Treating Diphenhydramine Overdose: A Literature Review of Currently Available Treatment Methods.

From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.

Successful Management of Severe Bupropion Toxicity with Lipid Emulsion Therapy: A Complex Case Report and Literature Review.

This case report presents the management of a 53-year-old female with a complex psychiatric history who ingested multiple medications, resulting in severe cardiovascular compromise and subsequent respiratory failure. The patient's ingestion included clonidine, fluoxetine, gabapentin, quetiapine and bupropion. Initial treatment involved supportive measures, including fluid resuscitation, bicarbonate infusion and correction of electrolyte imbalances. Despite these interventions, the patient remained haemodynamically unstable, requiring multiple vasopressors. Lipid emulsion therapy was initiated and led to a remarkable improvement in the patient's cardiovascular status. However, she developed acute respiratory distress syndrome (ARDS) and required prolonged mechanical ventilation. Steroid therapy was initiated to manage the ARDS, and the patient was successfully extubated on day 6. The case highlights the potential effectiveness of lipid emulsion therapy in managing bupropion toxicity, but emphasises the need for further research to establish clear guidelines on dosing, timing and safety protocols. Adverse effects associated with lipid emulsion therapy must be carefully considered. Individualised decision-making and patient-centred care is crucial in optimising outcomes in cases of bupropion toxicity. LEARNING POINTS: Recognise the cardiotoxic effects of bupropion toxicity: be vigilant in identifying cardiotoxic effects such as prolonged QTc, hypotension and arrhythmias in cases of bupropion toxicity.Consideration of intravenous lipid emulsion therapy for toxic injections of lipophilic drugs such as bupropion: in severe lipophilic drug ingestions, such as bupropion, consider using intravenous lipid emulsion therapy as a potential treatment option.Individualised decision-making and monitoring is necessary when using lipid emulsion therapy: tailor treatment based on the patient's condition and closely monitor for responses and potential adverse effects when using lipid emulsion therapy.

Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy.

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Complications After Dental Sedation: A Myotonic Mystery Case Report.

Myotonic dystrophy (dystrophia myotonica; DM) is an uncommon progressive hereditary muscle disorder that can present with variable severity at birth, in early childhood, or most commonly as an adult. Patients with DM, especially type 1 (DM1), are extremely sensitive to the respiratory depressant effects of sedative-hypnotics, anxiolytics, and opioid agonists. This case report describes a 37-year-old male patient with previously undiagnosed DM1 who received dental care under minimal sedation using intravenous midazolam. During the case, the patient experienced 2 brief episodes of hypoxemia, the second of which required emergency intubation after propofol and succinylcholine and resulted in extended hospital admission. A lipid emulsion (Liposyn II 20%) infusion was given approximately 2 hours after the last local anesthetic injection due to slight ST elevation and suspicion of local anesthetic toxicity (LAST). Months after treatment, the patient suffered a fall resulting in a fatal traumatic brain injury. Complications noted in this case report were primarily attributed to the unknown diagnosis of DM1, although additional precipitating factors were likely present. This report also provides a basic review of the literature and clinical guidelines for managing myotonic dystrophy patients for dental care with local anesthesia, sedation, or general anesthesia.

Knowledge, attitude and practice on usage and toxicity of local anaesthetic agents (LA) amongst health care professionals in obstetrics and gynaecology.

A sound knowledge of LA and their dosage is essential for effective anaesthesia and patient safety as LA toxicity could be potentially life-threatening and clinicians undertaking LA procedures must be competent in early recognition of toxicity and instigating remedial measures timely. This is a prospective national-level survey using self-administered questionnaires among health care professionals in Obstetrics and Gynaecology primarily based in Worcestershire Acute Hospital NHS Trust and further extended to other regions of the United Kingdom. The survey was focussed on evaluating the knowledge, attitude and practice (KAP) of the common local anaesthetic agents, their dosage, early recognition and management of LA systemic toxicity(LAST). We understood that all groups of health care professionals did not demonstrate adequate knowledge of safe and effective use of LA agents. We thereby propose an accredited knowledge-based learning module, laminated safety information cards for LA use and ensuring availability of Lipid-emulsion therapy in clinical areas.IMPACT STATEMENTWhat is already known on this subject? Health care professionals using LA should have sufficient knowledge of LA including the required and maximum dose allowance, pharmacokinetic properties, possible complications and management of systemic toxicity. The lack this can trigger potentially fatal and life-threatening complications if misused. Therefore, the key objectives of the use of LA in clinical settings are to optimise pain management while ensuring safe practice.What do the results of this study add? We understood that all groups of health care professionals did not demonstrate adequate knowledge of the safe and effective use of LA agents and appropriate management of its toxicity. This highlights the urgent need for extending awareness among the professionals on the safe administration of LA, early identification and prompt management of LAST. This will improve not only the safety but also the overall patient experience and quality of care.What are the implications of these findings for clinical practice and/or further research? We thereby propose that an accredited knowledge-based module on safe administration and safety concerns of LA must be made compulsory for all those administering LA. Laminated safety information cards on LA with explicit algorithms/guidelines should be made available in all clinical areas to avoid any delays in the management of toxicity. Moreover, all health-care institutions must ensure the availability of Lipid Emulsion Therapy.

A successful treatment with intravenous lipid emulsion therapy in a child with verapamil poisoning.

In recent years, intravenous lipid emulsion therapy (ILE) was used for lipophilic drug intoxications, and successful results were obtained. In the literature, there is a small number of reported cases about verapamil intoxication and ILE therapy in the pediatric age group. We used ILE therapy in a 14-year-old girl with verapamil intoxication in the 2nd h of the pediatric intensive care unit stay, before using traditional treatments such as glucagon and hyperinsulinemic euglycemia. She had resistant bradycardia and hypotension which was unresponsive to inotropic agents and a successful result was obtained after using ILE treatment. We believe our report may contribute to the early use of ILE therapy for toxicity with calcium channel blockers such as verapamil in pediatric patients.

First Case of Acute Poisoning with Amiodarone and Flecainide in Attempted Suicide Successfully Managed with Lipid Emulsion Therapy in the Emergency Department: Case Report and Literature Review.

Acute antiarrhythmics poisoning represents a challenge in the Emergency Department (ED). These patients often develop malignant arrhythmias in need of exceptional therapeutic measures in the ICU. We report a 47-year-old patient admitted to the ED 5 h after the ingestion of a large dose of amiodarone and flecainide in a suicide attempt. During their ED stay, the patient developed signs of cardiotoxicity evidenced by electrocardiogram and ventricular arrhythmias. The toxicological results showed a level of 4.8 mg/L amiodarone and 2.98 mg/L flecainide. He was successfully treated in the ED using a large dose of sodium bicarbonate and lipid emulsion therapy. After hospital admission, he remained stable, with no need for exceptional therapeutic measures such as mechanical circulatory support, cardiac pacing or ECMO. We emphasize the importance of an early start of pharmacological therapies in the ED, which might improve the outcome in antiarrhythmic acute poisoning.

A Case of Trazodone Overdose Successfully Rescued With Lipid Emulsion Therapy.

Trazodone is a very common medication prescribed to patients who suffer from insomnia. The toxic effects of trazodone remain ill-defined with no current known antidote therapy. Lipid emulsion therapy has been described as general rescue therapy in toxicology. Unfortunately, only select substance overdoses respond to lipid emulsion therapy. The authors present a unique application of lipid emulsion therapy in a post-cardiac arrest situation involving a trazodone overdose.

Bupropion Overdose Complicated by Cardiogenic Shock Requiring Vasopressor Support and Lipid Emulsion Therapy.

BACKGROUND: Bupropion overdose is a commonly encountered presentation in the emergency department (ED). While the majority of cases resolve with supportive care, serious adverse effects, including seizures, cardiogenic shock, and death, can occur. Intravenous lipid emulsion (ILE) therapy has been utilized for a multitude of poisonings with varying levels of success. Although a number of cases suggest the value of ILE therapy in cases of bupropion overdose, more recent data propose that its role may be overstated. CASE REPORT: A young woman presented to the ED with altered mental status complicated by seizure after bupropion overdose. She subsequently developed cardiogenic shock requiring vasopressor support. Bedside echocardiogram revealed a decreased left ventricular ejection fraction (LVEF). She received ILE therapy with significant improvement in both hemodynamic status and LVEF by bedside ultrasound. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although the majority of patients presenting with bupropion overdose improve with supportive care, life-threatening sequelae are possible. ILE therapy has shown promise in a variety of different overdose situations, although the evidence in cases of bupropion poisoning has been varied, and it has traditionally been utilized as a last-line rescue modality. Based on hemodynamic parameters and bedside ultrasound, this case suggests that early initiation of ILE therapy should be considered in these cases, as the potential benefits likely outweigh the theoretical risks.

