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Learning From Investigation After Death

Griffiths, Benedict T., MBBS1; Sebire, Neil J., MBBS2; Brierley, Joe, MBChB1

Pediatric Critical Care Medicine: August 2018 - Volume 19 - Issue 8S - p S72–S78
doi: 10.1097/PCC.0000000000001505
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Objectives: The acceptability of traditional postmortem examination to bereaved families, coupled with a misguided professional view about their limited utility, has led to decrease in this ultimate investigation. Research recurrently demonstrates that postmortem examination provides clinically relevant information despite ever-improving diagnostic techniques. This review examines postmortem examination for children who die in PICU—whether consented or nonconsented (legally mandated). It explores how such investigations might provide useful information and suggests that PICU and pathology teams work together to provide information for bereaved families to either enable them to consent to postmortem interventions or understand necessary forensic processes. Newer technologies such as postmortem imaging and laparoscope-assisted/ultrasound-guided tissue sampling are reviewed, with the hope that greater acceptability to families may lead to a welcome resurgence in postmortem information for clinicians, tempered by realization that widespread acceptance of their equivalence to standard techniques by most forensic services is awaited.

Data Sources: Literature review.

Study Selection: Journal articles describing practices in pediatric and adult postmortem examination.

Data Extraction: Not available.

Data Synthesis: Not available.

Conclusions: The PICU team have a duty to help bereaved parents understand what postmortem investigations are available, or might be mandated, after the death of their child. A thoughtful, unhurried, and compassionate discussion should be arranged with expert pathology teams and any specialists who have cared for the child to explain how investigations can provide information about what is involved—including availability and suitability of newer techniques. This should include information about when a child’s body, organs, or tissues will be available for the funeral, necessary legal procedures and how and when results will be explained to them.

1Paediatric & Neonatal Intensive Care, Great Ormond St Hospital, London, United Kingdom.

2Department of Pathology, Great Ormond St Hospital, London, United Kingdom.

The authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: joe.brierley@gosh.nhs.uk

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OVERVIEW

The word autopsy derives from the Greek “auto” meaning self and “optos” meaning “seen” and so means “seen for oneself.” In modern practice, autopsy refers to an invasive investigation after death and is used interchangeably with postmortem examination (PME). Traditional PME uses large surgical incisions to provide optimal histopathologic and anatomical diagnosis after death, but newer techniques mean that this is no longer necessarily the only means to achieve diagnostic information after death.

Although PME has been a tool for learning and discovery for centuries, the astonishing rate of medical progress accompanied by changes in societal views regarding the acceptability of human cadaveric dissection has been associated with a dramatic decline in PME (1).

PME rates vary around the world: 55% in South America, 26% in the United Kingdom, 20% in Switzerland, 17–75% in the United States, and 0% in Nigeria (2–6). Such variability results from differing sociocultural and scientific perceptions about the value of PME, the means by which PME data are obtained and crucially how PME processes may alter or interfere with bereavement.

Pediatric PME occurs either 1) as a mandated legal investigation into death by a coroner/forensic examiner or 2) with consent from parents/those with parental responsibility because clinicians and/or relatives wish to better understand what has caused death. In general, PME is mandated following sudden unexpected death, in deaths due to trauma, when issues with medical or other care might have contributed to death or if treating clinicians cannot provide a cause of death. In children, this most frequently occurs in sudden unexpected death in infancy or with child protection concerns, for example, possible nonaccidental injury. As the child has survived to PICU admission, the PICU team and pathology colleagues may need to participate in formal child protection, civil, or criminal procedures (7).

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THE VALUE OF PME

PME provides the ultimate opportunity to reevaluate medical diagnoses and treatment that has sadly neither been curative nor lifesaving. Presumptions that scientific understanding of the pathophysiology basis of those diseases leading to children’s deaths is near complete, given modern genetic, imaging, and microbiological techniques have contributed to falling PMEs (2). But, multiple studies suggest that despite such advances, PME continues to provide novel information, thereby benefiting bereaved parents, the healthcare team, and future children. PME clearly has the potential to provide medical information with the prospect of benefiting the treating teams by providing more knowledge about diseases and the effects of their treatments. In critical care, there are large knowledge gaps about the effects of many organ support techniques on the human body.

