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Post-mortem examination in the ICU 

Post-mortem examination in the ICU
Chapter:
Post-mortem examination in the ICU
Author(s):

Eva Tejerina

and Andrés Esteban

DOI:
10.1093/med/9780199600830.003.0391
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date: 27 November 2020

Key points

  • Post-mortem examination should be seen as a reliable method to improve quality of medical care by monitoring diagnostic accuracy and treatment of the critically ill patients.

  • Despite technological improvements in medicine, percentage of missed diagnosed had not changed over time, and some diseases remain particularly challenging to identify.

  • Autopsy remains the essential verification of the clinical diagnosis in critically ill patients, and provides a ‘gold standard’ to assess the accuracy of diagnostic tests.

  • Autopsy findings also offer relevant information for the advance of medical knowledge and the description of new disease entities.

  • Post-mortem examination rates have fallen worldwide during the past decades. So, it should encourage clinicians to remember the value of the autopsy.

Introduction

Autopsy has long been regarded as a valuable and reliable tool for quality control in medical practice. It may facilitate new discoveries about pathogenesis and therapy, give feed-back for clinical research protocols, provide epidemiological information, monitor public health, and serve to console and reassure grieving families. The autopsy also provides an excellent basis for teaching students the fundamentals of anatomy and the manifestations of disease. It provides important information on the effects of newer drugs on normal and on diseased tissues and is a source of relevant data for detecting and evaluating emerging diseases. The prestigious ‘Case Records of the Massachusetts General Hospital’ in the New England Journal of Medicine is a good example of the value of the autopsy as an educational tool. For decades it continued to publish, on a weekly basis, enigmas solved by autopsy findings.

Although autopsy remains a fundamental element of quality assurance in critical care medicine, post-mortem examination rates have fallen worldwide during the past decades [1,2,3]. A variety of factors has been attributed to this decrease: fear of potential legal repercussions, the time-consuming task of autopsies for the pathology departments, reluctance of families to give permission for the procedure, or exclusion of minimum mandatory autopsy rates as one of the accreditation criteria for hospitals. However, despite concerns that relatives will be unwilling to give permission for a post-mortem examination, a study in an ICU in a Spanish hospital has reported that if they are approached sensitively up to 43% of relatives may agree [4]‌. It has been suggested that how, and by whom, the family is approached are important factors in whether consent is obtained. Other reasons have also been attributed to the decline in autopsy rates, including the availability of new and more effective technologies for diagnostic procedures, particularly in terms of imaging techniques. In intensive care medicine, clinicians may be reluctant to perform post-mortem examinations in patients who have been intensively investigated and treated. Also, an autopsy may be performed more frequently if the diagnosis is not considered to be completely clear.

An autopsy rate of 25% is the minimal considered adequate for an accurate quality assurance of clinical diagnostic performance, whereas the rate considered optimum is of 35% [5]‌. A high autopsy rate requires that intensive care staff be persuaded of the importance of autopsies as part of the teaching and quality assurance programmes. It is also necessary to count on the Pathology Department collaboration. It is of paramount importance that the hospital administration assigns the autopsy cost to the teaching and quality assurance budget. Furthermore, in order for an autopsy to be an educational tool, the information that is obtained must be relayed to the primary caregivers in a timely fashion. Formal teaching sessions with reviews of autopsy and an individual discussion of each particular case must be regularly scheduled [6,7].

Diagnostic errors and quality assurance

A correct diagnosis is a complex interaction of cognitive skills and technical procedures in conditions of uncertainty. Confirmation of clinical diagnosis by necropsy strengthens clinical cognition because it can eliminate uncertainty about diagnosis in most cases. In addition, unexpected findings at autopsy contribute to the increasing pool of medical knowledge, which may lead to better patient care.

