Ultrasound for Critical Care Physicians: Sickle Cell Crisis

A 32 year old man was admitted a week earlier with sickle cell pain crisis. He had developed increasing dyspnea, oxygen desaturation and bilateral pulmonary infiltrates.  He had a pulseless electric activity code blue and an ultrasound of the heart was obtained (Figure 1).

Figure 1. Subxiphoid view ultrasound of the heart.

What does the ultrasound show?

1. Aortic dissection
2. Aortic stenosis
3. Enlarged left ventricle
4. Enlarged right ventricle
5. Pericardial effusion

Reference as: Raschke RA. Ultrasound for critical care physicians: sickle cell crisis. Southwest J Pulm Crit Care. 2013:7(2):110-1. doi: http://dx.doi.org/10.13175/swjpcc113-13 PDF

August 2013 Critical Care Case of the Month: My, That’s a Big One

Andrew Waas, M.D.

Pulmonary Sciences and Critical Care Medicine

University of Colorado Hospital

Denver, Co

History of Present Illness

A 75 year old male presented to the emergency department with complaints of three days of increasing nausea, generalized weakness, and dyspnea on exertion.  He had undergone a radical prostatectomy 13 days prior to presentation from which he was recovering well until the onset of these symptoms. There was no associated chest pain, cough, fevers, chills or weight loss.

PMH, SH, FH

He had a history of hypertension and prostate cancer for which he underwent a recent prostatectomy.

He was born in Colorado and had not traveled recently.  There was no history of tobacco use, he drank ethanol on rare occasions, and did not use any illicit drugs. 

There was no family history of illnesses of which he was aware.

Medications

• Dutasteride 0.5 mg daily
• Telmisartan 40 mg daily

Physical Exam

Blood pressure 142/85, heart rate 108, temperature 36.7 C, respiratory rate 25, saturating 95% on 2L oxygen. 

Generally, he was in no distress, but was slightly tachypneic.  Lungs were clear to auscultation bilaterally and he was tachycardic but regular.  Otherwise, his exam was normal. 

Laboratory

Laboratory evaluation revealed a mild leukocytosis at 13 x 10⁶ cells/mcL with 72% neutrophils and 20% lymphocytes.  His basic metabolic panel (including creatinine) was normal; his liver function tests were likewise normal. 

Chest Radiography

His initial portable chest x-ray is shown in Figure 1.

Figure 1. Initial portable chest x-ray

Which of the following best describes the chest x-ray?

1. Cardiomegaly
2. Cavitating lung mass
3. Multifocal infiltrates
4. All of the above
5. None of the above

Reference as: Waas A. August 2013 critical care case of the month: my, that's a big one. Southwest J Pulm Crit Care. 2013;7(2):66-74. doi: http://dx.doi.org/10.13175/swjpcc096-13 PDF

July 2013 Critical Care Case of the Month: The Fortuitous Critical Care Consult

Clement U. Singarajah, M.D.

Elijah Poulos, M.D.

Phoenix VA Medical Center

Phoenix, AZ

History of Present Illness

A 70 year old male with squamous cell cancer of the hypopharynx had undergone a laser ablation and debridement as an outpatient. The ENT surgeon placed a # 6 Shiley DCT tracheostomy tube and the patient did well after the procedure. His chest x-ray after the procedure revealed right lower lobe atelectasis but was interpreted as otherwise normal (Figure 1).

Figure 1. Portable chest-ray after laser ablation and tracheostomy placement.

Due to aspiration and feeding issues, he was scheduled 2 weeks later for percutaneous endoscopic gastrostomy (PEG) tube placement as an outpatient. However, the gastroenterologist cancelled the procedure due to copious secretions from tracheal site, described as purulent and some mild respiratory distress. He was admitted to the general medicine service at the Phoenix VA Medical Center.  

Physical Examination

On examination of the patient, was non-toxic, talking, and alert. Vital signs were within normal limits, but with he had mild dyspnea and moderately thick secretions. A tracheostomy tube was in place in the neck. There were no areas of tenderness over his neck. The remainder of his physical examination was normal.

Radiography

A chest x-ray was performed (Figure 2). 

  

Figure 2. Admission PA (Panel A) and lateral (Panel B) chest x-ray.

Which of the follow are abnormal findings of the chest radiography?

1. The distal tip of the tracheostomy tube is not aligned with the tracheal stripe
2. There is a right pleural effusion
3. There is an air-fluid level in the right lower lung
4. There is right lower lobe atelectasis and/or consolidation
5. All of the above 

Reference as: Singarajah CU, Poulos E. July 2013 critical care case of the month: the fortuitous critical care consult. Southwest J Pulm Crit Care. 2013;7(1):10-16. doi: http://dx.doi.org/10.13175/swpcc075-13 PDF 

Fluid in the Management of the Acute Respiratory Distress Syndrome

Sanjaya Karki* (drsanjaya.karki@yahoo.com)

Yong-Jie Yin* (corresponding author)-yongjieyin2003@yahoo.com.cn

Jing-Xiao Zhang*

Nijamudin Samani*

Dipesh Pradhan^‡

Sangeeta Singh Deuja (Karki)^†

Reshma Karki^#

Raghvendra Thakur**

Nan Zhao***

*Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, China

^‡ First hospital of Jilin University, China

^†University of Huddersfield, UK

^#Sri Birendra Hospital, Nepal

**Second Hospital of Jilin University

***Department of Chemistry, Jilin University, Changchun, China

Abstract

Introduction

Non-cardiogenic pulmonary edema is the hallmark of the acute respiratory distress syndrome (ARDS). The amount of fluid and which fluid should be used in these patients is controversial. 

Methods

43 patients with ARDS treated in the intensive care unit (ICU) of the Second Hospital, Jilin University between November 1, 2011-November 1, 2012 were prospectively analyzed and was observational. Volume and the type of fluid administered were compared to 90 day mortality and the 24 and 72 hour sequential organ failure assessment (SOFA) score, lactate level, oxygenation index (PaO2/FiO2), duration of ICU stay, total ventilator days, and need for continuous renal replacement therapy (CRRT).

Results

Mortality was increased when hydroxylethyl starch (HES) was used in the first day or plasma substitutes were used during the first 3 days (P<0.05, both comparisons). Volumes of fluid >3000 ml during the first 24 hours or >8000 ml during the first 72 hours were associated with higher SOFA scores at 24 and 72 hours (P<0.05, both comparisons). Colloid, especially higher volume colloid use was also associated with increased SOFA scores at either 24 or 72 hours.

Conclusions

Limiting the use of colloids and the total amount of fluid administered to patients with ARDS is associated with improved mortality and SOFA scores.

Introduction

Acute lung disease secondary to non-cardiogenic pulmonary edema has been termed the adult respiratory distress syndrome (ARDS) since first described in 1967 by Ashbaugh et al. (1,2). ARDS was later defined at a consensus conference in Berlin (3). The Berlin definition is based on timing, chest imaging, origin of edema and oxygenation.

Despite the presence of fluid within the alveoli, it has been unclear whether a conservative strategy or liberal strategy improves outcomes. The ARDS Clinical Trials Network demonstrated that a conservative strategy based on pulmonary artery wedge pressures or central venous pressures improved lung function and shortened the duration of mechanical ventilation although there was no mortality benefit (4). However, whether fluid replacement with colloid or crystalloid in ARDS results in better outcomes remains unknown.

Recently, there have been reports of increased mortality with the use of hydroxylethyl starch (HES) in sepsis (5).  Because sepsis is the most common cause of ARDS (1) this caused us to examine the use of colloids in ARDS. We found that use of colloids was associated with clinically worsening and increases mortality compared to low volumes of crystalloid in ARDS.

Materials and Methods

Subjects

This was an observational study of ARDS patients admitted to the intensive care unit (ICU) of the Norman Bethune College of Medicine, Jilin University Second Hospital, Changchun, China was conducted from November 1, 2011 to November 1, 2012.

ARDS was defined using the Berlin criteria (3).

Study Procedures

Patients were randomly divided into two groups. In one group patients were administered both crystalloid and colloid for the first 3 days of their ICU admission with ARDS. In the other group only crystalloid was used. The use of which colloid and the volume administered was left to the clinical discretion of the attending physician based on the clinical needs of the patient. Other treatment modalities such as the mode of ventilation and nutritional support were also left to the discretion of the patient although the tidal volume was kept < 7ml/kg.

Data was collected for the first 3 days of admission to the ICU. Clinical data recorded included sequential organ failure assessment (SOFA) scores, the use and amount of colloid or crystalloid, duration of ICU stay, ventilator days, need for continuous renal replacement therapy (CRRT), lactate and PaO2/FIO2. When patients received both colloid and crystalloid, volume was calculated as the sum of the volume of each. Mortality was the 90 day mortality rate.

Statistics

The data was recorded and compared using SPSS software and reported as mean + standard deviation. Comparisons between groups were performed by Student’s t-test. P values of less than 0.05 were considered significant.

Results

Patients. There were 43 patients (20 F, 23 M). The mean age was 62.7 + 18.9 years (range 20 to 85 years). The causes of ARDS was serious lung infection in 16 patients,  sepsis in 9 patients, trauma in 2 patients, and pancreatitis in 2 patients. The cause was unknown in 14 patients.

Volume of fluid. The results with differing volumes of fluid administered in the first 24 hours are shown in Table 1. [Editor's note: It may be necessary to enlarge the view on your browser in order to adequately display the tables.]

Table 1. Results based on volume of fluid used in the first day.

Mortality was unaffected by the volume of fluid used in the first 24 hours. However, the SOFA score at 24 and 72 hours was increased with volumes >3000 ml administered during the first 24 hours (P<0.05, both comparisons). The lactate level and the frequency of CRRT approached significance when volumes of >3000 ml were administered during the first 24 hours (P=0.05, both comparisons).

The results with volumes of greater or less than 8 liters are shown in table 2.

Table 2. Results based on volume of fluid used in the first 72 hours.

 

There were no significant effects of administration of greater or less than 8000 ml over 72 hours.

Type of fluid. Patients who received both crystalloid and colloid received 30 + 5% of the total volume as colloid during the first day of ICU admission. The results of administration of crystalloid compared to crystalloid and colloid during the first 24 hours are shown in Figure 3.

Table 3. Results based on type of fluid used in the first day of ICU admission.

There was no difference in mortality. The use of crystalloid alone was associated with a lower SOFA score at 72 hours (P<0.05). CRRT was more often needed for those patients given both crystalloid and colloid during the first 24 hours (P=0.05).

The results when albumin was used during the first 24 hours are in Table 4.

Table 4. Results based on albumin usage during the first day.

There was no significant effect on any of the measured outcomes when albumin was used in the first 24 hours.

The results with the use of plasma during the first 24 hours are shown in Table. 5.

Table 5. Results based on plasma usage during first day.

An increase in mortality approached statistical significance if plasma was used during the first 24 hours (P=0.05). The SOFA score was significantly higher at 72 hours if plasma used during the first day (P=0.01). The remaining outcomes were unchanged.

Results with hydroxylethyl starch (HES) use are shown in Table 6.

Table 6. Results based on hydroxylethyl starch (HES) usage during the first day.

  

Mortality was significantly higher if HES was used during the first 24 hours (P<0.05). In addition the SOFA scores were significantly higher at 24 and 72 hours if HES was administered during the first 24 hours (P<0.05, both comparisons). The lactate level was also significantly higher at 24 hours and 72 hours (P<0.05, both comparisons). The need for CRRT and the PaO2/FiO2 ratio approached significance (P=0.05, both comparisons).

Volume of colloid. The use of colloids affected several outcomes. Therefore, the amount of colloid used was examined (Table 7).

Table 7. Results based on volume of colloid used during first day. 

If colloid was used, mortality approached significance based on the volume of colloid used during the first 24 hours (P=0.05). Higher volumes of administered colloid (≥1000ml) were associated with a higher SOFA score at 72 hours (P=0.01). Lactate levels were significantly higher at 24 and 72 hours if colloid was used (P=0.04, both comparisons).PaO2/FiO2 was lower higher volumes of colloid usage (P=0.04).

Plasma, albumin or plasma substitutes during the first 72 hours. Some outcomes were higher with the use of colloids during the first 24 hours. Therefore, usage of plasma or albumin during the first 3 days was examined (Table 8).

Table 8. Effect of using of plasma or albumin during the first 3 days.

There was no significant effect on any of the outcomes with the use of plasma or albumin during the first 72 hours.

The effects of plasma substitutes during the first 72 hours are shown in Table 9.

Table 9. Results of using plasma substitutes during the first 3 days.

Higher mortality was associated with the use of plasma substitutes during the first 3 days (P=0.02).  SOFA scores at 24 and 72 hours were also increased with plasma substitute usage (P=0.03 and P=0.002 respectively). Higher Lactate levels were also observed at 24 hours and 72 hours (P<0.01, both comparisons).

Discussion

In the hospital setting there are two types of fluid physicians administer to patients-colloid or crystalloid. Crystalloid is easily accessible and can be stored at room temperature. The main purpose of this study was to compare the two different fluids and the volume fluid used. We found that use of certain colloids, particularly higher volumes, was associated with increased mortality and poorer SOFA scores.

There was increased mortality with HES and plasma substitutes and plasma approached statistical significance. This is consistent with studies done in sepsis where HES has been associated with increased mortality (5).  In contrast, there was no increase in mortality with albumin or adverse clinical outcomes, suggesting it was safe to use. The mechanism accounting for the adverse effects of colloids in ARDS and sepsis is unknown. However, the pharmokinetics of HES is known to be different from albumin and may play a role in the mortality rates (6). 

We found that administration of smaller volumes of fluid was associated with improved outcomes. This confirms previous studies done in ARDS demonstrating that a conservative strategy improves outcomes. Like the ARDS Network larger, multi-center study out smaller study was unable to find a reduction in mortality with lower volumes of fluid used.  From our studies it is unclear whether volume or the type of fluid is most important in determining survival. The data would seem to suggest that both are important. We also did not correct for differences in the equivalency of colloid compared to crystalloid solutions. Some authorities suggest that the volume expansive of colloid exceed crystalloid on absolute volume basis (7). However, corrections would likely accentuate the differences in mortality seen with volume.

It had been proposed that colloid infusion might be protective of the lungs by retaining fluid in the vascular space by oncotic pressure. However, recent studies have suggested show that colloids do not lower lung water (8). Furthermore, a recent meta-analysis found no evidence trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery (9). Furthermore, the use of hydroxyethyl starch might increase mortality. Our study is consistent with these studies.

Our trial has certain limitations. First, our study was single center. Second, the design did not include hemodynamic monitoring or other therapies. How these confounding variables might have affected the results is unknown. Third, only 43 patients were included in the trial. The trial was underpowered and confirmation of the results will be needed by larger trials.

This study demonstrates that the initial volume of fluid administered has effects on outcomes in patients with ARDS. The data in this manuscript support a dry or conservative strategy for management of ARDS. Furthermore, the choice of fluid also affects outcomes. The data in this paper would recommend the maintenance of relatively stable blood pressure with low volumes of crystalloid. As colloids are not associated with an improvement in survival, are less readily available, and are more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified.

Conflict of Interest

None of the authors declared a conflict of interest.

Acknowledgements

The concept of this research was built by Prof. Dr. Yong –Jie Yin and Dr Sanjaya Karki. However, most of the credit goes to Dr Jing Xiao Zhang in order to complete this research successfully. All the other co-authors have equally contributed.  

