Journal of Clinical Anesthesia (2011) 23, 5357

Original contribution

The efficacy of intravenous paracetamol versus tramadol

for postoperative analgesia after adenotonsillectomy
in children
Hale Yarkan Uysal MD (Specialist in Anesthesiology),
Suna Akin Takmaz MD (Specialist in Anesthesiology),
Ferda Yaman MD (Resident in Anesthesiology),
Blent Baltaci MD (Specialist in Anesthesiology),
Hlya Baar MD (Associate Professor and Head of Department)
Anesthesiology and Reanimation Clinic, The Ministry of Health, Ankara Training and Research Hospital, Ankara, Turkey
Received 29 September 2009; revised 14 May 2010; accepted 3 July 2010

Keywords:
Adennotonsillectomy;
Children;
Paracetamol;
Postoperative analgesia;
Tramadol

Abstract
Study Objective: To evaluate the efficacy and the quality of recovery with intravenous (IV) paracetamol
versus tramadol for postoperative analgesia after adenotonsillectomy in children.
Design: Prospective, randomized, double-blinded clinical trial.
Setting: Operating room and Postanesthesia Care Unit (PACU) of a university-affiliated hospital.
Patients: 64 ASA physical status I and II children, aged 6 to 16 years, scheduled for adenotonsillectomy.
Interventions: All patients were premedicated with oral midazolam 0.5 mg/kg 30 minutes before surgery.
Patients were randomized to two groups following induction of general anesthesia. The paracetamol
group (n = 32) received 15 mg/kg of IV paracetamol and the tramadol group (n = 32) received 1.0 mg/kg of
IV tramadol.
Measurements: Modified Hannallah pain scores, emergence agitation, Aldrete scores, sedation scores, time
to first administration of analgesic, heart rate, and mean arterial blood pressure were recorded for each patient.
Data were recorded every 5 minutes for the first 30 minutes and every 10 minutes for the remaining 30
minutes in the PACU, then at 2, 3, 4, 5, 6, 8, 12, and 24 hours in the ward. The frequency of postoperative
nausea and vomiting also was noted. Satisfaction of parents and nurses was determined on a 4-point scale at
the end of the study.
Main Results: No significant demographic differences between groups were noted. No statistically
significant difference was found in postoperative pain scores in either group. Agitation scores, Aldrete scores,
sedation scores, and number of patients who received rescue analgesia and time to administration of rescue
analgesia were similar in both groups.
Conclusions: The IV formulation of paracetamol was associated with similar analgesic properties and early
recovery to that of IV tramadol after adenotonsillectomy in children.
2011 Elsevier Inc. All rights reserved.

Corresponding author. . Eme Bulv., C. Atf Kansu Cad., 11.Sok., 8/7 Balgat, Ankara, Turkey.
E-mail address: haleuysal@gmail.com (H.Y. Uysal).
0952-8180/$ see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.jclinane.2010.07.001

54

1. Introduction
Adenotonsillectomy is a common surgical procedure in
children. Nonsteroidal anti-inflammatory drugs (NSAIDs)
are effective in reducing postoperative pain, with a lower risk
of postoperative nausea and vomiting (PONV). However,
they also introduce the possibility of increased bleeding due
to their antiplatelet effect [1,2]. Opioids provide satisfactory
analgesia and better emergence in children undergoing ear,
nose, and throat (ENT) surgery, but prolonged sedation due
to opioid use is one of the reasons for delayed discharge from
the hospital after day-case surgeries [3]. The efficacy of
tramadol in relieving post-tonsillectomy pain has been well
documented [4,5]. Due to its negligible effect on respiration,
tramadol may be preferable to traditional opioids, but side
effects such as PONV occur [2].
Paracetamol is a non-opioid analgesic that is devoid of
these risks. Its analgesic action is assumed to be mediated by
a serotonergic mechanism, and the antipyretic action is via
inhibition of cyclooxygenase-3 in the hypothalamus [6].
Paracetamol also has little antiplatelet activity and does not
affect bleeding time, unlike NSAIDs [7]. Although enteral
formulations of paracetamol are the most commonly used
analgesics for management of pain in children, their
analgesic efficacy is weak after ENT surgery [8,9]. An
intravenous (IV) formulation of paracetamol recently has
become available, and it achieves target plasma concentration more rapidly with reduced variability compared with the
rectal and oral formulations [10,11].
This randomized, double-blind, clinical study was
undertaken to evaluate the effectiveness of IV paracetamol
on postoperative pain and its effect on the quality of recovery
versus IV tramadol in children after adenotonsillectomy.
Comparison of the frequency of PONV and satisfaction of
the nurses and parents with the study drugs were secondary
objectives of the study.

