Ketamine Versus Fentanyl for Induction of Anesthesia in Septic Shock

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Ketamine
* Drug: Fentanyl
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine group<br>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<br>* Patients will receive :1 mg/Kg ketamine for induction of anesthesia<br>* Other names: Katalar;Drug: Midazolam<br>* Patients will receive 0.05 mg/Kg midazolam<br>* Other names: Dormicum;|
| Active Comparator: Fentanyl<br>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: Fentanyl<br>* Patients will receive :2.5 mcg/Kg fentanyl for induction of anesthesia<br>Drug: Midazolam<br>* Patients will receive 0.05 mg/Kg midazolam<br>* Other names: Dormicum;|

What is the study measuring?
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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 |