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79]

Original Article

Prophylactic intravenous paracetamol for

prevention of shivering after general anesthesia
in elective cesarean section
Ahmadreza S Gholami,
ABSTRACT
Mehdi Hadavi1

Department of Anesthesiology,
1
Aja University of Medical Sciences,
Besat Nahaja General Hospital,
Tehran, Iran
Address for correspondence:
Dr.Ahmadreza S Gholami,
Department of Anesthesiology,
Besat Nahaja General Hospital,
Tehran, Iran.
Email:shafa854@yahoo.com
Background: Postoperative shivering is an important common complication after general
anesthesia. This may lead to dissatisfaction and a sense of discomfort, especially in parturients
undergoing cesarean section. In addition to warming, many drugs have been investigated
for prevention of shivering. The aim of this study was to evaluate the efficacy of intravenous
paracetamol for prevention of shivering after general anesthesia in cesarean section.
Materials and Methods: In this prospective randomized doubleblind controlled clinical trial,
110 pregnant women, physical Status I or II, based on the classification of American Society
of Anesthesiologists (ASA), aged 1840 years, who were scheduled for elective cesarean
section under general anesthesia were included in the study. They were randomly divided into
two groups of 55 each. One group received 100ml normal saline, and another group received
1 g of paracetamol in 100ml normal saline intravenously, 15min after the delivery of the baby.
The anesthesia technique was similar in both the groups. Tympanic membrane temperature
was measured before and after the induction of anesthesia and every 15min till the end of
recovery from anesthesia. Postanesthetic shivering was graded on a scale of 0 to 4; if the
score was more than 2, it was treated with 25mg pethedine. Vital signs and side effects were
recorded during the surgery and recovery period.
Results: There were no significant differences between the two groups regarding age, weight,
height, and duration of surgery (P > 0.05). Shivering was seen in 5 parturients (9.1%) in
paracetamol group(groupA) and 28 parturients(50.9%) in the saline group(groupN). On a
scale of 0 to 4, shivering was of lower intensity in paracetamol group compared to the saline
group(P<0.05). There was a fall in core temperature in both the groups after induction of
anesthesia, which was statistically similar(P>0.05). There was no difference in the incidence
of hypotension, nausea, and vomiting among the two groups(P>0.05).
Conclusion: The prophylactic use of intravenous paracetamol during surgery is effective for
the prevention of postoperative shivering.
Key words: General anesthesia, paracetamol, shivering

INTRODUCTION anesthesia.[1] It can occur in 565% of patients after general

anesthesia.[2] Shivering has many side effects such as increase

P ostanesthetic shivering is one of the most common in oxygen consumption, blood pressure, and carbon dioxide
complications in the recovery period after general This is an open access article distributed under the terms of the
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Cite this article as: Gholami AS, Hadavi M. Prophylactic intravenous

DOI:
paracetamol for prevention of shivering after general anesthesia in elective
10.4103/2249-4472.191601
cesarean section. J Obstet Anaesth Crit Care 2016;6:81-85.

