To Compare the Effectiveness Of Low Dose Intravenous Ketamine Versus Pethidine For Postoperative Shivering In Surgical Patients Under General Anesthesia: A Prospective Cohort Study
Geresu Gebeyehu1*, Betelihem Girma1, Assefa Hika2
1 Department of Anesthesia, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
2 Department of Anesthesia, School of Medicine, Axum University, Axum, Ethiopia.
*Corresponding Author
Geresu Gebeyehu,
School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
Tel:+251929315616
E-mail: geressu.gebeyehu@aau.edu.et
Received: August 04, 2020; Accepted: April 08, 2021; Published: April 10, 2021
Citation: Geresu Gebeyehu, Betelihem Girma, Assefa Hika. To Compare the Effectiveness Of Low Dose Intravenous Ketamine Versus Pethidine For Postoperative Shivering In Surgical Patients Under General Anesthesia: A Prospective Cohort Study. Int J Anesth Res. 2021;09(02):619-623. doi: dx.doi.org/10.19070/2332-2780-21000123
Copyright: Geresu Gebeyehu© 2021. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Postanesthesia shivering is one of the potential complications of anesthesia which may increase patient morbidity.
Various methods had been employed to control postoperative shivering. This study assessed the effectiveness of prophylactic
low dose intravenous ketamine and pethidine for postoperative shivering after general anesthesia.
Methods and Materials: This prospective cohort study recruited 76 ASA I and II patients aged 18-65 years old and underwent
elective surgery under general anesthesia. The patients were grouped by blinded anesthetist to take either ketamine 0.5mg/kg
or pethidine 0.5 mg/kg 20 minutes before completion of the surgery.The incidence and severity of postoperative shivering
were compared between the two groups every 10 minutes until one hour postoperatively. The side effects of the study drugs
were also compared between the two groups in the recovery room. Categorical data were analyzed with the Chi-Square test.
Parametric andnon-parametric data between the groups were analyzed using independent samples t-test and Mann-Whitney U
test respectively. A p-value of <0.05 was considered statistically significant.
Results: The incidence of shivering between the ketamine and pethidine groups was11(28.2%) and 14 (35.9%) respectively
(p=0.467). The severity of shivering was not significantly different between the two groups (p=0.893).The occurrence of nausea
and vomiting and sedation attributed to the drugs was significantly less in the ketamine group (p<0.05). PACU stay duration
and occurrence of hallucination among the groups were comparable. (p>0.05)
Conclusion and Recommendation: This study revealed administering low dose IV ketamine (0.5mg/kg) 20 minutes before
completion of surgery reduced postoperative shivering as effectively as pethidine. The study also showed clinically better
outcomes in favor of ketamine since it was associated with fewer side effects. Thus, we recommend low dose IV ketamine 20
minutes before completion of surgery under general anesthesia to prevent postoperative shivering.
2.Introduction
3.Methodology
4.Results
5.Discussions
6.Conclusion
7.Acknowledgments
8.References
Keywords
Ketamine; Pethidine; General Anesthesia; Postoperative Shivering; Elective Surgery.
Abbreviations
ASA: American Society of Anesthesiologists; BMI: Body Mass Index; CO2: Carbon Dioxide; ECG: Electrocardiography;
GA: General Anesthesia; IV: Intravenous; NMDA: N-methyl-D aspartate; PACU: Postanesthesia Care Unit;
PAS: Post-Anesthesia Shivering.
Introduction
Shivering after surgery under general anesthesia is a very common
problem with the incidence of 65% but varies in severity. It can
sometimes cause a great deal of discomfort in surgical patients
recovering from general anesthesia [1, 2]. moreover, it may have
deleterious sequelae in the post-operative period I,e. increased
oxygen consumption, increased CO2 production, increased risk
of postoperative hypoxemia, increased catecholamine release,
increased cardiac workload and risk of perioperative myocardial
ischemia, increased recovery room stay, and disturbing the reading
of monitors [3]. The problem is more pronounced in developing
countries where surgery is undertaken in a poorly equipped and
devoid of a perioperative temperature control system and poorly
practiced modern anesthetics I,e. predominantly using volatile anesthetics
[4, 5].
