Analgesic Efficacy of Intravenous Ketamine as a Continuous Infusion vs PCA in the Management of Acute Postoperative Pain in Major Orthopedic Surgery.

April 8, 2025 updated by: Universidad de Antioquia

Analgesic Efficacy of Intravenous Ketamine as a Continuous Infusion vs PCA in the Management of Acute Postoperative Pain in Major Orthopedic Surgery: A Randomized Clinical Trial

The goal of this clinical trial is to determine whether treating pain after surgery with ketamine is more effective when administered intravenously as a continuous infusion or through a patient-controlled analgesia (PCA) pump. This study focuses on adult volunteers following major orthopedic surgery. We have two main questions to address:

  • Is a continuous intravenous infusion of ketamine as effective as ketamine administered through a PCA pump for managing pain after major orthopedic surgery.
  • Does a continuous intravenous infusion of ketamine result in lower opioid requirements compared to ketamine delivered through a PCA pump for pain management after major orthopedic surgery?

Participants will be divided into two groups. One group will receive ketamine via continuous infusion, while the other will receive it through a PCA pump. Both groups will also receive a placebo (a substance that looks like the drug but contains no active ingredients), ensuring that neither group knows whether they are receiving ketamine through the PCA pump (which always contains a painkiller) or as a continuous infusion.

Participants will be assigned to one of the two groups and will receive their assigned treatment for 48 hours while hospitalized. Researchers will visit participants during their first three days in the hospital to assess their pain levels and monitor for any side effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Managing postoperative pain is a primary concern for patients undergoing major surgery, especially in major orthopedic surgery. Effective pain management is crucial, as uncontrolled postoperative pain can lead to prolonged hospital stays, decreased patient satisfaction, and various complications, including pulmonary and gastrointestinal issues.

Current pain management strategies emphasize multimodal analgesia, which involves using multiple medications with different mechanisms of action to minimize side effects. Ketamine has been investigated in this context and has been found effective for treating postoperative pain following major surgeries while reducing the need for opioids. However, there is still some uncertainty regarding the optimal method for administering ketamine after surgery. The aim of this trial is to compare the effectiveness of intravenous ketamine in terms of pain control, measured by numerical pain scores, and opioid consumption within the first 24 hours postoperatively using two different strategies: continuous infusion versus patient-controlled analgesia (PCA) in adults undergoing non-cardiac surgery.

For this research, two hypotheses are proposed, as the objective involves two types of outcomes related to the analgesic effectiveness of intravenous ketamine: pain measured by a numerical pain scale and opioid consumption equivalent to oral morphine.

Based on data from previous studies, it is highly likely that continuous ketamine infusion will provide similar pain control efficacy at 24 hours compared to PCA ketamine. However, the data suggests that continuous infusion may result in lower opioid consumption than PCA. Therefore, the hypotheses are as follows:

**First Hypothesis** Continuous ketamine infusion is not inferior to PCA ketamine for pain control, as measured by a numerical pain scale at 24 hours postoperatively in patients undergoing major orthopedic surgery with a high risk of severe acute pain.

**Second Hypothesis** Continuous ketamine infusion is superior to PCA ketamine in reducing opioid consumption at 24 hours postoperatively in patients undergoing major orthopedic surgery at high risk of severe acute pain.

This trial will be a triple-blind, parallel-group, pragmatic, non-inferiority controlled clinical trial focused on pain management and superiority regarding opioid use, along with other secondary outcomes.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 050010
        • Recruiting
        • St. Vincent's Foundation University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patients over 18 years of age
  • Elective major orthopedic surgery.
  • ASA (American Association of Anesthesiology) classification 1, 2 or 3.

Exclusion Criteria:

  • Patients with a diagnosis of perioperative kidney injury or hepatic failure
  • Patients with active cardiac conditions
  • Patients with any cognitive impairment that disables the patient from operating the PCA pump or impedes the postoperative interview
  • Patients with scheduled ICU admission with invasive ventilatory support
  • Patients with known hypersensitivity to opioid medications
  • Patients with past medical history of severe adverse reactions to opioids or ketamine.
  • Pregnant patients
  • Patients undergoing continuous regional anesthetic techniques including peripheral nerve catheters or continuous epidural catheters
  • Patient refusal to participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ketamine infusion
Intravenous ketamine administered as a continuous infusion.
Drug: Ketamine infusion

A 10% ketamine solution will be prepared in a 250 cc bag of 0.9% saline (1 mg/cc) using 5 cc from a vial of ketamine that has a concentration of 50 mg/cc. The infusion will be initiated at the time of surgical site closure and will proceed as follows: a bolus of 0.35 cc/kg (equivalent to 0.35 mg/kg) will be administered, followed by a continuous infusion of 0.1 cc/kg/h (equivalent to 0.1 mg/kg/h) for up to 48 hours postoperatively.

