Combination of oral tramadol and midazolam vs midazolam alone as a premedication in children undergoing adenotonsillectomy

Combination of oral tramadol and midazolam vs midazolam alone as a premedication in children undergoing adenotonsillectomy Vrigga M, Papagiannopoulou P, Ntritsou V, Isaakidis A, Chatziioakimidis Ch, Kostoglou Ch, Zachariadou Ch. Department of Anesthesiology, “G. Gennimatas” General Hospital, Thessaloniki, Greece The aim of this study was to compare the combination of oral tramadol and midazolam to oral midazolam alone, in children undergoing adenotonsillectomy, as an oral premedication, regarding also sedation and postoperative pain relief. Sixty children selected for elective adenotonsillectomy were enrolled in this randomized, controlled prospective study. Patients were randomly allocated into two groups. Group M (n=30) received 0.5 mg.kg oral midazolam and group MT (n=30) received 0.2 mg.kgoral midazolam with 1 mg.kg oral tramadol as a premedication 30min preoperatively. Standard general anesthesia technique was used. A 5 points-sedation score (1 asleep to 5 agitated) on arrival to the operating room, a 3 points-acceptance score of separation from the parents and a 3 points-mask cooperation score at induction of anesthesia (1 easy to 3 markedly resistant) were used. Aldrete score, extubation time and intraoperatively consumption of remifentanil were also recorded. Pain intensity was assessed using a modification of the Hannallah pain score scale at 30min, 6h and 24h postoperatively. If pain score was higher than 3, additional analgesics were provided. Cumulative analgesic consumption in 24hrs was also noted. A satisfactory level of sedation scores were recorded in both groups. Group MT offered significantly more children in an awake, calm and quiet state, who were easily separated from their parents. The parental separation scores did not differ statistically significant The Greek E-Journal of Perioperative Medicine 2014; 12(b): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2014; 12(b): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal 37 ©2014 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2014 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος between groups. The mask acceptance was statistically significant easier in group MT, while children in midazolam group (group M) were statistically significant resistant compared to children in group MT. Pain and modified Aldrete scores were comparable between groups. The amount of remifentanil consumed intraoperatively was statistically significant lower in group MT. Postoperative analgesic consumption was lower in group MT compared to group M but with no statistical significance. Adding oral tramadol to midazolam as a premedication in children provides good quality of sedation and decreases perioperative analgesic requirements following adenotonsillectomy. INTRODUCTION The preoperative period is usually a stressful time for children and their parents. Uncooperative children, whether due to anxiety, phsychologic, developmental or mental disorders or repeated anesthesia, should be adequately treated in order to avoid postoperative behavior problems. Various interventions are used to allay the anxiety of a child during the perioperative period such as sedative premedications, parental presence during induction and preoperative preparation programs. Sedation remains one of the widely used methods for decreasing anxiety in young children. The oral route remains the most acceptable method of drug administration though various combinations of drugs and routes of administration are available. Adenotonsillectomy is a common pediatric surgical procedure associated with significant postoperative pain. Inadequate pain management after this procedure is a difficult task and could remain even over four days after surgery and results in poor oral intake, dehydration, long hospital stay, sleeping disorders, behavioral changes, nausea and vomiting. Various methods and medications are available to relieve and control preoperative stress and acute postoperative pain in children after adenotonsillectomy. Midazolam with its favorable pharmacodynamics (i.e. rapid onset, relatively short duration and lack of significant side effects), and pharmacokinetics is among the most popular pediatric premedicant in Europe and U.S.A. However good to excellent results are seen in only 60-80% of cases. Suitable doses of the major analgesics are routine for in-patient children’s surgery. However, fear of side effects such as nausea and vomiting or respiratory depression prevents the wide use of powerful opioids in children. Tramadol hydrochloride is a synthetic analogue of codeine used for the treatment of moderate to severe pain. It has a dual mechanism of action. Tramadol and its active metabolite, OThe Greek E-Journal of Perioperative Medicine 2014; 12(a): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2014; 12(a): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal 38 ©2014 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2014 