While there were different pharmacological and nonpharmacological
methods tried in the past to control shivering that occurs
intraoperatively and postoperatively, no novel methods and treatment
modalities discovered so far [6]. Pharmacological agents
used to prevent or treat the post-operative shivering, include
alfentanil, sufentanil, ketanserin, physostigmine, nefopam, urapidil,
doxapram, tramadol, nalbuphine, and pethidine, but the ideal
drug for this query has become questionable [7]. Among these
drugs, pethidine is the most effective drug but disadvantages I,e
nausea, vomiting, hallucination, and respiratory depression precludes
its utilization [8, 9, 18].
At several levels, N-methyl-d-aspartate receptor antagonists are
likely to modulate thermoregulation. Ketamine, the NMDA receptor
competitive antagonist, has different characteristics such
as cerebral vasodilatation, induction of relaxation of bronchial
smooth muscle, amnesia, ability to increase intracranial pressure,
cause transient, and marked increase of blood pressure by sympathetic
system stimulation, and analgesia. Ketamine can likely control
shivering, as a prophylactic agent [4, 9, 10]. This study aimed
to compare the effectiveness of prophylactic low dose ketamine
and pethidine as a way of preventing post-operative shivering after
general anesthesia.
Methodology
After obtaining ethical approval from the institutional ethics committee
of Addis Ababa University College of health sciences, a
prospective cohort study was conducted from January 01 to April
30, 2018, at Tikur Anbessa specialized hospital, Addis Ababa
Ethiopia. The study involved 76 ASA I and II patients aged 18-65
years old undergoing elective surgery under general anesthesia.
Sample size was calculated to compare two proportions based on
the following assumptions: significance level 5% (α= 0.05), and
power of study (1 – β) of 80%. From previous study, the effectiveness
of pethidine 0.5mg/kg and ketamine 0.5 mg/kg in preventing
postoperative shivering was found to be 88.9% and 62.2%
respectively (zabareh SMHT, et al. 2012) thus it’s computed as
follows:
n1 = n2 = p1(1 - p1) + p2(1 – p2) x (zα + zβ)2 / (p1 - p2
)2
= (0.889)(0.111)+(0.622)(0.378)x7.84/(0.889-0.622)2 = 37 per
each group
Where,
n1 = number of clients to take pethidine
n2 = number of clients to taken ketamine
Z = 95% confidence interval =1.96
F (α, β) = the power function at 80%= 7.84
P1 = Efficacy in percentage for pethidine (88.9%), Q1 is 1-P1
(11.1%)
P2 = Efficacy in percentage for ketamine (62.2%), Q2 is 1-P2
(37.8%)
By considering a contingency of 5%, the study involved 39 individuals.
Thus, the total sample for both groups was 39x2=78.
Two participants were excluded because of loss to follow up.
Thus, 76 participants completed the study.
The verbal consent was obtained from each participant to be involved
in the study. The participants were selected using a systematic
random sampling technique.
Patients induced with ketamine, BMI >30, thyrotoxicosis, psychiatric
problems, patients taking blood transfusion, hypertensive
patients, and convulsion were excluded from the study. The anesthetic
management of patients in both groups was according to
the hospital's routine practice guidelines. Anesthesia was induced
with propofol 2mg/kg, morphine 0.1mg/kg and vecuronium
0.1 mg/kg to facilitate tracheal intubation. Anesthesia was maintained
with intermittent bolus vecuronium0.1mg/kg and halothane
1-1.5%. In all patients, no active warming had been utilized
throughout the procedure. Patients were monitored using ASA
standard monitors. At about 20 minutes to complete the surgery,
patients were grouped to take either ketamine 0.5mg/kg IV or
pethidine0.5mg/kg IV as prophylaxis for postoperative shivering
by the anesthetist unaware about the study drugs. At the end of
the surgery, the trachea was extubated after successful antagonism
of neuromuscular blockade with neostigmine 0.04mg/kg and atropine
0.02mg/kg.
Patients were transferred to PACU once adequate depth and rate
of respiration ensured, and respond to commands. Patients were
monitored as per guidelines in the recovery room. Moreover, patients
were observed for the occurrence and severity of shivering
and side effects of the study drugs after arrival into PACU. The
severity of shivering was evaluated by a 5-grade scale.(Grade 0: no
shivering, grade I: peripheral vasoconstriction, grade II:shivering
involving one muscle group only, grade III: shivering in more
than one muscle group, and grade IV: shivering involving whole
body). Drug side effects like hallucination, sedation, nausea, and
vomiting were observed in the postoperative period.
