). Children with such prolonged ventilation are at a higher risk for poor overall outcome due to a variety of ventilator-associated morbidities (7, 8). Therefore, it is of practical value to protect the lungs and reduce the length of time mechanical ventilation is required.
Alveolar injury can be caused by the repetitive opening and closing of alveoli when inadequate positive end-expiratory pressure (PEEP) is provided and this can generate shear stress within the alveoli and promote injury (9-10). Lung recruitment maneuvers have been defined as transient increases in the transpulmonary pressure used to open recruitable collapsed alveoli and increase end expiratory lung volume (11-13). Recruitment maneuvers are often considered useful in patients, especially those with acute respiratory distress syndrome (ARDS), to potentially decrease ventilator-induced lung injury by improving oxygenation and lung compliance while reducing the risk of atelectrauma by re-opening and stabilizing collapsed alveoli (11,13-18).
Increased intrathoracic pressure can affect right and left ventricular preload due to decreased venous return, changed right ventricular afterload, and altered biventricular compliance (4,10,14,19-21). This may lead to decreased stroke volume leading to short periods of hypotension, bradycardia, and impaired cardiac output, which is of significant concern in patients with congenital cardiac disease (14). Many patients with congenital cardiac disease must undergo surgical procedures which lead to lung collapse after induction of general anesthesia and during mechanical ventilation (15,22). In those patients undergoing cardiac surgery with cardiopulmonary bypass, significant atelectasis occurs which impairs right ventricular (RV) function. However, lung recruitments using positive pressure have been shown to re-expand collapsed alveoli and improve RV function (23-26). There is a theoretical risk of developing barotrauma leading to pneumomediastinum or pneumothorax during a recruitment; however this is likely less a risk in cardiac surgical patients with relatively healthy lungs (10,27,28).
These cardiopulmonary interactions and hemodynamic concerns limit the willingness of many clinicians to perform positive-pressure recruitment maneuvers in patients with underlying cardiac pathology, making studies involving this population uncommon. One study (29) evaluated the use of a recruitment maneuver performed in twenty pediatric patients with congenital cardiac disease who underwent surgical repair. A single recruitment maneuver was performed shortly after coming off of cardiopulmonary bypass and repeated once in the intensive care unit. Although this study was able to demonstrate an improvement in oxygenation, dynamic lung compliance, arterial to end-tidal CO2 gradient, and end expiratory lung volume, it excluded patients with residual intracardiac lesions following surgery, patients with valvular regurgitation, or respiratory failure defined as FiO2 >0.8. Due to the relatively small number of patients included in this study, as well as their protocol prescribing only two recruitment maneuvers performed per patient, it is difficult to ascertain the overall long-term safety and potential benefits that repeated lung recruitments may provide.
In this study, we aimed to investigate the safety and efficacy of increment-decrement recruitment maneuvers in a larger pediatric patient population following surgery for congenital cardiac disease, hypothesizing that multiple recruitment maneuvers are physiologically beneficial and hemodynamically tolerated in these patients. The safety of these maneuvers was evaluated by examining changes in mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP) before, during, and after the recruitment maneuvers. The efficacy of the recruitment maneuvers was determined by changes in oxygenation index (OI) and dynamic lung compliance (Cdyn) following recruitment. To further evaluate the safety of repetitive recruitment we reviewed specific clinical outcomes that included length of mechanical ventilation, length of hospital stay (LOS), mortality and occurrence of pneumothorax and compared to a control group.
Materials and Methods
This study was reviewed and approved by the Institutional Review Board at Phoenix Children’s Hospital. Subjects who received lung recruitment maneuvers post-operatively, as identified in the electronic medical record, in the Phoenix Children’s Hospital cardiac intensive care unit, a quaternary referral center, from July 2011 through June 2012 following implementation of a lung recruitment protocol, were included in the study. Further inclusion criteria included subjects from 0-18 years of age who were admitted immediately after having open heart surgery with both single- and two-ventricle physiology and who remained on invasive mechanical ventilation. All subjects were mechanically ventilated with Servo-I ventilators (Maquet Critical Care, Solna, Sweden). Subjects with a tracheostomy or who were receiving extracorporeal membrane oxygenation (ECMO) support were excluded from the analysis. A comparison group of consecutive control subjects who did not receive recruitment maneuvers was selected in the following year from July 2012 to June 2013 following an institutional hiatus of the maneuvers during which time quality data was reviewed and the safety of the protocol was assessed. Recruitment maneuvers have subsequently been reinstated and are now standard care in our post-operative cardiac patients on invasive mechanical ventilation.
During the study period, lung recruitment maneuvers were a new standard of care implemented at our institution in the cardiac intensive care unit. They were performed by either the respiratory therapist or attending physician. Most patients had twice daily recruitment maneuvers unless more were clinically indicated based on chest x-ray findings or lung mechanics. The patients may also have fewer recruitment maneuvers if they were hemodynamically unstable, having other procedures, if there was ongoing resuscitation or at the discretion of the attending physician.
The recruitment maneuver was performed in pressure control mode regardless of the subject’s baseline mode of ventilation. Initial settings were adjusted to achieve a tidal volume of 6mL/kg. PEEP was increased from baseline by 1-2 cmH2O increments while maintaining a fixed inspiratory driving pressure (PIP-PEEP) with each increase sustained for one-minute intervals until either the tidal volume (VT) or dynamic compliance (Cdyn) declined (Figure 1).
Figure 1. Lung recruitment maneuver: recruitment maneuver protocol courtesy of Boriosi et al. (11). Each horizontal bar represents an incremental increase of PEEP by 2 cm H2O in one-minute increments from baseline PEEP.
The recruitment maneuver was terminated if the mean airway pressure surpassed 28 cm H2O. VT and Cdyn were documented with each increase in PEEP. Once the critical opening pressure was identified, PEEP was decreased in a step-wise manner in one-minute 1-2 cmH2O decrements to the critical closing pressure identified by a decrease in VT or Cdyn. Following this point, the PEEP was again increased to the identified critical opening pressure for one minute. It was then brought back down to 2 cmH2O above the critical closing pressure (i.e. “optimal PEEP” level demonstrated by improved compliance and increased tidal volume with less ventilating pressure). The subject was then placed back on their original mode of ventilatory support with the PEEP adjusted to the optimal level, as determined during the recruitment maneuver in order to maintain the newly recruited areas of the lungs open.
Data Collected: A database was generated with 61 subjects who had lung recruitment maneuvers, and a convenience sample of 59 matched control subjects were selected from our Society for Thoracic Surgeons (STS) database. Demographic data was collected including age, body surface area, associated anomalies or chromosomal abnormalities, cardiac diagnosis, and type of surgical procedure. Clinical outcomes data collected included length of mechanical ventilation, length of hospital stay, mortality, and occurrence of pneumothorax.
Hemodynamic variables including MAP, HR, and CVP were monitored and recorded by the bedside nurse and/or respiratory therapist. For each variable, the two hourly vital sign measurements prior to the start of the maneuver, two measurements during, and the first two hourly measurements following the maneuver were included for analysis. In an attempt to minimize error and to provide a more accurate representation of the subject’s status at the time of interest, the two vital sign measurements in each category were averaged as physiologic variables are dynamic. The respiratory physiologic variables monitored were dynamic compliance and oxygenation index. In order to further investigate the clinical effects of potentially decreased cardiac output, we reviewed the changes in inotropic and vasopressor support before, during, and after the performance of each recruitment maneuver.
Statistical Analysis: Subject demographic and clinical characteristics between the control and recruitment maneuver groups were reported as medians, interquartile ranges (IQR) for continuous variables and frequencies, percentages for categorical variables. The Wilcoxon Rank Sum was used to compare the continuous variables; while Chi-squared/Fisher’s Exact Tests were used to compare the categorical variables. The Linear Mixed Model was used to ascertain trends in hemodynamic outcomes (mean arterial pressure, heart rate, and central venous pressure) across three timepoints (before, during and after the recruitment maneuver). If the overall trend showed statistical significance, the Wilcoxon Signed Rank Test was used to ascertain differences via multiple comparisons followed by the Bonferroni adjustment for multiple comparisons. Before and after differences in physiological outcomes (oxygenation index and dynamic compliance) were assessed using the Wilcoxon Signed Rank. All p-values were 2-sided and p<0.05 was considered statistically significant. All data analyses were conducted using STATA version 14 (STATACorp; College Station, TX).
Results
A total of 61 subjects underwent lung recruitment from June 2011 to June 2012 (Table 1) accounting for a total of 439 recruitment maneuvers during this time.
Table 1. Comparison of subjects receiving recruitment maneuvers versus controls.
Recruitment was initiated in the post-operative period once deemed safe by the primary intensivist. The maneuvers were performed as frequently as every two hours but, on average, subjects in the cohort received 2 recruitment maneuvers per ventilator day. Both groups had similar congenital heart disease diagnoses with an average Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery Mortality Score of 3 in each group covering a variety of anatomical defects and surgical procedures performed. Subjects with residual intracardiac lesions on intraoperative transesophageal echocardiogram were included in the study.
Hemodynamics: All 61 subjects tolerated the maneuvers with no hemodynamic instability defined as hypotension, need for fluid bolus during the recruitment, bradycardia, or dysrhythmias. No subject had any of the maneuvers discontinued prematurely. We found no significant difference in the MAP (p = 0.13, 95% CI) (Figure 2a) or HR (p = 0.74, 95% CI) (Figure 2b) during the time intervals measured.
Figure 2. Hemodynamics: comparison of hemodynamic measurements before, during, and after the recruitment maneuvers. There was no significant change in MAP (Fig 2a), HR (2b), or CVP (2c) during or after the maneuvers. Boxplot with whiskers with minimum/maximum 1.5 IQR.
Due to the transient increase in intrathoracic pressure that theoretically results in a decrease in venous return and therefore cardiac output, CVP was monitored throughout the recruitments. The CVP measurement did not show a significant change with the recruitment maneuver (p = 0.79, 95% CI) (Figure 2c).
In order to further investigate the clinical effects of potentially decreased cardiac output, we reviewed the changes in inotropic and vasopressor support surrounding the performance of the recruitment maneuvers. All infusion rates of epinephrine, norepinephrine, vasopressin, dopamine, milrinone, and calcium were documented prior to, during, and after lung recruitments. Of the 439 recruitment maneuvers performed, 84% were performed without any change in inotropic support during or within 1 hour after completion of the maneuver. Inotropic support was decreased after the recruitment in 12% of maneuvers. Only 3% of maneuvers required an increase in support. No subjects had any significant hypotension requiring fluid bolus administration during or immediately after the maneuvers.
Efficacy: The efficacy of recruitment maneuvers on lung function was determined by measuring changes in the OI and Cdyn before and after recruitment. There was no statistically or clinically significant change in the OI with a median OI before recruitment of 7.3 (IQR 4.1-12.6) and after 7.7 (IQR 4.6-12.6) (p = 0.96, 95% CI) (Figure 3a).
Figure 3. Efficacy: comparison of physiologic measures used to assess efficacy of the recruitment maneuvers. No significant change was demonstrated in the OI before and after recruitment (3a). There was a significant increase in Cdyn by an average of 28% immediately after the maneuvers (3b). Boxplot with whiskers with minimum/maximum 1.5 IQR.
Of the 439 maneuvers, 83% resulted in a measurable improvement of the Cdyn with all 61 of the subjects demonstrating an increase at least once over the course of the interventions. The Cdyn increased from 0.45 ml/cmH2O/kg (IQR 0.37-0.57) to 0.58 ml/cmH2O/kg (IQR 0.47-0.75) afterwards (p < 0.001, 95% CI). (Figure 3b). The duration of improved Cdyn was an average of 8 hours +/- 11.4 hours. Subjects continued to show improvement with repeated efforts.
Clinical Outcomes. All subjects included in this study were on invasive mechanical ventilation support on return from cardiac surgery for a minimum of 24 hours. As shown in Table 2, there was no significant difference in the number of ventilator days between the recruitment maneuver and control groups (p = 0.26, 95% CI).
Table 2. Clinical outcomes.
There was also no difference in the occurrence of extubation failure requiring reintubation between both groups (p = 0.52). There was no difference in hospital LOS with the RM group staying 17.5 days (10.5 – 27) and control group 15 days (9.5 – 23) (p = 0.28, 95% CI) or in the rate of in-hospital mortality (p = 0.58, 95% CI). Despite the theoretical concern for development of pneumothorax with recruitment maneuvers, there was no significant difference in the occurrence between the two groups (p = 0.26, 95% CI).
Discussion
Our results suggest that lung recruitment maneuvers are well tolerated in the pediatric post-operative cardiac patient population both with and without residual intracardiac shunts, and may be repeated for the duration of their time requiring invasive mechanical ventilation. Despite being at high risk of hemodynamic instability shortly after surgery, especially following complex repair and prolonged cardiopulmonary bypass time, our subjects did not require significant preload optimization or escalation of inotropic support during the maneuvers. We were also able to demonstrate that there was an improvement in dynamic lung compliance following the maneuver. Not only were these maneuvers tolerated from a hemodynamic standpoint, but there were no adverse outcomes when compared to control subjects with no difference in the length of mechanical ventilation, LOS, mortality, or the occurrence of pneumothorax.
Advocacy for the optimization of oxygenation and ventilation through the use of an “open lung” strategy, especially in the treatment of ARDS, has been present in the critical care literature for decades. Multiple reports have described the importance of lung recruitment with high inspiratory pressures in addition to the appropriate PEEP above closing pressures to maintain optimal gas exchange and minimize hypercapnia (30). Recruitment maneuvers are recommended in the protective ventilation strategy in adult post-operative patients who have undergone cardiac surgery with significant benefits as compared to traditional ventilation (31,32). To our knowledge, there is very limited data on the use of lung recruitment maneuvers in the pediatric cardiac patient population with the majority of the pediatric literature focusing on the use of these maneuvers in patients with ARDS. Scohy et al. (29) previously evaluated the use of recruitment maneuvers in subjects undergoing surgery for congenital cardiac disease but excluded several key subgroups of these subjects and did not evaluate the continued use of recruitment maneuvers over the entire course of mechanical ventilation. Amorim et al. (6) assessed the tolerance of recruitment maneuvers in a small population of infants who were prone to pulmonary arterial hypertension and excessive pulmonary circulation just after skin closure for open heart surgery. In general, data on the safety of these maneuvers in pediatric patients is very limited.
