A Case of Athabaskan Brainstem Dysgenesis Syndrome and RSV Respiratory Failure

Tanner Ellsworth

Nahid Hiermandi DO

Diana Hu MD

Lisa M. Grimaldi MD

Cardiovascular Intensive Care Unit

Phoenix Children’s Hospital

Phoenix, Arizona USA

Abstract

Athabaskan Brainstem Dysgenesis Syndrome (ABDS) is a nonlethal, homozygous HOXA1 mutation typically marked by central hypoventilation, sensorineural deafness, horizontal gaze palsy, and developmental delay. In this report, we present a case of a 27-month-old Navajo female with a new diagnosis of ABDS after multiple failed attempts at extubation following anesthesia in the setting of respiratory syncytial virus (RSV) bronchiolitis. Her case is significant because she lacks sensorineural hearing loss, a defining feature of previously documented cases thereby underscoring the challenges of diagnosing this disease. This case expands the ever-growing spectrum of homozygous HOXA1 mutations and demonstrates unique junctions for diagnosis of ABDS in the critical care setting in patients lacking key features of the disease.

Introduction

Athabaskan Brainstem Dysgenesis Syndrome (ABDS) is an autosomal recessive, nonlethal, homozygous HOXA1 mutation. Though globally rare, incidence in Southwest Athabaskan (Navajo and Apache) populations spans 1/1000 to 1/3000 births (1)(2). This can be compared to Congenital Central Hypoventilation Syndrome (CCHS) with an estimated incidence of 1/200,000 births worldwide (3).

ABDS is marked by central hypoventilation, sensorineural deafness, horizontal gaze palsy, and developmental delay (2). Other features include cardiac outflow tract anomalies, swallowing dysfunction, vocal cord paralysis, facial paresis, seizures, hypotonia, and cerebrovascular maldevelopment (4)(5). Affected individuals span a broad spectrum with many asymptomatic cases. Similar syndromes include Moebius syndrome and Bosley-Salih-Alorainy Syndrome, though both lack central hypoventilation (5). Central hypoventilation in children should include consideration for primary neuromuscular, lung, or cardiac disease, along with brainstem lesions, CCHS, asphyxia, infection, trauma, tumor, and infarction (6). As more Athabaskan individuals leave reservations, medical professionals must gain familiarity with the spectrum of HOXA1 mutations to prevent avoidable complications and expedite appropriate therapies.

We present a 27-month-old Navajo female with a new diagnosis of ABDS after several failed attempts at extubation following anesthesia in the setting of respiratory syncytial virus (RSV) bronchiolitis.

Case Description

A 27-month-old Navajo female with global developmental delay, patent ductus arteriosus (PDA), and sleep apnea presented with an acute, febrile respiratory illness confirmed as RSV bronchiolitis. She was admitted to a rural hospital for supportive care including supplemental oxygen and methylprednisolone.

Birth and developmental history were significant for transient poor feeding, poor visual tracking since birth, three failed newborn hearing exams with a subsequent pass, and global developmental delay, evidenced by inability to ambulate independently or speak more than two words.

At the rural hospital, persistent hypoxemia prompted a cardiac evaluation with echocardiography that revealed left ventricular hypertrophy, a tortuous aortic arch with moderate obstruction, and a small PDA with left-to-right shunting. Considering these findings, she was transferred to a tertiary pediatric hospital for further workup and management.

On the pediatric floor, blood gas analyses showed hypercarbia with metabolic compensation, suspicious for chronic hypoventilation. She consistently demonstrated generalized hypotonia and inconsistent tracking, specifically restricted lateral eye movements. Persistent hypoxemia and abnormal echocardiogram prompted further cardiac evaluation. On hospital day (HD) 3, a cardiac CT under general endotracheal anesthesia confirmed coarctation of the aorta and hypoplastic transverse arch. She was unable to be extubated due to persistent hypoxia and hypercarbia and was transferred to the cardiovascular intensive care unit.

Extubation attempts were initially deferred due to Moraxella tracheitis, treated with antibiotics and airway clearance. She weaned ventilator settings and was extubated to non-invasive support with bilevel positive airway pressure (BiPAP) on HD7. Within hours, she developed hypercarbia due to hypoventilation with a blood pH of 6.98 requiring reintubation.

Persistent central hypoventilation, hypercarbia, and cardiac outflow tract anomaly prompted investigation for ABDS. Brain MRI showed diffuse parenchymal volume loss with no brainstem abnormalities. Brainstem Auditory Evoked Response (BAER) testing showed no evidence of sensorineural hearing loss. Chromosome microarray testing confirmed homozygous HOXA1 mutation, consistent with ABDS.

Ventilator settings were again weaned, caffeine therapy initiated, and sedation medications discontinued for several days to avoid exacerbation of central hypoventilation. Unfortunately, repeat extubation failed due to stridor and hypoventilation, so she was reintubated and underwent an airway evaluation that revealed posterior vocal fold granulomas, which were debrided.

On HD33, the patient was successfully extubated to BiPAP. She weaned to room air during the day and BiPAP at night which she continued after discharge on HD57.

Discussion

In the critical care setting, familiarity with ABDS is important because patients can present with severe symptomatology out of proportion to their underlying disease. Minor respiratory illnesses or anesthesia can greatly exacerbate central hypoventilation and potentially lead to prolonged endotracheal intubation, mechanical ventilation, and associated complications such as ventilator-associated pneumonia, airway trauma, and habituation to sedation medications (2). Patients like this, who lack certain key features of ABDS—namely sensorineural deafness—are particularly challenging since diagnosis can be delayed (2). This case further illuminates the spectrum of homozygous HOXA1 mutations and emphasizes the importance of maintaining a high index of suspicion for ABDS in Athabaskan patients to anticipate the illness course and provide tailored medical care.

Conclusion

Overall, as Athabaskan individuals spread geographically, this case underscores the importance of widespread familiarity with ABDS for physicians. Basic knowledge of the features of ABDS will help identify individuals who may present with events such as infection or anesthesia that unmask an underlying abnormality, and their care can be directed at the unique challenges they present.

References

1. Erickson RP. Southwestern Athabaskan (Navajo and Apache) genetic diseases. Genet Med. 1999 May-Jun;1(4):151-7. [CrossRef] [PubMed]
2. Holve S, Friedman B, Hoyme HE, Tarby TJ, Johnstone SJ, Erickson RP, Clericuzio CL, Cunniff C. Athabascan brainstem dysgenesis syndrome. Am J Med Genet A. 2003 Jul 15;120A(2):169-73. [CrossRef] [PubMed]
3. Bardanzellu F, Pintus MC, Fanos V, Marcialis MA. Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases. Curr Pediatr Rev. 2019;15(3):139-153. [CrossRef] [PubMed]
4. Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT, Tischfield MA, Engle EC, Erickson RP. The clinical spectrum of homozygous HOXA1 mutations. Am J Med Genet A. 2008 May 15;146A(10):1235-40. [CrossRef] [PubMed]
5. Erickson RP. Autosomal recessive diseases among the Athabaskans of the southwestern United States: recent advances and implications for the future. Am J Med Genet A. 2009 Nov;149A(11):2602-11. [CrossRef] [PubMed]
6. Weese-Mayer, DE, Marazita, ML, Rand, CM, et al. Congenital central hypoventilation syndrome. 2004 Jan 28. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1427/

Cite as: Ellsworth T, Hiermandi N, Hu D, Grimaldi LM. A Case of Athabaskan Brainstem Dysgenesis Syndrome and RSV Respiratory Failure. Southwest J Pulm Crit Care. 2020;21(5):124-6. doi: https://doi.org/10.13175/swjpcc053-20 PDF 

Management of Refractory Hypoxemic Respiratory Failure secondary to Diffuse Alveolar Hemorrhage with Venovenous Extracorporeal Membrane Oxygenation

Evanpaul Gill²

Mohamed A. Fayed^1,2,

Elliot Ho^1,2

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

1. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011 Nov 17;365(20):1905-14. [CrossRef] [PubMed]
2. Mulder M, Fawzy I, Lance MD. ECMO and anticoagulation: a comprehensive review. Neth J Crit Care. 2018;26:6-13.
3. 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).
4. 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]
5. 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]
6. 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]
7. 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

April 2018 Critical Care Case of the Month

Clement U. Singarajah, MD

Phoenix VA Medical Center

Phoenix, AZ USA

History of Present Illness

A 70-year-old man was admitted for shortness of breath (SOB) secondary to a “COPD exacerbation/ILD”. A pulmonary consult was placed for possible interstitial lung disease (ILD). A thoracic CT scan for pulmonary embolism showed no embolism and no obvious ILD. He was treated for a COPD exacerbation with the usual therapy of antibiotics, steroids, nebulized bronchodilators and oxygen. He started to improve.

A few days later as he was preparing for discharge, the patient suddenly decompensated becoming more SOB (once more proving that this a dangerous time for patients in hospital). There were reports that this began after he choked and perhaps aspirated on some food and drink. His blood pressure remained stable, but he became tachycardic to 130 beats/min, hypoxic on 100% non-rebreathing mask with saturations of 92%. Obvious clinical acute respiratory failure was present. The patient was started on non-invasive ventilation but continued to deteriorate.  He was deemed too unstable to obtain a CT scan. EKG showed sinus tachycardia. The patient was transferred to the ICU for respiratory failure. A chest x-ray was obtained (Figure 1).

Figure 1. Panel A: Admission chest x-ray which was interpreted as not different from the patient’s previous chest x-ray. Panel B: Portable chest x-ray taken shortly after initiation of non-invasive ventilation just after arrival in the intensive care unit.

The portable chest x-ray taken in the ICU shows a new right-sided consolidation and which of the following? (Click on the correct answer to proceed to the second of six pages)

1. Left pleural effusion and a loculated pneumothorax with tension physiology
2. Left pneumothorax with tension physiology
3. Left pneumothorax without tension physiology
4. Left sided tension hydropneumothorax
5. None of the above

Cite as: Singarajah CU. April 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(4):183-91. doi: https://doi.org/10.13175/swjpcc042-18 PDF

Increased Incidence of Eosinophilia in Severe H1N1 Pneumonia during 2015 Influenza Season

Benjamin Deaton MD

Nicholas Villalobos MD

Andrea Mytinger DO

Michel Boivin MD

Department of Internal Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

Abstract

Background: A portion of patients with influenza develop a severe, life t-threatening illness requiring intensive care. We observed a significant number of critically ill influenza patients with eosinophilia during the 2015 influenza season in New Mexico.

Methods: Patients were identified sequentially by reviewing disposition records of all patients admitted to the University of New Mexico Hospital medical intensive care unit between October 2015 and May 2016 for a diagnosis of influenza.

Results: Eleven patients were identified who developed respiratory failure from influenza. Average age was 43.7 + 11.3 (SD) with an average SAPS-2 score of 52.0 + 13.9 (SD) on admission. All 11 were found to have H1N1 influenza. All 11 required mechanical ventilation vasopressor support. Ten patients survived. Notably, 6 (54.5%) developed peripheral eosinophilia (>300/μL) during their hospitalization and all but one of these did not have peripheral eosinophilia at the time of admission. Bronchoalveolar lavage was performed in 5 patients (45.5%) and none were consistent with eosinophilic pneumonia. Further data analysis revealed exploration revealed no significant differences in multiple parameters and no clear cut cause of drug-induced eosinophilia was identified.

Conclusion: During the 2015 influenza season in New Mexico, a disproportionate number of patients with H1N1 influenza and respiratory failure developed peripheral eosinophilia. Type 2 errors could have occurred due to low sample size. Given the unusual frequency of peripheral eosinophilia further studies regarding the association of influenza A and peripheral eosinophilia is warranted.

Introduction

Influenza pneumonia remains a cause of significant morbidity and mortality (1). The re-emergence of H1N1 influenza in 2009 was associated with particularly severe respiratory illness, acute respiratory distress syndrome (ARDS) and mortality (2). The ARDS associated with H1N1 influenza appeared to disproportionately affect younger individuals, compared to other strains of influenza A (2). During the 2015 influenza season H1N1 circulated relatively late in the southwestern United States (3). Intensivists caring for patients with severe H1N1 pneumonia at the University of New Mexico hospital noticed a series of cases associated with significant peripheral eosinophilia. Eosinophilia with influenza or its treatments has rarely been described (4). We therefore sought to examine all cases of severe influenza pneumonia during the 2015 influenza season for the prevalence of peripheral eosinophilia and to assess for potential associations.

Methods

This study was reviewed and approved by the Institutional Review Board of the University of New Mexico Health Sciences Center. Patients from the University of New Mexico Hospital (UNMH) adult Medical Intensive Care Unit (MICU) admitted between October 2015 through May 2016 were retrospectively screened for inclusion. Inclusion criteria included a diagnosis of influenza (using a PCR based assay of nasal swab), admission to the UNMH MICU and age ≥ 18 years. Exclusion criteria included patients admitted to the MICU where influenza did not lead to significant respiratory failure.

In this retrospective cohort chart review, data was collected for demographics, clinical parameters at presentation and throughout their hospital course, and interventions received. Patients were assessed for the presence of eosinophilia at any point during their hospital course. Eosinophilia was defined as a serum eosinophil count that exceeded the upper limit of normal on a complete blood count (0.3x10³ cells/microliter). Values are reported with their standard deviation. Statistical analysis was performed using Stata 14 for Mac. The data was explored using two-sided t-tests, Fisher’s exact and Chi-squared tests between the 2 groups with and without eosinophilia. The paper was partially presented in poster form at the 2017 American Thoracic Society International Congress in Washington, DC (5).

Results

Thirteen patients with influenza were identified. Two patients were excluded from further analysis as they did not meet the criteria of having respiratory failure, the remaining eleven were included in this study. The average age of patients in the study was 43.7 ±11.3 years with an average SAPS-2 score of 52.0 ± 13.9 on admission. All eleven patients in the study admitted with severe influenza A leading to respiratory failure during the 2015-2016 influenza season were found to be infected by the H1N1 strain of influenza. See Table 1 for further descriptors of the cohort.

Table 1. Baseline and treatment characteristics by group.

The peak eosinophil count of the group with normal eosinophil count was 0.1(+0.1) X10³ cells/µl compared to 1.9 (+ 2.1) X10³ cells/µl in the group with significant peripheral eosinophilia (p=0.06). The range of eosinophilia in the group with normal eosinophil count was 0.0-0.3 X10³ cells/µl, and 0.5-4.8 X10³ cells/µl in the group with eosinophilia. The group with normal eosinophil count reached a “peak” count after an average of 4.6 days, and the group with an elevated eosinophil count after 17.1 days (p<0.02).None of the patients who underwent bronchoscopy had a significant elevation in the bronchoalveolar lavage eosinophil count.

Discussion

During the 2015-2016 influenza season in New Mexico, critically ill patients at UNM hospital admitted with influenza pneumonia were infected with the H1N1 subtype. Over 50 percent of these patients developed peripheral eosinophilia at some point of their hospital course. Among those who underwent bronchoscopy, significant alveolar eosinophilia was not observed, suggesting against a pulmonary cause of eosinophilia, such as acute or chronic eosinophilic pneumonia. All patients were treated with oseltamivir, so an association with this treatment could not be determined. No demographic differences were noted between patients who vashad peripheral eosinophilia and those that did not. The patients with significant peripheral eosinophilia trended to have a longer ICU and hospital length of stay (LOS) but this did not reach statistical significance in this small cohort.

