Acad J Surg, Vol. 1, No.

1-2 (2014) ORIGINAL REPORT

Effect of Ephedrine on Pain and Hemodynamic Status on Injection of Propofol

Hamidreza Sharifnia1, Kamran Shadvar2, Omid Azimaraghi1, Yasaman Aghajani1,
Maziar Molaghadimi1, Maliheh Khosravi1, Ali Movafegh3
1
Resident of Anesthesiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
2
Anesthesiologist, Tabriz University of Medical Sciences, Tabriz, Iran
3
Professor of Anesthesiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Received: 9 Aug. 2013; Received in revised form: 12 Nov. 2013; Accepted: 11 Jan. 2014

Abstract
Background: Propofol is one of the drugs most commonly used during induction of anesthesia. The induction
dose of propofol can lead to hemodynamic changes such as hypotension and bradycardia. Pain on injection is
another side effect of propofol. The purpose of this study was to evaluate the effect of two different doses of
ephedrine on hemodynamic status and pain on injection of propofol compared to lidocaine and placebo.
Methods: In the present study, 100 patients were enrolled. A 22 gauge cannula was inserted into the veins on
the non-dominant hand of all patients. The patients were randomly allocated to 4 groups and 10 ml/kg of saline
was administered over 10 minutes from each of the cannulas. Then, patients received either of these pre-
treatments: 2 ml of Saline (group S); 2 ml lidocaine 2% (40 mg) (group L); Ephedrine (30 ug/kg) (group E1);
or Ephedrine (70 ug/kg) (group E2). After 30 seconds all patients were administered 2.5 mg/kg of propofol
with a rate of 1 ml per second. The patients were asked to give a score from 0 to 10 (0 = no pain and 10 = most
severe pain) every 5 seconds until loss of consciousness. Systolic and diastolic pressures and heart rate were
recorded before induction of anesthesia, before intubation, and 1, 3, and 5 minutes after intubation.
Results: Systolic, diastolic, and mean arterial pressure and heart rate following induction in E1 and E2 groups
were higher than S and L groups (P < 0.001). There were no differences in systolic, diastolic, and mean arterial
pressure and heart rate 1, 3, and 5 minutes after intubation between groups. Lidocaine and both doses of
ephedrine reduced pain on injection of propofol similarly.
Conclusions: Lidocaine and high and low doses of ephedrine reduce the intensity of pain on injection of
propofol. Small doses of ephedrine attenuate blood pressure and heart rate reduction after induction of
anesthesia with propofol.
2014 Tehran University of Medical Sciences. All rights reserved.
Citation: Sharifnia H, Shadvar K, Azimaraghi O, Aghajani Y, Molaghadimi M, Khosravi M, Movafegh A.
Effect of Ephedrine on Pain and Hemodynamic Status on Injection of Propofol. Acad J Surg, 2014;
1(1-2): 11-4.

Keywords: Propofol, Ephedrine, Lidocaine, Pain, Hemodynamics

Introduction injection especially in children (7). Low dose ketamine

and ephedrine have also been studied on prevention of
Propofol is the drug most commonly used to induce hypotension caused by propofol induction (8,9). The
anesthesia (1). Propofol administration for induction of aim of the present study was to determine the effect of
anesthesia can result in hemodynamic changes such as two doses of ephedrine on prevention of injection pain
a decrease in systolic or diastolic blood pressure and and hemodynamic changes caused by propofol during
also heart rate, as well as pain on injection, with an induction of anesthesia.
incidence of 40 to 86% (3,4). Different methods have
been previously proposed to reduce the pain on Materials and Methods
injection of propofol, such as diluting the solution,
injection into large veins or pre-treatment by drugs The study protocol was approved by the Institutional
such as ondansetron, metoclopramide, or thiopental Ethics Committee. An informed written consent was
sodium (5,6). Lidocaine has also been previously obtained from all the participants. In this randomized,
suggested as a drug which may alleviate the pain on double-blinded, placebo-controlled clinical trial, 100

Corresponding Author: Ali Movafegh

Department of Anesthesiology and Critical Care, Shariati Hospital, North Kargar Street, 1411713135 Tehran, Iran.
Tel: +98 912 3021389/Fax: +98 21 88220032, E-mail: [email protected], [email protected]
Efedrine and pain on injection of propofol

patients aged between 19 to 50 years with American considering SD = 2.7 at a significance level of 0.05.
Society of Anesthesiologists (ASA) physical status This number was raised to 25 in each group to allow a
class I or II whom were candidates for elective predicted 10% drop.
laparoscopic cholecystectomy in Dr. Shariati Hospital Statistical analyses of the results were performed
were enrolled in the study. using SPSS for Windows (version 17.5, SPSS Inc.,
Patients with a history of chronic pain, diabetes Chicago, IL, USA). The distribution of data was
mellitus, vascular disease, and any contraindications to checked by the KolmogorovSmirnov test, they
injection of lidocaine, propofol, or ephedrine were not followed a normal distribution. The quantitative data
enrolled in the study. were analyzed by one way ANOVA, post-hoc Tukeys
In the preoperative visit the visual analog scale test, and repeated measure analysis of variance. Two-
(VAS) for pain (0 = no pain, 10 = most severe pain) tailed P value < 0.05 was considered as statistically
was thoroughly explained to all the patients. No significant.
pre-medications were administered to the patients.
On arrival to the operating room, all patients were Results
monitored with an electrocardiogram (ECG),
noninvasive blood pressure, and pulse oximetry. All A total number of 100 patients were enrolled in the
the required drugs were prepared in opaque syringes by study. There was no protocol violation and none of the
an anesthetist who was not involved in either the patients were excluded from the study. Basic
administration of drugs to patients or patients' characteristics of the patients including age, sex, and
evaluation; thus, both the anesthesiologist and the ASA class are presented in table 1. There was no
patients were blinded to the study. significant difference between the groups.
A 22 gauge cannula was inserted into the veins on There was no difference between mean systolic and
the non-dominant hand of all the patients and 10 ml/kg diastolic pressures and heart rate recorded before
normal saline was administered to the patients. Using a induction of anesthesia in the 4 groups (Table 2).
computerized program, the patients were randomly Following induction of anesthesia there were
allocated into 4 groups. In group C 2 mL of Saline, in statistically significant reductions in systolic and
group L 2 mL lidocaine 2% (40 mg), in group E1 30 diastolic blood pressure and heart rate in groups C and
g/kg ephedrine, and in group E2 70 g/kg was injected L (repeated measure analysis of variance, p = 0.002).
to the cannula following using a tourniquet to the same Tukeys post-hoc test showed no difference between
arm. After 30 seconds the tourniquet was released and groups E1 and E2. Systolic and diastolic blood pressure
all the patients received 2.5 mg/kg of propofol with a and heart rate did not drop in measured times in any of
rate of 1 ml per second. The patients were asked to give the groups.
a score from 0 to 10 (0 = no pain and 10 = most severe The VAS score for pain was less in groups L
pain) every 5 seconds until loss of consciousness. The (1.6 2.5), E1 (1.6 2.6), and E2 (1.5 2.7) than
highest score was recorded. Adverse effects were also group C (4.9 3.3) (P < 0.001, one way ANOVA)
recorded. Anesthesia was induced by propofol and (Table 2). There was no significant difference in
endotracheal intubation was facilitated with 0.5 mg.kg-1 groups A, B, and C (Tukeys post-hoc test).
atracurium. After tracheal intubation, anesthesia was
maintained by isoflurane 1-1.5% and N2O (50%); 0.1
mg.kg-1 atracurium and 1g.kg-1 fentanyl were Discussion
administered every half hour. Ventilation was adjusted
to maintain normocapnia (end-tidal carbon dioxide In this study it was observed that lidocaine and both
partial pressure 4.7-5.3 kilo Pascal (kPA)). Systolic and doses of ephedrine reduced the pain on injection of
diastolic pressures and heart rate were noted before propofol. Yet, no difference was observed between
induction of anesthesia, before intubation, and 1, 3, and groups L, E1, and E2. Moreover, both high and low
5 minutes following intubation. doses of ephedrine prevented a decrease in the blood
It was estimated that a minimum of 22 patients in pressure and heart rate following induction of
each group would be required in order to have a 95% anesthesia. This effect was not observed by
power of detecting three scores in the VAS for pain, administration of lidocaine or placebo.

