Clinical review: What is the role for autopsy in the ICU?
- Greet Yvonne Agnes De Vlieger1,
- Elien Marie Jeanne Lia Mahieu1 and
- Wouter Meersseman1Email author
Published: 28 May 2010
Abstract
The availability of advanced diagnostic tools has grown in the past decades. Hence, a growing false belief exists that everything is known about the patient before death. Moreover, intensivists may wrongly believe that autopsy findings do not contribute to the understanding of pathophysiological events. The immediate result is that few ICUs nowadays assemble enough autopsy cases with new and interesting clinicopathological features. However, we believe that, at least in tertiary ICUs, autopsies remain a valuable examination, as a tool for quality control, as a way of establishing gold standards for diagnostic examinations and as an aid in developing guidelines for treatment and diagnosis of diseases frequently encountered in the ICU. Finally, due to the ever-expanding armamentarium of immunosuppressive agents, a growing list of opportunistic infections is discovered during autopsy. The present article gives an overview of autopsy studies conducted in the ICU and discusses the pros and cons of performing these.
Keywords
Introduction
During the past decades, autopsy rates have been declining worldwide. The non-forensic, clinical autopsy rate at large hospitals in the United States dropped from 41% in 1964 to 22% in 1975 [1]. In spite of this decline, the post-mortem examination remains clinically relevant for time-honoured reasons: the information obtained helps to understand diseases; it provides essential feedback for the clinician and leads to quality assessment and education; and data from it are important for epidemiologists [2].
Classification of discrepancies between pre- and post-mortem diagnoses (according to Goldman and colleagues [3])
Major: important underlying conditions and all primary causes of death |
Class I: may have altered therapy or survival |
Class II: would not have altered therapy or survival |
Minor: unknown preexisting condition not directly related to the cause of death |
Class III: would not have altered therapy or survival |
Class IV: may have altered therapy or survival |
Nondiscrepancy |
Class V: complete agreement between clinical and post-mortem diagnosis |
Nonclassifiable |
Class VI: patients died immediately after admission with no diagnostic procedure or refused any diagnostic procedure. Autopsy was unsatisfactory, with no clear findings and no diagnosis could be established |
Reasons for the decline in autopsy rate
Costs
The costs for post-mortem analysis cannot be charged to family members since autopsy findings are irrelevant for the management of their relative. Hospital administrators are not easily convinced to spend money on procedures lacking an immediate impact on patient management and just for teaching purposes [4, 5]. In Belgium, the cost of an autopsy is estimated at 473 euros and is carried by the social security system. In London, the cost of one autopsy is 850 euros when the costs for building a mortuary are taken into account.
Judicial factors
In the US, some authors claim that the most important factor explaining the decrease in the autopsy rate is that a minimum number of autopsies is no longer needed for accreditation by the Joint Commission on Accreditation of Hospitals. Some clinicians also seem to be more reluctant to seek consent out of fear of litigation since autopsy can reveal missed diagnoses [4].
Communication with patients' relatives
Because of the growing impact of the opinions of patients and their relatives, physicians are often forced to discuss necropsy with them. As a result, the autopsy rate in France has markedly declined after 1994 (from 15% to 3%), the year that bioethics law impelled physicians to inform relatives about the performance of a post-mortem examination [6]. However, it is not clear what the attitude of relatives is. In a Swedish study, 84% reported accepting an autopsy for themselves and 80% for a next of kin [7]. In a study performed in a surgical ICU, relatives refused 2 of 27 autopsy requests. Nevertheless, the autopsy rate was only 25% [8]. This demonstrates that the low autopsy rate reflects a low autopsy request rate on the part of clinicians more than refusal by relatives.
Autopsies are less likely to be performed when not recommended strongly by the treating physician. In one study based on physician and surrogate responses, the expected autopsy rate was 42%, while the actual autopsy rate was 23% [9]. Training physicians how to recommend autopsies may increase autopsy rates.
