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.
This letter to the editor is in response to "Dangers of Mixed Martial Arts in the Development of Chronic Traumatic Encephalopathy" by authors Lim, Ho, and Ho, which was published in the International ...Journal of Environmental Research and Public Health (2019; 16: 254). This communication clarifies some potentially misleading word choices by the authors and addresses the insinuated, but not established, link between repeated transient choking episodes during martial arts training and a gradual decline in neuropsychiatric testing in the patient presented in the report.
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.
Background: Antimuscarinic delirium is associated with significant morbidity, and its management requires substantial resource allocation, including intubation, restraint, and intensive care unit ...(ICU) placement. There is controversy over the management of these patients. Physostigmine can rapidly reverse antimuscarinic delirium but has been associated with adverse effects. Objective: This study aims to assess the effect of physostigmine use on resource allocation and adverse events. Methods: This is a retrospective chart review of patients with an antimuscarinic toxidrome at a single hospital approved by the local institutional review board. A blinded abstractor recorded data from patient charts. Whether the patient was given physostigmine, intubated, restrained, or admitting to critical care was recorded. We recorded instances of seizure, vomiting, or bradycardia. The primary aim was to compare frequency of intubation as a function of physostigmine administration. Results: A total of 141 patients were identified. We found no difference between the groups in age, gender, or initial heart rate; 65 (46%) were given physostigmine, 45 (32%) were admitted to the ICU, and 29 (20%) were intubated. Patients who received physostigmine in the first 24 hours were less likely to be intubated and less likely to be admitted to an ICU. The instance of bradycardia (n = 16), vomiting (n = 27), and seizures (n = 7) was limited, and there were no significant differences between the groups. There were no associations noted between physostigmine administration and adverse effects. Conclusion and Relevance: This study demonstrated that physostigmine use is associated with decreased resource utilization (including intubation and ICU placement) without increasing rates of bradycardia, vomiting, or seizures.
Context: The opioid epidemic has included use of traditional drugs and recently newer synthetics. It is critically important to recognize and identify these new drugs both clinically and through ...appropriately designed toxicology testing. There is little available information on a synthetic gaining popularity, U-47700.
Case details: A 23-year-old female presented after using "U4" by nasal insufflation and injection. She was cyanotic with respiratory depression and responded to naloxone in the field. She was found to have non cardiogenic pulmonary edema and hemoptysis which improved with BiPAP. Urine and serum samples were analyzed using mass spectrometry, confirming 3,4-dichloro-N-(1R,2R)-2-(dimethylamino)cyclohexyl-N-methylbenzamide or U-47700. The sample was further analyzed elucidating metabolism specifics. Drug and metabolite concentrations were subsequently measured in both serum and urine. The parent compound of U-47700 was detected at 394 ng/mL and 228 ng/mL in serum and urine, respectively. Metabolites detected in appreciable amounts included the desmethyl (1964 ng/mL in urine), bisdesmethyl (618 ng/mL), desmethyl hydroxy (447 ng/mL), and bisdesmethyl hydroxy forms (247 ng/mL) of U-47700.
Discussion: U-47700 is a potent μ-opioid receptor agonist and has recently been used recreationally, contributing to hospitalizations and likely deaths in the community. This is a case report describing an exposure to U-47700 with subsequent laboratory analysis. Based upon this one case, parent U-47700 appear to be an appropriate marker of use in a serum sample. However, demethylated metabolites appear dominant as urinary markers of U-47700 use.
and ARP Position Statement: Based on the available body of scientific evidence and with the goals of promoting safety of combat sports athletes and striving for the advancement of clean sport, the ...Association of Ringside Physicians recommends the following regarding cannabis:• Use of marijuana or synthetic cannabinoids by combat sports athletes is discouraged due to unproven benefits and many known adverse effects. Acute use can impair cognition and complex motor function, which likely leads to reduced performance in combat sports. Chronic use can increase risk for heart and lung disease, several cancers, schizophrenia, and can reduce testosterone in men and impair fertility. Benefits from cannabis in most contexts, including athletic performance, have not been proven.• Use of topical purified CBD is neither encouraged nor discouraged.• Since acute cannabis intoxication can impair complex cognitive and motor function, any athlete suspected of acute intoxication at the time of competition - based on clinical judgment - should be banned from that competition.• Wide-scale regulation of cannabis based on quantitative testing has limited usefulness in combat sports, for the following reasons:∘ Cannabis is not ergogenic and is likely ergolytic.∘ Concentrations in body fluids correlate poorly with clinical effects and timing of use.∘ Access to testing resources varies widely across sporting organizations.and ARP Position Statement: Based on the available body of scientific evidence and with the goals of promoting safety of combat sports athletes and striving for the advancement of clean sport, the Association of Ringside Physicians recommends the following regarding cannabis:• Use of marijuana or synthetic cannabinoids by combat sports athletes is discouraged due to unproven benefits and many known adverse effects. Acute use can impair cognition and complex motor function, which likely leads to reduced performance in combat sports. Chronic use can increase risk for heart and lung disease, several cancers, schizophrenia, and can reduce testosterone in men and impair fertility. Benefits from cannabis in most contexts, including athletic performance, have not been proven.• Use of topical purified CBD is neither encouraged nor discouraged.• Since acute cannabis intoxication can impair complex cognitive and motor function, any athlete suspected of acute intoxication at the time of competition - based on clinical judgment - should be banned from that competition.• Wide-scale regulation of cannabis based on quantitative testing has limited usefulness in combat sports, for the following reasons:∘ Cannabis is not ergogenic and is likely ergolytic.∘ Concentrations in body fluids correlate poorly with clinical effects and timing of use.∘ Access to testing resources varies widely across sporting organizations.
