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.

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

percentage of change at each time point after drug administration in relation to the baseline measurement

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

The datasets used during the current study will be available from the corresponding author on reasonable request.