Reluctance of pathologists
Another reason for the decline in autopsy rates is the growing reluctance of pathologists to perform autopsies. Several studies analyzing the delay of pathology reports show a long delay (up to 90 days) [6]. This indicates a lack of interest in autopsy findings, both from pathologists and clinicians. The reasons for this are many. First, pathologists are experiencing an increasing workload. Secondly, since infectious diseases are rising, pathologists fear the risk of infection [10]. Finally, autopsies now contribute little to the scientific output of the pathology department, with only 6% of the published articles being based on autopsy findings [6].
Modern technology
It can be argued that the sensitivity of modern diagnostic methods would reduce diagnostic errors to an extent that autopsies would be unnecessary. However, this reasoning was not confirmed by a study by Goldman and colleagues [3], who studied the time course of diagnostic errors during the 1960s, 1970s and 1980s and found no differences among the three periods: in all three eras about 10% of the autopsies revealed a class I missed diagnosis (Table 1).
Analyses of diagnostic error rates, adjusted for case mix, country and autopsy rate, yielded stable figures for major missed diagnoses throughout the past three decades [11]. A possible explanation for the stability of the error rates is increased case selection by clinicians. Since fewer autopsies are performed, clinically challenging cases may be more likely to be selected for autopsy. However, several prospective studies performed in the 1960s, 1970s and 1980s have shown that clinicians have a poor ability to identify cases that will yield 'diagnostic surprises' [12–14]. A study performed by Cameron and colleagues [15] showed that 15% of main diagnoses were not confirmed by autopsy in cases where physicians said they would have requested an autopsy. The rate was similar at 14% in cases where physicians said they would not have requested an autopsy.
The lack of a decrease in the proportion of missed diagnoses during the past decades does not indicate a lack of progress in medical science since the types of missed diagnoses varied in the different eras [16]. Rather, it suggests that our clinical and technical investigations are less sensitive for new disease entities.
Why do autopsies still play an important role in the ICU?
Autopsies can be used to check the accuracy of existing diagnostic tools
The imperfect correlation between pre- and post-mortem findings illustrates that existing diagnostic tools do not always provide 100% certainty about the existence of a specific disease entity [5]. Autopsies yield important information on the rates of discrepancies between clinical diagnosis and histology. A few studies investigating this have been performed in the ICU. Combes and colleagues [17] performed the largest, prospective study, corroborating the results of other studies performed in the ICU; namely, that the overall type I error rate averages 10%. A study performed by Roosen and colleagues [18] with an autopsy rate of 93% revealed that fungal infection, cardiac tamponade, abdominal haemorrhage, and myocardial infarction are the diagnoses most frequently missed in a medical ICU.
Autopsies allow the accuracy of existing diagnostic tools to be checked. One example may clarify this matter. The role of Candida spp. in the airways of critically ill patients was examined in a prospective, controlled autopsy study performed in our medical ICU [19]. A survey by Azoulay and colleagues [20] demonstrated that 24% of French intensivists treat Candida spp. when found in the airways of mechanically ventilated patients. However, we did not find Candida pneumonia at autopsy despite the frequent pre-mortem occurrence of Candida spp. in the respiratory tract of critically ill patients. This finding argues against the use of expensive antifungal treatment in mechanically ventilated patients solely on the basis of isolation of Candida spp. from tracheal aspirates and broncho-alveolar lavage fluid. Recent published guidelines of the Infectious Diseases Society of America on the treatment of invasive candidiasis in intensive care reinforce this [21].