2016 Journal of Obstetric Anaesthesia and Critical Care | Published by Wolters Kluwer - Medknow 81
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Gholami and Hadavi: Paracetamol for prevention of shivering in general anaesthesia
production, distressing patients with coronary artery disease;
it can also cause pain and discomfort in patients. In general
anesthesia, vasodilation combined with a redistribution of
body heat from core tissues to peripherals causes heat lost.[3]
There are two ways to reduce shivering, including forced
warming of the patient[4] and use of pharmaceutical agents.
Many agents have been evaluated for the prevention or treatment
of shivering, including intravenous opioids, physostigmine,
dexmedetomidine,[5] ketamine, ondansetron, granisetron,[6]
clonidine, tramadol, [7] dexamethasone, doxapram, and
ephedrine.[2,8,9] Pethidine is one of the frequent choices to
prevent postoperative shivering. An important dangerous
complication of pethidine is respiratory depression, especially
in the presence of previously administered anesthetic drugs.
Furthermore, nausea and vomiting are also an important side
effect of opioids.[1,9] Intravenous acetaminophen(paracetamol)
is an effective and safe drug for managing mild to moderate
pain. In contrast to opioids, it does not cause sedation,
respiratory depression, constipation, or vomiting.[10] Shivering,
is a thermoregulatory defense mechanism. Antishivering
drugs decrease the shivering threshold.[11,12] Paracetamol acts
through a centrally mediated prostaglandin inhibition to
decrease the hypothalamic temperature set point.[1215] Rectal
administration of acetaminophen has been shown to be effective
for prevention of shivering in the therapeutic hypothermia;[13]
thus, paracetamol may be effective in preventing shivering
after general anesthesia.
The aim of this study was to assess the efficacy of prophylactic
paracetamol on postanesthetic shivering. To the best of our
knowledge, there is no study regarding intravenous paracetamol
as a prophylactic agent against postoperative shivering.
MATERIALS AND METHODS
The current study was a prospective randomized double blind
trial. The sample size of the study was calculated based on a typeI
error of 0.05, a study power of 80, and a minimum difference of
25% in the prevalence of postanesthetic shivering between the
two groups. Thus, 110 parturients aged 1840years, ASA status
I or II undergoing elective cesarean section were selected for
the study. The ethical approval was obtained from the ethical
committee of the University of Medical Sciences. A written
informed consent was obtained from all the participants. The
parturients were randomly to two equal groups(55 participants
in each group). The exclusion criteria included history of
allergy to paracetamol, cardiopulmonary disease, hypertension,
diabetes, renal disease (creatinine more than 1.5), chronic
lung disease, liver disease, history of alcohol abuse, and body
temperature more than 38C or less than 36C.The parturients
82 Journal of Obstetric Anaesthesia and Critical Care / Jul-Dec 2016 / Vol 6 | Issue 2
randomly received 100ml normal saline(N group, n=55), or
1 gram paracetamol in 100ml normal saline(A group, n=55)
intravenously, 15min after the delivery of the baby.
The anesthesia technique was similar in both groups. During
the surgery, the heart rate, blood pressure, oxygen saturation,
and end tidal carbon dioxide were monitored. Core temperature
was measured before and after induction of anesthesia and
every 15min till the end of recovery from anesthesia. Operation
room temperature was maintained at 2224C. Anesthesia was
induced with thiopental sodium 5mg/kg and succinylcholine
1.5 mg/kg was used for rapid sequence orotracheal intubation.
Anesthesia was maintained with 0.8 MAC isoflurane in 50%
oxygen and 50% nitrous oxide.
Cold fluid infusion was avoided. Muscle relaxation for surgery
was maintained with 0.5 mg/kg atracurium. After neonate
delivery, 2 g/kg fentanyl, 0.05 mg/kg midazolam, and
oxytocin 30IU were infused. Each woman received 15 ml/kg
intravenous warm crystalloid during surgery. Neuromuscular
blockade was reversed with neostigmine 0.04 mg/kg and
atropine 0.02 mg/kg at the end of operation. The patients
were extubated when they had a good respiratory pattern
and were awake enough to maintain their airway. Duration
of the surgery was recorded for each patient. In the recovery
room, all parturients were observed for 30min and they were
covered with a blanket.
Patients were observed and nausea and vomiting, respiratory
condition, hypotension, and shivering grade were recorded for
each patient. The person doing observation in postoperative
ward was blind to the group allocation.
The shivering was graded by Tsai and Chu method,[21] from
a score of 0 to 4, where 0 implies no shivering; 1 implies
one or more of the following: Piloerection, peripheral,
vasoconstriction, peripheral cyanosis with no other cause, but
no muscle activity; 2 implies visible muscular activity confined
to one muscle group; 3 implies visible muscular activity in more
than one muscle group; and 4 implies gross muscular activity
involving the whole body.
Shivering grade 3 or more was considered as shivering in
this study and treated with 25mg pethidine as the treatment
agent. Parturients with nausea and vomiting were treated with
ondansetron 4mg.
Statistical analysis
Data analyses were performed using the Statistical Package
for the Social Sciences(SPSS) version19.0 for windows (IBM
Corporation, New York, United States). The incidence of
shivering and side effects were compared using ttest and
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Gholami and Hadavi: Paracetamol for prevention of shivering in general anaesthesia

