Clinical trial NCT01065350: A Comparison of Ketofol (Ketamine and Propofol Admixture) Versus Propofol as Induction Agents on Hemodynamic Parameters
Official title: A Comparison of Ketofol (Ketamine and Propofol Admixture) vs. Propofol as Induction Agents on Hemodynamic Parameters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Pressure
Keywords: ketofol
hemodynamics
propofol
anesthesia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Dartmouth-Hitchcock Medical Center
First posted: 2010-02-09
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiologists (ASA) physical status I and II who are to undergo elective general, urologic, orthopedic, plastic, or gynecologic surgery.

Exclusion Criteria:

* patients with age less than 18 yr or over 60 yr,
* emergency surgery,
* patients undergoing neurosurgical procedures,
* any procedure with adjunctive analgesia,
* any patient on chronic opiate use,
* females who are known to be pregnant,
* patients who had ingested psychotropic or sedative medication within one month of investigation,
* patients with personality disorders,
* weight greater than 20% of ideal, and
* any known contraindications to ketamine or propofol.

Primary outcomes:
measure: Percent of Subjects With a Greater Than 20% Decrease in Systolic Blood Pressure (SBP) Following Induction of General Anesthesia
timeFrame: Baseline, 5 minutes, 10 minutes, 30 minutes post induction
Secondary outcomes:
measure: Percent of Subjects With a Greater Than 20% Decrease in Diastolic Blood Pressure (DBP) Following Induction of General Anesthesia
timeFrame: Baseline, 5 minutes, 10 minutes, 30 minutes post induction
measure: Percent of Subjects With a Greater Than 20% Decrease in Mean Arterial Pressure (MAP) Following Induction of General Anesthesia
timeFrame: Baseline, 5 minutes, 10 minutes, 30 minutes post induction
measure: Average Change in Cardiac Output (CO)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Cardiac Index (CI)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Heart Rate (HR)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Systolic Blood Pressure (SBP)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Diastolic Blood Pressure (DBP)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Mean Arterial Pressure (MAP)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Total Peripheral Resistance (TPR)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Total Peripheral Resistance Index (TPRI)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Stroke Volume (SV)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Stroke Volume Index (SVI)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
measure: Average Change in Stroke Volume Variation (SVV)
timeFrame: Baseline, 5 minutes, 10 minutes post induction
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Mayo Clinic
name: Nathan J Smischney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Matthew Koff, MD
role: STUDY_DIRECTOR
References:
citation: Smischney NJ, Beach ML, Loftus RW, Dodds TM, Koff MD. Ketamine/propofol admixture (ketofol) is associated with improved hemodynamics as an induction agent: a randomized, controlled trial. J Trauma Acute Care Surg. 2012 Jul;73(1):94-101. doi: 10.1097/TA.0b013e318250cdb8.