Tumescent Anesthesia for Dermatosurgical Procedures Other Than Liposuction.

CONTEXT: Tumescent local anesthesia is a form of local anesthesia, which is a technique in which a dilute local anesthetic solution is injected into the subcutaneous tissue until it becomes firm and tense. Originally developed to facilitate liposuction, the use of tumescent anesthesia has expanded to other dermatological and plastic surgery procedures, as well as to other disciplines, including endocrine and vascular surgeries. For infiltration local anesthesia, the conventional dosage of lidocaine is up to 4.5 mg/kg, and that with adrenaline is up to 7 mg/kg; however, in liposuction using tumescent anesthesia, the recommended maximum dose of lidocaine with adrenaline is up to 55 mg/kg. There are several important pharmacological, pharmacokinetic, and pharmacodynamic factors that need to be considered in the administration of tumescent anesthesia leading to considerable interdisciplinary differences of opinion with respect to the maximum dose of local anesthetic permissible. Although several studies and publications have studied these issues in liposuction extensively, the role of tumescent anesthesia in other indications has not been reviewed adequately. AIMS AND OBJECTIVES: The aim of this study was to discuss the science behind tumescent anesthesia, its applications, and safety considerations in different dermatosurgical procedures other than liposuction. MATERIALS AND METHODS: For this review, a systematic literature search in PubMed, Embase, Web of Science, Cochrane Library, Central, Emcare, Academic Search Premier, and ScienceDirect was conducted for safety studies on tumescent anesthesia. CONCLUSION: Tumescent anesthesia is generally very well accepted by patients and is relatively safe at the recommended doses. Nonetheless, one must be vigilant about the signs and symptoms of LAST, as they may not manifest until several hours after the procedure. Lipid emulsion therapy should be readily available and could prove life-saving in such situations.

Intravenous lipid emulsion modifies synaptic transmission in hippocampal CA1 pyramidal neurons after bupivacaine-induced central nervous system toxicity.

Local anesthetics can cause severe toxicity when absorbed systemically. Rapid intravenous administration of lipid emulsion (LE) is the standard of care for severe local anesthetic systemic toxicity which can cause cardiovascular and central nervous system (CNS) injury. The biological mechanism by which LE alleviates CNS toxicity remains unknown and understudied. Previous research has suggested that local anesthetics cause an imbalance of excitatory and inhibitory transmission in the brain. Therefore, this study aimed to observe the effect of LE on glutamate- and GABA-induced currents in CA1 pyramidal neurons after bupivacaine-induced CNS toxicity. We further characterized post-synaptic modifications in these cells to try to elucidate the mechanism by which LE mediates bupivacaine-induced CNS toxicity. Sprague-Dawley rats received intravenous bupivacaine (1 mg kg-1  min-1 ) in either normal saline or LE (or LE without bupivacaine) for 5 min. An acute brain slice preparation and a combination of whole-cell patch clamp techniques and whole-cell recordings were used to characterize action potential properties, miniature excitatory, and inhibitory post-synaptic currents, and post-synaptic modifications of excitatory and inhibitory transmission in CA1 hippocampal pyramidal neurons. The expression level of GABAA receptors were assessed with western blotting, whereas H&E and TUNEL staining were used to assess cytoarchitecture and apoptosis levels respectively. Bupivacaine treatment significantly increased the number of observed action potentials, whereas significantly decreasing rheobase, the first interspike interval (ISI), and hyperpolarization-activated cation currents (Ih) in CA1 pyramidal neurons. LE treatment significantly reduced the frequency of miniature inhibitory post-synaptic currents and enhanced GABA-induced paired pulse ratio with 50 ms interval stimulation in bupivacaine-treated rats. Regulation of GABAA levels is a promising mechanism by which LE may ameliorate CNS toxicity after systemic absorption of bupivacaine.

Successful Management of Adolescent Bupropion Overdose with Intravenous Lipid Emulsion Therapy.