Autopsies are useful for understanding pathophysiology
There are several examples of the value of autopsy in elucidating pathophysiological mechanisms of disease in the ICU. Extensive observational data have shown a consistent, almost linear relationship between blood glucose levels in hospitalized patients and adverse clinical outcomes, even in patients without established diabetes [22]. It has never been entirely clear, however, whether glycaemia serves as a mediator of adverse outcomes or merely as a marker of illness. Several early studies suggested a clinical benefit from strict glucose control during critical illness [23]. Recently, a large multicentre study called into question the beneficial findings of tight glycaemic control [24]. Autopsy might be of help in elucidating the potential toxic effects of hyperglycaemia on various organs. Vanhorebeek and colleagues [25] used post-mortem liver samples from the original Leuven study [23] and showed that mitochondrial function in hepatocytes was retained in patients with tight glycaemic control compared to the patients in the conventional treatment group. There was, however, no differential effect on mitochondrial function of myocytes. This autopsy report could encourage clinicians to perform histological and molecular studies in order to clarify the mechanisms of glucose toxicity and to what extent tight glycaemic control should be achieved.
Autopsies are useful in understanding epidemiology and describing new disease entities
An illustrative example of the value of autopsy in explaining certain epidemiological and pathophysiological features of new disease entities is the description of pathology specimens from patients dying of confirmed 2009 influenza A H1N1 infection. Autopsy studies have shown that the main pathological changes associated with 2009 influenza A H1N1 infection are located in the lungs, identifying three distinct histological patterns. Ongoing aberrant immune responses in lung specimens could be identified in patients dying of 2009 influenza A H1N1 infection [26]. Also, concurrent bacterial infection was found in autopsy specimens of 22 of 77 (29%) patients, including 10 Streptococcus pneumoniae infections. These autopsy findings underscore both the importance of pneumococcal vaccination for persons at increased risk for pneumococcal pneumonia and the need for early recognition of bacterial pneumonia in persons with influenza [27].
Autopsies continue to serve as an invaluable educational tool
Due to the ever-expanding armamentarium of immunosuppressant and immunomodulating drugs, there is a growing list of potentially lethal and difficult to diagnose opportunistic infections. Patients with these uncommon infections often present in an advanced state of their disease, the conditions of which are often discovered only post-mortem. The autopsy has an educational role in describing the histological features of these advanced disease states and their complications.
Moreover, the autopsy can be an integral part of the safety analysis of new drugs. Due to detailed brain autopsies, natalizumab, a novel antibody directed to the adhesion molecule a4 integrin, was identified as a risk factor for development of progressive multifocal leukoencephalopathy in patients with Crohn's disease or multiple sclerosis treated with this drug [28].
Shojania and colleagues [11] studied the effect of increasing autopsy rate on the incidence of major diagnostic errors. They found that major errors decreased at a rate of 12.4% for every 10% increase in autopsy rate, and class I errors decreased at a rate of 17.4% for every 10% increase in autopsy rate. This points to the important educational value of post-mortem examination and we believe that the decreasing autopsy rate is contrary to progress in medical diagnostics. We think that medical students should follow at least some autopsies to underline the importance of the necropsy.
However, it needs to be stressed that the procedure needs to be done according to certain criteria and ideally attended by the intensivist that took care of the patient. The autopsy has always been a valid monitor of clinical diagnostic performance if it meets four necessary conditions, according to Saracci [29]: a high necropsy rate (28 to 50%); specified and stable conditions under which necropsies are performed; calculation of sensitivity and specificity rather than overall accuracy; and an estimate of the error in post-mortem diagnoses. Durning and Cation [30] showed that autopsy cases were frequently evaluated as a valuable educational experience by attending physicians.
New, innovative techniques might improve the diagnostic yield of autopsies
A very intriguing field of interest is molecular investigations at autopsy. Even with normal structural findings, molecular analysis of frozen sections can ultimately resolve 'unsolved' cases of sudden death. Ackerman and colleagues [31] report the results of post-mortem molecular testing and the identification of a novel mutation in a young woman who died in the ICU after a near-drowning secondary to what turned out to be a form of congenital long-QT syndrome. Because of this molecular finding at autopsy, an asymptomatic sibling carrying the same mutation was able to receive prophylactic treatment. For sudden cardiac deaths the protocols for autopsy recommend freezing a piece of spleen for molecular analysis.