The efficacy of lung recruitment maneuvers in patients with ARDS remains controversial with some studies suggesting an improvement in oxygenation and dynamic or static compliance (1,11,20,21,33-35), some demonstrating brief or no improvement (36,37), and others that show improvement but suggest that the deleterious hemodynamic effects may outweigh the benefits (14). In children with ARDS, a staircase recruitment strategy has been described to improve oxygenation with increasing PaO2. In order to sustain improved oxygenation, the PEEP must be set above the critical closing pressure of the lung following recruitment (11,21,38,39). Boriosi et al. (11) further described that a “re-recruitment” maneuver that was performed at critical opening pressures for a short period of time improved the PaO2/FiO2 ratio for up to 12 hours and OI for up to four hours following the recruitment maneuver. In our study, we were not able to demonstrate an improvement in the OI. However, we did demonstrate a significant improvement in Cdyn of 29% following completion of each recruitment which was sustained for eight hours. The lack of improvement in oxygenation may be secondary to less primary lung injury in our patient population, or due to the common presence of residual intracardiac shunts. The increase in Cdyn may be a clinically significant change for some patients and could help reduce the time on invasive mechanical ventilation.
The overall goal of recruitment maneuvers is to open atelectatic alveoli, increase end expiratory lung volume, and improve gas exchange. However, as discussed, generation of high intrathoracic pressures during the maneuvers can theoretically result in hemodynamic instability (4,10,14,20,21). Currently, there is no specific non-invasive monitoring that is the best indicator for hemodynamic assessment during recruitment maneuvers, with vital sign changes serving as a surrogate marker for the safety of the recruitment maneuver (40). In our study, there was no change in MAP, HR, or CVP from baseline, during, or after the maneuvers indicating that they were well tolerated from a hemodynamic standpoint with 97% of the recruitment maneuvers using the same or less inotropic support and no subject required fluid bolus administration for hypotension during any of the maneuvers.
The occurrence of barotrauma, including pneumomediastinum and pneumothorax, has been reported with the intermittent increase in peak airway inspiratory pressures (10,27,28). In our study, there was no significant difference in the occurrence of pneumothorax between the two groups. With the preponderance of studies on recruitment maneuvers being performed in the adult ARDS patient population, there is limited data on pediatric outcomes in mortality and duration of mechanical ventilation. A Cochrane review performed by Hodgson et al. (41) demonstrated no reduction in mortality or length of mechanical ventilation following recruitment maneuvers in adult ARDS patients. In our study, we demonstrated similar findings in that there was no difference in mortality, length of mechanical ventilation, or LOS in pediatric post-operative congenital cardiac patients with or without the maneuvers.
There were several limitations to our study. This was a single-center, retrospective study that involved a small pediatric cardiac population. Our assessment of cardiac output was dependent on measurements of MAP and CVP. We also did not investigate the occurrence of hypercapnia during the recruitment maneuvers. Overdistension of open alveoli can occur resulting in an increase in pulmonary vascular resistance and a decrease in blood flow to the alveoli, thereby increasing dead space ventilation (21). There are a number of studies demonstrating that throughout recruitment maneuvers there is an increase in PaCO2, with a potential need to titrate the respiratory rate on the ventilator in order to maintain constant minute ventilation throughout the maneuver, as this development of hypercapnia during the maneuvers may result in adverse effects (11,34,36,41). A multifaceted approach to monitoring the effectiveness as well as any negative consequences of these maneuvers including end-expiratory lung volumes, dead space ventilation, pulmonary compliance, volumetric capnography as well as bedside ultrasound would be beneficial (40). This study was conducted prior to our institution utilizing volumetric CO2 analysis to monitor physiologic gas exchange as well as dead-space ventilation during mechanical ventilation.
Conclusion
Overall, our study demonstrated that pediatric post-operative cardiac subjects, having a wide variety of cardiopulmonary physiology, tolerated repeated recruitment maneuvers without significant hemodynamic changes or adverse outcomes. As has been the case in many previous studies, we did not find any significant improvement in oxygenation, length of mechanical ventilation, or length of stay. However, as recruitment maneuvers have been shown to be an integral part of lung protection strategies and to benefit adults following open heart surgery, it is possible that our pediatric post-operative cardiac patients could benefit from the integration of recruitment maneuvers into ventilator management strategies while on invasive mechanical ventilation. Future prospective studies need to be conducted to further evaluate the potential benefit and utility of lung recruitment maneuvers in pediatric patients without significant lung disease.
Acknowledgements
We would like to thank the staff of the Pediatric Cardiovascular Intensive Care Unit at Phoenix Children’s Hospital for their assistance and support in this study. We would also like to acknowledge the work of Juan P Boriosi, MD and his colleagues for use of their recruitment protocol and RM diagram (Figure 1) in our study.
Contributions: Renee L. Devor MD1,4,5,6, Harjot K. Bassi, MD1-6, Paul Kang MPH4, Tiffany Morandi MD1-3, Kristi Richardson RT2,3, John J. Nigro MD2, Christine Tenaglia RT2,3, Chasity Wellnitz RN, BSN, MPH2,4, and Brigham C. Willis MD3,6
1Literature search, 2Data collection, 3Study Design, 4Analysis of data, 5Manuscript preparation, 6Review of manuscript
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Cite as: Devor RL, Bassi HK, Kang P, Morandi T, Richardson K, Nigro JJ, Tenaglia C, Wellnitz C, Willis BC. Safety and efficacy of lung recruitment maneuvers in pediatric post-operative cardiac patients. Southwest J Pulm Crit Care. 2020;20(1):16-28. doi: https://doi.org/10.13175/swjpcc068-19 PDF
January 2020 Critical Care Case of the Month: A Code Post Lung Needle Biopsy
Sarika Savajiyani MD and Clement U. Singarajah MBBS
Phoenix VA Medical Center
Phoenix, AZ USA
A 67-year-old man with a history of stage IIA rectal adenocarcinoma post neoadjuvant chemoradiation presented with a near code event after elective CT guided biopsy of an enlarging left lower lobe lung nodule. The patient became bradycardic and profoundly hypotensive immediately after the CT guided biopsy with the following vital signs: Systolic BP < 90 mmHg, HR 40/min sinus bradycardia, SpO2 on 100% oxygen non rebreather was 90%. Telemetry and EKG showed ST elevation in the anterior leads. He complained of vague arm and leg weakness and tingling, but did not lose consciousness or suffer a cardiac arrest.
A CT scan was performed about 2-3 minutes after the patient deteriorated (Figure 1).
Figure 1. A-E: Representative images from CT scan in soft tissue windows. Lower: Video of CT scan in soft tissue windows.
What radiographic finding likely explains the patient’s clinical deterioration? (Click on the correct answer to be directed to the second of six pages)
Cite as: Savajiyani S, Singarajah CU. January 2020 critical care case of the month: a code post lung needle biopsy. Southwest J Pulm Crit Care. 2020;20(1):1-6. doi: https://doi.org/10.13175/swjpcc042-19 PDF
October 2019 Critical Care Case of the Month: Running Naked in the Park
Spencer Jasper MD
Matthew Adams DO
Jonathan Boyd MD
Jeremiah Garrison MD
Janet Campion MD
The University of Arizona College of Medicine
Tucson, AZ USA
History of Present Illness
A 34-year-old man with a history of IV drug abuse was brought into emergency department by EMS and Tucson Police Department after complaints of naked man running and behaving erratically in a park. On arrival to emergency department patient was acting aggressively towards staff, spitting and attempting to bite. The ER staff attempted multiple times to sedate the patient with benzodiazepines, however, due to continued aggressive behavior, ongoing encephalopathy and the need for increased sedation, the patient was intubated for airway protection.
The patient was febrile (40.6° C), tachycardic (122) and hypertensive (143/86). On physical exam patient was not cooperative, was diaphoretic, cachectic, with reactive constrictive pupils, track marks in antecubital fossa bilaterally. No clonus or hypertonicity. During intubation, there was noted to be nuchal rigidity.
He was then admitted to the medical ICU. Drug intoxication from possible methamphetamines was the presumptive diagnosis of encephalopathy but given nuchal rigidity and fevers there was concern for other etiologies.
Physical Exam
- Vitals: T 40.6 °C, HR: 122, RR: 22, BP: 143/86, SpO2: 97% WT: 55 kg
- General: Intubated and sedated, cachectic
- Eye: Pupils constricted but reactive to light
- HEENT: Normocephalic, atraumatic
- Neck: Stiff, non-tender, no carotid bruits, no JVD, no lymphadenopathy
- Lungs: Clear to auscultation, non-labored respiration
- Heart: Normal rate, regular rhythm, no murmur, gallop or peripheral edema
- Abdomen: Soft, non-tender, non-distended, normal bowel sounds, no masses
- Skin: Skin is warm, dry and pink, multiple abrasions on the lower extremities bilaterally, track marks noted in the antecubital fossa bilaterally. Large abrasion with bruising around the right knee and erythema and welts on the right shin. Erythematous area on the dorsal surface of the right hand
- Neurologic: Nonfocal prior to intubation, no clonus or hypertonicity noted
Drug overdose/intoxication was presumptive diagnosis for his acute encephalopathy. Based on physical exam and vitals, what other etiologies should be considered? (click on the correct answer to be directed to the second of seven pages)
Cite as: Jasper S, Adams M, Boyd J, Garrison J, Campion J. October 2019 critical care case of the month: running naked in the park. Southwest J Pulm Crit Care. 2019;19(4):110-8. doi: https://doi.org/10.13175/swjpcc054-19 PDF
Severe Accidental Hypothermia in Phoenix? Active Rewarming Using Thoracic Lavage
Michael Mozer BS1
Guy Raz, MD2
Ryan Wyatt, MD2
Alexander Toledo, DO, PharmD2
1University of New England College of Osteopathic Medicine
Biddeford, ME USA
2Department of Emergency Medicine
Maricopa Medical Center, Phoenix, AZ USA
Abstract
Hypothermia can progress quickly and become life threatening if left untreated. Rewarming in the severely hypothermic patient is of critical importance and is achieved with active and passive techniques. Here we present a case of a hypothermic patient with cardiac instability for whom thoracic lavage was ultimately used. We will review the treatment of hypothermia and discuss the technical aspects our approach.
Case Presentation
A 53 year-old male with a past medical history of substance abuse, chronic hepatitis C, and poorly controlled type 2 diabetes mellitus complicated by a recent hospitalization for osteomyelitis was brought to the emergency department after being found lying on a road in a shallow pool of water in the early morning hours of a rainy day in Phoenix, Arizona. The ambient temperature that night was 39 °F (3.9 °C). Emergency Medical Services (EMS) noted a decreased level of consciousness and obtained a finger stick glucose of 15 mg/dl. EMS reported a tympanic membrane temperature of 23.9 °C. En route, the patient was administered 2mg naloxone and 25g dextrose intravenously with no improvement in his mental status. On Emergency Department (ED) arrival, the patient had a GCS of 8 (Eyes 4, Verbal 1, Motor 3) and exhibited intermittent posturing. His foot wound appeared clean and without signs of infection. The initial core temperature recorded was 25.9°C via bladder thermometer, systolic blood pressure was 92/50, and heart rate fluctuated between 50 and 90 beats per minute.
After removing wet clothing, initiation of warmed saline, and placing a forced warm air blanket on the patient, he was intubated for airway protection and vasopressors were initiated. Osborn waves were evident on the initial EKG (Figure 1).
Figure 1. Initial EKG with Osborn Waves (arrows).
A warmed ventilator circuit was initiated with only 0.5 °C increase in temperature in first 30 minutes. Despite these measures, he remained hypotensive and unstable. Significant laboratory findings were a white blood cell count of 25.5 thousand (92% neutrophils), lactic acid of 7.6, potassium of 5.8, serum creatinine of 1.05, glucose of 283, INR of 1.1, and urine drug screen positive for cocaine. Given his recalcitrance to norepinephrine and risk of death secondary to fatal dysrhythmia with temperatures below 28 °C intrathoracic lavage initiated.
The right hemithorax was selected for irrigation because left-sided tube placement can induce ventricular fibrillation in a perfusing patient (1). Using standard sterile technique, two 36 French thoracostomy tubes were placed; the first in the second intercostal space along the mid-clavicular line, and the second in the 5th intercostal space in the posterior axillary line (1-3). The tips of the thoracostomy tubes were oriented such that the anterior-superior tube was positioned near the right apex and the lateral-inferior tip was positioned low in the thoracic cavity (1,3). To maintain the temperature of the instilled fluid, a fluid warmer system (Level 1; Smiths Medical; Minneapolis, MN) was used and set to 41 °C. A Christmas tree adapter was used to connect the IV tubing to the superior thoracostomy tube, and a water seal chamber was attached to the inferior tube for passive drainage (3). Flow through the system was targeted to maintain steady passive drainage as described in the literature (1-6).
Thoracic cavity lavage with 41 °C saline was performed and the patient was transferred to the medical ICU after 3 hours in the ED. When he was transferred his core temperature was 29 °C and he remained on norepinephrine for hemodynamic instability. After 2 hours of continued rewarming in the MICU, his core temperature was 32 °C. Osborn waves evident on initial EKG were resolved (Figure 2).
Figure 2. Repeat EKG showing resolution of Osborn waves.
The patient left against medical advice from the hospital 4 days later neurologically intact and without sequela.
Discussion
Hypothermia can be clinically classified as mild, moderate or severe (7). Mild hypothermia, defined as core temperatures of 32-35 °C, presents with shivering. Amnesia, dysarthria, ataxia, tachycardia, and tachypnea can also be seen (1). Moderate hypothermia, defined as core temperatures of 28-32 °C, usually can present with or without shivering. Stupor, hypoventilation, paradoxical undressing and non-fatal arrhythmias such as atrial fibrillation and junctional bradycardia may also be seen (1). Patients with severe hypothermia, generally defined as temperatures below 28 °C, can present with coma, areflexia, pulmonary edema, bradycardia, and hypotension (1). There is a significant risk of fatal cardiac dysrhythmias without rapid therapeutic rewarming (1,7,8).
