RECENT ADVANCES in CLINICAL MEDICINE
Tramadol and Meperidine effect in Postanaesthetic Shivering
FATEMEH HAJI MOHAMMADI
Anesthesiology Department– Amir Alam Hospital
Tehran University Medical Sciences
Saadi Shomali st. – Tehran - Iran
MOHAMMAD REZA KHAJAVI
Anesthesiology Department – Sina Hospital
Tehran University Medical Sciences
Imam Khomeini st. – Tehran - Iran
FARSAD IMANI
Anesthesiology Department – Sina Hospital
Tehran University Medical Sciences
Imam Khomeini st.
Tehran - Iran
SHOKOOH SADR AZODI
Anesthesiology Department – Amir Alam Hospital
Tehran University Medical Sciences
Saadi Shomali st.
Tehran - Iran
BAHADOR TAVAKOLI
Anesthesiology Department – Amir Alam Hospital
Tehran University Medical Sciences
Saadi Shomali st.
Tehran - Iran
PATRICIA KHASHAYAR
Research and Development center - Sina Hospital
Tehran University Medical Sciences
Imam Khomeini st.
Tehran - Iran
Email: patricia.kh@gmail.com
Abstract
Postanaesthetic shivering is the existence of involuntary, spontaneous movements in skeletal muscles, giving
rise to discomfort. Different drugs are identified to be effective on reducing this complication. The purpose
of this study was to compare the effectiveness of tramadol and meperidine in controlling postoperative
shivering. The present study was performed as a double blind clinical trial on patients suffering from
shivering following a general anesthesia for a urologic operation. In the recovery room, the patients received
1mg/kg Tramadol or 0.5mg/kg Meperidine (IV in 30 seconds) based on a randomized table, if PAS of grade
II or higher occurred. Shivering was reported to disappear in 40% following the use of tramadol and 53.3%
after the consumption of meperidine. Both drugs were effective in reducing the severity of shivering; PAS,
however, remained unchanged in a case in tramadol group and 2 in the meperidine group. Tramadol is as
effective as the commonly used meperidine in tackling post-anesthetic shivering.
Key Words – Postanaesthetic Shivering – Meperidine – Tramadol – General Anesthesia
The origin of postoperative shivering is unclear.
Several hypotheses have been raised to explain its
occurrence. Perioperative hypothermia is the
primary cause, which sets in due to anesthetic
induced inhibition of thermoregulation; however,
the muscular activity may be increased following
anesthesia even in non hypothermic patients [3-5].
1 Introduction
Postanaesthetic shivering (PAS) is the existence of
involuntary, randomized, spontaneous movements
in skeletal muscles; giving rise to discomfort and
unpleasant feeling [1]. It is known to be a frequent
complication, reported in 40-70% of patients at
recovery [2].
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nesdonal (Na-thiopental) 4 mg/kg and atracurium
0.5 mg/kg for induction. After tracheal intubation,
anesthesia was maintained by N2O-O2 50% (total
flow 3 lit) and isoflurane 1-1.5%. The temperature
of the operating room was set to be between 2224°c during the operation period and the injected
fluids had the same room temperature.
The patients were extubated after the muscular
relaxant effects of atropine were reversed
following the administration of neostigmin 0.05
mg/kg and 0.02 mg/kg. The patients were under a
close observation in the recovery room so that the
responsible resident would be informed in case
shivering would happen.
Table-1 outlines the classification of the severity of
post anesthetic shivering. The patients received
1mg/kg Tramadol or 0.5mg/kg Meperidine (IV in
30 seconds), in case they displayed PAS of grade II
or higher. The responsible resident used drugs in
the syringes labeled as A or B based on a
randomized table. These syringes were filled by a
single technician who was not informed of the
objectives of the study. Normal Saline was added
in order that both syringes would have the same
volume. The interval between the beginning and
disappearance of shivering was also noted.
Disappearance or any decline in the severity of the
shivering was defined as a positive effect of the
drug while nausea, vomiting, lethargy, decrease in
arterial O2 saturation and other complications were
defined as complication. The complications were
gathered in an especial form. The patients were
under observation for 30 minutes for possible
shivering.