References

1. Matthay AM, Zimmerman AG. Acute lung injury and the acute respiratory distress syndrome. Am J Respir Cell Mol Biol. 2005;33(4),319-327. [CrossRef] [PubMed]
2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319-23. [CrossRef] [PubMed]
3. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33. [CrossRef] [PubMed]
4. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564-75. [CrossRef] [PubMed]
5. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012;367(2):124-34. [CrossRef] [PubMed]
6. Bellmann R, Feistritzer C, Wiedermann CJ. Effect of molecular weight and substitution on tissue uptake of hydroxyethyl starch: a meta-analysis of clinical studies. Clin Pharmacokinet 2012;51:225-36. [CrossRef] [PubMed]
7. The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-2256. [CrossRef] [PubMed]
8. van der Heijden M, Verheij J, van Nieuw Amerongen GP, Groeneveld AB. Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia. Crit Care Med. 2009;37(4):1275-81. [CrossRef]  [PubMed]
9. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. [CrossRef] [PubMed]

Reference as: Karki S, Yin Y-J, Zhang J-X, Samani N, Pradhan D, Deuja SS, Karki R, Thakur R, Zhao N. Fluid in the management of the acute respiratory distress syndrome. Southwest J Pulm Crit Care. 2013;6(6):289-98. doi: http://dx.doi.org/10.13175/swjpcc044-13 PDF

June 2013 Critical Care Case of the Month: Scratch Where It Itches

Robert A. Raschke, M.D.

Banner Good Samaritan Medical Center

Phoenix Arizona

History of Present Illness

The patient is a 64 year old man who had suffered a non-orthostatic syncopal episode at home, shortly after the onset of lightheadedness.  The patient was transported to an outlying hospital where he was described to be confused, wheezing, and in respiratory distress.  He was said to be hypotensive (but no blood pressures were recorded in the transfer medical record). He was resuscitated with intravenous saline and underwent endotracheal intubation.

Past Medical History

On arrival at our hospital, further history revealed that the patient had a truncal rash for more than 20 years.  He had two previous syncopal episodes associated with delirium, hypotension and respiratory failure.  None of these episodes had any clear precipitating event.  After the first event, two years previously, a cardiac evaluation resulted in coronary artery bypass surgery. He also had a history of type 2 diabetes mellitus and was taking glipizide and metformin. There was a history of glaucoma and he was receiving timolol.

Physical Exam

Vital Signs: blood pressure 111/60 mm Hg, RR 16 breaths/min, HR 72 beats/min, temperature 37.5° C. 

HEENT: epistaxis and an oral endotracheal tube. The ETT tube had bloody pulmonary secretions.

Heart and lung: examination was unrevealing. 

Skin: venous and arterial puncture sites were oozing blood.  An erythematous and tan maculopapular rash covered his trunk (shown in figure 1).

Figure 1. Tan maculopapular rash on patient’s back (Panel A) and abdomen (Panel B)

Laboratory

Glucose 50 mg/dL (normal 70-100 mg/dL).

Activated partial thromboplastin time (aPTT) > 200 sec (normal < 30 seconds), prothrombin time (PT) > 120 secs (normal <30 seconds), and a fibrinogen of 39 mg/dL (normal 200-400 mg/dL), D-dimer 2.1 mcg/mL (normal <0.5 mcg/mL), haptoglobin <10 mg/dL (normal 41 - 165 mg/dL),  LDH 508 U/L (normal 140-280 U/L), hemoglobin 9 gms/dL (normal 13-17 gms/dL), platelet count 274,000 cells/mcL (normal 150,000-450,000 cells/mcL).

Which of the following is (are) true?

1. The glucose of 50 is just below the normal range and does not need treatment
2. The patient’s elevated D-dimer is diagnostic of a pulmonary embolism
3. The patients abnormal coagulation panel is most consistent with a history of taking anticoagulants
4. The coagulation panel is consistent with disseminated intravascular coagulation
5. All of the above

Reference as: Raschke RA. June 2013 critical care case of the month: scratch where it itches. Southwest J Pulm Crit Care. 2013;6(6):255-62. PDF

May 2013 Critical Care Case of the Month: Not an Air-Filled Sac

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 66 year old woman presented to outside hospital with hematemesis and hematochezia. She was intubated for airway control and received 4 units of packed red blood cells. She was transferred to the Mayo Clinic Arizona due to an inability to control her upper gastrointestinal bleeding. During her transfer she required vasopressors.

PMH

She has a history of hepatitis C with cirrhosis and esophageal varices. In addition, she was diagnosed with a B-cell lymphoma 3 months prior to admission and had received 3 cycles of rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin® (vincristine) and prednisone (R-CHOP).  

Physical Examination

She was intubated and receiving oxygen at a FiO2 of 0.4.

Vital signs: P 100 beats/min; B/P 113/78 mm Hg; Afebrile; R 20 breaths/min; SpO2 99%

Chest: clear to auscultation.

Laboratory

Her hemoglobin was 9.3 g/dL and her hematocrit was 29%.

Radiology

Her admission chest x-ray is shown in Figure 1.

Figure 1. Admission portable chest-x-ray.

Which of the following should be done initially?

1. Bronchoscopy with bronchoalveolar lavage
2. Endoscopy
3. Administer octreotide to control hypotension
4. Administer 2 units of packed red blood cells to stay ahead of the bleeding
5. All of the above

Reference as: Wesselius LJ. May 2013 critical care case of the month: not an air-filled sac. Southwest J Pulm Crit Care. 2013;6(5):209-17. PDF

April 2013 Critical Care Case of the Month: Too Many Diagnoses

Elijah Poulos, MD

David M. Baratz, MD

Banner Good Samaritan Regional Medical Center

Phoenix, AZ

History of Present Illness

A 71 year old diabetic woman was admitted for 6-8 weeks of progressive dyspnea, non-productive cough, orthopnea, generalized edema and intermittent fevers. She has a history of living-related donor renal transplant from her husband in 1999 and was diagnosed with locally advanced pancreatic adenocarcinoma in October 2012. She was treated with insulin for diabetes; the immunosuppressants tacrolimus, mycophenolate and low-dose prednisone for her renal transplant; and weekly gemcitabine beginning in 11/2012 for her pancreatic cancer. Her course was complicated by left lower extremity deep venous thrombosis in January 2013 and she was treated with full dose enoxaparin at 1 mg/kg BID. She was tolerating her chemotherapy poorly with a myriad of complaints including fatigue, skin ulcerations, poor appetite, weakness, dysphagia, malaise, nausea and intermittent chest pains. Her most recent chemotherapy was held because of pancytopenia. She was admitted to our hospital in early March 2013 with the above symptoms.

Physical Examination

Vital signs: Temp 98.8°F, BP 125/65 mm Hg, HR 84 beats/min, RR 18/min, O2 saturation 85% on room air.

General: She was an obese woman in no distress but with conversational dyspnea

Neck: Jugular venous distention could not be appreciated secondary to obesity.

Lungs: Bibasilar rales

Heart: regular rhythm with distant heart sounds, but no murmur or gallop.

Lungs: Bibasilar rales

Abdomen: Soft and non-tender without palpable organomegaly or masses.

Ext: 2+ bilateral lower extremity pitting edema to above the knees.

Radiography

Her chest x-ray was interpreted as showing cardiomegaly with radiographic sequelae of pulmonary venous hypertension (Figure 1).

Figure 1. Admission PA (Panel A) and lateral (Panel B) chest radiography.

A thoracic CT scan was performed and was interpreted as showing vague diffuse bilateral groundglass opacities (Figure 2).

  

Figure 2. Movies of axial thoracic CT (upper panel) and  coronal thoracic CT (lower panel).  

Which of the following is a cause of ground glass opacities?

1. Pulmonary edema
2. Pneumonia
3. Hypersensitivity pneumonitis
4. Drug reaction
5. All of the above

Reference as: Poulos E, Baratz DM. April 2013 critical care case of the month: too many diagnoses. Southwest J Pulm Crit Care. 2013;6(4):161-7. PDF

March 2013 Critical Care Case of the Month: Beware the Escargot

Allen R. Thomas, MD

Suresh Uppalapu, MD

Phoenix VA Medical Center

Phoenix, Arizona

History of Present Illness

A 29 year old woman presented to the Phoenix VA Medical Center with complaints of headache and diffuse generalized weakness most pronounced in the lower extremities. She also noted recent fecal and urinary incontinence, abdominal pain, back pain, numbness in the feet and a non pruritic skin rash on the trunk. Onset of symptoms was about 2 weeks prior to her presentation.  Since her symptoms began she had seen in multiple local emergency departments for these same complaints as they worsened and was discharged home in each case with suspected viral syndrome.

PMH, SH, FH

She had no allergies and her past medical history was only significant for post- traumatic stress disorder. She has had no major surgery in her life so far and her family history was not contributory to her current presentation. She smokes marijuana for recreational purposes and drinks alcohol socially. She was not taking any medications on regular basis.

She had been in the military until six months prior to her presentation and her service included tours in Alaska and Hawaii.  She had recently returned from Fiji.  During her stay in Fiji, she reported eating snails and other uncooked food as well as drinking unpurified water

Physical Exam

Vital signs on presentation- T 98.4°C, P 102 beats/min, R 18 breaths/min, BP150/78 mm Hg  O2 sat 97% on room air

She was awake, alert, and oriented. She had mild nuchal rigidity and left ptosis. Lungs were clear and her cardiac exam was normal. Abdominal exam showed diffuse tenderness to palpation with hypoactive bowel sounds. Strength was 5/5 in the upper extremities, 4/5 on the right lower extremity, and 3/5 left lower extremity.  Sensation was Intact throughout.  Deep tendon reflexes were 1+.  Exam was thought to be somewhat limited due to poor effort.

Laboratory findings

White blood cell count was 12,400 mm³ with 75% neutrophils and 8% eosinophils.

Hemoglobin- 13.8 mg/dl; Hematocrit-41%; Platelet count was 317,000/mm³

Complete metabolic profile was normal.

CPK was elevated at 696 IU/Liter.

Radiology 

Chest x-ray showed some blunting of the left costophrenic angle with clear lung fields.

Which of the following are appropriate?

1. Observation. She probably has a viral syndrome.
2. Head CT scan
3. Cerebral angiogram
4. Nerve conduction studies
5. Liver ultrasound

Reference as: Thomas AR, Uppalapu S. March 2013 critical care case of the month: beware the escargot. Southwest J Pulm Crit Care. 2013;6(3):103-111. PDF

February 2013 Critical Care Case of the Month: Thoracentesis Through the Looking Glass

Clement U. Singarajah MD

Jay E. Blum

Allen R. Thomas MD

Henry Luedy MD

Elijah Poulos MD

Tonya Whiting DO

Phoenix VA Medical Center

Phoenix, AZ

History of Present Illness

A 62 year old man was recently diagnosed with Stage 4 squamous cell left lung cancer with metastases to the pleura, brain and mediastinum. He also had known chronic obstructive pulmonary disease (COPD) with a FEV1 = 1.96 L and a known left side pleural effusion (see Figure 1).

Figure 1. Baseline chest radiograph showing left pleural effusion (red arrow).

He was seen as an outpatient for symptomatic shortness of breath and underwent real time ultrasound guided left sided thoracentesis removing 500 ml of straw-colored fluid. The procedure was uneventful except that near the end, the patient started to cough.  He denied any symptoms post procedure apart from some minor puncture site pain. A routine post procedure chest x-ray was performed (Figure 2).

Figure 2. Post-thoracentesis x-ray (Panel A) and its negative image (Panel B).

What new abnormality is identified on the post-procedure chest x-ray?

1. Left pneumothorax
2. Right pneumothorax
3. Lung “sliding” on the left
4. New pneumonia in the left upper lobe
5. Left hilar retraction

Reference as: Singarajah CU, Blum JE, Thomas AR, Luedy H, Poulos E, Whiting T. February 2013 critical care case of the month: thoracentesis through the looking glass. Southwest J Pulm Crit Care. 2013;6(2):63-74. PDF

January 2013 Critical Care Case of the Month: Different Name, Same Disease...or Is It?

Nathaniel Reyes MD (NReyes@deptofmed.arizona.edu)

Jarrod Mosier MD (JMosier@aemrc.arizona.edu)

University of Arizona- AHSC/Pulmonary

1501 N Campbell Ave.

Tucson, AZ 85724-5030

History of Present Illness

A 50-year-old female who presented with 2-weeks of worsening cough and shortness of breath.  She presented to another hospital 2-weeks prior to presentation complaining of cough productive of yellow sputum and was diagnosed with bronchitis and discharged home with a normal chest x-ray.  Her symptoms persisted and one day prior to admission she experienced one episode of hemoptysis which prompted her presentation to our emergency department.  She denied fever, chills, night sweats, and complained only of dyspnea on exertion.

PMH/SH

Granulomatous polyangitis (GPA) was diagnosed by renal biopsy in 2004. She subsequent developed end-stage renal disease and has been receiving peritoneal dialysis.  She has never required immunosuppresive therapy. There is no history of tobacco use.  She has lived in Arizona for many years.  She is retired but previously worked as an information technology manager. 

Physical Exam

Vital signs were normal except for an O2 saturation of 91% on room air.  Physical exam was significant only for pale sclerae and bilateral dry crackles.

Laboratory Data

Hemoglobin: 5.4 g/dL; Hematocrit: 17%.  BUN: 43 mg/dL; creatinine: 10.7 mg/dL.   

ABG: PaO2 75; PaCO2 39; pH 7.43 on 2L O2.

P-ANCA: Positive

Myeloperoxidase antibody titer: 83 U/mL

C-ANCA/proteinase 3 antibody titer/Anti-GBM antibodies: negative.

Imaging

Chest X-ray showed diffuse areas of consolidation (Figure 1).

Figure 1. PA Chest X-ray

Which of the following is not appropriate in her management?

1. Admit to the intensive care unit.
2. Computerized tomography of the chest.
3. High dose corticosteroids
4. Bronchoscopy
5. Coccidioidomycosis serology

The authors report no conflict of interest.

Reference as: Reyes N, Mosier J. Critical care case of the month: different name, same disease...or is it? Southwest J Pulm Crit Care 2013;6(1):5-11. PDF

December 2012 Critical Care Case of the Month: Sepsis-like Syndrome in a Returning Traveler

Eric Chase, MD

Eric Ong, MD

John Bloom, MD

University of Arizona

Division of Pulmonary and Critical Care Medicine

Tucson, AZ

History of Present Illness

The patient is a 56 year old male with a past medical history that is significant only for well controlled hypertension presenting with acute onset of fever, hematuria, jaundice and fatigue. He had been hospitalized in Mexico for the last 5 days. When he failed to improve his friends chartered an airplane and brought him to the U.S. Prior to his hospitalization in Mexico he had traveled to Sierra Leone related to his work as a geologist.

PMH, SH, FH

Past Medical History: Hypertension, gastroesophageal reflux disease

Past Surgical History: Vasectomy

Medications:  Omeprazole, Lisinopril

Social History:  Works as a geologist with recent travel to Sierra Leone, no history of alcohol abuse, intravenous drug abuse, or HIV

Physical Examination

Vital signs: Temperature 97.5° F, Pulse 87 beats/min, Respiratory Rate 18 breaths/min, Blood Pressure 111/84 mm Hg, and SaO2 89% on room air. 

The patient was initially alert, oriented and appropriate.

His pulmonary examination revealed faint bibasilar rales. 

His abdomen was obese, soft, non-tender and non-distended. 

His skin had obvious jaundice and his sclerae were icteric. 

He later decompensated, became altered and developed significant tachypnea.

Admission Laboratory Studies

Significant initial laboratory studies are as follows:  Hemoglobin 11.5 g/dl, Hematocrit 35%, Platelet Count 25,000/uL, Chloride 115 mMol/L, CO2 17 mMol/L, BUN 35mg/dL, Creatinine 1.6 mg/dL, Albumin 1.5 g/dL, Total Bilirubin 13.2 mg/dL, ALT 38 IU/L, AST 97 IU/L, INR 1.7, Fibrinogen 270 mg/dL, D-Dimer 8.37 ug/ml, Venous Lactate 3.9 mMol/L, Urinalysis: Small Blood, 2 RBCs/HPF, Moderate Bilirubin, Urobilinogen 2.0 mg/dL.                    

