Oral midazolam and oral butorphanol premedication
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《美国医学杂志》
Department of Anesthesiology, King George's Medical University, Lucknow, India
Abstract
Objective: To evaluate the efficacy of oral midazolam and oral butorphanol for their sedative analgesic effects in children. Methods: Sixty children, aged 2 to 10 yrs, of ASA physical status I and II, scheduled for surgical procedures of 1 to 2 hrs duration were randomized to one of the two groups. Group I: children received midazolam 0.5mg/kg orally and Group II: children received butorphanol 0.2mg/kg orally. Score of the children was assessed every 5 minutes till the induction of anesthesia. Intraoperative and postoperative analgesic requirement was recorded alongwith postoperative recovery and complications. Results: The groups were identical regarding the patient's characteristics, hemodynamic variables, duration of surgery and awakening time. Less time was required for the onset and time of maximum sedation in the butorphanol group (p<0.05). Sedation scores were similar among the groups at all time intervals, while the scores were higher in the butorphanol group at the time of induction (p<0.05). Less number of children required intraoperative and postoperative rescue analgesia in the butorphanol group (p<0.05). Statistically significant difference was found among the groups in respect to complete amnesia (50% in group I vs 80% I group II, p<0.05) and recollection (40% in group I vs 10% in group II, p<0.05). Conclusion : Oral butorphhanol is comparable to oral midazolam in children but analgesia alongwith sedation is an additional advantage which makes it better than midazolam without a significant increase in side effects.
Keywords: Oral premedication; Children; Midazolam; Butorphanol; Sedation; Analgesia
Fear of painful and unpleasant procedures, separation from parents, and unacceptability of face mask may produce the levels of anxiety that is troublesome in unpremedicated patients. Based on both behavioral and physiological responses, Kain et al[1] have indicated that induction of anesthesia appears to be most stressful procedure the child experiences during the perioperative period.
Numerous premedications have been advocated to facilitate the separation of children from their parents and to reduce the anxiety associated with the unfamiliar and intimidating environment of the operating theater. The fact that no single premedication has achieved universal acceptance suggests that each has its disadvantages. Therefore, we have conducted a prospective, randomized, double blind trial to compare the efficacy of oral midazalam and oral butorphanol for their sedative-analgesic effects in children.
Materials and Methods
After approval by the Ethics committee, written informed consent was obtained from the parents. Sixty children, aged between 2 to 10 yrs of American Society of Anesthesiologist physical status I or II, scheduled for short surgical procedures of 1 to 2 hrs duration, were included for this trial.
If the premedication was not completely ingested or retained, that child was excluded from further analysis. The children who had history of hypersensitivity reactions to benzodiazepine/butorphanol, central nervous system disorder or on sedative/analgesic drugs were also excluded from this trial. The children were randomly assigned to one of the study groups using a computer generated random number list.
Group I - children received midazolam 0.5 mg/kg orally mixed in sugar water.
Group II - children received butorphanol 0.2mg/Kg orally mixed in sugar water.
The medications were freshly prepared in identical syringes in sugar water to the total volume of 2ml and mixed thoroughly. Demographic data including age, sex, weight and the duration of surgery were recorded. Sedation and anxiolysis along with hemodynamic variables (HR and MAP) were assessed at baseline (before premedication) and at 5, 10, 15, and 20 minutes (separation of the child from his/her parents) after administration of premedication table1. Neither the patient nor the observer knew about the drug given in premedication. Twenty minutes after administration of the premedication, each child was separated from his or her parents and taken directly to the operating room. Child's score at venepuncture (25 minutes after premedication) was recorded and acceptability for the face mask was recorded at induction of anesthesia (30 minutes after premedication). All measurements of separation and anxiolysis in this study were completed by the same investigator to minimize interobserver variability. Anesthesia was induced with IV thiopentone sodium 5 mg/kg and atropine 10 - 20 μg/kg. IV succinylcholine 1.5 mg/kg was then administered to facilitate endotracheal intubation. The anesthesia was maintained with 60% N2O in oxygen with 0.5% halothane and vecuronium. The lungs were ventilated mechanically. Rescue analgesia in the form fentanyl 2μg/kg was given whenever there was 25% increase in heart rate or MAP from the baseline. At the conclusion of surgery, all anesthetic drugs were discontinued simultaneously and patients were reversed with neostigmine 0.05mg/kg and atropine 0.01mg/kg. The trachea was extubated when the child had resumed spontaneous ventilation and the gag reflex had returned. Pain was assessed in the recovery room using objective modified pain score[2] and analgesia in the form of paracetamol syrup 10 mg/kg was administered if the child had score ￡ 4.