Bupropion overdose in the pediatric setting poses significant potential for toxicity. We present the case of a 15-year-old female patient presenting with intentional bupropion overdose resulting in generalized tonic-clonic seizures, severe acidosis, vomiting, and tachycardia after ingestion of between 1,650 to 9,000 mg (24-133 mg/kg) of bupropion. The patient was admitted to pediatric intensive care unit (PICU) where toxicity was resolved promptly following administration of intravenous lipid emulsion (ILE) infusion. ILE is a first-line treatment for other forms of toxicity including unintended local anesthetic administration. ILE use is not a first-line treatment in this setting, but this case presents a positive subsequent patient outcome.

Re-elevation of serum amlodipine level after lipid emulsion therapy in an overdose case.

WHAT IS KNOWN AND OBJECTIVE: Amlodipine overdose is common; however, the dose and timing of intravenous lipid emulsion (ILE) therapy as a management strategy remain debatable. CASE DESCRIPTION: A 73-year-old man received a single bolus (1.5 mL/kg) of ILE therapy following massive ingestion of multiple drugs, including amlodipine. After approximately 20 hours of ILE therapy, the serum amlodipine level that had decreased from 90.2 to 49.9 ng/mL increased to 70.8 ng/mL. WHAT IS NEW AND CONCLUSION: A single bolus (1.5 mL/kg) of ILE therapy is probably insufficient to completely capture and partition serum amlodipine following amlodipine overdose.

Intravenous lipid emulsion therapy for acute clomipramine intoxication in rats.

AIM: In this study, to assess the utility of lipid emulsion (ILE) therapy as a treatment option for overdoses of lipophilic drugs, we examined the detoxification effect of ILE therapy in rats that were administered overdoses of the tricyclic antidepressant clomipramine hydrochloride (CMI). METHODS: Female Wistar rats were orally administered 50 mg/kg CMI five times in 2-h intervals to examine whether intralipos accelerated the elimination of CMI in the peripheral blood. Rats were divided into the intralipos (i.v. 2 g/kg intralipos) and placebo (i.v. saline) groups. The concentrations of CMI and desmethylclomipramine (DMCMI), a metabolite of CMI, in blood were measured over time by high-performance liquid chromatography. We then gave the animals 100 mg/kg CMI orally to examine whether intralipos could inhibit the distribution of CMI. The CMI and DMCMI concentrations in peripheral blood, liver, and brain were measured 60 min after intralipos administration. RESULTS: The blood concentration of CMI was significantly higher in the intralipos group than in the placebo group at 60 and 120 min. After a single administration of 100 mg/kg CMI, the ratio of the concentration of CMI in liver/serum was significantly lower in the intralipos group than in the placebo group. We also found a significantly faster elimination rate for CMI in peripheral blood in the intralipos group than in the placebo group. CONCLUSION: The distribution of CMI from blood to tissue was suppressed by intralipos. Therefore, ILE therapy is a promising candidate for the treatment of overdoses of lipophilic drugs.

The Use of High-dose Insulin Infusion and Lipid Emulsion Therapy in Concurrent Beta-blocker and Calcium Channel Blocker Overdose.

Patients admitted with the presumed coingestion of beta-blockers (BBs) and calcium channel blockers (CCBs) should be initially managed in accordance with standardized resuscitation protocols (the airway, breathing, and circulation (ABC) approach). Additionally, more specific interventions should be promptly attempted. Intravenous glucagon and calcium salts have long been used in the treatment of BB and CCB toxicities. We present a case of a severe, concurrent BB and CCB toxicity resulting in cardiovascular collapse refractory to vasopressors. The administration of high-dose insulin (HDI) and lipid emulsion therapy (LET) resulted in a significant improvement in hemodynamics with an overall favorable outcome in the patient.

Treatment of Amlodipine Intoxication with Intravenous Lipid Emulsion Therapy: A Case Report and Review of the Literature.

We report the case of a 25-year-old female presenting to the emergency department after committing suicide by ingesting 100 mg amlodipine. The patient was initially treated with intravenous fluids, calcium gluconate, catecholamines and glucagone without effect. The clinical condition of the patient improved quickly and dramatically on the 20th minute of intravenous lipid emulsion (ILE) therapy. Different treatment methods have been developed for calcium channel blocker intoxication over the last years. Among these, lipid emulsion therapy has risen over the last decade as a salvation in cases which do not respond to other treatments. However, given the paucity of data, there are conflicting recommendations about the indications, dose and timing of ILE in the literature. In the light of this case report, we review the literature and discuss whether ILE therapy can find itself a place among first-line therapy recommendations.