Rewarming in the hypothermic patient is of critical importance and is achieved with passive and/or active techniques. Attempts to limit heat loss are often unsuccessful, especially in the absence of a normal shiver response. It however remains as the first line treatment for hypothermia (8-10). Passive rewarming is attempted by the removal of cold/wet clothing and keeping the patient covered (8-10). Active external rewarming (AER) is the next line of treatment and consist of the use of externally rewarming devices such as warmed blankets, warm environment, forced air warming (Bair Hugger; 3M; Maplewood, MN) or warm hot water bladders placed in the groin and axilla (1,7-10). Active Internal Rewarming (AIR) techniques can be used to achieve more rapid increases in core temperature and are primarily utilized in cases of cardiac instability or if AER is unsuccessful (8). When available, the method of choice for active internal rewarming (AIR) is cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) as they can achieve the fastest increase in core temperature (9 °C/hr and 6 °C/hr respectively) and provide cardiovascular support (1,8,11,12). Several techniques are described in the literature that can be considered if CPB or ECMO are unavailable. These include esophageal warming devices, endovascular catheters, hemodialysis, and endocavitary lavage (1,2,4-6,13-15). While no randomized controlled trials exist, several case reports and reviews have tried to compare various techniques. These sources to do not seem to favor any particular technique over another but rather reports the rates of temperature rise (1-3,5-7,13-15). Classically, lavage techniques are attempted in the thoracic cavity, the peritoneum, the bladder, the stomach, the esophagus, or the colon. These techniques are generally coupled with warm IV fluids and warming air through the ventilator to limit loss of body heat to iatrogenic procedures during the rewarming attempt (1,7). Thoracic lavage is effective with a reported rewarming rates of 3-6 °C/hr and with excellent outcomes in case reports (1,2,4-6). Here we present a case of a hypothermic patient with cardiac instability where thoracic lavage is used and discuss the technical aspects of this approach.
Our case demonstrates the efficacy of utilizing thoracic cavity lavage for rapid rewarming in patients with severe hypothermia with a pulse and at high risk of fatal cardiac arrhythmia. In multiple case reports, thoracic lavage has been used successfully in hypothermic patients who suffered complete cardiopulmonary collapse requiring CPR (2,4,5). Although warm thoracic lavage is not the treatment of choice in these circumstances, in a facility not equipped with ECMO or CPB and a patient too unstable to transfer, it seemed to us to be the best technique. Gastric, colonic, and bladder lavage offer very minimal heat transfer due to limitations in surface area (2).
Hemodialysis would have required for us to call in a technician and would have required approval by a nephrologist at our institution. Available central venous rewarming catheters require bypass of a failsafe mechanism that does not allow rewarming to be initiated below 30 °C (1). Peritoneal lavage was a plausible choice but does not directly warm the mediastinum (2). While an open mediastinal technique has been used, we did not feel it was appropriate in a patient with a concurrent pulse (1,3). Thoracic lavage is therefore an effective alternative that should be used in cases where CPB and ECMO are unavailable especially in a patient that is hemodynamically unstable and may not survive transfer. The equipment is readily available to any Emergency Medicine or Critical Care physician. In addition, this case exemplifies the positive outcomes that are associated with rapid rewarming in the hypothermic patient with a pulse. We believe our case demonstrates the efficacy of this technique for myocardial protection from hemodynamic collapse, a topic which has not been adequately studied in the literature.
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- Zafren K, Giesbrecht GG, Danzl DF, et al. Wilderness Medical Society practice guidelines for the out-of-hospital evaluation and treatment of accidental hypothermia: 2014 update. Wilderness Environ Med. 2014 Dec;25(4 Suppl):S66-85. [CrossRef] [PubMed]
- Schober A, Sterz F, Handler C, et al. Cardiac arrest due to accidental hypothermia-A 20 year review of a rare condition in an urban area. Resuscitation. 2014;85(6):749-56. [CrossRef] [PubMed]
- Saczkowski RS, Brown DJA, Abu-Laban RB, Fradet G, Schulze CJ, Kuzak ND. Prediction and risk stratification of survival in accidental hypothermia requiring extracorporeal life support: An individual patient data meta-analysis. Resuscitation. 2018;127:51-7.[CrossRef] [PubMed]
- Primozic KK, Svensek F, Markota A, Sinkovic A. Rewarming after severe accidental hypothermia using the esophageal heat transfer device: a case report. Ther Hypothermia Temp Manag. 2018 Mar;8(1):62-4. [CrossRef] [PubMed]
- Murakami T, Yoshida T, Kurokochi A, et al. Accidental hypothermia treated by hemodialysis in the acute phase: three case reports and a review of the literature. Intern Med. 2019 Jun 7. [CrossRef]
- Klein LR, Huelster J, Adil U, et al. Endovascular rewarming in the emergency department for moderate to severe accidental hypothermia. Am J Emerg Med. 2017 Nov;35(11):1624-9. [CrossRef] [PubMed]
Cite as: Mozer M, Raz G, Wyatt R, Toledo A. Severe accidental hypothermia in Phoenix? Active rewarming using thoracic lavage. Southwest J Pulm Crit Care. 2019;19(2):79-83. doi: https://doi.org/10.13175/swjpcc038-19 PDF
Left Ventricular Assist Devices: A Brief Overview
Bhargavi Gali MD
Department of Anesthesiology and Perioperative Medicine
Division of Critical Care Medicine
Mayo Clinic Minnesota
Rochester, MN, USA
Introduction
Second and third generation left ventricular assist devices (LVAD) have been increasingly utilized as both a bridge to transplantation and as destination therapy (in patients who are not considered transplant candidates) for advanced heart failure. Currently approximately 2500 LVADs are implanted yearly, with an estimated one year survival of >80% (1). Almost half of these patients undergo implantation as destination therapy. A recent systematic review and meta-analysis found no difference in one-year mortality between patients undergoing heart transplantation in comparison with patients undergoing LVAD placement (2).
Early LVADs were pulsatile pumps, but had multiple limitations including duration of device function, and requirement for a large external lead that increased risk of infection. Currently utilized second and third generation devices are continuous flow (first generation were pulsatile flow). Second generation devices have axial pumps (HeartMate II®). The third generation LVADs ((HeartMate III®), HVAD®) are also continuous flow, with centrifugal pumps, which are thought to decrease possibility of thrombus formation and increase pump duration in comparison to the second generation axial pumps. It is also felt that a lack of mechanical bearings contributes to this effect.
LVADs support circulation by either replacing or supplementing cardiac output. Blood is drained from the left ventricle with inflow cannula in the left ventricular apex to the pump, and blood is returned to the ascending aorta via the outflow cannula (3) (Figure 1).
Figure 1. Third generation Left Ventricular Assist Device. Heartware System ™. Continuous flow left ventricular assist device (LVAD) configuration. One of the third generation LVADs is the HeartWare System. With this device the inflow cannula is integrated into the pump. The pump is attached to the heart in the pericardial space, with the outflow cannula in the aorta. A driveline connects the device to the control unit. This control unit is attached to the two batteries. (Figure used with permission from Medtronic).
The device assists the left ventricle by the action of the axial (second generation) or centrifugal (third generation) pump that rotates at a very high speed and ejects the blood into the aorta via the outflow cannula. A tunneled driveline connects the pump to the external controller that operates the pump function. The controller connects to the power source via two cables, which can be battery or module-powered.
LVADs offload volume from the left ventricle, and decrease left ventricular work. Pulmonary pressures and the trans pulmonary gradients are also decreased by the reduced volume in the left ventricle (4). End organ perfusion is improved secondary to enhanced arterial blood pressure and micro perfusion.
There are four main parameters of pump function:
- Pump speed: the speed at which the LVAD rotors spin, and is programmed. Measured in RPM.
- Pump power: the wattage needed to maintain speed and flow, which is the energy needed to run the pump. Measured in Watts.
- Pump flow: estimate of the cardiac output, which is the blood returned to the ascending aorta, and is based on pump speed and power. Measure in L/min
- Pulsatility index (PI): a calculated value that indicates assistance the pump provides, in relation to intrinsic left ventricular A higher number indicates higher left ventricular contribution to pulsatile flow.
The cardiac output of currently utilized LVADs is directly related to pump speed and inversely related to the pressure gradient across the pump. As the pump speed is fixed, right ventricular failure can decrease the volume of blood transmitted to the pump and decrease LVAD flow (3, 4). With right ventricular failure, inotropic support may be needed to improve the LVAD pump flow. High afterload, such as may be seen with an increase in systemic vascular resistance can decrease pump flow.
Complications
Adverse events occur in more than 70% of LVAD patients in the first year (5). These complications include infections, bleeding, stroke, and LVAD thrombosis. More than 50% of patients are readmitted within the first 6 months after LVAD implantation (6).
Driveline infections are the most commonly reported LVAD infection, and are the most likely to respond to treatment (7). Pump pocket infections may require debridement plus/minus antibiotic bead placement. Bloodstream infections are less commonly reported, and more difficult to treat, and many patients are placed on chronic suppressive antibiotic therapy (7). There is a possible association between stroke and bloodstream infection, reported in some studies. Patients who were younger and had a higher body mass index were noted to have a higher incidence of LVAD infections.
Gastrointestinal bleeding is a major cause of nonsurgical bleeding, reported in almost 30% of patients after LVAD placement (1). Patients may develop acquired von Willebrand factor deficiency secondary to high shear forces in the LVAD that lead to breakdown of von Willebrand protein (6). Antithrombotic therapy is commonly instituted after LVAD implantation which also increases risk of bleeding. A high incidence of arteriovenous malformations is reported in these patients, although the etiology is not clear. Transfusion, holding antithrombotic therapy, and identifying possible sources are included in the standard approach to management.
There is a high risk of both ischemic and hemorrhagic strokes in the first year after LVAD placement (8). Surgical closure of the aortic valve and off-axis positioning of the cannulas have been suggested as altering shear forces, increasing thrombotic risk, and thus risk of stroke. Post-surgical risks may include pump thrombosis, infections, supratherapeutic INR, and poorly controlled hypertension. Early diagnosis has led to consideration of interventions such as thrombectomy (8).
LVAD thrombosis can occur on either cannula (inflow or outflow) or the pump. Typically patients receive ongoing anticoagulation, commonly with warfarin, and antiplatelet agents, and often aspirin. Heartmate II® may have higher rate of thrombosis than HVAD or Heart Mate 3, although this is under debate (6). Thrombotic complications range in severity from asymptomatic increase in lactate dehydrogenase or plasma-free hemoglobin, to triggering of LVAD alarms, up to development of heart failure. The inflow and outflow cannulas and pump can be the site of thrombosis. Management typically involves revising the antithrombotic management. If there is no improvement or worsening, replacement of LVAD may be indicated. There is limited evidence to suggest that systemic thrombolysis may be of benefit in treating pump thrombosis, particularly in regards to the HVAD, though better data would be useful
Procedural Management
When a patient with an LVAD requires non cardiac surgery, optimal management includes having an on-site VAD technician, and close involvement of VAD cardiology and cardiac surgery in consultation. Anticoagulation will often be transitioned to heparin infusion prior to elective procedures (9). Suction events (LV wall is sucked into the inflow cannula) can occur secondary to under filled left heart, and this can become more apparent perioperatively. This can also decrease right heart contractility by moving the interventricular septum to the left, and thus decrease cardiac output. Management often involves fluid bolus. Suction events can lead to decreased flow, left ventricular damage, and ventricular arrhythmias. Hemodynamic management can be challenging with non-pulsatile flow, and placement of an arterial line can facilitate optimal management. Postoperative care in a monitored setting is beneficial in case of further volume related events and to watch for bleeding.
Emergent Complications
Arrhythmias occur in many patients after LVAD implantation. Atrial arrhythmias are reported in up to half of LVAD patients, and ventricular arrhythmias in 22-59% (10, 11). Loss of AV synchrony can lead to decreased LV filling and subsequent RV failure. Rhythm or rate control with rapid atrial arrhythmias is necessary to decrease development of heart failure. Ventricular arrhythmias may be hemodynamically tolerated for some time secondary to the LVAD support (6). If there is concern that the inflow cannula is touching the LV septum, as may occur with severe hypovolemia, echocardiography can help determine if volume resuscitation should be the initial step in treating ventricular arrhythmia.
If cardiac arrest occurs, the first step of cardiopulmonary resuscitation in patients with LVAD is assessment of appropriate perfusion via physical examination (12). If perfusion is poor or absent, assessment of LVAD function should take place. If the LVAD is not functioning appropriately, checking for connections and power is the next step. If unable to confirm function or restart LVAD, chest compressions are indicated by most recent guidelines from the American Heart Association. There is always concern of dislodgement of LVAD cannula or bleeding during these situations.
Conclusion
Currently implanted LVADS are continuous flow, and provide support via a parallel path from the left ventricle to the aorta. As the number of patients with LVADs increase all medical providers should have a basic understanding of the function and common complications associated with these devices. This will enhance the ability to initiate appropriate care.