As part of the workup for possible hemolysis a peripheral blood smear was obtained (Figure 1).

Figure 1. Peripheral smear of the patient’s blood.

Which of the following is the diagnosis?

1. Malaria
2. Babesosis
3. Ehrlichiosis
4. Relapsing fever
5. American trypanosomiasis (Chagas disease)

Reference as: Chase E, Ong E, Bloom J. December 2012 critical care case of the month: sepsis-like syndrome in a returning traveler. Southwest J Pulm Crit Care 2012;5:279-85. PDF

Fatal Dynamic Hyperinflation Secondary to a Blood Clot Acting As a One-Way Valve at the Internal Orifice of a Tracheostomy Tube

Robert A Raschke MD MS

robert.raschke@bannerhealth.com 

Professor of Clinical Medicine

Banner Good Samaritan Regional Medical Center

Phoenix, Arizona

Abstract

We report the case of a patient who suffered fatal cardiopulmonary effects of a mobile blood clot adherent to the internal orifice of her tracheostomy tube. We believe the clot acted as a one-way valve, leading to dynamic hyperinflation and elevated intrinsic positive end expiratory pressure (iPEEP). This complication of a tracheostomy tube was suggested by clinical findings of expiratory wheezing, hypotension, increasing peak inspiratory pressure, and unusual but distinctive radiographic findings. Confirmation of one-way tracheostomy tube obstruction was difficult, even with a bronchoscopic examination. When this diagnosis is suspected, tracheostomy tube exchange should be rapidly performed.

Case Report 

The patient was a 59-year old woman who had undergone elective colostomy for symptomatic colonic atony. The patient developed a post-operative anastomotic leak, and septic shock. Despite surgical intervention and broad-spectrum antibiotics, acute respiratory distress syndrome ensued, necessitating prolonged mechanical ventilation. On the 29th day of admission, an 8.0 DCT Shiley tracheostomy tube was placed in an open procedure.

On day 33, a chest radiograph demonstrated persistent diffuse pulmonary infiltrates that had not significantly improved over the preceding 3 weeks (Figure 1).

Figure 1.  Portable chest x-ray the morning before the code arrest.

Minor bleeding was noted from the tracheostomy tube. Shortly thereafter, peak inspiratory pressures suddenly rose to the point that adequate tidal volumes could not be delivered by a mechanical ventilator. The inner cannula of the tracheostomy tube was removed. A suction catheter passed easily though the external cannula lumen, and a small amount of blood was suctioned out. However, attempts to bag-ventilate the patient became progressively more difficult. The patient's head and neck became cyanotic and mottled, and a pulse could no longer be detected. Advanced cardiac life support was initiated. Examination was significant for pan-expiratory wheezes throughout the thorax interrupted only by strenuous attempts to at bag-mask inspiration. The trachea was midline, and there was no subcutaneous crepitus. The abdomen was soft.  A bronchoscope passed through the tracheostomy tube easily, revealing a widely patent trachea and major airways. Bag ventilation transiently improved, cyanosis resolved, and a blood pressure of 150/85 was briefly obtained.  Inhaled albuterol and intravenous corticosteroids were administered.  A chest x-ray was performed (Figure 2). 

Figure 2. CXR performed during the code arrest, showing flattening of the diaphragms, and acute narrowing of the cardiac silhouette/vascular pedicle, and acute clearing of pulmonary infiltrates, consistent with hyperinflation.

Bag-ventilation became progressively more difficult, and the patient once more became hypotensive and cyanotic. The bronchoscope again passed easily through the tracheostomy and revealed the same findings as before. Needle thoracostomy was considered to treat possible pneumothorax, but the chest x-ray returned to the bedside demonstrated no evidence of barotrauma. The radiograph demonstrated striking improvement in pulmonary edema, a reduction in the size of the cardiac silhouette and vascular pedicle, and flattening of the diaphragms (see Figure 2 - note: the large radio-opacity overlying the mid-portion of the left lung is the shadow of an adherent transcutaneous pacing pad, not a pneumothorax). Further resuscitative efforts were unsuccessful.

The possibility of tracheostomy dysfunction was re-considered at some length in a postmortem debriefing. We concluded that the most likely explanation for the patient's clinical and radiological findings was dynamic hyperventilation and hemodynamic consequences of severe iPEEP induced by a dysfunction of the tracheostomy tube. 

Autopsy Findings

The tracheostomy tube was left in place, and the pathologist carefully dissected the trachea open from the carina in a caudal direction to expose the internal tip of the tracheostomy tube in-situ. A blood clot was found that nearly completely occluded the internal orifice of the tube (Figure 3, Panel A). The clot swung out of the way of some IV tubing passed inward through the external orifice of the tracheostomy tube, but swung shut again when the IV tube was removed, like a trap door (Figure 3, Panel B).

Figure 3.  Longitudinal view of the open tracheal lumen at autopsy.  Orientation: the left side of the figure is rostral. In panel A, the distal orifice of the tracheostomy tube can be seen to be nearly completely obstructed by a thrombus (black arrow). In panel B, the thrombus (black arrow) can be seen to be pushed aside by the passage of a plastic catheter (white arrow),

This clot appeared to function as a one-way valve, allowing inward passage of air, suction catheters, and a bronchoscope, but severely obstructing exhalation. We reasoned that such an obstruction could lead to wheezing and dynamic hyperinflation, and could explain the clinical and radiographic findings. Ultimately, severe iPEEP compromised cardiac preload, leading to pulselessness and death. 

No other cause for the patient's clinical syndrome was found - specifically, the patient had no antecedent history of asthma, had received no new medications on the day of the arrest, nor had any dermatological findings suggestive of anaphylaxis. The autopsy failed to reveal pulmonary embolism, mucous plugging, pneumothorax, or any histological evidence of asthma. 

Discussion

We are not the first to report dynamic hyperinflation as a complication of uni-directional tracheostomy tube obstruction (1). Several experienced clinicians at our institution recall dealing with this entity before, therefore, we suspect that it is not as rare as the paucity of clinical reports suggests. We felt that the clinical, radiological and postmortem findings in our case are sufficiently interesting, and the danger of missing this diagnosis sufficiently great, to warrant a brief review. 

Other types of tracheostomy tube dysfunction can cause high airway pressure and hypotension. Bi-directional tube obstruction from blood, dried secretions, or balloon hyperinflation is the most common (2,3). Barotrauma related to tracheostomy tubes may occur when they become displaced into the soft tissues of the neck, or into the pleural space, or when the cutaneous tracheostomy wound is sutured in an overly constrictive manner (4). 

We learned three important lessons from this unfortunate case:

1. Clinical and radiographic findings can suggest the diagnosis of expiratory tracheostomy obstruction in a patient ventilated through a tracheostomy tube. The key clinical findings are: expiratory wheezing, hypotension, increasing iPEEP, and increasing peak inspiratory pressure.  Unexpected radiographic improvement in pulmonary edema may suggest the presence of occult iPEEP if it is not directly measured. 
2. The diagnosis of unidirectional obstruction of a tracheostomy tube can be difficult to confirm.  The easy passage of suction catheters, or a bronchoscope, does not rule it out.  If bronchoscopy is performed emergently, the internal lumen and internal orifice of the tracheostomy tube should be examined with extreme deliberation.  This can be difficult during cardiopulmonary resuscitation.  If visualized, the potential detriment of small mobile clots should not be under-estimated.
3. Alternative airway access should be immediately pursued in patients with tracheostomy tubes who are difficult to ventilate.  In dire clinical situations, the best diagnostic test might be to simply see if the patient improves with a new airway.  If the tracheostomy tract is likely to be mature (> 5 days old), the tracheostomy tube can simply be exchanged.  If the tract is immature, or if tube displacement is suspected, oral laryngoscopic intubation should be performed immediately.  The tracheostomy tube may need to be pulled out in order to accommodate the endotracheal tube in the trachea.  Either of these actions would likely have saved our patient's life.

References

1. Timmus HH.  Tracheostomy: An Overview of implications, management, and morbidity.  Advances in Surgery 1973;7:199-233.
2. Saini S, Taxak S, Singh MR.  Tracheostomy tube obstruction caused by an overinflated cuff.  Otolaryngol Head Neck Surg 2000;122:768-9.
3. Rowe BH, Rampton J, Bota GW.  Life-threatening luminal obstruction due to mucous plugging in chronic tracheostomies: three case reports and a review of the literature.  J Emerg Med 1996;14:565-7.
4. Tayal VS. Tracheostomies. Emerg Med Clin North Am 1994;12:707-27.

The author reports no financial support and no conflict of interest for this publication.

Reference as: Raschke RA. Fatal dynamic hyperinflation secondary to a blood clot acting as a one-way valve at the internal orifice of a tracheostomy tube. Southwest J Pulm Crit Care 2012;5:256-61. PDF

November 2012 Critical Care Case of the Month: I Just Can’t Do It Captain! I Can’t Get the Sats Up!

Bridgett Ronan, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 61 year old man was seen in consultation after undergoing a laparoscopic repeat Nissen fundoplication with mesh reinforcement.  He developed worsening hypoxia postoperatively. He was initially extubated without difficulty to nasal cannula. However, he had progressive hypoxemia requiring a nonrebreathing mask, followed by BiPAP and eventually reintubation. Discussion with the surgeons revealed he had gastric contents present on intraoperative esophagogastroduodenoscopy (EGD). There was a small perforation of the fundus, with possible contamination of the peritoneum.

PMH, FH, SH

He has a long history of a paraesophageal hernia and reflux esophagitis and had previously undergone a Nissen fundoplication. There was also a history of atrial flutter and a 4.8 cm thoracic aortic aneurysm. A pre-operative echocardiogram was othewise normal. There was no remarkable family history. He was a non-drinker and non-smoker.

Physical Examination

Vital signs: Heart rate 79 beats/min, BP 95/67 mm Hg, Temperature 99.4°F, SpO2 78% on 100% FiO2.

His lungs were clear interiorly.

No murmurs or gallops were heard on cardiac auscultation.

His abdomen was post-surgical and distended but soft and nontender.

Which of the following is true regarding hypoxemia?

1. Most hypoxia is secondary to alveolar-capillary block
2. A normal pCO2 excludes hypoventilation as a cause of hypoxemia
3. Low inspired FiO2 is a common cause of hypoxia in the ICU because of attaching air to the oxygen line on the ventilator.
4. A normal chest x-ray excludes ventilation-perfusion mismatch as a cause of hypoxemia
5. The patient’s age of 61 excludes a congenital heart lesion

Reference as: Ronan B. November 2012 critical care case of the month: I just can’t do it captain! I can’t get the sats up! Southwest J Pulm Crit Care 2012;5:235-41. PDF

October 2012 Critical Care Case of the Month

Henry Luedy, MD

Clement U. Singarajah, MD

Phoenix VA Medical Center

Phoenix, AZ

History of Present Illness

An 85 year old patient was admitted with hypotension and respiratory failure. He was intubated shortly after arrival and mechanical ventilation was begun. Fluids and vasopressors were begun for his hypotension.

PMH, SH, FH

His past medical history included peripheral vascular disease, abdominal aortic aneurysm repair, type 2 diabetes mellitus, hypertension, alcohol use, coronary artery disease, chronic obstructive pulmonary disease and hyperlipidemia.

Physical Examination

His vital signs were a temperature of 98.6 degrees F, heart rate 110 beats/min, respiratory rate 14 breaths per minute while intubated and receiving mechanical ventilation, and BP of 95/65 mmHg on vasopressors.

He was sedated. Lungs were clear and the heart had a regular rhythm without murmur or gallop. Abdominal examination was unremarkable and neurologic exam was limited because of sedation but without localizing signs. Plantar reflexes were down-going.

Admission Laboratory

Significant initial laboratory findings included a white blood cell count of 21,000 cells/μL, blood lactate level of 10 mmol/L and creatinine of 12 mg/dL. Urinanalysis showed pyuria and was positive for nitrates. At this time which of the following are diagnostic possibilities?

1. Sepsis secondary to urinary tract infection (urosepsis)
2. Community-acquired pneumonia
3. Cardiogenic shock secondary to myocardial infarction
4. Critical illness related corticosteroid insufficiency
5. All of the above

Reference as: Luedy H, Singarajah CU. October 2012 critical care case of the month. Southwest J Pulm Crit Care 2012;5:179-85. PDF

September 2012 Critical Care Case of the Month

Robert A. Raschke, MD

Banner Good Samaritan Regional Medical Center

Phoenix, AZ

History of Present Illness

A 45 year old man was transferred from another medical center. He was found unresponsive, with muscle spasticity. After arrival at the outside medical center his vital signs were temperature 106.4 degrees F, heart rate 160 beats/min, respiratory rate 44 breaths per minute, and BP of 70/45 mm Hg. He was orally intubated for respiratory distress with induced by vecuronium.  His white blood cell count was 21,000 cells/μL. Chest x-ray showed bilateral consolidations and he was given fluids and gatifloxacin. His blood pressure improved to 130/94 and he was transferred.

PMH, SH, FH

He has a past medical history of quadriplegia at the C6 level with a history of severe back pain because syringomyelia.  He has a history of autonomic dysreflexia. Despite his disability he is quite functional working as a personal injury lawyer. He had been managed with a variety of medications including benzodiazepams, narcotics and baclofen. The later two were administered via an intrathecal pump which had been weaned over several weeks, and totally discontinued the day prior to admission. There is no history of smoking or alcohol abuse.

Physical Examination

His vital signs were temperature of 102.6 degrees F, heart rate 160 beats/min,  respiratory rate 14 breaths per minute, and BP of 130/50 mmHg.

He was paralyzed and mechanically ventilated. There was tenting of the skin and mottling of neck and knees. He had calloused hands and excoriated forearms. Lungs had diffuse rales and the heart rate was regular but rapid. A subcutaneous pump device was palpable in the left lower abdominal quadrant. There was a pressure sore on the coccyx.

Admission Laboratory and X-ray

His admission chest x-ray showed a diffuse 5-lobe consolidation. White blood cell count was elevated at 21,000 cells/μL.

At this time which of the following are diagnostic possibilities?

1. Sepsis secondary to Staphylococcus aureus
2. Pneumonia secondary to aspiration
3. Neuroleptic malignant syndrome
4. Benzodiazepam withdrawal
5. All of the above

Reference as: Raschke RA. September 2012 critical care case of the month. Southwest J Pulm Crit Care 2012;5:121-5. (Click here for a PDF version)

Correlation of Compliance with Central Line Associated Blood Stream Infection Guidelines and Outcomes: A Review of the Evidence

Jessica Hurley, MD¹

Roxanne Garciaorr, MD¹

Henry Luedy, MD¹

Christan Jivcu, MD¹

Emad Wissa, MD¹

Joshua Jewell, MD¹

Tonya Whiting, MD¹

Richard Gerkin, MD¹

Clement U. Singarajah, MD²

Richard A. Robbins, MD²

¹Banner Good Samaritan Medical Center and ²Phoenix Pulmonary and Critical Care Medicine Research and Education Foundation, Phoenix, AZ

Abstract

Background 

Clinical practice guidelines are developed to assist in patient care but the evidence basis for many guidelines has been called into question.

Methods 

We conducted a literature review using PubMed and analyzed the overall quality of evidence and made strength of recommendation behind 8 Institute of Health Care (IHI) guidelines for prevention of central line associated blood stream infection (CLABSI). Quality of evidence was assessed by the American Thoracic Society (ATS) levels of evidence (levels I through III). We also examined data from our intensive care units (ICUs) for evidence of a correlation between guideline compliance and the development of VAP.

Results 

None of the guidelines was graded at level I. Two of the guidelines were graded at level II and the remaining 6 at level III. Despite the lack of evidence, 2 of the guidelines (hand hygiene, sterile gloves) were given a strong recommendation. Chlorhexidine and use of nonfemoral sites were given a moderate recommendation. In our ICUs compliance with the use of chlorhexidine correlated with a reduction in CLABSI (p<0.02) but the remainder did not.