The data was analyzed using SPSS version 20after it is cleaned
and coded. Independent samples t-test and Mann-Whitney U test
were used for quantitative data analysis that was distributed normally
and non-normally respectively.A Chi-square test was used
to analyze categorical data. Shapiro Wilks and Levene’s tests were
used to checking the normality of data and homogeneity of variances
respectively. A P-value of less than 0.05 was considered a
statistically significant difference in observation.
Results
A total of seventy-six ASA I and II patients were enrolled in the
study and were grouped into ketamine and pethidine group each
group containing 38 patients to compare the effectiveness of low
dose ketamine and pethidine as a way of preventing postoperative
shivering. The comparison of demographic and operative characteristics
including age, sex, height, weight, BMI, and ASA showed
no significant difference between the two groups. (Table 1)
The number of shivering patients in ketamine and pethidine
groups was 11(29%) and 14(36.8%) respectively (p=0.467). The
severity of shivering among the two groups was compared and no
statistically significant difference was observed (p>0.05). (Figure
1)
The comparison of intraoperative factors such as type and duration
of surgery, amount of blood loss, and total fluid adminis tered has shown no statistically significant difference among the
groups. (p>0.05) (Table 2)
The patients were observed for possible side effects such as sedation,
hallucination, nausea, and vomiting, and duration of PACU
stay. (Figure 2)
Discussions
Postoperative shivering had remained one of the common adverse
events in the patients recovering from general anesthesia.
Furthermore, it is associated with a major deal of discomfort to
both the patients and the medical care team. This prospective observational
study compared the effectiveness of prophylactic intravenous
ketamine 0.5mg/kg and pethidine 0.5mg/kg in elective
surgical patients under general anesthesia.
The antishivering effect of pethidine was suggested by several
reports. Its antishivering effect pertains to the k- opioid receptor
but not due to μ-receptor-mediated [9, 11, 12]. Even though, it
had been a novel antishivering drug, side effects related to pethidine
preclude its utilization in some situations [13].
The preventive effect of ketamine for postoperative shivering was
realized in many studies. However, its mechanism of action became
difficult to predict due to the pharmacological complexity
of the drug. The possible speculation for its anti-shivering effect
would be its action on the thermoregulatory center via NMDA
antagonism. Inhibition of NE reuptake at postganglionic fiber by
ketamine induces peripheral vasoconstriction which in turn decreases
core to peripheral redistribution of heat [11, 12, 14].
In this study, demographic factors like age, gender, weight, height,
ASA physical status, and BMI were all found to be comparable between
the two groups; the type and duration of surgery, amount
of blood loss and total fluid intake which were considered as risk
factors for perioperative hypothermia and shivering [15], were all
comparable between the two groups (p>0.05).
In this study, the overall incidence of postoperative shivering was
32.1%. This rate is higher than the report from the study conducted
in Isfahan University of medical sciences, Iran by Zabareh
SMHT et al. In their study, the overall shivering rate was 26.7%
which is smaller than the rate of our study [12]. The cause for this
might be a variation in intraoperative and postoperative patient
management. Another speculation could be Intraoperative use of
fentanyl which also has an anti-shivering effect, and higher operation
room ambient temperature in their study.
In this study, the number of shivering patients was 11(28.2%)
and 14(35.9%), p=0.467 for ketamine, and pethidine group respectively.
Although the difference was statistically insignificant,
it seems practically a better outcome in favor of ketamine. This
finding is in line with the study conducted in India by Dar AM,
et al. Their study showed no statistically significant difference
found between ketamine and pethidine groups (p>0.05) [16].
