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

Information source: Hospital Arquitecto Marcide
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pain, Postoperative

Intervention: Ketamine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Hospital Arquitecto Marcide

Official(s) and/or principal investigator(s):
Manuel Camba Rodriguez, M.D., Study Chair, Affiliation: Hospital Arquitecto Marcide
Beatriz Nistal Nuno, M.D., Principal Investigator, Affiliation: Complexo Hospitalario Universitario A Coruna
Enrique Freire-Vila, M.D., Study Director, Affiliation: Complexo Hospitalario Universitario A Coruna
Francisco Castro Seoane, M.D., Principal Investigator, Affiliation: Hospital Arquitecto Marcide

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.

Clinical Details

Official title: Preoperative Low-dose Ketamine Has no Preemptive Analgesic Effect in Opioid-nave Patients Undergoing Colon Surgery When Nitrous Oxide is Used

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Visual Analog Scale (VAS) score

Secondary outcome: morphine consumption

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.

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Hospital Arquitecto Marcide, Ferrol, A Coruna 15405, Spain
Additional Information

Starting date: September 2001
Last updated: September 15, 2014

Page last updated: August 23, 2015

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