Conclusions 

The IHI CLABSI guidelines are based on level II or III evidence. Data from our ICUs supported the use of chlorhexidine in reducing CLABSI. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current IHI guidelines to direct patient care decisions or as an assessment of the quality of care.

Introduction

The past three decades have seen the growth of numerous medical regulatory organizations. Many of these organizations have developed medical regulatory guidelines with over 10,000 listed under treatment/intervention in the National Guideline Clearinghouse (1). Many of these guidelines were rapidly adopted by healthcare organizations as a method to improve care. However, recent evidence suggests that many are based on opinion rather than randomized trials and most have not been shown to improve patient outcomes (2-5). We examined the IHI guidelines for prevention of CLABSI because these guidelines have been widely implemented despite what appeared to be a weak evidence basis (6). 

Methods

The study was approved by the Western Institutional Review Board.

Literature Search

In each instance PubMed was searched using central line associated blood stream infection which was cross referenced with each component of the CLABSI bundle (as modified by the Veterans Administration) using the following search terms: 1. hand hygiene; 2. cap (worn by inserter); 3. mask (worn by inserter); 4. sterile gloves (worn by inserter); 5. sterile gown (worn by inserter); 6. full body drape; 7. chlorhexidine used instead of povidone iodine (betadine); and 8. femoral sites not used. Additional studies were identified from the Related Citations in PubMed and the manuscript bibliographies. Each study was assessed for appropriateness to the guideline. Studies were required to be prospective and controlled in design. Only studies that used the incidence of CLABSI as a primary outcome measure were included in assessing the quality of evidence. 

Grading of level of evidence. The American Thoracic Society grading system was used to assess the underlying quality of evidence for the IHI CLABSI guidelines (7) (Table 1). A consensus was reached in each case. 

Table I. Levels of Evidence

Level of Evidence	Definition
Level I (high)		Evidence from well-conducted, randomized controlled trials.
Level II (moderate)		Evidence from well-designed, controlled trials without randomization (including cohort, patient series, and case-control studies). Level II studies also include any large case series in which systematic analysis of disease patterns was conducted, as well as reports of data on new therapies that were not collected in a randomized fashion.
Level III (low)		Evidence from case studies and expert opinion. In some instances, therapy recommendations come from antibiotic susceptibility data without clinical observations.

Strength of recommendations. Seven pulmonary and critical care fellows made strength of recommendations for each guideline. This was based not only the strength of evidence but also on clinical knowledge and judgment.

Guideline Compliance and CLABSI Incidence. We also assessed our ICUs for additional evidence of the effectiveness of the individual components of the CLABSI bundle. Data were collected monthly for a period of 50 months from January, 2007 through February, 2011. This was after the Veterans Administration requirements for CLABSI reporting and compliance was instituted. Diagnosis and compliance were assessed by a single quality assurance nurse using a standardized protocol (8). Compliance with each component of the bundle was analyzed individually and expressed as a percentage. This was correlated with the incidence of CLABSI during that month expressed in line-days. Each of the following was recorded by the quality assurance nurse: (1) line days, (2) number of CLABSI and (3) the number of audits or checklists completed during central line insertion and from those checklists (4) the number of times individual bundle practices were used including femoral location. In addition to data being kept locally, data was also entered into a centralized VA website. Entry into the website required completion of a learning session and a test correctly identifying CLABSI infections in case scenarios based on CDC definitions. The program included audits because the audit tool teaches critical bundle elements and facilitates communication about bundle adherence between team members.

Statistical analysis.  In some cases data were reanalyzed from original papers by Fisher’s exact test with a two-tailed comparison. For the data from our ICUs analyses were done using a Pearson correlation coefficient with a two-tailed test. Significance was defined as p<0.05. 

Results

Literature Review

Numbers of articles identified by PubMed search and used for grading the level of evidence and strength of recommendation are given in Table 2. Also included are the level of evidence and the strength of the recommendation.

Table 2.

*Includes maximum barrier compared to standard barrier studies.

Barrier Protection. Five of the guidelines (cap worn by inserter; mask worn by inserter; sterile gown worn by inserter; and full body drape on patient) can be grouped under maximal barrier precautions as originally described by Raad et al. (9). This single site study compared 343 randomized patients to have nontunneled central catheters inserted under maximal sterile barrier precautions or control precautions (sterile gloves and small drape only). The catheters were for non-emergency venous access for chemotherapy and/or bone marrow transplantation. All patients were followed for 3 months and there were a total of four catheter infections in the test group and 12 in the control group (p= 0.03, chi-square test). However, examination of Table 3 of the manuscript revealed that 6 of the 12 in the control and 3 of the 4 in the test group had colonization rather than septicemia. Furthermore, of the remaining 7 patients only 2 developed septicemia within 30 days (both in the control group at 7 and 10 days). The remaining patients developed septicemia long after any expected benefit from barrier precautions during insertion (35-98 days). Development of septicemia this long after insertion and would seem more likely to represent contamination during handling of the catheter. Eliminating those subjects with colonization alone and septicemia after 30 days leaves 2 of 167 in the control and none of 176 in the maximum barrier precautions group. Recalculation reveals no statistically significant reduction by (p=0.24). Consistent with this reanalysis, a recent randomized, multicenter trial comparing maximum sterile barrier precautions vs. standard precautions reported by Ishikawa et al. (10) did not demonstrate a reduction in CLABSI. CLABSI developed in 5 of 211 patients with the use of maximum sterile barrier precautions compared to 6 of 213 patients with standard precautions (gloves and drape, p=1.00). Combining Raad’s revised data with Ishikawa’s data did not demonstrate a statistically significant difference between maximum and standard barrier precautions (p=0.42).  

Two other studies were considered. One was a prospective but observational study by Lee et al. (11). Data from this study demonstrate a lower rate of infection with maximum sterile precautions (p=0.02) but was excluded because of the nonrandomization. Another study by Rijnders et al. (12) was a randomized study comparing maximum barrier precautions and standard precautions but with arterial lines. Maximum barrier precautions did not significantly lower the infection rate (p>0.1) but the study was excluded because it dealt with arterial rather than central venous lines.

It is also important to note that CLABSI has been directly linked to the organisms growing on the skin at the insertion site. Carrer et al. (21) found maximal sterile barrier precautions, when compared to standard care, decreased skin colonization at the insertion site for the first 48 hours (39% vs. 69%). However, within 48 hours skin colonization was no different than at 5 days. Furthermore there was no statistical difference in device colonization found between the groups (p=0.10) indicating barrier precautions did not change the rate of CLABSI. Kim and colleagues (22) found the maximal barrier precautions successfully decreased the number of gram-positive infections (p=0.05) but actually increased fungal infections (p=0.04) while having no effect on gram-negative organisms. Given the natural flora of the skin is nearly all gram-positive organisms, sole reduction of gram-positive infections alone in this study reiterates the minimal overall effect maximal barrier precautions has on CLABSI in relation to the skin organisms at the central line insertion site and suggests CLABSI often occurs in the setting of future contamination post-insertion (22).

Based on the data and a lack of clear cut rationale into a mechanism of why maximum barrier precautions should reduce CLABSI, a weak recommendation was given to each of the components of maximum barrier precautions (cap, mask, gown and drape).

Hand hygiene and sterile gloves. The effects of hand hygiene and/or sterile gloves on the development of CLABSI have not been validated in randomized controlled trials. Observational studies have demonstrated a significant decrease in the incidence of nosocomial infections with improvements in hand hygiene and use of sterile gloves (13). Decreased mortality associated with the implementation of hand hygiene dates back to Semmelweis in 1847 (14). As the simplest and least expensive means of reducing CLABSI, hand hygiene and the use of sterile gloves were strongly recommended.

Chlorhexidine. One single institution study compared 492 arterial line insertions combined with 176 central venous catheters (15). Patients were randomized to povidone iodine (227 patients), alcohol (227 patients) and chlorhexidine (224 patients) for use in insertion as well as every 48 hour cleansing of the insertion site. Seven, six and one of the patients in each group developed bacteremia respectively. Chlorhexidine use resulted in a statistically significant reduction in bacteremia if compared to the combined povidone iodine and alcohol groups. However, statistical significance was lost when analyzed on a 3x2 table or comparing povidone iodine or alcohol with chlorhexidine individually (p>0.05, all comparisons).

Mimoz et al. (16) reported a single center study in both arterial and central venous line insertions. Patients were randomly assigned to either a solution composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol or 10% povidone iodine. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. The use of the chlorhexidine containing solution was more efficacious in preventing line related sepsis compared to povidone iodine in preventing Gram + but not Gram negative infections but there was no overall reduction of CLABSI with chlorhexidine (3 CLABSI out of 170) compared to povidone-iodine (4 CLABSI out of 145).

Another multicenter prospective, randomized, controlled trial reported by Humar et al. (17) compared 0.5% tincture of chlorhexidine to 10% povidone-iodine as cutaneous antisepsis for central venous catheter in intensive care units. Four cases of documented catheter-related bacteremia out of 193 patients were found in the chlorhexidine group compared to 5 of 181 the povidone-iodine group (p>0.05).

Combining the above studies resulted in no significant reduction with the use of chlorhexidine (8 CLABSI out of 577) compared to povidone-iodine (15 CLABSI out of 553, p=0.14).

The results of a more recent 3-year, multi-institutional, interrupted time-series design (October 2006 to September 2009), with historical control data in the pediatric intensive care unit produced differing results (18). A nested, 18-month, nonrandomized, factorial design was used to evaluate chlorhexidine scrub and chlorhexidine-impregnated sponge compliance rates. Neither was associated with a reduction in CLABSI. Due to the results only being reported in CLABSI rate per 1000 line days it was not possible to combine the data with the other studies.

One of the randomized studies showed decreased CLABSI with chlorhexidine (15). Two of the three studies showed decreased colonization as well as decreased rates of line related sepsis while the third showed decreased exit site infections (all other findings of that study did not quite make significance). All three studies were in the ICU setting, two in surgical, evaluating both central venous catheters as well as arterial lines. In this setting with likely minimal cost difference, equal to better ease of use, and smaller studies of both venous and arterial lines, the strength of recommendation was judged as moderate.

Insertion Site. One randomized study compared infections using the femoral and internal jugular sites (19). In this study the rate of CLABSI did not differ (3/313 vs. 5/313). Another study compared the femoral and subclavian sites. It also did not show a reduction with a nonfemoral site (2/127 vs. 6/100) (20). Combining the two studies did not show a significantly lower infection rate with a nonfemoral site (7/440 nonfemoral vs. 9/413 femoral, p= 0.45). Two other nonrandomized studies examined femoral compared to subclavian and internal jugular sites (23,24). One did not show a difference between the sites (23). The other, larger study showed a lower rate with non-femoral sites (24). Three other studies were considered but were found to be nonrandomized (25-27). However, complications appear higher with the femoral route including thrombosis and hematomas (28,29).

The one observational study and the higher rate of non-infectious complications resulted in the group recommending a non-femoral site when possible. The strength of this recommendation was judged as moderate.

Guideline Compliance CLABSI Incidence. In our ICUs, 1133 audits representing 11470 line-days were assessed monthly (Appendix 1). An average of 1.3 CLABSI infections/1000 line-days occurred. Correlation between the monthly compliance with each component of the CLABSI bundle with the monthly CLABSI incidence revealed only chlorhexidine use was associated with reduced CLABSI (r=-0.35, p=0.01).

Discussion

This manuscript questions the validity of the CLABSI bundles as proposed by the IHI. We found that a systematic review of the literature revealed predominantly weak evidence to support these guidelines. Only one guideline (chlorhexidine) was supported by a randomized trial (15). However, data from our own ICUs showed a correlation between use of chlorhexidine and a reduction in CLABSI.

The diagnosis of CLABSI is difficult, requiring clinical judgment even in the presence of objective clinical criteria (8). The difficulty in diagnosis, along with the negative consequences for failure to follow the IHI guidelines, makes before and after comparisons of the incidence of CLABSI unreliable. Therefore, we sought evidence for the effectiveness of CLABSI prevention guidelines reasoning that the better the compliance with the guidelines, the lower the incidence of CLABSI. We were unable to show that improved CLABSI guideline compliance correlated with a reduced incidence of CLABSI with the exception of use of chlorhexidine.

Particularly disappointing is the data on maximum barrier precautions and reduction in CLABSI. The evidence presented in the first randomized trial was weak (9). Furthermore, when we carefully examined the data we found inclusion of catheter colonization and delays in diagnosis of over 30 days in the time from catheter insertion. It seems unlikely that contamination at the time of insertion would take over 30 days to present with sepsis. If the insertion technique was faulty (e.g., no barrier use) the infection should present within a matter of days not weeks. Many studies conflate catheter colonization with a true catheter related infection. The two entities are managed quite differently and thus need to be carefully separated (8). Reanalysis of the data eliminating the colonized patients and those who took over 30 days to present showed no reduction in CLABSI with maximum barrier protection. A more recent randomized, multicenter study would support the conclusion that there is no significant difference between maximum and standard barrier precautions (10).

We could find no randomized studies of hand hygiene and gloves in the context of CLABSI prevention. However, studies in the operating room and the intensive care unit have both demonstrated that hand hygiene decreases infection (13). Both have become standards of practice. Therefore, our group felt ardently that this should be a strong recommendation.

Use of povidone iodine or chlorhexidine is largely dependent on what is stocked at the time of central line insertion. We are unaware of data supporting physician preference for povidone iodine over chlorhexidine; in fact, our group almost universally prefers chlorhexidine. Although the evidence basis for chlorhexidine over povidone iodine is marginal, it seems reasonable to use chlorhexidine until the time that additional data are available, and therefore, chlorhexidine use was given a moderate recommendation.

The data using non-femoral sites showed no clear cut reduction in CLABSI. The femoral site may have advantages particularly in emergency situations including ease of placement, compressibility and being distant from the head and neck during resuscitation. However, it appears to come at a higher price of both hematomas and thrombosis (19,20). Based on this our group felt a moderate recommendation was justified in nonemergent situations.

Our study has several limitations. No literature review is totally comprehensive. It is possible that studies relevant to the IHI CLABSI guidelines, especially those written in a foreign language, were not identified. Second, the Phoenix VA data may be underpowered to show a small beneficial effect despite having over 11,000 line-days. Third, as with other healthcare facilities, the CLABSI guidelines at our institution were mandated and monitored. The threat of negative consequences may have compromised the objective assessment of the self-reported data, likely invalidating a before and after comparison. Fourth, correlation between guideline compliance and CLABSI incidence is not a substitute for a randomized trial. Unfortunately, the later is not possible given that guideline compliance is mandated.

In the above context, this report both confirms some aspects but differs in others from a recent report by the Veterans Administration (30). In this report the VA reported data from all ICUs and found a reduction in CLABSI and an increase in compliance from 2006-9. Although the database is much larger than the data in this report from a single institution, it suffers from the same weaknesses as our data. Not reported are the death or morbidity rates from CLABSI. Interestingly, CLABSI rates were much lower in smaller hospitals (level 4). Whether these hospitals had increased compliance was not reported, but these smaller hospitals are known to have higher all cause mortality, surgical mortality and surgical morbidity (31).

Guidelines have taken on the aura of law which is substituted for clinical judgment. For example, a nurse practitioner attempted to prevent a senior critical care physician in one of our facilities from inserting a central line because the physician was not wearing a cap. However, since the patient had no line access and was in extremis, the physician decided to proceed. Other examples are the decisions to place a femoral catheter during emergencies, when other venous access is unavailable, when a pneumothorax might be catastrophic, or when major bleeding is a risk (the femoral vein is compressible). Clinical judgment might weigh the risks of internal jugular or subclavian insertions compared to the femoral vein and conclude that the femoral site might be the best choice for the patient.