Chisquare test. The results were reported as meanstandard temperature in the room, and cold fluids infusion, are risk
deviation (SD). P value less than 0.05 was considered to be factors for postoperation shivering,[18] thus, the operation room
significant.
Table1: Demographic and surgical characteristics of
RESULTS parturients enrolled in the study
Variable Group Group P value
saline(N) Apotel(A)
There were no differences in parturient characteristics between
Age(years) 25.365.582 25.584.894 0.828
the two groups in the baseline study[Table1]. The number
Weight(kg) 63.055.268 62.675.306 0.706
of parturients with postoperative shivering in the recovery Height(cm) 162.934.996 162.474.776 0.627
room till 30minutes after delivery were significantly less in Duration of surgery(min) 53.697.885 54.118.139 0.785
groupA(paracetamol) compared to group N(saline), as shown Data are given as meanSD
in Table2(P<0.05). Twentyeight parturients(50.9%) shivered
at grade3 or 4 in groupN, however, only 6 parturients(9.1%)
Table2: Number of parturients with different grades
reached grade3 shivering in groupA[Figure1]. There was a of shivering in the two groups
fall in core temperature in both the groups after induction of Shivering Score Group Saline(N) Group Apotel(A) P value
anesthesia, which was statistically similar(P>0.05)[Figure 2, 0 20 45 <0.05
Table 3]. There were no significant differences in postoperative 1 3 3
nausea and vomiting or hypotension between the two 2 4 2
groups (P > 0.05). None of parturients had respiratory 3 27 5 <0.05
depression[Table4]. None of the women in the study groups 4 1 0
had episodes of oxygen desaturation and cardiovascular P<0.05 compared with other groups using the Chisquare test

complication.
Table3: Core temperature and its variation in two
DISCUSSION groups(meanSD)
Variable Group Group P value
Saline(N) Apotel(A)
During postanesthetic period, shivering is an important,
Preanesthesia temperature 36.780.15 36.690.20 0.993
harmful, and widespread side effect caused by general Postanesthesia temperature 35.710.23 35.820.28 0.721
anesthesia.[17] It can cause hypoxia, pain, and lactic acidosis. Early recovery temperature 35.810.23 35.860.26 0.387
Furthermore, it may interfere with the monitoring devices. Late recovery temperature 35.920.30 35.960/29 0.389
Thus, prevention of shivering is important especially in patients P<0.05 compared with the other groups, using the Chisquare test
with cardiopulmonary disease or elderly patients.[1619]
Table4: Side effects between two groups after
Hypothermia may cause postanesthetic shivering by change of operation(meanSD)
thermoregulatory mechanism.[20] However, a relationship has Variable Group Saline(N) Group Apotel(A) P value
been observed between core temperature and occurrence of Hypotension 3 3 1.000
shivering.[2] The result of this study showed that intravenous Nausea, vomiting 6 5 0.912
paracetamol was effective in preventing shivering due to Respiratory 0 0
general anesthesia. Age, long duration of surgery, cold depression
P<0.05 compared with the other groups, using the Chisquare test

Figure 1: Comparision of shivering Figure 2: Measured body core temperature in two groups