Goldman et al (8) explored the diagnostic value of PMEs over 3 decades, (60s, 70s, 80s) finding in 10% of 100 randomly selected autopsies from each a major diagnosis that would have changed therapy if known before death (class 1 error—Table 1) and in a further 12% a missed diagnosis that would not. Specifically in children, one European center reported a major diagnostic error in 23% of cases (3); a U.S. study reported a consistent 36% PME rate (1984–1993) with persisting additional information in 34% of child deaths (9); more specifically for children with an established diagnosis of cancer, PME provided information unknown to clinicians in 23% of cases (10) (Table 2).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

Limited invasive PME sampling soon after death can be useful, for example, child dying from fibrotic lung disease undergoing postmortem open lung biopsy on PICU having been too unstable in life, before rapid burial. Similarly, the PICU team can obtain blood, urine, and cerebrospinal fluid to look for infection and/or liver, skin and muscle biopsies for cellular/mitochondrial or fibroblast culture to investigate suspected metabolic or neuromuscular disease.

The message seems clear! Investigation after death can provide useful clinical information and a unique opportunity for medical teams to learn and reflect on their practice and crucially can provide understanding and closure for the family (Table 3).

TABLE 3

TABLE 3

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BARRIERS TO PME

Child death is a devastating event for parents, and clinicians must act with great care and compassion. Discussion about investigations after the death of a child can be portrayed as a challenging conversation to “need to have” with bereaved parents, arguably occurring in the setting of the failure of a PICU team to save the life of the child and representing an acknowledgement of uncertainty by the treating team. It has been reported that clinicians do not routinely offer PME to parents for fear of causing upset (12, 14). Increasingly, research with bereaved parents about postmortem and organ donation discussions shows that they actually value clear, open and honest communication about these ostensibly challenging areas (15, 16).

We suggest that effective conversations with families about PME in children should occur as part of holistic end-of-life care with pathology/mortuary experts accompanying the PICU team and relevant specialist clinicians who have cared for the child.

Concerns about the acceptability of PME for certain religious or cultural groups should not preclude an open exploration of the potential benefits of such investigations with parents, although great sensitivity must be used. Newer less invasive investigations might be more acceptable, and advice from community and religious leaders can ensure that parents have thorough medical and faith-based information to make their decisions (17).

Although discussed elsewhere in this supplement, it should be noted that organ and tissue donation is compatible with other investigations after death, such as PME, tissue sampling and imaging, and this includes mandated legal PME with permission of the coroner (18).

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CONSENT FOR PME

Although an older child might discuss postmortem investigations before their death, in reality, PME consent is obtained from those with parental responsibility.

Physicians’ lack of knowledge of the consent process for PME has been cited as a barrier to approaching parents to discuss the matter (14). Consent for investigation after death should be based on the same principle as for any procedure: the provision of fully informed consent. Those taking consent should clearly be well informed, so they can discuss all available options, which should now include any effective noninvasive alternatives to standard PME. The simplest way to ensure this is for pathology/mortuary staff together with PICU staff and relevant specialists to take time with the family to explain what is recommended, what alternatives exist, and what they mean for arrangements such as the child’s funeral. Explicit information about surgical/other procedures and the options for eventual disposal of any organs or tissues retained—even slides taken—should be provided. Although ideally this should occur for nonconsented PME, there are understandable limits regarding forensic matters.

Mandated PME will be arranged by the coroner, and there is no requirement for consent, indeed parents cannot refuse. Optimal investigation into such deaths, sometimes not only in previously apparently healthy children but also in those with complex medical backgrounds, still requires collaboration between specialist pediatric forensic teams and clinicians who have cared for the child to optimize forensic investigations.