It is unclear why the IHI guidelines have received such wide acceptance given their weak evidence basis. Agencies involved in guideline writing should show restraint in guideline formulation based on opinion or weak or conflicting evidence. Only those interventions based on strong evidence which can make a real difference to patients should be designated as guidelines.

Acknowledgements

The authors acknowledge Janice Allen, MSN, RN who collected the CLABSI data reported from the Phoenix VA.

References

1. http://www.guideline.gov/ Accessed 12-1-2011.
2. Lee DH, Vielemeyer O. Analysis of overall level of evidence behind infectious diseases society of America practice guidelines. Arch Intern Med 2011;171:18-22.
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4. Padrnos L, Bui T, Pattee JJ, Whitmore EJ, Iqbal M, Lee S, Singarajah CU, Robbins RA. Analysis of overall level of evidence behind the Institute of Healthcare Improvement ventilator-associated pneumonia guidelines. Southwest J Pulm Crit Care 2011;3:40-8.
5. Robbins RA, Gerkin R, Singarajah CU. Relationship between the Veterans Healthcare Administration Hospital Performance Measures and Outcomes. Southwest J Pulm Crit Care 2011;3:92-133.
6. http://www.ihi.org/explore/centrallineinfection/Pages/default.aspx (accessed 12-1-11).
7. Schünemann H, Jaeschke R, Cook DJ, et al. An Official ATS Statement: Grading the Quality of Evidence and Strength of Recommendations in ATS Guidelines and Recommendations. Am J Resp Crit Care Med 2006;174:605-14.
8. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-32.
9. Raad II, Hohn DC, Gilbreath BJ, Suleiman N, Hill LA, Bruso PA, Marts K, Mansfield PF, Bodey GP. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994;15:231-8.
10. Ishikawa Y, Kiyama T, Haga Y, Ishikawa M, Takeuchi H, Kimura O, Harihara Y, Sunouchi K, Furuya T, Kimura M. Maximal sterile barrier precautions do not reduce catheter-related bloodstream infections in general surgery units: a multi-institutional randomized controlled trial. Ann Surg 2010 ;251:620-3.
11. Lee D-h, Jung KY, Choi Y-H. Use of maximal sterile barrier precautions and/or antimicrobial- coated catheters to reduce the risk of central venous catheter–related bloodstream infection. Infect Control Hosp Epidemiol 2008;29:947-50.
12. Rijnders BJ, Van Wijngaerden E, Wilmer A, Peetermans WE. Use of full sterile barrier precautions during insertion of arterial catheters: a randomized trial. Clin Infect Dis 2003;36:743-8.
13. Larson E. A causal link between handwashing and risk of infection? Examination of the evidence. Infect Control 1988;9:28-36.
14. Cork DP, Maxwell PJ 4th, Yeo CJ. Remembering Semmelweis: hand hygiene and its importance on today's clinical practice. Am Surg 2011;77:123-5.
15. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet. 1991;338:339-43.
16. Mimoz O, Pieroni L, Lawrence C, Edouard A, Costa Y, Samii K, et al. Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med 1996;24:1818-23.
17. Humar A, Ostromecki A, Direnfeld J, Marshall JC, Lazar N, Houston PC, Boiteau P, Conly JM. Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis. 2000;31:1001-7.
18. Miller MR, Niedner MF, Huskins WC, Colantuoni E, Yenokyan G, Moss M, Rice TB, Ridling D, Campbell D, Brilli RJ; the National Association of Children's Hospitals and Related Institutions Pediatric Intensive Care Unit Central Line–Associated Bloodstream Infection Quality Transformation Teams. Reducing PICU Central Line-Associated Bloodstream Infections: 3-Year Results. Pediatrics 2011;128:e1077-e1083.
19. Parienti JJ, Thirion M, Mégarbane B, Souweine B, Ouchikhe A, Polito A, Forel JM, Marqué S, Misset B, Airapetian N, Daurel C, Mira JP, Ramakers M, du Cheyron D, Le Coutour X, Daubin C, Charbonneau P; Members of the Cathedia Study Group. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial. JAMA 2008;299:2413-22.
20. Merrer J, De Jonghe B, Golliot F, Lefrant JY, Raffy B, Barre E, Rigaud JP, Casciani D, Misset B, Bosquet C, Outin H, Brun-Buisson C, Nitenberg G; French Catheter Study Group in Intensive Care. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700-7.
21. Carrer S, Bocchi A, Bortolotti M, Braga N, Gilli G, Candini M, Tartari S. Effect of different sterile barrier precautions and central venous catheter dressing on the skin colonization around the insertion site. Minerva Anestesiol 2005;71:197-206.
22. Kim JS. Holtom P. Vigen C. Reduction of catheter-related bloodstream infections through the use of a central venous line bundle: epidemiologic and economic consequences. American Journal of Infection Control 2011;39:640-6.
23. Deshpande KS, Hatem C, Ulrich HL, Currie BP, Aldrich TK, Bryan-Brown CW, et al. The incidence of infectious complications of central venous catheters at the subclavian, internal jugular, and femoral sites in an intensive care unit population. Critical Care Medicine 2005;33:13-20.
24. Lorente L, Henry C, Martin MM, Jimenez A, Mora ML. Central venous catheter-related infection in a prospective and observational study of 2,595 catheters. Critical Care (London, England) 2005;9:R631-5.
25. Casanegra AI, Brannan S, Dadu R, Ong P, Berner M, Spinning K, Hughes T, Marrinan G, Zinn K, Manthous C. Short-term femoral vein catheterization rarely causes thrombosis or bacteremia. J Hosp Med 2011;6:33-6.
26. Hsu JF, Tsai MH, Huang HR, Lien R, Chu SM, Huang CB. Risk factors of catheter-related bloodstream infection with percutaneously inserted central venous catheters in very low birth weight infants: a center's experience in Taiwan. Pediatr Neonatol 2010;51:336-42.
27. Tsai MH, Lien R, Wang JW, Huang HR, Chiang CC, Chu SM, Hsu JF, Huang YC. Complication rates with central venous catheters inserted at femoral and non-femoral sites in very low birth weight infants. Pediatr Infect Dis J 2009;28:966-70.
28. Trottier SJ, Veremakis C, O’Brien J, Auer AI. Femoral deep vein thrombosis associated with central venous catheterization: results from a prospective, randomized trial. Crit Care Med 1995;23:52-9.
29. Ge X, Cavallazzi R, Li C, Pan SM, Wang YW, Wang FL. Central venous access sites for the prevention of venous thrombosis, stenosis and infection. Cochrane Database Syst Rev 2012;3:CD004084.
30. Render ML, Hasselbeck R, Freyberg RW, Hofer TP, Sales AE, Almenoff PL. Reduction of central line infections in Veterans Administration intensive care units: an observational cohort using a central infrastructure to support learning and improvement. BMJ Qual Saf 2011;20:725-732.
31. Robbins RA, Gerkin R, Singarajah CU. Relationship between the veterans healthcare administration hospital performance measures and outcomes. Southwest J Pulm Crit Care 2011;3:92-133.

Refernce as: Hurley J, Garciaorr R, Luedy H, Jivcu C, Wissa E, Jewell J, Whiting T, Gerkin R, Singarajah CU, Robbins RA. Correlation of compliance with central line associated blood stream infection guidelines and outcomes: a review of the evidence. Southwest J Pulm Crit Care 2012;4:163-73. (Click here for a PDF version of manuscript)

Critical Care Review: the High Price of Sugar

Reference as: Robbins RA, Singarajah CU. Critical care review: the high price of sugar. Southwest J Pulm Crit Care 2011;3: 78-86. (Click here for PDF version)

Richard A. Robbins, MD

Clement U. Singarajah, MD

The Phoenix Pulmonary and Critical Care Research and Education Foundation, Phoenix, AZ

Abstract

The intensive control of blood glucose had been proposed to be important in increasing survival in the intensive care unit (ICU) despite only one positive randomized trial. The concept was supported by guidelines released by several regulatory organizations including the Joint Commission of Healthcare Organizations and the Institute of Healthcare Improvement. However, the large, randomized, multi-center NICE-SUGAR trial published in 2009 showed tight control of glucose in the ICU is actually hazardous with a 14% increase in mortality. The historical basis and data used to support intense control of glucose in the ICU are reviewed and illustrate the harm that can result when guidelines are based on weak evidence.

Intensive Control of Glucose in Diabetes

Diabetes has long been associated with vascular complications. These are divided into microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, stroke, and peripheral vascular disease). The concept that intense control of glucose results in improved vascular outcomes in diabetes dates back decades but has been plagued with controversy. The University Group Diabetes Program Study (UGDPS), which began in 1959, was designed to evaluate the relationship between blood sugar control and vascular complications in patients with newly diagnosed type II diabetes. The investigators found that control of blood sugar levels was ineffective in preventing the micro- and macrovascular complications associated with diabetes, regardless of the type of therapy (1). This prompted the American Diabetes Association (ADA) and the American Medical Association to withdrawn their support of UDGPS (2). In 1978, at a meeting of diabetes researchers, clinicians, and epidemiologists from the ADA, the National Institutes of Health (NIH), the Centers for Disease Control, and various university centers, it was concluded that there was “no definite evidence that treatment to regulate blood sugar levels is effective beyond relieving symptoms and controlling acute metabolic disturbances” (2).

This controversy prompted the NIH to organize the Diabetes Control and Complications Trial. This was a large, multi-center, randomized study which compared intensive to conventional treatment in preventing vascular complications in insulin-dependent, type I diabetics. Published in 1993, the results of this trial demonstrated that intensive therapy effectively delayed the onset and slowed the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with insulin-dependent diabetes (3). However, the mortality rate, incidence of macrovascular complications, and incidence of diabetic ketoacidosis were not significantly reduced. Weight gain and episodes of hypoglycemia were significantly more common in the intensive therapy group.

Published in 1998 but started in 1977, the UK Prospective Diabetes Study (UKPDS) was designed to determine if intensive blood glucose control reduced the risk of micro- or macrovascular complications in type II diabetes (4). This study is important since over 90% of adult diabetics, including the majority of diabetics in an adult ICU, have type II diabetes. This large, multi-center, randomized study compared conventional therapy with diet alone to an intense glucose control with diet and either a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or insulin. The goals of the study were to maintain fasting blood glucose of less than 270 mg/dL (15 mmol/L) in the conventional group and less than 108 mg/dL (6 mmol/L) in the intensive control group. Consistent with the blood sugar goals of the study, the hemoglobin A1C was reduced in the intensive therapy group compared to the conventional group (7.0% vs. 7.9%, p<0.05). The results in this study of type II diabetics were similar to the Diabetes Control and Complications Trial in type I diabetics. Microvascular complications, particularly retinal complications, were significantly reduced in the intensive therapy group but macrovascular complications were not. Mortality was not reduced and hypoglycemia and weight gain were more common in the intensive therapy group.

Intensive Control of Blood Glucose in the ICU

Hyperglycemia associated with insulin resistance is common in critically ill patients, even those who have not previously had diabetes (5-7). It had been reported that pronounced hyperglycemia might lead to complications. For example, studies reported that in acute myocardial infarction therapy to maintain blood glucose below 215 mg /dL (11.9 mmol/L) improved long-term outcomes (8-10). Furthermore, high serum levels of insulin-like growth factor-binding protein 1, which reflect insulin resistance, increase the risk of death (11, 12).

Spurred by the above data and the overwhelming opinion of diabetes experts that intensive control of glucose improves outcomes in diabetes and should in the ICU, van den Berge et al. (13) compared intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg/dL) to conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg/dL and maintenance of glucose at a level between 180 and 200 mg/dL) in ICU patients. The study was large with 1548 subjects but was a single center study from a surgical intensive care unit with 63% of the patients post-cardiac surgery. Reported in 2001, the results showed that intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (p<0.04). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy; p=0.005).

The results of van den Berge’s original study were supported by a nonrandomized, single center study reported by Krinsley (14) in 2004. This study from a combined 14 bed medical/surgical ICU consisted of 800 consecutive patients after initiation of a intensive control protocol compared to 800 patients admitted immediately preceding initiation, i.e., a before and after design. The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Hospital mortality decreased 29.3% (p=0.002), and length of stay in the ICU decreased 10.8% (p=0.01) with intensive control of glucose. Despite the before and after comparison, some considered this single center study as confirmatory evidence for the mortality benefit of intensive glucose control.

It has been pointed out that van den Berge’s study had multiple limitations (15). Van den Berge’s 2001 study was a non-blinded, single center and including predominately patients after cardiac surgery, Other limitations included the unusual practices of most patients receiving intravenous glucose on arrival at the intensive care unit (ICU) at 200 to 300 g/d (the equivalent of 2-3 L of 10% glucose per day) and initiation of total parenteral nutrition, or enteral feeding, or combined feeding for all patients within 24 hours. Also, the mortality of cardiac surgery patients in the control group was 5.1% which is unacceptably high in most centers.

Kringsley’s study also had limitations (15). This was a single-center, retrospective, unblinded study and likely reflect a powerful Hawthorne effect (intense glucose control = investigator commitment and bedside presence, more tests, more attention, more patient visits, more interventions, and overall better care). Intensive insulin therapy comes at a substantial price: a greater than 6-fold increase in the risk of hypoglycemia and a marked increase in bedside nurse workload.

When many regulatory guidelines were initiated in the mid 2000’s,  not all data about glucose control and insulin in acute illness pointed to a benefit. The Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 study with more than 1000 randomized patients with myocardial infarction to intense compared to conventional glucose control failed to show a mortality benefit (16). Similarly, the Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation (CREATE)-Estudios Cardiologicas Latin America Study Group (ECLA) study with over 20,000 randomized patients with myocardial infarction failed to show a benefit of a glucose, insulin and potassium infusion regimen compared to usual care (17).

Regulatory Guidelines

By 2005 the Joint Commission on Accreditation of Healthcare Organization (Joint Commission) and the Institute for Healthcare Improvement (IHI) recommended tight glucose control for the critically ill as a core quality of care measure for all U.S. hospitals (18). Furthermore, an international initiative by several professional societies, including the American Thoracic Society, promoted a care “bundle” for severe sepsis that also includes intensive glycemic control.

Concerns about Intensive Glucose Control in the ICU

The medical literature is rife with initially positive trials followed by studies with equivocal or negative trials and occasionally followed by studies with actual harm to patients (19). Intensive control of glucose is a good example of this progression in medical research.

In late 2005, editorials urged waiting on further studies before widespread implement of tight control of glucose as usual care in the ICU. Bellomo and Egi (17) recommended awaiting the results of two large multi-center, randomized trials of tight control of glucose in the ICU, the GluControl study and the NICE SUGAR study. Angus and Abraham (18) echoed the limitations of van den Berge’s study and also advocated caution in the widespread initiation of intensive glucose control in the ICU.

Van den Berge’s group that initially reported the positive results in surgical ICU patients followed their 2001 publication with a report of medical ICU patients in 2006 (20).  In this prospective, randomized study of adult patients admitted to the medical ICU, the authors were unable to reproduce the reduction of in-hospital mortality with intensive glucose control seen in their surgical ICU patients (40.0 vs. 37.3% mortality, p= 0.33). However, the authors reported a significant improvement in morbidity with a reduction in newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. However, among the 433 patients who stayed in the medical ICU for less than three days, mortality was greater among those receiving intensive insulin therapy.  Since the mean length of stay in our medical intensive care at the Phoenix VA was a little less than 3 days, many of our group became concerned that intensive control of glucose would not improve mortality and might actually prove harmful.