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Gholami and Hadavi: Paracetamol for prevention of shivering in general anaesthesia
temperature was maintained at 2224C and cold infusion was
avoided in this study. Although many pharmacological agents
have been used to treat or prevent postanesthesia shivering,
the ideal treatment has not yet been found. Paracetamol is a
safe and effective analgesic agent for mild to moderate pain.[10]
Intravenous infusion of acetaminophen(paracetamol) results
in a rapid elevation in plasma concentration, approximately
within 1520min after the injection, which declines after 4 h. In
2010, the Food and Drug Association(FDA) approved the use
of intravenous acetaminophen for the management of pain and
fever.[21] The mechanism of intravenous acetaminophen may
involve central inhibition of COX2, inhibition of NO generation
via blockade of NmethylDaspartate (NMDA) receptors,
activation of descending serotonergic pathways, and inhibition
of COX3.[14,2224] Serotonergic pathways are part of the descending
pain system, and it has been accepted that the activation of
serotonergic pathways plays a key role in the analgesic effect of
paracetamol.[2428] Paracetamol acts on the heatregulatory center
by inhibition of prostaglandin synthesis.[1114,24] Conversion
of paracetamol to Narachidonoylphenolamine (AM404),
an endocannabinoid reuptake inhibitor, appears to be an
important in pain control.[24,29]
Lack of adverse effects associated with other antishivering
drugs is the main advantage of paracetamol.[30,31] Many studies
have reported adverse side effects for other antishivering
medications. Benzodiazepines can cause sedation and delayed
awakening.[11] Propofol has hemodynamic side effects such
as hypotension, bradycardia, and sedation. Clonidine and
dexmetomidine may cause hypotension. Tramadol can
decrease sweating and seizure threshold.[12] Ketamine has
psychotomimetic adverse effects such as hallucination and
bad dreams.[22]
Among these drugs, pethidine is still the best effective drug
used for prevention and management of shivering, however,
it can produce sedation, nausea, and vomiting or respiratory
distress.[2] Although many studies have approved the analgesic
effect of intravenous paracetamol,[3234] the present study was
the first evaluation of intravenous paracetamol for prevention
of postoperative shivering.
CONCLUSION
This study showed the efficacy of prophylactic paracetamol
on postanesthetic shivering, which can be a good agent for
treatment of shivering in a recovery room to reduce the use of
opioids and its related side effects such as sedation, respiratory
depression, nausea, and vomiting.
Financial support and sponsorship
Nil.
84 Journal of Obstetric Anaesthesia and Critical Care / Jul-Dec 2016 / Vol 6 | Issue 2
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Iqbal A1, Ahmed A, Rudra A, Wankhede RG, Sengupta S, Das T, etal.
Prophylactic granisetron vs pethidine for the prevention of postoperative
shivering: Arondomized control trial. Indian J Anaesth 2009;53:3304.
2. Asl ME, Isazadefar KH, Mohammadian A, Khoshbaten M. Ondansetron
and meperidine prevent postoperative shivering after general anaesthesia.
Middle East J Anaesth 2011;21:6770.
3. Alfonsi P. Postanaesthetic shivering, epidemiology, pathophysiology
and approaches to prevention and management. Minerva Anestesiol
2003;69:43842.
4. Chung SH1, Lee BS, Yang HJ, Kweon KS, Kim HH, Song J, etal. Effect of
preoperative warming during cesarean section under spinal anesthesia.
Korean J Anesthesiol 2012;62:45460.
5. Abdelmageed WM, Al Taher WM. Intramuscular dexmedetomidine for
prevention of shivering after general anesthesia in patients undergoing
arthroscopic anterior cruciate ligament reconstruction. AinShams J
Anesthesiol 2014;7:15662.
6. Shakya S, Chaturvedi A, Sah BP. Prophylactic low dose ketamine and
ondansetron for prevention of shivering during spinal anaesthesia.
JAnaesthesiol Clin Pharmacol 2010;26:4659.
7. Reddy VS, Chiruvella S. Clonidine versus tramadol for post spinal
shivering during cesarean section: Arandomized double blind clinical
study. JObstet Anaesth Crit Care 2011;1:26.
8. Piper SN, Rohm KD, Malek WH, Fent MT, Sutiner SW, Boldt J.
Dolasetron for preventing postanaesthetic shivering. Anesth Analg
2002;94:10611.
9. EIDeeb A, Barakat R. Could ephedrine replace meperidine for
prevention of shivering in women undergoing cesarean section
under spinal anesthesia? A randomized study. Egyptian J Anaesth
2012;28:23741.
10. Kouchek M, Mansouri B, Mokhtari M, Goharani R, Miri MM,
Sistanizad M. A comparative study of intravenous paracetamol and