References
- Kirklin JK, Pagani FD, Kormos RL, et al. Eighth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Transplant. 2017 Oct;36(10):1080-6. [CrossRef] [PubMed]
- Theochari CA, Michalopoulos G, Oikonomou EK, et al. Heart transplantation versus left ventricular assist devices as destination therapy or bridge to transplantation for 1-year mortality: a systematic review and meta-analysis. Annals of Cardiothoracic Surgery. 2017;7(1):3-11. [CrossRef] [PubMed]
- Lim HS, Howell N, Ranasinghe A. The physiology of continuous-flow left ventricular assist devices. J Card Fail. 2017;23(2):169-80. [CrossRef] [PubMed]
- Roberts SM, Hovord DG, Kodavatiganti R, Sathishkumar S. Ventricular assist devices and non-cardiac surgery. BMC Anesthesiology. 2015;15(1):185. [CrossRef] [PubMed]
- Miller LW, Rogers JG. Evolution of left ventricular assist device therapy for advanced heart failure: a review. JAMA Cardiol. 2018 Jul 1;3(7):650-8. [CrossRef] [PubMed]
- DeVore AD, Patel PA, Patel CB. Medical management of patients with a left ventricular assist device for the non-left ventricular assist device specialist. JACC Heart Fail. 2017 Sep;5(9):621-31. [CrossRef] [PubMed]
- O'Horo JC, Abu Saleh OM, Stulak JM, Wilhelm MP, Baddour LM, Rizwan Sohail M. Left ventricular assist device infections: a systematic review. ASAIO J. 2018 May/Jun;64(3):287-294. [CrossRef] [PubMed]
- Goodwin K, Kluis A, Alexy T, John R, Voeller R. Neurological complications associated with left ventricular assist device therapy. pert Rev Cardiovasc Ther. 2018 Dec;16(12):909-17. [CrossRef] [PubMed]
- Barbara DW, Wetzel DR, Pulido JN, et al. The perioperative management of patients with left ventricular assist devices undergoing noncardiac surgery. Mayo Clinic Proceedings. 2013;88(7):674-82. [CrossRef] [PubMed]
- Enriquez AD, Calenda B, Gandhi PU, Nair AP, Anyanwu AC, Pinney SP. Clinical impact of atrial fibrillation in patients with the heartmate ii left ventricular assist device. J Am Coll Cardiol. 2014 Nov 4;64(18):1883-90. [CrossRef] [PubMed]
- Nakahara S, Chien C, Gelow J, et al. Ventricular arrhythmias after left ventricular assist device. Circ Arrhythm Electrophysiol. 2013 Jun;6(3):648-54. [CrossRef] [PubMed]
- Peberdy MA, Gluck JA, Ornato JP, et al. Cardiopulmonary resuscitation in adults and children with mechanical circulatory support: a scientific statement from the American Heart Association. Circulation. 2017;135(24):e1115-e34.`[CrossRef] [PubMed]
Cite as: Gali B. Left ventricular assist devices: a brief overview. Southwest J Pulm Crit Care. 2019;19(2):68-72. doi: https://doi.org/10.13175/swjpcc039-19 PDF
July 2019 Critical Care Case of The Month: An 18-Year-Old with Presumed Sepsis and Progressive Multisystem Organ Failure
Robert A. Raschke, MD
The University of Arizona College of Medicine – Phoenix
Phoenix, AZ USA
History of Present Illness
An 18-year-old female student from Flagstaff was transferred to our hospital for refractory sepsis. She had presented with a 2 week history of fever, malaise, sore throat, myalgias, arthralgias and a rash.
PMH, SH and FH
She reported no significant past medical history or family history. She attended cosmetology school, denied smoking or drug abuse and was sexually monogamous. She had only traveled in-state, did not hike or camp and her only animal exposure was playing with her two pet Great Danes.
Physical Examination
The patient had a fever of 38.5°C. on original presentation. HEENT exam was reported as unrevealing. Lungs were clear. There were no heart murmurs and the abdominal exam was unremarkable. No joint effusions were apparent. A rash was mentioned, but not described and it apparently disappeared shortly after admission.
Initial laboratory testing was significant for WBCC of 12.1 K/mm3, creatinine of 1.5 mg/dL and AST of 45 IU/L. A rapid influenza screen, urinalysis and chest radiography were unrevealing. Blood cultures were drawn and intravenous fluids, piperacillin/tazobactam and azithromycin were administered. Over the next four days, the fever persisted and the blood cultures resulted in no growth. Serial laboratory values demonstrated progressive worsening in renal function and increasing hepatic enzymes. The patient became dyspneic and developed rales and progressive hypoxia prompting transfer.
On arrival in our ICU, the patient was alert, in mild respiratory distress and hypotensive to 78/43 mmHg, requiring immediate initiation of intravenous norepinephrine. She reported nausea and severe diffuse myalgia and arthralgia. On examination, she was ill-appearing with blood pressure 101/58 (on norepinephrine at 25 mcg/min), heart rate 104 beats/min, respiratory rate 33 breaths/min, temperature 38.8°C. She had mild oropharyngeal erythema, some shotty cervical lymph nodes, bilateral rales, mild epigastric and right upper quadrant tenderness, and a macular erythematous rash approximately 14 x 29 cm on her left forearm that disappeared within several hours.
Her ICU admission chest x-ray is shown in Figure 1.
Figure 1. Admission ICU portable chest X-ray showing bilateral areas of consolidation.
Her laboratory evaluation showed the following:
- WBCC: 2,500/mm3 63% segs with toxic granulation/vacuolated segs
- Hemoglobin/Hematocrit: 7.9 g/dL/26.7%
- Platelets: 50,000/mm3
- BUN/creatinine: 23/1.25 mg/dL
- AST/ALT: 246/189 IU/L (normal 10-40 and 7-56)
- PT: 20.9 sec
- Lactate: 4.5 mmol/L
- Urinalysis: bland sediment, without bacteria or leukocytes
- ABG: 7.33, pCO2 34, pO2 78 (on 45% FiO2 by ventimask)
- Transthoracic echocardiogram showed normal LV and RV size and systolic function with no vegetations
- US abdomen showed hepatosplenomegaly, retroperitoneal lymphadenopathy, and normal kidneys and ureters.
What are diagnostic considerations at this time? (Click on the correct answer to be directed to the second of six pages)
- Rocky mountain spotted fever (RMSF)
- Acute retroviral syndrome
- Still’s disease
- Systemic lupus erythematosus (SLE)
- All of the above
Cite as: Raschke RA. July 2019 critical care case of the month: an 18-year-old with presumed sepsis and progressive multisystem organ failure. Southwest J Pulm Crit Care. 2019;19(1):1-9. doi: https://doi.org/10.13175/swjpcc043-19 PDF
An Observational Study Demonstrating the Efficacy of Interleukin-1 Antagonist (Anakinra) in Critically-ill Patients with Hemophagocytic Lymphohistiocytosis
Kyle Henry MD, Banner University Medical Center
Robert Raschke MD, University of Arizona College of Medicine-Phoenix
Phoenix, AZ USA
Abstract
Secondary Hhmophagocytic lymphohistiocytosis (HLH) is an underrecognized cause of multisystem organ failure (MSOF) in critically ill adults, associated with high mortality even when recommended etoposide-based treatments are administered. Anakinra, an interleukin-1 receptor antagonist, has shown promise in treating children with HLH. This retrospective case series describes seven adult patients who presented to our ICU with a unremitting syndrome consistent with sepsis / MSOF, who were subsequently diagnosed with secondary HLH and received anakinra. Five of seven (71%) survived. Two non-survivors died secondary to opportunistic fungal infections. Our study contributes to mounting observational evidence regarding anakinra’s possible efficacy in critically ill adults with HLH, and also raises awareness of possible infectious complications of its use.
Introduction
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by immune dysregulation, hypercytokinemia and tissue infiltration by activated cytotoxic lymphocytes and macrophages (1-3). Primary HLH is a familial syndrome in which gene mutations causing abnormalities of cytotoxic T-lymphocyte and natural killer (NK) cell function result in a systemic hyperinflammatory state. Primary HLH typically presents in the first years of life, progressing to multisystem organ failure (MSOF) and death unless successfully treated with chemotherapy and bone marrow transplantation. Secondary HLH shares clinical features with primary HLH but typically occurs later in life after an underlying illness triggers a dysregulated inflammatory response (3, 4). The diagnosis of primary or secondary HLH is made when five of eight criteria proposed by the International Histiocyte Society are met (Table 1) (5). Heterogeneous groups of patients may satisfy HLH diagnostic criteria, including those in whom HLH is triggered by sepsis, malignancy, and rheumatologic disease (4). Macrophage Activation Syndrome (MAS) is a specific HLH subcategory describing those patients with secondary HLH due to underlying rheumatologic disease (2). The clinical course of secondary HLH is highly variable, progressing relatively slowly in some patients in whom a diagnosis may be made in an outpatient oncology or rheumatology clinic (2, 4, 6-9). Other patients deteriorate rapidly and may require ICU care before the diagnosis of HLH is suspected (3). It has been increasingly recognized that subgroups of patients with HLH have distinctive clinical features, and require special treatment considerations (1, 3-5, 10).
One distinct subgroup consists of adults who present to the intensive care unit (ICU) with sepsis syndrome and MSOF with progressive deterioration despite standard therapy for sepsis (3). Life threatening manifestations in such patients suspected of experiencing HLH may force consideration of presumptive immunotherapy before all HLH diagnostic tests have resulted. Infectious and/or rheumatologic triggers for secondary HLH are eventually found in many, but a clear distinction between sepsis and HLH cannot be made in some (3, 4, 10, 11). The standard treatment protocol for HLH incorporates etoposide – a myelosuppressive chemotherapy agent generally regarded as the standard of care, but has known serious side effects, especially in the setting of hepatic or renal dysfunction typical of sepsis (5, 12). Furthermore, etoposide-based HLH treatment may cause severe immunosuppression leading to opportunistic infections. The mortality of secondary HLH in the adult ICU exceeds 50% (13-16) regardless of the underlying catalyst for the hypercytokinemia. New therapeutic options are desperately needed.
Mounting observational evidence suggests that Anakinra, a recombinant interleukin-1 receptor antagonist (IL-1Ra), may have promise in the treatment of HLH (6,17). Naturally-occurring IL-1Ra is secreted by immune cells to inhibit the pro-inflammatory effects of interleukin 1β (IL-1β) – a key cytokine in the pathogenesis of sepsis and HLH (7, 18). Anakinra was originally developed as a potential therapy for sepsis (7), but is now FDA-approved for use in rheumatoid arthritis. A single case-series describes the successful use of anakinra in critically-ill children with secondary HLH and a few case reports describe its use in critically-ill adults (6, 8, 19, 20). More recently, Wohlfarth and colleagues showed that anakinra is a reasonable option for critically ill patients adults with HLH. At the same time Wohlfarth et al were studying these effects in an Austrian population, we demonstrated similar results in a series of adult patients in the United States who presented to the ICU with sepsis syndrome and underwent treatment with anakinra for secondary HLH.
Methods
This retrospective study was approved by our institutional review board. The setting was the medical and surgical ICU at Banner-University Medical Center Phoenix – a 72-bed ICU in a 650-bed academic tertiary referral center. We identified consecutive adult patients at least 18 years old admitted with sepsis syndrome (known or suspected infection plus acute organ system dysfunction) (21) who subsequently met five or more HLH-2004 diagnostic criteria (Table 1) and received anakinra as part of their treatment regimen between May 2013 and May 2016.
Table 1. HLH-2004 Diagnostic Criteria for Secondary HLH: At least five of eight criteria needed for diagnosis.
Clinical management of patients was not strictly protocolized, but care was provided by an academic 24/7 on-site intensivist service with strong internal consensus regarding the management of HLH. All patients had at least daily complete blood counts and basic metabolic panels. In our practice, diagnostic workup for HLH generally commences upon recognition of unremitting sepsis syndrome with MSOF and bicytopenia. Such patients underwent workup for sepsis and potential causes of secondary HLH that included at minimum: blood cultures, ferritin, fibrinogen, triglycerides, bone marrow aspiration and biopsy, PCR and/or serological testing for systemic lupus erythematosus (SLE), Epstein-Barr virus (EBV), cytomegalovirus, herpes simplex virus, human immunodeficiency virus, hepatitis viruses and coccidioidomycosis (a mycosis endemic in the region). The decision to start HLH therapy was typically based on clinical suspicion plus consistent preliminary laboratory results such as hyperferritinemia, hypofibrinogenemia and/or hypertriglyceridemia, while awaiting the complete results of bone marrow aspiration/biopsy and send-out tests such as soluble interleukin-1 receptor and NK cell functional assays. Presumptive treatment of HLH began with corticosteroids - typically intravenous dexamethasone 10mg/m2 daily. Additional therapies were added at the discretion of the intensivist with consideration of the rapidity of clinical deterioration and likely intolerance of some therapies due to kidney, liver, and/or bone marrow failure. Choice of HLH therapies was based on the HLH-1994 therapy protocol, and influenced by our prior unfavorable experience with etoposide (discussed in conclusions) and recognition of observational literature suggesting that anakinra might be efficacious in patients with secondary HLH. Anakinra was typically given in a dose of 100mg subcutaneously daily, except in patients with creatinine clearance <30ml/min who were dosed every other day.
We retrospectively performed chart reviews to abstract demographics and clinical features related to sepsis and MSOF including infections present on admission, mental status, acute respiratory failure requiring mechanical ventilation, acute renal failure requiring hemodialysis, shock requiring intravenous vasopressors, and liver injury (defined as total bilirubin >2 mg/dL and aminotransferase greater than two times upper limit of normal) (22). The sequential organ failure assessment (SOFA) score was calculated for each patient (21). HLH-2004 diagnostic criteria and the underlying disease process thought to have triggered HLH were abstracted. We documented all treatments including antibiotics and immunosuppressive therapy for HLH, including the dose and duration of anakinra. Outcomes included survival to hospital discharge, duration of fever, mechanical ventilation and renal replacement therapy and ICU length of stay indexed to the time anakinra commenced. Infectious complications occurring during admission after HLH therapy started were also documented. Simple descriptive statistics were performed.
The H Score for each patient was also calculated retrospectively. The H Score is a score used to estimate an individual's risk for having secondary HLH and was recently validated in a 147 patient cohort by Debaugnies et al. (23).
Results
Seven patients were treated with anakinra for a diagnosis of secondary HLH in our ICU between May 2013 and May 2016. Patient ages ranged from 22-59 years – three were female. All patients initially presented to our ICU with a febrile illness consistent with sepsis and received broad-spectrum intravenous antibiotics. Microbiological testing eventually documented infections in two patients – due to influenza A and EBV, respectively. All patients were encephalopathic, five required mechanical ventilation, four required hemodialysis due to acute renal failure, four had liver injury and three required vasopressors due to shock (Table 2).