The GluControl study was undertaken in 2004 to test the hypothesis that intensive control of glucose (80-110 mg/dL) improves survival of patients treated in  medical/surgical intensive care units (ICU) compared to a control target of 140-180 mg/dL. Planned enrollment was 3500 subjects but the trial was stopped in 2006 after a little over 1000 subjects because interim analysis revealed numerous protocol violations resulting in hypoglycemia. The results were initially reported as an abstract at the 20th Congress of the European Society of Intensive Care in 2008 and a full length manuscript was published in 2009 (21,22). ICU, 28-day and hospital mortality were similar in both groups. ICU and hospital length of stay were identical. Hypoglycemia defined as a blood glucose below 40 mg/dL was seen in 8.7% of the intensive therapy group vs. 2.7% in the conventional group.

Further concern about the concept of intensive glucose control was raised by Weiner et al. (23) in 2008. They searched the medical literature (MEDLINE, the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society and the Society of Critical Care Medicine) and identified 29 randomized controlled trials totaling 8432 patients.  A meta-analysis did not reveal a significant difference between intensive glucose control and usual care overall (21.6% vs. 23.3%) but did reveal an increased risk of hypoglycemia (glucose ≤40 mg/dL, 13.7% vs. 2.5%). In fact, the only study that showed a mortality advantage was van den Berge’s original study in 2001.

The NICE SUGAR Study

The landmark NICE SUGAR study (24) was published in the spring of 2009. This large study randomized 6104 patients to either intensive glucose control, with a target blood glucose range of 81 to 108 mg/dL, or conventional glucose control, with a target of <180 mg/dL. The main finding of the study was that intensive glucose control resulted in a 14% increase in morality. Furthermore, the adverse treatment effect on mortality did not differ significantly between surgical patients and medical patients. As in previous trials, severe hypoglycemia (blood glucose level ≤40 mg /dL) was significantly more common in the intensive-control group (6.8%) compared to the conventional-control group (0.5%, p<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU or hospital, the median number of days of mechanical ventilation or days of  renal-replacement therapy (p>0.05, all comparisons).

Follow up data was presented by Egi et al. (25) in patients admitted to 2 ICUs. The authors analyzed all those who had a blood glucose of <81 mg/dL to determine if there was an independent association between hypoglycemia and outcome. Of the 4946 patients admitted to the ICUs, 1109 had at least 1 episode of hypoglycemia. Mortality was higher in these patients (36.6%) compared with 19.7% in the nonhypoglycemic control patients (p<0.001). Mortality increased significantly with increasing severity of hypoglycemia (p<0.001). In fact, a minimum glucose of <36 mg/dL was associated with over a four-fold increase in ICU mortality compared to a minimum blood sugar of 72-81 mg/dL. After adjustment for insulin therapy, hypoglycemia was independently associated with increased risk of death, cardiovascular death, and death due to infectious disease.

Regulatory Agency Guidelines Following the NICE SUGAR Study

Following publication of the NICE SUGAR study most regulatory agencies dropped their recommendations for intensive glucose control in the ICU. However, remnants of the concept persist. IHI continues to promote “…effective glucose control in the intensive care unit (ICU) [which] has been shown to decrease morbidity across a large range of conditions and also to decrease mortality” (26). In another posting entitled “Establish a Glycemic Control Policy in Your ICU” (27) IHI states, “Typically, clinicians’ fear of inducing hypoglycemia is the first obstacle to overcome in launching an improvement effort. Doctors remain wary of inducing hypoglycemia and may not have confidence in selecting appropriate doses. Nurses fear hypoglycemia and remain concerned about protocolized adjustments to intravenous insulin rates of administration. The balance of evidence suggests, however, that once these barriers are addressed, ICU patients receive better care with appropriate glycemic control.”  Since hypoglycemia is associated with increased mortality in the ICU (22), this doctor and nurse fear of hypoglycemia seems well founded.

Hyperglycemia

Even though hypoglycemia is associated with excess mortality, hyperglycemia is also undesirable. As Falciglia et al. (28) point out, mortality increases with increasing admission glucose in the ICU. Although this is not the same as saying correcting the hyperglycemia improves mortality, it does suggest that hyperglycemia is undesirable. Furthermore, it has long been known that mortality is increased in patients with myocardial infarction and hyperglycemia (29). However, this increase in mortality with hyperglycemia does not apply to all disease states. For example, hyperglycemia in COPD or liver failure is not associated with increased mortality (28). This may have implications if the patients in a particular ICU population have predominately cardiac, respiratory or liver disease. However, even in this study an increase in mortality was noted with an admission blood sugar of <70 mg/dL to the ICU compared to a blood sugar of 70-100 mg/dL and approximates the mortality seen with an admission glucose of >300 mg/dL.

Conclusions and Recommendations

Based on the available evidence, we would suggest maintaining blood glucose levels of less than 180-200 mg/dL while avoiding blood sugars less than 80 mg/dL in the ICU. Intensive control of glucose is not evidence based, harmful, and should be discouraged. One might be somewhat more aggressive to maintain the blood sugar below 150 mg/dL in patients who are post-operative cardiac patients or receiving large infusions of glucose such as in van den Berge’s original study (13). However, avoidance of hypoglycemia is probably more important than maintaining a blood sugar below a certain level.

The rush to publish guidelines creating a standard of care of intensive regulatory control of glucose in the ICU seems irrational in retrospect and demonstrates a potentially continued threat to patient safety. In addition, these guidelines increased the workload of both nurses and clinicians. Although often thought to be revenue neutral, these mandates come at the price of increasing personnel costs both in implementation and monitoring of a guideline. Since personnel costs account for about 60-70% of the total costs in most health care systems, such mandates may be quite costly, or as the mandate for intensive glucose regulation illustrate, may actually be harmful. If the increase in mortality of 14% with intense glucose control is true as in the NICE SUGAR trial, this would calculate to one excess death for every 84 patients treated with this protocol (24,30). It seems unlikely that any ICU guidelines mandated in the future could compensate for the excess deaths caused by the mandated implementation of intense control of glucose. Fortunately, it is doubtful that implementation was 100%.

In an editorial entitled “Intensive insulin therapy in critical illness: when is the evidence enough?” Angus and Abraham (18) addressed the issue of when there is sufficient evidence for a concept to be widely applied as a guideline. Comparing the evaluation of intensive control of glucose in the ICU to evaluation of novel pharmacologic therapies, they point out that promising phase II studies are insufficient for regulatory approval. Instead, one, and usually two, large multicenter phase III trials are necessary to confirm reliability. The same principle is echoed in evidence-based medicine, where grade A recommendations are based on two or more large, positive, randomized, and multicenter trials. This seems a reasonable suggestion. Strong recommendations of this clinical importance should only be made when two or more large randomized controlled trials concur. However, it also seems unlikely that a mere review article such as this or the multiple recommendations from clinicians such as occurred with intensive control of glucose in the ICU will attenuate the exuberance of regulatory agents to mandate physicians and nurses to conform to their guidelines. Perhaps what is needed is an independent Federal or private agency to review and approve guidelines, and as Angus and Abraham suggest require at least two randomized, multicenter trials before implementation. As long as regulatory agencies accept no responsibility for harmful recommendations, it seems likely that in the absence of regulation, mistakes similar to the mandate to intensively regulate glucose in the ICU are likely to reoccur.

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15. Bellomo R, Egi M. Glycemic Control in the Intensive Care Unit: Why We Should Wait for NICE-SUGAR. Mayo Clin Proc 2005;80:1546-8.
16. Malmberg K, Ryden L, Wedel H, et al., DIGAMI 2 Investigators. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005;26:650-661. 
17. Mehta SR, Yusuf S, Diaz R, et al. CREATE-ELCA Trial Group Investigators. ST-segment elevation myocardial infarction: the REATE-ECLA randomized controlled trial. JAMA 2005;293:437-446.
18. Angus DC, Abraham E. Intensive insulin therapy in critical illness: when is the evidence enough? Am J Resp Crit Care 2005;172:1358-9.
19. McGauran N, Wieseler B, Kreis J, Schüler YB, Kölsch H, Kaiser T. Reporting bias in medical research - a narrative review. Trials 2010;11:37.
20. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulin therapy in the medical ICU. New Engl J Med 2006;354:449-61.
21. Devos P, Preiser JC, Melot C. Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the Glucontrol study. Intensive Care Med 2007;33:S189 [abstract].
22. Preiser JC, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, Wernerman J, Joannidis M, Stecher A, Chioléro R. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009;35:1738-48.
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Analysis of Overall Level of Evidence Behind The Institute of Healthcare Improvement Ventilator-Associated Pneumonia Guidelines

Reference as: Padrnos L, Bui T, Pattee JJ, Whitmore EJ, Iqbal M, Lee S, Singarajah CU, Robbins RA. Analysis of overall level of evidence behind the Institute of Healthcare Improvement ventilator-associated pneumonia guidelines. Southwest J Pulm Crit Care 2011;3:40-8. (Click here for PDF version of manuscript)

Leslie Padrnos^1,4(lpadrnos@email.arizona.edu)

Tony Bui^1,4 (tony.bui@cox.net)

Justin J. Pattee^2,4 (backageyard@gmail.com)

Elsa J. Whitmore^2,4 (elsa_whitmore@hotmail.com)

 Maaz Iqbal^1,4 (maaziqbal@gmail.com)

Steven Lee^3,4 (timmah2k@gmail.com)

Clement U. Singarajah^2,4 (clement.singarajah@va.gov)

 Richard A. Robbins^1,4,5 (rickrobbins@cox.net)

¹University of Arizona College of Medicine

²Midwestern University-Arizona College of Osteopathic Medicine

³Kirksville College of Osteopathic Medicine

⁴Phoenix VA Medical Center

⁵Phoenix Pulmonary and Critical Care Research and Education Foundation

None of the authors report any significant conflicts of interest.

Abstract

Background 

Clinical practice guidelines are developed to assist in patient care but the evidence basis for many guidelines has recently been called into question.

Methods 

We conducted a literature review using PubMed and analyzed the overall quality of evidence and made strength of recommendation behind 6 Institute of Health Care (IHI) guidelines for prevention of ventilator associated pneumonia (VAP). Quality of evidence was assessed by the American Thoracic Society levels of evidence (levels I through III) with addition of level IV when evidence existed that the guideline increased VAP. We also examined our own intensive care units (ICUs) for evidence of a correlation between guideline compliance and the development of VAP.

Results 

None of the guidelines could be given more than a moderate recommendation. Only one of the guidelines (head of bed elevation) was graded at level II and could be given a moderate recommendation. One was graded at level IV (stress ulcer disease prophylaxis). The remainder were graded level III and given weak recommendations. In our ICUs compliance with the guidelines did not correlate with a reduction in VAP (p<0.05).

Conclusions 

Most of the IHI guidelines are based on level III evidence. Data from our ICUs did not support guideline compliance as a method of reducing VAP. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current IHI VAP guidelines to direct patient care decisions or as an assessment of the quality of care.

Introduction

The growth of guideline publications addressing nearly every aspect of patient care has been remarkable. Over the past 30 years numerous medical regulatory organizations have been founded to improve the quality of care. Many of these organizations have developed medical regulatory guidelines with 6870 listed in the National Guideline Clearinghouse (1). Many of these guidelines were rapidly adopted by healthcare organizations as a method to improve care.

Interest has grown in critically appraising not only individual clinical practice guidelines but also entire guideline sets of different medical (sub)specialties based on their rapid proliferation and in many instances an overall lack of efficacy in improving care (2,3). We assessed the quality of evidence underlying recommendations from one medical regulatory organization, the Institute for Healthcare Improvement (IHI), regarding one set of guidelines, the ventilator associated pneumonia (VAP) guidelines or VAP bundles (4). This was done by senior medical students during a month long rotation in the Phoenix Veterans Administration ICU. 

Methods

The study was approved by the Western Institutional Review Board.

Literature Search

In each instance PubMed was searched using VAP which was cross referenced with each component of the VAP bundle (as modified by the Veterans Administration) using the following MESH terms: 1. Elevation of the head of the bed; 2. Daily sedation vacation; 3. Daily readiness to wean or extubate; 4. Daily spontaneous breathing trial; 5. Peptic ulcer disease prophylaxis; and 6. Deep venous thrombosis prophylaxis. In addition, each individual component of the term was cross referenced with VAP. We also reviewed “Related citations” as listed on PubMed. Additional studies were identified using the “Related citations” in Pubmed from studies listed as supporting evidence on the IHI website and from the references of these studies.

Each study was assessed for appropriateness to the guideline. Studies were required to be prospective and controlled in design. Only studies demonstrating a reduction in VAP were considered, i.e., surrogate outcomes such as reduction in duration of mechanical ventilation were not considered. 

The American Thoracic Society grading system was used to assess the underlying quality of evidence for the IHI VAP guidelines (5) (Table 1). Only evidence supporting a reduction in VAP was considered. We added category IV when there was literature evidence of potentially increasing VAP with the use of the recommendation. A consensus was reached in each case. 

Table I. Levels of Evidence

Level of Evidence	Definition
Level I (high)	Evidence from well-conducted, randomized controlled trials.
Level II (moderate)	Evidence from well-designed, controlled trials without randomization (including cohort, patient series, and case-control Studies). Level II studies also include any large case series in which systematic analysis of disease patterns was conducted, as well as reports of data on new therapies that were not collected in a randomized fashion.
Level III (low)	Evidence from case studies and expert opinion. In some instances, therapy recommendations come from antibiotic susceptibility data without clinical observations.
Level IV	No evidence of improvement with some evidence of an increase in a negative outcome.

Guideline Compliance and VAP Incidence

We also assessed our ICUs for additional evidence of the effectiveness of the VAP bundle. Data was collected for a period of 50 months from January, 2007 through February, 2011. This was after the Veterans Administration requirements for VAP reporting and IHI compliance was instituted. Diagnosis and compliance were assessed by a single quality assurance nurse using a standardized protocol (6). Statistical analysis was done using a Pearson correlation coefficient with a two-tailed test. Significance was defined as p<0.05.

Results

Literature Review

Numbers of articles identified by PubMed search and used for grading the level of evidence and strength of recommendation are given in Table 2. Also included are the level of evidence and the strength of the recommendation.

Table 2.

Guideline

Total Articles

No. of Articles Used (references)

Level of Evidence

Strength of Recommendation

Elevation of the head of the bed	31	8 (7-14)	II	Moderate
Daily sedation vacation	66	4 (15-18)	III	Weak
Daily readiness to wean or extubate	47	3 (19-21)	III	Weak
Daily spontaneous breathing trial	29	1 (22)	III	Weak
Peptic ulcer disease prophylaxis	52	9 (23-29)	IV	Weak
Deep venous thrombosis prophylaxis.	14	2 (30-31)	III	Weak

Head of Bed Elevation

A literature search identified 31 articles of which 8 were used in evaluating this guideline (7-14). However, only 2 specifically studied head of bed elevation with one supporting and another not supporting the intervention (7,8). Consequently it was graded as level II and the strength of recommendation was graded as moderate.

Daily Spontaneous Breathing Trial, Daily Readiness to Wean, and Daily Sedation Vacation

From 1-4 studies were identified for each of these interventions, however, none demonstrated a reduction in VAP. Consequently, it was judged that the evidence basis was level III and the strength of recommendation was graded as weak.

Stress Ulcer Disease Prophylaxis

We found no evidence that stress ulcer disease prophylaxis decreased VAP (23-29). There was some evidence that acid suppressive therapy increased pneumonia and VAP. Consequently, it was judged to be a level IV (possibly increasing VAP). 

Deep Venous Thrombosis Prophylaxis

We could find no evidence that deep venous thrombosis prophylaxis decreased VAP (30,31).

