September 2012 Critical Care Journal Club
Tuesday, October 2, 2012 at 12:19PM
Rick Robbins, M.D. in acute kidney injury, acute tubular necrosis, autopsy, benzodiazepine, missed diagnosis, myocardial dysfunction, sedation, septic shock, viral pneumonia

We had a great group of attending discussants at this J club – thanks to all who participated including Drs. Jay Blum, Al Thomas, Clement Singarajah, Rick Robbins, Tom Bajo, Huw Owen Reece, and Roxanne Garcia Orr.   

Winters B, Custer J, Galvagno SM Jr, et al.  Diagnostic errors in the intensive care unit: a systematic review of autopsy studies.  BMJ Qual Saf 2012 Jul 24. [Epub ahead of print] Abstract

The authors reviewed 45 years of autopsy studies of ICU patients to determine the most common missed diagnoses.  Thirty-one studies including 5863 autopsies were included. Eight percent revealed a missed diagnosis with an adverse impact survival that would likely have changed therapy.  More than 80% of these were vascular events (such as pulmonary embolism or acute myocardial infarction) and infections.  Strangely, the authors detail all diagnostic categories except infection – this seems to have been an oversight error on their part. 

The authors extrapolated their data to conclude that 34,000 patients per year might die in the ICU from missed diagnoses.  But this calculation is based on the false assumption that there is nothing special about patients who ultimately undergo autopsy.  Many physicians specifically request autopsy because they want to find out if they missed anything.  Extrapolation of data with this selection bias would likely greatly overestimate deaths due to missed diagnoses.

There was some controversy between us in regards to the intent of this research.  Some felt that it was a condemnation of clinicians by pathologists, looking through the retrospect-o-scope to find our shortcomings.  Others pointed out that we often make mistakes as clinicians - even the best of us miss things.  It’s best to accept this and try to learn from it.  Experienced clinicians in the discussion all agreed that throughout their careers, few autopsies revealed important findings – and almost never determined a cause of death that wasn’t clinically suspected.  But most could remember a case or two that surprised them.  This paper should not be used as an indictment of bedside care by policy-makers, but as a reminder to physicians to maintain an open-minded and inquisitive diagnostic approach.


Choi SH, Hong SB, Ko GB, et al.  Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med 2012;186:325-32. Abstract

This article was thoroughly flawed, but it prompted a very interesting discussion.  This cohort study analyzed microbiological studies performed on critically ill patients with pneumonia (CAP and HCAP combined) and concluded that 36% of patients had a bacterial pneumonia and 36% had a viral pneumonia – most commonly rhinovirus.  Only 58% of the patients in the cohort underwent bronchoalveolar lavage.   The authors assumed any potentially pathogenic organism isolated was the cause of pneumonia.  However, many of the microbiological tests performed did not establish causality.  No one would argue that influenza virus in the bronchoalveolar lavage of a patient with pneumonia is clearly pathogenic, the same cannot be said for finding rhinovirus in a nasal swab.  Previous studies that used autopsies and microbiological examination of lung tissue obtained at autopsy have shown that bacteria isolated from BAL are often not causative of pneumonia.     


Dr. Thomas pointed out that widespread use of the term “Community-acquired pneumonia” might have the deleterious effect of mindlessly lumping together clinically distinct pneumonia syndromes instead of using bedside clinical skills to make a sound diagnosis.  We call everything “CAP”, give the recommended empirical antibiotics, and then depend on the lab to sort it out for us.  This point was emphasized when a resident asked when anti-influenza treatment should be given empirically for CAP – the answer is: when the clinical syndrome is consistent with influenza -for instance, in a patient with fever, dry cough, myalgias, arthalgias and headache.   This presentation is distinct from classic pneumococcal pneumonia, Pneumocystis jiroveci pneumonia, and coccidioidomycosis – although all 3 could be diagnosed as CAP upon presentation. 


We all agreed that the study was interesting in the aspect of pointing out how little we know about pneumonia.  It’s certainly possible that many patients admitted for CAP and urgently treated with antibiotics do not have bacterial pneumonia.  But a consistent microbiological approach and rigorous interpretation of the results will be required to sort this out in a valid analysis.


