Clinical trial NCT01065350
Conditions: Blood Pressure
Keywords: ketofol hemodynamics propofol anesthesia
Sponsor: Mayo Clinic
Start date: 2010-12-01; Completion date: 2011-03-01
Enrollment: 85 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a pilot study to compare the hemodynamic changes that occur during induction with a novel drug combination known as ketofol (propofol and ketamine admixture with that of propofol alone (prototypic anesthesia induction agent). Propofol and ketamine are widely used as induction agents and their effects on patient hemodynamics are well known. Some of these drug-induced hemodynamic changes are undesirable and lead to deleterious effects on patient hemodynamics. We seek to investigate the hemodynamic changes associated with a novel drug combination known as ketofol (ketamine/propofol admixture) during induction and compare them to propofol. If we determine that the changes produced by ketofol are favorable compared with propofol, we then will seek to test its use in the trauma setting in a subsequent randomized controlled trial.

Detailed description:
This is a pilot study to compare the hemodynamic changes that occur during induction with a novel drug combination known as ketofol with that of propofol. Propofol and ketamine are widely used as induction agents and their effects on patient hemodynamics are well known. Many of these drug-induced changes are undesirable and when used alone sometimes lead to hemodynamic effects on opposite ends of the spectrum, ie. hypotension (propofol) and hypertension (ketamine). We will investigate the hemodynamic changes associated with this drug combination referred to as "ketofol" (ketamine/propofol admixture) during induction compared with propofol as the gold standard induction agent used widely in anesthetic practice. If we validate that the changes produced by the ketofol admixture are favorable, we will then test its use in a wider setting of patient populations including emergency department intubations and the trauma setting.

Background: Propofol is a non-opioid, non-barbiturate, sedative-hypnotic agent with rapid onset and short duration of action. It possesses many favorable effects such as an antiemetic effect and reliably produces sedation and amnesia (Felfernig Jour of Royal Naval Medical Service, '06; White International Anesth Clinics, '88; Willman Ann of Emer Med, '07). However, there are several undesirable side effects such as cardiovascular and respiratory depression. In addition, Propofol as a sole agent has no analgesic properties. These drug-induced side effects have led to alternative drugs being used with the hopes of a more favorable side effect profile. Ketamine is an example of one such drug. Ketamine is a phencyclidine derivative commonly classified as a dissociative sedative with fairly rapid onset and short duration of action (Felfernig Jour of Royal Naval Medical Service, '06; White International Anesth Clinics, '88; Willman Ann of Emer Med, '07). It causes little or no respiratory and cardiovascular depression and unlike propofol, has pain relieving properties. Ketamine as a single induction agent, however, is limited by emergence phenomena including postoperative dreaming and hallucinations, however these are attenuated by the administration of benzodiazepines. Also ketamine in induction doses 1-4.5 mg/kg can have some undesirable effects on hemodynamics (opposite of propofol) in certain patient populations including ischemic heart disease (IHD), and patients with increases in intracranial hypertension and intracranial pressure (ICP). Effectiveness of the two agents in combination has been recently demonstrated and this new combination could allow a novel induction agent with favorable effects on hemodynamics (Felfernig Jour of Royal Naval Medical Service, '06; Hui Jour of Amer Soc of Anesth, '95; Willman Ann of Emer Med, '07). To date, this combination known as ketofol has been used most extensively for procedural sedation in the Emergency Department but has not yet been standardized as an induction agent. We are obtaining funding for a pilot study to validate the use of ketofol as an induction agent.

Arms: arm 1: As part of the induction, patients will be given 2 milligrams of propofol per kilogram (mg/kg) of body weight. The clinician will receive a 20 milliliter (mL) syringe of propofol. If the dose, 2 mg/kg, does not add up to a total of 20 mL, normal saline will be added to make up for the 20 mL. arm 2: As part of the induction, patients will be given 20 mL syringe of an admixture called "ketofol," which combines ketamine and propofol in one syringe. The dose is weight-based such that ketamine will represent 0.75 mg/kg of the dose and propofol, 1.5 mg/kg of the dose.
Interventions: intervention 1: Propofol intervention 2: Ketamine
Intervention descriptions: intervention 1: As part of the induction, subjects will be given 2 milligrams per kilogram of body weight (mg/kg) of propofol. The clinician will receive a 20 milliliter (mL) syringe of propofol. If the dose, 2 mg/kg, does not add up to a total of 20 mL, normal saline will be added to make up for the 20 mL. The clinician and observer will be blinded to the medication and doses being administered during induction given that both syringes, syringes in the propofol and ketofol groups, will look identical (will both appear to be propofol only). The propofol group will also be given an additional 10 mL syringe of propofol due to any patient responding to stimulus after induction. The 10 mL syringe represents 1 mg/kg of propofol. If patient receives both the 20 and 10ml syringe, he or she will receive a total of 3mg/kg of propofol. intervention 2: As part of the induction, patients will be given 20ml syringe of ketofol which is weight based such that ketamine will represent 0.75mg/kg of the dose and propofol, 1.5mg/kg. The clinician and observer will be blinded to the medication and doses being administered during induction given that both 20ml syringes (propofol group and ketofol group) will look identical (will both appear to be propofol only). Additional 10ml syringe will be given due to any patient responding to stimulus after induction. The 10ml syringe will represent 0.25mg/kg of ketamine and 0.5mg/kg of propofol. If the patient receives both the 20 and 10ml rescue syringe, he or she will receive a total of 1mg/kg of ketamine and 2mg/kg of propofol.

Protocol documents: