The Molecular Autopsy: A Review of Interprofessional Integration of Post-Mortem Biochemistry and Laboratory Forensics in Unexplained Surgical & Anesthetic Mortality
Abstract
Background: Unexplained deaths occurring intraoperatively or in the immediate postoperative period present profound diagnostic and medico-legal challenges. Traditional autopsy may be non-diagnostic for metabolic, pharmacogenetic, or subtle biochemical fatal events. Aim: This narrative review examines the convergence of forensic medicine and medical laboratory science in the form of the "molecular autopsy," analyzing the interprofessional framework required to investigate such mortality. Methods: A comprehensive literature search (2010-2024) was conducted across PubMed, Scopus, and Web of Science. Relevant studies on post-mortem biochemistry (thanatochemistry), forensic toxicology, and interdisciplinary death investigation protocols were synthesized.
Results: The molecular autopsy integrates post-mortem biochemical analyses (tryptase for anaphylaxis, serum electrolytes, creatine kinase for malignant hyperthermia) with detailed procedural and pharmacological context. Its efficacy is contingent upon rigorous interprofessional collaboration, including operating room staff (specimen integrity), pharmacy (medication reconciliation), nursing (clinical timeline), and infection control. Standardized protocols for sample collection, timing, and interpretation are paramount but inconsistently applied. Conclusion: The molecular autopsy is an indispensable adjunct to traditional autopsy for unexplained surgical deaths. Its systematic implementation requires formalized interprofessional protocols, standardized laboratory assays, and shared interpretive frameworks to elucidate causes like malignant hyperthermia, anaphylaxis, and toxic overdose, thereby improving patient safety and medico-legal accountability.
Full text article
References
Al-Khateeb, H., Epiphaniou, G., & Daly, H. (2019). Blockchain for modern digital forensics: The chain-of-custody as a distributed ledger. In Blockchain and clinical trial: securing patient data (pp. 149-168). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-030-11289-9_7
Banner, J., Basso, C., Tolkien, Z., Kholova, I., Michaud, K., & Gallagher, P. J. (2021). Autopsy examination in sudden cardiac death: a current perspective on behalf of the Association for European Cardiovascular Pathology. Virchows Archiv, 478(4), 687-693. https://doi.org/10.1007/s00428-020-02949-8
Carlson, K. J., Sun, S. A., Swan, C., Koenig, M., & Derkay, C. S. (2022). Management of patients susceptible to malignant hyperthermia: A surgeon's perspective. International Journal of Pediatric Otorhinolaryngology, 159, 111187. https://doi.org/10.1016/j.ijporl.2022.111187
Chen, J. H., Inamori-Kawamoto, O., Michiue, T., Ikeda, S., Ishikawa, T., & Maeda, H. (2015). Cardiac biomarkers in blood, and pericardial and cerebrospinal fluids of forensic autopsy cases: A reassessment with special regard to postmortem interval. Legal medicine, 17(5), 343-350. https://doi.org/10.1016/j.legalmed.2015.03.007
Cohen, M., Sadhasivam, S., & Vinks, A. A. (2012). Pharmacogenetics in perioperative medicine. Current Opinion in Anesthesiology, 25(4), 419-427. DOI: 10.1097/ACO.0b013e3283556129
Davies, S., Johnston, A., & Holt, D. (Eds.). (2019). Forensic toxicology: drug use and Misuse. Royal Society of Chemistry.
Dawidowska, J., Krzyżanowska, M., Markuszewski, M. J., & Kaliszan, M. (2021). The application of metabolomics in forensic science with focus on forensic toxicology and time-of-death estimation. Metabolites, 11(12), 801. https://doi.org/10.3390/metabo11120801
Edston, E., & van Hage-Hamsten, M. (2005). Postmortem diagnosis of anaphylaxis. In Forensic pathology reviews (pp. 267-281). Totowa, NJ: Humana Press.
Ferrara, S. D., Cecchetto, G., Cecchi, R., Favretto, D., Grabherr, S., Ishikawa, T., ... & Bajanowski, T. (2017). Back to the Future-Part 2. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences. International journal of legal medicine, 131(4), 1085-1101. https://doi.org/10.1007/s00414-017-1585-7
Grassi, S., Martínez-Barrios, E., Cazzato, F., Cesar, S., Ortega-Sánchez, M. L., Barberia, E., ... & Campuzano, O. (2023). Samples Used in Molecular Autopsy: An Update. In Unlocking the Mysteries of Death-New Perspectives for Post-Mortem Examination. IntechOpen. DOI: 10.5772/intechopen.1002204
Hemphill, S., McMenamin, L., Bellamy, M. C., & Hopkins, P. M. (2019). Propofol infusion syndrome: a structured literature review and analysis of published case reports. British journal of anaesthesia, 122(4), 448-459. https://doi.org/10.1016/j.bja.2018.12.025
Hernández-Romero, D., Valverde-Vázquez, M. D. R., Hernandez del Rincon, J. P., Noguera-Velasco, J. A., Pérez-Cárceles, M. D., & Osuna, E. (2021). Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death. Diagnostics, 11(4), 614. https://doi.org/10.3390/diagnostics11040614
Hopkins, P. M., Girard, T., Dalay, S., Jenkins, B., Thacker, A., Patteril, M., & McGrady, E. (2021). Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists. Anaesthesia, 76(5), 655-664. https://doi.org/10.1111/anae.15317
Laurenza, C., Ansart, L., & Portier, K. (2020). Risk factors of anesthesia-related mortality and morbidity in one equine hospital: a retrospective study on 1,161 cases undergoing elective or emergency surgeries. Frontiers in Veterinary Science, 6, 514. https://doi.org/10.3389/fvets.2019.00514
Madea, B. (2022). Duties of Forensic Medicine and the Forensic Medicine Practitioner. Handbook of Forensic Medicine, 1, 19-25. https://doi.org/10.1002/9781119648628.ch2
Mondello, C., Baldino, G., Cianci, V., Forzese, E., Asmundo, A., Ieni, A., & Ventura Spagnolo, E. (2023). Postmortem biochemistry and immunohistochemistry in anaphylactic death due to hymenoptera sting: a forensic case report. International Journal of Environmental Research and Public Health, 20(9), 5640. https://doi.org/10.3390/ijerph20095640
Mullins, M. F. (2018). Malignant hyperthermia: a review. Journal of Perianesthesia Nursing, 33(5), 582-589. https://doi.org/10.1016/j.jopan.2017.04.008
Nijkamp, N., & Foran, P. (2021). The effects of staffing practices on safety and quality of perioperative nursing care-an integrative review. Journal of Perioperative Nursing, 34(1), 15-22. https://search.informit.org/doi/10.3316/informit.999137202967991
Palmiere, C., & Mangin, P. (2012). Postmortem chemistry update part I. International journal of legal medicine, 126(2), 187-198. https://doi.org/10.1007/s00414-011-0625-y
Palmiere, C., Bardy, D., Mangin, P., & Werner, D. (2013). Postmortem diagnosis of unsuspected diabetes mellitus. Forensic science international, 226(1-3), 160-167. https://doi.org/10.1016/j.forsciint.2013.01.004
Palmiere, C., Tettamanti, C., Augsburger, M., Burkhardt, S., Sabatasso, S., Lardi, C., & Werner, D. (2016). Postmortem biochemistry in suspected starvation-induced ketoacidosis. Journal of forensic and legal medicine, 42, 51-55. https://doi.org/10.1016/j.jflm.2016.04.013
Peters, F. T. (2021). Principles of Forensic Toxicology, (2020). https://doi.org/10.1093/jat/bkab020
Poovaragavan, V., Vidua, R. K., Kumar, A., Ponmani, P., Keche, A. S., Sahoo, N., & Agarwal, P. K. (2023). Estimation of time since death using biochemical markers in synovial fluid. The American Journal of Forensic Medicine and Pathology, 44(3), 183-187. DOI: 10.1097/PAF.0000000000000861
Ramanathan, R., Suman, S. P., & Faustman, C. (2020). Biomolecular interactions governing fresh meat color in post-mortem skeletal muscle: A review. Journal of Agricultural and Food Chemistry, 68(46), 12779-12787. https://doi.org/10.1021/acs.jafc.9b08098
Riazi, S., Kraeva, N., & Hopkins, P. M. (2018). Updated guide for the management of malignant hyperthermia. Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 65(6), 709-721. https://doi.org/10.1007/s12630-018-1108-0
Rosenberg, H., Pollock, N., Schiemann, A., Bulger, T., & Stowell, K. (2015). Malignant hyperthermia: a review. Orphanet journal of rare diseases, 10(1), 93. https://doi.org/10.1186/s13023-015-0310-1
Rousseau, G., Reynier, P., Jousset, N., Rougé-Maillart, C., & Palmiere, C. (2018). Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses. Clinical Chemistry and Laboratory Medicine (CCLM), 56(11), 1819-1827. https://doi.org/10.1515/cclm-2018-0153
Saukko, P., & Knight, B. (2015). Knight's forensic pathology. CRC press.