Patients in this group will have access to a PCA pump with morphine for analgesic rescue and to monitor daily opioid consumption.
Active Comparator: PCA Ketamine
Intravenous ketamine administered along with opioid in a single saline bag using a Patient Controlled Analgesia pump
Drug: PCA Ketamine

A mixture of 5% ketamine and 5% morphine will be prepared in a 100 cc bag of 0.9% saline. This will be achieved by using 1 cc of a ketamine vial (50 mg/cc) and 5 cc of a morphine ampule (10 mg/cc). This results in a final concentration of 0.5 mg of ketamine and 0.5 mg of morphine per cc in the 100 cc saline bag.

The pump settings will be configured as follows:

  • PCA (Patient-Controlled Analgesia) dose: 2 cc (which delivers 1 mg of ketamine and 1 mg of morphine)
  • Lockout interval: 6 minutes
  • Maximum dose limit: 15 doses over a 4-hour period

The pump will be available for patient use for up to 48 hours postoperatively.

Other Names:
  • Ketamine PCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative pain
Time Frame: 24 hours after surgery
Visual Analog Scale (VAS) for dynamic (during movement) pain. The VAS for pain is a unidimensional measure of pain intensity in adults.The pain VAS is a continuous visual scale from 0 to 100 mm, with 0 mm representing "no pain" and 100 mm representing maximum pain (e.g. "worst pain imaginable").
24 hours after surgery
Postoperative opioid use
Time Frame: 24 hours after surgery
Daily opioid use expressed in morphine equivalents (morphine equivalent daily dose MEDD)
24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dynamic and rest postoperative pain
Time Frame: 12, 24, 48, and 72 hours after surgery
Visual Analog Scale (VAS) for dynamic and rest postoperative pain . The VAS for pain is a unidimensional measure of pain intensity in adults.The pain VAS is a continuous visual scale from 0 to 100 mm, with 0 mm representing "no pain" and 100 mm representing maximum pain (e.g. "worst pain imaginable")
12, 24, 48, and 72 hours after surgery
Postoperative opioid use
Time Frame: 48 and 72 hours after surgery
Daily opioid use expressed in morphine equivalents (morphine equivalent daily dose MEDD)
48 and 72 hours after surgery
Time to ambulation
Time Frame: 72 hours after surgery
Time measured in days for the patient to begin ambulation after surgery.
72 hours after surgery
Hospital stay
Time Frame: From date of randomization until the date day of discharge or date of death from any cause, whichever came first, assessed up to 36 months
Days of hospital stay
From date of randomization until the date day of discharge or date of death from any cause, whichever came first, assessed up to 36 months
Postoperative nausea and vomiting
Time Frame: 24 hours after surgery
Proportion of patients with at least one episode of nausea or vomiting after surgery
24 hours after surgery
Respiratory depression
Time Frame: 72 hours after surgery
Proportion of patients with any episode of respiratory rate <8 breaths per minute accompanied by supplemental oxygen requirement higher than a simple nasal cannula; or the requirement of facial mask ventilation or tracheal intubation; or requirement of naloxone reversal
72 hours after surgery
Oversedation
Time Frame: 2, 12, 24, 48, and 72 hours after surgery
Proportion of patients with any episode of sedation measured as a level 4 or higher using Ramsay's sedation scale
2, 12, 24, 48, and 72 hours after surgery
Psychomimetic symptoms
Time Frame: 72 hours after surgery

Proportion of patients with at least one of the following symptoms:

  • Hallucinations: Defined as any tactile, visual, auditory, or sensory experience in the absence of an appropriate stimulus, referred by the patient as real
  • Nightmares: Defined as any vivid dream with a negative or dysphoric emotional content
72 hours after surgery
Delirium
Time Frame: 72 hours after surgery
Proportion of patients diagnosed with delirium using the Confusion Assessment Method scale
72 hours after surgery
Hemodynamic measurements - Arterial pressure
Time Frame: 2, 12, 24, 48, and 72 hours after surgery
Systolic, diastolic, and mean arterial pressure in mmHg.
2, 12, 24, 48, and 72 hours after surgery
Hemodynamic measurements - Heart rate
Time Frame: 2, 12, 24, 48, and 72 hours after surgery
Heart rate in beats per minute.
2, 12, 24, 48, and 72 hours after surgery
Urinary retention
Time Frame: 72 hours after surgery
Proportion of patients with any event of impossibility for spontaneous micturition reported by the patient requiring physical measures or urinary catheter insertion for resolution
72 hours after surgery
Pruritus
Time Frame: 72 hours after surgery
Proportion of patients reporting any episode of itching in any body region
72 hours after surgery
Time to first bowel movement
Time Frame: 72 hours after surgery
Measured in time to initiation of the first passing of stool or flatus
72 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad de Antioquia

Collaborators

Hospital San Vicente Fundación

Investigators

  • Study Chair: Fabian D Casas, Professor, Universidad de Antioquia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2025

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

June 15, 2027

Study Registration Dates

First Submitted

January 7, 2025

First Submitted That Met QC Criteria

January 13, 2025

First Posted (Actual)

January 14, 2025

Study Record Updates

Last Update Posted (Actual)

April 11, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 36-2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It was not approved by our Institutional Research Board.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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