The results were entered in SPSS version 11.5 and
analyzed. Demographic information, anesthetic
duration, the initiation and disappearance time of
shivering was compared using a t-test, whereas for
the severity and the complications chi square and
non-parametric tests were utilized.
Pain, sympathetic over activity, release of pyrogen
products, adrenal inhibition, spinal reflex
hyperactivity and respiratory alkalosis are other
known causes [4]. Shivering results in a 200-500
% increase in oxygen consumption index along
with raised CO2 production, ventilation and
cardiac output [6, 7]. Vasoconstriction and
increased vascular resistance leading to inadequate
circulation
especially
in
patients
with
atherosclerosis and therefore, aggravated cardiac
ischemia are other complications following the
condition [4].
Various medications help prevent postanaesthetic
shivering. Meperidine is an analgesic, whose effect
on reducing the postanaesthetic shivering is fully
understood [8-10]; the effect of other medications
such as morphine, fentanyl, and alfentanil,
however, are not shown [10].
Tramadol is an opioid widely used during the
postoperative periods because of its analgesics
properties with the aim of controlling the pain and
preventing the respiratory depression. Previous
studies, however, have shown controversial results
regarding
its
effectiveness
in
reducing
postoperative shivering [2, 8, 11, 12].
As a result, the present study was designed to
evaluate the impact of tramadol on postoperative
shivering and to compare its effects with those of
meperidine.
2 Materials and Methods
After being approved by the Institutional Ethics
Committee of Tehran University of Medical
Sciences, the study was performed as a double
blind clinical trial on 60 patients suffering from
shivering following a general anesthesia.
All the patients in physical status, ASA class I and
II, who did not have any contraindication for
receiving the specified drugs were enrolled in this
study. They were selected from those willing to
undergo a urology operation of less than 2 hours
(except prostatectomy and transurethral resection
(TUR) of the prostate, which are associated with
an exchange of a great amount of fluid and blood).
The patients in an emergent condition, and those
having hyperthermia (oral T >37.5 °) or receiving
any medication with a confounding effect on drugs
prescribed in this study were excluded.
After signing an informed written consent, the
subjects were divided in two groups randomly
using random allocation software.
The patients' blood pressure, pulse oximetery,
temperature and ECG changes were monitored all
thorough the operation. All the patients received
anesthesia similarly with midazolam 0.03 mg/kg
and fentanyl 2 mcg/kg as premedication and
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2.1 Statistics
The minimum of required sample size was
calculated based on the findings retrieved from a
previously published report [12] which reported
PAS to cease by 87% and 93% in patients
receiving Tramadol and Meperidine, respectively.
3 Results
Sixty patients were enrolled in this study (30 cases
in each group), 32 of which were male and 28 were
female. The mean age of the patients was 36.2
±16.3, and 40% of them were in 25-34 years age
group. There was not a statistically significant
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severity of the condition is also slightly higher in
the very group.
The results of this study are in contrast with
previous researches, many of which had
considered tramadol as an appropriate alternative
for meperidine. In a study performed by Bhatnagar
et al, they showed a significant decrease in
shivering in 10 minutes following the operation,
using intravenous tramadol 1mg/kg compared with
meperidine 0.5mg/kg (12 out of 15 patients VS. 4
out of 15). Reoccurrence of shivering was not
reported in patients receiving tramadol. In the
mentioned study, intravenous tramadol 1mg/kg
was suggested to be more effective than 0.5 mg/kg
meperidine in controlling the postoperative
shivering [11]. Other studies also reported the
difference between the mean age, gender, length of
anesthesia between the two groups (Table 2).
Shivering was reported to disappear in 40%
following the use of tramadol and 53.3% after the
consumption of meperidine. Both drugs were
reported effective in reducing the severity of
shivering; PAS, however, remained unchanged in a
case in tramadol group and 2 in the meperidine
group (Table-3).
The mean length of anesthesia and the duration of
PAS (the interval between the initiation and the
disappearance of shivering) was 91.1± 41.1 and
6.5± 4.0 minutes, respectively. The mean interval
between the injection of the drug injection
(tramadol and meperidine) and the disappearance
of the shivering was reported to be 2.18 and 2.25
minutes, respectively. Table 4 outlines these results
in each group. There was no significant difference
between the initiation time of PAS (interval
between operation and initiation of shivering),
duration of PAS (interval between drug
administration and disappearance of shivering) and
the severity of shivering between the two groups.
