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Preoperative Ketamine Has no Preemptive Analgesic Effect in Patients Undergoing Colon Surgery.

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ClinicalTrials.gov Identifier: NCT02241278
Recruitment Status : Completed
First Posted : September 16, 2014
Last Update Posted : September 16, 2014
Sponsor:
Collaborator:
Complexo Hospitalario Universitario de A Coruña
Information provided by (Responsible Party):
Beatriz Nistal Nuno, Complexo Hospitalario Universitario de A Coruña

Tracking Information
First Submitted Date  ICMJE September 11, 2014
First Posted Date  ICMJE September 16, 2014
Last Update Posted Date September 16, 2014
Study Start Date  ICMJE September 2001
Actual Primary Completion Date June 2002   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2014)
  • Visual Analog Scale (VAS) score [ Time Frame: at 0 hours postoperatively (arrival at recovery room) ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 1 hour postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 2 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 4 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 8 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 12 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 16 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
  • Visual Analog Scale (VAS) score [ Time Frame: at 24 hours postoperatively ]
    The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2014)
morphine consumption [ Time Frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively ]
The cumulative amounts of morphine (mg) administered through the Patient-Controlled-Analgesia (PCA) device as a basal infusion and the incremental supplemental bolus required by the patient were documented at these time points.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 15, 2014)
  • Blood Pressure (BP) systolic [ Time Frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively ]
    Measured in mm Hg. We evaluated these hemodynamic parameters as an indirect measure of pain.
  • Blood Pressure (BP) diastolic [ Time Frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively ]
    Measured in mm Hg. We evaluated these hemodynamic parameters as an indirect measure of pain
  • Heart rate [ Time Frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. ]
    We evaluated these hemodynamic parameters as an indirect measure of pain
  • Respiratory rate [ Time Frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. ]
    We evaluated these hemodynamic parameters as an indirect measure of pain.
  • Time for the first demand of analgesia [ Time Frame: 24 h postoperatively. ]
    The time interval to first solicited rescue analgesia in the 24 h postoperatively (in minutes). This rescue analgesia was administered if the established analgesic treatment was not sufficient to alleviate pain.
  • Number of rescue doses [ Time Frame: 24 h postoperatively ]
    The number of times a rescue analgesic dose was administered as a supplement in the first postoperative 24 hours.
  • Satisfaction score [ Time Frame: 24 hours postoperatively ]
    Global patient satisfaction (0-3), regarding pain control, was measured 24 hours after the operation
  • Side effects [ Time Frame: 24 hours postoperatively ]
    Number of Participants with Serious and Non-Serious Adverse Events in the 24 hours postoperatively
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Preoperative Ketamine Has no Preemptive Analgesic Effect in Patients Undergoing Colon Surgery.
Official Title  ICMJE Preoperative Low-dose Ketamine Has no Preemptive Analgesic Effect in Opioid-naïve Patients Undergoing Colon Surgery When Nitrous Oxide is Used
Brief Summary

The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. In the literature, the value of this anesthetic for preemptive analgesia in the control of postoperative pain is uncertain. The objective of this study was to ascertain whether preoperative low-dose ketamine reduces postoperative pain and morphine consumption in adults undergoing colon surgery.

In a double-blind, randomized trial, 48 patients were studied. Patients in the ketamine group received 0.5 mg/kg intravenous ketamine before surgical incision, while the control group received normal saline. The postoperative analgesia was achieved with a continuous infusion of morphine at 0.015 mg∙kgˉ¹∙hˉ¹ with the possibility of 0.02 mg/kg bolus every 10 min. Pain was assessed using the Visual Analog Scale (VAS), morphine consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. We quantified times to rescue analgesic (Paracetamol), adverse effects and patient satisfaction.

Detailed Description

In spite of the techniques we have at our disposal and the elementary nature of incisional pain, optimal pain management remains a challenge. Because the severity of early postoperative pain relates to residual pain after some types of surgery, perioperative pain management can considerably influence the long-term quality of life in patients.

Woolf, in 1983, first introduced the theory of preemptive analgesia to attenuate postoperative pain, confirming the presence of a central factor of post-injury pain hypersensitivity in experimental research. After this, experimental studies showed that various anti-nociceptive methods applied before injuries were more effective in reducing post-injury central sensitization in contrast to administration after injury.

