Comparative Resuscitation Measures for Drug Toxicities Utilizing Lipid Emulsions

This study will be a prospective, experimental, between subjects design investigating a comparative analysis of resuscitative techniques in a swine model in which the animals received a toxic dose of lipophilic drugs.   Current trends in pain relief are leading to an increased use of local anesthetics to manage pain. Unfortunately, accidental intravascular absorbtion of toxic levels of  local anesthetics leads to seizures and can lead to cardiovascular collapse. Treatment for these incidents involve ACLS protocols often with little success. Recently there have been case reports of patients that received a toxic dose of local anesthetic and recovered after receiving a 20% Intralipid infusion. Concurrently, there have been case reports of patients arriving in the ER after ingesting a toxic dose of antidepressants, antipsychotics or other lipophilic drugs. These patients were saved with  20% intralipid infusion after prolonged resuscitation.  Our study is  constructed  with 3 major aims. 

The first aim is to compare the effectiveness of  seven methods of resuscitation in the face of toxic levels of local anesthetics (bupivacaine, ropivacaine,  lidocaine) The resuscitation methods include, epinephrine, vasopressin, lipid emulsion, vasopressin with lipid, epinephrine with lipid infusion, epinephrine with vasopressin, and CPR only.  The second aim uses the same interventions as above, except the lethal cardiovascular collapse is caused by three different classes of lipophilic drugs used in accidental overdose or suicide. (anti-depressants, anti-psychotics,  and tri-cyclic antidepressants). The criteria for successful resuscitation in the first 2 aims involves the return of spontaneous return of circulation.  The third aim examines the plasma level of bupivacaine during resuscitation, before and after lipid emulsion infusion. This last aim examines the pharmacokinetics of local anesthetic toxicity levels in the mileu of resuscitation and lipid emulsion infusion over a designated time frame. A repeated analysis of variance (RANOVA) will be used to determine if there are statistically significant differences in the groups. If there are statisically significant differences , a Tukey post-hoc test will be used to determine where the significant differences lies.

Final Report available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2015104...