Type 2 errors (failure to detect a true difference between groups due to small numbers of subjects) could have occurred due to low sample size while exploring etiologies. Potential etiologies that could have explained the observed eosinophilia included drug effect, possibly due to oseltamivir, antibiotics, diuretics or other medications. A review of the literature reveals case reports of associations between eosinophilia and influenza vaccine (6,7). Acute eosinophilic pneumonia has also been associated with H1N1 infection, but eosinophilia was not demonstrated on broncho-alveolar lavage in our series (8.9). Potentially this could have been a reaction to epitopes of this particular strain of H1N1 influenza. However, there have yet to be reports of eosinophilia during the 2015-2016 influenza season in the literature. Perhaps local factors could have contributed to an increased incidence of significant peripheral eosinophilia. Anecdotally, the authors do not however recall an increased incidence of eosinophilia in patients admitted for diagnoses other than H1N1. Patients were screened for other causes of viral pneumonia, and there was no clear co-infection that was associated with influenza associated eosinophilia. It was also noted the time to peak eosinophil count was much later in the elevated eosinophil group, and in most it took 14 days for the count to peak. This suggests the stimulus for the eosinophilia was ongoing for considerable time during the admission.

In conclusion, we describe an unusually high incidence of peripheral eosinophilia in patients with severe H1N1 influenza during the 2015 flu season. This eosinophilia was not associated with alveolar eosinophilia. Further observation for the recurrence of this association of H1N1 influenza A and peripheral eosinophilia is warranted during future influenza seasons.

References

1. Rotrosen ET, Neuzil KM, Influenza: a global perspective. Pediatr Clin North Am. 2017;64:911-36. [CrossRef] [PubMed]
2. Davlin SL, Blanton L, Kniss K, et al. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine.MMWR Morb Mortal Wkly Rep. 2016 Jun 10;65(22):567-75. [CrossRef] [PubMed]
3. Uyeki TM. Influenza. Ann Intern Med. 2017 Sep 5;167(5):ITC33-ITC48. [CrossRef] [PubMed]
4. Deaton, BR., Mytinger, AK, Ahmed, S, et al. Peripheral eosinophilia associated with 2016 H1N1 influenza. Am J Resp Crit Care. 2017;195:A5787 [Abstract],
5. Hayashi R, Shimomura N, Hosojima M, et al. A case of non-episodic angioedema with eosinophilia induced by influenza vaccine. Eur J Dermatol. 2017;27:554-5. [CrossRef] [PubMed]
6. Solak B, Dikicier BS, Kara RO, Erdem T. DRESS syndrome potentially induced by allopurinol and triggered by influenza vaccine. BMJ Case Rep. 2016 Mar 30;2016. [CrossRef] [PubMed]
7. Larrañaga JM, Marcos PJ, Pombo F, Otero-González I. Acute eosinophilic pneumonia as a complication of influenza A (H1N1) pulmonary infection. Sarcoidosis Vasc Diffuse Lung Dis. 2016 Mar 29;33(1):95-7. [PubMed]
8. Jeon EJ, Kim KH, Min KH. Acute eosinophilic pneumonia associated with 2009 influenza A (H1N1). Thorax. 2010;65:268-70. [CrossRef] [PubMed]

Cite as: Deaton B, Villalobos N, Mytinger A, Boivin M. Increased incidence of eosinophilia in severe H1N1 pneumonia during 2015 influenza season. Southwest J Pulm Crit Care. 2018;16(3):146-9. doi: https://doi.org/10.13175/swjpcc021-18 PDF 

May 2017 Critical Care Case of the Month

Sapna Bhatia, MD

David Ling, DO

Michel Boivin, MD

Division of Pulmonary, Critical Care and Sleep Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

History of Present Illness

A 54-year-old Hispanic male who was incarcerated 3 days prior to hospital admission was brought into the emergency room from prison for alcohol related withdrawal seizures.

Physical Examination

Upon arrival to the ER, the patient was noted to be hypoxic with copious thick secretions in his mouth. He was intubated for airway protection, started on propofol and fentanyl drips as well as intravenous thiamine and folic acid.

Radiography

A chest radiograph was performed (Figure 1).

Figure 1. Portable anterior-posterior (AP) radiograph of the chest.

Which of the following are true regarding management of this patient?

1. Phenytoin should be administered for prevention of seizures
2. Prophylactic antibiotics for aspiration pneumonia should be administered
3. Thiamine and folic acid should be administered
4. 1 and 3
5. All of the above

Cite as: Bhatia S, Ling D, Boivin M. May 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;14(5):192-8. doi: https://doi.org/10.13175/swjpcc051-17 PDF

January 2017 Critical Care Case of the Month

Seth Assar, MD

Clement U. Singarajah, MD

Pulmonary and Critical Care Medicine

Banner University Medical Center Phoenix – Phoenix

Phoenix VA Medical Center

Phoenix, AZ USA

History of Present Illness

The patient is a 48-year-old man who presented with two days of progressive shortness of breath and non-productive cough. There were no associated symptoms and the patient specifically denied fever, chills, night sweats, myalgia or other evidence of viral prodrome. He had no chest pain or tightness, nausea, vomiting, or leg swelling and he could lay flat. He had no recent travel or sick contacts and was Influenza-immunized this season.

Past Medical History

• Hypertension
• Hyperlipidemia
• Type 2 diabetes mellitus with a recent hemoglobin A1C of 11%        

Social History

• Cook at pizzeria
• Gay and lives at home with roommate of several years
• Smokes marijuana weekly.
• Prior history of cocaine use

Family History

• Noncontributory

Physical Examination

• Vitals: T 99.1º F / HR 125 / BP 193/93 / RR 24 / SpO2 88%
• General: Tachypneic. Alert and oriented X 4.
• Lungs: Crackles at bases bilaterally, no wheezes
• Heart: tachycardia
• Abdomen: NSA
• Skin: no needle marks or cellulitis

Laboratory

• CBC: WBC 11,700 cells/mcL with 80% polymorphonuclear leukocytes, otherwise normal
• Basic metabolic panel: normal
• Brain natriuretic peptide: 120 pg/ml
• Urine drug screen was negative for cocaine but positive for marijuana.
• D-dimer: 0.32 mcg/mL

Hospital Course

He was admitted to the ICU but quickly deteriorated and was intubated for hypoxemia. Empiric ceftriaxone and levofloxacin were begun.

Chest x-ray demonstrated bilateral patchy airspace opacities (Figure 1).

Figure 1. Admission chest x-ray.

Which of the following should be done next? (click on the correct answer to proceed to the second of six pages)

1. Bedside cardiac ultrasound
2. Coccidioidomycosis serology
3. CT scan of the chest
4. 1 and 3
5. All of the above

Cite as: Assar S, Singarajah CU. January 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;14(1):6-13. doi: https://doi.org/10.13175/swjpcc143-16 PDF

November 2016 Critical Care Case of the Month

Richard A. Robbins, MD

Phoenix Pulmonary and Critical Care Research and Education Foundation

Gilbert, AZ USA

History of Present Illness

A 45-year-old Iraqi War Veteran was seen in the outpatient clinic after referral for COPD based on abnormal blood gases. He denies any dyspnea or cough.

PMH, SH and FH

He has a history of a lower back injury and uses a motorized wheelchair. His pain is managed with morphine sulfate ER 60 mg daily and morphine sulfate 10 mg every 4 hours as needed for breakthrough pain.