2. Materials and methods

The study protocol was approved by the Institutional
Ethics Commitee of Ankara Training and Research Hospital.
Written, informed consent were obtained from the parents
and from the children over 8 years of age. A total of 66
healthy, ASA physical status I and II children, aged between
6 and 16 years, and scheduled for adenotonsillectomy
operation, were enrolled in the study. Exclusion criteria were
a known history of allergy to the study drugs; active and
severe renal, hepatic, respiratory, or cardiac disease; and
neurological or neuromuscular disorders.
Children were fasted from solid foods for 6 hours before
the procedure; clear liquids were permitted until two hours
prior to surgery. All study patients were premedicated with
oral midazolam 0.5 mg/kg 30 minutes before surgery. In

H.Y. Uysal et al.

the operating room: electrocardiography (ECG), noninvasive blood pressure, and pulse oximetry monitors
were attached. Anesthesia was induced with IV fentanyl
1.0 lg/kg and IV propofol 2.0 to 3.0 mg/kg. Vecuronium
bromide 0.1 mg/kg was given for muscle relaxation. After
tracheal intubation, the lungs were mechanically ventilated
with the pressure-controlled mode (pressure-controlled
ventilation at 15 cm H2O), and end-tidal carbon dioxide
(ETCO 2) tension was maintained at 30-35 mmHg.
Intravenous fluid management included administration of
lactated Ringer's solution. Fluid deficit was calculated to be
replaced over three hours, and maintenance fluid was
calculated according to patients' weights.
Anesthesia was maintained with 1.5k to 2.5k sevoflurane
and 50k nitrous oxide in oxygen at a total fresh gas flow of
2.0 L/min. No additional opioids were given intraoperatively.
At the end of the operation, residual neuromuscular block was
reversed with neostigmine 0.04 mg/kg and atropine 0.02 mg/
kg, and the endotracheal tube was removed when respiration
was regular and adequate in rate and depth. Heart rate (HR),
systolic (SBP) and diastolic (DBP) arterial blood pressures,
oxygen saturation (SpO2), and ETCO2 were monitored
continuously during the procedure.
After induction of anesthesia and before the surgical
incision, the children were randomized to one of the two
groups using a computer-generated random numbers table,
with 33 patients in each group. Patients in the paracetamol
group received 15 mg/kg of IV paracetamol (Perfalgan) and
the tramadol group patients received 1.0 mg/kg of IV
tramadol (Tramadolor) over 15 minutes. The medications
were diluted with saline to a total volume of 75 mL. All study
drugs were prepared by an anesthesiologist who was blinded
to the details of the study.
After patient arrival at the PACU, postoperative observational pain scores, emergence agitation, Aldrete scores [12],
HR, and mean arterial blood pressure (MAP) were recorded
every 5 minutes during the first 30 minutes, then every 10
minutes for the remaining 30 minutes of the PACU stay.
Patients were then transferred to the ward. At the ward,
observational pain scores, HR, and MAP were recorded at 2,
3, 4, 5, 6, 8, 12, and 24 hours postoperatively. All
postoperative observations and scores were performed by
the same anesthesiologist who was unaware of the patients'
group assignment.
Pain was assessed using a modification of the pain score
scale originally described by Hannallah et al [13]. This assessment allowed for a maximum score of 10 and a minimum of 0.
This scale has been validated in infants and children and has
been used to score pain after ENT surgery [3,14]. During the
first 6 hours, patients with a pain score of 4 or more received
rescue analgesia with IV meperidine 0.5 mg/kg, to a total dose
of 1.0 mg/kg until the pain score was b 4. Thereafter, oral
paracetamol 20 mg/kg was administered every 6 hours. Any
patient with a pain score of 4 or more, in spite of having
received oral paracetamol, received oral ibuprofen 10 mg/kg.

IV paracetamol in children post-tonsillectomy

55
were compared using the Mann Whitney U test. The
Bonferroni correction was applied for all possible comparisons. For categorical comparisons, Chi-square analysis or
Fisher's Exact test were used where appropriate. A P-value
less than 0.05 was considered statistically significant.