Table 1. Basic Characteristics of the patients

Ephedrine Ephedrine
Lidocaine Placebo
70 g/kg 30 g/kg
Age (year) 33.2 9 33.8 3.8 32 5.6 31.7 4.5
Sex (Female/Male) 13/12 14/11 14/11 12/13
ASA class (I/II) 15/10 16/9 14/11 16/9
Weight (kg) 70.3 9.1 72 8 70.1 9 68.3 7.5
Data are presented as mean SD, ASA: American Society of Anesthesiologists

12 Acad J Surg, Vol. 1, No. 1-2 (2014)

 Sharifnia H, et al.

Table 2. Hemodynamic variables recorded before induction of anesthesia, and 1, 3, and 5 minutes after intubation
Ephedrine Ephedrine
Lidocaine Placebo
70 ug/kg 30 ug/kg
Systolic blood pressure
Before induction 117.32 12.26 116.6 12.17 117.2 12.58 116.67 12.6
Before intubation 106.4 12/03* 102.6 10.61* 82.2 9.02 82.29 9.32
1 min after intubation 133.2 17.73 134.2 14.98 127.2 12.59 126.07 13.35
3 min after intubation 125.4 16.07 122.6 13.39 112.2 12.59 11.04 12.16
5 min after intubation 11.2 14.24 118.8 11.89 106.8 11.89 104.37 11.54
Diastolic blood pressure
Before induction 75.82 10.16 75.8 10.47 75.60 10.14 76.04 10.63
Before intubation 68.28 8.38 65.6 10.13 48.8 9.38 50.79 10.05
1 min after intubation 86.64 12.44 86 10.89 81.6 11.7 83.33 11.85
3 min after intubation 80.56 10.56 80.6 10.83 71.6 9.32 63.54 23.96
5 min after intubation 74.28 9.83 70.8 10.47 67 9.57 66.66 9.63
Mean arterial pressure
Before induction 89.65 10.13 89.73 9.92 89.46 9.93 89.58 10.34
Before intubation 80.98 8.61 77.93 9.38 57.26 8.51 59.95 8.66
1 min after intubation 102.16 12.71 102.06 10.92 96.8 10.90 97.57 11.33
3 min after intubation 95.5 11.02 94.6 10.52 85.13 9.32 79.37 16.74
5 min after intubation 86.58 9.92 84.46 9.95 80.26 9.21 79.23 9.4
Heart rate
Before induction 98.88 14.35 98.28 12.74 100.48 12.79 98.33 11.93
Before intubation 87.8 13.69* 84.4 12.84 54.60 12.25 56.83 11.46
1 min after intubation 117.24 14.71 113.16 14.81 110.68 13.75 110.5 13.71
3 min after intubation 113.92 13.37 109.64 14.06 106.6 13.31 106.58 13.23
5 min after intubation 106.36 25.49 106.76 13.79 103.36 13.06 102.7 12.63
Visual analogue scale 1.52 2.7* 1.64 2.62 1.56 2.46* 4.87 3.26
*P < 0.05; Data are presented as mean SD

The incidence of pain on injection of propofol is high dose, pretreatment with low dose ephedrine not
estimated to be 40 to 86.6% in adults (12,13). In a only reduces pain on injection of propofol, but also
study conducted by Cheong et al. the incidence of pain helps stabilize patients' systolic and diastolic blood
was reported to be 86.6% (3). pressure and heart rate following induction of
The underlying mechanism of pain caused by anesthesia. As both low (30 ug/kg) and high doses of
injection of propofol is unknown, although the kinin ephedrine (70 ug/kg) reduce pain on injection of
cascade has been proposed as one of the probable propofol, the use of low dose is more rational.
mechanisms (14). Between different drugs proposed to Although Cheong et al. did not report any adverse
reduce pain on injection of propofol, lidocaine is the hemodynamic effects after tracheal intubation using
most commonly used drug. Lidocaine is either injected higher doses of ephedrine (110-150 ug/kg), some
as a bolus dose prior to propofol or is added to the adverse effects are possible in patients with
propofol solution before injection; however, even cardiovascular disease. Therefore, these high doses
patients who had received lidocaine reported an should be used with caution in such groups of patients.
incidence of 32 to 48% pain on injection (12-14). This study shows that both low (30 ug/kg) and high
Granisetron has also been reported to be effective in (70 ug/kg) dose ephedrine, injected 30 seconds before
reducing pain on injection of propofol (1). The two induction of anesthesia with propofol, reduce pain on
most efficacious interventions to reduce pain on injection and stabilize patients hemodynamic profile.
injection of propofol were use of the antecubital vein
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