Sisodia, U. (2022). Chain of custody: scaling the investigation to the event. In Crime Scene Management within Forensic Science: Forensic Techniques for Criminal Investigations (pp. 407-418). Singapore: Springer Singapore. https://doi.org/10.1007/978-981-16-6683-4_16
Tanno, L. K., Simons, F. E. R., Annesi-Maesano, I., Calderon, M. A., Aymé, S., Demoly, P., & Joint Allergy Academies. (2017). Fatal anaphylaxis registries data support changes in the who anaphylaxis mortality coding rules. Orphanet journal of rare diseases, 12(1), 8. https://doi.org/10.1186/s13023-016-0554-4
Tattoli, L., Dell’Erba, A., Ferorelli, D., Gasbarro, A., & Solarino, B. (2019). Sepsis and nosocomial infections: the role of medico-legal experts in Italy. Antibiotics, 8(4), 199. https://doi.org/10.3390/antibiotics8040199
Tejedor-Alonso, M. A., Vallejo-de-Torres, G., Escayola, E. N., Martínez-Fernandez, P., Moro-Moro, M., & Masgrau, N. A. (2020). Postmortem tryptase cutoff points and main causes of fatal anaphylaxis. The Journal of Allergy and Clinical Immunology: In Practice, 8(2), 761-763.
Unuma, K., Makino, Y., Sasaki, Y., Iwase, H., & Uemura, K. (2019). Presepsin: A potential superior diagnostic biomarker for the postmortem differentiation of sepsis based on the Sepsis-3 criteria. Forensic Science International, 299, 17-20. https://doi.org/10.1016/j.forsciint.2019.03.034
Van, S., Lam, V., Patel, K., Humphries, A., Siddiqi, J., Van, S. V., & Lam, V. T. (2023). Propofol-related infusion syndrome: a bibliometric analysis of the 100 most-cited articles. Cureus, 15(10). DOI 10.7759/cureus.46497
Yang, L., Tautz, T., Zhang, S., Fomina, A., & Liu, H. (2020). The current status of malignant hyperthermia. Journal of biomedical research, 34(2), 75. https://doi.org/10.7555/JBR.33.20180089
Zheng, Z., Zhao, C., Xiong, H., Zhang, L., Wang, Q., Li, Y., & Li, J. (2021). Significance of detecting postmortem serum IgE in frozen corpses for the diagnosis of anaphylaxis in forensic. Legal Medicine, 53, 101930. https://doi.org/10.1016/j.legalmed.2021.101930
Zribi, M., Ennouri, H., Turki, M., Amar, W. B., Grati, M. A., Hammami, Z., ... & Maatoug, S. (2021). Diagnostic value of high-sensitivity troponin T in postmortem diagnosis of sudden cardiac death. Journal of Forensic and Legal Medicine, 78, 102127. https://doi.org/10.1016/j.jflm.2021.102127
Authors
Copyright (c) 2024 Mohammed Hathal Thunayyan Alotaibi, Modhi Falaj Herbash Alotaibi, Mohammed Abdulrahman M Abobaker, Mohammed Eid S Aljohany, Talal Eid Alanazi, Khairat Majrshi, Abdallah Ali Mohammed Hakami, Saleh Alenazi, Ahmed Ghurmallah Alzahrani, Ghadeer Abduh Mohammed Baeshen, Ismail Ahmad Ismail Alnumi
This work is licensed under a Creative Commons Attribution 4.0 International License.