Meta-Analysis

. 2023 Apr;70(4):749-770.

doi: 10.1007/s12630-023-02418-1. Epub 2023 May 2.

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis

Nicole K McKinnon^{1

2

3}, Christina Maratta^{4

5}, Lionel S Zuckier^{6

7}, J Gordon Boyd^{8

9}, Michaël Chassé^{10

11}, Laura Hornby¹², Andreas Kramer¹³, Julie Kromm^{13

14}, Owen T Mooney¹⁵, Prakash Muthusami^{16

17}, Roy Nitulescu¹¹, Jaewoo Park¹⁸, Marat Slessarev¹⁹, John Basmaji¹⁹

Affiliations

¹ Department of Critical Care, The Hospital for Sick Children (SickKids), 555 University Avenue, Toronto, ON, M5G 1X8, Canada. nicole.mckinnon@sickkids.ca.
² Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. nicole.mckinnon@sickkids.ca.
³ Department of Neuroscience and Mental Health, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada. nicole.mckinnon@sickkids.ca.
⁴ Department of Critical Care, The Hospital for Sick Children (SickKids), 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
⁵ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Division of Nuclear Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
⁷ Departments of Medicine and Radiology, University of Ottawa, Ottawa, ON, Canada.
⁸ Departments of Medicine (Neurology) and Critical Care Medicine, Kingston General Hospital, Kingston, ON, Canada.
⁹ Department of Medicine, Queen's University, Kingston, ON, Canada.
¹⁰ Department of Medicine, Université de Montréal, Montreal, QC, Canada.
¹¹ Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, QC, Canada.
¹² Canadian Blood Services, Ottawa, ON, Canada.
¹³ Departments of Critical Care Medicine and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
¹⁴ Hotchkiss Brain Institute, Alberta Health Services, Calgary, AB, Canada.
¹⁵ Section of Critical Care, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁶ Department of Diagnostic Imaging, Hospital for Sick Children (SickKids), Toronto, ON, Canada.
¹⁷ Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁸ Department of Emergency Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁹ Department of Medicine, Western University, London, ON, Canada.

PMID: 37131035
PMCID: PMC10203011
DOI: 10.1007/s12630-023-02418-1

Meta-Analysis

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis

Nicole K McKinnon et al. Can J Anaesth. 2023 Apr.

. 2023 Apr;70(4):749-770.

doi: 10.1007/s12630-023-02418-1. Epub 2023 May 2.

Authors

Affiliations

¹ Department of Critical Care, The Hospital for Sick Children (SickKids), 555 University Avenue, Toronto, ON, M5G 1X8, Canada. nicole.mckinnon@sickkids.ca.
² Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. nicole.mckinnon@sickkids.ca.
³ Department of Neuroscience and Mental Health, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada. nicole.mckinnon@sickkids.ca.
⁴ Department of Critical Care, The Hospital for Sick Children (SickKids), 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
⁵ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Division of Nuclear Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
⁷ Departments of Medicine and Radiology, University of Ottawa, Ottawa, ON, Canada.
⁸ Departments of Medicine (Neurology) and Critical Care Medicine, Kingston General Hospital, Kingston, ON, Canada.
⁹ Department of Medicine, Queen's University, Kingston, ON, Canada.
¹⁰ Department of Medicine, Université de Montréal, Montreal, QC, Canada.
¹¹ Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, QC, Canada.
¹² Canadian Blood Services, Ottawa, ON, Canada.
¹³ Departments of Critical Care Medicine and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
¹⁴ Hotchkiss Brain Institute, Alberta Health Services, Calgary, AB, Canada.
¹⁵ Section of Critical Care, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁶ Department of Diagnostic Imaging, Hospital for Sick Children (SickKids), Toronto, ON, Canada.
¹⁷ Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁸ Department of Emergency Medicine, University of Manitoba, Winnipeg, MB, Canada.
¹⁹ Department of Medicine, Western University, London, ON, Canada.

PMID: 37131035
PMCID: PMC10203011
DOI: 10.1007/s12630-023-02418-1

Abstract
in English, French

Purpose: We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children.

Source: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies.

Principal findings: Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations (n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical ^99mTc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00).

Conclusion: The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation.

Study registration: PROSPERO (CRD42021278788); registered 16 October 2021.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique et une méta-analyse pour déterminer la précision des tests diagnostiques des examens auxiliaires pour la déclaration du décès selon des critères neurologiques (DCN) chez les nourrissons et les enfants.

Sources: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et Cochrane de leur création jusqu’en juin 2021 pour trouver des études randomisées contrôlées, des études observationnelles et des résumés pertinents publiés au cours des trois dernières années. Nous avons identifié les études pertinentes utilisant la méthodologie PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) et une revue en deux étapes. Nous avons évalué le risque de biais en utilisant l’outil QUADAS-2 et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d’évaluer la certitude des données probantes. Un modèle à effets fixes a été utilisé pour méta-analyser les données de sensibilité et de spécificité regroupées pour chaque examen auxiliaire avec au moins deux études.

Constatations principales: Trente-neuf manuscrits admissibles évaluant 18 examens auxiliaires uniques (n = 866) ont été identifiés. La sensibilité et la spécificité variaient de 0,00 à 1,00 et de 0,50 à 1,00, respectivement. La qualité des données probantes était faible à très faible pour tous les examens auxiliaires, à l’exception des études de circulation nucléaire dynamique, pour lesquelles elle a été classée comme modérée. La scintigraphie nucléaire à l’aide du produit radiopharmaceutique lipophile 99mTc- hexa-méthyl-propylène amine oxime (HMPAO) avec ou sans imagerie tomographique était à la base des examens auxiliaires les plus précis, avec une sensibilité combinée de 0,99 (intervalle de densité le plus élevé [IDE] à 95 %, 0,89 à 1,00) et une spécificité de 0,97 (IDE à 95 %, 0,65 à 1,00).

Conclusion: L’examen auxiliaire pour un DCN chez les nourrissons et les enfants offrant la plus grande précision semble être la scintigraphie nucléaire utilisant le HMPAO avec ou sans imagerie tomographique; cependant, la certitude des données probantes est faible. Les modalités sans imagerie réalisées au chevet du patient nécessitent un examen plus approfondi. Enregistrement de l’étude: PROSPERO (CRD42021278788); enregistrée le 16 octobre 2021.

Keywords: ancillary testing; brain death; death determination; neurologic; pediatrics.

PubMed Disclaimer

Conflict of interest statement

Laura Hornby is a paid consultant for Canadian Blood Services.

Figures

**Figure 1**
PRISMA flow diagram. Details of the citation search and screening process in this systematic review

See this image and copyright information in PMC

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Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis

Affiliations

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis

Authors

Affiliations

Abstract
in English, French

Conflict of interest statement

Figures

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Cited by

References

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MeSH terms

LinkOut - more resources

Full Text Sources

Abstract in English, French

Conflict of interest statement

Figures

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Cited by

References

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Full Text Sources

Abstract
in English, French