Complications such as nausea and vomiting were
reported in 9 patients in the tramadol group while
only 4 in the other group were reported to have
lethargy and respiratory depression, neither of
which needed re-intubation.
greater antishivering and analgesic properties
of tramadol in treating PAS when compared to
meperidine [23-26].
In another study, Kranke et al studied the
antishivering efficacy of different doses of IV
tramadol (0.5, 1, 2, and 3 mg/kg), indicating that
the efficacy of the drug improved in higher doses.
Comparing patients who received tramadol and
meperidine, they showed that there was no
difference in the reoccurrence rate of shivering and
the resultant complications between the two
groups. Retreatment was also less required in these
2 groups compared with the controls [9].
Tsai et al also showed tramadol to be an effective
drug in the treatment of shivering following
epidural anesthesia in pregnant women because of
its low affinity for opium receptors and modulatory
effects on central monoaminergic tracts. The anti
shivering effects of tramadol (0.5mg/kg),
meperidine (0.5mg/kg), and amitriptiline (1520mg) were evaluated in this study. Response to
treatment (disappearance of shivering in 15
minutes after drug injection) was reported in 93,
87, and 13% of patients receiving meperidine,
tramadol and amitriptiline, respectively. The
interval between drug injection and disappearance
of shivering was 5.1±3.6, 4.2±2.3 in those
receiving tramadol and meperidine, respectively.
Lethargy was more frequently seen in patients
receiving meperidine (33% VS. 7% and 0 in those
receiving tramadol and amitriptiline). As a result,
meperidine and tramadol revealed a rapid response
in cutting off the shivering, while tramadol resulted
in less lethargy [12].
Saha et al reported that tramadol significantly
reduces the incidence and severity of shivering
following open and laparoscopic cholecystectomy
operation [27]. Heid et al, similarly, reported that
intraoperative administration of tramadol is an
effective medication in lowering the incidence and
extent of postoperative shivering with out
4 Discussion
Postanesthetic shivering is a common complication
reported in 5 to 65% of cases undergoing general
anesthesia [13]. A decrease in the core temperature
secondary to sympathetic block, leading to
peripheral vasodilatation, increased cutaneous
blood flow, and subsequent increased heat lost via
skin, is considered as one of the rationales
contributing to the condition [14]. Various
strategies such as the use of reflective blankets,
cutaneous forced-air warming devices, warm
humidified anaesthetic gases and radiant heat are
adopted to lower the incidence of the condition
[15-17]. The use of drugs such as Nefopam,
Tramadol, Physostigmine, Morphine, Fentanyl,
and Pethidine are considered as an alternative but
effective solution; it, however, is associated with
side-effects such as nausea, vomiting and
respiratory depression [18-20].
Opioids such as morphine and tramadol are the
main drugs used to prevent and treat the condition
[18, 21, 22].
The present study showed that patients experience
more postanaesthetic shivering after receiving
tramadol compared to meperidine; the difference,
however, was not significant. Additionally, the
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[3] De Witte JL, Kim JS, Sessler DI,
Bastanmehr H, Bjorksten AR. Tramadol reduces
the sweating, vasoconstriction, and shivering
thresholds. Anesth Analg, 87, 1, 1998, pp 173-9.
[4] Sessler DI. Temprature monitoring. In:
Miller RD, ed. Anesthesia. New York,
edinburgh, London, Madrid, Melbourne, Milan,
Tokyo: Churchill Livingstone, 1994; 1363-82.
[5] Horn EP, Sessler DI, Standl T, et al. Nonthermoregulatory
shivering
in
patients
recovering from isoflurane or desflurane
anesthesia. Anesthesiology, 89, 1998, pp 878-86.
[6] Bay J, Nunn JF, Prys-Roberts C. Factors
influencing arterial PO2 during recovery from
anesthesia. Br J Anesth, 40, 1968, pp 398-407.
[7] Macintyre PE, Pavlin EG, Dwersteg JF.
Effect of meperidine on oxygen consumption,
carbon dioxide production, and respiratory gas
exchange in postanesthesia shivering. Anesth
Analg, 66, 1987, pp 751-5.
[8] Zahedi H. Comparison of tramadol and
pethidine for postanesthetic shivering in
elective cataract surgery. J of Research in Med
Sci, 5, 2004, pp 37-41.
[9] Kranke P, Eberhart LH, Roewer N, Tramer
MR. Single-dose parenteral pharmacological
interventions
for
the
prevention
of
postoperative shivering: a quantitative
systematic review of randomized controlled
trials. Anesth Analg, 99, 3, 2004, pp 718-27.
[10] Alfonsi P. Postanaesthetic shivering:
epidemiology,
pathophysiology,
and
approaches to prevention and management.
Drugs, 61, 15, 2001, pp 2193-205.
[11] Bhatnagar S, Saxena A, Kannan TR, Punj
J, Panigrahi M, Mishra S. Tramadol for
postoperative shivering: a double-blind
comparison with pethidine. Anaesth Intensive
Care, 29, 2, 2001, pp 149-54.
[12] Tsai YC, Chu KS. A comparison of
tramadol, amitriptyline, and meperidine for
postepidural anesthetic shivering in parturients.
Anesth Analg, 93, 5, 2001, pp 1288-92.
[13] Crossley A W A. Perioperative shivering.
Anaesthesia, 47, 1992, pp 193-5.
[14] Talakoub R, Noori Meshkati Sh. Tramadol
versus meperidine in the treatment of shivering
during spinal anesthesia in cesarean section.
JRMS, 11, 3, 2006, pp 151-155
[15] Buggy D, Hughes N. Pre-emptive use of
the space blanket reduces shivering after
general anaesthesia. Br J Anaesth, 72, 1994, pp
393-6.
[16] Camus Y, Delva E, Just B, Lienhart A.
Leg warming minimises core hypothermia
during abdominal surgery. Anesth Analg, 77,
1993, pp 995-9.
influencing the pain perception in lumbar disc
surgery [28].
Talakoub et al, moreover, reported both tramadol
and meperidine to be effective in treating postspinal shivering in women undergoing cesarean
section [14]. In line with these findings, the present
revealed no significant difference between the
postoperative shivering control rate and the
resulted complications following the use of
tramadol and meperidine, suggesting that despite
the fact that tramadol can help reduce
postanaesthetic shivering it does not provide the
patient with additional benefits compared to the
commonly used meperidine.
These findings are on the contrary to previous
studies in which various doses of tramadol have
shown
promising
effects
in
reducing
postanaesthetic shivering. Different individuals are
reported to show various responses to opiums, so
the difference between the findings of the present
study and those of previous researches can be
contributed to the differences between Iranians and
other populations in whom the researches were
conducted. Moreover, the difference in the type of
operations for which the patient was anesthetized
can be another reason leading to the differences.
It is recommended to perform larger studies to
compare the real effects of various doses of
tramadol with meperidine on postanaesthetic
shivering.
Considering the fact that all studies carried out in
this field have chosen adults as their target
population, so it is recommended to perform a
similar study on children in order to evaluate the
effect of these drugs on this age, as well.
Moreover, the temperature changes were not
recorded in the present study, so it is recommended
to keep a record in these changes in the following
studies.
5 Acknowledgment
We are indebted to the Research and Development
Center of Amir Alam Hospital for their support.
References
[1] Eberhart LHJ, Doderlein F, Eisenhardt G,
Kranke P, Sessler DI, Torossian A, Wulf H,
Morin AM. Independent Risk factors for
Postoperative Shivering. Anesth Analg, 101,
2005, pp 1849-57.
[2] Mathews S, Al Mulla A, Varghese PK,
Radim K, Mumtaz S. Postanaesthetic shivering-a new look at tramadol. Anaesthesia, 57, 4, 2002,
pp 394-8.
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[24] De Witte J, Deloof T, De Veylder J,
Housemans PR. Tramadol in the treatment of
postanaesthetic
shivering.
Acta
Anaesthesiological Scandinavica, 41, 1997, pp
506-10.