In the United Kingdom, consent procedures for PME are governed by the Human Tissue Authority (HTA) established in 2005 in response to issues around removal and storage of the tissues and organs of deceased children without “consent.” (19) A paternalistic system had evolved in which clinicians had not wanted to trouble bereaved parents with requests for PME, which was technically not unlawful at the time. But, the actions of pathologists in keeping the organs of deceased children without their parents’ knowledge, irrespective of the great advances in congenital heart surgery their work allowed, was considered abhorrent by a society whose moral framework had evolved faster than medical practice or the law.

The subsequent Act of Parliament, the Human Tissue Act 2004, was needed to restore and protect public trust and led to the formation of the HTA, which operates independently with extensive powers to govern all aspects of tissue management after death, including a framework for consent in both PME and deceased organ donation.

The HTA mandates unprecedented authority to U.K. parents to determine specific aspects of disposal of their child’s body after consented PME including the management of slides and any retained full organs with options including respectful hospital disposal, return to the family for second funeral processes, deferral of the funeral until everything can be reunited, or retention for research. Although some clinicians might feel challenged about engaging in such depth raw discussions, this can be addressed by our suggestion of engaging pathology services—the voices of parents have told us this is what they “require” at this time (20). These issues have surely influenced parental attitudes to PME in the United Kingdom, but the overall impact remains uncertain (21).

Although physicians’ attitudes toward PME have undoubtedly changed over the last century, the crucial consideration remains parental attitudes, especially for consented investigations. Exploration of parental refusal of PME in the literature often highlights strong fear of disfigurement (22), with traditional PME perceived to include large incisions which are becoming less acceptable to parents, especially from certain ethnic and cultural groups (23–26). However, the development of noninvasive imaging diagnostic modalities presents an opportunity for less invasive examinations, which may be able to provide the information required in a manner more acceptable to parents and clinical teams alike.

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HIGH-QUALITY PME

Traditional pediatric PME consists of several components, all incorporated into the overall autopsy report which include review of the clinical case notes, detailed external examination, postmortem imaging, (precise modality of choice dependent on age, clinical history, and organ or system to be visualized), and systematic examination of all internal organs. Parents may wish to limit examination to specific organ(s) or body cavities if there is a query about a particular diagnosis or clinical issue. Standard open internal examination is performed via a midline incision from manubrium to pelvis, and internal organs inspected, examined, and then removed to be weighed and dissected.

More recently, it has been demonstrated that other approaches, such as laparoscope-assisted or ultrasound-guided techniques, can be used, in conjunction with postmortem imaging, to obtain tissue samples via a much smaller incision (1–2 cm incision permits sampling of all abdominal and thoracic organs). This approach allows direct visualization of organs and permits photography, video recording, and sampling. Its accuracy for specific diagnoses compared with standard PME across a range of clinical scenarios remains to be established. Regardless of approach, in situ sampling for microbiology, genetic studies, virology, and histology can be performed, to minimize invasiveness of the procedure.

It is widely acknowledged in the literature that quality and yield from pediatric and perinatal autopsy improves when performed by those specialized in the field (27). In the United Kingdom and other countries, this led to centralized pediatric pathology services, typically around large specialist children’s hospitals with associated pediatric pathology departments. However, a proportion of children die outside those institutions. Links with specialist pediatric pathologists do exist but are often remote, and discussing the merits of autopsy in specific cases becomes more difficult.

Clinical pediatric medicine has evolved, and consequently, the role of examination after death must also evolve to deal with an ever more complex and chronic population. The concept of “Investigation After Death” may therefore more accurately reflect the future of this approach, with personalized investigations performed targeted to address the specific issues of particular cases, to improve the quality of information gained and increase parental acceptability. Such investigation requires that decisions made and approaches used are primarily based around the wishes and expectations of the parents, and pathologists and clinicians alike should work together to shift the emphasis toward personalized investigation by providing the advantages and disadvantages of all options to address a meaningful clinical question.

It should be noted that, for many parents, the possibility to contribute to research and therefore potentially help others has been reported to be a significant factor in their decision-making, and clinicians should not fear discussing this.

The standard approach for neuropathologic examination is to remove the brain for a period of fixation prior to dissection and sampling and so parents should be made aware that this will delay the final autopsy report. Postmortem imaging approaches provide excellent anatomical detail for many structural CNS abnormalities, and it is likely that requirements for brain removal may reduce in the future.

Histologic sampling provides a morphologic diagnosis of pathology and can exclude or confirm the presence of disease. While tissue diagnosis remains critically important in some scenarios, the evidence for benefit of extensive sampling is limited. It is therefore likely that targeted sampling protocols may be indicated according to the clinical features, without reduction in diagnostic accuracy. Tissue samples obtained for microscopic examination are processed into small paraffin wax blocks and glass microscope slides for examination by the pathologist under a microscope, but with technological laboratory advances, it is likely that in future such samples will undergo a range of genomic, proteomic, metabolomic, and other investigations, resulting in improved diagnostic accuracy from smaller tissue samples, reducing further sampling requirements.

Samples required for genetic studies, fibroblast culture, or metabolic studies should be obtained as soon as possible following death rather than during formal PME to maximize the chance of successful analysis. If a sample is fixed in formalin/formaldehyde, it will no longer be suitable for culture or standard karyotyping, although DNA extraction is possible. Other ancillary investigations that may be indicated include microbiological and virologic analyses, as well as metabolic screening studies (blood and bile spots for acylcarnitine profiling by tandem mass spectrometry, or enzyme assays using cultured fibroblasts harvested from a postmortem skin biopsy), and cytogenetic and DNA analysis.

In the vast majority of cases, there is no need to retain organs and delay funeral arrangements. However, in some circumstances, it may be necessary for the pathologist to temporarily retain an organ for fixation and further detailed examination, for example, specialist CNS or cardiac examination.

The complete final postmortem report should describe all significant macroscopic and microscopic findings, the results of ancillary investigations, and a specific summary of the findings with clinicopathologic correlation. Although parents are entitled to be provided with a copy of the report, it is generally recommended that postmortem reports are issued to the referring clinician so that the contents can be discussed with the parents in person, since aspects of technical terminologies used in such reports may be distressing and confusing.

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POSTMORTEM IMAGING

Postmortem (PM) cross-sectional imaging such as MRI (PM-MRI) or CT (PMCT) are noninvasive investigations which provide excellent anatomical details and high concordance with standard autopsy for structural abnormalities (28). Furthermore, in cases where a structural organ abnormality is detected, PMMRI may be used to guide less invasive organ examination and tissue sampling in conjunction with postmortem ultrasound scanning or endoscopic examination (21, 29). Imaging will likely become the investigation of choice for structural abnormalities.

PMMR has been validated, but there is a learning curve in PMMR acquisition and reporting, particularly in correct interpretation of normal PM changes which occur such as fluid redistribution (subcutaneous edema, pleural and pericardial effusions, and ascites). PMMR is particularly good for congenital anatomical abnormalities, such as intracranial hemorrhage, brain malformations, renal anomalies, congenital heart disease, and skeletal dysplasias. Conventional PMMR is however poor at detecting microscopic changes such as renal dysplasias and disseminated sepsis, which often have no imaging correlate.

The main advantages of PMCT over PMMR are speed of acquisition, widespread availability, and the better bone detail that is achieved using unenhanced CT. However, in children, PMCT has several disadvantages, including reduced soft-tissue contrast due to reduced abdominal and subcutaneous fat, poor contrast in the brain, and without vascular contrast medium, assessment of the thoracic and abdominal cavity is particularly challenging; unenhanced PMCT performs worse than PMMR in this group, but PMCT is becoming particularly useful at detecting rib fractures and detailed abnormalities of other bone injuries.

