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Low Doses of Ketamine and Postoperative Quality of Recovery

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ClinicalTrials.gov Identifier: NCT02571153
Recruitment Status : Completed
First Posted : October 8, 2015
Results First Posted : March 6, 2017
Last Update Posted : March 6, 2017
Sponsor:
Information provided by (Responsible Party):
Eduardo Toshiyuki Moro, Pontificia Universidade Catolica de Sao Paulo

Tracking Information
First Submitted Date  ICMJE October 2, 2015
First Posted Date  ICMJE October 8, 2015
Results First Submitted Date  ICMJE September 28, 2016
Results First Posted Date  ICMJE March 6, 2017
Last Update Posted Date March 6, 2017
Study Start Date  ICMJE September 2015
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 12, 2017)
Quality of Postoperative Recovery Assessed by QoR-40 Questionnaire 24 Hours After Surgery [ Time Frame: 24 hours ]
Quality of postoperative functional recovery assessed by the questionnaire QoR40 The quality of postoperative functional recovery was assessed by the QoR-40 questionnaire, which assesses five dimensions of recovery (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items; physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR-40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). The QoR-40 was administered by a blind investigator 24 hours after surgery.
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2015)
QoR-40 [ Time Frame: 24 hours ]
Quality of postoperative functional recovery assessed by the questionnaire QoR40
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2017)
  • Length of PACU Stay [ Time Frame: During the stay at postanesthesia recovery room (about 90 to 120 minutes) ]
    Length of stay at postanesthesia recovery room
  • Occurrence of Postoperative, Nausea and Vomiting [ Time Frame: 24 hours ]
    Percentage of participants with postoperative nausea and vomiting at the PACU and during the hospital ward stay
  • Occurrence of Pain at PACU Using a 0-10 Numeric Pain Rating Scale [ Time Frame: 90 minutes postanesthesia at recovery room ]
    Occurrence of pain at the PACU. Average Pain will be calculated. The pain score will be evaluated using a 0-10 numeric pain rating scale, where zero mean no pain and 10 the worst imaginable pain.
  • Morphine Consumption (mg) at PACU [ Time Frame: During the stay at postanesthesia recovery room (about 90 to 120 minutes) ]
    Morphine consumption (mg) at PACU (about 90 to 120 minutes)
  • The Severity of Postoperative Pain [ Time Frame: 24 hours ]
    The severity of postoperative pain was rated the higher score of pain (NRS) during the hospital ward stay. Pain was evaluated using a 0-10 numeric pain rating scale (NRS), where zero meant no pain and 10 the worst imaginable pain.
  • Percentage of Participants With Tramadol Consumption [ Time Frame: 24 hours ]
    Percentage of Participants with Tramadol during the ward stay
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2015)
  • Length of PACU Stay [ Time Frame: 5 minutes ]
    Length of stay at postanesthesia recovery room
  • PONV [ Time Frame: 24 hours ]
    Occurrence of nausea and vomiting at the PACU and during the hospital ward stay
  • Pain [ Time Frame: 24 hours ]
    Occurrence of pain at the PACU and during the hospital ward stay
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Doses of Ketamine and Postoperative Quality of Recovery
Official Title  ICMJE Effects of Low Doses of Ketamine on Postoperative Quality of Recovery After Total Intravenous Anesthesia
Brief Summary There are evidences that intraoperative administration of low doses of ketamine may contribute to control the postoperative pain by acting on the N-methyl-D-aspartate (NMDA) channel, reducing the effects related to the tolerance and hyperalgesia induced by opioids. This study aims to evaluate the effects of administration of this agent not only as an analgesic but also its role in the quality of recovery from anesthesia, which includes observation of emotional, psychological and physical aspects. Patients who were scheduled to undergo total intravenous anesthesia (TIVA) for laparoscopic cholecystectomy will be enrolled in this clinical study. After induction of anesthesia, patients will receive one of three solutions according to the randomly selected group: ketamine 0,2 mg/kg; ketamine 0,4 mg/kg or saline. In the recovery room and on the ward, data related to the presence of pain, analgesic consumption, the incidence of nausea and vomiting, dizziness or hallucinations will be recorded. The next day, the quality of recovery will be evaluated by application of the questionnaire QoR40 (Quality of Recovery Questionnaire-40).
Detailed Description

Introduction It is known that nociceptive stimuli, triggered by surgery and tissue inflammation can cause peripheral sensitization and primary hyperalgesia, increases spinal responsiveness to stimuli, whether harmful or not, due to the wind-up phenomenon, and other mechanisms, with induction central sensitization. Additionally, opioids commonly employed during general anesthesia may activate, both, the antinociceptive system and the pro-nociceptive system which can lead to acute tolerance and hyperalgesia. There is evidence that NMDA receptors are involved in the development of these changes and that low doses of ketamine (< 1mg/kg) may control of postoperative pain to bind to the receptor phencyclidine the NMDA channel and inhibit the activation of the channel by glutamate non-competitively. Recently, there has been a change in pain management, which includes the observation of non-traditional variables such as those related to the concepts of satisfaction and quality of life related to health. To this end, a growing number of authors went on to assess the opinion of patients as a way to determine the quality of recovery from anesthesia, meaning the observation not only of pain intensity, but also aspects related to emotional state, comfort and independence physical. The QoR-40 questionnaire (Quality of recovery-40), a validated instrument for this purpose, allows an objective approach of these factors that can influence the perception of the patient and allows you to compare different therapeutic ways. There are no recent data on the application of this instrument to assess the effects of giving, or not, of low doses of ketamine on the quality of recovery of patients undergoing total intravenous anesthesia.

