AN INTRAOPERATIVE SMALL DOSE OF KETAMINE PREVENTS REMIFENTANIL-INDUCED POSTANESTHETIC SHIVERING Hilary Wagner RN, BSN, SRNA Oakland University-Beaumont/MSN- Anesthesia Class of 2013

Nakusuji, M., Nakamura, M., Imanaka, N., Tanaka, M., Nomura, M., & Suh, S. H. (2011). An intraoperative small dose of ketamine prevents remifentanil- induced postanesthetic shivering. Anesthesia & Analgesia, 113 (3).

INTRODUCTION  Published in the September 2011 edition of Anesthesia & Analgesia  The study was approved by the Human Ethics Review Committee of Kansai Denryoku Hospital in Japan

STUDY OBJECTIVES/PURPOSE  Postanesthetic shivering (PAS) is frequently encountered in patients after discontinuation of remifentanil infusion  Remifentanil is more likely to cause PAS than other opioids  However, the exact cause of remifentanil- induced PAS remains undetermined at this time

STUDY OBJECTIVES/PURPOSE  To investigate whether or not a ketamine infusion while using remifentanil during gynecological laparotomy cases reduces the incidence of PAS

STUDY  Patients were enrolled in this study from August 2009 to October 2010  Randomized controlled trial  Prospective study  Dependent variable = Postanesthetic shivering  Independent variable = Ketamine infusion

INCLUSION CRITERIA  ASA status of I or II  Under age 60  Surgical time less than 3.5 hours (surgical times longer than 3.5 hours are correlated with PAS)  Patients were automatically excluded if they were:  undergoing emergency surgery  scheduled for radical hysterectomy

METHODS  Signed written consent form was obtained from each subject  64 patients meeting inclusion criteria were randomly assigned to receive either 0.5 mg/kg ketamine at induction followed by an infusion of 0.3 mg/kg/hr for the duration of surgery (n=32) or a similar volume of saline (n=32).  The patients were randomly assigned via envelope randomization

METHODS (CONT.)  In both groups, all patients received:  Midazolam IM (2.5-5 mg) 15 minutes before OR arrival  An epidural catheter at the T12-L1 interspace  Epidural ropivacaine titrated intraoperatively to maintain systolic arterial blood pressure within 20% or less of preoperative blood pressure  General anesthesia induced with propofol at mg/kg IV and a remifentanil infusion at mcg/kg/min (for analgesia)  Vecuronium bromide for tracheal intubation at 0.1 mg/kg IV

METHODS (CONT.)  Total IV anesthesia with propofol titrated to maintain a target Bispectral Index (BIS) value between  FiO 2 at 0.40 (a mix of oxygen and air, no nitrous oxide was used)  100 mcg of fentanyl via the epidural catheter after closure of the peritoneum  1.25 mg of droperidol at the end of the case to prevent postoperative nausea and vomiting  Forced air blanket to lower extremities at 32C which was discontinued when rectal temperature reached 37C  Lactated ringer’s solution infused at ambient temperature of 25-27C

METHODS (CONT.)  The OR staff were unaware as to which patients were part of the experimental and control groups  The staff monitored the patients for PAS while in the OR and for 30 minutes post-emergence

OUTCOME MEASURES(CONT.)  Measured shivering with a 5-point rating scale 0: no shivering 1: peripheral vasoconstriction with no visible muscular activity 2: visible muscular activity confined to only 1 muscle group 3: visible muscular activity in more than 1 muscle group 4: gross muscular activity involving the whole body  A score between 3 and 4 indicated PAS

METHODS (CONT.)  The anesthesia provider remained absent during the PAS evaluation so as not to allow bias related to anesthetic regimen knowledge  Postoperative pain was also evaluated using the visual analog scale from 0 (no pain) to 10 (worst pain)  PAS was then treated using a warm blanket  If PAS persisted longer than 15 minutes, 50 mg of flurbiprofen axetil was administered (COX inhibitor)

A flow diagram of inclusion and exclusion criteria applied in this study, based on the CONSORT (Consolidated Standards of Reporting Trials) statement. Nakasuji M et al. Anesth Analg 2011;113:

STATISTICAL ANALYSIS  Student t test and the Mann-Whitney U test were used for statistical comparisons  Differences between the groups were considered statistically significant when the P value was <0.05  Normality and equal variance tests were applied to all data (expressed as mean ± SD)

RESULTS  No significant difference in temperature throughout anesthesia between both groups  All patients were found to be pain free for 30 minutes post emergence from anesthesia using the visual analog scale

RESULTS (CONT.)  Incidence of PAS in ketamine group  n=2, 6%  Incidence of PAS in control (saline) group  n=12, 38%, P=0.005

DISCUSSION  The study showed that the incidence of remifentanil-induced PAS during the early recovery period was markedly reduced when ketamine was also administered intraoperatively  Exact mechanism of this remains to be discovered  Other factors which may have influenced the incidence of PAS were well controlled in this study (such as postoperative pain and hypothermia)

STRENGTHS  Another study demonstrated decreased incidence of PAS when using intraoperative magnesium sulfate (a noncompetitive NMDA receptor antagonist) in patients receiving propofol/remifentanil based anesthesia  This suggests that the stimulation of NMDA receptors may be the underlying mechanism of remifentanil-induced PAS

LIMITATIONS  Small sample size (n=64)  Short duration of observation  Patients were only observed for 30 minutes after emergence  They may have developed PAS after transfer to the GYN floor  Cannot entirely exclude the possibility of residual sedative and analgesic effects being the cause of the differences observed

CONCLUSION  While the mechanism of the reduced incidence of PAS is still not fully understood, ketamine should be considered when using high dose remifentanil during surgery