Autopsies might protect physicians from subsequent malpractice litigation
Strategies to improve autopsy rate
Efforts by the pathological department |
Coordinate autopsies with the schedules of requesting physicians |
Faster processing of the autopsy reports |
Provision of resources for performing autopsies |
Creation of regional autopsy centres |
Provides opportunities to improve autopsy quality |
Develops strategies for using autopsy results to improve clinical performance |
Improvement of training for pathology residents |
Better education of medical students |
Quality control of performed autopsies (different pathologists interpreting the same autopsy specimens) in order to improve diagnostic value |
Provide opportunities to improve autopsy quality by specialization |
Efforts by physicians |
Allow physicians complete discretion in requesting autopsies (arbitrary sampling as a result will augment the numbers of important misdiagnoses) |
Analyse data from regional centres to identify patterns of missed diagnoses and to generate prediction rules that would enhance the process of case selection |
Augment autopsy numbers with widespread use of structured death reviews and structured reports of epidemiological statistics on various diseases encountered in the ICU |
Communicate the conclusion of the autopsy report to the relatives |
Efforts by both departments |
Clinicopathological conferences on a monthly basis attended by the treating intensivist, the radiologist and the pathologist |
Interesting cases should be published with the aim of education and improving knowledge of epidemiology |
Clinicopathological conferences should take place on a regular (for example, monthly) basis. This means a joint effort of both intensivists and pathologists. The clinicians need to inform the pathologist about the patient's pre-mortem status, the expected findings and the unsolved questions. The pathologist needs to understand the importance of the results of autopsy in medical development. Autopsies can lead to an increased awareness for rare and emerging diseases and eventually result in better daily clinical practice.
Information for relatives
The information gained by autopsy findings can help relatives to understand the cause of death of their loved ones. Sadly enough, autopsy results are often not communicated to them. In a study performed by Burton and colleagues [9], 78% of relatives reported that autopsy results were not discussed.
Overview of recent studies performed in the ICU
Overview of recently performed autopsy studies in the ICU setting
Author | Period | Studied population | Type of hospital* | Study design | Autopsy rate (%) | Number of autopsies | Major error†(%) | Class I error (%) |
---|---|---|---|---|---|---|---|---|
Roosen et al. [18] | 1996 | Medical | Referral, Belgium | Retrospective | 93 | 100 | 36 | 16 |
Combes et al. [17] | 11/1995 to 10/1998 | Mixed | Referral, France | Prospective | 53 | 167 | 31.7 | 10.2 |
Dimopoulos et al. [41] | 1999 | Mixed | Referral, Belgium | Retrospective | 45 | 222 | 8.5 | 5.4 |
Maris et al. [42] | 1/2004 to 12/2005 | Mixed | Referral, Belgium | Retrospective | 37 | 289 | 19 | 6 |
Nadrous et al. [33] | 1/1998 to 12/2000 | Mixed | Referral, USA | Retrospective | 33 | 455 | 21 | 4 |
Tai et al. [16] | 1/1994 to 12/1995 | Medical | Referral, USA | Retrospective | 22 | 91 | 19.78 | 8.79 |
Mort et al. [43] | 7/1986 to 7/1992 | Surgical | Referral, USA | Retrospective | 29 | 149 | 23 | 9.5 |
Podbregar et al. [44] | 1/1998 to 12/1999 | Medical | Referral, Slovenia | Retrospective | 46 | 126 | 52.4 | 12 |
Twigg et al. [45] | 6/1996 to 5/1999 | Mixed | District, UK | Retrospective | 40 | 97 | 23.71 | 4.12 |
Silfvast et al. [37] | 1/1996 to 12/2000 | Mixed | Referral, Finland | Retrospective | 89 | 346 | 5 | 2.3 |
Fernandez-Segoviano et al. [46] | 5/1983 to 12/1985 | Mixed | Referral, Spain | Prospective | 51 | 100 | 22 | 7 |
Pastores et al. [34] | 1/1999 to 9/2005 | Oncologic | Referral, USA | Retrospective | 13 | 86 | 26 | 17 |
Ong et al. [47] | 1/1997 to 12/1998 | Trauma and burns | Referral, USA | Retrospective | 97 | 153 | 18.95 | 3 |
Al-Saidi et al. [48] | 11/1994 to 6/1999 | Bone marrow transplant | Referral, Canada | Retrospective | 47 | 28 | 10.7 | 3.6 |