Post anesthesia recovery (immediately and till the first 24 hours postoperatively, after completion of surgery) was assessed by the information obtained from the patient or attendant in terms of following parameters:
(a) Awakening time, (b) Jaw thrust required, (c) Nausea/ Vomiting. (d) Crying, (e) Psychomimetic behaviour (dysphoria, hallucination etc), (f) Involuntary movements, (g) Restlessness, (h) Nocturnal enuresis, (i) Complete amnesia and (j) Recollection - OT surrounding, Puncture/induction and Pain
The study was designed to detect a difference in the onset of sedation of at least 2 minutes and a minimum of 20% difference in the requirement of rescue analgesia among the groups to provide 95% power for two tail 't' test at the level of 5% significance. A minimum sample size of 20 patients was determined in each group. To allow increased variability in effect size, 30 children were included in each group.
Parametric data were reported as arithmetic means ± standard deviation and analyzed using student unpaired 't' test. For sedation and anxiolysis measurements, the proportion of children who were drowsy at each measurement period was compared with the proportion at baseline using Chi-square test. Nominal data (incidence of vomiting, restlessness, recollection etc) were analyzed using Fisher's exact test. Statistical significance, p<0.05, was accepted.
Results
Twelve of 72 children who were initially recruited for the trial refused to take their premedication. Sixty children were divided equally between the two groups. The groups were matched with respect to age, weight, sex distribution and ASA physical status table2. Baseline mean arterial pressure, heart rate and sedation and anxiolysis scores did not differ among the groups. In both the groups, none of the children were sedated to an extent that they could not be awakened during the study period. In addition, there were no episodes of apnoea or airway obstruction after midazolam or butorphanol administration.
Regarding the hemodynamic variables, no statistically significant difference was found from the baseline within the groups and among the groups at any time interval. As per time variables, statistically significant difference was found regarding onset of sedation and time of maximum sedation among the groups (p<0.05) i.e. in the butorphanol group, the onset and time of maximum sedation were less as compared to the midazolam group table2.
Sedation scores increased at the time of separation from parents (20 min) in both the groups, compared to baseline values. Sedation scores were comparable in both the groups at all time intervals except at the time of induction, i.e. sedation scores were higher in the butorphanol group as compared to the midazolam group (p<0.05) table3.
During the surgery, on the basis of 25% increase in heart rate or mean arterial pressure, 9 children (30%) in midazolam group supplemented with 2μg/Kg fentanyl, while only 3 children (10%) in the butorphanol group required rescue analgesia. This difference was found to be statistically significant (p < 0.05). After completion of the surgery in the first 24 hrs, 8 children (26.7%) in the midazolam group and 2 children (6.7%) in the butorphanol group required analgesia in the form of oral paracetamol syrup (10mg/Kg) (p <0.05)( table4. None of the children in both the groups required more than one dose of analgesic medication. Regarding the recovery profile, there was no significant difference among the groups i.e. jaw thrust required, nausea and vomiting, dysphoria or involuntary movements. Significant difference (p <0.05) was found among the groups in respect to postoperative crying i.e. 15 (50%) children in midazolam group were crying within 6 hours of completion of surgery compared to only 6 children (20%) in the butorphanol group table5.
Forty-two (70%) out of 60 postoperative behavioral questionnaires were completed because of the low literacy rate in the present set of patients and their parents. In respect to postoperative behavioural changes, both the groups were identical regarding restlessness/fear of dark, nightmares and nocturnal enuresis. Statistically significant difference was found among the groups regarding complete amnesia (50% in group I vs 80% in group II, p <0.05) and recollection (40% in group I vs 10% in group II, p<0.05). Five and two patients, respectively, in midazolam groups were able to recollect the venepuncture and pain while in the butorphanol group, 3 and 0 children, respectively were able to do so table5. Of the 42 questionnaires, 40 parents responded that their children were "adequately relaxed" at the time of separation. The parents of 7 children who had undergone previous surgeries without premedication believed that both oral premedication drugs had been of benefit to their children during their surgery.
Discussion
Preanesthetic medication in children are meant to relieve anxiety, reduce the trauma associated with separation from their parents, and facilitate induction of anesthesia without prolonging the recovery period. Although various combination of drugs and routes of administration[3] have been used in children for preanesthetic sedation, the oral route remains the least threatening method of drug administration.[4], [5]
Several studies have reported that preanesthetic sedative premedications facilitate separation of children from their parents and improve their behavior during induction of anesthesia.[1], [6] Analogous to a previous study[7], this investigation suggests that both oral midazolam and butorphanol are safe and effective preanesthetic medication. Variable efficacy of oral midazolam and butorphanol may be explained in part by the relatively narrow time frame during which conditions for induction of anesthesia are optimal ( i.e., 20-30 min after oral administration).
Midazolam, a water soluble benzodiazepine, possesses many desirable properties of a premedicant for children undergoing surgery, like rapid onset, short duration of action and minimal side effects. The route of administration, the short waiting time and half life, in combination with a level of sedation, are the principal advantages of orally administered midazolam.[7] It also does not delay the discharge of children undergoing general anesthesia.[8] The anterograde amnesia produced by midazolam[9] should help to reduce the psychological trauma of anesthesia and surgery. Butorphanol is a mixed agonist-antagonist with intrinsic activity at receptors of the μ opioid type (morphine like). It is also an agonist at Kappa opioid receptors. Its interactions with these receptors in the CNS apparently mediate most of its pharmacological effects, including analgesia and sedation. Butorphanol is useful as a preanesthetic medication and as a component of balanced anesthesia. The efficacy of butorphanol in this scenario helps in reducing the dosages of other anesthetic drugs used concomitantly. Peak analgesia with oral butorphanol is within 1 to 2 hrs. In the investigation, both after oral midazolam or butorphanol, children had anterograde amnesia and butorphanol was found to be superior in this regard. Oral midazolam has been compared with oral fentanyl for premedication in children and fentanyl was found to be as effective as midazolam in aiding compliance with anesthesia in children but fentanyl was significantly better in appeal to children and emergence characteristics.[10] In a recent trial it was found that low dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurance anesthesia.[6] The results of the present study indicate that midazolam or butorphanol premedication promotes smooth and satisfactory induction of anesthesia and reduces the psychological effects of hospitalization in children undergoing surgery. But oral butorphanol is better and superior to oral midazolam in respect to onset of sedation which is relatively faster, recovery characteristic i.e., post-operative crying or recollection and requirement of rescue analgesia.
No study has been conducted till date to evaluate the sedative-analgesic property of butorphanol as oral premedicant in pediatric patients. Oral butorphanol has been used for chronic pain[11] or cancer pain[12] in literature. It was found safe and no drug-related abnormalities with respect to blood pressure, body weight or laboratory data were evident.[11] Butorphanol with diazepam as sedative analgesic combination has been compared in oral surgery for outpatient sedation with fentanyl diazepam[13] or meperidine diazepam[14] combination and it was found superior for outpatient conscious sedation. Butorphanol as local anesthetic adjunct in oral surgery has been compared with midazolam and it was found better and superior because it has analgesic property along with sedation while midazolam has only sedation.[15] From the present study, we can also state that regarding sedative-analgesic properties butorphanol is superior to midazolam as significantly less number of children required rescue analgesia in the intraoperative/postoperative period after oral butorphanol premedication.
Conclusion
Lastly, we conclude that oral butorphanol is comparable to oral midazolam as premedication in children but analgesic property along with sedation is an additional advantage which makes it better than midazolam without a significant increase in side effects.
We recommend further trials to evaluate not only the premedicants for sedation in children but the sedative as well as analgesic aspect of the drugs to reduce the requirement of rescue analgesia perioperatively.
Acknowledgement
The authors are extremely grateful to Mr. A. P. Dhar Dwivedi, Department of Neurosurgery, SGPGIMS, Lucknow for secretarial assistance.
References
1. Kain ZN, Mayes L, Wang SM, Hofstandter MB, Bagnall A. Effect of premedication on postoperative behavioral outcomes in children. Anesthesiology 1997; 87: 3A.
2. Wolf AR, Hughes D, Wade A, Mather SJ, Prys-Roberts C. Postoperative analgesia after pediatric orchiopexy: evaluation of a bupivacaine morphine mixture. Br J Anesth 1990; 64: 430- 435.
3. Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: a comparison of four routes of administration. Pediatr Anaesth 2002; 12 (8): 685-689.
4. Tamura M, Nakamura K, Kitamura R, Kitagawa S, Mori N, Ueda Y. Oral premedication with fentanyl may be a safe and effective alternative to oral midazolam. Eur Anaesthesiol 2003; 20(6): 482-486.
5. McErlean M, Bartfield JM, Karunalar TA, Whitman MC, Turley DM. Midazolam syrup as premedication to reduce the discomfort associated with pediatric intravenous catheter insertion. J Pediatr 2003; 142 (4): 429-430.
6. Ko YP, Huang CJ, Hung YC, Su NY, Tsai PS, Chen C, Cheng CR. Premedication with low-does oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurance anesthesia. Acta Anaesthesiol Sin 2001; 39 (4): 169-177.
7. Erlandsson AL, Backman B, Stenstrom A, Stecksen-Blicks C> Conscious sedation by oral administration of midazolam in paediatric dental treatment. Swed Dent J 2001; 25 (3): 97-104.
8. Horgesheimer JJ, Pribble CG, Lugo RA. The effect of midazolam premedication on discharge time in pediatric patients undergoing general anesthesia for dental restorations. Pediatr Dent 2001; 23 (6): 491-494.
9. Payne KA, Coetzee AR, Mattheyse FJ. Midazolam and amnesia in pediatric premedication. Acta Anaesthesiologica Belgica 1991; 42: 101-105.
10. Howell TK, Smith S, Rushman SC, Walker RW, Radivan F: A comparison of oral transmucosal fentanyl and oral midazolam for premedication in children. Anesthesia 2002; 57 (8): 798-805.
11. Rangel-Guerra R: An open evaluation of oral butorphanol as long-term therapy in out-patients suffering from moderate to severe chronic pain. J Int Med Res 1981; 9 (2): 120-123.
12. De la Garza J. Oral butorphanol tartrate for the long-term treatment of out-patients with moderate to severe cancer pain. J Int Med Res 1981; 9 (2): 124-127.
13. Day OL 2nd, Nespeca JA, Ringgold C, Behr DA, Evens RP. Outpatient sedation for oral surgery: a comparision of butorphanol and fentanyl. Acute Care 1988; 12 (Suppl1): 63 -69.
14. Zallen RD, Cobetto GA, Bohmfalk C, Steffen K. Butorphanol/diazepam compared to meperidine/diazepam for sedation in oral maxillofacial surgery: a double-blind evaluation. Oral Surg Oral Med Oral Pathol 1987; 64 (4): 395-401.
15. Mekkey ME: Midazolam versus butorphanol as local anaesthetic adjuncts in oral surgery. A clinical assessment. Egypt Dent J 1987; 33 (4): 363-374.(Singh Vinita, Pathak Manu)
Abstract
Objective: To evaluate the efficacy of oral midazolam and oral butorphanol for their sedative analgesic effects in children. Methods: Sixty children, aged 2 to 10 yrs, of ASA physical status I and II, scheduled for surgical procedures of 1 to 2 hrs duration were randomized to one of the two groups. Group I: children received midazolam 0.5mg/kg orally and Group II: children received butorphanol 0.2mg/kg orally. Score of the children was assessed every 5 minutes till the induction of anesthesia. Intraoperative and postoperative analgesic requirement was recorded alongwith postoperative recovery and complications. Results: The groups were identical regarding the patient's characteristics, hemodynamic variables, duration of surgery and awakening time. Less time was required for the onset and time of maximum sedation in the butorphanol group (p<0.05). Sedation scores were similar among the groups at all time intervals, while the scores were higher in the butorphanol group at the time of induction (p<0.05). Less number of children required intraoperative and postoperative rescue analgesia in the butorphanol group (p<0.05). Statistically significant difference was found among the groups in respect to complete amnesia (50% in group I vs 80% I group II, p<0.05) and recollection (40% in group I vs 10% in group II, p<0.05). Conclusion : Oral butorphhanol is comparable to oral midazolam in children but analgesia alongwith sedation is an additional advantage which makes it better than midazolam without a significant increase in side effects.
Keywords: Oral premedication; Children; Midazolam; Butorphanol; Sedation; Analgesia
Fear of painful and unpleasant procedures, separation from parents, and unacceptability of face mask may produce the levels of anxiety that is troublesome in unpremedicated patients. Based on both behavioral and physiological responses, Kain et al[1] have indicated that induction of anesthesia appears to be most stressful procedure the child experiences during the perioperative period.
Numerous premedications have been advocated to facilitate the separation of children from their parents and to reduce the anxiety associated with the unfamiliar and intimidating environment of the operating theater. The fact that no single premedication has achieved universal acceptance suggests that each has its disadvantages. Therefore, we have conducted a prospective, randomized, double blind trial to compare the efficacy of oral midazalam and oral butorphanol for their sedative-analgesic effects in children.
Materials and Methods
After approval by the Ethics committee, written informed consent was obtained from the parents. Sixty children, aged between 2 to 10 yrs of American Society of Anesthesiologist physical status I or II, scheduled for short surgical procedures of 1 to 2 hrs duration, were included for this trial.
If the premedication was not completely ingested or retained, that child was excluded from further analysis. The children who had history of hypersensitivity reactions to benzodiazepine/butorphanol, central nervous system disorder or on sedative/analgesic drugs were also excluded from this trial. The children were randomly assigned to one of the study groups using a computer generated random number list.
Group I - children received midazolam 0.5 mg/kg orally mixed in sugar water.
Group II - children received butorphanol 0.2mg/Kg orally mixed in sugar water.