He does not smoke cigarettes but does use marijuana for pain. He denies alcohol abuse.

Physical Examination

Physical examination shows a lethargic man in a wheelchair who intermittently falls asleep during questioning and examination. When aroused he is oriented to time, place and person and frequently mentions that his pain is a 10. His vital signs are normal expect his SpO2 is 75% on room air. His lungs were clear and his heart had a regular rhythm without murmur. His pupil size is approximately 2 mm bilaterally and muscle strength is difficult to determine due to his inability to remain alert or fully cooperate.

Radiography

A chest x-ray had been performed about a week previously (Figure 1).

Figure 1. Initial chest x-ray.

Spirometry had been performed earlier in the day (Figure 2).

Figure 2. Spirometry.

Which of the following are indicated at this time? (Click on the correct answer to proceed to the second of four pages)

1. Arterial blood gases (ABGs)
2. Immediate intubation
3. Intensive care unit (ICU) admission
4. 1 and 3
5. All of the above

Cite as: Robbins Ra. November 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;13(5):196-201. doi: http://dx.doi.org/10.13175/swjpcc103-16 PDF

October 2016 Critical Care Case of the Month

Stephanie Fountain, MD

Banner University Medical Center Phoenix

Phoenix, AZ USA

Critical Care Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours 

Lead Author(s): Stephanie Fountain, MD.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

A 27-year-old Caucasian man with past medical history of opioid abuse (reportedly sober for 10 years on buprenorphine), post traumatic stress disorder, depression and anxiety presented to the emergency department complaining of dysarthria after taking diphenhydramine and meclizine in addition to his prescribed trazodone and buprenorphine to try to sleep. He was discharged to home after his symptoms appeared to improve with intravenous fluid.

He returned to the emergency department the following afternoon with worsening dysarthria, dysphagia, and subjective weakness. The patient was non toxic appearing, afebrile, vital signs were stable and his strength was reported as 5/5. Computed tomography  of his head did not show any evidence of acute intracranial abnormality. Given his ongoing complaints, he was admitted for observation to the general medicine wards.

That night a rapid response was initiated when the nurse found the patient to be unresponsive, but spontaneously breathing. The patient’s clinical status did not change with naloxone administration. An arterial blood gas obtained demonstrated a profound respiratory acidosis with a pH of 7.02 and a pCO2 of 92. He was emergently intubated. A chest x-ray was performed (Figure 1).

Figure 1. Panel A: admission portable chest x-ray. Panel B: chest -ray immediately after intubation. 

Which of the following are present on his chest X-ray? (Click on the correct answer to proceed to the second or four panels)

1. Left lung atelectasis
2. Left pleural effusion
3. Right mainstem intubation
4. 1 and 3
5. All of the above

Cite as: Fountain S. October 2016 critical care case of the month. Soutwest J Pulm Crit Care. 2016:13(4):159-64. doi: http://dx.doi.org/10.13175/swjpcc095-16 PDF

December 2015 Critical Care Case of the Month

Samir Sultan, DO 

Banner University Medical Center Phoenix

Phoenix, AZ 

History of Present Illness

The patient is a 32-year-old woman who presented with flank pain for 3 days to an outside hospital. She was diagnosed with pyelonephritis and begun on ceftriaxone. She was discharged against medical advice on cephalexin.

She returned to the same hospital 3 days later by ambulance with labored breathing and weakness and was emergently intubated. She was transferred for ventilator management and respiratory failure.

Past Medical History

She has a long history of poorly controlled diabetes mellitus.

Physical Examination

She is orally intubated and sedated.

Vitals: Temperature - 100.9º F, Blood Pressure - 117/75 mm Hg, Heart Rate - 148 beats per minute,  Respiratory Rate - 31 breaths/min, SpO2 - 88 % on assist control of 30, tidal volume of 350 mL, PEEP 15, and an FiO2 100%.

There is scatted rhonchi and rales but the remainder of the physical examination is unremarkable.

Radiography

Her admission portable chest X-ray is shown in Figure 1.

Figure 1. Admission portable AP of the chest.

Which of the following should be ordered as part of her initial work-up? (Click on the correct answer to proceed to the second of five panels).

1. Administer broad spectrum antibiotics
2. Blood and urine cultures
3. Rapid influenza test
4. 1 and 3
5. All of the above

Cite as: Sultan S. December critical care case of the month. Southwest J Pulm Crit Care. 2015;11(6):246-51. doi: http://dx.doi.org/10.13175/swjpcc147-15 PDF

Ultrasound for Critical Care Physicians: Take a Deep Breath

David Ling, DO

Michel Boivin, MD

Division of Pulmonary, Critical care and Sleep Medicine

University of New Mexico School of Medicine

Albuquerque, NM

A 40 year old man with a past medical history of intravenous drug abuse presented to the emergency department with difficulty walking and lower extremity weakness. He did admit to recent heroin use. He became somnolent in the ED and was given naloxone. However, he did not improve his level of consciousness sufficiently and was intubated for hypercarbia. The patient was transferred to the MICU and was evaluated for respiratory failure. He later that day passed a spontaneous breathing trial after he awoke and was extubated. However, he was soon thereafter was re-intubated for poor respiratory efforts and a weak cough. 

With an unexplained etiology for the respiratory failure, CT of the head, MRI of the brain and lab evaluation were pursued but were negative.  At that point, a bedside ultrasound of the right hemi-diaphragm in the zone of apposition was obtained and is shown below:

Figure 1. Ultrasound of the right hemi-diaphragm at low depth, at the zone of apposition. The diaphragm is visualized above the liver as three parallel echogenic stripes.

Figure 2. M-mode image of the right hemi-diaphragm. The m-mode image is on the left, and the corresponding 2D image is on the right.

What does the video and M-mode of the diaphragm demonstrated above predict for the potential result of the patient’s extubation? (Click on the correct answer for the answer and explanation)

1. Success
2. Failure
3. Has no predictive value

Reference as: Ling D, Boivin M. Ultrasound for critical care physicians: take a deep breath. Southwest J Pulm Crit Care. 2015;11(1):38-41. doi: http://dx.doi.org/10.13175/swjpcc091-15 PDF

February 2015 Critical Care Case of the Month: A Bloody Mess

Mily Sheth, MD

Carmen Luraschi, MD

Matthew P. Schreiber, MD, MHS

University of Nevada School of Medicine: Las Vegas

Department of Internal Medicine

Division of Pulmonary/Critical Care

Las Vegas, NV

History of Presenting Illness:

A 23-year-old Ethiopian woman with a known history of systemic lupus erythematosus (SLE) but of unknown duration presented with the chief complains of cough and generalised weakness for 1 week. She had a recent history of travelling to Ethiopia 3 months ago for 3 weeks. She complained of subjective fevers and one episode of blood tinged sputum. She also complained of fatigue and an episode of syncope which prompted her hospitalization.

PMH, SH and FH:

The patient has a past medical history of SLE diagnosed in Ethiopia of which no records were available. She is a student and denied alcohol, smoking or drug abuse. She denied any family history of autoimmune disorders. She did not take any medications at home.

Physical Examination:

Initial admission vital signs were temperature of 100.5 F, heart rate of 130, respiratory rate of 30 and blood pressure of 92/48. Oxygen saturation was 96% on 2 L/min via nasal cannula.

She appeared to be in moderate distress but was speaking in full sentences. Skin examination revealed a malar rash on her face. Her upper and lower extremities had excoriated plaques. Her anterior chest had flat non blanchable, macular rash. CVS examination revealed tachycardia without any murmurs. Respiratory exam was positive for bilaterally diffuse bronchial breath sounds. The remainder of her exam was within normal limits.

Laboratory and Radiology:

CBC: WBC 6.7 million cells/mcL, hemoglobin 7.1 g/dL, hematocrit 20.9, platelet 160,000 cells/mcL

Renal panel: within normal limits.

Troponin 0.01, creatine kinase 457 U/L, lactic acid 1.1 mm/L, HIV non-reactive

Liver function tests: AST 288 U/L, ALT 93 U/L alkaline phosphatase 136 IU/L, total bilirubin 0.9 mg/dL

Radiography:

Her initial chest x-ray is shown in figure 1. It was interpreted as showing diffuse pulmonary infiltrates, right lung greater than left. No pleural effusions. No pneumothorax.

Figure 1. Initial chest x-ray.

In a patient with these characteristics, which other test(s) would you order? (Click on the correct answer to proceed to the second of five panels)

1. Arterial blood gases and lactic acid
2. Cardiac angiogram
3. Computed tomography (CT) of the chest without contrast
4. VATS lung biopsy
5. All of the above

Reference as: Sheth M, Luraschi C, Schreiber MP. February 2015 critical care case of the month: a blood mess. Southwest J Pulm Crit Care. 2015;10(2):63-9. doi: http://dx.doi.org/10.13175/swjpcc148-14 PDF

Ultrasound For Critical Care Physicians: Neutropenic Patient With Fever and Shortness of Breath

Erik Kraai MD

Michel Boivin MD

Division of Pulmonary / Critical Care and Sleep

University of New Mexico

Albuquerque, NM

A 63 year old female with a history of acute myelogenous leukemia presents with shortness of breath, fever and hypotension to the ICU. She is in septic shock on norepinephrine, and has been treated on the oncology unit with vancomycin, cefepime, acyclovir and voriconazole. She has been neutropenic for 1 month. The patient develops a progressive right lower chest opacity. This opacity has progressed in spite of antibiotics and antifungals. The portable AP chest radiograph is presented below (Figure 1). 

Figure 1. Portable AP of chest.

An ultrasound of the right chest was performed for further evaluation of the opacity (figure 2). 

Figure 2. Ultrasound of right hemithorax.

Question: What pathology does the ultrasound reveal in the right hemithorax? (Click on the correct answer to proceed to the next panel)

1. Air filled cavity
2. Chest wall abscess
3. Fractured ribs
4. Pleural effusion and suspected empyema
5. Simple consolidation

Refernece as: Kraai E, Boivin M. Ultrasound for critical care physicians: neutropenic patient with fever snd shortness of breath. Southwest J Pulm Crit Care. 2014;8(6):330-3. doi: http://dx.doi.org/10.13175/swjpcc073-14 PDF

June 2014 Critical Care Case of the Month: Acute Exacerbation in Cystic Fibrosis

Seongseok Yun, MD PhD¹ 

Juhyung Sun, BS²

Laura Howe, MD¹

Roberto Bernardo, MD¹

Sepehr Daheshpour, MD¹

Department of Medicine¹

College of Medicine²

University of Arizona

Tucson, AZ 85724

History of Present Illness

A 28 year-old woman with a history of cystic fibrosis, presented with worsening shortness of breath and cough associated with productive secretions. She was diagnosed with cystic fibrosis when she was 14 months old, and has a history of multiple inpatient admissions for acute pulmonary exacerbation of cystic fibrosis. Her most recent hospitalization was a month prior to this admission, and sputum culture demonstrated methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and Achromobacter xylosoxidans. She was treated with linezolide, meropenum, colistin, and azithromycin with significant symptom improvement, then, discharged home with ciprofloxacin, linezolide and zosyn. However, she developed worsening respiratory distress again and came back to hospital. In the emergency department she required 10 L/min of oxygen to maintain an SpO₂ above 90 %.

PMH

• Cystic fibrosis
• Seizure
• Kidney stone
• Portacath placement
• Gastrostomy tube placement

Medications

• Azithromycin 500 mg 3 times a day
• Dornase alpha 1 mg/ml nebulizer twice a day     
• Fluticasone-salmeterol 500-50 mcg/dose inhaler twice a day
• Lipase-protease-amylase 21,000-37,000-61,000 unit 4 caps a day
• Cholecalciferol  2,000 unit capsule daily
• Ferrous sulfate 325 mg PO twice a day
• Ascorbic acid 250 mg PO twice a day
• Oxycodone-acetaminophen  10-325 mg 4 times a day as needed

Social History

• No smoking
• No alcohol use
• No recreational drug use

Physical Examination

Vital signs: Temperature 37.3 °C, heart rate 114 beats/min, respiratory rate 20-24 breaths/min, blood pressure 99/69mmHg, SpO2 88-90 % on 10 L NC

General: Alert and oriented X 3, acutely distressed, tachypneic and dyspneic

Skin: Diaphoretic. No rash or lesions.

HEENT: Unremarkable.

Respiratory: Diffuse rales in all lung fields, no wheezing, no stridor

CVS: Tachycardic, regular rhythm, no murmur.

Abdomen: Soft, non-tender, no tenderness, no guarding, no hepato-splenomegaly, PEG tube placed

Lymphatics: No cervical or axillary lymphadenopathy

Extremities: No clubbing, no cyanosis, no peripheral edema, normal tone, normal range of movement

Neurological: Normal speech, no focal neurologic deficit, CN exam within normal range

Laboratory

CBC: WBC 11.9X 10³ /μL, Hb 9.8 g/dL, Hct 30.7%, Platelets 356,000 /μL.

Chemistries: Na⁺ 137 meq/L, K⁺ 4.1 meq/L, Cl^- 107 meq/L, CO₂ 22 mmol/L, blood urea nitrogen (BUN) 13 mg/dL, creatinine 0.7 mg/dL, glucose 106 mg/dL, calcium 8.0 mg/dL, albumin 2.6 g/dL, liver function tests within normal limits.

Prothrombin time (PT) 14.0 sec, international normalized ratio (INR)1.1, partial thromboplastin time (PTT) 37.2sec

Pulmonary Function Test

FVC 48 % (1.95 L), FEV₁ 36 % (1.25 L), FEF_25-75 14 % (0.55 L/sec)

Radiography

An old chest x-ray and thoracic CT scan were reviewed (Figure 1).

Figure 1. Previous PA (Panel A), lateral (Panel B) chest x-ray and representative image from the thoracic CT scan (Panel C).

Which of the following are findings of cystic fibrosis on chest x-ray? (Click on the correct answer to move to the next panel)

1. Bronchiectasis
2. Hyperinflation
3. Lobar collapse
4. Prominent pulmonary arteries
5. All of the Above

Reference as: Yun S, Sun J, Howe L, Bernardo R, Daheshpour S. June 2014 critical care case of the month: acute exacerbation in cystic fibrosis. Southwest J Pulm Crit Care. 2014;8(6):305-19. doi: http://dx.doi.org/10.13175/swjpcc047-14 PDF

May 2014 Critical Care Case of the Month: Second Wind

Kenneth K. Sakata, MD

Sudheer Penupolu, MD 

Robert W. Viggiano, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 65 year old woman was admitted for gastrointestinal bleeding as evidence by hematochezia. At the time of admission she denied any respiratory symptoms other than mild dyspnea. However, she rapidly developed respiratory failure, was transferred to the ICU and required emergent intubation.

PMH, FH, SH

She has a history of rheumatoid arthritis with a cervical spine fusion. There is also a history of sarcoidosis and she was receiving prednisone 30 daily up until the time of admission. There is no significant family history. She does not smoke or drink.