Table 2. Patient characteristics and some clinical outcomes.
The median SOFA score was 13 (range: 3-17) predicted poor outcome for the group overall (13-16). H Scores for this cohort ranged from 122-263. HLH diagnostic criteria and presumed etiologies are listed in Table 3.
Table 3. Suspected etiology and positive HLH-2004 diagnostic criteria for secondary HLH in patients treated with anakinra: Five of eight criteria required to diagnose HLH.
Two patients were known to have SLE prior to ICU admission and four others were subsequently diagnosed with underlying autoimmune diseases demonstrating a preponderance of MAS in this cohort.
All patients initially received corticosteroids (dexamethasone 10mg/m2 or methylprednisolone >500mg every 12 hours) followed by anakinra. Three patients also received cyclosporine, three underwent plasmapheresis and two received IVIG. Only one patient received etoposide and this was later transitioned to anakinra due to lack of response. Anakinra was started a median of seven days after ICU admission (range 2-58 days). All patients received anakinra 100mg daily, but Q48 hour dosing was used temporarily in five patients who transiently experienced creatinine clearances <30mL/min. Duration of anakinra therapy was 10-159 days - we were unable to determine duration of anakinra after discharge in one patient.
All patients appeared to clinically improve after initiation of anakinra. Of six patients experiencing fever at the time anakinra was started, five defervesced within 24 hours. In five patients that had follow-up ferritin levels within two weeks of starting anakinra, ferritin fell from a median of 7,371 ng/L (range 2,217->40,000) to 4,535 ng/L (range 2,137-26,634). Five of seven patients (71%) survived to hospital discharge with an ICU length of stay (LOS) ranging from 6-17 days and an overall LOS of 17-103 days. Once anakinra was started, liberation from the ventilator occurred within 1-3 days, transfer out of the ICU within 3-5 days, discharge from the hospital within 10-32 days and discontinuation of hemodialysis within 10-44 days.
Death in both non-survivors was due to opportunistic fungal infections - necrotizing pulmonary aspergillosis and disseminated mucormycosis (which occurred despite prophylaxis with amphotericin B). Three other secondary infections all occurred in a single survivor: methicillin-sensitive S. aureus and E coli bacterial ventilator-associated pneumonias and C. difficile colitis all of which responded favorably to treatment while anakinra was continued.
Discussion
Secondary HLH may be more common in the ICU than previously recognized (3), overlapping with and at times indistinguishable from sepsis (3, 4, 10, 11). Rapid clinical deterioration in patients with suspected HLH may force treatment decisions to be made before full diagnostic test results are available. The risk of myelosuppression due to etoposide-based HLH treatment regimens may be intolerable in critically-ill, possibly septic patients with MSOF (4, 12). A therapeutic agent with a more HLH-specific mechanism of action and better safety profile is badly needed.
Anakinra is a recombinant IL-1Ra originally investigated as a potential immune-modulatory treatment for sepsis (7). Phase I and II studies established acceptable safety for further study in sepsis, but a phase III trial failed to demonstrate an overall survival benefit (7). A post-hoc analysis of data from this trial showed that septic patients with hepatobiliary dysfunction, hypofibrinogenemia and thrombocytopenia, such as often seen in secondary HLH, had significantly improved survival if they received anakinra vs placebo (65% vs. 35% 28-day survival, p=0.0007) (7). Anakinra was later approved for use in rheumatoid arthritis (18). Observational studies suggested efficacy in adult onset Still’s disease and systemic juvenile arthritis (9, 24, 25) and in non-critically-ill patients with secondary HLH triggered by these rheumatologic diseases (9, 25, 26). Case reports described the use of anakinra in critically-ill children with secondary HLH (25, 26, 27) and Rajasekaran and colleagues published a case series describing their experience using anakinra in eight critically-ill pediatric patients with secondary HLH/sepsis syndrome (6). All eight patients survived their initial illness, and no infectious complications were attributed to anakinra.
Fourteen cases describing the use of anakinra in adults with secondary HLH have previously been published (6, 8 ,17, 19, 20, 28). Four were due to infections (EBV, CMV, MAC, histoplasmosis, four to autoimmune disease (two with AOSD, SLE antisynthetase syndrome), two post transplantation immunosuppression, one due to acute lymphocytic leukemia and three of unknown trigger. Twelve of 15 (80%) required life support (mechanical ventilation, hemodialysis, vasopressors). All but two received corticosteroids and just over half IVIg. Overall survival was 67%, and no complications of immunosuppression were reported.
The mechanism by which anakinra might ameliorate secondary HLH is not fully elucidated. Secondary HLH (and some forms of sepsis) are characterized by high levels of circulating cytokines including interleukin-6 (IL-6), tumor necrosis factor and interferon-gamma (IFN-γ) (2, 4, 7, 18, 29) - constituting what some have called a “cytokine storm”. Many investigators believe that hypercytokinemia is pathogenic in HLH. Renal failure, cytopenia, coagulopathy and cholestasis have been associated with elevated levels of IL-6 and IFN-γ (2, 18, 28). IL-1β activates lymphocytes responsible for production of these same cytokines (2, 7, 18, 28). IL-1Ra is a competitive inhibitor of IL-1β (7, 29). Therefore IL-1 receptor antagonism by anakinra might inhibit the maladaptive hypercytokinemia characteristic of secondary HLH. This brief explanation oversimplifies a complex and poorly-understood process that requires much further research.
The observed survival rate in our adult patients treated with anakinra (71%) appears favorable compared to that described in other comparable groups of patients (13-16) with survival rates ranging from 25-41%, although we cannot definitively attribute this to treatment effect. It is notable that the majority of our patients had MAS, which has a improved prognosis compared to other forms of HLH when it presents in the outpatient setting, but similar high mortality once the patient develops MSOF and requires intensive care (13-16). This finding supports the concept that secondary HLH of any cause is related to a cytokine storm universal to all underlying catalysts, and that after a critical point the inflammatory cascade becomes increasingly difficult to reverse.
We have previously diagnosed and treated a total of 29 cases of secondary HLH in our ICU. Survival among 22 patients who did not receive anakinra was 14%. This group included eight patients who received etoposide, all of whom died or developed severe neutropenia (WBC <0.5 X 109/L) within a week of its initiation. The patient who survived etoposide did so after her regimen transitioned to anakinra. Statistical comparison of patients in our practice who did or did not receive anakinra was not undertaken due to potential bias and confounding. Controlled prospective trials are required to determine whether anakinra will improve survival of patients with secondary HLH. One such trial is currently under way (ClinicalTrials.gov Identifier: NCT02780583) specifically in regards to MAS.
Two of our patients died from opportunistic fungal infections. Fatal fungal infections have previously been reported to occur in patients receiving treatment for HLH who did not receive anakinra (28) and are likely a result of multiple risk factors including the underlying immune dysregulation associated with HLH, other immunosuppressive therapies and invasive procedures related to ICU care (30, 31), and therefore these infections cannot be specifically attributed to anakinra. We consider prophylactic posaconazole or amphotericin therapy in selected ICU patients at high risk for fungal infections given the evidence of invasive fungal infection prophylaxis including mucormycosis in similarly immunocompromised patients (30, 31).
Conclusions
Our study contributes to mounting observational evidence supporting the hypothesis that anakinra may be efficacious in adult patients presenting to the ICU with life-threatening secondary HLH. In our opinion, it can be considered as first line therapy, in combination with corticosteroids and IVIg, in selected patients for whom renal, hepatic and bone marrow dysfunction put them at higher risk of toxicity due to etoposide. Vigilance is warranted in relation to opportunistic infections, particularly those due to fungi. Prospective controlled trails are needed to definitively establish effective therapy of HLH.
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Cite as: Henry K, Raschke RA. An observational study demonstrating the efficacy of interleukin-1 antagonist (anakinra) in critically-ill patients with hemophagocytic lymphohistiocytosis. Southwest J Pulm Crit Care. 2019;18(6):177-86. doi: https://doi.org/10.13175/swjpcc034-19 PDF
Editor's Note: The July 2019 Critical Care Case of the Month is a case presentation of HLH with 0.5 Hour CME credit. Click on the link to be directed to the case.
Which Half Are You? Almost Half of Pediatric Oncologists and Intensivists Are Burnt Out……
K. Sarah Hoehn, MD, MBe1
Manjusha Abraham, MD2
John Gaughan, PhD3
Brigham C. Willis, MD4
1Department of Pediatric Critical Care, University of Chicago Comer Children’s Hospital, Chicago IL
2Department of Pediatrics, Section of Critical Care, St. Mary’s Hospital, St Louis MO
3Biostatistics Consulting Center, Temple University School of Medicine, Philadelphia, PA
4Division of Cardiovascular Intensive Care, Department of Child Health, University of Arizona College of Medicine – Phoenix and Phoenix Children’s Hospital, Phoenix, AZ
Abstract
Objective: To study the prevalence of burnout, secondary traumatic stress, and wellbeing among pediatric critical care and pediatric hematology and oncology physicians
Design: Observational cohort study
Setting: Online survey
Patients: Active American Academy of Pediatrics (AAP) members of the section of critical care and the section of hematology and oncology
Interventions: Surveys containing three validated instruments (the Maslach Burnout Inventory, the secondary traumatic stress scale and the Personal Wellbeing Index, as well as questions on demographics and lifestyle) were emailed out via the AAP.
Measurements and Main Results: We had 231 respondents with a response rate of 15.8% among PICU physicians and 26.1% among hematology-oncology physicians. 45.9% of our participants consisted of hematology-oncology physicians and 54.1% of pediatric critical care physicians. The population was a balanced gender mix but was predominantly Caucasian (82% Caucasian and 10% Asian). The overall rate of burnout was 46.6% (47.8% among hematology-oncology physicians and 45.8% among pediatric intensivists). We found significant rates of emotional exhaustion, with 43.0% of respondents scoring high on this subscale.
The prevalence of secondary traumatic stress was 46.8% (42.5% among hematology-oncology physicians and 50.9% among pediatric intensivists). Physicians in practice over 10 to 15 years had significantly higher rates of secondary traumatic stress (p < 0.05). No other demographic or lifestyle variable was significantly associated with an increased risk of burnout or secondary traumatic stress.
Conclusion: Our study reports concerning rates of burnout and secondary traumatic stress among pediatricians in the specialties of Hematology/Oncology and Pediatric Critical Care Medicine. The results raise concern for better screening and prevention for burnout in these high risk specialties. Promoting recognition of early symptoms is crucial, as well as creating a work environment that promotes mental health.
Background
For millennia, physicians have promised to take care of patients to the best of our abilities. In doing so, physicians make personal sacrifices and face challenging situations, including significant administrative burdens of the electronic medical record; all of which may contribute to burnout (1). This led to the AMA supporting a Charter of Physician Well Being, highlighting the importance of building resilience among physicians (2). The topic of physician burnout as one of the leading stories in 2017 (3). Physicians have a have a higher rate of burnout compared to US workers in other fields (4). Burnout has been defined as “a syndrome of emotional exhaustion and cynicism that occurs frequently among individuals who do ‘people-work’ of some kind” (5). Burnout syndrome has 3 key dimensions: emotional exhaustion, depersonalization and lack of personal accomplishment. These problems can affect not only physicians themselves but also patient care. Studies show that burnout is more common among physicians who are 11-20 years in practice (6). A German study suggests that female senior physicians having children are at the greatest risk for burnout (7).
Along with burnout, physicians may face post-traumatic stress. It has become increasingly more evident that trauma does not only affect the individual(s) directly involved, but also others around them, including healthcare workers. Thus, the concept of secondary traumatic stress has been defined. Secondary traumatic stress (STS) is defined as “the natural, consequent behaviors and emotions resulting from knowledge about a traumatizing event experienced by a significant other. It is the stress resulting from helping or wanting to help a traumatized or suffering person” (8). STS has been studied in a variety of caregiving populations, including social workers, nurses, chaplains, and child life specialists, but there is only limited to no data on STS among pediatric physicians (9-12).
In studying the prevalence of burnout and secondary traumatic stress among physicians, we would be remiss not to also assess the overall wellbeing of these individuals. Wellbeing is defined as “a relative state where one maximizes his or her physical, mental, and social functioning in the context of supportive environments to live a full, satisfying, and productive life”. The measurement of wellbeing in all Americans is a Healthy People 2020 objective (13).
We used standardized instruments to assess the prevalence of burnout, the prevalence of secondary post-traumatic stress, and the overall wellbeing of high-risk pediatric physicians. We hypothesized that pediatric critical care physicians and pediatric hematology/oncology physicians would have similarly high rates of burnout, STS and adverse effects on overall wellbeing.
Methods
The study was reviewed and approved by the Institutional Review Board of Kansas University Medical Center via expedited review. Four questionnaires (Maslach Burnout Scale, Secondary Traumatic Stress, Personal Wellbeing Index, demographic survey) were emailed to the section of critical care medicine and the section on pediatric hematology and oncology of the American Academy of Pediatrics. Reminders to complete the surveys were sent out at 4 and 6 weeks after the initial email. No identifiable data was recorded.
Maslach Burnout Inventory (MBI)
The Maslach Burnout Inventory (MBI) was developed to study burnout syndrome, and has 3 sub scales focusing on the areas of emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA). It consists of 22 items on a questionnaire that uses a six point Likert scale (Appendix 1). A high degree of burnout is reflected by high scores on the emotional exhaustion and depersonalization scale in addition to low scores on the personal accomplishment scale. The MBI has been shown to have coefficient alpha between 0.70 to 0.80 in 84 different studies that used the MBI to assess burnout, indicating that the MBI has good internal consistency in low stakes testing (14). Since its initial publication in 1980, the MBI has been shown to adequately assess the presence or absence of burnout in a variety of physician groups (15-19). In our study we defined burnout as the presence of at least one of the following: EE ≥ 37 or DP ≥ 13 or PA < 31 (15).
