BACKGROUND: The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning (AOPP). 相似文献
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. 相似文献
BACKGROUND:Penehyclidine is a newly developed anticholinergic agent.We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning(OP)patients.METHODS:We searched the Pubmed,Cochrane library,EMBASE,Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical literature(CBM)and Wanfang databases.Randomized controlled trials(RCTs)recruiting acute OP patients were identifi ed for meta-analysis.Main outcomes included cure rate,mortality rate,time to atropinization,time to 60%normal acetylcholinesterase(AchE)level,rate of intermediate syndrome(IMS)and rate of adverse drug reactions(ADR).RESULTS:Sixteen RCTs involving 1,334 patients were identifi ed.Compared with the atropineor penehyclidine-alone groups,atropine combined with penehyclidine significantly increased the cure rate(penehyclidine+atropine vs.atropine,0.97 vs.0.86,RR 1.13,95%CI[1.07–1.19];penehyclidine+atropine vs.penehyclidine,0.93 vs.0.80,RR 1.08,95%CI[1.01–1.15])and reduced the mortality rate(penehyclidine+atropine vs.atropine,0.015 vs.0.11,RR 0.17,95%CI[0.06–0.49];penehyclidine+atropine vs.penehyclidine,0.13 vs.0.08,RR 0.23,95%CI[0.04–1.28]).Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery,the rate of IMS and the rate of ADR.Compared with a single dose of atropine,a single dose of penehyclidine also signifi cantly elevated the cure rate,reduced times to atropinization,AchE recovery,and rate of IMS.CONCLUSION:Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate,mortality rate,time to atropinization,AchE recovery,IMS rate,total ADR and duration of hospitalization.Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone. 相似文献
1.?Organophosphorus pesticides (OPs) are known to interact with human ATP-binding cassette drug efflux pumps. The present study was designed to determine whether they can also target activities of human solute carrier (SLC) drug transporters.
2.?The interactions of 13 OPs with SLC transporters involved in drug disposition, such as organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), organic anion transporters (OATs) and organic anion transporting polypeptides (OATPs), were mainly investigated using transporter-overexpressing cell clones and fluorescent or radiolabeled reference substrates.
3.?With a cut-off value of at least 50% modulation of transporter activity by 100?µM OPs, OAT1 and MATE2-K were not impacted, whereas OATP1B1 and MATE1 were inhibited by two and three OPs, respectively. OAT3 activity was similarly blocked by three OPs, and was additionally stimulated by one OP. Five OPs cis-stimulated OATP2B1 activity. Both OCT1 and OCT2 were inhibited by the same eight OPs, including fenamiphos and phosmet, with IC50 values however in the 3–30?µM range, likely not relevant to environmental exposure.
4.?These data demonstrated that various OPs inhibit SLC drug transporter activities, especially those of OCT1 and OCT2, but only when used at high concentrations not expected to occur in environmentally-exposed humans. 相似文献