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος desmethyl tramadol, bind to μ opioid receptors thus exerting their effect on GABAergic transmission. They also inhibit reuptake of 5hydroxy tryptamine (serotonin) and noradrenaline. These latter effects are likely to be an important element in analgesia and may also account for triggering two significant adverse events seizures and serotonin syndrome. These may develop during tramadol monotherapy either at routine or excessive doses, but are particularly likely during tramadol administration in epileptic patients. Tramadol has been licensed for use in children over 1 year of age in many European countries, although others have limited its use to children over 12 years of age. Pharmacokinetic data is available in young children following intravenous and caudal routes of administration, but few kinetic studies have been published using oral drop administration in children. Midazolam and tramadol can be used in different dosage combinations with variable effects and outcomes. A combination with lower doses of them could provide adequate anxiolysis, sedation and postoperative pain relief with lesser fewer side effects. Therefore, the authors thought that a combination of midazolam with tramadol may be useful to enhanced preoperative stress and postoperative pain relief after adenotonsillectomy. Thus, the goal was to study the combination of oral tramadol and midazolam to oral midazolam alone, in children undergoing adenotonsillectomy, as an oral premedication, regarding also sedation and postoperative pain relief. MATERIAL AND METHODS Following institutional approval and written informed parental consent, which abided with the Declaration of Helsinki, 60 children, 3-12 years of age with ASA physical status I or II, scheduled for elective adenotonsillectomy, as in-patients, were recruited in this prospective randomized double blinded study. All operations were performed by the same surgeon who was blind to the study drug, using the same surgical technique. Exclusion criteria included children with ASA physical status III or higher, neurological and cardiovascular system disorders, history of seizures or epilepsy, increased intracranial pressure, upper respiratory tract infection and documented allergies. Patients who developed bleeding or hypersensitivity to tramadol and those who refused to swallow or vomited the premedication mixture also were excluded from the study. All children were randomly assigned in two groups, using computer-generated random numbers. Group M (n=30) received 0.5 mg.Kg oral midazolam and group MT (n=30) low dose combination of oral midazolam (0.2 mg.kg) and tramadol drops (1 mg.kg). Both The Greek E-Journal of Perioperative Medicine 2014; 12(a): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2014; 12(a): 36-48 (ISSN 1109-6888) www.anesthesia.gr/ejournal 39 ©2014 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2014 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος medications were mixed in 5 ml apple juice by a nurse not involved in the study and administrated to the patients 30 minutes prior to anesthesia induction. On arrival at the operating room children were evaluated with a scoring system for premedication assessment, which consisted of a 5 pointssedation score (1 asleep to 5 agitated), a 3 points-acceptance score of separation from the parents and a 3 points-mask cooperation score at anesthesia induction (1 easy to 3 markedly resistant) (Table 1). Table 1.The scoring system for premedication assessment in children Scores 2 and 3 in the sedation score were defined as ‘effective’ and score 3 for separation from the parents and mask cooperation at anesthesia induction was defined as ‘poor’. All study patients received a standard anesthetic protocol. Anesthesia was induced with sevoflurane in 100% oxygen administrated via mask and breathing circuit. Monitoring consisted electrocardiogram, pulse oximetry, automated non-invasive blood pressure, end-tidal carbon-dioxide, inhalation agent concentration and an FiO2 (fraction of inspired oxygen) analyser. After obtaining intravenous (i.v) access, fentanyl (3 mcg /kg), lidocaine (1 mg/kg) and rocuronium (0.6 mg/kg) were administrated, followed by tracheal intubation using an appropriate-sized endotracheal tube. Anesthesia was maintained with sevoflurane in oxygen 40% titrated to clinical response. Intermitted positive pressure ventilation was used. Intraoperative analgesia was provided with remifentanil i.v infusions of 0.05 to 1 mcg/kg/min, with bolus doses of 1 mcg/kg if needed, in order to maintain heart rate and systolic blood pressure within 20% of the baseline levels. Intraoperative consumption of remifentanil was noted during the study. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine (50 mcg/kg) and atropine (20 mcg/kg). After adequate neuromuscular recovery and return of airway reflexes, the trachea was extubated. The duration of surgical procedure and anesthesia and the time interval between disconFive points-sedation score Asleep, not readily arousable 1 Asleep, but arousable 2