AN INTRAOPERATIVE SMALL
DOSE OF KETAMINE PREVENTS
REMIFENTANIL-INDUCED
POSTANESTHETIC SHIVERING
Hilary Wagner RN, BSN, SRNA
Oakland University-Beaumont/MSNAnesthesia
Class of 2013
Nakusuji, M., Nakamura, M., Imanaka, N.,
Tanaka, M., Nomura, M., & Suh, S. H.
(2011). An intraoperative small dose
of ketamine prevents remifentanilinduced 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 remifentanilinduced 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 1.5-2 mg/kg IV
and a remifentanil infusion at 0.25-0.5 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 30-50
 FiO2 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;113:484-487
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