Table 1 Patient characteristics and duration of anesthesia

and surgery
Variable

Paracetamol
Tramadol
P-value
group (n = 32) group (n = 32)

Age (yrs)
Weight (kg)
Gender
(women/men)
Duration of
anesthesia (min)
Duration of
surgery (min)

10 (6-16)
34 (33-58)
15/17

10 (6-15)
35 (33-70)
19/13

0.551
0.443
0.316

55.7 F 17.13

52.3 F 17.27

0.108

44.6 F 16.89

39.3 F 15.59

0.056

3. Results
Although 66 children were enrolled in the study, one child
was excluded from the paracetamol group because of
rebleeding that required reoperation one hour after surgery,
and one child was excluded from the tramadol group because
of early discharge to home. Therefore, the number of patients
entered into analysis was 32 in each group.
No statistical differences in age, weight, duration of
surgery, duration of anesthesia (Table 1), or observational
pain scoring at specific time intervals were noted between the
two groups (Fig. 1).
There were also no significant differences between
groups in the number of patients who received rescue
analgesia. Intravenous meperidine was given to 10
(31.25k) paracetamol group patients and to 9 (28.1k)
tramadol group patients (P = 0.784) (Table 2). The mean
time to administration of rescue meperidine analgesia was
10.5 F 6.0 minutes in the paracetamol group and 18.9 F
20.1 minutes in the tramadol group (P = 0.968) (Table 2).
One child receiving IV paracetamol and two children
receiving tramadol needed two doses of meperidine
postoperatively (P = 0.313). At the ward, two children in
the paracetamol group and none in the tramadol group
received oral ibuprofen (P = 0.492).
Eighteen (56.2k) patients in the paracetamol group had an
Aldrete score of 10 at admission to the PACU compared with
16 (50k) in the tramadol group (P = 0.616) (Table 2). The
median Aldrete scores at PACU admission were 10 (6-10) in
the paracetamol group and 10 (8-10) in the tramadol group
(P N 0.05) (Table 2). The mean (SD) time to reach an Aldrete
score of 10 was 10.6 F 17.8 minutes in the paracetamol group
and 18.1 F 22.6 minutes in the tramadol group (P = 0.444)

Data are medians (minimum-maximum) for age and weight, absolute

numbers for gender, and means F SD for duration of anesthesia
and surgery.

5
4
3
2
1

14
40

72
0

48
0

36
0

30
0

24
0

18
0

12
0

60

50

40

30

25

20

15

10

0
0

Observational Pain Scores

The Pediatric Anesthesia Emergence Delirium (PAED)

Scale devised by Sikich and Lerman was used to assess
emergence agitation [15]. At the same time points, adverse
effects such as PONV, sedation, and rebleeding were
recorded. Nausea was defined as an unpleasant feeling
associated with an inclination to vomit, and vomiting was
defined as the forceful ejection of gastric contents through
the mouth. Sedation was assessed using a 4-point scale,
where 0 = fully awake, 1 = awake but drowsy, 2 = sleeping,
but arousable by light touch or speech, and 3 = sleeping, not
arousable). At the end of the study, parents and ward nurses
were asked to assess the quality of postoperative analgesia
using the following satisfaction scale: 1 = bad, 2 = poor, 3 =
good, 4 = excellent.
A power analysis based on a previous article [16] showed
that a sample size of 20 patients per group was required to
achieve a power of 90k and an a of 0.05 for detection of a
difference of 2 in objective pain scale (OPS) scores between
study groups. All statistical analyses were performed using
SPSS for Windows, version 11.5 (SPSS, Chicago, IL, USA).
Data are shown as means (SD) and medians (minimummaximum) for continuous variables and frequencies with
percentages for categorical variables, respectively. Means

Time (minutes)
Paracetamol Group

Fig. 1

Tramadol Group

Mean observational pain scores in the two groups throughout the study period.

56

H.Y. Uysal et al.

Table 2 Recovery and analgesic requirements in the

study groups
Variable

Paracetamol
group (n = 32)

Tramadol
group (n = 32)

P-value

Aldrete score
at PACU
admission
No. of patients
with an Aldrete
score of
10 at PACU
admission (k)
Time to reach an
Aldrete score
of 10 (min)
No. of patients
requiring
rescue
analgesia (k)
Time to first
rescue
analgesia (min)

10 (6-10)

10 (8-10)

0.767

18 (56.2)

16 (50.0)

0.616

10.62 F 17.85

18.12 F 22.6

0.444

10 (31.2)

9 (28.1)

0.784

10.5 F 5.98

18.88 F 20.12

0.968

Data are medians (minimum-maximum), means F SD, or absolute

numbers of patients (k).
PACU = Postanesthesia Care Unit.

(Table 2). The two groups were comparable regarding

emergence agitation scores at the PACU.
Sedation scores did not change significantly over the
course of the assessment period in any group (P = 0.270). No
differences in mean HR or MAP were noted between the two
groups during the study period (P N 0.05).
The frequency of nausea was not significantly different
between the two groups (22k in the paracetamol group and
38k in the tramadol group) (P = 0.171). Postoperative
vomiting occurred in 19k of paracetamol group patients and
34k of tramadol group patients (P = 0.157).
Parents' and nurses' satisfaction scores regarding the
quality of pain management were similar in both groups (P =
0.779, P = 0.385) (Table 3 and Table 4).

