Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats.


Journal

Clinical toxicology (Philadelphia, Pa.)
ISSN: 1556-9519
Titre abrégé: Clin Toxicol (Phila)
Pays: England
ID NLM: 101241654

Informations de publication

Date de publication:
05 2019
Historique:
pubmed: 12 10 2018
medline: 25 2 2020
entrez: 12 10 2018
Statut: ppublish

Résumé

In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning. In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays. Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment. The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals. Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.

Sections du résumé

BACKGROUND
In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.
METHODS
In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.
RESULTS
Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.
DISCUSSION
The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.
CONCLUSION
Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.

Identifiants

pubmed: 30307341
doi: 10.1080/15563650.2018.1520241
doi:

Substances chimiques

Analgesics, Opioid 0
Anesthetics, Intravenous 0
Biomarkers 0
Cholinesterase Inhibitors 0
GPI-Linked Proteins 0
Soman 96-64-0
Acetylcholinesterase EC 3.1.1.7
Ache protein, rat EC 3.1.1.7
Thiopental JI8Z5M7NA3
Fentanyl UF599785JZ
Propofol YI7VU623SF

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

343-349

Auteurs

Katharina Marquart (K)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

Julia Herbert (J)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

Niko Amend (N)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

Horst Thiermann (H)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

Franz Worek (F)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

Timo Wille (T)

a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.

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Classifications MeSH