This might be due to the utilization of the same dose of the study
drugs. Another study conducted in Mashhad, Iran by Masomeh
et al also reported pethidine and ketamine can similarly reduce
post-operative shivering [17]. Our study result also supported by
a study in Tabriz University of Medical Sciences, Iran by Eydi M.
et al in 2014 [18]. The result of their study showed that ketamine
and pethidine are both equally effective in reducing postoperative
shivering. This could be due to a similar study design. Also, another
study, conducted by Ayatollahi V et al in Iran had reported
a similar finding to our study. Their study reported prophylactic
use of low doses of intravenous ketamine (0.3 or 0.5 mg/kg) was
found to be effective to prevent postanesthetic shivering. However,
administration of 0.3 mg/kg ketamine lowered the rate of
hallucination as compared with 0.5 mg/kg. [13]. This might be
related to different drug responses. A prospective RCT conducted
in Isfahan University of medical sciences, Iran by Zabareh SMHT
et al reported a contradictory finding in favor of pethidine. They
said pethidine seems to be the most appropriate choice for preventing
postoperative shivering [12]. The difference in the study
design could have contributed to this discrepancy.
Another prospective randomized study conducted by Emine Arzu
et al in Hacceteppe University, Turkey showed ketamine in doses
of 0.5-0.75 mg/kg had better reduced post-operative shivering
than pethidine. But ketamine 0.75 mg/kg associated with more
hallucination [19]. This might be caused by a higher dose of ketamine.
Another contradictory result to our finding was reported
by the study conducted in Motahari Hospital in Jahrom (Iran),
by Zabetian H, et al in 2016 [20]. The possible explanation could
be due to the usage of a small dose of ketamine than this study.
The severity of postoperative shivering was compared between
the two groups and the difference was not statistically significant
(p=0.874). A randomized double-blind study conducted by Dar
AM, et al showed similar findings to this study.The number of
patients with grade 1shivering was 7 and 9in ketamine and pethidine
group respectively while 3 patients in each group developed
grade shivering.This result is in line with the prospective RCT
conducted by Masomeh et al. [17] In their study, while only one
patient in ketamine group developed grade 1 shivering, no patient
has developed either grade 2 or 3 shiverings. But their finding for
the pethidine group was similar to the result of this study. This
could be due to less dose pethidine used to prevent postoperative
shivering. This study was also supported by a randomized study
conducted by Dar AM et al, which showed the number of patients
with grade 1 and 2 shivering were 4 and 3 in both ketamine
and pethidine groups respectively (p>0.05).
In this study, side effects likehallucination, nausea, and vomiting,
duration of PACU stay, and sedation associated with the study
drugs were compared between the two groups.
The number of sedated patients was significantly higher in pethidine
than ketamine group: 6(15.8%) versus 16(42.1%) for ketamine and pethidine group respectively, p=0.012. This could be
due to differences in the duration of elimination for ketamine
and pethidine. Another difference might be due to the combined
effects of pethidine with intraoperative morphine, inhalational
anesthetics, and perioperative hypothermia.
In this study, nausea and vomiting were observed among the
groups and found to be significantly different, p=0.025. The
possible explanation could be opioid-induced activation of the
chemoreceptor trigger zone.
PACU stay time between the groups was found to be comparable
(48.85 ± 6.73 and 50.13 ± 5.90 minutes for ketamine and pethidine
groups respectively, p=0.374). The result of a study conducted
in Iran by Ayatollahi et al. revealed the duration of PACU
stay for ketamine and pethidine group was 64.50 ± 1.43 minutes
and 56.67 ± 1.27 minutes respectively. (14) In the same study,
the length of PACU stay was 49.37 ± 1.22 minutes and 43.10 ±
1.60 minutes in those who took ketamine 0.3 mg/kg and control
group. Thus, PACU stay time in previous groups was slightly long.
The reason could be attributed to the higher dose of study drugs.
This is the first study in our country; thus it could be an important
source of information for clinical researchers. However, the
lack of randomization and control for room temperature and the
temperature of intravenous fluids in the institution might be the
limitation of this study.
Conclusion
This study has proved prophylactic low dose ketamine could prevent
post-operative shivering as effectively as pethidine and associated
with fewer side effects. We recommend using ketamine
0.5 mg/kg 20 minutes before the end of operation to prevent
postoperative shivering. We also recommend ketamine because it
is easily available in the operation room and cost-effective.
Acknowledgments
The authors would like to thank the almighty GOD for all his
support. Our gratitude also goes to Addis Ababa University College
of health sciences, department of anesthesia for their cooperation
to invest our time in this study and those who provided
constructive support on this research project. We would
also like to thank Tikur Anbessa specialized hospital anesthetists,
staffmembers, and participants for their voluntariness to facilitate
a study process.
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