Pulido JN, Afessa B, Masaki M, et al.  Clinical spectrum, frequency and significance of myocardial dysfunction in severe sepsis and septic shock.  Mayo Clinic Proc 2012;87:620-8.  Abstract

We reviewed this article briefly.  This is a cohort study that reviewed echocardiographic findings of 100 patients with septic shock.  The thing that caught my attention when I screened this article was that the authors found that the 64% of patients with sepsis had myocardial dysfunction, and that many presented with isolated right ventricular dysfunction (31%) or with left ventricular diastolic dysfunction (37%). I had always thought that acute cardiomyopathy of sepsis was primarily a disease of left ventricular systolic dysfunction, but in this study, this was the least frequent finding - only 27%. 


Unfortunately, the patients in the cohort did not all have echocardiograms prior to their presentation, so it was unclear how many of them might simply have chronic left ventricular diastolic dysfunction unrelated to sepsis.  This confusion wasn’t helped but the lack of completeness in report of the follow-up echocardiograms.  The authors state that left ventricular systolic function often repaired, but don’t mention the outcomes in patients with diastolic dysfunction – if diastolic dysfunction had been shown to acutely resolve, that would have supported the idea that it might have been caused by sepsis.


It would have also been interesting to report the pulmonary status of the patients with acute right heart dysfunction – you couldn’t help wondering whether these patients had severe ARDS causing right ventricular dysfunction.  Altogether, the study was thought-provoking, but was not properly designed to make convincing conclusions.  


Ely EW, Skrobik Y.  Point/counterpoint editorials:  Should benzodiazepines be avoided in mechanically-ventilated patients?  (both sides of the debate).  Chest 2012;142:281-7. No abstract available.

It was great to have Dr. Huw Owen Reece with us to discuss this article – Dr. Owen Reece has ongoing interest in this area of study, and has worked on reducing delirium in our ICU.  There was no clear winner in this debate.  Both authors agree that adequate sedation is beneficial, and that excessive sedation is harmful. It’s possible that any of the drugs we currently use could cause or worsen delirium if given inappropriately.  Our faculty generally agreed with Dr. Ely that the pharmacokinetic and pharmacodynamics properties of some of the newer sedative hyponotics (such as propofol and dexmethetomidine) are favorable, and seem less likely to cause excessive sedation.  Future studies will be needed to see whether this clearly translates into a lower incidence of ICU delirium and reduced ICU length of stay.


Bellomo R, Kellum JA, Ronco C. Acute kidney injury.  Lancet  2012;380:756-66.  Abstract

This article is highly recommended reading for residents and fellows, but it reads like a chapter in a Critical Care textbook, and we will not attempt to summarize it here – it just has too much meat in it.  We have previously reviewed articles by Bellomo and we appreciate his skeptical approach to clinical dogma.


Bellomo points out that our traditional clinical diagnosis of “acute tubular necrosis” (ATN) - resulting from a reduction in renal blood flow due to the hemodynamic changes of sepsis - is likely an incorrect diagnosis in most patients.   The diagnosis of ATN is based on pathological findings that are almost never confirmed in septic patients with renal failure.  If ATN were due to a temporary reduction in renal perfusion, it should resolve as rapidly as any other case of prerenal failure.  Studies have increasingly shown that the pathogenesis of acute kidney injury is far more complex than we used to think, and terms like ATN should likely be discarded.


Bellomo also argues for earlier use of renal replacement therapy to manage fluid overload in septic patients with oliguria or anuria, pointing out that even moderate fluid overload can contribute to morbidity and mortality.  He postulates that a congested state may be directly related to the causation of acute kidney injury.   We know from reviewing some of Bellomo’s other recent papers in Journal Club that he challenges the dogma of aggressive fluid resuscitation in septic shock – this article furthers that argument.

We digressed a little - discussing our typical approach of aggressive fluid resuscitation of septic shock.  Our clinical impression is that goal-directed resuscitation tends to result in fluid overload in many patients.  We often find ourselves implementing massive diuresis of patients once their blood pressure recovers (often after vasopressors are discontinued).  Many articles we have reviewed over the past year add to our growing impression that this approach is of unclear benefit, and possible harm. 

Robert Raschke MD MS

Associate Editor, Critical Care Medicine

Reference as: Raschke RA. September 2012 critical care journal club. Southwest J Pulm Crit Care 2012;5:193-6. PDf

Article originally appeared on SOUTHWEST JOURNAL of PULMONARY & CRITICAL CARE (
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