Gerain et al. [36] | 11/1985 to 10/1986 | Oncologic | Referral, Belgium | Retrospective | 69 | 34 | 59 | Unknown |
In all studies, infections were most frequently missed. Medical development has led to new treatments, such as new cytotoxic agents, and organ and stem cell transplantation, which have led to an increased number of viral and fungal infections with unusual clinical presentations [3, 16, 33–35]. In a study performed at our medical ICU, fungal infections occurred in 16% of deceased patients. In 30% of all cases, the diagnosis was not considered premortem [18]. Veress and Alufuzoff [2] found a significant increase in infectious diseases in autopsy patients, from 27% in the 1970s to 32% in the 1980s, and an increase in undiagnosed infections of 30%. Gerain and colleagues [36] studied the causes of death in oncology patients who died in an ICU. In 23.5% of all deaths the primary cause was infectious disease, with fungal disease in 87.5%. Cancer itself was the direct cause of death in only 10%. Silfvast and colleagues [37] showed that 62% of class I diagnostic errors were found in patients with pneumonia or other already known infections. This finding emphasises the difficulty of diagnosing unexpected or new pathogens in patients with existing infections.
Pulmonary embolism remains one of the major missed diagnoses throughout the past three decades (8.9%) [38]. In autopsied patients who died from pulmonary embolism, the diagnosis was unsuspected in 14 of 20 (70%). Most of these patients had advanced associated disease [38]. As Gold man postulates, the persistent high rate of missed pulmonary embolism is more a reflection of the high mortality of the pathology when this diagnosis is missed [35]. The availability of new diagnostic techniques can also give misleading information. The frequency of a false-positive diagnosis of pulmonary embolism (when the clinician ascribed the death to pulmonary embolism not confirmed at autopsy) rose from 33% in 1959 to 44% in 1999/2000 [39].
Intra-abdominal and retroperitoneal bleeding and more general acute abdominal complications are underdiagnosed in the ICU. Altered mental status, narcotic medication, immunosuppression and mechanical ventilation make the bedside diagnosis difficult. Angiography or computed tomography are often not an option in these unstable patients and bedside ultrasound is frequently inconclusive. Papadakis and colleagues [40] studied the diagnostic discrepancy in veteran soldiers receiving mechanical ventilation. Thirty-nine percent of the class I errors were potentially treatable abdominal disorders. In two-thirds, the errors arose because clinicians failed to consider the diagnosis, and not because the clinicians had misleading or inconclusive information from diagnostic procedures.
Conclusion
Over the past decades, autopsy rates have been declining and studies on autopsy findings are scarce. We are convinced that the performance of necropsy is necessary for many reasons. First, studies have shown that despite technical improvements, the frequency of missed disorders has not diminished compared to the 1960s and 1970s. The reason is the advent of several new pathologies with more opportunistic infections in an era of HIV and influenza A H1N1 pandemics, new immunosuppressive treatments for transplant recipients and auto-immune diseases. Second, we argue that the post-mortem examination can be useful for relatives, especially if the cause of death is not clear. We regret the fact that autopsy results are often not reported to the relatives. Moreover, clinicians and pathologists do not communicate well with each other. Input from the clinician can motivate the pathologist to find new, rare or unsuspected diseases.
The costs of post-mortem examination are negligible compared to the overall costs of ICU stay. Since the results may improve our daily practice, we should not consider the costs as a reason to forestall autopsies.
We ask that the importance of post-mortem examinations be reconsidered, since autopsy remains the ultimate tool of accountability for clinical evaluation and management of new and old diseases.
Declarations
Acknowledgements
We thank Professor Dr S Vanderschueren for thoroughly reading the article and giving additional suggestions.
Authors’ Affiliations
References
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