Traditionally, unexpected autopsy findings have been categorized as Class I or major discrepancies and Class II or minor discrepancies, using the Goldman criteria [1]‌. Class I error was an autopsy findings for which an accurate premortem diagnosis would have altered therapy and survival. And, Class II diagnostic error was defined as an unsuspected diagnosis related to death, but it would not, however, have changed immediate management for any of the following reasons: the patient was already receiving appropriate therapy even though the diagnosis was not known; effective therapy was not available; or the patient refused further investigations or treatment. Several studies have shown that major discrepancies are frequent, and in 5–40% of all hospitalized patients, and in 7–32% of adult intensive care patients a treatable condition that might have altered outcome, had it been recognized, is identified at post-mortem examination [2,3,8,9,10,11,12]. These differences in discrepancy rates among studies may be explained by different populations and also by differences in the indications for autopsy. Studies from hospitals in which autopsies are predominantly performed in complicated cases may be expected to show higher discrepancy rates. On the other hand, it is likely that unexpected autopsy findings in cases with apparently well-established diagnoses are actually the most interesting ones.

Despite technological improvements in medicine, percentage of missed diagnosed had not changed over time, although the spectrum of diseases identified at autopsy has evolved [1,13]. Some diseases remain particularly challenging to identify, despite advanced medical technology, improved diagnostic tests and techniques, and increased clinical awareness. Events such as missed infections, thromboembolic disease and myocardial infarction remain very prevalent and often unrecognized conditions [1,2,8], emphasizing the importance of maintaining a high index of suspicion for these diagnoses in the critically ill. The intensive care unit patient, exposed to a wide spectrum of invasive procedures and indwelling medical devices, is placed at a higher risk to develop nosocomial infections coupled with more virulent and resistant strains of infectious agents. Critically ill patients are also frequently colonized with pathogens, leading to difficulties of separating colonization from active infection. It provides an immense challenge to the ICU care team to accurately and quickly establish the source of infection. Indeed, infectious diagnoses compromise the majority of missed causes of death in the various autopsy studies [2,3,9,10,11], especially when reporting cases from the ICU setting.

Other possible explanation for the stability of these rates is increased selection by clinicians. A selection bias due to the hypothesis that only families with concerns about management or outcome gave consent or, alternatively, that caregivers were more persistent when they perceived a need for post-mortem examination. It might also have influenced the incidence of discrepancies. With progressively fewer autopsies performed over time, clinical selection for diagnostically challenging cases might offset true gains in diagnostic accuracy. However, more recently, some authors [13] noted that the frequency of major discrepancies significantly decreased over time.

Recently, a prospective study of all consecutive autopsies performed on patients who died in the ICU between January 1982 and December 2007 was conducted [14]. Of 2857 deaths during the study period, autopsies were performed in 866 patients (30.3%). Autopsy reports were available in 834 patients, of whom 63 (7.5%) had class I errors and 95 (11.4%) had type II errors. The most frequently missed diagnoses were pulmonary embolism, pneumonia, secondary peritonitis, invasive aspergillosis, endocarditis, and myocardial infarction (Table 391.1). The autopsy did not determine the cause of death in 22 patients (2.6%). Our rate of diagnostic discrepancy remained relatively constant over time (Fig. 391.1), and the conditions leading to discrepancies have slightly changed, with pneumonia showing a decline in diagnostic accuracy in the last years.

Table 391.1 Major discrepancies found at post-mortem examination of 834 patients who died in the ICU

Diagnosis

Number

Infectious disorders

  Pneumonia

23

  Secondary peritonitis

12

  Invasive aspergillosis

8

  Pulmonary tuberculosis

3

  Intra-abdominal abscess

3

  Mediastinitis

2

  Meningoencephalitis

2

Cardiovascular disorders

  Endocarditis

8

  Myocardial infarction

8

  Aortic dissection

3

  Cardiac tamponade

2

Pulmonary disorders

  Pulmonary embolism

24

  Aspiration pneumonitis

2

Gastrointestinal disorders

  Gastrointestinal haemorrhage

7

  Mesenteric ischaemia

6

  Acute pancreatitis

5

Oncologic disorders

  Lymphangitis carcinomatosa

3

  Lung cancer

2

Other

4

Data from Tejerina E et al., 'Clinical diagnoses and autopsy findings: discrepancies in critically ill patients', Critical Care Medicine, 2012, 40(3), pp. 842–6.