Methods After arrival in the operating room, standard American Society of Anesthesiologists (ASA) monitors will be applied. Midazolam 0.06 mg/kg and 1% lidocaine (30 mg) will be administered intravenously immediately after venoclysis. After anesthesia induction, capnographic monitoring will be added and the neuromuscular blockade will be evaluated using acceleromyography (TOF Watch). Induction and maintenance of anesthesia will be performed as follows: remifentanil, induction dose 0.5 μg/kg/min, followed by a maintenance dose of 0.3 μg/kg/min. Propofol, initial bolus (2.0 mg/kg) followed by infusion at 4 to 6 mg/kg/h. Each patient will receive rocuronium (0.6 mg/kg) before tracheal intubation. Ventilation will be controlled by adjusting the flow volume and respiratory rate to keep the end-tidal carbon dioxid (CO2) level between 30 and 40 mmHg. In the case of inadequate depth of anesthesia (movements, sweating, tachycardia, blood pressure increase >10% of the pre-induction value), propofol infusion or sevoflurane rate will be increased (by 1%); if this was not sufficient, the remifentanil infusion rate will be also increased (by 0,1 μg/kg/min). Patients who exhibit reductions in systolic arterial pressure (SAP) greater than 30% or heart rate (HR) reductions to less than 50 bpm will be given ephedrine (10 mg) and atropine (0.5 mg), respectively. After induction patients will receive one of three intravenous solutions: ketamine 0.2 mg/kg - diluted in saline until the volume of 5 mililiters (mL) (k2 group); ketamine 0.4 mg/kg diluted in saline until the volume of 5 ml (k4 group) or 5mL of 0.9% normal saline (K0 group). Hydration will be maintained with 0.9% normal saline 2 ml/kg/h. All of the participants were given dexamethasone (8 mg) and ketoprofen (100 mg) at the onset of surgery and dimenhydrinate (30 mg), dipyrone (1 g) and morphine (0.1 mg/kg) 15 minutes prior the end of the procedure. Atropine (0.01 mg/kg) and neostigmine (0.05 mg/kg) were used to achieve T4/T1>0.9 on the TOF monitor. Extubation was performed after awakening. When stable vital signs and respiration was confirmed, all patients were transferred to the postanesthesia care unit (PACU). Data related to the occurrence of pain, nausea, vomiting, dizziness or hallucinations at the PACU will be recorded as will be the length of stay in the PACU. Pain will be assessed every 15 minutes using a 0-10 numeric pain rating scale, where zero meant no pain and 10 the worst imaginable pain. Morphine (1 to 2 mg) will be administered intravenously every 10 minutes to maintain the pain score below 4 (1 mg when the pain score was <7 and 2 mg when it was ≥7). Following discharge from the PACU (minimum stay 60 minutes and Aldrete & Kroulik index >9), all of the participants will be given ketoprofen (100 mg) every 12 hours and dipyrone (30 mg/kg, maximum 1 g) every six hours intravenously. Whenever patients judged that their analgesia was insufficient, tramadol (100 mg) will be administered intravenously at eight-hour minimum intervals as needed. Postoperative nausea and vomiting (PONV) will be treated with dimenhydrinate (30 mg) intravenously. Pain score, use of analgesics, and the occurrence of nausea, vomiting, and other complications during the hospital ward stay will be recorded.

QoR40 The quality of postoperative functional recovery will be assessed by the QoR40 questionnaire, which assesses five dimensions of recovery (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items; physiological support - 7 items; and pain - 7 items). Each item is rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). The QoR40 will be administered by a blind investigator 24 hours after surgery.

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
  • Postoperative Pain
  • Postoperative Nausea and Vomiting
Intervention  ICMJE
  • Drug: Ketamine 0.4 mg/kg
    Intravenous ketamine 0.4 mg/kg after induction of anesthesia
  • Drug: Normal saline
    Intravenous normal saline 0.9% 5 mL
  • Drug: Ketamine 0.2 mg/kg
    Intravenous ketamine 0.2 mg/kg after induction of anesthesia
Study Arms  ICMJE
  • Placebo Comparator: Saline group
    Normal saline 0.9% (5 mL)
    Intervention: Drug: Normal saline
  • Experimental: Ketamine 0.2
    ketamine 0.2 mg/kg (5 mL)
    Intervention: Drug: Ketamine 0.2 mg/kg
  • Experimental: Ketamine 0.4
    ketamine 0.4 mg/kg (5 mL)
    Intervention: Drug: Ketamine 0.4 mg/kg
Publications *

*   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: January 12, 2017)
135
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2015)
150
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • American Society of Anesthesiologists physical status I or II
  • Patients scheduled to undergo laparoscopic cholecystectomy

Exclusion Criteria:

  • Patients who refuse to participate in the study
  • Patients who are not able to communicate due to alterations in the level of consciousness, or neurologic, or psychiatric disease
  • Contraindication of any of the drugs used in the study
  • Patients who are superobese (BMI>40)
  • History of alcohol or drug dependence
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02571153
Other Study ID Numbers  ICMJE PUCSP 057539/2015
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eduardo Toshiyuki Moro, Pontificia Universidade Catolica de Sao Paulo
Study Sponsor  ICMJE Pontificia Universidade Catolica de Sao Paulo
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eduardo T Moro, PhD School of Medical and Health Sciences, Pontificial Catholic University of São Paulo - PUCSP
PRS Account Pontificia Universidade Catolica de Sao Paulo
Verification Date January 2017

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