Secondary Traumatic Stress Scale (STSS)
The Secondary Traumatic Stress Scale (STSS) was developed by Bride and colleagues (20) by using the seventeen symptoms of post traumatic stress disorder from the DSM-IV, and has seventeen items that are answered using a five point Likert type scale. It has been found to have an overall coefficient alpha of 0.94. There are three subscales and each subscale has a coefficient alpha as well: intrusion, 0.80; avoidance, 0.87; arousal 0.79.
Personal Wellbeing Index (PWI)
The Personal Wellbeing Index (PWI) scale contains 7 questions, each one addressing a quality of life domain: standard of living, achieving in life, health, relationships, safety, community-connectedness, and future security. In regards to reliability, the Cornbach alpha lies between 0.70 and 0.85 in Australia and overseas and the index has shown good test-retest reliability with an intra-class correlation coefficient of 0.84 (21).
Demographic Survey
The demographic questionnaire is a self-constructed survey with common factors (years in practice, hours of sleep at night, hours of exercise per week, healthy diet, marital status, number of children, religion) that can be associated as a risk versus protective factors for burnout, secondary traumatic stress and overall wellbeing. Each factor had a comment section for qualitative analysis.
Data Analysis
Variables measured on a continuous scale are presented as means with standard deviations. Groups were compared using the Wilcoxon rank sum test and ANOVA on ranks. Categorical measurements are presented as frequencies with percentages. Groups were compared using Fisher’s exact test and chi-square. A value of < 0.05 was considered statistically significant. All analyses were carried out using SAS V9.2 statistical software (SAS Institute, Cary, NC).
Results
Demographics
Our study population consisted of 231 participants, in which hematology/oncology physicians and pediatric critical care physicians were evenly distributed (45.89% vs 54.1%). Initially the study was sent out to 732 members of AAP section of pediatric critical care and 445 members of the AAP section of hematology and oncology. The response rate was 15.8% among PICU physicians and 26.1% among hematology and oncology physicians. We attribute our low response rate to the automated depersonalized email from a website, rather than individual requests to members. Surveys that were started but were determined to be incomplete were excluded.
The population was gender balanced (female 51.8%, male 48.2 %), but predominantly Caucasian. 82.5% identified themselves as Caucasian, 10.8% as Asian, 0.9% as African American and 5.8% as others. With regard to religion more than half identified themselves as Christians (56.1%) followed by 25.3% who chose not to specify their religion. 11.8% identified themselves as Jewish, 3.6% as Hindus and 3.2% as Muslims. Most of our participants (76.8%) were married. 35.1% had 2 children followed by 22.1% who had no children. This study group mostly consisted of physicians who were > 20 years in practice (40.6%). 75.5% sleep 5-7 hours per night and 58.4% exercise 2-3 times per week. Half of this group (53.1%) claimed to consume a healthy diet (Table 1-2).
Table 1. Demographic Characteristics (n=231)
Table 2. Habits (n=231)
Maslach Burnout Inventory
The overall burnout rate was 46.8% (45.8% among pediatric critical care physicians and 47.8% among hematology/oncology physicians) (Table 3).
Table 3: Comparison of burnout, secondary traumatic stress and wellbeing rates between pediatric critical care and hematology oncology physicians
Almost half of the participants scored high (42.9%) on the emotional exhaustion subscale and 20.2% scored high for depersonalization. 50.5% also scored high on the personal accomplishment scale. 52.4% of burned out physicians were female. One third of physicians at risk for burnout had 2 children, but the number of children did not correlate with an increased risk of burnout. No demographic factors were identified as a risk or a protective factor for the development of burnout.
Secondary Traumatic Stress Scale
STS was defined as a total score of > 38. The rate of STS was 46.7% (Table 3). A higher total STSS score was noted for physicians practicing for 10- 15 years compared to those practicing for 5-10 years (p=0.04) with a higher score on the arousal subscale (p=0.03). Physicians who followed a healthy diet had a lower total STS score (p=0.01) and a lower score on all three subscales. The same group also seems to have higher scores on the wellbeing scale (p=0.01).
Personal Wellbeing Index
A Personal Wellbeing Index score of >35 was defined as a positive score, which means that an individual was satisfied with his personal life. The overall rate of satisfaction was 95.3% (Table 3). There was no significant difference for PWI scores for critical care and hematology/oncology physicians. With regard to hours of sleep per night, there was no significant difference in burnout or STS rate. However, physicians who slept >7h had a higher score on the PWI scale compared to those who sleep 3-5h (p=0.008) and 5-7h (p=0.02). Married physicians scored higher on the wellbeing scale compared to single physicians (p=0.04). Neither the number of children nor any other lifestyle or demographic factors were associated with increased wellbeing.
Discussion
Our results demonstrate high rates of burnout and secondary traumatic stress in pediatric critical care and pediatric hematology/oncology physicians. This is consistent with recent studies showing that burn out starts during pediatrics residency (18). Fields et al studied burnout rates among PICU physicians 20 years ago and found a rate of 14%, which is significantly lower than our findings. Garcia et al reported a burnout rate of 50% among general pediatricians and pediatric intensivists (19), in line with our findings. Burn out is not unique to Americans. Other studies have reported a rate of 41% at high risk for burnout among pediatric critical care physicians in Argentina (22). Interestingly, this study also found the highest rates among academic pediatricians working in a university setting. Comparing with other specialties, surgeons had similar rates of burnout, ranging from 39-41% (4).
Interestingly our study shows that physicians that are in practice for >20 years had higher scores on the depersonalization subscale. This is in contrast to prior studies that showed that physicians in the middle of their career (11-20 years in practice) are at the greatest risk for burnout (4). Another study by Downey et al assessed burnout among anesthesiologists and came to the conclusion that doctors who are 5-15 years in practice are at the greatest risk for burnout. In our study, physicians who are 10-15 years into their careers had higher secondary traumatic stress scores. Unfortunately, there is not much literature to compare our rates of secondary traumatic stress to and available data is mainly focused on military physicians (22).
We did find that a number of factors can mitigate burnout and STS rates. A healthy diet, sleep and religion positively influenced wellbeing and secondary traumatic stress rates. A subjectively healthy diet was associated with decreased total secondary traumatic stress scores and increased scored on the personal wellbeing scale. Consuming fruits and vegetables is associated with lower incidents of depression and higher rates of happiness and higher life satisfaction (23-25). Along with a healthy diet, more than 7 hours of sleep is also associated with physician wellbeing. It is well known that sleep deprivation is associated with decreased cognitive function, memory and reaction time (26).
Burnout poses a risk for the physician and the patient. High scores on the depersonalization and emotional exhaustion subscale are associated with alcohol abuse or dependence (27). Oreskovich et al. (28) sampled 25,073 surgeons, out of which 15.4% were identified to have an alcohol abuse disorder. Participants who were burned out (odds ratio, 1.25; P = .01) and depressed (odds ratio, 1.48; P < .001) were more likely to have alcohol abuse or dependence. Other studies have identified a correlation between burnout rates (specifically emotional exhaustion) and patient safety risks. Clinicians who scored high on the emotional exhaustion subscale of the MBI had higher standardized mortality ratios (29). A Mayo Clinic study also clearly linked burnout with self-perceived medical errors in both internal medicine residents and surgeons (30). In contrast, a recent study conducted in the adult ICU setting established that there is an increased rate of medical errors by depressed physicians, but burn out did not seem to correlate with an increase rate of medical errors (31). Another prospective cohort study done in three children’s hospitals on pediatric residents have had similar results. (32). In our study we did not measure depression or assess for medical errors related with physician burnout. More studies are needed in the future to elicit if burnout leads to an increase rate of medical errors and the potential risks for the patients.
One important limitation of this study is that it was sent to members of the American Academy of Pediatrics, where 40.63% of the physicians are >20 years in practice. This could have skewed the outcomes. One limitation in our study may be that respondents to our survey could be those who are more likely to suffer from burnout and more likely to want to report their issues, or conversely, those most severely affected may have chosen not to participate. We also did not separately analyze burnout and STS against each other, and we presumed that the similar rates were in the same respondents, but that may not be accurate.
Conclusion
The rates of burnout and secondary traumatic stress are high in both pediatric critical care physicians and pediatric hematologist / oncologists. It may be that lifestyle factors, such as a healthy diet, sleep and exercise may serve as protective factors and increase overall wellbeing. Further studies need to be done to assess burnout, secondary traumatic stress rates among other pediatric subspecialties and to analyze proper coping mechanisms.
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Cite as: Hoehn KS, Abraham M, Gaughan J, Willis BC. Which half are you? Almost half of pediatric oncologists and intensivists are burnt out…… Southwest J Pulm Crit Care. 2019;18(6):167-76. doi: https://doi.org/10.13175/swjpcc029-19 PDF
Management of Refractory Hypoxemic Respiratory Failure secondary to Diffuse Alveolar Hemorrhage with Venovenous Extracorporeal Membrane Oxygenation
Evanpaul Gill2
Mohamed A. Fayed1,2,
Elliot Ho1,2
University of California San Francisco - Fresno Medical Education Program
1Pulmonary and Critical Care Division
2Department of Internal Medicine
Fresno, CA USA
Abstract
Uncontrolled bleeding has been a relative contraindication for the use of venovenous extracorporeal membrane oxygenation (VV ECMO), but current practice is relatively institution dependent. With the recent advances in circuit technology and anticoagulation practices, the ability to manage patients with ongoing bleeding with ECMO support has increased. We report the case of a 66-year-old patient with refractory hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage (DAH) from underlying anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis who was successfully supported through his acute illness with VV ECMO. ECMO is often used to manage patients with refractory hypoxemic respiratory failure but the usage in the setting of DAH is less known given the risk of bleeding while receiving anticoagulation. Our patient was successfully managed without anticoagulation during his initial ECMO course and his respiratory failure rapidly improved after cannulation. Once managed through the acute phase of his illness and treatment started for his underlying disease process, anticoagulation was started. After being de-cannulated from ECMO and a 3 week stay in the acute rehabilitation unit, our patient was discharged home with complete recovery from his illness. We highlight that patients with refractory hypoxemic respiratory failure and suspicion of DAH as an etiology, ECMO without anticoagulation should be considered as supportive salvage therapy until the underlying process can be treated.
Case Presentation
A 66-year-old man presented with cough, fever, and dyspnea for 1 week. Upon presentation he was found to be in hypoxemic respiratory failure with bilateral pulmonary infiltrates on chest x ray (Figure 1) and positive testing for Influenza A.
Figure 1. Portable AP of chest on initial presentation showing bilateral infiltrates more prominent on the right.
He had an elevated creatinine of 8.1 mg/dl and an acute anemia with a hemoglobin of 7.4 g/dl during the initial work up. He was intubated on hospital day one and transferred to our center for a higher level of care early morning on hospital day two. He developed refractory hypoxemic respiratory failure despite maximum ventilator support as well as standard acute respiratory distress syndrome (ARDS) treatment including neuromuscular blockade. Prone positioning was not possible secondary to hemodynamic instability during the initial treatment plan. Infectious and autoimmune work up was sent. A thoracic CT scan showed extensive bilateral consolidation (Figure 2).
Figure 2. A representative image from the thoracic CT scan showing extensive bilateral consolidation.
At this point a decision was made to apply venovenous double lumen (VVDL) ECMO support as a supportive salvage therapy pending further evaluation into the etiology of his respiratory failure and ARDS. Etiologies at this point included severe influenza infection and DAH from an underlying vasculitis. Anticoagulation with heparin was not initiated given the significant anemia requiring multiple blood transfusions at that point. BUN was elevated, but no other signs of acute gastrointestinal bleeding were identified. Given the underlying renal failure, continuous renal replacement therapy (CRRT) was started on hospital day 2 with citrate used as the anticoagulant. After initiation of ECMO, he improved significantly in the next 72 hours, however, he developed bleeding from the endotracheal tube on day 4. Bronchoscopy was subsequently performed and showed bloody secretions throughout the respiratory bronchial tree, consistent with DAH. His ECMO course had been unremarkable with no thrombotic complications requiring changing of the circuit. Target flows were achieved with a Cardiohelp centrifugal pump and his Avalon 31F double lumen catheter was without complication. On day 5, his autoimmune panel showed a positive ANCA, with myeloperoxidase elevated at 82 AU/ml and serine protease elevated at 314 AU/ml. His anti-nuclear antibody (ANA) was also positive with his titer at 1:2,560. After rheumatology consultation, he was diagnosed with ANCA associated vasculitis with pulmonary hemorrhage and renal failure. His influenza infection was thought to be the trigger for the exacerbation of his underlying autoimmune disease. He was initiated on pulse dose steroids and plasmapheresis with significant clinical improvement and was de-cannulated from ECMO on day 8 with extubation following shortly afterward. He later had renal biopsy performed and it showed diffuse crescentic glomerulonephritis secondary to ANCA vasculitis. He was able to discontinue dialysis after requiring 8 days of CRRT and a further 3 weeks of intermittent hemodialysis. A chest x-ray showed complete clearing of the consolidation (Figure 3).
Figure 3. Chest x-ray just prior to discharge showing complete clearing of the consolidations.
He was eventually discharged home after a 3-week period in acute inpatient rehab.
Discussion
VV ECMO is increasingly being used as a viable treatment option in patients with refractory acute respiratory failure, especially in patients with underlying ARDS. The ability to allow lung protective ventilation by use of an extracorporeal circuit is of significant value in the acute phase of severe respiratory failure. The general principle of VV ECMO involves removing deoxygenated blood from a venous catheter and passing it through a closed circuit which is comprised of a centrifugal pump and membrane oxygenator (1). This membrane oxygenator takes over the function of the diseased lungs and allows gas exchange to occur, mainly oxygenating the blood and removing carbon dioxide.1 This blood is then returned into the venous circulation and eventually makes it to the systemic circulation to oxygenate the tissues.
Given that native blood is being passed through an artificial circuit, the risk for thromboembolism is thought to be relatively high. The pathophysiology behind this risk stems from contact of blood components with the artificial surface of the ECMO circuit (2). Proteins found in blood, mainly albumin and fibrinogen, will stick to the artificial surface (2). This results in other blood components congregating, which leads to the formation of a protein layer that servers as an anchor for platelet activation and the formation of insoluble fibrin clots (2). Given the risk of thromboembolism, Extracorporeal Life Support (ELSO) guidelines recommend routine anticoagulation for patients undergoing extracorporeal support (3).
