Hemodynamic Effects of Bolus of Ketamine Versus Fentanyl in Patients With Septic Shock

Comparing the Hemodynamic Effects of Bolus of Ketamine and Fentanyl in Patients With Septic Shock: a Randomized Controlled Trial

Ketamine is a commonly used drug for sedation and induction of anesthesia in patients with shock and/or cardiac dysfunction. Ketamine is characterized by its cardiovascular stimulatory effect due to increase release of endogenous catecholamines. On the other hand, laboratory data on the isolated human myofibers suggest that ketamine had a direct myocardial depressive effect; accordingly, many experts believe that ketamine might have a negative hemodynamic effect in catecholamine depleted patients such as critically ill patients. In critically ill patients, there are contradicting results for the effect of ketamine on the hemodynamic profile and there is paucity of clinical data about the effect of ketamine on cardiac contractility and cardiac output (CO). Cardiac output is the primary determinant of global oxygen delivery to organs and maintaining stable CO in critically ill patients is at most importance to avoid further organ damage in such patients.

Therefore, this study is designed to evaluate the effect a single bolus of ketamine on CO in patients with septic shock in comparison to fentanyl bolus.

Study Overview

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

Detailed Description

Patients meeting the inclusion criteria will receive the study drug according to the randomization, if a bolus of sedation is required for resuming sedation after sedation vacation. All patients will be monitored by 5-lead electrocardiogram, pulse oximetry, and noninvasive blood pressure.

Hypotension defined as mean arterial pressure < 65 mmHg and will be managed by increasing the norepinephrine infusion rate by 20%.

Bedside echocardiography will be used to measure the cardiac output by an experienced physician who is not aware of the nature of the study drug. The left ventricular outflow diameter (LVOT) will be measured in the parasternal long-axis view. Then velocity time integral (VTI) will be measured from the apical five-chamber view. The average of three VTI readings will be calculated.

The cardiac output will be calculated by the equation:

CO = π X (LVOT diameter/2) X VTI X heart rate Delta CO% will be calculated as percentage of change at each time point in relation to the baseline measurement the CO, heart rate, mean blood pressure will be measured before drug administration and at 3, 6, 10 and 15 min after drug administration

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11432
    • Ahmed Mohamed Hasanin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (>18 years) patients.
• With septic shock on vasopressor therapy
• Mechanically ventilated
• Need for sedation

Exclusion Criteria:

• Hemodynamic instability (MAP <65 mmHg) despite appropriate volume replacement and vasopressor therapy
• Noradrenaline infusion rate <0.05 mcg/kg/min
• Poor cardiac window on the ultrasound.
• Known allergy to study drugs
• Neurocritical patients with signs of increased intracranial tension

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine group; bolus of sedation for resuming sedation after sedation vacation	Drug: Ketamine; 100 mg of ketamine diluted in 10 mL saline (10 mg /mL) and patient will receive 0.1 mL/kg
Active Comparator: Fentanyl group; bolus of sedation for resuming sedation after sedation vacation	Drug: Fentanyl; 100 mcg of fentanyl diluted in 10 mL saline (10 mcg /mL) and patient will receive 0.1 mL/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minutes Delta CO%	percentage of change at 6 min after drug administration in relation to the baseline measurement	at 6 minutes after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta CO%	percentage of change at each time point after drug administration in relation to the baseline measurement	3, 6, 10 and 15 minutes after drug administration
heart rate	beat per minute	3, 6, 10 and 15 minutes after drug administration
mean blood pressure	mmHg	3, 6, 10 and 15 minutes after drug administration
norepinephrine dose	mcg/kg/min	3, 6, 10 and 15 minutes after drug administration

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: ahmed hasanin, MD, Cairo University Kasr Alainy Faculty of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

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; Adjuvants, Anesthesia; Ketamine; Fentanyl
• Other Study ID Numbers: MS-47-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The datasets used during the current study will be available from the corresponding author on reasonable request.

Drug and device information, study documents

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