fentanyl for pain management in ICU. Iran J Pharm Res 2013;12:1938.
11. Smith C, Coleman A, AlBaghdadi Y, Orlewicz M. Therapeutic
hypothermia in PEA cardiac arrest for global and local cerebral
protection: Acase report and minireview. Romanian J Anaesth Intensive
Care 2011;18:153-5.
12. Choi HA, Ko SB, Presciutti M, Fernandez L, Carpenter AM, Lesch C,
etal. Prevention of shivering during therapeutic temperature modulation:
The Columbia antishivering protocol. Neurocrit Care 2011;10:94747.
13. Honasoge A, Parker B, Wesselhoff K, Lyons N, Kulstad E. First use of
a new device for administration of buspirone and acetaminophen to
suppress shivering during therapeutic hypothermia. Ther Hypothermia
Temp Manag 2016;6:4851.
14. Kasner SE, Wein T, Piriyawat P, VillarCordova CE, Chalela JA,
Krieger DW, etal. Acetaminophen for Altering Body Temperature in
Acute Stroke: Arandomized clinical trial. Stroke 2002;33:1304.
15. Ayoub SS, Botting RM, Goorha S, ColvilleNash PR, Willoughby DA,
Ballou LR. Acetaminopheninduced hypothermia in mice is mediated
by a prostaglandin endoperoxide synthase 1 gene derived protein. Proc
Nat Acad Sci U S A 2004;101:111659.
16. Tsai Ye, Chu KS. A comparison of tramadol, amitriptyline, and
meperidine for postepidural anesthetic shivering in parturients. Anesth
analg 2001;93:128892.
17. Kranke P, Eberhart LH, Roewer N, Tramer MR. Single dose paracetamol
pharmacological interventions for the prevention of postoperative
shivering: Aquantitative systemic review of randomized controlled trials.
Anesth Analg 2004;99:71827.
18. Sagir O, Gulhas N, Yucel TA, Begee Z, Ersoy O. Control of shivering
[Downloaded free from http://www.joacc.com on Tuesday, June 13, 2017, IP: 120.188.92.79]
Gholami and Hadavi: Paracetamol for prevention of shivering in general anaesthesia
during regional anaesthesia: Prophylactic ketamine and granisetron.
Acta Anaesiol Scand 2004;51:444.
19. Chan AM, Ng KF, Tong EW, Jan GS. Control of shivering under
regional anaesthesia in obstetric patients with tramadol. Can J Anaesth
1999;46:2538.
20. Vanderstappen I, Vandermeersch E, Vanacker B, Mattheussen M,
Herijgers P, Van Aken H. The effect of prophylactic clonidine on
postoperative shivering: A large prospective double blind study.
Anaesthesia 1996;51:3515.
21. Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB,
etal. Arandomized doubleblind placebocontrolled, multicenter, repeat dose
study of two intravenous acetaminophen dosing regimens for the treatment
of pain after abdominal laparascopic surgery. Clin Ther 2010;32:234869.
22. Vadivelu N, Mitra S, Narayan D. Recent advances in postoperative pain
management. Yale J Biol Med 2010;83:1125.
23. Mauger AR, Taylor L, Harding C, Wright B, Foster J, Castle PC. Acute
acetaminophen (paracetamol) ingestion improves time to exhaustion
during exercise in the heat. Exp Physiol 2014;99:16471.
24. Mattia C, Coluzzi F. What anesthesiologists should know about
paracetamol(acetaminophen). Minerva Anestesiol 2009;75:64453.
25. Smith SH. Potential analgesic mechanisms of acetaminophen. Pain
Physician 2009;12:26980.
26. Graham GG, Scott KF. Mechanism of action of paracetamol. Am J
Therapeutics 2005;12:4655.
Journal of Obstetric Anaesthesia and Critical Care / Jul-Dec 2016 / Vol 6 | Issue 2 85
27. RocaVinardell A, OrtegaAlvaro A, GilbertRahola J, Mic JA. The
role of 5HT1A/B autoreceptors in the antinociceptive effect of systemic
administration of acetaminophen. Anesthesiology 2003;98:417.
28. Bujalska M. Effects of nitric oxide synthase inhibition on antinociceptive
action of different doses of acetaminophen. Polish J Pharma
2004;56:60510.
29. Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic
activity of paracetamol is prevented by the blockade of cannabinoid CB1
receptors. Eur J Pharmacol 2006;531:2801.
30. Pasero C, Stannard D. The role of intravenous paracetamol in acute pain
management: Acaseillustrated review. Pain Manag Nurs 2012;13:10724.
31. Apfel CC, Homuss C. Intravenous paracetamol reduces postoperative
nausea and vomiting: Asystemic review and metaanalysis. Int Assoc
Study Pain 2013;154:67789.
32. Arici S, Gurbet A, Trker G, Yavacaolu B, Sahin S. Preemptive analgesic
effects of intravenous paracetamol in total abdominal hysterectomy. Agri
2009;21:5461.
33. Alhashemi JA, Alotaibi QA, Mashaat MS, Kaid TM, Mujallid RH,
Kaki AM. Intravenous acetaminophen vs oral ibuprofen in combination
with PCIA after cesarean delivery. Can J Anesth 2006;53:12006.
34. Cakan T, Inan N, Culhaoglu S, Bakkal K, Baar H. Intravenous
paracetamol improves the quality of postoperative analgesia but
does not decrease narcotic requirements. J Neurosurg Anesthesiol
2008;20:16973.