4. Discussion
The analgesic efficacy of IV paracetamol 15 mg/kg and
tramadol 1.0 mg/kg in children undergoing adenotonsillectTable 3

Parent satisfaction scores.

Satisfaction
scores *

Paracetamol group
(n = 32)

Tramadol group
(n = 32)

P-value

1
2
3
4

0 (0)
4 (12.5)
23 (71.9)
5 (15.6)

0
3
22
7

0.779

(0)
(9.4)
(68.8)
(21.9)

Data are absolute numbers of patients (k).

1 = bad, 2 = good, 3 = very good, 4 = excellent.

Table 4

Nurse satisfaction scores

Satisfaction
scores *

Paracetamol group
(n = 32)

Tramadol group
(n = 32)

P-value

1
2
3
4

2
9
20
1

0 (0)
8 (25)
23 (71.9)
1 (3.1)

0.385

(6.3)
(28.1)
(62.5)
(3.1)

Data are absolute numbers of patients (k).

1 = bad, 2 = good, 3 = very good, 4 = excellent.

omy was evaluated, and no statistical difference was found

between groups regarding postoperative pain scores, rescue
analgesic consumption, or PONV. We also failed to show a
significant difference in recovery characteristics between
the groups.
There are conflicting results about the efficacy of IV
paracetamol for postoperative analgesia after tonsillectomy
in children. According to Pendeville et al, IV proparacetamol
30 mg/kg resulted in higher postoperative pain scores than
did IV tramadol 3.0 mg/kg given before surgical incision
[17]. Administration of high doses of tramadol 3.0 mg/kg
may have contributed to the pronounced low postoperative
pain scores in their study. However, in another study,
Alhashemi and Daghistani reported that IV paracetamol 15
mg/kg was an efficient analgesic similar to intramuscular
(IM) meperidine 1.0 mg/kg for children undergoing
tonsillectomy [18].
Evaluation of recovery characteristics and rescue analgesic medication were the other objectives of our study.
Alhashemi and Daghistani found earlier readiness for
recovery room discharge in pediatric patients undergoing
dental restoration with IV paracetamol when compared with
IM meperidine [16]. Similarly, in the present study, although
statistically no difference was detected in recovery characteristics of both drugs, the mean (SD) time to reach an Aldrete
score of 10 in the PACU was shorter in the paracetamol group
(10.6 F 17.8 min vs. 18.1 F 22.6 min in the tramadol group).
Early readiness for PACU discharge was clinically, not
statistically, different in this study, suggesting that IV
paracetamol may offer the advantage of early recovery and
early discharge from hospital, which leads to beneficial
economic aspects for day-case surgeries in children.
Despite the high number of patients receiving rescue
analgesia, pain scores in both groups were lower over the
course of the assessment period in this study. The meperidine
rescue analgesia may have influenced the subsequent low
pain scores in both groups. These data were in disagreement
with the results of Alhashemi and Daghistani [18], who
reported a high percentage of patients requiring rescue
morphine analgesia in the IV paracetamol group versus the
meperidine group. This may be due to the fact that
meperidine was more effective than tramadol for pain relief
after tonsillectomy in children [19].
Vomiting occurred in 40k to 65k of children after
tonsillectomy due to swallowed blood and oropharyngeal

IV paracetamol in children post-tonsillectomy

irritation [20-22]. Tracheal intubation and use of opioids and
nitrous oxide all have been implicated as anesthetic factors
increasing the rate of PONV [23]. The administration of
tramadol for postoperative analgesia also may have an
additive effect on the incidence of PONV [24,25]. In our
study, the frequency of PONV was not as high as has been
stated in previous reports. These data may result in part from
the anesthetic regimen that we used in both groups. Another
explanation for the discrepancy in vomiting data may be the
intraoperative administration of tramadol as an IV infusion
over 15 minutes, which reduces the frequency of PONV
compared with postoperative administration [5,25].
One limitation of our study was the lack of a true placebo
group. We administered intraoperative opioid to all patients
in the study because we believed that children in a placebo
group would awaken in pain and require rescue meperidine
analgesia in the early postoperative period, which would
have influenced postoperative pain scores, agitation scores,
and sedation scores.
In conclusion, the postoperative analgesia and early
readiness for discharge from the PACU provided by IV
paracetamol 15 mg/kg was similar to the outcome with IV
tramadol 1.0 mg/kg in children after adenotonsillectomy.

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