The medications were freshly prepared in identical syringes in sugar water to the total volume of 2ml and mixed thoroughly. Demographic data including age, sex, weight and the duration of surgery were recorded. Sedation and anxiolysis along with hemodynamic variables (HR and MAP) were assessed at baseline (before premedication) and at 5, 10, 15, and 20 minutes (separation of the child from his/her parents) after administration of premedication table1. Neither the patient nor the observer knew about the drug given in premedication. Twenty minutes after administration of the premedication, each child was separated from his or her parents and taken directly to the operating room. Child's score at venepuncture (25 minutes after premedication) was recorded and acceptability for the face mask was recorded at induction of anesthesia (30 minutes after premedication). All measurements of separation and anxiolysis in this study were completed by the same investigator to minimize interobserver variability. Anesthesia was induced with IV thiopentone sodium 5 mg/kg and atropine 10 - 20 μg/kg. IV succinylcholine 1.5 mg/kg was then administered to facilitate endotracheal intubation. The anesthesia was maintained with 60% N2O in oxygen with 0.5% halothane and vecuronium. The lungs were ventilated mechanically. Rescue analgesia in the form fentanyl 2μg/kg was given whenever there was 25% increase in heart rate or MAP from the baseline. At the conclusion of surgery, all anesthetic drugs were discontinued simultaneously and patients were reversed with neostigmine 0.05mg/kg and atropine 0.01mg/kg. The trachea was extubated when the child had resumed spontaneous ventilation and the gag reflex had returned. Pain was assessed in the recovery room using objective modified pain score[2] and analgesia in the form of paracetamol syrup 10 mg/kg was administered if the child had score ￡ 4.
Post anesthesia recovery (immediately and till the first 24 hours postoperatively, after completion of surgery) was assessed by the information obtained from the patient or attendant in terms of following parameters:
(a) Awakening time, (b) Jaw thrust required, (c) Nausea/ Vomiting. (d) Crying, (e) Psychomimetic behaviour (dysphoria, hallucination etc), (f) Involuntary movements, (g) Restlessness, (h) Nocturnal enuresis, (i) Complete amnesia and (j) Recollection - OT surrounding, Puncture/induction and Pain
The study was designed to detect a difference in the onset of sedation of at least 2 minutes and a minimum of 20% difference in the requirement of rescue analgesia among the groups to provide 95% power for two tail 't' test at the level of 5% significance. A minimum sample size of 20 patients was determined in each group. To allow increased variability in effect size, 30 children were included in each group.
Parametric data were reported as arithmetic means ± standard deviation and analyzed using student unpaired 't' test. For sedation and anxiolysis measurements, the proportion of children who were drowsy at each measurement period was compared with the proportion at baseline using Chi-square test. Nominal data (incidence of vomiting, restlessness, recollection etc) were analyzed using Fisher's exact test. Statistical significance, p<0.05, was accepted.
Results
Twelve of 72 children who were initially recruited for the trial refused to take their premedication. Sixty children were divided equally between the two groups. The groups were matched with respect to age, weight, sex distribution and ASA physical status table2. Baseline mean arterial pressure, heart rate and sedation and anxiolysis scores did not differ among the groups. In both the groups, none of the children were sedated to an extent that they could not be awakened during the study period. In addition, there were no episodes of apnoea or airway obstruction after midazolam or butorphanol administration.
Regarding the hemodynamic variables, no statistically significant difference was found from the baseline within the groups and among the groups at any time interval. As per time variables, statistically significant difference was found regarding onset of sedation and time of maximum sedation among the groups (p<0.05) i.e. in the butorphanol group, the onset and time of maximum sedation were less as compared to the midazolam group table2.
Sedation scores increased at the time of separation from parents (20 min) in both the groups, compared to baseline values. Sedation scores were comparable in both the groups at all time intervals except at the time of induction, i.e. sedation scores were higher in the butorphanol group as compared to the midazolam group (p<0.05) table3.
During the surgery, on the basis of 25% increase in heart rate or mean arterial pressure, 9 children (30%) in midazolam group supplemented with 2μg/Kg fentanyl, while only 3 children (10%) in the butorphanol group required rescue analgesia. This difference was found to be statistically significant (p < 0.05). After completion of the surgery in the first 24 hrs, 8 children (26.7%) in the midazolam group and 2 children (6.7%) in the butorphanol group required analgesia in the form of oral paracetamol syrup (10mg/Kg) (p <0.05)( table4. None of the children in both the groups required more than one dose of analgesic medication. Regarding the recovery profile, there was no significant difference among the groups i.e. jaw thrust required, nausea and vomiting, dysphoria or involuntary movements. Significant difference (p <0.05) was found among the groups in respect to postoperative crying i.e. 15 (50%) children in midazolam group were crying within 6 hours of completion of surgery compared to only 6 children (20%) in the butorphanol group table5.