Fig. 391.1 Major error rates over time (Goldman class I and II).

Fig. 391.1 Major error rates over time (Goldman class I and II).

Data from Tejerina E et al., 'Clinical diagnoses and autopsy findings: Discrepancies in critically ill patients', Critical Care Medicine, 2012, 40(3), pp. 842–6.

The high-risk, critically-ill population is exposed to sophisticated trauma and critical care management and procedures, coupled with invasive and immunocompromising technology. Subsequently, the terminal diagnosis and cause of death may differ considerably from the initial disease state that prompted the ICU admission. It might be expected that the longer a patient stays in an ICU, the more likely the clinical and autopsy diagnoses would agree. Other authors have suggested that diagnostic accuracy may decrease with increasing hospital time due to the failure of doctors to recognize new problems in patients who are already being treated for other diseases [2,11]. However, most studies found no statistically significant correlation between the length of stay in the ICU or hospital and the discrepancy rate [3,8].

The persisting discordance between clinical and autopsy diagnoses is also an argument for continuing to perform autopsies, and reinforces the importance of the post-mortem examination in detecting otherwise unexpected diagnoses. The autopsy has historically helped define how cases that previously appeared atypical could more commonly be recognized antemortem. Repeated detection of certain missed diagnoses may result in the recognition that some patterns of presentation are more typical than previously appreciated.

Technically adequate autopsies fail to establish the cause of death in 1–5% of cases [15]. Despite an expert histopathological examination, there remain a proportion of adult deaths for which no definite cause of death can be found. This could be explained either because post-mortem examinations of adults who were apparently healthy, but died suddenly and unexpectedly sometimes reveal no morphological abnormalities or because different pathologies coexisted in a patient, which could be responsible for death. Even in these cases, autopsy may help to exclude some suspected conditions as the cause of death.

Standard for accuracy

Autopsy remains the essential verification of the clinical diagnosis in critically ill patients, and provides a ‘gold standard’ to assess the accuracy of diagnostic tests. Specifically, pulmonary pathology represents a major diagnostic challenge because of the low yield of clinical criteria and because pulmonary infiltrates may be due to different processes that affect patients receiving mechanical ventilation.

Several studies have reported a noticeable rate of missed diagnoses of pneumonia [2,9,14], illustrating the difficulty in establishing this diagnosis in ventilated patients. Clinical criteria used to define pneumonia have included radiographic appearance of a new or progressive pulmonary density, fever, leucocytosis, or purulent tracheal aspirates. Patients receiving mechanical ventilation, however, frequently develop other conditions that either obscure these findings or give rise to a similar clinical picture. Alternative diagnosis that may mimic ventilator-associated pneumonia includes alveolar oedema, either cardiogenic or non-cardiogenic, alveolar haemorrhage, atelectasis, pulmonary infarction, and the fibroproliferative phase of ARDS. Post-mortem lung histologic studies of patients receiving mechanical ventilation have found clinical parameters and antemortem chest radiographs present a high inaccuracy rate in predicting ventilator-associated pneumonia. Our group analysed in a recent study [16] 253 deaths and found that 142 (56%) patients had pneumonia diagnosed by histological criteria. In comparison with autopsy findings, antemortem clinical diagnosis of pneumonia had a sensitivity of 64.8% and a specificity of 36%, applying as diagnostic criteria the presence of chest radiograph infiltrates and two of three clinical criteria (leukocytosis, fever, purulent respiratory secretions). If the diagnostic criteria for pneumonia were more strict (chest radiograph infiltrates and all of the clinical criteria), the sensitivity was 91% and the specificity 15.5%.

