PMID- 38231204
OWN - NLM
STAT- MEDLINE
DCOM- 20240411
LR  - 20240425
IS  - 1437-1596 (Electronic)
IS  - 0937-9827 (Print)
IS  - 0937-9827 (Linking)
VI  - 138
IP  - 3
DP  - 2024 May
TI  - Morphine concentrations in fatalities after palliative treatment of acute burn 
      injury.
PG  - 839-847
LID - 10.1007/s00414-024-03164-9 [doi]
AB  - The evaluation of a morphine concentration in postmortem blood is routine for a 
      forensic toxicologist. We here report three fatal cases where we found high 
      morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have 
      to be estimated as unusually high. All these individuals died due to severe burn 
      injuries and obtained morphine in the context of their palliative care in the 
      last hours of their lives. According to the autopsy results, the cause of death 
      in case 1 was burn disease with burns of about 90% of the body surface area 
      (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, 
      fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium 
      were detected in femoral blood. The findings fitted well with the detailed 
      clinical documentation. Further evidence of therapeutic concentrations of 
      quetiapine, duloxetine, and melperone could be matched to preexisting medication 
      of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was 
      applied, developed for the intravenous administration of morphine, to find an 
      explanation for the high morphine concentrations in femoral blood. Quantification 
      of morphine in body fluids and tissue was performed to calculate morphine tissue 
      concentration ratios to the morphine concentration in femoral blood. The 
      presented cases show that pharmacokinetic simulations can reflect decreased renal 
      clearance and decreased hepatic metabolism in general. However, this prediction 
      is not sufficient to explain the high morphine concentrations in femoral blood 
      measured here. It can be assumed that burn shock in particular leads to altered 
      pharmacokinetics, namely decreased distribution of morphine.
CI  - (c) 2024. The Author(s).
FAU - Bickel, Julian
AU  - Bickel J
AUID- ORCID: 0000-0001-8913-6649
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Aboutara, Nadine
AU  - Aboutara N
AUID- ORCID: 0000-0001-6577-0231
AD  - Research Centre Borstel Leibniz Lung Centre, Borstel, Germany.
FAU - Jungen, Hilke
AU  - Jungen H
AUID- ORCID: 0000-0002-9101-4269
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Szewczyk, Anne
AU  - Szewczyk A
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Muller, Alexander
AU  - Muller A
AUID- ORCID: 0000-0002-5566-3907
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Ondruschka, Benjamin
AU  - Ondruschka B
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Iwersen-Bergmann, Stefanie
AU  - Iwersen-Bergmann S
AUID- ORCID: 0000-0001-7687-1388
AD  - Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, 
      Hamburg, Germany. S.Iwersen-Bergmann@uke.de.
LA  - eng
PT  - Journal Article
DEP - 20240117
PL  - Germany
TA  - Int J Legal Med
JT  - International journal of legal medicine
JID - 9101456
RN  - 76I7G6D29C (Morphine)
RN  - YI7VU623SF (Propofol)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Humans
MH  - Morphine/pharmacokinetics
MH  - Palliative Care
MH  - *Propofol
MH  - Diazepam
MH  - *Burns/metabolism
PMC - PMC11004028
OTO - NOTNLM
OT  - Acute burn injury
OT  - Forensic toxicology
OT  - Morphine concentrations
OT  - Palliative treatment
OT  - Pharmacokinetic modelling
OT  - Postmortem analysis
COIS- The authors declare no competing interests.
EDAT- 2024/01/17 12:43
MHDA- 2024/04/11 06:43
PMCR- 2024/01/17
CRDT- 2024/01/17 11:03
PHST- 2023/08/28 00:00 [received]
PHST- 2024/01/08 00:00 [accepted]
PHST- 2024/04/11 06:43 [medline]
PHST- 2024/01/17 12:43 [pubmed]
PHST- 2024/01/17 11:03 [entrez]
PHST- 2024/01/17 00:00 [pmc-release]
AID - 10.1007/s00414-024-03164-9 [pii]
AID - 3164 [pii]
AID - 10.1007/s00414-024-03164-9 [doi]
PST - ppublish
SO  - Int J Legal Med. 2024 May;138(3):839-847. doi: 10.1007/s00414-024-03164-9. Epub 
      2024 Jan 17.