Feasibility of Intermittent Hemodialysis in Metformin Toxicity With Shock.

BACKGROUND: Metformin toxicity can lead to profound shock and has a high mortality rate. Supportive care and enhanced elimination are the mainstays of therapy. Intermittent hemodialysis (HD) produces a higher clearance of metformin than continuous veno-venous hemofiltration or hemodiafiltration (CVVH/HDF). Nevertheless, CVVH/HDF has been proposed as an alternative in critically ill patients with the suggestion that hypotension may limit the use of HD. OBJECTIVE: This study sought to analyze the feasibility of performing hemodialysis in patients with persistent shock from metformin toxicity. METHODS: We performed a 6-year (2012-2017) retrospective chart review of patients with metformin toxicity managed at a large academic institution with a toxicology service. We included patients with persistent shock on vasopressor support who were treated with HD. Baseline characteristics, complications from treatment, timing of dialysis, and differences between mean arterial pressures before, during, and at the end of dialysis were recorded and analyzed. RESULTS: Despite critical mean peak lactate (23.9 mMol/L [range 17.6-27.9]), pH (6.91 [range 6.78-7.01]), and metformin levels (range 25-58 µg/mL], 6 of 7 patients recovered. All patients required prolonged HD (mean 19 h). Upon completion of HD, hemodynamics had improved (45 mm Hg [95% confidence interval 35-55 mm Hg] vs. 80 mm Hg [95% confidence interval 74-86 mm Hg]) and vasopressor support decreased. Mortality in this patient cohort was 14.3% (1/7). CONCLUSION: Intermittent HD is feasible in metformin toxicity despite persistent shock and high-dose vasopressor support. Mean arterial pressures improved during the course of HD and high blood flow rates were tolerated.

Multimodal analgesia in crotalid snakebite envenomation: A novel use of femoral nerve block.

Snakebite envenomations occur throughout the United States, with most envenomations resulting from Crotalid bites. These envenomations can result in severe pain despite aggressive analgesia due to effects of venom toxins. We report a case in which we treated a 44- year-old man who sustained a Copperhead (Agkistrodon contortrix) bite to his left hallux with progressive local toxicity, including severe pain radiating into his upper leg, without evidence of compartment syndrome or coagulopathy. His pain was unresponsive to multiple doses of opioids. We performed a fascia iliaca compartment femoral nerve block under dynamic ultrasound guidance with 20 mL of 0.25% bupivacaine, which provided substantial pain relief in his upper leg. To our knowledge, this is a novel application of regional anesthesia with peripheral nerve block. We demonstrate fascia iliaca compartment femoral nerve block may be a safe, beneficial technique for emergency physicians to utilize in providing multimodal analgesia in Crotalid envenomation.

Hyperammonemia in acetaminophen toxicity.

INTRODUCTION: Acetaminophen-induced hepatotoxicity can result in hyperammonemia, but it is not clear if elevated ammonia concentrations predict encephalopathy. METHODS: We retrospectively studied patients with acetaminophen toxicity at a liver transplant center over 8 years (January 1, 2010-December 31, 2017), who developed hepatotoxicity (AST and/or ALT >1000 IU/L) or hyperammonemia (ammonia > 40 µmol/L). We recorded baseline characteristics, laboratory data, documented grade of encephalopathy, and treatments administered. Sensitivity and specificity values were calculated for varying ammonia concentrations. RESULTS: A total of 102 patient encounters were included with 75 having ammonia concentrations. On presentation, 40% (30/75) of patients had concentrations greater than 100 µmol/L. However, an [ammonia] > 100 µmol/L was neither sensitive (46 % [95% CI: 26-67%]) nor specific (63% [48 - 76%]) for encephalopathy. Only an increasing ammonia concentration had a significant, but small (1.53 (95% CI: 1.06 - 2.20)) positive likelihood ratio for the development of hepatic encephalopathy. DISCUSSION: Animal models have suggested that in acetaminophen toxicity, encephalopathy may be secondary to an alternative mechanism other than hyperammonemia which may explain the lack of correlation between initial hyperammonemia and encephalopathy in this cohort. Additionally, a lack of empiric treatment for hyperammonemia did not appear to alter the course of any of the patients. None of these patients developed encephalopathy. CONCLUSION: In cases of acetaminophen-induced hepatotoxicity, ammonia concentrations do not correlate with encephalopathy and empiric treatment for hyperammonemia does not appear to be beneficial.

Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity.

BACKGROUND: In cases of ethylene glycol (EG) toxicity requiring hemodialysis (HD), fomepizole is dosed every four hours. HD efficiently clears EG and its toxic metabolites, and it's unclear if multiple doses (MD) of fomepizole improve patient outcomes or whether a single dose (SD) prior to initiation of HD is sufficient. METHODS: We reviewed cases of EG toxicity at a toxicology referral center from 2008 to 2018. Patients treated with HD with EG levels greater than 20 mg/dL were included. Duration of dialysis, creatinine at discharge, hospital length of stay (LOS), and complications were analyzed. We compared patients who received a single dose of fomepizole prior to HD to those who received continued dosing during and after HD. RESULTS: Twenty-five patient encounters were identified (MD: 20; SD: 5). Initial bicarbonate (11 [SD] vs. 9 mg/dL [MD]) and pH (7.1 vs. 7.1) were similar between the groups; however, there was a trend toward a greater proportion of patients with renal dysfunction in the MD group: 11 (55%) vs. 1 (20%). HD was initiated a median interval of 5.2 h [SD] vs. 5.7 h [MD] after a dose of fomepizole. There was one death in the MD group and none in the SD group. Median creatinine on the day of discharge was 0.7 mg/dL (IQR: 0.57-3.8) in the SD group and 2.0 mg/dL (0.90-7.0) in the MD group. LOS was similar (5.8 days [95% CI 3.6-8.0] vs. 7.6 days [5.3-9.9]) (p = .61). CONCLUSION: Patients with moderately severe EG toxicity (acidosis and no initial renal dysfunction) treated with a single dose of fomepizole prior to HD had similar outcomes to those receiving continued dosing of fomepizole during or after HD. This raises the possibility that a single dose of fomepizole may be sufficient if HD is initiated quickly.

Serotonin toxicity from isolated bupropion overdoses.

Background: Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity.Methods: A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015-2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria.Results: Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome.Conclusion: The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.

Neurotoxic envenomation by the South African coral snake (Aspidelaps lubricus): A case report.

The South African coral snake (Aspidelaps lubricus, Elapidae) has not previously been reported to cause any neurotoxic envenomations in humans. We recently treated a 44-year-old man who was bitten twice, once in each hand, by a captive South African coral snake (Aspidelaps lubricus) while feeding the female snake who had recently laid eggs. Approximately one hour after receiving the bite, he developed vomiting, respiratory failure requiring mechanical ventilation, and paralysis of the bulbar and upper extremity muscles, with retention of voluntary motor control in the lower extremities. Supportive care was provided, and paralysis and respiratory failure resolved spontaneously 12 hours after onset. No antivenom for this species is available. To our knowledge, this is the first published case report of significant human envenomation by Aspidelaps lubricus. Physicians, first responders, and herpetologists should be aware of the potential for neurotoxicity in humans.