Precipitated opioid withdrawal in a patient started on olanzapine/samidorphan.

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.

Prolonged venom-induced consumptive coagulopathy following Mangshan pit viper (Protobothrops mangshanensis) envenomation despite Hemato Polyvalent antivenom administration.

This case report summarizes an envenomation by the Mangshan pit viper (Protobothrops mangshanensis), a rare, endangered, venomous snake endemic to Mount Mang of China, and the first reported use of Hemato Polyvalent antivenom (HPAV) for this species. The snakebite occurred in a United States zoo to a 46-year-old male zookeeper. He presented via emergency medical services to a tertiary center after sustaining a single P. mangshanensis bite to the abdomen and was transported with antivenom from the zoo. Within 2 hours of envenomation, he developed oozing of sanguineous fluid and ecchymosis at the puncture site, and about 4 hours post-bite, was treated with HPAV. His coagulation profile fluctuated with the following pertinent peak/nadir laboratory values and corresponding hospital day (HD): undetectable fibrinogen levels, d-dimer 8.89 mg/L and 7.43 mg/L, and INR 2.97 and 1.46 on HD zero and three, respectively. Other peak/nadir values included hemoglobin 9.7 g/dL and creatinine phosphokinase 2410 U/L on HD four and platelets 81 × 109/L on HD seven. The patient received a total of 30 vials of HPAV over 5 days and 1 unit of cryoprecipitate on HD six. Upon discharge on HD eight, laboratory studies were normalizing, except for platelets, and edema stabilized. This case describes an acute, recurrent, and prolonged venom-induced consumptive coagulopathy despite prompt administration and repeated doses of HPAV.

Outcomes of Emergency Department Patients With Opioid Use Disorder Utilizing a Virtual Addiction Bridge Clinic: A Case Series.

OBJECTIVES: Within the last decade, there has been a dramatic increase in the rate of emergency department (ED) visits and death from opioid overdose. Those who present to the ED are at high risk for subsequent morbidity and mortality. Despite effective treatment, many patients do not get rapidly connected to outpatient care. The aim of this investigation was to describe outpatient treatment engagement after ED discharge among patients with opioid use disorder (OUD) enrolled in a virtual Addiction Bridge Clinic (ABC). METHODS: This was a retrospective case series describing an ED-initiated referral for rapid telehealth follow-up among patients with OUD. The primary outcome was addiction treatment engagement among those who completed the initial virtual ABC visit (engaged in ABC) vs. those who did not complete an ABC visit (Not engaged in ABC) at 1 week, 1 month, and 3 and 6 months timepoint intervals after the initial ED presentation. RESULTS: Of the N = 201 patients referred to the ABC between March and December 2021, a majority were Black (71%) and male (77%). Of the 201 referrals, 85 (42%) completed an initial ABC telehealth visit. Subsequent treatment engagement was 26% at 1 week, 26% at 1 month, 22% at 3 months, and 18% at 6 months after the index ED visit. CONCLUSIONS: A telehealth-enabled virtual addiction bridge clinic is one potential approach to reduce barriers to rapid treatment access. Strategies are needed to improve subsequent addiction treatment engagement after a virtual addiction bridge clinic visit.

Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.

Background: Buprenorphine treatment has been associated with reduced non-prescribed opioid use and opioid related overdose (OD). We evaluated initial outcomes of rapid induction onto extended-release injectable buprenorphine (BUP-XR) within 7 days of emergency department presentation for unintentional OD. Methods: Between February 2019-February 2021, N = 19 patients with opioid use disorder received buprenorphine/naloxone (4/1 mg), followed by BUP-XR (300 mg) at induction and continued BUP-XR outpatient for 6 months. Primary outcomes included adverse events, repeat OD, and death. Results: For patients who received at least one dose of BUP-XR, there were no treatment related serious adverse events or symptoms of precipitated withdrawal. In addition, there were no repeat visits for ODs or deaths within 6 months of the initial OD. Discussion: These preliminary findings support the need for larger controlled clinical trials to examine the safety and efficacy of rapid induction of BUP-XR in patients with opioid use disorder at high risk of opioid OD. Rapid induction onto long-lasting injectable buprenorphine may be a promising and protective treatment approach in the future.

