Ketamine Versus Fentanyl for Induction of Anesthesia in Septic Shock

Ketamine-based Versus Opioid-based for Rapid-sequence Induction of Anesthesia in Patients With Septic Shock

The aim of this work is to compare two protocols (ketamine-midazolam versus fentanyl-midazolam) for induction of anesthesia in patients with septic shock aiming to find the most safe protocol with regards to hemodynamic status of patients

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam; Drug: Fentanyl

Detailed Description

Induction of anesthesia in hemodynamically compromised patients is a challenge for every anesthetist. Most of the intravenous induction agents have a negative effect on arterial blood pressure and cardiac output. Theoretically, the "ideal" emergency induction intravenous anesthetic should achieve rapid hypnosis and maintain the hemodynamic stability.

Ketamine has been reported as an induction anesthetic with a sympathomimetic activity. In patients with intact autonomic nervous system ketamine increases heart rate, cardiac output, and arterial blood pressure (ABP). Despite its sympathomimetic activity in hemodynamically stable patients, the hemodynamic response to ketamine in unstable cardiovascular conditions is not clear. No studies to the best of our knowledge compared Ketamine-based and opioid-based protocols in rapid sequence induction of anesthesia in hemodynamically unstable patients.

In this study, patients with severe sepsis or septic shock scheduled for surgery will be assigned to receive either ketamine or fentanyl for induction of anesthesia. After induction of anesthesia, endotracheal tube will be inserted aided by succinyl choline. Invasive blood pressure will be monitored through a transducer connected to arterial catheter. Electrical velocimetry (cardiometry) device will be used for non-invasive monitoring of cardiac output and stroke volume.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sepsis patients
• With shock index (heart rate divided by systolic blood pressure) >0.7. or Sepsis patients with norepinephrine infusion.

Exclusion Criteria:

• Traumatic brain injury
• Cerebrovascular disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine group; This group of patients will receive: 1 mg/Kg ketamine + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.	Drug: Ketamine; Patients will receive :1 mg/Kg ketamine for induction of anesthesia; Other Names: Katalar; Drug: Midazolam; Patients will receive 0.05 mg/Kg midazolam; Other Names: Dormicum
Active Comparator: Fentanyl; 2.5 mg/Kg fentanyl + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.	Drug: Midazolam; Patients will receive 0.05 mg/Kg midazolam; Other Names: Dormicum; Drug: Fentanyl; Patients will receive :2.5 mcg/Kg fentanyl for induction of anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure	Mean arterial blood pressure measured by invasive transducer attached to arterial catheter	30 minutes after induction of anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac output	cardiac output measured in litres per minute measured by electrical velocimetry	30 minutes after induction of anesthesia
Stroke volume	cardiac stroke volume in milliliters measured by electrical velocimetry	30 minutes after induction of anesthesia
heart rate	heart rate measured in beat per minute	30 minutes after induction of anesthesia
serum lactate	serum lactate measured in mmol/liter	30 minutes after induction of anesthesia
total norepinephrine dose	total dose of norepinephrine measured in micrograms	30 minutes after induction of anesthesia
Intra-operative inhalational anesthetic concentration	the concentration of inhalational anesthetic (%)	30 minutes
Incidence of post-induction hypotension	The percent of patients with severe hypotension after induction of anesthesia requiring stoppage of inhalational anesthesia or increasing the dose of vasopressors	5 minutes

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Director: Ahmed Mukhtar, Head of research committee section in anesthesia department

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): December 25, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: August 12, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 25, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Fentanyl; Midazolam
• Other Study ID Numbers: N-12-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No