Comparative study of the analgesic efficacy of rectal tramadol versus intravenous tramadol for adult tonsillectomy.

BACKGROUND: The optimal method for intra- and post-operative analgesia for adult tonsillectomy is uncertain. Tramadol hydrochloride is an analgesic with mixed mu and nonopioid activities, having less/no respiratory depression. AIM: The aim of our study was to compare the analgesic efficacy and nausea/vomiting produced by tramadol via intravenous and rectal administration during the first 24 h after anesthesia for adult tonsillectomy.
MATERIALS AND METHODS: The study design was prospective, randomized, single blind and hospital based. Forty adult patients of ASA grade 1 and 2 posted for tonsillectomy were randomized to receive either intravenous tramadol (1 mg/kg) (n=20) Group A or rectal tramadol (1.5-2 mg/kg), maximum 100 mg (n=20), Group B immediately after the induction of anesthesia. Pain measurement was performed using visual analogue scale. Rescue analgesia was given when the VAS was ≥3 in the postoperative period up to 24 h. Complaint of nausea/vomiting was recorded during the same period.
RESULTS: Duration of analgesia was prolonged and requirement of rescue analgesics was less with the suppository group. Nausea and vomiting were lower with the suppository group.
CONCLUSION: The rectal route of tramadol is a better alternative to the intravenous route in comparison with the duration of analgesia and nausea/vomiting for adult tonsillectomy.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Pain is an unpleasant sensory and emotional experience of varying intensity, caused by actual or potential damage or described in such type of damage. The optimal method for intra- and post-operative analgesia for adult tonsillectomy is uncertain. It poses much discomfort due to involvement of the oropharyngeal airway. Tramadol hydrochloride is a centrally acting opioid analgesic, which acts on mu opioid receptors, and is classified as a phase II analgesic according to the WHO pain score.[1] Tramadol is an analgesic with mixed opioid and nonopioid activities.[23] The nonopioid component is mediated through alfa-2 agonist and serotonergic activity, which it exerts by inhibiting the reuptake of norepinephrine and 5-hydroxytryptamine in the central nervous system and possibly by displacing the stored 5-HT from the nerve endings.[45] The aim of our study was to compare the analgesic efficacy and the nausea/vomiting produced by tramadol via intravenous and rectal administration for adult tonsillectomy. However, after i.v. and oral administration, peak concentrations are reached rapidly, and this has been associated with postoperative nausea and vomiting.[6] This limits the use of tramadol as a postoperative analgesic, especially in day surgery and oropharyngeal surgery, like tonsillectomy, in which we want to avoid the postoperative nausea and vomiting. Rectal administration of tramadol may be an alternative in this situation. It is convenient to use and is the established treatment for postoperative pain in adults.[7] It is important to stress that rectal absorption of tramadol showed a low variability. O-demethylated metabolite (M1) contributes to the analgesic effect by stimulation of the mu-opioid receptors. Tramadol is increasingly used for the treatment of acute and postoperative chronic pain of intermediate or severe intensity.[1]

MATERIALS AND METHODS

The study design was prospective, randomized, single blind and hospital based. After institutional ethical clearance, adult patients of ASA grade 1 and 2 posted for tonsillectomy were included in the study. Patients with history of allergy to any drug (in the form of cutaneous swelling, erythema, generalized itching, eruptions, etc.), old age, obesity, on monoamine oxidase inhibitors, anorectal complaints or other systemic diseases (cardiovascular, neurological, respiratory, hepatic, renal) were excluded from the study. All the patients were explained about the procedure and use of visual analogue scale (VAS) scoring system in the evening prior to surgery. Pain measurement was performed using a VAS, a 10 cm line with 0 cm equaling no pain and 10 cm equaling the worst pain ever felt. After written informed consent, all 40 patients were divided into two groups of 20 each. Group A (n=20) patients received intravenous tramadol hydrochloride 1 mg/kg (Supridol-50 mg/ml; Neon Laboratories India, India) while Group B (n=20) patients received tramadol 1.5–2 mg/kg, maximum 100 mg in the form of suppository (Supridol-100 mg; Neon Laboratories India). The groups were similar with respect to age, weight and duration of surgery. All the patients were premedicated with inj. Glycopyrrolate 0.004 mg/kg i.v. and inj. Midazolam 0.02 mg/kg i.v. 10 min prior to induction. Preoxygenation was carried out with 100% O2 for 3 min, induction with inj. Sodium Thiopentone 5 mg/kg i.v., followed by inj. Succinyl choline 1.5 mg/kg i.v. and intubation with an appropriate-sized oral, cuffed, portex endotracheal tube in the first attempt was successful in all the patients. Immediately after induction, in Group A patients, intravenous tramadol hydrochloride injection 1 mg/kg was given while Group B patients received tramadol hydrochloride suppository 1.5–2 mg/kg via the rectal route. This is considered 0 h. Anesthesia was maintained with 66% N2O in 33% O2 and inj. Vecuronium Bromide with a loading dose of 0.1 mg/kg and maintenance of 0.02 mg/kg, IPPV via circle system was given. Intraoperatively, the following parameters were recorded: pulse rate, blood pressure, spo2. After completion of surgery, when hemostasis was confirmed and when all the criteria for extubation were fulfilled, reversal with inj. Neostigmine 0.05 mg/kg and inj. Glycopyrrolate 0.008 mg/kg was given. Patients were extubated and observed in the ward. Before extubation, inj. Ondansetron 0.08 mg/kg i.v. was given slowly as a prophylactic measure to avoid postoperative nausea and vomiting. Assessment was carried out at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 20 and 24 h. Duration of surgery was 30-60 min. No operation lasted for more than 60 min. A ward nurse, who was blinded to the group allocation of the patient, recorded postoperative pain according to the VAS, pulse rate and blood pressure, nausea, vomiting, need for rescue analgesics and local burning. When the score was ≥3 by VAS, rescue analgesic in the form of intravenous Dynapar-AQ (Diclofenac sodium) 75 mg diluted with 100 ml normal saline was given.