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RESULT DISCLOSURE

The decision to permit PME on their child must be one of the most difficult any parent can make and receiving results equally difficult—especially as even with technological advances, results often follow death by several weeks. Parents must be counseled that PME may not necessarily provide new information about their child’s death but does represent the last chance to learn what exactly has happened. Clear information about how, and when, results are likely to be provided must form part of the consent process.

Legally mandated PME may not have been the parents wish, and awareness of this is imperative to ensure sensitive and appropriate delivery of the results. Irrespective of the type of PME, the parents must be kept informed about how investigations are proceeding. PICU clinicians should seek support from specialists in explaining reports with speciality-specific diagnoses and organize any appropriate follow-up such as genetic counseling. The actual discussion of PME results should be done in conjunction with other bereavement services, coordinated by PICU Family Liaison Nurses. These may include psychology, relevant bereavement teams, and spiritual care. Results must be communicated to local family doctors, any specialist clinicians, and, via the parents, relevant future teams such as obstetric services and genetics services where relevant.

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CONCLUSIONS

Both pediatric intensive care medicine and the parents of children who die there have much to gain from investigation after death. Collaboration between the PICU team, any specialist clinicians involved, and, crucially, specialist pathology services should ensure that the correct information is provided to bereaved parents in the context of holistic end-of life care. This includes types of examination available, what will happen to any samples and what it means for funeral processes—specifically, how appropriate and acceptable tools will be used to answer remaining questions about the death of their child. This will allow them to either determine the type of PME that is to occur or to understand the mandated legal process better. Technical advances in PME promise an increased acceptability for parents with cultural or personal concerns about the traditional approach, and we encourage PICU teams to explore the local provision of such individualized investigations for their patients.