Physical Examination

Afebrile. Pulse 78. BP 105/65 mm Hg. Respirations: 28. SpO2 96% while receiving an FiO2 of 60% at the time of transfer to the ICU.

Neck: No jugular venous distention.

Lungs: Scattered rales and rhonchi.

Cardiovascular: Regular rhythm. 

Abdomen: no hepatosplenomegaly.

Radiography

A portable chest x-ray taken after intubation is shown in figure 1.

Figure 1. Portable chest x-ray taken shortly after intubation.

Which of the following best describe the chest x-ray? (Click on the correct answer to move to the next panel)

1. Chronic interstitial disease
2. Diffuse consolidation
3. Endotracheal tube in the right mainstem bronchus
4. Small right pneumothorax
5. All of the above

Reference as: Sakata KK, Penupolu S, Viggiano RW. May 2014 critical care case of the month: second wind. Southwest J Pulm Crit Care. 2014;8(5):258-65. doi: http://dx.doi.org/10.13175/swjpcc033-14 PDF

Fat Embolism Syndrome: Improved Diagnosis Through the Use of Bedside Echocardiography

Douglas T. Summerfield, MD

Kelly Cawcutt, MD

Robert Van Demark, MD

Matthew J. Ritter, MD

Departments of Anesthesia and Pulmonary/Critical Care Medicine

Mayo Clinic

Rochester, MN

Case Report

A 77 year old female with a past medical history of dementia, chronic atrial fibrillation requiring anticoagulation, hypertension, biventricular congestive heart failure with a preserved left ventricular ejection fraction, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD) presented to the emergency room after she sustained a ground level fall while sitting in a chair. The patient reportedly fell asleep while sitting at the kitchen table, and subsequently fell to her right side. According to witnesses, she did not strike her head, and there was no observed loss of consciousness. As part of her initial evaluation, at an outside hospital, radiographs of the pelvis, hip, and knee were obtained. These identified a definitive right superior pubic ramus fracture with inferior displacement and a questionable fracture of the right femoral neck. Shortly thereafter, the patient was transferred to our hospital for further management. On exam, the patient had a painful right hip limiting active motion and her right lower extremity was neurovascularly intact without paresthesias or dysesthesias. The remainder of the exam was unremarkable. In the emergency room, a repeat radiograph showed no evidence of a right femur fracture. Later in the evening a CT scan of the pelvis with intravenous contrast showed acute fractures through the right superior and inferior pubic rami with associated hematoma. Multiple tiny bony fragments were noted adjacent to the superior pubic ramus fracture (Figure 1).

Figure 1. CT scan demonstrating acute fractures through the superior and inferior pubic rami with associated hematoma. Multiple tiny bone fragments are adjacent to the superior pubic ramus fracture.

The CT did not show an apparent femur fracture. MRI of the pelvis and hip were ordered to assess for a femoral fracture; however this was not obtained secondary to patient confusion thus no quality diagnostic images were produced. The orthopedic service concluded that surgery was not required for the stable, type 1 lateral compression injury that resulted from the fall.

The patient was admitted to a general medicine floor for non-surgical management which included weight bearing as tolerated as well as therapy with physical medicine and rehabilitation. On admission, her vital signs were stable, including a heart rate of 89, blood pressure of 159/89, respirations of 20, with the exception of her peripheral oxygen saturation which was 89% on room air. Over the next several hospital days, she continued to have low oxygen saturations, began requiring fluid boluses to maintain an adequate mean arterial blood pressure (secondary to systolic blood pressure falling to the 70-80mmHg range intermittently) and she developed acute kidney injury with her creatinine increasing to 4.2 from her baseline of 1.1.  Nephrology was consulted to evaluate the acute kidney injury and their impression was acute renal failure secondary to contrast administration for the initial CT scan, in the setting of chronic spironolactone and furosemide use. The patient’s mental status remained altered, her speech although typically understandable was non-coherent, and she remained bed-bound. Due to her underlying dementia, her baseline mental status was difficult to determine and this combined with her opioids for pain control were felt to contribute to her mental status.

During her first dialysis session, the patient developed hypotension and hypoxemia which necessitated a rapid response call and transfer to the intensive care unit (ICU). The impression at the time of transfer to the ICU was septic shock with multi-organ dysfunction syndrome, presumably from a urinary source. The initial exam by the ICU team demonstrated what was thought to be considerable acute mental status change with agitation and moaning, hypotension, hypoxemia, and continued renal failure. Further review of her hospital course revealed that these changes had slowly been progressing since admission. Stabilization in the ICU included placement of a right internal jugular central venous catheter, blood pressure support with vasopressors, as well as intubation and high level of ventilatory support, including inhaled alprostadil, for severe hypoxemic respiratory failure. In addition, she was also placed on continuous renal replacement therapy.

In order to better assess the patient’s fluid status, the service fellow assessed the vena cava with the bedside ultrasound. While observing the collapsibility of the IVC, small hyperechoic spheres were observed traveling through the IVC proximally towards the right heart. A subcostal window focusing on the right ventricle demonstrated the same hyperechoic spheres whirling within the right ventricle. These same spheres were seen in both the four chamber view (Figure 2), as well as the short axis view and were present for several hours.

Figure 2. Four chambered view revealing right ventricular bowing as well as small hyperechoic spheres present in the right ventricle and atria.

Two hours later, a formal bedside echocardiogram was performed to evaluate the right heart structure and function. The estimated right ventricular systolic pressure was at 70 mm Hg, indicating severe pulmonary hypertension. The right ventricle was enlarged, and there was severe tricuspid regurgitation. Again there continued to be small hyperechoic spheres within her right ventricle as well as her right atria. Per the formal cardiologist reading, these were consistent with fat emboli. Further laboratory evaluation, including the presence of urinary fat, helped confirm the diagnosis of fat emboli syndrome.

Supportive care was continued, but without obvious improvement. After a family care conference, she was transitioned to palliative care and died.

Background

Fat emboli (FE) and fat emboli syndrome (FES) have been described clinically and pathologically since the 1860’s. Early work by Zenker in 1862 first described the pathologic significance of fat embolism with the link of fat to bone marrow release during fractures was discovered by Wagner in 1865. Despite the 150 years since its discovery, the diagnosis of Fat Embolism remains elusive. FE is quite common with the presence of intravascular pulmonary fat seen in greater than 90% of patients with skeletal trauma at autopsy (1). However, the presence of pulmonary fat alone does not necessarily mean the patient will develop FES. In a case series of 51 medical and surgical ICU patients, FE was identified in 28 (51%) of patients, none of whom had classic manifestations of FES (2).

The three major components of FES have classically consisted of the triad of petechial rash, progressive respiratory failure, and neurologic deterioration. The incidence following orthopedic procedures ranges from 0.25% to 35% (3). The wide variation of the reported incidence may in part be due to the fact that FES can affect almost every organ system and the classic symptoms are only present either transiently or in varying degrees, and may not manifest for 12-72 hours after the initial insult (4). The patient we present represents both the lack of the classic triad and the delayed onset of signs and symptoms, illustrating the elusiveness of the diagnosis.

Of the major clinical criteria, the cardio-pulmonary symptoms are the most clinically significant. Symptoms occur in up to 75% of patients with FES and range from mild hypoxemia to ARDS and/or acute cor pulmonale. The timing of symptoms may coincide with manipulation of a fracture, and there have been numerous reports of this occurring intraoperatively with direct visualization of fat emboli seen on trans-esophageal echo (TEE) (5-8).

The classic petechial rash, which was not noted in our patient, is typically seen on the upper anterior torso, oral mucosa, and conjunctiva. It is usually resolved within 24 hours and has been attributed to dermal vessel engorgement, endothelial fragility, and platelet damage all from the release of free fatty acids (9). The clinical manifestation of this “classic” finding varies widely and has been reported in 25-95% of the cases (4, 10).

Neurologic dysfunction can range from headache to seizure and coma and is thought to be secondary to cerebral edema due to multifactorial insults. These neurologic changes are seen in up to 86% of patients, and on MRI produce multiple small, non-confluent hyper intensities that appear within 30 minutes of injury. The number and size correlate to GCS, and subsequently reversal of the lesions is seen during neurologic recovery. (11,12).

Temporary CNS dysfunction usually occurs 24-72 hours after initial injury and acute loss of consciousness immediately post-operatively has been documented. Of note, this loss of consciousness may not be a catastrophic event. In a case report by Nandi et al., a patient with acute loss of consciousness made full neurologic recovery within four hours (13). In the retina, direct evidence of FE and FES manifests as cotton-wool spots and flame-like hemorrhages (1). However these findings are only detected in 50% of patient with FES (14)

FES also affects the hematological system, producing anemia and thrombocytopenia 37% and 67% of the time, respectively (15, 16). Thrombocytopenia is correlated to an increased A-a gradient, which Akhtar et al. noted that some clinicians include this finding in the criteria to diagnose FES (1).

Diagnosis

Given the broad and varying manifestations of FES, others have broadened the criteria. The Lindeque criteria require a femur fracture. The FES Index is a scoring system which includes vitals, radiographic findings, and blood gas results. Weisz and colleagues include laboratory values such as fat macroglobulenemia and serum lipid changes. Miller and colleagues (17) even proposed an autopsy diagnosis using histopathic samples. The most widely used criteria are set forth by Gurd and Wilson and require two out of three major criteria be met, or one major plus four out of five minor criteria. Major criteria include pulmonary symptoms, petechial rash, and neurological symptoms. Minor criteria include pyrexia, tachycardia, jaundice, platelet drop by >50%, elevated ESR, retinal changes, renal dysfunction, presence of urinary or sputum fat, and fat macroglobulinemia (1). Of note, none of the proposed diagnostic criteria include direct visualization of fat emboli via ultrasound or echocardiography (18-22) (Table 1).

Table 1: Gurd's Criteria for Diagnosis of FES

Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;52(4):732-7. [PubMed]

Mechanism

Two theories explain the systemic symptoms seen in FES. The mechanical theory describes how intramedullary free fat is released into the venous circulation directly from the fracture site or from increased intramedullary pressure during an orthopedic procedure. The basis for the theory is that the fat particles produce mechanical obstruction. However, not all fat emboli translocated into the circulation are harmful. It is estimated that fat particles larger than 8 μm embolize (23-25). As they accumulate in the lungs, aggregates larger than 20 μm occlude the pulmonary vasculature (26). Particles 7-10 μm particles can cross pulmonary capillary beds to affect the skin, brain, and kidneys. On a larger scale, the embolized free fatty acids produce ischemia and the subsequent release of inflammatory markers (27). The mechanism of this systemic spread beyond the pulmonary capillaries is not well understood. Patients without a patent foramen ovale or proven pulmonary shunt develop FES (28). Interestingly enough, other patients with a large fat emboli burden in the pulmonary microvasculature have not progressed to FES (29). One possible explanation for this may be elevated right-sided pressures force pulmonary fat into systemic circulation (1).

The biochemical theory has also been proposed to explain the systemic organ damage. The mechanism describes that enzymatic degradation of fat particles in the blood stream brings about the release of free fatty acids (FFA) (30, 31). FFA and the toxic intermediaries then cause direct injury on the lung and other organs. The fact that many of the symptoms are seen much later than the initial injury would support the Biochemical Theory. This theory also has an obstructive component to it as it recognizes that large fat particles coalesce to obstruct pulmonary capillary beds (11).

Discussion

Fat emboli syndrome is a rare and difficult clinical diagnosis. Currently there is no diagnostic test for FES and even the reported incidence is quite variable. The wide clinical presentation of FES makes the diagnosis challenge, and classic pulmonary involvement does not always occur (31). Furthermore, the symptoms overlap with other illness such as infection, as it did in this patient who was initially thought to be septic. The delayed onset of symptoms may further confound its identification. Finally, the traditional criteria used to diagnosis FES are variable depending on which source is referenced. Case-in-point is the Lindque criteria which require the presence of a femur fracture. By this requirement the patient presented in this case would not have been diagnosed with FES as she presented with a pelvic fracture.

The patient in this case was likely suffering from undiagnosed FES from the time of her admission. Since it did not present in the classic fashion, her progressive respiratory failure and neurologic deterioration were incorrectly attributed to congestive heart failure and opioid administration.

In this patient, the diagnosis of FE was somewhat unexpected, although it was within the differential. For this case the implementation of bedside ultrasound proved critical to the correct diagnosis and subsequent outcome. Instead of following other possible diagnoses and treatment options such as sepsis in this tachycardic, hypotensive patient, supportive care was employed with the diagnosis of fat embolism in mind.

The use of ultrasound imaging is not well studied for the diagnosis of FES, however it may provide an additional tool for making this difficult diagnosis when the classic triad of rash, cardiopulmonary symptoms, and neurologic changes is not seen or is in doubt. When used to evaluate for cardiogenic causes of acute hypotension, bedside cardiac ultrasound may reveal findings suggestive of FES, as it did in this case.

Review of the literature (5-8) confirms similar echogenic findings from fat emboli as seen by TEE intraoperatively during orthopedic procedures. However, similar spheres can be seen in a number of other instances. Infusion of blood products, such as packed red blood cells, may create similar acoustic images. No blood products had been given to the patient at the time of the bedside ultrasound. Additionally cardiologists have traditionally used agitated saline to look for patent foramen ovale. This and air embolism after placement of a central venous catheter can both produce similar images. In this case the emboli were seen traveling through the inferior vena cava, inferior and distal to the right side of the heart. The right internal jugular catheter would not have showered air emboli to that location, additionally once these were seen circulating in the right ventricle, the first action performed was to ensure all ports on the central line were secure. Given that these hyperechoic spheres were present for hours, air emboli would be less likely to be the underlying etiology. The images were later seen during the formal cardiac echo, and again validated by the cardiologist as being consistent with fat emboli.

To our knowledge this is the first case report of critical care bedside echocardiography (BE), assisting with the diagnosis of fat emboli syndrome. This is in contrast to TEE which has been used to diagnose FE and presumed FES in hemodynamically unstable patients in the operating room (5-8).

BE is attractive as it requires less training than TEE and can be repeated at the bedside as the clinical picture changes. By itself BE cannot differentiate FE from FES, but since the practitioner using it is presumably familiar with the patient’s condition, it can be used to augment the diagnosis when other findings are also suggestive of FE.

It has been suggested that a basic level of expertise in bedside echocardiography can be achieved by the non-cardiologist in as little as 12 hours of didactic and hands-on teaching. Given this amount of training, the novice ultrasonographer should be able to identify severe left or right ventricular failure, pericardial effusions, regional wall motion abnormalities, gross valvular abnormalities, and volume status by assessing the size and collapsibility of the inferior vena cava (32-37). Potentially, based on this case, the list could include FE with FES in the correct clinical context, pending further clinical validation.

In conclusion, this is the first reported case of bedside ultrasonography assisting in the diagnosis of FES in the ICU. The case illustrates the diagnostic challenge of FE and FES and also highlights the potential utility of bedside ultrasonography as a diagnostic tool.

References

1. Akhtar S. Fat Embolism. Anesthesiology Clinics. 2009;27:533-50. [CrossRef] [PubMed] 
2. Gitin TA, Seidel T, Cera PJ, Glidewell OJ, Smith JL. Pulmonary microvascular fat: The significance? Critical Care Medicine. 1993;21(5):673-7. [CrossRef] [PubMed] 
3. Raza SS, Noheria A, Kesman RL. 21-year-old man with chest pain, respiratory distress, and altered mental status. Mayo Clin Proc. 2011;86(5):e29-e32. [CrossRef] [PubMed]
4. Capan LM, Miller SM, Patel KP. Fat embolism. Anesthesiol Clin North America. 1993;11:25–54.
5. Shine TS, Feinglass NG, Leone BJ, Murray PM. Transesophageal echocardiography for detection of propagating, massive emboli during prosthetic hip fracture surgery. Iowa Orthop J. 2010;30:211-4. [PubMed] 
6. Heinrich H, Kremer P, Winter H, Wörsdorfer O, Ahnefeld FW. Transesophageal 2-dimensional echocardiography in hip endoprostheses. Anaesthesist. 1985;34(3):118-23. [PubMed] 
7. Pell AC, Christie J, Keating JF, Sutherland GR. The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. A study of 24 patients with femoral and tibialfractures. J Bone Joint Surg Br 1993; 75:921-5. [PubMed]
8. Christie J, Robinson CM, Pell AC, McBirnie J, Burnett R. Transcardiac echocardiography during invasive intramedullary procedures. J BoneJoint Surg Br 1995;77:450-5. [PubMed]
9. Pazell JA, Peltier LF. Experience with sixty-three patients with fat embolism. Surg Gynecol Obstet 1972;135(1):77–80. [PubMed] 
10. Gossling HR, Pellegrini VD Jr. Fat embolism syndrome: a review of the pathophysiology and physiological basis of treatment. Clin Orthop Relat Res. 1982;165:68–82. [PubMed] 
11. Shaikh N, Parchani A, Bhat V, Kattren MA. Fat embolism syndrome: Clinical and imaging considerations: Case report and review of literature. Indian J Crit Care Med. 2008;12(1):32-6. [CrossRef] [PubMed]
12. Butteriss DJ, Mahad D, Soh C, Walls T, Weir D, Birchall D. Reversible cytotoxic cerebral edema incerebral fat embolism. AJNR Am J Neuroradiol. 2006;27(3):620-3. [PubMed]
13. Nandi R, Krishna HM, Shetty N. Fat embolism syndrome presenting as sudden loss of consciousness. J Anaesthesiol Clin Pharmacol. 2010;26(4):549-50. [Pubmed]
14. Adams CB. The retinal manifestations of fat embolism. Injury. 1971;2(3):221-4. [CrossRef]
15. Mellor A, Soni N. Fat embolism. Anaesthesia. 2001;56:145-54. [CrossRef]
16. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg. 1997;132:435-9. [CrossRef] [PubMed]  
17. Miller P, Prahlow JA. Autopsy diagnosis of fat emboli syndrome. Am J Forensic Med Pathol. 2011;32(3):291-9. [CrossRef] [PubMed] 
18. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;52(4):732-7. [PubMed]
19. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br 1974;56(3):408-16.
20. Weisz GM, Rang M, Salter RB. Posttraumatic fat embolism in children: review of the literature and of experience in the Hospital for Sick Children, Toronto. J Trauma. 1973;13:529-34. [CrossRef] [PubMed] 
21. Lindeque BG, Schoeman HS, Dommisse GF, Boeyens MC, Vlok AL. Fat embolism and the fat embolism syndrome. A double-blind therapeutic study. J Bone Joint Surg Br 1987;69(1):128-31. [PubMed] 
22. Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammerschmidt DE, Jacob HS. Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients. Ann Intern Med. 1983;99:438-43. [CrossRef] [PubMed] 
23. Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med. 1993;329:926-9. [CrossRef] [PubMed] 
24. Argenziano M. The incidental finding of a patent foramen ovale during cardiac surgery: should it always be repaired? Anesth Analg. 2007;105:611-2. [CrossRef] [PubMed] 
25. Emson HE. Fat embolism studied in 100 patients dying after injury. J Clin Pathol. 1958;11(1):28-35. [CrossRef] [PubMed]
26. Batra P. The fat embolism syndrome. J Thorac Imaging. 1987;2(3):12–17. [CrossRef] [PubMed] 
27. Meyer N, Pennington WT, Dewitt D, Schmeling GJ. Isolated cerebral fat emboli syndrome in multiply injured patients: a review of three casesand the literature. J Trauma. 2007;63:1395-1402. [PubMed] 
28. Nijsten MW, Hamer JP, ten Duis HJ, Posma JL. Fat embolism and patent foramen ovale [letter]. Lancet 1989;1(8649):1271. [CrossRef]
29. Aoki N, Soma K, Shindo M, Kurosawa T, Ohwada T. Evaluation of potential fat emboli during placement of intramedullary nails after orthopedic fractures. Chest. 1998;113(1):178-81. [CrossRef] [PubMed] 
30. Talbot M, Schemitsch EH. Fat embolism syndrome: history, definition, epidemiology. Injury. 2006;37S:S3-S7. [CrossRef] [PubMed] 
31. Levy D. The fat embolism syndrome. A review. Clin Orthop Relat Res. 1990;261:281-6. [PubMed] 
32. Vignon P, Mücke F, Bellec F, Marin B, Croce J, Brouqui T, Palobart C, Senges P, Truffy C, Wachmann A, Dugard A, Amiel JB. Basic critical care echocardiography: Validation of a curriculum dedicated to noncardiologist residents. Crit Care Med. Apr 2011;39(4):636-42. [CrossRef] [PubMed] 
33. Vignon P, Dugard A, Abraham J, Belcour D, Gondran G, Pepino F, Marin B, François B, Gastinne H. Focused training for goal-oriented hand-held echocardiography performed by noncardiologist residents in the intensive care unit. Intensive Care Med. 2007;33(10):1795-99. [CrossRef] [PubMed] 
34. Manasia AR, Nagaraj HM, Kodali RB, Croft LB, Oropello JM, Kohli-Seth R, Leibowitz AB, DelGiudice R, Hufanda JF, Benjamin E, Goldman ME. Feasibility and potential clinical utility of goal-directed transthoracic echocardiography performed by noncardiologist intensivists using a small hand-carried device (SonoHeart) in critically ill patients. J Cardiothorac Vasc Anesth. 2005;19(2):155-9. [CrossRef] [PubMed] 
35. Melamed R, Sprenkle MD, Ulstad VK, Herzog CA, Leatherman JW. Assessment of left ventricular function by intensivists using hand-held echocardiography. Chest. Jun 2009;135(6):1416-20. [CrossRef] [PubMed] 
36. Vignon P, Chastagner C, François B, Martaillé JF, Normand S, Bonnivard M, Gastinne H. Diagnostic ability of hand-held echocardiography in ventilated critically ill patients. Crit Care. 2003;7(5):R84-91. [CrossRef] [PubMed]
37. Mayo PH, Beaulieu Y, Doelken P, Feller-Kopman D, Harrod C, Kaplan A, Oropello J, Vieillard-Baron A, Axler O, Lichtenstein D, Maury E, Slama M, Vignon P. American College of Chest Physicians/La Societe de Reanimation de Langue Francaise statement on competence in critical care ultrasonography. Chest. 2009;135(4):1050-60. [CrossRef] [PubMed]

Reference as: Summerfield DT, Cawcutt K, Van Demark R, Ritter MJ. Fat embolism syndrome: improved diagnosis through the use of bedside echocardiography. Southwest J Pulm Crit Care. 2013;7(4):255-64. doi: http://dx.doi.org/10.13175/swjpcc109-13 PDF