Other entities such as acute respiratory distress syndrome (ARDS) show similar diagnostic difficulties in patients with mechanical ventilation. Our group had also published a study [17] comparing clinical diagnostic criteria for ARDS with autopsy findings in 382 patients, of whom 127 (33%) met the clinical criteria, and 112 (29%) had diffuse alveolar damage. In all patients, the sensitivity of the clinical definition was 75% and the specificity was 84%. In this series, the accuracy of the clinical definition for ARDS was only moderate.

Impact of the autopsy on clinical performance and future research

Information gained from the routine use of post-mortem examinations in ICU may allow the development of strategies for the early detection of diagnoses. Possibly, some patients could have been managed more appropriately, by analysing preventability of deaths, iatrogenic lesions caused by therapeutic measures, or assigning blame to human or system errors.

However, no intervention study has directly addressed the impact of autopsy findings on clinical practice or performance improvement. Given the absence of any studies, the current literature provides no direct evidence for or against an impact of post-mortem findings on clinical performance at the level of individual practitioners or institutions. This does not invalidate the potential role of the autopsy in relation to clinical practice or performance improvement, but instead reveals an important gap in the literature.

Furthermore, maintaining a high autopsy rate and merging accurate hospital discharge data and autopsy data are effective ways to improve the accuracy of survival estimates and mortality prediction models, and to estimate mortality attributable to diagnostic failures.

Autopsy findings also offer relevant information for the advance of medical knowledge and the description of new disease entities. As an example, a recent pandemic was originated by a novel influenza A (H1N1) virus, and severe cases were characterized by ARDS, shock, and acute kidney injury. Lung histopathological changes in fatal cases showed signs of diffuse alveolar damage, necrotizing bronchiolitis, and occasional alveolar haemorrhage [18]. And, kidney pathological changes are consistent with acute tubular necrosis and persistence of viral infection despite antiviral treatment [19].

The health care system as a whole can thus benefit enormously from autopsy data, by, substantially enhancing the accuracy of vital statistics, which play important roles in research, funding, and other policy decisions. Future research opportunities include characterizing the factors leading to errors in clinical diagnosis, establishing optimal means of using autopsy data in performance improvement strategies, exploring different mechanisms for encouraging autopsies, and testing the efficiency of these improvements with new correlations between clinical and autopsy diagnoses.

Ongoing controversy

An ongoing controversy raises the question whether autopsy is still needed as a tool to monitor diagnostic accuracy in ICUs, and therefore, there is an urgent need to reverse the decline in the rate of post-mortem examinations.

Some arguments against the continuation of performing autopsies are cost containment, progress in diagnostic procedures, lack of time and interest by both pathologists and clinicians, and persisting distrust of families. It has been suggested [20] that, in the future, autopsies should be performed at regional autopsy centres, staffed by pathologists specially trained in autopsy, where autopsies could be performed safely and where the information obtained from autopsy materials could be used more effectively. It should be coupled with a distribution mechanism for decentralized autopsy resource, whose materials could be used for the detection and analysis of emerging diseases, the identification of public health or epidemiological issues, outcome analysis, quality improvement investigations, and possibly for human tissue studies. Undoubtedly, this model has important limitations mainly related to the transfer of the corpse, which is time-consuming, may affect the family consent to practice the post-mortem examination, and make communication difficult between clinicians and pathologists.

By contrast, it can be argued that the autopsy offers relevant information for teaching and for the advancement of medical knowledge. The description of new disease entities continue to be based upon autopsy findings. It is also an important source of relevant data to assess the effect of surgical interventions or other novel therapeutics. Furthermore, the autopsy provides information unavailable by any other method, and should be considered in every patient who dies in the ICU.

Conclusion

During the past few decades, autopsy rates have decreased worldwide. However, significant discrepancies are found between clinical diagnoses before death and post-mortem findings, despite advances in diagnostic technology. This reinforces the importance of the post-mortem examination in detecting otherwise unexpected diagnoses, even in patients under the close investigation and scrutiny that follows ICU admission. It should encourage clinicians to remember the value of the autopsy as a reliable tool in assuring and improving the quality of medical care by monitoring diagnostic accuracy and treatment of the ICU patient.

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