[25] Mathews S, Al Mulla A, Varghese PK,
Radium K, Mumtaz S. Postanaesthetic
shivering a new look at tramadol. Anaesthesia,
57, 2002, pp 394-8
[26] Bhatnagar S, Saxena A, Kannan TR, Punj
J, Panigrohi M, Mishra S. Tramadol for
postoperative shivering; a double blind
comparison with pethidine. Anaesthesia and
Intensive Care 29, 2001, pp 149-54
[27] Saha E, Ray M, Mukherjee G. Effect of
tramadol in prevention of postanaesthetic
shivering following general anaesthesia for
cholecystectomy. Indian J. Anaesth, 49, 3,
2005, pp 208 – 212
[28] Heid F, Grimm U, Roth W, Piepho T, Kerz
T, Jage J. Intraoperative tramadol reduces
shivering but not pain after remifentanilisoflurane general anaesthesia. A placebocontrolled, double-blind trial. Eur J
Anaesthesiol, 25, 6, 2008, pp 468-472.
[17] Sharkey A, Gulden R H, Lipton J M,
Giesecke A H. Effect of radiant heat on the
metabolic cost of postoperative shivering. Br J
Anaes, 70, 1993, pp 449-50.
[18] Crossley AWA. Perioperative shivering.
Anaesthesia, 47, 1992, pp 193-5
[19] Bhattacharya1 PK, Bhattacharya L, Jain
RK, Agarwal RC. POST ANAESTHESIA
SHIVERING (PAS): A REVIEW. Indian J.
Anaesth, 47, 2, 2003, pp: 88-93.
[20] Cheong KF, Chen FG, Yau GHM.
Postanaesthetic Shivering—A Comparison of
Thiopentone and Propofol. Ann Acad Med
Singapore, 27, 1998, pp 729-32.
[21] Crossley A. Six months of shivering in a
district general hospital. Anaesthesia, 47, 1992,
pp 845-8.
[22] Sessler
D
I.
Perianaesthetic
thermoregulation and heat balance in humans.
FASEB J, 7, 1993, pp 638-44
[23] Mohta M, Kumari N, Tyagi A, Sethi
AK, Agarwal D, Singh M. Tramadol for
prevention of postanaesthetic shivering: a
randomised double-blind comparison with
pethidine. Anaesthesia 64, 2, 2008, pp
141 – 146
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TablesTable 1- The severity score of postanaesthetic shivering [14]
PAS
Score
No shivering
0
Peripheral vasoconstriction associated with sensation of coldness, without any
1
visible shivering
Muscular contraction in a group of muscles
2
Muscular contraction in more than a group of muscles but not generalized
3
Generalized shivering
4
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Table 2 – Demographic Data of the patients enrolled in each group
Meperidine
Tramadol
(n=30)
(n=30)
17.9 ± 36.3
14.7 ± 36.1
Male
17 (28.3%)
15 (25%)
Female
13 (21.6%)
15 (25%)
Weight
67.1 ± 8.67
70.1 ± 10.5
0.78
Duration of PAS (min)
25.1 ± 93.2
37.3 ± 89.0
0.699 *
Initiation of PAS (min)
6.2 ± 3.8
6.8 ± 4.2
0.520 *
Severity of PAS
2.9 ± 1.1
3.1 ± 0.8
0.726 **
Age
Sex
P- Value
0.962 *
* independent t-test
** X 2
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Table 3- PAS severity before and following drug administration
PAS severity
Tramadol (%)
Meperidine (%)
1
10 (33.3)
8 (26.6)
2
11 (36.7)
12 (40)
3
7 (23.3)
6 (20)
4
2 (6.7)
4 (13.3)
0
12 (40)
16 (53.3)
Following
1
13 (43.3)
11 (36.7)
drug administration
2
4 (13.3)
1 (3.3)
3
1 (3.3)
2 (6.7)
Before
drug
administration
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Table 4 – Outcome in each group
Meperidine
Tramadol
(n=30)
(n=30)
Duration of PAS (min)
25.1 ± 93.2
37.3 ± 89.0
0.699 *
Initiation of PAS (min)
6.2 ± 3.8
6.8 ± 4.2
0.520 *
Severity of PAS
2.9 ± 1.1
3.1 ± 0.8
0.726 **
P- Value
* independent t-test
** X 2
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ADDITIONAL FILE 1- CONSORT FLOWCHART
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