Evaluation of Strontium Interference in Calcium Measurement Procedures and Content in Supplements as Measured by ICP-MS.

BACKGROUND: Bone health supplements containing strontium are available without prescription, however, the effects of strontium interference on clinical laboratory calcium measurement procedures are unknown. METHODS: To evaluate strontium interference on total calcium measurements, plasma pools with exogenously added strontium were measured by 3 total calcium measurement procedures. For ionized calcium measurements, whole blood pools prepared with exogenously added strontium were measured by 2 ionized calcium measurement procedures. An inductively coupled plasma mass spectrometry assay (ICP-MS) was validated for research measurements of strontium content in commercially available supplements. RESULTS: Exogenous strontium addition to plasma caused positive bias for total calcium measurements. Strontium concentrations of 1.0 mg/dL (0.114 mmol/L), 2.5 mg/dL (0.284 mmol/L), and 5.0 mg/Dl (0.568 mmol/L) resulted in mean biases of 1.9% to 3.5%, 4.9% to 9.0%, and 10.8% to 19.2%, respectively, for total calcium measurement procedures. Biases for ionized calcium measurements were less than 4.5% for a strontium concentration of 5.0 mg/dL (0.568 mmol/L). An in-house-developed ICP-MS assay for strontium in commercially available supplements exhibited within-laboratory and within-run coefficients of variation of less than 3%, and a linear response was obtained over the assay analytical measurement range of 10 to 100 000 ng/mL (0.0001 to 1.141 mmol/L). Strontium recovery for the ICP-MS assay was 97.1% to 105.3%. The largest amount of strontium measured in dietary supplements was 395 mg in a 1054 mg tablet. CONCLUSIONS: Some dietary supplements contain larger amounts of strontium than indicated on the product label. High concentrations of strontium may cause significant interference for total calcium measurement procedures, but ionized calcium measurement procedures are not significantly affected.

Clinical characteristics and outcomes using dexmedetomidine in nonintubated patients: A poison center observational study.

PURPOSE: Dexmedetomidine is a central α2 agonist commonly used on intubated patients. It is increasingly being used off-label in nonintubated agitated patients. We sought to determine the overall clinical course, adverse effects, and need for subsequent mechanical ventilation in toxicology patients after treatment with dexmedetomidine. METHODS: This was a retrospective cohort study conducted by chart review of electronic records from the Virginia Poison Control Center from January 1, 2019 to February 4, 2022. Inclusion criteria consisted of all poison center cases where dexmedetomidine was used. The primary outcome was the presence or absence of clinical improvement following dexmedetomidine use. Secondary outcomes included adverse effects, subsequent intubation, or death. RESULTS: During this study period, there were 220 cases in which dexmedetomidine was used to treat agitation. After exclusions, 70 cases were analyzed. The categories included antimuscarinic (n = 19), polysubstance (n = 16), sedative withdrawal (n = 10), unknown agitation (n = 7), sympathomimetic (n = 5), baclofen withdrawal (n = 3), unknown ingestion (n = 3), sedative/hypnotic (n = 2), antipsychotic (n = 2), hallucinogenic (n = 2), and opioid withdrawal (n = 1). Clinical improvement occurred in 62 of 70 patients (89%). There were no deaths. A total of 4 patients were intubated after starting dexmedetomidine, 2 for refractory agitation and 2 for hypoxia after aspiration. CONCLUSION: Global clinical improvement was observed in the agitated toxicology patients administered dexmedetomidine. There was one case of intubation secondary to oversedation. Dexmedetomidine could be a useful adjunctive treatment for agitated toxicologic patients but should be studied further before routinely used.

Retained bullets and lead toxicity: a systematic review.

INTRODUCTION: Lead toxicity secondary to retained bullet(s) (RB) after a penetrating gunshot wound is a rare but likely underdiagnosed condition, given the substantial number of firearm injuries in the United States. There is currently no consensus on the indications for surveillance, chelation, or surgical intervention. OBJECTIVE: The purpose of our review is to summarize the literature on systemic lead toxicity secondary to RBs to help guide clinicians in the management of these patients. METHODOLOGY: The primary literature search was conducted in Medline (PubMed), EMBASE, Cochrane, and CENTRAL using the following MESH terms: "chelation" and "lead poisoning" or "lead toxicity" or "lead" and "bullet" or "missile" or "gunshot", or "bullet". RESULTS: The search identified 1,082 articles. After exclusions, a total of 142 articles were included in our final review, the majority of which were case reports. Several factors appear to increase the risk of developing lead toxicity including the location of the RB, the presence of a fracture or recent trauma, number of fragments, hypermetabolic states, and bullet retention duration. Particularly, RBs located within a body fluid compartment like an intra-articular space appear to be at a substantially higher risk of developing lead toxicity. Even though patients with lead toxicity from RBs will have similar symptoms to patients with lead toxicity from other sources, the diagnosis of lead poisoning may occur months or years after a gunshot wound. Symptomatic patients with high blood lead levels (BLLs) tended to improve with a combination of chelation and surgical removal of RBs. CONCLUSIONS: We suggest surveillance with serial BLLs should be performed. Patients with intra-articular RBs appear to be at increased risk of lead toxicity and if possible, early surgical removal of the RBs is warranted, especially given that signs of toxicity are vague, and patients may not have access to follow-up. Long-term chelation should not be used as a surgical alternative and management should be multidisciplinary.

Systemic toxicity from subcutaneous brimonidine injection successfully treated with naloxone.

Brimonidine is a topical ophthalmic alpha-2 adrenergic agonist solution used to treat glaucoma. The toxidrome includes drowsiness, lethargy, hypotension, bradycardia, and respiratory depression when ingested in infants. We report a case of intentional subcutaneous injection of brimonidine in an elderly patient resulting in hypotension and CNS depression that responded to naloxone. A 73-year-old female with a past medical history significant for glaucoma, hypertension, and indwelling pacemaker presented to the emergency department after injecting her brimonidine tartrate ophthalmic solution subcutaneously (SQ). The patient was not taking any antihypertensive medications or opioids. Initial presentation consisted of lethargy, a paced rhythm of 60 bpm, and blood pressure of 91/24 mmHg with a MAP of 46. Due to central nervous system depression, 3 mg of intranasal naloxone was administered. The patient was treated with intravenous fluids and escalating doses of naloxone and required a continuous infusion. Mental status and vital signs subsequently improved. The patient was admitted to the ICU and naloxone was subsequently weaned over 12 h. Systemic central alpha-2 adrenergic agonist toxicity resulted from SQ brimonidine injection. Central alpha-2 adrenergic agonist overdoses present as sympatholytic effects including CNS depression, bradycardia, hypotension, and may mimic the opioid toxidrome. Brimonidine SQ injection has not previously been reported and this case has similar findings to other central alpha-2 adrenergic agonist poisonings. Naloxone has previously shown variable reversal of CNS depression in central alpha-2 overdose. In this case, high-dose naloxone was useful for reversing CNS depression and hemodynamic instability.

Skin Necrosis Following Inadvertent Dermal Injection of Extended-release Buprenorphine.

INTRODUCTION: Extended-release subcutaneous buprenorphine injection is a relatively new formulation and clinicians are still gaining experience with its use. There is sparse literature available on adverse events. We describe a case of skin necrosis associated with the injection site of extended-release buprenorphine. CASE REPORT: A 35-year-old reported immediate swelling and eventual skin breakdown near his buprenorphine injection site. He was found to have ulceration down to the subcutis with no evidence of infection. The patient followed up with dermatology and underwent debridement of the site. The injection site healed with scar formation. DISCUSSION: Although mild to moderate adverse events related to the injection site have been reported in Phase 3 studies of extended-release buprenorphine injection, this is a rare case of skin necrosis requiring surgical intervention and excision of the depot. CONCLUSIONS: This case highlights the potential complication of skin necrosis after inadvertent dermal of extended-release buprenorphine and reviews proper administration techniques.

Pressure Necrosis Requiring Fasciotomy After Kratom Overdose.

INTRODUCTION: Kratom (Mitragyna speciosa) is a popular plant-based extract that has dose-dependent stimulatory and sedative effects. It has been used for self-treatment of opioid withdrawal and can result in seizures, hepatotoxicity, and infectious complications from bacterial contamination. Reports of morbidity and mortality associated with Kratom may be confounded by coingestants. We report a case of severe rhabdomyolysis and pressure necrosis leading to fasciotomy in a patient who was using Kratom. CASE REPORT: A 31-year-old male with substance use presented to the emergency department after loss of consciousness for 6 hours after smoking Kratom. He was found to have rhabdomyolysis, acute renal and hepatic injury, and electrolyte disturbances. No ethanol was detected, and urine drug screen was negative. Over the next 3 hours, the patient developed signs of compartment syndrome and he was transferred to the operating room for fasciotomy. He required continuous renal replacement therapy for 48 hours and his labs and clinical status improved. He was discharged 18 days later. A serum and urine sample from the first day of presentation were analyzed for mitragynine and 7-hydroxymitragynine using an Ultra Performance Liquid Chromatography-Tandem Mass Spectrometer (UPLC-MSMS) method. The serum mitragynine was 5 ng/mL and the urine mitragynine 6 ng/mL. CONCLUSIONS: Although there are numerous reports of opioids resulting in prolonged periods of immobilization and rhabdomyolysis, this is not commonly reported in Kratom overdoses.This case report highlights the profound sedative effect of Kratom and the potential of pressure necrosis injury resulting in rhabdomyolysis and compartment syndrome requiring fasciotomy.

Evaluation of prehospital hydroxocobalamin use in the setting of smoke inhalation.

BACKGROUND: The indications for prehospital hydroxocobalamin are not well defined. The aim of this study was to evaluate prehospital signs and symptoms in patients who received hydroxocobalamin to improve future use. METHODS: In this retrospective study, all patients who received prehospital Hydroxocobalamin at a tertiary care burn center from December 2012 to March 2018 were reviewed. Each case was evaluated for evidence of suspected cyanide toxicity: hypotension, syncope, CNS depression/altered mentation, seizures, respiratory or cardiac arrest. A determination was made whether or not hydroxocobalamin was indicated. RESULTS: In this study, EMS providers administered hydroxocobalamin to 42 patients between December 2012 and March 2018. The majority (71%) of suspected cyanide exposures were from house fires. The most common prehospital findings were coma or depressed CNS (36%), followed by hypotension (16%) and cardiac arrest (12%). Sixty percent of patients treated with hydroxocobalamin had none of the six clinical indicators for potential cyanide toxicity. Carboxyhemoglobin and serum lactate were significantly different in patients that had a clinical indication for hydroxocobalamin compared to those who did not. CONCLUSIONS: Prehospital hydroxocobalamin was used empirically however, indications are unclear. Using defined clinical indications may provide greater clarity for providers and reduce unnecessary use of hydroxocobalamin.

Negligible Nux Vomica: Homeopathic Nux Vomica remedies don't contain strychnine?

INTRODUCTION: The St. Ignatius bean of the Strychnos ignatii tree and Nux Vomica homeopathic products presumably could contain the toxic alkaloids strychnine and brucine. This study aimed to determine the amount of these toxic alkaloids in some commercially available Nux Vomica products and the St. Ignatius bean and to determine if overdose of these products could result in clinically significant toxicity. METHODS: Using ultra-performance liquid chromatography-tandem mass spectrometry, various formulations of Nux Vomica products and St. Ignatius beans were analyzed for strychnine, and brucine with detection limits set at 0.1 ng/g. RESULTS: None of the analyzed Nux Vomica products contained any detectable strychnine or brucine, while the expected strychnine dose from a St. Ignatius bean would be < 0.001 mg. CONCLUSIONS: Overall, our study reveals that the amount of strychnine in homeopathic Nux Vomica products or St. Ignatius beans are not likely to result in clinically significant strychnine toxicity.

Descriptive epidemiology of clinically significant occupational poisonings, United States, 2008-2018.

INTRODUCTION: References listing common occupational poisons often include agents that were observed decades prior to the introduction of worker protective laws and regulations. Current causes of work-related acute poisonings have not been characterized. This study's primary objective was to describe the most common poisons and routes of exposure responsible for clinically significant occupational poisonings. A secondary objective was to determine the crude rate of clinically significant occupational poisonings and occupational poisoning-related deaths over the study period. METHODS: This was a retrospective cohort study using electronic data from the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS), and open source data from the United States Bureau of Labor Statistics (BLS). The NPDS was queried for all cases with exposure reason coded as "Unintentional-Occupational" for the period 1 January 2008 to 31 December 2018. A case of clinically significant occupational poisoning (CSOP) was defined as a case with moderate or severe clinical effects reported, to include fatal cases. A descriptive analysis was conducted using unadjusted odds ratios to assess the strength of association between main variables of interest and CSOP. RESULTS: 329,437 exposure cases were available for analysis. Of these, 54,254 were considered CSOP and included 196 deaths. The top five poisons responsible for occupational fatalities were hydrogen sulfide, ammonia, carbon monoxide, simple asphyxiants, and chlorines. Fatalities were 3.7 times (OR: 3.7; 95% CI: 2.2-6.4) more likely to be men and 5.7 times (OR: 5.7; 95% CI: 4.0-8.1) more likely to have had an inhalational exposure, compared to those workers with CSOP without fatality. The crude rate of occupational fatal poisoning reported to US poison centers was 11.3 deaths per 100,000,000 worker-years during the study period. The crude rate of clinically significant occupational poisoning was 3.1 per 100,000 worker-years. These rates remained generally stable over the study period. CONCLUSION: Occupational poisonings continue to be a significant cause of morbidity and mortality in the workplace despite significant improvements in workplace chemical safety over the last four decades. Workplace education and proper preventive measures devoted to inhalational toxicants and respiratory protection are opportunities for improvement.

Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine.

BACKGROUND: Recent recognition of "massive" acetaminophen (APAP) overdoses has led to the question of whether standard dosing of N-acetylcysteine (NAC) is adequate to prevent hepatoxicity in these patients. The primary aim of this study was to evaluate the clinical outcome for patients with massive APAP overdose who received standard intravenous NAC dosing of 300 mg/kg over 21 h. METHODS: This was a single-center retrospective cohort study conducted by chart review of APAP overdoses reported to a regional poison center from 1 January 2010 to 31 December 2019. Massive APAP overdose was defined by single, acute overdose resulting in an APAP concentration exceeding 300 mcg/mL at 4 h post-ingestion. Standard univariate statistical analysis was conducted to describe the cohort, and a multivariate logistic model was utilized to calculate adjusted odds ratios for risk of hepatoxicity. RESULTS: 1425 cases of APAP overdose were reviewed. 104 cases met the inclusion criteria of massive APAP overdose. Overall, 79 cases (76%) had no acute liver injury or hepatotoxicity, and 25 (24%) developed hepatoxicity. Nine percent (n = 4) of cases receiving NAC within 8 h developed hepatotoxicity. Crude odds for hepatoxicity was 5.5-fold higher for cases who received NAC after 8 h. CONCLUSIONS: Standard NAC dosing received within 8 h prevented hepatoxicity in 91% (n = 40) of cases in our series of massive APAP overdoses. Additional data is needed to determine the clinical outcomes of massive APAP overdose using current intravenous NAC dosing.

Patterns of transaminase elevation in rhabdomyolysis versus acetaminophen toxicity.

BACKGROUND: Transaminase elevations can occur from liver injury or in the setting of rhabdomyolysis. The goal of this study is to evaluate indices that could differentiate acetaminophen toxicity from muscle injury in the setting of transaminase elevations. METHODS: A retrospective chart review of consecutive cases reported to our regional poison center. Patients with transaminase (AST and ALT) elevation were grouped as those with acetaminophen exposure (AT) and those with elevated creatine phosphokinase (CPK) without evidence of acetaminophen exposure (RHB). RESULTS: Of the 345 patients included in the study, elevated AST/ALT levels were attributed to rhabdomyolysis in 168 patients and attributed to acetaminophen toxicity in 177 patients. The median AST: ALT values also differed between groups, with patients in the RHB group had higher median ratios (p < 0.001). Using an AST: ALT value of 2.02 as a diagnostic cutoff produced a specificity of 0.52 (95% CI: 0.37, 0.64) and sensitivity of 0.84 (95% CI: 0.73, 0.94) for acetaminophen detection in the test dataset (N = 104). CONCLUSIONS: Elevated transaminases due to liver injury from acetaminophen ingestion had a different pattern than elevated transaminases due to rhabdomyolysis. Lower AST:ALT ratios were found in acetaminophen cases, however, the specificity using a ratio threshold of ≤1 would be 83%.