Compare the Effect of Propofol vs. "Ketofol" on Hemodynamic Stability During Induction of General Anesthesia

Patients With ASA 3 Designation Clinical Trial

Official title:

A Randomized-Controlled Trial to Compare the Effect of Propofol vs. "Ketofol" on Hemodynamic Stability During Induction of General Anesthesia

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02282891
• Other study ID #: 1406014189
• Status: Withdrawn
• Phase: Phase 2
• First received: October 31, 2014
• Last updated: December 14, 2016
• Start date: January 2015
• Est. completion date: August 2016

Study information

• Verified date: December 2016
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the hemodynamic effects of a standardized induction of general anesthesia with either propofol or ketofol in patients with physical status classification ASA 3. The study will be a double blinded, randomized controlled trial (RCT) with two arms of treatment groups. One arm will consist of induction of general anesthesia using a mixture of 1.5mg/kg:0.75mg/kg Propofol/ketamine (ketofol) and the induction dose will be 1.5mg/kg of propofol and 0.75mg/kg of ketamine; the second arm will consist of induction of general anesthesia using propofol 2mg/kg. The primary outcome of the intervention will consist of hemodynamic changes during the first 30 minutes after induction of general anesthesia.

Description:

The anesthetic agent propofol can result in hypotension when used for induction of general anesthesia. Recent trials suggest that even a short duration of hypotension during induction of anesthesia can adversely affect organ function and overall outcome.1 To overcome the hypotensive effect of propofol, ketamine, which has sympathomimetic effects, has been combined with propofol to produce a mixture labeled "ketofol", which has been used both for procedural sedation and induction of general anesthesia. Clinical trials have shown that ketofol can attenuate the hypotensive effects of propofol during procedural sedation or induction of general anesthesia in patients whose physical status is 1 or 2 according to the American Society of Anesthesiologists (ASA 1-2), i.e., healthy patients or those with mild-moderate systemic illness.2,3 Clinically, it is important to demonstrate the efficacy of ketofol in attenuating hypotensive effects of propofol in sicker patients, i.e., patients with physical status ASA 3. The purpose of this study is to compare the hemodynamic effects of a standardized induction of general anesthesia with either propofol or ketofol in patients with physical status classification ASA 3. The study will be a double blinded, randomized controlled trial (RCT) with two arms of treatment groups. One arm will consist of induction of general anesthesia using a mixture of 1.5mg/kg:0.75mg/kg Propofol/ketamine (ketofol) and the induction dose will be 1.5mg/kg of propfol and 0.75mg/kg of ketamine; the second arm will consist of induction of general anesthesia using propofol 2mg/kg. The primary outcome of the intervention will consist of hemodynamic changes during the first 30 minutes after induction of general anesthesia.

Baseline demographics collected for each patient will include:

1. age

2. sex

3. ASA physical status

4. Hx of HTN

5. Hx of PONV

6. Preoperative pain score

The standardized induction of anesthesia will consist of intravenous administration of midazolam 0.04mg/kg, lidocaine 1 mg/kg, fentanyl 1-2 mcg/kg, glycopyrrolate 0.004 mg/kg, an unlabeled pre-prepared, covered syringe which will be prepared by the Yale Anesthesia satellite pharmacist containing either propofol 2mg/kg or a mixture propofol 1.5mg/kg and ketamine 0.75mg/kg, the amount of which will be pre-determined based on the patient weight, and rocuronium 0.6 mg/kg. A backup 10cc syringe of the study drug will be available as well if the initial dose is inadequate. The choice of propofol and ketamine dosing is based on a study cited earlier by Smischney et al in 2012 that addresses ASA 1-2 patients undergoing induction of general anesthesia. Endotracheal intubation will take place after adequate muscle relaxation has been determined using fade of train of four on a nerve stimulator placed over the ulnar nerve. Additional medication to facilitate induction will be used according to the judgment of the anesthesia provider with a backup syringe of the same study drug. Inhalational anesthesia will be administered after confirmation of endotracheal intubation. Treatment of hypotension will be according to the anesthesia provider. Amounts of intravenous fluids as well as doses of vasopressor that are used during induction and in the subsequent 30 minutes after endotracheal intubation will be obtained from the anesthesia record.

The first blood pressure (BP) upon arrival to the operating room before any anesthetic medications are administered will be the reference (baseline) blood pressure. BP will be measured every 1 minute from one minute before induction until 30 minutes after endotracheal intubation.

The primary outcome of the study will be the number of time points during which the blood pressure was below 20% of the baseline BP. Secondary outcomes will include:

1. Severity of hypotension as determined by the gradient of each blood pressure measurement from the baseline BP.

2. The total dosage of vasopressors administered during induction and up to 30 minutes after endotracheal intubation

3. The total amount of IV fluids administered during induction and up to 30 minutes after endotracheal intubation.

4. The total amount of additional medications used during induction and up to 30 minutes after endotracheal intubation.

5. Total intraoperative as well as postoperative opioid dosage used.

6. Presence or absence of PONV and severity

7. Intraoperative prophylaxis and postoperative treatment of PONV

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients age 18-80 scheduled for elective surgery

• Physical status ASA 3.

Exclusion Criteria:

• Patients with a physical status of ASA 1,2, 4 or 5,

• Prior adverse reaction to propofol, ketamine or both

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Patients With ASA 3 Designation

Intervention

Drug:
• Propofol
Induction of general anesthesia using propofol 2mg/kg
• Propofol-Ketamine
Induction of general anesthesia using a mixture of 1.5 mg/kg:0.75 mg/kg propofol/ketamine

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of time points during which blood pressure was below 20% of baseline BP	The number of time points during which the blood pressure was below 20% of the baseline BP. The first blood pressure upon arrival to the operating room before any anesthetic medications are administered will be the reference (baseline) blood pressure. BP will be measured every 1 minute from one minute before induction until 30 minutes after endotracheal intubation.	up to 30 minutes after intubation	Yes
Secondary	Severity of hypotension	As determined by the gradient of each blood pressure measurement from the baseline BP	up to 30 minutes after intubation	Yes
Secondary	Total dosage of vasopressors administered	The total dosage of vasopressors administered during induction and up to 30 minutes after endotracheal intubation	up to 30 minutes after intubation	No
Secondary	Amount of IV fluids administered	The total amount of IV fluids administered during induction and up to 30 minutes after endotracheal intubation.	up to 30 minutes after intubation	No
Secondary	Additional Medication Usage	The total amount of additional medications used during induction and up to 30 minutes after endotracheal intubation.	up to 30 minutes after intubation	No
Secondary	Total Opioid Dosage Used	Total intraoperative as well as postoperative opioid dosage used.	up to 30 minutes after intubation	No
Secondary	Post Operative Nausea and Vomiting (PONV) Severity	Presence or absence of PONV and severity within 72 hours of surgery	72 hours post surgery	No
Secondary	Treatment of Post Operative Nausea and Vomiting (PONV)	Number and dose of anti-emetics given within 72 hours of surgery	72 hours post surgery	No