Iranian Journal of Pharmacology & Therapeutics, Vol. 5, No. 2, 2006, pp. 131-133

Research Article

Farhad Heshmati, Heidar Noroozinia, Rahman Abbasivash, Alireza Mahoori and Helen Gharaee

Current Author Addresses: Farhad Heshmati, MD. Associate professor of anesthesiology, Urmia University of Medical Sciences, Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran.Fax: +98 (441) 3469935 E-mail: f_heshmati@umsu.ac.ir (Corresponding author).
Heidar Noroozinia, MD. Assistant professor of anesthesiology, Urmia University of Medical Sciences, Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran.
Rahman Abbasivash, MD. Assistant professor of anesthesiology, Urmia University of Medical Sciences, Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran.
Alireza Mahoori, MD. Assistant professor of anesthesiology, Urmia University of Medical Sciences, Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran.
Helen Gharaee, MD. Anesthesiologist, Urmia University of Medical Sciences, Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran.

Received May 24, 2006; Revised September 28, 2006; Accepted October 3, 2006

Code Number: pt06022

ABSTRACT

The most important role in postoperative pain management is still played by opioid administration through various modes. For the last few years, there has been an intensive search for alternative mode of opioid administration in pain management. The intranasal modes of opioid administration seems to be an attractive alternative. Sixty boys (aged 0.5-6 yr); ASA (American Society of Anesthesiologists) physical status I, who were candidates for lower abdominal surgery, were included in this prospective randomized, controlled study. Five minutes before extubation, patients were randomized to two groups and allocated to receive intranasal sufentanil (0.7 µg/kg) or normal saline, using a double-blinded study design. Satisfactory analgesia was achieved with intranasal sufentanil. It was effective after 10 minutes with the least pain scores (pain score 2.3±0.4 vs. 4.1±0.5) (p = 0.001). Pain scores in 15, 20 and 25 minutes were similar in sufentanil group. None of patients had bradycardia, hypotension or SpO₂ (arterial O₂ saturation) <95%. High bioavailability of sufentanil after intranasal administration due to direct entrance of the drug into the systemic circulation and avoidance of the hepatic first- pass effect makes sufentanil an opioid with rapid onset and limited duration. As it has minimal side effects, sufentanil is one of the best choices for postoperative pain control in children. We used 0.7 µg/kg of intranasal sufentanil and found satisfactory analgesia accompanied with least side effects.

Keywords: Analgesia, Intranasal, Sufentanil, Pediatric, Postoperative pain

It is now accepted that pain should be anticipated, safely and effectively controlled in all children, whatever their age, maturity or severity of illness. Unfortunately the postoperative pain in pediatric patient is not adequately managed [1]. The most important role in postoperative pain management is still played by opioids administered through various modes. In the last few years, there has been an intensive search for alternative mode of opioid administration in pain management. The intranasal mode of opioid administration seems to bean attractive alternative, especially in patients who have not intravenous access.

Supported by extensive research into novel form of drug delivery, nasal administration of medications is emerging as a promising method of delivering drug with several advantages [2]. Pharmacokinetic studies have demonstrated a high bioavailability (71%, 65% and 78%) and a rapid rise in plasma concentrations follow intranasal fentanyl, alfentanil and sufentanil. Sufentanil is the most extensively used for sedation [3]. The elimination half life of intravenous sufentanil is 15-20 minutes [4]. Intranasal administration induces no clinically significant change in vital signs, whereas after intravenous sufentanil, a clinically significant decrease in PaO₂ (arterial partial pressure of oxygen) is seen at 5 min [5].

After approval by University Research Committee and obtaining parental consent, sixty normal healthy boys, aged 0.5-6 yr, scheduled to lower abdominal surgery (such as, herniorrhaphy, orchiopexy, hydrocellectomy, urethroplasty) undergoing general anesthesia enrolled in this prospective double blinded study. Exclusion criteria included emergency operations and upper respiratory tract infection. All patients received fentanyl 1mg/kg and atropine 10 µg/kg before induction of anesthesia. Induction of anesthesia accomplished with thiopenthal Na 6 mg/kg and atracurium 0.6 mg/kg (for facilitation of tracheal intubation). Anesthesia was maintained by administration of halothane and N2O in 50% O₂. Patients randomized (according to table of randomized numbers) in two groups, group 1 (n=30) received intranasal normal saline (N/S) and group 2 (n=30) received intranasal sufentanil (0.7 µg/kg), 5 min before extubation. Heart rate, blood pressure, respiratory rate, arterial O₂ saturation (PaO₂), vomiting, pain and sedation scores were recorded by a nurse who was not informed of the content of administrated solutions. Pain was measured according to FACEs pain rating scale (Fig 1) and sedation was measured according to Ramsay Sedation Scale at arrival and every 5 min until 30 min in recovery room. We considered FACEs pain rating scale < 4 as satisfactory postoperative analgesia and Ramsay Sedation Scale ³4 as over sedation.

Data Analysis

To analyze differences between two groups Log linear models was used. Fisher-Exact test was considered for nominal data using SPSS software. Statistically differences between two groups of patients was considered at p<0.05.

There was no difference between the groups, with respect to age, weight, duration of surgery and anesthesia. Pain scores were significantly reduced in sufentanil group vs. normal saline group (pain score 2.3±0.4 vs. 4.1±0.5) (p=0.001). Sufentanil was effective after 10 minutes with the least pain scores (Fig 2, Fig 3). Pain scores in 15, 20 and 25 minutes were similar in sufentanil group. Patients did not have bradycardia, hypotension or SpO₂ <95%. Two patients in sufentanil group had nausea, which in one of them occurred immediately after instillation of drug. This problem might be not related to sufentanil. It seems the cause of nausea in this patient was related to awake extubation. Four patients in sufentanil group and two patients in normal saline group had over sedation. But none of them SpO₂ <95% or loss of protective reflexes.

Our results show that intranasal sufentanil is quite effective in relieving pain in pediatric patients. Most patients experienced significant pain relief after 10 min.

Sufentanil 1.5 µg/kg IV ten minutes before the end of surgery had very satisfactory results for postoperative pain relief [12]. Using intranasal sufentanil for break through and incident cancer – associated pain, has been reported with no adverse effects such as vomiting or respiratory depression [13].

In a study intranasal sufentanil (1.5, 3.0, or 4.5 µg /kg) was compared by placebo (normal saline, 0.03 ml/kg). Induction of anesthesia was completed with 5% halothane and O₂ via facemask. After tracheal intubation, anesthesia was maintained with N₂O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Sufentanil, 4.5 µg/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day [14]. Intranasal sufentanil (10 or 20 µg) has been successfully used for preoperative sedation in adult patients [15].

We chose sufentanil because of its high bioavailability, rapid onset, short duration and minimal side effects. According to these studies, we used 0.7 µg/kg sufentanil and found it very effective and safe. Side effects such as nausea and over sedation were in acceptable range. We recommend using it as postoperative analgesic in operating room and post anesthesia care unit (PACU), as premedication or even as triage nurse- initiated administration in the emergency department.

References

Copyright © 2006 by Razi Institute for Drug Research (RIDR)