The major complications regarding anticoagulation in the setting of ECMO is bleeding (4). The risk generally comes from acquired thrombocytopenia and anticoagulation (2). ELSO has guidelines regarding management of anticoagulation in VV ECMO but the current practice is relatively institution dependent. This was highlighted in a systematic review done by Sklar and colleagues (4) that investigated many different approaches to anticoagulation for patients on VV ECMO. The main anticoagulant used in those studies was unfractionated heparin and the means to measure its effect was activated clotting time (ACT) and partial thromboplastin time (PTT). They concluded that currently there is no high-quality data that can be employed in decision making regarding anticoagulation for patient’s on VV ECMO support for respiratory failure and that randomized controlled trials are needed for high quality evidence (4). Our own institution’s protocol uses unfractionated Heparin for anticoagulation with a PTT goal of 60-80.
The traditional risk of anticoagulation with ECMO has improved as the component technology of the ECMO circuit has progressed (2). Development of heparin coated inner tubing along with shorter circuit lengths are recent strategies that have been employed to help decrease the amount of thrombotic complications (2). ECLS guidelines state that patients can be managed without anticoagulation if bleeding cannot be controlled with other measures and that the use of high flow rates is recommended to help prevent thrombotic complications (3). The strategies mentioned above are non-chemical ways of preventing thrombosis and could potentially allow management of VV ECMO patients without anticoagulation for the initial period. This was demonstrated in a case report done by Muellenbach and colleagues (5). In their case series, they describe three cases of trauma patients with intracranial bleeding and severe ARDS refractory to conventional mechanical ventilation that were managed with VV ECMO without systemic anticoagulation for a prolonged time period. In their situation, anticoagulation could not be given secondary to severe traumatic brain injury (TBI) and intracranial bleeding (5). They stated that because newer circuits are completely coated by heparin and because circuit lengths have been shortened by specialized diagonal pumps and oxygenators, systemic anticoagulation can be reduced (5)
VV ECLS, as mentioned above, is commonly used in acute respiratory failure but use of VVECLS in DAH is a less known use due to the risk of anticoagulation in this clinical setting. Per ECLS guidelines, one of the relative contraindications for initiation of ECLS is risk of systemic bleeding from anticoagulation (3), and patients with DAH definitely fit this risk profile. But as mentioned above; with improving shortened ECMO circuits, use of heparin coated tubing, and high flow rates, the ability to initially manage patients without systemic anticoagulation until they are stabilized is very important in clinical settings such as our patient with DAH. Many case reports have been published that highlight the successful management of acute respiratory failure due to DAH with VV ECMO (6,7). Our patient was initially managed without systemic anticoagulation and required multiple blood transfusions given the significant bleeding appreciated from the endotracheal tube. Once the diagnosis of ANCA related DAH was made and the appropriate treatment initiated, bleeding significantly decreased and the patient was able to be started on anticoagulation. This highlights that patients with suspicion of DAH as an etiology of respiratory failure not be excluded from consideration VV ECMO as supportive salvage therapy given the potential for great clinical outcome if managed through the acute phase of bleeding.
References
- Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011 Nov 17;365(20):1905-14. [CrossRef] [PubMed]
- Mulder M, Fawzy I, Lance MD. ECMO and anticoagulation: a comprehensive review. Neth J Crit Care. 2018;26:6-13.
- Brogan TV, Lequier L, Lorusso R, MacLaren G, Peek G. Extracorporeal Life Support: The ELSO Red Book. Fifth Edition. Extracorporeal Life Support Organization; 2017. Thomas V. Brogan and Laurance Lequier (eds).
- Sklar MC, Sy E, Lequier L, Fan E, Kanji HD. Anticoagulation practices during venovenous extracorporeal membrane oxygenation for respiratory failure. A systematic review. Ann Am Thorac Soc. 2016 Dec;13(12):2242-50. [CrossRef] [PubMed]
- Muellenbach RM, Kredel M, Kunze E, Kranke P, Kuestermann J, Brack A, Gorski A, Wunder C, Roewer N, Wurmb T. Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. J Trauma Acute Care Surg. 2012 May;72(5):1444-7. [CrossRef] [PubMed]
- Abrams D, Agerstrand CL, Biscotti M, Burkart KM, Bacchetta M, Brodie D. Extracorporeal membrane oxygenation in the management of diffuse alveolar hemorrhage. ASAIO J. 2015 Mar-Apr;61(2):216-8. [CrossRef] [PubMed]
- Patel JJ, Lipchik RJ. Systemic lupus-induced diffuse alveolar hemorrhage treated with extracorporeal membrane oxygenation: a case report and review of the literature. J Intensive Care Med. 2014 Mar-Apr;29(2):104-9. [CrossRef] [PubMed]
Cite as: Gill E, Fayed MA, Ho E. Management of refractory hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage with venovenous extracorporeal membrane oxygenation. Southwest J Pulm Crit Care. 2019;18(5):135-40. doi: https://doi.org/10.13175/swjpcc007-19 PDF
Amniotic Fluid Embolism: A Case Study and Literature Review
Ryan J Elsey DO1*, Mary K Moats-Biechler OMS-IV2, Michael W Faust MD3, Jennifer A Cooley CRNA-APRN4, Sheela Ahari MD4, and Douglas T Summerfield MD1
Departments of Internal Medicine1,Obstetrics and Gynecology3,and Anesthesia4
1Mercy Medical Center—North Iowa
Mason City, IA USA
2A.T. Still University
Kirksville, MO USA
Abstract
Amniotic fluid embolus is a rare and life threatening peripartum complication that requires quick recognition and emergent interdisciplinary management to provide the best chance of a positive outcome for the mother and infant. The following case study demonstrates the importance of quick recognition as well as an interdisciplinary approach in caring for such a condition. A literature review regarding the current recommendations for management of this condition follows as well as a proposed treatment algorithm.
Introduction
Amniotic fluid embolus (AFE) is a rare and life-threatening complication of pregnancy; a recent population-based review found an estimated incidence ranging from 1 in 15,200 deliveries in North America and 1 in 53,800 deliveries in Europe (1). Mortality rates vary but have been reported to range from 11% to more than 60%, with the most recent population-based studies in the United States reporting a 21.6% fatality rate (1-4). Despite best efforts, it remains one of the leading causes of maternal death (1,5,6). However, rapid diagnosis of AFE and immediate obstetric and intensive care has proven to play a decisive role in maternal prognosis and survival (7-9).
In 2016, uniform diagnostic criteria were proposed for reporting on cases of AFE. First, a report of AFE requires a sudden onset of cardiorespiratory arrest, which consists of both hypotension (systolic blood pressure < 90 mmHg) and respiratory compromise (dyspnea, cyanosis, or SpO2 < 90%). Secondly, overt disseminated intravascular coagulation (DIC) must be documented following the appearance of signs or symptoms using a standardized scoring system. Coagulopathy must be detected prior to a loss of sufficient blood to account for dilutional or shock-related consumptive coagulopathy. Third, the clinical onset must occur during labor or within 30 minutes of delivery of the placenta. Fourth, no fever ≥ 38.0° C during labor can occur (10).
The following case study qualifies as a reportable incidence of an AFE under the above criteria and further demonstrates the ability to successfully stabilize a patient with AFE due to quick recognition, interdisciplinary cooperation, and effective supportive management.
Case Presentation
A 34-year-old gravida 5, para 1-1-2-2, presented at 36 weeks and 1-day gestation for induction of labor. Her past medical history included esophageal atresia at birth and a past pregnancy complicated by preterm, premature rupture of the membranes. Initial labs at admission were significant for a hemoglobin of 12.2 g/dL and a platelet count of 234 x103 u/L. The patient was subsequently started on lactated ringers at 125 ml/hr. As the patient's labor progressed, an epidural was placed 3 hours after admission. Four hours and 42 minutes after admission, an artificial rupture of the membranes was performed.
Eighteen minutes after the artificial rupture of the membranes was performed, the patient was noted to have seizure-like activity. She was given an intravenous (IV) fluid bolus and ephedrine, and the anesthesia provider was emergently contacted. When anesthesia arrived, the patient was noted to be cyanotic in bed. Patient vitals and exam were significant for emesis, a heart rate of 50 beats per minute (bpm), systolic blood pressure in the low 70s (mmHg), and a fetal heart rate in the 70s.
The differential diagnosis at this time was broad and included anesthesia drug reactions such as an intravascular epidural migration, pulmonary thromboembolism, eclampsia, or even an aortic dissection. A pulmonary embolism was felt to be unlikely due to the patient's bradycardia and sudden neurologic changes. Eclampsia was less likely at the time due to no signs of pre-eclampsia in the patient as well as the patient's current bradycardia and hypotension. Given the patient's absence of Marfan syndrome, aortic dissection was not considered to be a high probability. The patient did have signs consistent with an intravascular epidural including altered mental status, cyanosis, bradycardia, hypotension, vomiting, and a low fetal heart rate. However, at the time anesthesia felt she was more likely suffering from an acute embolic process given the timeframe between the artificial rupture of the membranes and the onset of her symptoms.
Given the patient's instability, she was emergently taken for a cesarean section and intubated to provide airway stabilization. The cesarean section began 15 minutes after seizure like symptoms started and upon delivery, the infant was subsequently transferred to a tertiary center for therapeutic hypothermia.
Intraoperatively, the patient was noted to maintain a peripheral capillary oxygen saturation (SpO2) of >90%. However, end tidal C02 was elevated to 54 mmHg despite hyperventilation and peak airway pressures were elevated to 38 cmH2O. Albuterol and sevoflurane were subsequently utilized in an attempt to increase bronchodilation. Following completion of the caesarian section, peak airway pressures normalized to less than 30 cmH2O but end tidal CO2 levels remained as high as 52 mmHg despite hyperventilation. Blood pressure was significant for systolic pressure of 80 mmHg. IV phenylephrine was administered. Additionally, uterine massage was performed to aid in hemorrhage control and the patient was administered IV oxytocin, methylergonovine maleate, carboprost, and vaginal misoprostol. A repeat complete blood count was performed one hour after symptom onset which showed a hemoglobin of 10.3 g/dL and a platelet count of 103 x103 u/L.
In this case, the patient’s care team had a high suspicion of an AFE with symptoms that followed the uniform diagnostic criteria for an AFE. The patient had hemodynamic instability, coinciding with the recent rupture of membranes. Her systolic blood pressure was < 90 mmHg and her end tidal C02 levels (in mmHg) were elevated to the high 40s and low 50s. The critical care team was notified of her condition and the patient was subsequently transferred to the Intensive Care Unit (ICU) on mechanical ventilation and sedated with fentanyl and versed.
Upon arrival to the ICU, a DIC panel was performed revealing DIC. Labs showed a fibrinogen level of 52 mg/dL, A D-dimer greater than 128,000 ng/mL, and a platelet count of 80,000 u/L despite the administration of one pooled unit of platelets. The patient's international normalized ratio (INR) was 1.3 with a baseline INR of 0.9. Due to multiple laboratory abnormalities and a clinical condition consistent with DIC, aggressive transfusions were performed per the standard of care for patients suffering with DIC. A peripheral smear was obtained revealing schistocytes (Figure 1) which verified the DIC diagnosis.
Figure 1. The patient's peripheral blood smear four hours after onset of symptoms which demonstrates schistocytes indicative of DIC.
Hematology was emergently consulted and it was recommended to avoid additional platelet transfusions unless platelet counts dropped below 10,000 to 20,000 u/L. One milligram (mg) of subcutaneous phytonadione was also given five hours after symptom onset in an effort to decrease bleeding.
Cardiology was consulted and performed an emergent echocardiogram to assess the patient’s heart function and rule out any cardiac abnormalities. Given her past history of esophageal atresia, there was particular concern about an underlying ventricular septal defect, patent ductus arteriosus, or tetralogy of Fallot (11). The echocardiogram revealed a dilated, yet functional right ventricle, which was expected in the setting of an AFE. ICU physicians at a tertiary care center were provisionally consulted to confirm that the patient was a candidate for arteriovenous extracorporeal membrane oxygenation (AV-ECMO) should she suffer further cardiopulmonary collapse. Labs, including hemoglobin, platelets, fibrinogen activity, and ionized calcium were drawn every two hours during the acute phase of the patient's management and abnormalities were addressed as required over the subsequent two hours. The patient's hemoglobin was noted to decline to as low as 6.7 g/dL. Of note, lab draws did suffer some sample lysis due to the patient's coagulation abnormalities. The patient did initially require phenylephrine for blood pressure support. Additionally, she was placed on an experimental septic shock protocol which involved the administration of 1500 mg of ascorbic acid every six hours, 60 mg of methylprednisolone every six hours, and 200 mg of thiamine every 12 hours. The patient began to stabilize around 10 to 12 hours after her AFE symptoms began and pressor support was titrated off, at which point blood draws were liberalized to every four hours. The patient continued to improve and remained stable overnight.
On hospital day two, the patient was noted to be alert and was successfully extubated. Following extubation, the physical exam found her to be neurologically and hemodynamically intact. During her stay in the ICU, the patient received a total of eight units of packed red blood cells, five units of fresh frozen plasma, one pooled unit of platelets, and one unit of cryoprecipitate. The patient was ultimately discharged from the hospital on day four with no long-term sequelae noted.
The patient was informed that data from the case would be submitted for publication and gave her consent.
A Review of the Literature
AFE remains one of the leading causes of direct, maternal mortality among developed countries (1,12,13). Multiple reviews have studied the incidence of AFE, which varies widely, from 1.9 per 100,000 to 7.7 per 100,000 pregnancies, with the reported fatality rate due to AFE ranging from 11% to more than 60%, depending on the study (1,2,4,14). The difficulty in reporting an accurate incidence and fatality rate is likely secondary to the fact that AFE remains a diagnosis of exclusion. AFE is traditionally diagnosed clinically during labor in a woman with ruptured membranes and a triad of symptoms, including unexplained cardiovascular collapse, respiratory distress, and DIC. (1,2,15-18). Additional symptoms may include hypotension, frothing from the mouth, fetal heart rate abnormalities, loss of consciousness, bleeding, uterine atony, and seizure-like activity (15,16,19).