Lesson of the month 1: Acute flecainide overdose and the potential utility of lipid emulsion therapy.

Lipid-emulsion therapy (Intralipid®) has been advocated as a potential treatment for the management of cardio-toxicity arising from lipid-soluble drugs, particularly those acting upon sodium channels. This, on the basis of a number of ex vivo studies and animal models, suggests that partitioning a drug into lipid could alter its pharmacokinetics and result in significant clinical improvements. Its subsequent use in clinical case series has been seen as confirmation of this mechanism of action. While there are undoubtedly instances where lipid emulsion therapy has been associated with a desirable outcome in humans, as described in this case report, clinicians are reminded that they should not attribute causality, on this basis alone.

Clinical applications of intravenous lipid emulsion therapy.

Intravenous lipid emulsion (ILE; Intralipid) therapy, a standard treatment in local anesthetic toxicity, has demonstrated therapeutic efficacies for a number of different drug class-mediated toxicities. Some of these varied drug groups include antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. To meet the objective of describing the growing number of indications for Intralipid therapy and any diverse effects and/or failures of Intralipid therapy in reversing multiple drug toxicities, we queried several Internet search engines with the key words "intravenous lipid emulsion therapy," "Intralipid," "lipid emulsion," and "local anesthetic systemic toxicity," resulting in the identification of 31 case reports for descriptive analysis. These case reports included 49 separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The education of clinicians regarding the beneficial and varied roles of Intralipid therapy in different clinical settings is warranted, particularly in terms of the potential for Intralipid therapy to reverse the toxicities of non-local anesthetic drugs.

Uso de las emulsiones lipídicas en intoxicaciones por anestésicos locales y otras intoxicaciones: evidencia actual / Use of lipid emulsions in poisoning by local anesthetics and other poisonings: current evidence

Objetivo: realizar una revisión narrativa con la evidencia de la composición, mecanismo de acción e indicaciones para el uso de emulsiones lipídicas como antídoto, en la toxicidad por anestésicos locales y otras intoxicaciones. Métodos: se realizó una búsqueda bibliográfica en PubMed, Scielo y Lilacs usando las palabras claves "lipid emulsion", "therapy toxicology", "lipid therapy toxicology", "intravenous lipid therapy toxicology", "fat emulsion toxicology" "local anesthetic toxicity" y "lipid sink", identificando información relevante relacionada con su fisiopatología y su uso publicada entre 1960 y 2013. Resultados: las emulsiones lipídicas usualmente se han utilizado como suplemento nutricional, su uso también se aprobó para el tratamiento de la intoxicación por anestésicos locales como bupivacaína gracias a diferentes mecanismos de acción como: el efecto de inmersión lipídica, lipid flux y los efectos en el transporte de ácidos grasos en la mitocondria, entre otros. Aunque los resultados en intoxicaciones con beta-bloqueadores, bloqueadores de canales de calcio y antidepresivos tricíclicos han sido controversiales y no deben anteponerse al manejo tradicional, registros como el LIPAEMIC evidencian mejoría en resultados como escalas de coma Glasgow, algunas variables hemodinámicas y mayor sobrevida. Conclusiones: no existe una forma de predecir la respuesta a la terapia lipídica ni las consecuencias y hasta la fecha no deben reemplazar tratamientos que el médico considere apropiados para el manejo del paciente.

Objective: To perform a narrative review with evidence of the composition mechanism of action and indications for the use of lipid emulsions as an antidote in local anesthetic toxicity and other poisonings. Methods: We performed a bibliographic research by using PubMed, Scielo and Lilacs using the keywords "lipid emulsion therapy toxicology", "lipid therapy toxicology", "intravenous lipid therapy toxicology", "fat emulsion toxicology" and "lipid sink", identifying relevant information related to, published between 1960 and 2013. Results: Lipid emulsions have been used as a nutritional supplement, its use is also approved for the treatment of poisoning by local anesthetics such as bupivacaine through different mechanisms of action such as: the effect of lipid sink, lipid flux and effects on transport fatty acids in mitochondria, among others. Although the results in other poisonings as beta-blockers, calcium channel blockers and tricyclics have been controversial and should not take precedence over traditional management. LIPAEMIC record show improved results as Glasgow coma scale, hemodynamic variables and survival. Conclusion: There is no way to predict the response to lipid therapy nor the consequences, and that's why until this day it should not replace any treatment that the physician considers appropriate for the management of his patient.