Forty-two (70%) out of 60 postoperative behavioral questionnaires were completed because of the low literacy rate in the present set of patients and their parents. In respect to postoperative behavioural changes, both the groups were identical regarding restlessness/fear of dark, nightmares and nocturnal enuresis. Statistically significant difference was found among the groups regarding complete amnesia (50% in group I vs 80% in group II, p <0.05) and recollection (40% in group I vs 10% in group II, p<0.05). Five and two patients, respectively, in midazolam groups were able to recollect the venepuncture and pain while in the butorphanol group, 3 and 0 children, respectively were able to do so table5. Of the 42 questionnaires, 40 parents responded that their children were "adequately relaxed" at the time of separation. The parents of 7 children who had undergone previous surgeries without premedication believed that both oral premedication drugs had been of benefit to their children during their surgery.
Discussion
Preanesthetic medication in children are meant to relieve anxiety, reduce the trauma associated with separation from their parents, and facilitate induction of anesthesia without prolonging the recovery period. Although various combination of drugs and routes of administration[3] have been used in children for preanesthetic sedation, the oral route remains the least threatening method of drug administration.[4], [5]
Several studies have reported that preanesthetic sedative premedications facilitate separation of children from their parents and improve their behavior during induction of anesthesia.[1], [6] Analogous to a previous study[7], this investigation suggests that both oral midazolam and butorphanol are safe and effective preanesthetic medication. Variable efficacy of oral midazolam and butorphanol may be explained in part by the relatively narrow time frame during which conditions for induction of anesthesia are optimal ( i.e., 20-30 min after oral administration).
Midazolam, a water soluble benzodiazepine, possesses many desirable properties of a premedicant for children undergoing surgery, like rapid onset, short duration of action and minimal side effects. The route of administration, the short waiting time and half life, in combination with a level of sedation, are the principal advantages of orally administered midazolam.[7] It also does not delay the discharge of children undergoing general anesthesia.[8] The anterograde amnesia produced by midazolam[9] should help to reduce the psychological trauma of anesthesia and surgery. Butorphanol is a mixed agonist-antagonist with intrinsic activity at receptors of the μ opioid type (morphine like). It is also an agonist at Kappa opioid receptors. Its interactions with these receptors in the CNS apparently mediate most of its pharmacological effects, including analgesia and sedation. Butorphanol is useful as a preanesthetic medication and as a component of balanced anesthesia. The efficacy of butorphanol in this scenario helps in reducing the dosages of other anesthetic drugs used concomitantly. Peak analgesia with oral butorphanol is within 1 to 2 hrs. In the investigation, both after oral midazolam or butorphanol, children had anterograde amnesia and butorphanol was found to be superior in this regard. Oral midazolam has been compared with oral fentanyl for premedication in children and fentanyl was found to be as effective as midazolam in aiding compliance with anesthesia in children but fentanyl was significantly better in appeal to children and emergence characteristics.[10] In a recent trial it was found that low dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurance anesthesia.[6] The results of the present study indicate that midazolam or butorphanol premedication promotes smooth and satisfactory induction of anesthesia and reduces the psychological effects of hospitalization in children undergoing surgery. But oral butorphanol is better and superior to oral midazolam in respect to onset of sedation which is relatively faster, recovery characteristic i.e., post-operative crying or recollection and requirement of rescue analgesia.
No study has been conducted till date to evaluate the sedative-analgesic property of butorphanol as oral premedicant in pediatric patients. Oral butorphanol has been used for chronic pain[11] or cancer pain[12] in literature. It was found safe and no drug-related abnormalities with respect to blood pressure, body weight or laboratory data were evident.[11] Butorphanol with diazepam as sedative analgesic combination has been compared in oral surgery for outpatient sedation with fentanyl diazepam[13] or meperidine diazepam[14] combination and it was found superior for outpatient conscious sedation. Butorphanol as local anesthetic adjunct in oral surgery has been compared with midazolam and it was found better and superior because it has analgesic property along with sedation while midazolam has only sedation.[15] From the present study, we can also state that regarding sedative-analgesic properties butorphanol is superior to midazolam as significantly less number of children required rescue analgesia in the intraoperative/postoperative period after oral butorphanol premedication.
Conclusion
Lastly, we conclude that oral butorphanol is comparable to oral midazolam as premedication in children but analgesic property along with sedation is an additional advantage which makes it better than midazolam without a significant increase in side effects.
We recommend further trials to evaluate not only the premedicants for sedation in children but the sedative as well as analgesic aspect of the drugs to reduce the requirement of rescue analgesia perioperatively.
Acknowledgement
The authors are extremely grateful to Mr. A. P. Dhar Dwivedi, Department of Neurosurgery, SGPGIMS, Lucknow for secretarial assistance.
References
1. Kain ZN, Mayes L, Wang SM, Hofstandter MB, Bagnall A. Effect of premedication on postoperative behavioral outcomes in children. Anesthesiology 1997; 87: 3A.
2. Wolf AR, Hughes D, Wade A, Mather SJ, Prys-Roberts C. Postoperative analgesia after pediatric orchiopexy: evaluation of a bupivacaine morphine mixture. Br J Anesth 1990; 64: 430- 435.
3. Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: a comparison of four routes of administration. Pediatr Anaesth 2002; 12 (8): 685-689.
4. Tamura M, Nakamura K, Kitamura R, Kitagawa S, Mori N, Ueda Y. Oral premedication with fentanyl may be a safe and effective alternative to oral midazolam. Eur Anaesthesiol 2003; 20(6): 482-486.
5. McErlean M, Bartfield JM, Karunalar TA, Whitman MC, Turley DM. Midazolam syrup as premedication to reduce the discomfort associated with pediatric intravenous catheter insertion. J Pediatr 2003; 142 (4): 429-430.
6. Ko YP, Huang CJ, Hung YC, Su NY, Tsai PS, Chen C, Cheng CR. Premedication with low-does oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurance anesthesia. Acta Anaesthesiol Sin 2001; 39 (4): 169-177.
7. Erlandsson AL, Backman B, Stenstrom A, Stecksen-Blicks C> Conscious sedation by oral administration of midazolam in paediatric dental treatment. Swed Dent J 2001; 25 (3): 97-104.
8. Horgesheimer JJ, Pribble CG, Lugo RA. The effect of midazolam premedication on discharge time in pediatric patients undergoing general anesthesia for dental restorations. Pediatr Dent 2001; 23 (6): 491-494.
9. Payne KA, Coetzee AR, Mattheyse FJ. Midazolam and amnesia in pediatric premedication. Acta Anaesthesiologica Belgica 1991; 42: 101-105.
10. Howell TK, Smith S, Rushman SC, Walker RW, Radivan F: A comparison of oral transmucosal fentanyl and oral midazolam for premedication in children. Anesthesia 2002; 57 (8): 798-805.
11. Rangel-Guerra R: An open evaluation of oral butorphanol as long-term therapy in out-patients suffering from moderate to severe chronic pain. J Int Med Res 1981; 9 (2): 120-123.
12. De la Garza J. Oral butorphanol tartrate for the long-term treatment of out-patients with moderate to severe cancer pain. J Int Med Res 1981; 9 (2): 124-127.
13. Day OL 2nd, Nespeca JA, Ringgold C, Behr DA, Evens RP. Outpatient sedation for oral surgery: a comparision of butorphanol and fentanyl. Acute Care 1988; 12 (Suppl1): 63 -69.
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