Ketamine-fentanyl VS Fentanyl for Analgosedation in SICU

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03879564
• Other study ID #: Si783/2018
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 5, 2019
• Est. completion date: June 2024

Study information

• Verified date: November 2023
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: June 2024
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill
• Pain, Postoperative

Intervention

Drug:
• Ketamine
ketamine in NSS (1 mg/ml) IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr
• Normal saline
NSS IV bolus 0.3 ml/kg then drip 0.09 ml/kg/hr

Locations

Country	Name	City	State
Thailand	Faculty of medicine Siriraj hospital	Bangkok Noi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Psychomimetic adverse effects	incidence of delirium assess by CAM ICU hallucination nightmare	72 hours after admitted to ICU
Secondary	Duration of mechanical ventilation		30 days after admitted to ICU
Secondary	ICU length of stay		30 days after admitted to ICU
Secondary	bowel motility	first pass stool day	72 hours after admitted to ICU
Secondary	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
Secondary	cardiovascular effect	Number of participants that experience tachyarrhythmia;- Supraventricular/ventricular tachycardia during ketamine infusion	72 hours after admitted to ICU
Secondary	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
Secondary	cardiovascular effect	Number of participants that experience sinus tachycardia rate >130 bpm	72 hours after admitted to ICU
Secondary	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
Secondary	Long-term effect	Number of participants that has traumatic memories associated with severe pain.	12 to 60 months after ICU discharge
Secondary	Long-term effect	Number of participants that screening test positive for PTSD	12 to 60 months after ICU discharge