Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. METHODS: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. RESULTS: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. CONCLUSION: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity.

BACKGROUND: The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy. METHODS: A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded. RESULTS: The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances. CONCLUSIONS: Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low.

[Comparative analysis of 607 autopsy cases of poisoning death].

OBJECTIVE: To provide references for forensic expertise by investigating the kinds of toxicant, routes of exposure and manners of poisoning deaths, etc. METHODS: Six hundred and seven autopsy cases of poisoning deaths from 1957 to 2008 in Department of Forensic Medicine, Tongji Medical College (Tongji Forensic Science Identification Center of Hubei), were comparatively reviewed. RESULTS: In 218 cases from 1999 to 2008, more than 50% of decedents were male in the ages of 30-49. The toxicants are usually taken orally and the most common manner of death was accidental. The common substances involved in poisoning death were rodenticide, poisoning gas and insecticide. Compared to the data of 1983-1998 and 1957-1982, the common toxic agents had changed significantly. The number of cases involving insecticide and cyanide poisoning decreased in recent years, and the number of cases of rodenticide, poisoning gas, alcohols poisoning displayed an increase tendency, especially for drugs abuse. CONCLUSION: Poisoning deaths of pesticides remain a major public health problem for a long time and the awareness of prevention need to be raised, especially for the prevention of deaths from multiple poisons.

Genotoxic effects of anesthetic agents: an update.

INTRODUCTION: Exposure to anesthetics in the health environment may entail a health risk for patients and operating room personnel. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support for anesthesia care providers to improve treatment performance, increase patient safety and reduce the risks for patients and staff in the operating room. AREAS COVERED: Relevant literature was identified using MEDLINE, CINAHL® and Cochrane Library databases. Over 200 abstracts for articles published from 1980 to 2010 were examined. Original articles were reviewed and relevant citations from these articles were also considered. EXPERT OPINION: Despite some conflicting results, the current available data indicate that exposure to anesthetics, especially nitrous oxide and halogenated agents, is associated with general and genotoxic risks, whereas intravenous agents, such as propofol and its metabolites are not associated with genotoxic effects. Moreover, given that different anesthetic drugs are used in combination it is, thus, very difficult to understand whether the observed effects or absence of effects are due to an individual agent action or linked to a synergy action of different anesthetics involved. Further clinical and experimental evidence is warranted.

Treatment of local-anesthetic toxicity with lipid emulsion therapy.

PURPOSE: The use of lipid emulsion to treat local-anesthetic toxicity is discussed. SUMMARY: Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia. There is increasing evidence that lipid emulsion may be an effective treatment to reverse the cardiac and neurologic effects of local-anesthetic toxicity. A literature search identified seven case reports of local-anesthetic toxicity in which lipid emulsion was used. Lipid emulsion was found to be successful in the treatment of local-anesthetic toxicity associated with various regional anesthetic techniques and multiple local anesthetics. The majority of patients in the case reports reviewed were unresponsive to initial management of local-anesthetic toxicity with standard resuscitative measures, but all recovered completely after receiving lipid emulsion therapy. The initial dose of lipid emulsion administered varied among the case reports, as well as whether a lipid emulsion infusion was started and at what point during resuscitation. Based on the case reports reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min as soon as local-anesthetic toxicity is suspected seems most beneficial. The pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic toxicity has not been fully elucidated but likely involves increasing metabolism, distribution, or partitioning of the local anesthetic away from receptors into lipid within tissues. CONCLUSION: Lipid emulsion has been reported useful in the treatment of systemic toxicity caused by local anesthetics. The mechanism of effect is unclear, and evidence for the benefit of lipid therapy in humans is from case reports only.

Comparative analysis of 607 autopsy cases of poisoning death / 法医学杂志

OBJECTIVE@#To provide references for forensic expertise by investigating the kinds of toxicant, routes of exposure and manners of poisoning deaths, etc.@*METHODS@#Six hundred and seven autopsy cases of poisoning deaths from 1957 to 2008 in Department of Forensic Medicine, Tongji Medical College (Tongji Forensic Science Identification Center of Hubei), were comparatively reviewed.@*RESULTS@#In 218 cases from 1999 to 2008, more than 50% of decedents were male in the ages of 30-49. The toxicants are usually taken orally and the most common manner of death was accidental. The common substances involved in poisoning death were rodenticide, poisoning gas and insecticide. Compared to the data of 1983-1998 and 1957-1982, the common toxic agents had changed significantly. The number of cases involving insecticide and cyanide poisoning decreased in recent years, and the number of cases of rodenticide, poisoning gas, alcohols poisoning displayed an increase tendency, especially for drugs abuse.@*CONCLUSION@#Poisoning deaths of pesticides remain a major public health problem for a long time and the awareness of prevention need to be raised, especially for the prevention of deaths from multiple poisons.

Human exposures to immobilising agents: results of an online survey.

