title: Cardiovascular and metabolic effects of high-dose insulin in a porcine septic shock model.
abstract: OBJECTIVE
  High-dose insulin (HDI) has inotropic and vasodilatory properties in various clinical conditions associated with myocardial depression. The authors hypothesized that HDI will improve the myocardial depression produced by severe septic shock and have beneficial effects on metabolic parameters. In an animal model of severe septic shock, this study compared the effects of HDI treatment to normal saline (NS) resuscitation alone.
  
  
  METHODS
  Ten pigs were randomized to an insulin (HDI) or NS group. All were anesthetized and instrumented to monitor cardiovascular function. In both arms, Escherichia coli endotoxin lipopolysaccharide (LPS) and NS infusions were begun. LPS was titrated to 20 mug/kg/hour over 30 minutes and continued for 5 hours, and saline was infused at 20 mL/kg/hour throughout the protocol. Dextrose (50%) was infused to maintain glucose in the 60-150 mg/dL range, and potassium was infused to maintain a level greater than 2.8 mmol/L. At 60 minutes, the HDI group received an insulin infusion titrated from 2 to 10 units/kg/hour over 40 minutes and continued at that rate throughout the protocol. Survival, heart rate (HR), mean arterial pressure (MAP), pulmonary artery and central venous pressure, cardiac output, central venous oxygen saturation (SVO(2)), and lactate were monitored for 5 hours (three pigs each arm) or 7 hours (two pigs each arm) or until death. Cardiac index, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), O(2) delivery, and O(2) consumption were derived from measured data. Outcomes from the repeated-measures analysis were modeled using a mixed-effects linear model that assumed normally distributed errors and a random effect at the subject level.
  
  
  RESULTS
  No significant baseline differences existed between arms at time 0 or 60 minutes. Survival was 100% in the HDI arm and 60% in the NS arm. Cardiovascular variables were significantly better in the HDI arm: cardiac index (p < 0.001), SVR (p < 0.003), and PVR (p < 0.01). The metabolic parameters were also significantly better in the HDI arm: SVO(2) (p < 0.01), O(2) delivery (p < 0.001), and O(2) consumption (p < 0.001). No differences in MAP, HR, or lactate were found.
  
  
  CONCLUSIONS
  In this animal model of endotoxemic-induced septic shock that results in severe myocardial depression, HDI is associated with improved cardiac function compared to NS resuscitation alone. HDI also demonstrated favorable metabolic, pulmonary, and peripheral vascular effects. Further studies may define a potential role for the use of HDI in the resuscitation of septic shock.
authors.affiliation: Department of Emergency Medicine, Regions Hospital, St. Paul, MN, USA. Joel.S.Holger@Healthpartners.com
authors.forename: Joel S
authors.initials: JS
authors.lastname: Holger
authors.forename: David J
authors.initials: DJ
authors.lastname: Dries
authors.forename: Kelly W
authors.initials: KW
authors.lastname: Barringer
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Peake
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Flottemesch
authors.forename: John J
authors.initials: JJ
authors.lastname: Marini
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D016001:Confidence Intervals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012307:Risk Factors; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D007328:Insulin; D007773:Lactates; D010100:Oxygen