Ketamine-fentanyl VS Fentanyl for Analgosedation in SICU

Efficacy of Ketamine-fentanyl VS Fentanyl for Analgosedation in Postoperative Ventilated SICU Patients

This is a randomized, double-blinded study to evaluate the analgosedative effect of ketamine in a surgical intensive care unit. The patients who will receive continuous fentanyl infusion for either pain control or sedation will be recruited in this trial. Fentanyl will be titrated with initial loading doses of 20 mcg until the numeral rating scale(NRS) less than 4 or critical care pain observation tool (CPOT) less than 3 or Richmond agitation sedation score (RASS) -2-0. Then the patients will be randomised in to receive saline infusion in control group (Group C) or ketamine infusion in ketamine group (Group K). Ketamine will be administered with an initial bolus of 0.3 mg/kg followed by a perfusion of1.5 mcg/kg/min during the first 48 h. The dose of fentanyl will be protocolized adjusted according to NRS or CPOT or RASS. We tested the research hypothesis that low-doseketamine infusion is associated with a reduced fentanyl dose without increased vulnerability to its psychotropic effects.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Critically Ill
• Intervention / Treatment: Drug: Normal saline; Drug: Ketamine

Detailed Description

Upon SICU admission, patient eligibility will be assessed, and informed consent will be obtained. A fentanyl bolus will be titrated by attending physicians to reach the target of patients' NRS pain scores at < 4 (self-report) or CPOT scores < 3 (unable to self-report pain) or patients' Richmond agitation and sedation scale (RASS) scores between -2 and 0.

After enrollment, patients will be randomly assigned in a 1:1 ratio by their sequential number of enrollment to receive either ketamine infusion (Group K) or placebo (Group C) together with fentanyl at 20 mcg/hr, initially. Randomization will be performed using a computer-generated randomization table derived from www.randomization.com. This process will be performed by an investigator (K.W.) who has no other role in patient enrollment or management. The other investigators, the patients, the patients' relatives, the attending physicians, and the nurses will all blinded to the study assignment. The study drug (ketamine or placebo) will be prepared by a pharmacist, who has no other role in the trial. The study drugs are packaged in identically shaped containers labeled with sequential numbers according to the randomization table order. For the study drug, 50 mg of ketamine is mixed with 50 ml of 0.9% NaCl (NSS), giving a final ketamine concentration of 1 mg/ml. For the placebo comparator, 50 ml of NSS will be prepared. The study drug will infuse via either peripheral line or central venous catheter (when available) at an individually adjusted rate according to the patient's body weight to achieve a dose of ketamine of 1.5 mcg/kg/min. The study drug will infuse for a period of 48 hours or until discontinue if narcotic medication without titration in both groups.

All eligible patients will receive narcotic and sedative medication according to the pain and sedation protocol. This included infusion of narcotic medication (fentanyl) and sedative medication to keep target NRS scores at < 4 and RASS scores between 0 and -2. Additional 20-mcg fentanyl IV bolus every 10 minutes will be administrated if needed. If more than 2 boluses are given per hr, the fentanyl rate will be increased by 10 mcg/hr to achieve pain and sedation goals. Blinded nurses will record pain scores, RASS, and medication doses every 4 hours.

Fentanyl IV infusion will be held if the RASS score is less than -2, indicating oversedation. If fentanyl is not administered for over one hour and the patient's RASS score remained below -2, the study drug will be discontinued.

A telephone follow-up will be conducted 12-60 months after ICU discharge using the Thai version of the Posttraumatic Symptom Scale (PTSS-10 questionnaire) to screen for the occurrence of PTSD as well as traumatic memories in the ICU. The interviews will be conducted by a research team unaware of the patients' group assignment.

Primary outcome is fentanyl consumption within 24 hours after randomization. Secondary outcomes are adverse effects of ketamine which will be assessed during study drug administration and long-term follow up (12-60 months) of the patient using questionnaires on traumatic memories from their ICU stay and post-traumatic stress disorder (PTSD) screening questionnaire (PMID: 10470573).

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Older than 18 years.
• Need ICU care
• Need continuous iv fentanyl as an sedative of analgesia drug

Exclusion Criteria:

• Pregnant women
• Known allergy to ketamine
• Severe cardiovascular disorders (ejection fraction< 30%, acute myocardial infarction, decompensated heart failure, significant tachyarrhythmia)
• Acute psychosis
• coma patient
• receive
• Renal insufficiency (creatinine clearance < 30 mL/min)
• Unable to assess pain with either NRS or CPOT
• Neurosurgery/ CVT patients/ trauma patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control; 0.9% NaCl IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr	Drug: Normal saline; NSS IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr
Experimental: ketamine; ketamine in NSS (1 mg/ml) IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr	Drug: Ketamine; ketamine in NSS (1 mg/ml) IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fentanyl consumption	the amount of fentanyl in microgram/kg in the patients who receive ketamine compare with who receive NSS	24 hours after initial fentanyl infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation		30 days after admitted to ICU
ICU length of stay		30 days after admitted to ICU
Psychomimetic adverse effects	incidence of delirium assess by CAM ICU hallucination nightmare	72 hours after admitted to ICU
bowel motility	first pass stool day	72 hours after admitted to ICU
cardiovascular effect	Number of participants that experience episode of unexplained hypertension (sustained (> 30 min) increase in MAP + 25% from baseline) during ketamine infusion	72 hours after admitted to ICU
cardiovascular effect	Number of participants that experience tachyarrhythmia;- Supraventricular/ventricular tachycardia during ketamine infusion	72 hours after admitted to ICU
cardiovascular effect	Number of participants that experience atrial fibrillation with rapid ventricular response, rate > 110 bpm during ketamine infusion	72 hours after admitted to ICU
cardiovascular effect	Number of participants that experience sinus tachycardia rate >130 bpm	72 hours after admitted to ICU
Long-term effect	Number of traumatic memories that might be associated with ketamine per participant: Nightmares, severe anxiety or panic, and feeling of suffocation.	12 to 60 months after ICU discharge
Long-term effect	Number of participants that has traumatic memories associated with severe pain.	12 to 60 months after ICU discharge
Long-term effect	Number of participants that screening test positive for PTSD	12 to 60 months after ICU discharge

Collaborators and Investigators

• Sponsor: Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2019
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Disease Attributes; Pain, Postoperative; Critical Illness; 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; Ketamine
• Other Study ID Numbers: Si783/2018

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