Guideline Compliance and VAP Incidence

Beginning in the first quarter of fiscal year 2007 there was a significant decrease in the incidence of VAP in our hospital (33). This coincided with the requirement for the monitoring of VAP, compliance with the VAP bundles and our adoption of endotracheal aspiration with nonquantitative culture of the aspirate as opposed to bronchoalveolar lavage which had been out standard practice. We changed practices because bronchoalveolar lavage with quantitative cultures appeared to offer no improvement in clinical outcomes to endotracheal aspiration (34). In our medical and surgical ICUs, 5097 audits representing 5800 ventilator-days were assessed. Nineteen cases of VAP were identified with an average of 2.1 VAP infections/1000 ventilator-days.  We assessed our surgical and medical ICUs, combined and separately, for a correlation between total bundle compliance and each component of the VAP bundle with VAP incidence (Appendices 1-3). There was no significant correlation between compliance with the bundles and VAP (p<0.05).

Discussion

This manuscript questions the validity of the VAP bundles as proposed by the IHI. We found that a systematic review of the literature revealed predominately weak evidence to support these guidelines. Only one guideline (head of bed elevation) was supported by a randomized trial (7), but an additional, larger trial showed no decrease in VAP (8). Furthermore, data from our own ICUs showed no evidence of IHI VAP guideline compliance with a reduction in VAP.

Head of bed elevation is a relatively simple and easy to perform intervention which may reduce VAP. Studies examining aspiration have shown a reduction in critical care patients with the head of bed elevation but it is unclear whether this translates into a reduction in VAP (36,37). Drakulovic et al. (7) reported a randomized controlled trial in 86 mechanically ventilated patients assigned to semi-recumbent or supine body position.  The trial demonstrated that suspected cases of ventilator-associated pneumonia had an incidence of 34 percent while in the semi-recumbent position suspected cases had an incidence of 8 percent (p=0.003).  However, another study in 221 subjects demonstrated that the target head elevation of 45 degrees was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients (8). The achieved difference in treatment position (28 degrees vs. 10 degrees) did not prevent the development of ventilator-associated pneumonia. The other 5 articles identified either did not identify head of bed elevation directly or as part of a bundle. Most were a before and after design and not randomized. Therefore, it is difficult to draw any meaningful conclusions.

The IHI groups daily "sedation vacations" and assessing the patient’s “readiness to extubate.” The logic is that more rapid extubation leads to a reduction in VAP. Kress et al. (15) conducted a randomized controlled trial in 128 adult patients on mechanical ventilation, randomized to either daily interruption of sedation irrespective of clinical state or interruption at the clinician’s discretion. Daily interruption resulted in a reduction in the duration of mechanical ventilation from 7.3 days to 4.9 days (p=0.004). However, in a retrospective review of the data, the authors were unable to show a significant reduction in VAP (16).

Stress ulcer prophylaxis and deep venous thrombosis prophylaxis are routine in most ICUs. However, stress ulcer prophylaxis with enteral feeding is probably as effective as acid suppressive therapy and acid suppressive therapy may increase the incidence of VAP (38). Deep venous thrombosis prophylaxis has been shown to decrease the incidence of pulmonary emboli but not improve mortality (32). Although we use these interventions in our ICU, we would suggest that these would be more appropriate for recommendations rather than guidelines.

The diagnosis of VAP is difficult, requiring clinical judgment even in the presence of objective clinical criteria (6). The difficulty in diagnosis, along with the negative consequences for failure to follow the IHI guidelines, makes before and after comparisons of the incidence of VAP unreliable. Therefore, we sought evidence for the effectiveness of VAP prevention guidelines reasoning that the better the compliance with the guidelines, the lower the incidence of VAP. We were unable to show that improved VAP guideline compliance correlated with a reduced incidence of VAP.

The IHI guidelines would not meet the criteria outlined earlier in an editorial in the Southwest Journal of Pulmonary and Critical Care for a good guideline:

Our study has several limitations. No literature review is totally comprehensive. It is possible that studies relevant to the IHI VAP guidelines, especially those written in a foreign language, were not identified. Second, the Phoenix VA data may be underpowered to show a small beneficial effect despite having over 5000 patient audits. Third, as with other healthcare facilities, the VAP guidelines at our institution were mandated and monitored. The threat of negative consequences may have compromised the objective assessment of the data, likely invalidating a before and after comparison. Fourth, correlation between guideline compliance and VAP incidence is not a substitute for a randomized trial. Unfortunately, the later is not possible given that guideline compliance is mandated.

It is unclear why the IHI guidelines have received such wide acceptance given their weak evidence basis. Agencies involved in guideline writing should show restraint in guideline formulation based on opinion or weak or conflicting evidence. Only those interventions based on strong evidence which can make a real difference to patients should be designated as guidelines.

Acknowledgements

The authors acknowledge Janice Allen, MSN, RN who collected the VAP data reported from the Phoenix VA.

References

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Appendices

Click here for Appendix 1. VAP rate in all ICUs

Click here for Appendix 2. VAP in medical ICU

Click here for Appendix 3. VAP in surgical ICU

ARTERIAL AMMONIA LEVELS IN THE MANAGEMENT OF FULMINANT LIVER FAILURE

Robert Raschke

Steven Curry

Silke Remke

Ester Little

Richard Gerkin

Richard Manch

Alan Leibowitz

Banner Good Samaritan Regional Medical Center, Phoenix, AZ

Reference as:  Raschke R, Curry S, Remke S, Little E, Gerkin R, Manch R, Leibowitz A. Arterial ammonia levels in the management of fulminant liver failure. Southwest J Pulm Crit Care 2011;2:85-92. (Click here for PDF version)

Abstract

Previous studies have suggested that an arterial ammonia level greater than 150 mmol/L is highly sensitive for predicting subsequent development of cerebral edema in patients with fulminant liver failure. We performed a prospective cohort study to confirm this relationship. We enrolled 22 consecutive patients who presented to our transplant hepatology service with grade 3-4 encephalopathy associated with fulminant liver failure. All patients underwent placement of an intraparenchymal ICP monitor, and every 12 hourly arterial ammonia levels. The prevalence of intracranial hypertension (IHTN) in our population was 95% (21/22 patients), with 82 discrete episodes recorded. The sensitivity of arterial ammonia levels to predict the onset of IHTN was 62% (95% CI: 40.8 to 79.3) at a cut point of 150 mmol/L. Arterial ammonia levels preceding the first intracranial hypertension event were less than 150 mmol/L in 8 of 21 patients (39%). Fifty nine of 82 episodes of IHTN (73%) occurred when arterial ammonia levels were less than 150 mmol/L. We conclude that the arterial ammonia level is not useful in making decisions regarding management related to cerebral edema in patients with fulminant liver failure. In fact, since almost all our study patients with grade III or IV encephalopathy secondary to fulminant liver failure went on to develop intracranial hypertension, our study supports the contention that all such patients might benefit from ICP monitoring regardless of arterial ammonia levels.

Background

Cerebral edema is the most common cause of death in fulminant liver failure (FLF) (1,2), occurring in 80% of patients with advanced encephalopathy (3). Cerebral edema causes brain injury by compromising cerebral perfusion pressure and/or by causing cerebral herniation. Intracranial hypertension (IHTN) is the most reliable sign of cerebral edema, and is defined as an intracranial pressure (ICP) greater than 20 mmHg (4-6). Many authors have recommended ICP monitoring in FLF to guide management of cerebral edema (7,8) although this procedure entails significant hemorrhagic risk (9,10).

The pathogenesis of cerebral edema in FLF is likely multifactorial, but substantial evidence supports a causal role for hyperammonemia. Elevated ammonia levels alter neurotransmitter synthesis, and interfere with mitochondrial function causing oxidative stress and neuronal apoptosis (4,5,6,11-16). Increased delivery of ammonia to astrocytes provides substrate for the accumulation of intracellular glutamine (17-18). The resulting osmotic effect causes astrocyte swelling and cerebral edema (6,7,19). Clinical studies have repeatedly shown that arterial ammonia levels around 150 mmol/L have a statistically significant association with the development of IHTN and cerebral edema in humans (8,20-22).

Clemmensen and colleagues (8) measured arterial ammonia levels at the onset of grade III encephalopathy in 44 patients with FLF. Fourteen of those patients subsequently developed cerebral herniation. The patients who developed cerebral herniation had significantly higher mean arterial ammonia levels (230 vs. 118 μmol/L P<0.001), and all had ammonia levels > 146 μmol/L. At this cut point, arterial ammonia had a sensitivity of 100%, a specificity of 73% and a PPV of 64% for the subsequent development of cerebral herniation (8).

The results of this study raised the possibility that arterial ammonia levels could be used to select FLF patients likely to benefit from ICP monitoring. If arterial ammonia levels above 146 μmol/L were highly sensitive for predicting the development of IHTN, patients with arterial ammonia levels below this threshold would not likely benefit from ICP monitoring, therefore the significant hemorrhagic risk of monitor placement could be avoided (20,23).

The primary aim of our study was to confirm this premise by reassessing the sensitivity of the arterial ammonia concentration for predicting the onset of intracranial hypertension (IHTN). We chose IHTN as our dependent variable since cerebral herniation is uncommonly seen in patients managed with our neuroprotective treatment protocol (24), and because intracranial hypertension can cause brain injury by compromising cerebral perfusion in the absence of herniation. The secondary aim of our study was to determine whether following serial arterial ammonia levels are valuable in predicting the timing of recurrent IHTN episodes before and after liver transplantation.

Methods

A prospective case series was approved by the Institutional Review Board at Banner Good Samaritan Regional Medical Center, a 650 bed community teaching hospital in Phoenix Arizona. The Transplant Hepatology service identified consecutive patients admitted with FLF, as defined by standard criteria (20) between May 2004 and September 2006. All patients underwent serial neurological examinations by an intensivist, and those who developed grade 3-4 encephalopathy were evaluated for study participation. Eligible patients’ families were asked to provide informed consent.

Serial arterial ammonia levels were obtained in study patients. An arterial catheter was placed and 5 cc of arterial blood was drawn into a sodium heparin-containing tube every 12 hours. These samples were transported to the chemistry laboratory on ice within 30 minutes. Quantitative plasma ammonia concentrations were performed using an enzymatic kinetic assay (Roche Diagnostics, Mannheim Germany). This assay has a reportable range of 5.87-587 mmol/L and a coefficient of variability of 2%.

An intraparenchymal ICP monitor (Codman MicroSensor^® - Codman/Johnson & Johnson Professional, Inc., Randolph, MA) was placed in the non-dominant frontal lobe under local anesthesia by a neurosurgeon. The ICP was monitored continuously thereafter. Hemostatic therapy and ICP management used in the study have been previously described (24). ICP monitors were removed post-transplantation when the patient could tolerate lowering of their head to zero degrees without precipitating IHTN. In patients who did not undergo transplantation, ICP monitors were removed upon clinical recovery or death.  

Our main independent variable was the arterial plasma ammonia level. Our main dependent variable was intracranial hypertension, defined as an ICP > 20 mmHg for > 20 mins.  We performed 3 separate sets of analyses to examine the relationship between arterial ammonia levels and IHTN: 1) we analyzed the arterial ammonia level that most closely preceded the onset of the first episode of IHTN in each patient; 2) we analyzed all arterial ammonia levels in relation to all episodes of IHTN; and 3) we analyzed all arterial ammonia levels in relation to all episodes of IHTN occurring post liver transplantation. The second and third analyses involved data values that were not independent of each other, therefore standard statistical techniques were not appropriate and time series analysis was performed. Statistical analyses were performed using SPSS 13.0 (SPSS Inc. Chicago IL.) Operating characteristics of arterial ammonia levels were calculated at a cut point of 150 mmol/L.  

Results

Twenty two patients were entered – their clinical characteristics at study entry are listed in Table 1.

Table 1:  Patient Characteristics:
Mean age:	32.7 years (S.D. 10.3 yrs, range 15-56)
Gender:	17/22 (77%) female
Etiology:	acetaminophen toxicity (12 patients) hepatitis A (3) hepatitis B (1) anticonvulsant hypersensitivity syndrome (1) sulfa hypersensitivity syndrome (1) Wilson’s disease (1) Cryptogenic (3)
Encephalopathy grade:	8 patients (36%) Grade III 14 patients (64%) Grade IV

Our 22 patients cumulatively underwent 3252 hours of ICP monitoring. Mean monitor duration was 147.8 +/- 143.3 hours. Monitors were left after liver transplantation in nine patients for 85.6 +/- 60.6 hours.

The prevalence of IHTN in our population was 95% (21/22 patients). Eighty-two discrete episodes of intracranial hypertension occurred. 62 occurred prior to, 4 during, and 16 after liver transplantation. The peak ICP during IHTN events was 33 +/- 13 mmHg (mean +/- S.D.) and the median duration was 60 minutes.

Relationship between arterial ammonia levels and the first episode of IHTN: The mean arterial ammonia level preceding the first intracranial hypertension event in each patient was 185 +/- 67 mmol/L (range: 96 – 337 mmol/L). The sensitivity of arterial ammonia levels to predict the onset of IHTN was 62% (95% CI: 40.8 to 79.3) at a cut point of 150 mmol/L. Arterial ammonia levels preceding the first intracranial hypertension event were less than 150 mmol/L in 8 of 21 patients (39%). We could not accurately calculate specificity or area under the receiver operator curve (AUROC) since only one patient did not develop IHTN.  

Relationship between arterial ammonia levels and all episodes of IHTN: The mean arterial ammonia levels just prior to each of the individual 82 episodes of IHTN were 122 +/- 80 mmol/L (range: 15 – 270 mmol/L). Fifty nine of 82 episodes of IHTN (73%) occurred when arterial ammonia levels were less than 150 mmol/L.

Relationship between arterial ammonia levels and all episodes of IHTN occurring post liver transplantation: Nine patients underwent liver transplantation. Seventy-nine ammonia levels were obtained post-liver transplantation in these patients. Four transplant recipients experienced 16 post-operative IHTN events. The mean arterial ammonia just prior to each of these events was 70 +/- 48 mmol/L (range: 15 – 161 mmol/L). The sensitivity of the arterial ammonia level preceding each IHTN event was 13% and the specificity was 100% at a cut point of 150 mmol/L. Arterial ammonia levels were statistically lower in post-transplant IHTN episodes than in pre-transplant episodes (P<0.001).

Discussion

Our study showed that almost all patients with grade III or IV encephalopathy secondary to fulminant liver failure will develop intracranial hypertension – this supports the possible benefit of intracranial pressure monitoring in all such patients regardless of arterial ammonia levels. Although the high prevalence of IHTN in our study population prevented us from calculating the specificity of arterial ammonia levels, sensitivity is the key characteristic of this test in terms of our research question. Our study shows that arterial ammonia levels > 150 mmol/L are not sensitive for subsequent development of IHTN, and therefore should not be used to identify a subset of patients unlikely to benefit from ICP monitoring.

Our study did not confirm the clinical utility of arterial ammonia levels in predicting neurological injury in patients with FLF, as suggested by Clemmensen et al (8). This could be because the clinical event of interest in the two studies differed – Clemmensen focused on cerebral herniation, and we measured IHTN directly. Cerebral herniation occurred in 14 of Clemmensens’ 44 patients, but it was not observed in our patients. Our study utilized a management protocol specifically designed to prevent cerebral herniation (24). It is unknown how many of our patients with IHTN would have gone on to herniate if IHTN had not been detected and aggressively treated.           

Several other studies have examined the predictive value of arterial ammonia levels for cerebral edema and IHTN in patients with acute liver failure. Bernal and colleagues studied 165 patients with acute liver failure and grade 3-4 encephalopathy and found that arterial ammonia on admission was higher in those who later developed IHTN (121 vs 109 mmol/L p<0.05 (20). However, the sensitivity of an ammonia cut-point of 150 mmol/L was only 40%, and the positive predictive value (probability that a patient with ammonia > 150 mmol/L would develop IHTN) was only 16%.   

Bhatia and colleagues studied 80 patients with ALF, 58 of whom had grade 3-4 encephalopathy (21). They calculated an optimal cut-point for arterial ammonia for predicting mortality was 124 mmol/L by ROC analysis. Patients with ammonia levels above this cutpoint had a higher frequency of cerebral edema (47% vs. 22% P=0.02). Sensitivity and positive predictive values can be calculated from data presented in their paper, and are 71% and 48% respectively.  

