title: A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.
abstract: BACKGROUND
  High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS.
  
  
  METHODS
  This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died.
  
  
  RESULTS
  2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization.
  
  
  CONCLUSIONS
  HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.
authors.affiliation: Department of Emergency Medicine, Regions Hospital, Saint Paul, MN, USA. jon.cole@hcmed.org
authors.forename: J B
authors.initials: JB
authors.lastname: Cole
authors.forename: S J
authors.initials: SJ
authors.lastname: Stellpflug
authors.forename: H
authors.initials: H
authors.lastname: Ellsworth
authors.forename: C P
authors.initials: CP
authors.lastname: Anderson
authors.forename: A B
authors.initials: AB
authors.lastname: Adams
authors.forename: K M
authors.initials: KM
authors.lastname: Engebretsen
authors.forename: J S
authors.initials: JS
authors.lastname: Holger
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000506:poisoning; D000818:Animals; D017849:Animals, Inbred Strains; D062186:Arterial Pressure / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D010919:Placebos / Q000008:administration & dosage; D011042:Poisons / Q000633:toxicity*; D011433:Propranolol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000506:poisoning; D011446:Prospective Studies; D012770:Shock, Cardiogenic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D034421:Sus scrofa; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D011042:Poisons; D011433:Propranolol; D005947:Glucose