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REFERENCES

1. Turnbull A, Osborn M, Nicholas N. Hospital autopsy: Endangered or extinct? J Clin Pathol 2015; 68:601–604
2. Narayanan A, Thorburn K, Baines P. Autopsies in children continue to reveal unanticipated discrepancies between autopsy findings and antemortem clinical diagnoses. Arch Dis Child 2009; 94:645
3. Widmann R, Caduff R, Giudici L, et al. Value of postmortem studies in deceased neonatal and pediatric intensive care unit patients. Virchows Arch 2017; 470:217–223
4. Meert KL, Keele L, Morrison W, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: End-of-life practices among tertiary care PICUs in the United States: A multicenter study. Pediatr Crit Care Med 2015; 16:e231–e238
5. Cardoso MP, Bourguignon DC, Gomes MM, et al. Comparison between clinical diagnoses and autopsy findings in a pediatric intensive care unit in São Paulo, Brazil. Pediatr Crit Care Med 2006; 7:423–427
6. Ijezie E, Okpokowuruk F, Nwafor C. Pediatric death audit with special emphasis on autopsy at the University of Uyo Teaching Hospital, Uyo, Nigeria: A 6-year review. International Journal of Pediatric Research 2:80–87
7. The Royal College of Pathologists: Sudden Unexpected Death in Infancy And Childhood - The Report of a Working Group Convened by The Royal College of Pathologists and endorsed by The Royal College of Paediatrics and Child Health, 2016. Available at: https://www.rcpath.org/resourceLibrary/sudden-unexpected-death-in-infancy-and-childhood-report.html. Accessed February 1, 2018
8. Goldman L, Sayson R, Robbins S, et al. The value of the autopsy in three medical eras. N Engl J Med 1983; 308:1000–1005
9. Kumar P, Taxy J, Angst DB, et al. Autopsies in children: Are they still useful? Arch Pediatr Adolesc Med 1998; 152:558–563
10. Buckner T, Blatt J, Smith SV. The autopsy in pediatrics and pediatric oncology: A single-institution experience. Pediatr Dev Pathol 2006; 9:374–380
11. Goldstein B, Metlay L, Cox C, et al. Association of pre mortem diagnosis and autopsy findings in pediatric intensive care unit versus emergency department versus ward patients. Crit Care Med 1996; 24:683–686
12. von Dessauer B, Velozo L, Benavente C, et al. Postmortem studies in the contemporary pediatric intensive care unit. Pediatr Crit Care Med 2011; 12:617–621
13. ten Berge J, de Gast-Bakker D-AH, Plötz FB. Circumstances surrounding dying in the paediatric intensive care unit. BMC Pediatr 2006; 6:XXX22.
    14. Rose C, Evans M, Tooley J. Falling rates of perinatal postmortem examination: Are we to blame? Arch Dis Child Fetal Neonatal Ed 2006; 91:F465
    15. Lewis C, Hill M, Arthurs OJ, et al. Factors affecting uptake of postmortem examination in the prenatal, perinatal and paediatric setting. BJOG 2018; 125:172–181
    16. Darlington AS, Long-Sutehall T, Randall D, et al. Parents’ experiences of requests for organ and tissue donation: Evidence from a qualitative study. Presented at Congress of the European Society of Organ Transplantation, September 24–27, 2017Barcelona.
    17. Mohammed M, Kharoshah MA. Autopsy in Islam and current practice in Arab Muslim countries. J Forensic Leg Med 2014; 23:80–83
    18. Twamley H, Haigh A, Williment C, et al. Prospective audit to evaluate the potential of the coronial system to increase solid organ donation. BMJ Open 2016; 6:e010231
    19. Royal Liverpool Childrens Inquiry: The Royal Liverpool Children’s Inquiry Summary and recommendations. Royal Liverpool Children’s Inquiry. 2001London, The Stationary Office.
    20. Sque M, Long T, Payne S, et al. The UK postmortem organ retention crisis: A qualitative study of its impact on parents. J R Soc Med 2008; 101:71–77
    21. Breeze AC, Statham H, Hackett GA, et al. Perinatal postmortems: What is important to parents and how do they decide? Birth 2012; 39:57–64
    22. McHaffie HE. Consent to autopsy for neonates. Arch Dis Child Fetal Neonatal Ed 2001; 85:4F–7
    23. Sieswerda-Hoogendoorn T, van Rijn RR. Current techniques in postmortem imaging with specific attention to paediatric applications. Pediatr Radiol 2010; 40:141–152; quiz 259
    24. Arthurs OJ, Taylor AM, Sebire NJ. The less-invasive perinatal autopsy: Current status and future directions. Fetal Matern Med Rev 2013; 24:45–59
    25. Sebire NJ, Weber MA, Thayyil S, et al. Minimally invasive perinatal autopsies using magnetic resonance imaging and endoscopic postmortem examination (“keyhole autopsy”): Feasibility and initial experience. J Matern Fetal Neonatal Med 2012; 25:513–518
    26. Thayyil S, Sebire NJ, Chitty LS, et al; MARIAS collaborative group: Post-mortem MRI versus conventional autopsy in fetuses and children: A prospective validation study. Lancet 2013; 382:223–233
    27. Cartlidge PH, Dawson AT, Stewart JH, et al. Value and quality of perinatal and infant postmortem examinations: Cohort analysis of 400 consecutive deaths. BMJ 1995; 310:155–158
    28. Ruder TD, Hatch GM, Ebert LC, et al. Whole body postmortem magnetic resonance angiography: Postmortem mr angiography. J Forensic Sci 2012; 57:778–782
    29. Ben-Sasi K, Chitty LS, Franck LS, et al. Acceptability of a minimally invasive perinatal/paediatric autopsy: Healthcare professionals’ views and implications for practice. Prenat Diagn 2013; 33:307–312
    Keywords:

    autopsy; end-of-life care; pediatric intensive care unit; postmortem examination

    ©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies