Angiotensin II Use in Treatment of Refractory Shock Due to Benazepril and Amlodipine Toxic Ingestion.

INTRODUCTION: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. CASE REPORT: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin .06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. DISCUSSION: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients.

Iatrogenic Propylene Glycol Intoxication Due to High-Dose Pentobarbital for Refractory Intracranial Hypertension: A Case Report.

Propylene glycol is a rarely reported toxicity from high-dose administration of certain intravenous drugs, including lorazepam and pentobarbital. We present a case of iatrogenic propylene glycol toxicity secondary to a high-dose pentobarbital infusion for the treatment of refractory intracranial hypertension due to cerebral venous sinus thrombosis. The patient developed metabolic acidosis and acute kidney failure secondary to propylene glycol toxicity. After initiation of continuous renal replacement therapy, the patient's acute renal failure and lactic acidosis resolved. Using the Naranjo scale, this case received a score of 5, defining it as a "probable" adverse drug event. In patients who develop lactic acidosis and acute renal failure after initiation of high-dose pentobarbital, propylene glycol toxicity should be higher up in the differential diagnosis. Monitoring the serum osmolality while on pentobarbital could help provide valuable information to prevent iatrogenic propylene glycol toxicity.

Safety and Efficacy of Intermittent Bolus and Continuous Infusion Neostigmine for Acute Colonic Pseudo-Obstruction.

PURPOSE: To compare clinical response of intermittent bolus versus continuous infusion neostigmine for acute colonic pseudo-obstruction (ACPO). Acute colonic pseudo-obstruction occurs due to reduced colonic parasympathetic activity. Neostigmine is an acetylcholinesterase inhibitor that increases frequency of smooth muscle contraction by increasing acetylcholine at autonomic nervous system synapses. Although these administration modalities have been studied separately, they have never been compared. METHODS: This retrospective study compared bolus versus continuous infusion neostigmine for ACPO. The primary outcome was initial clinical response, defined as bowel movement (BM) within 4 hours of bolus dose or 24 hours of initiation of continuous infusion. Secondary outcomes included time to BM, bowel diameter reduction at 24 hours, incidence of bradycardia, additional neostigmine requirements, and need for colonic decompression or surgical intervention. RESULTS: Seventy-five patients were included (bolus n = 37; infusion n = 38). Median total 24-hour neostigmine dose was 2.0 mg (interquartile range [IQR]: 2.0-2.6) with bolus and 9.6 mg (IQR: 6.3-9.6) with continuous infusion. Initial clinical response was similar (infusion 81.6% vs bolus 62.2%, P = .06), but continuous infusion was associated with greater bowel diameter reduction (73.7% vs 40.5%, P = .004). Bolus administration had shorter time to BM (1.4 vs 3.5 hours, P = .0478) and increased need for colonic decompression (67.6% vs 39.5%, P = .0148). Bolus dosing was associated with less bradycardia (13.5% vs 39.5%, P = 0.011), with no difference in atropine usage (10.8% vs 5.3%, P = .43). CONCLUSION: Initial clinical response was similar between groups; however, continuous infusion neostigmine was associated with greater bowel diameter reduction at 24 hours. Bolus administration resulted in less bradycardia; however, given the lack of difference in atropine use, clinical significance is unknown. This study is the first to compare bolus versus continuous infusion neostigmine for ACPO. Further studies are needed to confirm findings.