Intravenous lipid emulsion in the management of amlodipine overdose.

OBJECTIVE: To report a case of amlodipine overdose successfully treated with intravenous lipid emulsion (ILE). CASE SUMMARY: A 47-year-old, 110 kg female ingested at least 350 mg of amlodipine with an unknown amount of ethanol. Initial blood pressure was 103/57 mm Hg, mean arterial pressure (MAP) 72 mm Hg, and heart rate 113 beats per minute. In the early clinical course, activated charcoal, intravenous fluid, and calcium boluses were administered. Worsening hypotension prompted a 100 mL bolus of 20% ILE. Stable hemodynamics were maintained for 2 hours. Subsequently, profound hypotension and shock developed (MAP 38 mm Hg), which failed to fully respond to 3 vasopressor agents, calcium, and glucagon. With continuing shock despite optimized vasopressors, an infusion of 2,300 mL 20% ILE was administered over 4.5 hours (20.9 mL/kg infusion total). By completion of the infusion, 2 vasopressors were tapered off and MAP remained above 70 mm Hg; within 12 hours, no further interventions were required. Possible adverse events of ILE, lipemia and hypoxia, were experienced but quickly resolved. The patient survived to hospital discharge within 8 days. DISCUSSION: Toxicity of amlodipine presents similar to distributive shock as both are due to marked peripheral vasodilation. There are numerous interventions in the management of amlodipine overdose, despite which many patients continue to suffer life-threatening shock as observed with this patient. ILE has been used with promising preliminary results as salvage therapy in case reports of other lipophilic molecules. This is the first report of lone amlodipine overdose treated with ILE. CONCLUSION: ILE is a novel antidote for overdoses of lipophilic substances and demonstrated efficacy in this case of amlodipine overdose without the use of hyperinsulinemic euglycemia.

Nonpharmacologic approach to minimizing shivering during surface cooling: a proof of principle study.

PURPOSE: This study had 2 objectives: (1) to quantify the metabolic response to physical cooling in febrile patients with systemic inflammatory response syndrome (SIRS) and (2) to provide proof for the hypothesis that the efficiency of external cooling and the subsequent shivering response are influenced by site and temperature of surface cooling pads. METHODS: To quantify shivering thermogenesis during surface cooling for fever, we monitored oxygen consumption (VO(2)) in 6 febrile patients with SIRS during conventional cooling with cooling blankets and ice packs. To begin to determine how location and temperature of surface cooling influence shivering, we compared 5 cooling protocols for inducing mild hypothermia in 6 healthy volunteers. RESULTS: In the patients with SIRS, core temperature decreased 0.67 °C per hour, all patients shivered, VO(2) increased 57.6%, and blood pressure increased 15% during cooling. In healthy subjects, cooling with the 10 °C vest was most comfortable and removed heat most efficiently without shivering or VO(2) increase. Cooling with combined vest and thigh pads stimulated the most shivering and highest VO(2) and increased core temperature. Reducing vest temperature from 10 °C to 5 °C failed to increase heat removal secondary to cutaneous vasoconstriction. Capsaicin, an agonist for the transient receptor potential cation channel subfamily V member 1 (TRPV1) warm-sensing channels, partially reversed this effect in 5 subjects. CONCLUSIONS: Our results identify the hazards of surface cooling in febrile critically ill patients and support the concept that optimization of cooling pad temperature and position may improve cooling efficiency and reduce shivering.

Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation.

Chronic repeated exposure to hyperthermia in humans results in heat acclimation (HA), an adaptive process that is attained in humans by repeated exposure to hyperthermia and is characterized by improved heat elimination and increased exercise capacity, and acquired thermal tolerance (ATT), a cellular response characterized by increased baseline heat shock protein (HSP) expression and blunting of the acute increase in HSP expression stimulated by re-exposure to thermal stress. Epidemiologic studies in military personnel operating in hot environments and elite athletes suggest that repeated exposure to hyperthermia may also exert long-term health effects. Animal models demonstrate that coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia can profoundly affect the course of experimental infection and injury, but these models do not represent HA. In this study, we demonstrate that CD-1 mice continuously exposed to mild hyperthermia (ambient temperature ~37°C causing ~2°C increase in core temperature) for 5 days and then exposed to a thermal stress (42°C ambient temperature for 40 min) exhibited some of the salient features of human HA, including (1) slower warming during thermal stress and more rapid cooling during recovery and (2) increased activity during thermal stress, as well as some of the features of ATT, including (1) increased baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain; and (2) blunted incremental increase in HSP72 expression following acute thermal stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild hyperthermia induces a state that resembles the physiologic and cellular responses of human HA. This model may be useful for analyzing the molecular mechanisms of HA and its consequences on host responsiveness to subsequent stresses.