This letter to the editor is in response to "The King-Devick test in mixed martial arts: the immediate consequences of knock-outs, technical knock-outs, and chokes on brain functions" by authors ...Hubbard et al., published in Brain Injury (2019; 33: 349-354). This study explored the impact of events significant enough to end mixed martial arts training sessions or matches, with "event" meaning a knock-out, technical knock-out, or event without head trauma; the measuring stick was the King-Devick test (K-D). This communication clarifies the portion of their study and manuscript focusing on "events without observed head trauma." These events without head trauma were choke-outs, near choke-outs, and non-choke submissions. Fourteen athletes sustained these types of events; nine had worse post-event K-D times, one had no change, and five had post-event improvement. Despite this non-significant result, the authors frame an argument that these non-traumatic events cause anoxic brain injury resulting in similar cerebral changes that occur in concussive injuries. This is not founded on the results in their study, nor in the literature available on the topic, which is also misrepresented in this manuscript.
Thirteen episodes of oesophageal food impaction (EFI) per 100 000 people present to a medical setting each year. Several pharmacological interventions meant to relieve such impactions have been ...explored; none have proven superior.
Perform a single-arm feasibility study of oral nitroglycerin solution for EFI.
Twenty adult patients presenting to a single urban tertiary medical centre thought to have EFI were given up to three doses of 0.4 mg nitroglycerin solution orally and evaluated for resolution of symptoms, new symptoms and vital signs. Patients with intractable vomiting, haemodynamic instability, airway compromise, oesophageal perforation, coronary ischaemia or presentation delayed greater than 12 hours were excluded.
17 of 20 enrolled subjects received the intervention. The average duration of symptoms prior to intervention was 285 min (SD=187). Four subjects did not tolerate the intervention (inability to swallow or headache). Two of 17 (11.8%) subjects obtained temporally proximal symptom resolution: 11 min after the second dose, and 7 min after the third dose. Seven also received glucagon during their visit, with 0% temporally proximal symptom resolution. Fifteen underwent endoscopy, with food bolus identified in 12. One subject had brief and mild hypotension with spontaneous resolution. Two subjects developed a headache after nitroglycerin administration. The median length of stay for those who found relief without endoscopy was 195 min (range 129-261) vs 374 min (range 122-525) among those with endoscopy.
The observed rate of relief after oral nitroglycerin solution for EFI is disappointing but comparable to previous glucagon, benzodiazepines and effervescent beverage studies, and that of placebo. Oral nitroglycerin solution appears to be well tolerated among those able to swallow, although in our sample several subjects were unable to tolerate swallowing entirely.
The manuscript purpose is to provide a resource for clinicians on the functionality and pitfalls of the rapid urine drug screen for clinical decision making. Many providers remain under-informed ...about the inherent inaccuracies. The rapid urine drug screen is the first, and often only, step of drug testing. In the majority of emergency departments the urine drug screen is a collection of immunoassays reliant on an interaction between the structure of a particular drug or metabolite and an antibody. Drugs in separate pharmacologic classes often have enough structural similarity to cause false positives. Conversely, drugs within the same pharmacologic class often have different enough structures that they may result in inappropriate negatives. This lack of sensitivity and specificity significantly reduces the test utility, and may cause decision-making confusion. The timing of the drug screen relative to the drug exposure also limits accuracy, as does detection threshold. Confirmatory steps following the initial immunoassay include chromatography and/or mass spectrometry. These are unavailable at many institutions and results rarely return while the patient is in the emergency department. In addition, institutional capabilities vary, even with confirmatory testing. Confirmation accuracy depends on a number of factors, including the extent of the catalog of drugs/metabolites that the facility is calibrated to detect and report. In summary, the standard emergency department urine drug screen is a test with extremely limited clinical utility with multiple properties contributing to poor sensitivity, specificity, and accuracy. The test should be used rarely, if ever, for clinical decision making.
Metformin is a common and generally well-tolerated medication in the treatment of diabetes but rarely has been implicated as the cause for metformin-associated lactate acidosis. This is usually ...caused by decreased elimination from renal dysfunction but is rarely described after an acute ingestion. We present a case of an acute intentional overdose of metformin in a metformin-naïve patient without renal dysfunction. The patient gradually developed altered mental status, tachypnea, hypotension, hyperglycemia, hypoglycemia, hypothermia, and vasoplegic shock unresponsive to vasopressor support. Despite attempts at alkalinization, the patient developed a lactic acidosis with a pH of 6.9 and lactate of 33 mmol/L. Hemodialysis was performed with rapid improvement of clinical status. This case provides a clinical context in the acute setting and illustrates the rare need for extracorporeal support in this setting, which may be lifesaving.
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