The majority of women who fail to survive an AFE die during the acute phase (median of one hour and 42 minutes after presentation) (2,6). Surviving beyond the acute phase dramatically improves their overall chance of survival; however, survival is not without long term morbidities. Analysis performed in the United Kingdom in 2005 and again in 2015 showed that 7% of woman surviving AFE have permanent neurological injury, including persistent vegetative state/anoxic/hypoxic brain injury or cerebrovascular accident (2,7). Among survivors,17% were shown to have other comorbidities, including sepsis, renal failure, thrombosis or pulmonary edema and 21% required a hysterectomy (2,6).
Despite several decades of research, the pathogenesis of an AFE continues to remain somewhat clouded. Multiple theories have been postulated concerning the clinical manifestations occurring with an AFE and their relationship with the passage of amniotic fluid into the systemic maternal circulation. The first theory proposed described amniotic debris passing through the veins of the endocervix and into maternal circulation, resulting in an obstruction (1,6). This theory has fallen out of favor as there is no physical evidence of obstruction noted on radiologic studies, autopsies, or experimentally in animal models (1,20,21). Additionally, multiple studies have found that that the passage of amniotic and fetal cells into maternal circulation are very common during pregnancy and delivery (6). Thus, most theories today focus on humoral and immunological factors and how they affect the body (5,22,23). Current research focuses on the effect of amniotic fluid on the body after it has already entered into maternal circulation. It is theorized that the amniotic fluid results in the release of various endogenous mediators, resulting in the physiologic changes that are seen with an AFE. Proposed mediators include histamine (22), bradykinin (24), endothelin (25,26), leukotrienes (27), and arachidonic acid metabolites (28).
The hemodynamic response to AFE is biphasic in nature. It consists of vasospasm, resulting in severe pulmonary hypertension, and intense vasoconstriction of the pulmonary vasculature secondary to the amniotic fluid itself, which can lead to ventilation-perfusion mismatch and resultant hypoxia (5,6,29). On an echocardiogram, the initial phase of an AFE consists of right ventricular failure demonstrated by a severely dilated, hypokinetic right ventricle with deviation of the interventricular septum into the left ventricle (18). Following the initial phase of right ventricular failure, which can lasts minutes to hours, left ventricular failure along with cardiogenic, pulmonary edema becomes the prominent finding (1,5). This occurs due to a reduction in preload as well as systemic hypotension. These changes may decrease coronary artery perfusion, which can result in myocardial injury, precipitation of cardiogenic shock, and worsening of distributive shock (1,6,30).
DIC is present in up to 83% of patients experiencing an AFE; however, its onset during presentation can be variable (31). It may present within the first ten minutes following cardiovascular collapse, or it may precipitate up to nine hours following the initial clinical manifestation (5,31,32). The precipitating pathophysiology behind DIC in AFE is poorly understood, but is likely to be consumptive, rather than fibrinolytic, in nature. In an AFE it is currently theorized that tissue factor, which is present in amniotic fluid, activates the extrinsic pathway by binding with factor VII, triggering clotting to occur by activating factor X, resulting in the consumptive coagulopathy (1,33-35). Ultimately, it is felt that this coagulation leads to vasoconstriction of the microvasculature and thrombosis by producing thrombin that is secreted into the endothelin, leading to the changes seen in DIC (1,5,6,14,18).
Recommended Management for AFE Based on Current Literature
Early recognition of AFE and immediate obstetric and intensive care has proven to play a decisive role in maternal prognosis and survival (7,8). In order to survive an an AFE, patients require immediate multidisciplinary management with a focus on maintaining oxygenation, circulatory support, and correcting coagulopathy (1,6).
A literature review of the current management for patients presenting with AFE recommends standard initial lifesaving supportive care. This should begin with immediate protection of the patient's airway via endotracheal intubation and early, sufficient oxygenation using an optimized positive end-expiratory pressure (FiO2:PEEP) ratio, which also decreases the risk of aspiration (1,5,29). Two large bore IV lines should be placed for crystalloid fluid resuscitation. In the setting of a cardiopulmonary arrest, cardiopulmonary resuscitation should be initiated and an immediate caesarian section within three to five minutes should be performed in the presence of a fetus ≥ 23 weeks gestation (5,18,36-38). This serves several purposes, including decreasing the risk of the infant suffering from long term neurologic injury secondary to hypoxia, improving venous flow to the right heart by emptying the uterus, and reducing pressure on the inferior vena cava to decrease impedance to blood flow, which decreases systemic blood pressure (1,5,31,39,40).
During the initial phase, attention should be paid to avoid hypoxia, acidosis, and hypercapnia due to their ability to increase pulmonary vascular resistance and lead to worsening of right heart failure and recommendations include sildenafil, inhaled or injected prostacyclin, and inhaled nitric oxide (6). Recommendations to treat for hypotension during this phase include the utilization of vasopressors, such as norepinephrine or vasopressin (1,6,18,37,41). Hemodynamic management during the second phase should focus on the patient's left-sided heart failure by optimizing cardiac preload via vasopressors to maintain perfusion and utilizing inotropes such as dobutamine or milrinone to increase left ventricular contractility (1,6,18).
Due to the relationship between AFE and DIC, current recommendations suggest early assessment of the patient's coagulation status. Additionally, in the setting of a massive hemorrhage, blood product administration should not be delayed while awaiting laboratory results (18). Early corrective management of the patient's coagulopathy should be aggressive in nature, especially in the setting of a massive hemorrhage. Tranexamic acid and fibrinogen concentrate (for fibrinogen levels below 2 g/L) are essential in the treatment of hyper-fibrinolysis. Additionally, multiple obstetric case studies have shown fibrinogen replacement to benefit from bedside rotational thromboelastometry if available due to its ability to rapidly diagnosis consumptive versus fibrinolytic coagulopathy at the bedside (5,42,43). Hemostatic resuscitation with packed red blood cells, fresh-frozen plasma, and platelets at a ratio of 1:1:1 should be administered (6,18). Cryoprecipitate replacement is recommended as well due to the consumptive nature of DIC in AFE, and its importance should not be understated. A 2015 population-based cohort study showed that women with AFE who died or had permanent neurologic injury were less likely to have received cryoprecipitate than those who survived and were without permanent neurologic injury (1,2). Furthermore, due to the dynamic processes of chemodynamical labs, including hemoglobin, platelet count, and fibrinogen must be monitored closely to prevent complications or over transfusion (14).
Uterine atony is a common feature with AFE and it is recommended to immediately administer uterotonics during the postpartum period to prevent its occurrence (5,44). Should it occur, uterine atony should be managed aggressively via uterotonics such as oxytocin, ergot derivatives, and prostaglandins; refractory cases may require packing material for uterine tamponade, uterine artery ligation, or even a hysterectomy for the most severe (5,8,18).
In addition to the treatments listed above, multiple case reports support the use of aggressive or novel therapeutic modalities to aid in the treatment of AFE; however, for many of the treatments, evidence supporting increased survival of an AFE is merely anecdotal (18). Among the best supported ancillary treatments is nonarterial extracorporeal membrane oxygenation as a possible therapeutic treatment for patients with refractory acute respiratory distress syndrome. However, due to the profoundly coagulopathic state of AFE and the active hemorrhage occurring with AFE, the use of anticoagulation may profoundly worsen bleeding. Consequently, extracorporeal membrane oxygenation is controversial and not routinely recommended in the management of AFE (6,18). Similarly, post-cardiac arrest therapeutic hypothermia with a range of 32°C to 34°C is often avoided in patients with AFE due to the increased risk of hemorrhage given their predisposition for DIC (18). However, in patients not demonstrating DIC and overt bleeding, targeted temperature management to 36°C and preventing hyperthermia is an option that should be considered (17,45,46). Factor VIIa procoagulant, which increases thrombin formation, has been utilized anecdotally, but strong supporting data is lacking; it should only be considered if following the replacement with massive coagulation factors, hemostasis and bleeding fail to improve (5,47). Additionally, it is important to note that factor VIIa replacement is only effective if other clotting factors have been replaced (1,6,48,49). Novel therapeutic modalities mentioned in the literature also include continuous hemofiltration, cardiopulmonary bypass, nitric oxide, steroids, C1 esterase inhibitor concentrate, and plasma exchange transfusion. While there are case reports published to suggest that all of the aforementioned therapies may provide some level of improvement in patients with AFE, the positive results from these cases may be due to their administration during the intermediate phase of AFE as opposed to the acute phase of AFE, where the majority of mortality occurs—once patients have surpassed the early, acute phase, survival chances greatly improve with continued supportive care (1,6).
AFE has traditionally been viewed as a condition associated with poor outcomes and a high mortality rate for both the mother and the infant. However, with quick AFE recognition, high quality supportive care, and interdisciplinary cooperation, patients can have positive outcomes. Based on the success with the patient presented in this case and the review of the current literature as seen above, the authors have proposed an algorithm (Figure 2) for the treatment of future patients experiencing AFE.
Figure 2. Proposed interdisciplinary treatment algorithm for acute management of an AFE.
By following the algorithm, the authors believe that the outcomes for AFE patients can be improved.
Abbreviations
PEEP: positive end-expiratory pressure; BP: blood pressure; TV: tidal volume; ACLS: Advanced cardiac life support; ABG: Arterial blood gas; CBC: Complete blood count; CMP: Complete metabolic profile; INR: International normalized ratio; PTT: Partial prothrombin time; ART line: Arterial line; NO: Nitric oxide; ARDS: Acute respiratory distress syndrome; ECMO: Extracorporeal membrane oxygenation; FFP: Fresh frozen plasma; Plt: Platelet; pRBCs: Packed red blood cells; NE: Norepinephrine.
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Cite as: Elsey RJ, Moats-Biechler MK, Faust MW, Cooley JA, Ahari S, Summerfield DT. Amniotic fluid embolism: A case study and literature review. Southwest J Pulm Crit Care. 2019;18(4):94-105. doi: https://doi.org/10.13175/swjpcc105-18 PDF
April 2019 Critical Care Case of the Month: A Severe Drinking Problem
Francisco J. Marquez II MD
Department of Pulmonary and Critical Care Medicine
Banner University Medical Center/University of Arizona – Phoenix
Phoenix, AZ USA
History of Present Illness
A 55-year-old Caucasian man, presented to an outside hospital with altered mental status.
Past Medical/Social History
- Severe alcohol and intermittent fentanyl abuse
- Homelessness
Physical Exam
- Hypothermic and hypertensive.
- Patient encephalopathic without any acute deficits
- Pupils are normal sized and react to light
Which of the following should be obtained or done in his initial evaluation? (Click on the correct answer to proceed to the second of six pages)
Cite as: Marquez FJ II. April 2019 critical care case of the month: A severe drinking problem. Southwest J Pulm Crit Care. 2019;18(4):67-73. doi: https://doi.org/10.13175/swjpcc003-19 PDF
Ultrasound for Critical Care Physicians: An Unexpected Target Lesion
Jantsen Smith, MD
Department of Internal Medicine
University of New Mexico Hospital
Albuquerque, NM USA
A 39-year-old woman was admitted to the hospital for shortness of breath. Her medical history was significant for human immunodeficiency virus infection (not on anti-retroviral therapy), superior vena cava (SVC) syndrome with history of SVC stenting, cerebrovascular accident complicated by seizure disorder and swallowing difficulties, moderate pulmonary hypertension, end-stage renal disease on hemodialysis with past episodes of acute hypoxic respiratory failure related to fluid overload. Shortly after admission, the patient experienced a cardiac arrest due to hypoxia and necessitated emergent intubation. This was presumed to be due to fluid overload. Nephrology was consulted for emergent dialysis (the patient had a right upper extremity fistula for dialysis access). Dialysis was initiated through a right arm fistula. On day three of admission, the patient was noted to have worsening right upper extremity and breast swelling and pain. Physical exam revealed indurated edema of the skin of the breast. Point of care ultrasound was performed of the patient’s right neck, and the following ultrasound was obtained approximately 4cm above the clavicle in the right lateral neck.
Video 1. Ultrasound image of the right neck in the transverse plane.
What is the most likely cause of this patient’s right upper extremity and breast swelling? (Click on the correct answer for an explanation).
- Right breast cellulitis
- Ascending SVC thrombus
- Lymphatic blockage of right axillary nodes
- Fluid overload complicated by third spacing in the R upper extremity
Cite as: Smith J. Ultrasound for critical care physicians: An unexpected target lesion. Southwest J Pulm Crit Care. 2019;18(3):63-4. doi: https://doi.org/10.13175/swjpcc011-19 PDF
January 2019 Critical Care Case of the Month: A 32-Year-Old Woman with Cardiac Arrest
Sarah A. Watkins, DO1
Geoffrey Smelski, PharmD1
Robert N.E. French, MD1
Michael Insel, MD2
Janet Campion MD2
1Arizona Poison and Drug Information Center and 2Division of Pulmonary, Allergy, Critical Care and Sleep
University of Arizona
Tucson, AZ USA
History of Present Illness
A 32-year-old woman with history of chronic neck pain and opioid abuse complained of dizziness and palpitations shortly before suffering a witnessed cardiac arrest in her home. She was given bystander cardiopulmonary resuscitation until emergency medical services arrived on scene, at which point intermittent polymorphic ventricular tachycardia with a pulse was noted on the cardiac monitor and physical exam (Figure 1).
Figure 1. Rhythm strips showing ventricular tachycardia (A) and a prolonged QT interval (B).
Which of the following is (are) the most likely cause(s) of the cardiac arrythmia? (Click on the correct answer to be directed to the second of seven pages)
Cite as: Watkins SA, Smelski G, French RNE, Insel M, Campion J. January 2019 critical care case of the month: A 32-year-old woman with cardiac arrest. Southwest J Pulm Crit Care. 2019;18(1):1-7. doi: https://doi.org/10.13175/swjpcc121-18 PDF