Statistical analysis

The results were expressed as mean, with standard deviation. Statistical analysis was carried out using the paired t-test. A P-value of <0.05 was considered significant and <0.001 was considered highly significant.

RESULTS

Table 1 shows the demographic data and length of operation in both the groups, which was similar. Tables 2 and 3 show the postoperative VAS score in the i.v. group and the suppository group, respectively. Table 4 shows the time and frequency of the rescue analgesic. Table 5 shows the total duration of analgesia, which was 426±80.36 (360–600) min and 504±146.96 (360–720) min with the i.v. and the suppository groups, respectively. It was statistically highly significant (P < 0.001). Postoperative nausea and vomiting was observed in three patients of Group A and one patient of Group B. None of the patients complained local burning in the suppository group.

Table 1

Demographic data

Table 2

VAS in intravenous tramadol

Table 3

VAS in tramadol suppository

Table 4

Rescue analgesia

Table 5

Duration of analgesia in minutes

DISCUSSION

This study evaluates the role of tramadol by two different routes in adult tonsillectomy. Postoperative pain is associated with grave psychological trauma, resulting in a restless and uncooperative patient. It thus seems that tramadol may be suitable to treat postoperative pain. However, after i.v. and oral administration, peak concentrations are reached rapidly, and this has been associated with postoperative nausea and vomiting. This limits the use of tramadol as a postoperative analgesic, especially in day surgery.[6] Rectal administration of tramadol may be an alternative in this situation. It is convenient to use and is the established treatment for postoperative pain in adults.[7] Patients generally dislike being given suppositories when awake and it is a common method to administer them at anesthetic induction. In our study also we introduced tramadol immediately after induction to avoid patient discomfort. A rectal dose of 1.5–2.0 mg/kg is therapeutic.[1] Therefore, a dose of 100 mg was used in our study for suppository. Tramadol is rapidly distributed after i.v. administration, with a distribution half-life in the initial phase of 6 min, and the onset is fast.[2] Following rectal administration, tramadol was detected from 5 min up to 10 h in dogs. After suppository, absorption of the active ingredient was rapid, but its metabolism quickly transformed the parent drug to high levels of N-desmethyl-tramadol (M2) and N,O-didesmethyl-tramadol (M5).[8] Studies are not available showing the duration of analgesia after tramadol suppository. In our study, it was shown that 65% of the patients needed first rescue analgesia at 6 h in Group A while it was only 5% in patients in Group B, which was a significantly lower proportion. With the suppository group, 50% needed first rescue analgesia at 8 h and another 5% needed the same at 10 h. Thus, only 60% of the patients required rescue analgesia in Group B within 10 h of the postoperative period. Another 40% of the patients in Group B did not require rescue analgesia at all, which was not seen with Group A. In Group A, 100% of the patients required rescue analgesia within 10 h of the postoperative period. Forty percent of the patients in Group A required rescue analgesia a second time at 18 h while in Group B this was only 16% (out of patients who required first rescue analgesia) at 20 h. The duration of analgesia was prolonged with Group B, which was observed by time for need for first rescue analgesic and percentage of patients who required it in both groups. The mean duration of analgesia was prolonged with Group B, which was statistically highly significant (P<0.001). The maximal plasma concentrations of tramadol and its metabolite (O-demethylatedtramadol) were 200 (60) and 35 (15) ng/ml at 2.4 (1.0) and 3.9 (1.1) h after rectal administration.[1] The time interval during which tramadol concentrations would be at least 100 ng/ml could not be calculated after a dose of 1 mg/kg. After the 2 mg/kg dose, the time interval would be 8.6 (1.1) h, which could be correlated with the duration of analgesia.[1] M1 contributes to the analgesic effect of rectally administered tramadol, one- to four-times higher than the parent compound, which was reflected by the lower analgesic efficacy of tramadol in patients with low serum concentrations of M1.[1] The mean absolute bioavailability after rectal administration is 78%.[9] Simulations suggest that at least tramadol 1.5 mg/kg is necessary to reach therapeutic concentrations.[1] After rectal administration of the tramadol suppositories, the absorption of the active ingredient is rapid enough for therapeutic purposes and that the extent of the absolute bioavailability is higher than after the oral administration of tramadol-HCI, probably due to a reduced first-pass metabolism. Intravenous tramadol is associated with postoperative nausea and vomiting.[610] No patient was complaining of local burning in the suppository group. Various oral, rectal and parenteral formulations of tramadol are available. The rectal route may represent a practical alternative, and rectal administration is now well accepted for delivering tramadol as it is easy to manage, requires a minimal level of expertise and may avoid parenteral administration. Although individual variations exist, there is sufficient absorption of drugs after rectal administration.[11] Further prospective studies are warranted to investigate the analgesic efficacy of rectal tramadol vs. standard treatment.

CONCLUSION

Duration of analgesia is prolonged with the rectal route, which decreases the requirement of rescue analgesia. It also increases the patient comfort by avoiding nausea and vomiting compared with the intravenous route. The rectal route is a safe, easy, reliable, noninvasive, comfortable and painless means for pain relief in adult tonsillectomy. Tramadol has proved to be a valuable addition to the range of effective analgesic drugs.