Our results confirm those of Bernal and Bhatia in that all 3 studies showed that the operating characteristics of the arterial ammonia test are insufficient for triaging ALF patients in regards to invasive ICP monitoring. But our study has several important differences. IHTN or cerebral edema was detected in only 29% of Bernal’s patients and 35% of Bhatia’s. Both studies relied heavily on physical examination to diagnose these outcomes despite evidence that it lacks the sensitivity to do so (1,3,25-27). Our study utilized the gold standard (ICP monitoring) in all our patients. We found a much higher prevalence of IHTN – 95% in patients with grade 3-4 encephalopathy. This high prevalence explains the higher positive predictive value in our study, and suggests that previous studies may have suffered from significant underdetection of IHTN and cerebral edema.

Our study is also unique in that we performed repeated measures of arterial ammonia. This was important in terms of our hypothesis that patients’ risk for IHTN might change over time in response to treatments such as lactulose, continuous renal replacement therapy, and liver transplantation. Unfortunately, we found that repeated measures of arterial ammonia were no more clinically useful than the single levels used in previous studies.

Our study has several important limitations. Our limited sample size produced wide confidence intervals about our estimation of sensitivity. Our study only included patients with advanced encephalopathy - it’s possible that arterial ammonia levels might demonstrate improved prognostic significance earlier in the course of FLF. We did not attempt to analyze the effect of cumulative ammonia exposure over time.

 Our findings, and those of previous investigators, suggest that other factors besides peak ammonia levels are important in the pathogenesis of FLF-induced cerebral edema. Two other proposed causative factors are pathological alterations in cerebral blood flow (28-32) and systemic inflammatory response (30,33-34). The interplay of all three factors may be critical to the pathogenesis of cerebral edema in FLF and this might explain why simple measurement of serum ammonia is not sufficient to predict IHTN.

   Further work is needed to elucidate the pathogenesis of IHTN in FLF and identify variables that predict which patients will develop this life-threatening complication. Until then, we suggest that all patients with grade 3 or 4 encephalopathy secondary to FLF are at high risk. Our study shows that arterial ammonia levels in these patients cannot be relied upon to accurately triage patients in regards to their risk for IHTN. Thus, it is not helpful in determining which patients might benefit from ICP monitoring, nor determining when ICP monitoring can safely be discontinued.

Conclusions

An arterial ammonia level of 150 mmol/L is poorly sensitive for determining which patients with ALF will develop IHTN and should not be used to determine which patients are likely to benefit from ICP monitoring. The prevalence of IHTN in FLF patients with grade 3-4 encephalopathy is so high that no other predictive test is likely to be of added value. Although arterial ammonia levels are correlated with episodes of IHTN, most individual IHTN episodes occur when arterial ammonia levels are < 150 mmol/L. After successful transplantation IHTN events can continue to occur even as ammonia levels enter the normal range.

References

1. Lee WM. Management of acute liver failure. Semin Liver Dis 1996; 16:369-378.

2. Ellis AJ, Wendon J. Circulatory, respiratory, cerebral and renal derangement in acute liver failure: pathophysiology and management. Semin Liver Dis 1996; 16: 379-389.

3. Gill R., Sterling R, Acute Liver Failure. Journal of Clinical Gastroenterology 2001; 33 (3.:191-198.

4.Blei AT, Brain edema and portal-systemic encephalopathy. Liver Transplantation. 2000;6(Suppl 1.:S14-S20.

5. Kato M, Hughes RD, Keays RT, Williams R. Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure. Hepatology. 1992;15:1060-66.

6. Blei AT, Olafsson S, Therrien G, Butterworth RF. Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. Hepatology. 1994;19:1437-44.

7. Takahashi H, Koehler RC, Brusilow SW, Traystman RJ. Inhibition of brain glutamine accumulation prevetns cerebral edema in hyperammonemic rats. Am J Physiol. 1991;261:H825-H829.

8. Clemmessen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patient with acute liver failure is correlated with arterial ammonia concentration. Hepatology 1999;29:648-653.

9. Lee WM. Acute liver failure. N England J Med 1993; 329: 1862.

10. Blei AT, Olafsson S, Webster S, Levy R. Complications of intracranial pressure monitoring in fulminant hepatic failure. Lancet. 1993;341: 157-8.

11. Vaquero J, Chung C, Blei AT. Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy. Annals of Hepatology. 2003;2:12-22.

12. Tofteng F, Jorgensen L, Hansen BA, Ott P, Koadrap J, Larsen FS. Cerebral microdialysis in patients with fulminant hepatic failure. Hepatology. 2002;36:1333-40.

13. Kosenko E, Felipo V, Montolia C, Grisolia S, Kaminsky Y. Effectos of acute hyperammonemia in vivo on oxidative metabolism in nonsynaptic rat brain mitochondria. Metabolic Brain Diseases. 1996;12:69-82.

14. Norenberg MD. Oxidative and nitrosative stress in ammonia neurotoxicity. Hepatology. 2003;37:245-8.

15. Vaquero J, Chung C, Cahill ME, Blei AT. Pathogenesis of hepatic encephalopathy in acute liver failure. Seminars in liver disease. 2003;23:259-69.

16. Widmer R, Kaiser B, Engels M, Jung T, Grune T. Hyperammonemia causes protein oxidation and enhanced proteasomal activity in response to mitochondria-mediated oxidative stress in rat primary astrocytes. Arch Biochem Biophys. 2007;464:1-11.

17. Swain M, Butterworth RF, Blei AT. Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats. Hepatology. 1992;15:449-53.

18. Cordoba J, Gottstein J, Blei AT. Glutamine, myo-inositol, and organic osmolytes after portocaval anastomosis in the rat: Implications for ammonia-induced brain edema. Hepatology. 1996;24:919-23.

19. Tofteng F, Hauerberg J, Hansen BA, Pedersen CB, Jorgensin L, Larsen FS. Persistant arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure. J Cereb Bood Flow Metab. 2006;26:21-7..

20. Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46:1844-52.

21. Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006;55:98-104.

22. Kundra A, Jain A, Banga A, Bajaj G, Kar P. Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clin Biochem. 2005;38:696-9.

23. Bass NM. Monitoring and treatment of intracranial hypertension. Liver Transplantation 2000; 6(4. Supp1:S21-S26

23. Davern TJ. Predicting prognosis in acute liver failure: Ammonia and the risk of cerebral edema. Hepatology. 2007;46:1679-81.

24. Raschke RA, Curry SC, Rempe S, Gerkin R, Little E, Manch R, Wong M, Ramos A, Leibowitz AI. Results of a Protocol for the Management of Patients with Fulminant Liver Failure. Critical Care Medicine. 2008;36:2244-8.

25. Hoofnagle JH, Carithers RL, Shapiro C, Ascher N. Fulminant hepatic failure: Summary of a workshop. Hepatology. 1995;21:240-52.

26. Canalese J, Gimson AES, Davis C, Mellon PJ, Davis M, Williams R. Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure. Gut 1982;23:625-9.

27. Brajtbord D, Parks RI, Ramsay MA, Paulsen AW, Valek TR, Swygert TH, Klintmalm GB. Management of acute elevation of intracranial pressure during hepatic transplantation. Anesthesiology. 1989;70:139-141.

28. Wendon JA, Harrison PM, Keays R, Williams R. Cerebral blood flow and metabolism in fulminant liver failure. Hepatology. 1994;19:1407-13.

29. Sari A, Yamashita S, Ohosita S, Ogasahara H, Yamada K, Yonei A, Yokota K. Cerebrovascular reactivity to CO₂ in patients with hepatic or septic encephalopathy. Resuscitation. 1990;19:125-34

30. Jalan r, Olde Damink SWM, Hayes PC, Deutz NEP, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: Inflammation, ammonia and cerebral blood flow. Journal of Hepatology. 2004;41:613-20.

31. Kramer D, Aggarwal M, Darby J, Obrist W, Rosenbloom A, Murray G, Linden P, et al. Management options in fulminant hepatic failure. Transplant Proc. 1991;23:1895-8.

32. Jalan R, Olde Damink SWM, Deutz NEP, Hayes PC, Lee A. Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia. Hepatology. 2001;34:50-4.

33. Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000;32:734-9

34. Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee W, Blei AT, and the U.S. Acute Liver Failure Study Group. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology.2003;125:755-64.     

RIGHT PLEURAL INSERTION OF A SMALL BORE FEEDING TUBE

Clement U. Singarajah

 Tyler Glenn

Richard A. Robbins

Phoenix VA Medical Center, Phoenix, AZ

Reference as: Singarajah CU, Glenn T, Robbins RA. Right pleural insertion of a small bore feeding tube. Southwest J Pulm Crit Care 2011;2:71-6. (Click here for PDF version)

Abstract

We report a case of a 56 year old man who had a feeding tube inadvertently malpositioned into the right pleural space and had approximately 600 ml of tube feedings infused. After the malposition was recognized, the patient underwent chest tube placement, followed by video assisted thoracic surgery 5 days later. He made an uneventful recovery. The case illustrates the problems with identification and treating feeding tube insertion into the lung.  

Case Presentation

History of Present Illness

A 56 year old male was transferred from another hospital where he had been admitted 9 days earlier for severe community acquired pneumonia secondary to penicillin sensitive Streptococcus pneumoniae, respiratory failure and sepsis syndrome. He had a past medical history of morbid obesity, type 2 diabetes mellitus, hepatitis C, hypertension and had received a pneumococcal vaccination 8 years earlier. His course was complicated by prolonged mechanical ventilation, hypotension resulting in oliguric acute renal failure and atrial fibrillation with a fast ventricular response requiring cardioversion. He had sufficiently improved with antibiotics, hemodialysis and supportive therapy that he was able to be transferred to our hospital. He had a prolonged but uncomplicated course in our intensive care unit (ICU). He was initially unable to be weaned from mechanical ventilation and underwent tracheostomy but was eventually able to tolerate tracheostomy collar and intermittent use of a tracheostomy tube with a speaking valve. He was noted to be intermittently confused and agitated. After 17 days in our ICU, transfer was planned to a general medical floor.  However, prior to leaving our ICU he pulled his feeding tube and another small bore feeding tube was inserted. An abdominal film was performed and he was transferred to the medical floor. After transfer he complained through the night of chest pain and shortness of breath and required increasing inspired oxygen concentrations in order to maintain adequate oxygen saturation. .

Physical Examination

Physical examination was not markedly changed from the previous day. He had a tachycardia of 110, blood pressure of 139/97, respirations of 24, temperature of 36.3 degrees C and weight of 140.6 kilograms. He was not oriented to time or place and seemed to be in moderate discomfort. Pertinent findings including a small bore feeding tube in his left nostril, a tracheotomy in place and rhonchi over both lungs. Abdomen was protuberant but soft and there was no presacral or pretibial edema.

Laboratory Findings

Pertinent laboratory findings included arterial blood gases showing a pH of 7.44, pCO2 of 32 mm Hg, and pO2 of 65.3 on a FiO2 of 0.7. Blood glucose was elevated at 275 and his white blood cell count had increased from 6000/microL on the day of transfer to the floor to 11,400/microL with a left shift.

Radiography

Initial abdominal films are show in figure 1.

Figure 1. Panel A and B are abdominal x-rays taken for feeding tube placement. Panel A shows the feeding tube below the diaphragm indicated by the arrow. Panel B, labeled at the same time and with the same acquisition number does not show the tube below the diaphragm but shows a tube apparently in the right chest. Panel C is an inverted image of Panel B.

A chest X-ray was taken on the patient’s return to the intensive care unit (Figure 2).

Figure 2. A. Chest X-ray shows feeding tube in trachea and right mainstem bronchus, looping in lower right chest and extending to upper right chest (arrows). B. Inverted image of A.

Hospital Course

Because of his high oxygen requirements and dyspnea, the patient was placed on mechanical ventilation. Bronchoscopy confirmed that the tube was in the lung. Due to concern for a pneumothorax should the tube be removed, a chest tube was placed first and directed to drain the pleural effusion. The feeding tube was removed and a follow up chest x-ray confirmed a pneumothorax that was treated with another chest tube. It was estimated that about 600 ml of feeding formula had been infused into the chest. Approximately 700 ml of milky fluid consistent with feeding was collected by the thoracostomy tube. Thoracic surgery consultation was obtained and recommended video-assisted thoracic surgery which was performed 5 days latter. A small amount of what appeared to be feeding formula was removed. He made a slow and uneventful recovery and was discharged to an extended care facility after a total duration of 43 days in our hospital.

Discussion

Malposition of feeding tubes is relatively common (1,2). Given that the tubes are small, relatively flexible and blindly inserted this is not surprising. In a series of more than 2000 insertions, Sorokin and Gottlieb (1) reported a 2.4% rate of lung insertion while de Aguilar-Nascimento and Kudsk (2) found a 3.2% incidence of lung malposition. Most malpositions occurred in the intensive care unit with 95% of the patients having an abnormal mental status and more than half with an endotracheal tube. Therefore, our patient was typical of the patient prone for feeding tube malposition.

To prevent feeding tube malposition, many hospitals insert the tubes under fluoroscopic guidance (3). Perhaps more commonly, other hospitals require radiographic confirmation before beginning feeding (1,2) . The later is the policy at our hospital, but as this case illustrates, mishaps can occur even with this safeguard.

In our case, several errors were made leading to the adverse event. Although recorded at the same time, the initial abdominal films were actually taken at different times. The patient had pulled his first feeding tube and a second tube had been inserted by the ICU nurse into the lung. The medicine house officer who read the films was not informed that two films were taken and saw the tube below the diaphragm on the first film. The house officer missed the tube in the chest on the second film. However, on this and three subsequent films, all read by separate radiologists, the tube malposition was also not identified. It can be difficult with multiple densities, from chest cardiac leads, suction tubing, intravenous tubing, etc. to identify potentially misplaced feeding tubes.

Generally, feeding tube malposition is reasonably well tolerated although aspiration and pneumothorax may result (1-3). Removal of the tube usually results in little apparent clinical harm. Our case is unusual in that an enteral feeding formula was introduced into the pleural space. Although there are previous reports of pneumothorax complication feeding tube insertion, these are relatively uncommon and we were uncertain how to proceed (4).  Eventually we decided on video assisted thoracic surgery with removal of any residual fluid. In this case the patient made an uneventful but prolonged recovery.  

When a feeding tube is in the lung, it may or may not have punctured the pleura. If it has, as was clear in this case by the course it took, (multiple loops), the chance of a pneumothorax on removal may be high. It is a matter of opinion as to whether or not in this situation; a prophylactic chest tube should be placed prior to removal of the feeding tube. In this case, this was performed as he was on mechanical ventilation. In situations where the feeding tube is clearly in a mainstem bronchus, removal is probably safe without due concern for a pneumothorax.

The errors in the formal radiology readings may be reduced by inverting the images within the radiology viewing program, and making sure that the full course of the feeding tube from oropharynx to tip is noted. In some obese patients, such as this one, an abdominal x-ray and chest x-ray may be required to do this.

References

1. Sorokin R, Gottlieb JE. Enhancing patient safety during feeding-tube insertion: a review of more than 2,000 insertions. JPEN J Parenter Enteral Nutr 2006;30:440-5.

2. de Aguilar-Nascimento JE, Kudsk KA. Clinical costs of feeding tube placement. JPEN J Parenter Enteral Nutr 2007;31:269-73.

3. Huerta G, Puri VK. Nasoenteric feeding tubes in critically ill patients (fluoroscopy versus blind). Nutrition 2000;16:264-7.

4. Wendell GD, Lenchner GS, Promisloff RA. Pneumothorax complicating small-bore feeding tube placement . Arch Intern Med 1991;151:599-602.