Cases of human exposure to veterinary injectable anaesthetics were reviewed following a literature search and completion of an online questionnaire in an attempt to provide an objective approach to the problem. The modified Glasgow Coma Scale was used to rank cases according to their severity. From the cases examined, results showed that intoxication with potent opioids, such as etorphine, carfentanil and thiafentanil, need to be treated with antagonists such as naloxone, nalmefene or naltrexone, and not with antagonists with agonistic properties, such as diprenorphine. With regard to the alpha(2)-agonists xylazine, detomidine, medetomidine and romifidine, no antagonist is currently accredited for human use. Atipamezole, a specific alpha(2)-antagonist, is widely used in veterinary medicine and has been used experimentally to reverse dexmetomidine in a study in human medicine. The high concentrations of alpha(2)-agonists being used in zoo and wildlife medicine warrant the accreditation of atipamezole for use in cases of human exposure. Knowledge and availability of the appropriate antagonist are essential in cases of human intoxication with injectable anaesthetics. Preventive measures, such as wearing gloves and eye protection, need to be used more regularly to reduce the risk of exposure.

[Crisis management during regional anesthesia including peripheral nerve block, epidural anesthesia and spinal anesthesia].

Crisis management during regional anesthesia including peripheral nerve block, epidural anesthesia and spinal anesthesia was reviewed. Common crisis which is encountered during regional anesthesia includes toxic reaction to local anesthetic drugs, allergic reaction induced by local anesthetic drugs, reaction induced by epinephrine, nerve injury, hematoma etc. Concerning peripheral nerve block, crisis encountered during brachial plexus block, interscalene block and supraclavicular block used for surgical operation of upper extremity was discussed. On the other hands, there are various common crises encountered during epidural anesthesia and spinal anesthesia. These crises include hypotension, bradycardia, total spinal anesthesia, postspinal headache and infection, and hematoma in the spinal canal. Especially, epidural hematoma and epidural abcess have possibility to cause nerve defect symptoms such as motor paralysis and sensory disturbance if appropriate treatment was not started in early stage. Moreover crisis such as cauda equina syndrome and anterior spinal cord syndrome have possibility to remain permanent and hard to cure. We anesthesiologists should make efforts to prevent crisis, to detect crisis in early stage, and to treat it in early stage.

Best evidence topic report: endotracheal intubation in gamma-hydroxybutyric acid intoxication and overdose.

A short cut review was carried out to establish whether intubation is always required in patients presenting with a decreased conscious level after gamma-hydroxybutyrate ingestion. Altogether 95 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

An unusual presentation from xylazine-ketamine.

Veterinary anesthestics have gained popularity as drugs of abuse. A case of multiple drug abuse by a 36-y-old veterinarian involved the injection of xylazine-ketamine, resulting in gastrointestinal, cardiovascular and central nervous system effects, and unexpected hypertension, tachycardia and electrocardiogram changes.

Doctors who kill themselves: a study of the methods used for suicide.

Medical practitioners have a relatively high rate of suicide. Death entry data for doctors who died by suicide or undetermined cause between 1979 and 1995 in England and Wales were used to compare methods used for suicide by doctors with those used by the general population. Methods used were analysed according to gender, occupational status and speciality, to assess the extent to which access to dangerous means influences the pattern of suicide. Self-poisoning with drugs was more common in the doctors than in general population suicides (57% vs. 26.6%; OR=3.65, 95% CI 2.85-4. 68), including in retired doctors. Barbiturates were the most frequent drugs used. Half of the anaesthetists who died used anaesthetic agents. Self-cutting was also more frequently used as a method of suicide. The finding that the greater proportion of suicide deaths in doctors were by self-poisoning may reflect the fact that doctors have ready access to drugs, and have knowledge of which drugs and doses are likely to cause death. The specific finding that a large proportion of suicides in anaesthetists involved anaesthetic agents supports this explanation. Availability of method may be a factor contributing to the relatively high suicide rate of doctors. This fact might influence clinical management of doctors who are known to be depressed or suicidal.

Severe hepatic failure occurring with T61 ingestion in an attempted suicide. Early recovery with the use of intravenous infusion of reduced glutathione.

A case of acute hepatic failure following ingestion of the veterinary euthanasia drug T61 is described. Presenting symptoms were drowsiness, disorientation, muscle hypertonia, and upper limb myoclonus, which faded within a few hours. Two days later, acute liver failure occurred, manifested as encephalopathy, jaundice, and a severe coagulopathy. The hepatic damage was thought to be due to the solvent dimethylformamide, which is the only known hepatotoxin included in the preparation utilized in the suicide attempt. High-dose (1.2 g/day) intravenous reduced glutathione was administered, with a rapid improvement of liver function. The patient was discharged after 17 days. Normalization of all liver function tests was achieved within two months. The favorable outcome in this case stands in contrast to the report of a previous case of lethal T61-induced hepatic failure. Although a different amount of dimethylformamide was ingested in each case (0.45 vs 0.60 ml/kg body wt) and individual differences in susceptibility to the effects of the hepatotoxic agent may have played a major role in these two cases, it is not unlikely that the infusion of high doses of glutathione to our patient contributed to her survival and hepatic recovery.