Pain, Postoperative, Opioid Use, Major Surgery
Conditions
Keywords
postoperative pain, ketamine, patient controlled analgesia, continuous infusion, major surgery, pain, abdominal surgery, thoracic surgery, spine surgery, opioid, major orthopedic surgery
Brief summary
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.
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.
Interventions
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.
DRUGPCA 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.
Sponsors
Hospital San Vicente Fundación
Universidad de Antioquia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Treating Anesthesiologist: The anesthesiologist responsible for the case and intraoperative management will be blinded to the assigned intervention. The assignment will be carried out by another anesthesiologist who is not involved in the case. This external anesthesiologist will be present in the operating room, and after opening the envelope, will inform the nursing staff regarding which drug mixtures to prepare. Data Collection and Analysis Staff: Data will be collected during the hospital stay, up to three days, by two researchers. The researchers will be blinded to the assignment and will not have access to information about the prepared drug mixtures.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain | 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). |
| Postoperative opioid use | 24 hours after surgery | Daily opioid use expressed in morphine equivalents (morphine equivalent daily dose MEDD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to ambulation | 72 hours after surgery | Time measured in days for the patient to begin ambulation after surgery. |
| 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 | Days of hospital stay |
| Postoperative nausea and vomiting | 24 hours after surgery | Proportion of patients with at least one episode of nausea or vomiting after surgery |
| Respiratory depression | 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 |
| Oversedation | 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 |
| Psychomimetic symptoms | 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 |
| Dynamic and rest postoperative pain | 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) |
| Hemodynamic measurements - Arterial pressure | 2, 12, 24, 48, and 72 hours after surgery | Systolic, diastolic, and mean arterial pressure in mmHg. |
| Hemodynamic measurements - Heart rate | 2, 12, 24, 48, and 72 hours after surgery | Heart rate in beats per minute. |
| Urinary retention | 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 |
| Pruritus | 72 hours after surgery | Proportion of patients reporting any episode of itching in any body region |
| Time to first bowel movement | 72 hours after surgery | Measured in time to initiation of the first passing of stool or flatus |
| Delirium | 72 hours after surgery | Proportion of patients diagnosed with delirium using the Confusion Assessment Method scale |
| Postoperative opioid use | 48 and 72 hours after surgery | Daily opioid use expressed in morphine equivalents (morphine equivalent daily dose MEDD) |
Countries
Colombia
Contacts
Primary ContactFabian D Casas, Professor
Backup ContactMateo Aristizabal, Resident
Outcome results
None listed