After activation of C-fibers by noxious stimuli, sensory neurons become more sensitive to peripheral inputs, a process called central sensitization. 'Wind up, another mechanism activating spinal sensory neurons, is seen after reiterated stimulation of C-fibers. These sensitizations produce c-fos expression in sensory neurons, and are related to the activation of N-methyl-D-aspartic acid (NMDA) and neurokinin receptors. These genes produce long-lasting changes in the pain-processing system, resulting in hyperexcitation. According to Wall, protection of sensory neurons against central sensitization may provide relief from pain after surgery. Based on this assumption, preemptive analgesia has been recommended as an effective aid to control postsurgical pain. NMDA antagonists have been demonstrated to block the induction of central sensitization and revoke the hypersensitivity once it is established.

Ketamine is an old drug that is increasingly being considered for the treatment of acute and chronic pain. Its pharmacology and mechanism of action as an NMDA receptor antagonist are adequately known, but in clinical practice it presents irregular results. Since ketamine is an NMDA-receptor antagonist, it is supposed to avoid or revoke central sensitization, and thus to attenuate postoperative pain.

This antihyperalgesic action can be achieved by smaller doses than those required for anesthesia. Small-dose ketamine has been specified as not more than 1 mg/kg when given as an iv bolus, and not higher than 20 µg∙kgˉ¹∙minˉ¹ when given as a constant infusion.

Low-doses preemptive ketamine administered iv seem to reduce postoperative pain and/or analgesic consumption. According to one study, a single dose of ketamine 1 mg/kg, when administered in conjunction with local anesthetics, opioids or other anesthetics, provides good postoperative pain control.

Regardless of the overwhelming effectiveness of preemptive ketamine in animal experiments, clinical reports are mixed; some authors have described positive effects while others have not.

While early reviews of clinical findings were mostly contradictory, there is still conviction in the effectiveness of preemptive analgesia.

To our knowledge, no prior controlled study has determined the effectiveness of preoperative low-dose iv ketamine as contrasted with placebo in adults after open colon surgery. Thus, this clinical trial was designed to examine the postoperative analgesic effectiveness and opioid-sparing effect of single low-dose iv ketamine in contrast with placebo administered preoperatively.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Pain, Postoperative
Intervention  ICMJE Drug: Ketamine
In the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision (a single dose).
Other Name: ketamine chlorhydrate
Study Arms  ICMJE
  • Placebo Comparator: Control
    In the operating room, the anesthesiologist administered 50 mL of 0.9% saline intravenously to patients in the control group 30 minutes before surgical incision.
  • Experimental: Ketamine
    In the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision. (a single dose).
    Intervention: Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 15, 2014)
48
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2002
Actual Primary Completion Date June 2002   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age between 18 and 75 years
  • normal Body Mass Index (18.5 - 24.9)
  • American Society of Anesthesiologists (ASA) class I, II or III
  • elective surgery
  • surgery time between 60-150 min
  • understanding of the Visual Analog Scale (VAS)
  • lack of allergies or intolerance to anesthetics
  • absence of psychiatric illness

Exclusion Criteria:

  • cognitive deterioration
  • inability to use the Patient-Controlled-Analgesia (PCA) device
  • history of chronic pain syndromes
  • chronic use of analgesics, sedatives, opioids or steroids
  • liver or hematologic disease,
  • history of drug or alcohol abuse
  • intolerance to ketamine or Paracetamol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02241278
Other Study ID Numbers  ICMJE MK334037
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Beatriz Nistal Nuno, Complexo Hospitalario Universitario de A Coruña
Study Sponsor  ICMJE Hospital Arquitecto Marcide
Collaborators  ICMJE Complexo Hospitalario Universitario de A Coruña
Investigators  ICMJE
Study Chair: Manuel Camba Rodriguez, M.D. Hospital Arquitecto Marcide
Principal Investigator: Beatriz Nistal Nuno, M.D. Complexo Hospitalario Universitario A Coruna
Study Director: Enrique Freire-Vila, M.D. Complexo Hospitalario Universitario A Coruna
Principal Investigator: Francisco Castro Seoane, M.D. Hospital Arquitecto Marcide
PRS Account Hospital Arquitecto Marcide
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP