Oral midazolam compared with diazepam-droperidol and trimeprazine as premedicants in children

Ninety children were assigned randomly to one of three groups for premedication with oral midazolam 0.5 mg·kg⁻¹, diazepam 0.25 mg·kg⁻¹ with droperidol 0.25 mg·kg⁻¹, or trimeprazine 2 mg·kg⁻¹. On arrival at the anaesthetic room, anxiolysis was satisfactory in 26 out of 29 (90%) children who received midazolam compared with 23 out of 29 (79%) who received diazepam-droperidol and 18 out of 29 (62%) who received trimeprazine ( P <0.05); at induction of anaesthesia these proportions were 24 out of 29 (83%), 16 out of 29 (55%) and 11 out of 29 (40%) respectively ( P <0.001). When individual groups were compared, anxiolysis was significantly greater in the midazolam group compared with the trimeprazine group on arrival in the anaesthetic room ( P <0.05) and significantly greater in the midazolam group than in either the diazepam-droperidol or the trimeprazine groups at induction of anaesthesia ( P <0.05 and P <0.001 respectively). There were no significant differences in times to early recovery between the groups (25.4, 24.4 and 28.5 min). Analysis of behavioural questionnaires completed two weeks after hospitalization showed a trend towards fewer postoperative behavioural disturbances in children who received midazolam or diazepam-droperidol compared with trimeprazine (47 and 44% vs 75%); when the results for the benzodiazepine-containing premedicants were combined, the difference between these groups and trimeprazine was statistically significant ( P <0.05).     

Rectal midazolam as premedicant in children: a dose response study

Rectally administered midazolam has proved to be a reliable and acceptable way of premedicating children. In order to determine the optimal dose 80 children were randomized in a double-blind manner to receive one of four different dosages of midazolam (0.2–0.3–0.4–0.5 mg·kg⁻¹) in combination with atropine 0.02 mg·kg⁻¹ rectally. Observations before and after premedication showed no clinically relevant differences in ventilatory and cardiovascular parameters. Neither did the groups differ as regards acceptance of the mask or awakening from anaesthesia. Regardless of group the level of sedation was increased, but only children receiving 0.4 or 0.5 mg·kg⁻¹ of midazolam showed an increase in the level of anxiolysis. For this reason a low dose of midazolam (0.2 mg·kg⁻¹) can be used, except in cases where pronounced anxiolysis is required.     

Comparison between three transmucosal routes of administration of midazolam in children

Midazolam was applied transmucosally in 47 children randomly assigned to three different groups. Group N received 0.2 mg·kg⁻¹ nasally, group R 0.5 mg·kg⁻¹ rectally, and group S 0.2 mg·kg⁻¹ sublingually. All groups were treated 60 min prior to a planned i.v. puncture with EMLA^®. Reliable and valid psychological parameters (such as emotional situation, shivering, awareness, respiratory rate and facial colour) were scored after premedication and before and after i.v. puncture, 20 min after premedication and until induction. A blood sample was drawn 10, 30 and 60 min after premedication and the levels of midazolam, alpha-hydroxy-midazolam, ACTH, glucose and cortisol were measured. In all three groups the plasma levels of midazolam 10 min after premedication were higher than 70 ng·ml⁻¹ (accepted as a sedative level). 30 min after premedication the midazolam level in the sublingual group was statistically significantly higher than in the nasal group and the psychological parameters in all three groups were significantly changed (10 min after premedication). The psychological parameters were not significantly different between the three groups over the whole study. Sublingual premedication has some advantages (most readily accepted, highest plasma levels and lowest deviations) and could be the first choice in premedication of children. All three transmucosal applications are safe and well accepted, although nasal application was rejected by two of the children.     

Oral transmucosal ketamine: an effective premedication in children

The oral cavity offers a simple, painless way of drug administration. For this reason, we used oral transmucosal ketamine (5–6 mg·kg⁻¹) for premedication in 15 children and compared it with intranasal ketamine (5–6 mg·kg⁻¹), placebo and intramuscular ketamine (5–6 mg·kg⁻¹). Oral transmucosal ketamine (OTK) provided effective sedation, facilitated i.v. line insertion and was accepted with pleasure by the patients (as lollipops). The lollipops produced a slight increase in gastric volumes but did not affect gastric pH. In conclusion OTK has been shown to be an effective, harmless preoperative medication in paediatric patients.     

Midazolam following open heart surgery in children: haemodynamic effects of a loading dose

Our objective was to establish the safety and effectiveness of a loading dose of midazolam for postoperative sedation of children recovering from open heart surgery; a prospective randomized placebo-controlled double-blind study was done with subjects randomized to three groups according to loading dose. I=0.08 mg·kg⁻¹; II=0.04 mg·kg⁻¹; and III=0.00 mg·kg⁻¹ (placebo). An open label continuous midazolam infusion protocol followed. Haemodynamic parameters were monitored. The study was discontinued following an adverse event involving the 23rd subject. When data for all 23 subjects were combined, there was a mean decrease of 10% in blood pressure (BP) 30 min after the loading dose ( P <0.001). Heart rate change was less significant. Clinicians identified four hypotensive episodes as temporally associated with the midazolam load, two each in Groups I (0.08 mg·kg⁻¹) and III (placebo). One subject in Group I (the 23rd) became hypotensive within five min of receiving the loading dose, had a difficult clinical course and died four weeks postoperatively. We cannot conclude that the loading dose of midazolam had any systematic haemodynamic effect in our study population. Although the clinical course of the 23rd subject suggests a subset of more susceptible children (those who receive opioid analgesia with midazolam, are volume-restricted, and/or undergo more complex forms of surgical correction), many critical care patients are inherently physiologically unstable, and concluding clinically that blood pressure fluctuation is drug related may be erroneous.     

Intranasal flumazenil and naloxone to reverse over-sedation in a child undergoing dental restorations

We describe a 3-year-old child who became over-sedated after receiving intranasal (IN) midazolam (0.53 mg·kg⁻¹) and IN sufentanil (1 mcg·kg⁻¹) for dental restorations in the dental office. Desaturation was attributed to laryngospasm, which was managed with positive pressure ventilation and oxygen. The sedation was reversed with a combination of IN flumazenil and naloxone.     

Does thiopentone delay recovery in children premedicated with midazolam?

This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30–60 min duration received midazolam 0.5 mg·kg⁻¹ with atropine 0.03 mg·kg⁻¹ and were randomized to either halothane (Group 1, n =50) or a thiopentone induction (Group 2, n =50) technique, followed by a standardized anaesthetic-protocol. Time to extubation was significantly greater in the thiopentone group (8.8±4 min vs 7.1±3 min, P <0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9±1.5, 3.3±1.7, respectively P <0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.     

Premedication in children: a comparison of oral midazolam and oral clonidine

BACKGROUND: Oral premedication is widely used in pediatric anesthesia to reduce preoperative anxiety and ensure smooth induction. Midazolam is currently the most commonly used premedicant, but good results have also been reported with clonidine. The aim of the present study was to compare clinical effects of oral midazolam and oral clonidine. METHODS: We performed a prospective open study in 64 children who were randomly assigned to receive either oral midazolam 0.5 mg.kg (-1) (group M) or oral clonidine 4 microg.kg (-1) (group C) prior to mask induction. Drug acceptance, preoperative sedation and anxiolysis, quality of mask acceptance, recovery profile and parental satisfaction were evaluated. RESULTS: The taste of oral clonidine was judged as significantly better; 14% of children rejected oral midazolam. Onset of sedation was significantly faster after premedication with midazolam (30+/-13.1 min) than with clonidine (38.5+/-14.6 min), but level of sedation was significantly better after premedication with clonidine. Quality of mask induction was equally successful in both groups. A steal-induction was performed in 66% of patients of group C, but none in group M. We observed a trend towards an increased incidence of emergence agitation after premedication with midazolam. Parental satisfaction was significantly higher in group C. CONCLUSIONS: In this study, premedication with oral clonidine appeared to be superior to oral midazolam. Quality of mask acceptance was comparable between groups, but oral clonidine was better accepted by the child, produced more effective preoperative sedation, showed a trend towards better recovery from anesthesia and had a higher degree of parental satisfaction.     

Comparison of sevoflurane and ketamine for anesthetic induction in children with congenital heart disease

Background:  Sevoflurane is widely used in pediatric anesthesia for induction. Ketamine has been preferred in pediatric cardiovascular anesthesia. Aim of this study was to compare the hemodynamic effects and the speed of ketamine and sevoflurane for anesthesia induction in children with congenital heart disease.
Materials and methods:  Children with congenital heart disease undergoing corrective surgery were included in the study. After oral premedication with midazolam (0.5 mg·kg⁻¹), anesthesia induction was started with 5 mg·kg⁻¹ intramuscular ketamine (group K). In the second group, induction was achieved with sevoflurane (group S); the first concentration was 3% and increased after every three breaths. Intravenous access time and intubation times were enrolled for each child. Hemodynamic data and oxygen saturation were recorded every 2 min and any event during induction period was also noted.
Results:  Forty-seven children were included in the study; 23 in group K and 24 in group S. Heart rates and oxygen saturation values were similar between groups during the study. No difference was found between intravenous access time and intubation times. However, blood pressure levels were significantly lower in group S after recording baseline values till the intubation time (at 4, 6, and 8 min). Respiratory complications observed during the study were mild and were less frequent in group K than in group S (4 vs 13).
Conclusion:  Ketamine appears a good alternative for induction in patients with congenital heart disease. It permits preservation of hemodynamic stability with minimal side effects.     

The optimum concentration of levobupivacaine for intra-operative caudal analgesia in children undergoing inguinal hernia repair at equal volumes of injectate

Probit analysis was used to predict the median effective concentration (EC₅₀) and the 95% effective concentration (EC₉₅) values of levobupivacaine for caudal analgesia in children at equal volumes of injectate. Sixty children scheduled for inguinal herniorrhaphy were recruited. Anaesthesia was induced with sevofurane and nitrous oxide. Then caudal block (total volume of local anaesthetic 1 ml.kg⁻¹) was performed. Patients randomly received one of six concentrations (0.08%, 0.10%, 0.12%, 0.14%, 0.16% or 0.18%) of levobupivacaine. Thereafter, inhalational anaesthetics were discontinued and intravenous midazolam 0.1 mg.kg⁻¹ was administered to maintain sedation. The effective caudal analgesia was defined as an absence of gross movements and a haemodynamic (heart rate or blood pressure) reaction < 20% compared with baseline in response to surgical incision. Our data indicated that the EC₅₀ and EC₉₅ values of levobupivacaine for caudal analgesia were 0.109% (95% confidence intervals 0.098–0.120%) and 0.151% (95% confidence intervals 0.135–0.193%) when using the same volume (1 ml.kg⁻¹), respectively.     

Intranasal ketamine preinduction of paediatric outpatients

A double-blinded, placebo-controlled study compared the outcomes of intranasal ketamine premedication with placebo in outpatients. Forty paediatric outpatients were assigned randomly in a prospective fashion to one of two separate study groups of equal size (20 patients per group). A placebo group received 2 ml of intranasal saline, 1 ml per naris. The study group received intranasal ketamine, 3 mg·kg⁻¹, diluted to 2 ml with saline, 1 ml per naris. Using a cooperation index, a play therapist scored resistance to nasal instillation, separation of the child from parents at ten min, and acceptance of anaesthesia monitors and face mask at 15 min. Differences in age, weight, episodes of vomiting, recovery and discharge times among the two groups were not significant. Intranasal ketamine, 3 mg·kg⁻¹, was asssociated with a significantly better ( P =0.013) cooperation index than intranasal placebo. Intranasal ketamine, permitted pleasant and rapid separation of children from their parents, cooperative acceptance of monitoring and of mask inhalation induction, and did not cause prolonged postanaesthetic recovery or delayed discharge home.     

The perioperative effects of oral premedication in children

The pre- and postoperative effects of oral diazepam (0.5 mg/kg), trimeprazine (4 mg/kg), pentobarbitone (3 mg/kg) and a placebo were compared in a randomized double-blind clinical trial in 149 children, aged one to ten years, undergoing adenotonsillectomy. The anaesthetic was standardised and each patient received intraoperative intramuscular papaveretum (0.3 mg/kg). Preoperative sedation was assessed in the ward before transfer onto the theatre trolley, on leaving the ward, on arrival on the theatre floor, on arrival in the induction room and on induction of anaesthesia. There was no significant difference in sedation between the four drug groups except for the placebo group which had a significantly greater unsatisfactory rating at the stage of induction of anaesthesia (P = 0.001). There were no differences in waking times between the diazepam, pentobarbitone and placebo groups, but the trimeprazine group's waking times were significantly prolonged (P less than 0.001). However, the trimeprazine group exhibited significantly less distress in the recovery unit (P = 0.02) and had half the incidence of vomiting (P less than 0.001) than did the other premedication groups.     

Efficacy of ondansetron and metoclopramide for preventing postoperative emesis following strabismus surgery in children

A double-blind, randomised, placebo-controlled trial was conducted to compare the efficacy of metoclopramide with the 5-HT₃ antagonist, ondansetron, for the prevention of postoperative emesis in children undergoing elective strabismus surgery. None of the children received any premedication and a similar anaesthetic technique was used for all. Ondansetron 0.15 mg.kg⁻¹, metoclopramide 0.25 mg.kg⁻¹ or saline placebo were administered following intravenous catheter placement. Episodes of emesis were recorded for the first 24 h for the intervals of 0–2, 2–6 and 6–24 h. The incidence of emesis in the first 24 h was observed to be 71.7% in the placebo group, 34.4% in the ondansetron group (p < 0.001) and 61.4% in the metoclopramide group (p = NS). The severity of vomiting was less in the ondansetron group as compared with metoclopramide (p < 0.01) and placebo (p < 0.001). Recovery room scores were comparable in all the groups. No serious side-effects were observed in the ondansetron group. We conclude that prophylactic ondansetron is effective and superior to metoclopramide in the prevention of postoperative emesis in children following elective strabismus surgery.     

Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy

Previous studies have shown over 70% of children require analgesics following bilateral myringotomy and tube placement (BM&T). This double-blind, placebo-controlled study compared the postoperative analgesic effects of preoperatively administered oral acetaminophen or ibuprofen. Forty three ASA I or II children age six months or older scheduled for elective BM&T were randomized to receive acetaminophen (paracetamol) 15 mg·kg⁻¹, ibuprofen 10 mg·kg⁻¹, or placebo. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) upon arrival to the PACU and at 5, 10, 15, 30, 45, and 60 min. CHEOP scores did not differ between the groups at any time. There was no difference in the number of children receiving rescue analgesia. This study showed no benefit of preoperatively administered oral ibuprofen 10 mg·kg⁻¹ or acetaminophen 15 mg·kg⁻¹ over placebo for the relief of postoperative pain in children undergoing BM&T.     

The effect of clonidine on sevoflurane requirements for anaesthesia and hypnosis

We evaluated the effects of clonidine given orally on sevoflurane requirements for anaesthesia and hypnosis. Patients received either clonidine (5 μg.kg⁻¹) by mouth ( n  =21) 90 min before surgery or no premedication ( n  =21) by random allocation. MAC was calculated using repeated tetanic nerve stimulation with end-tidal sevoflurane concentration increased or decreased by 0.3 vol.% depending on the previous response. MAC awake was calculated according to the response to verbal command. The mean (SD) MAC in the clonidine-treated patients was 1.53 (0.20)% compared with 1.83 (0.15)% in the control group (p <0.001). Similarly, MAC awake was reduced in the clonidine group (0.50 (0.08)% compared with 0.60 (0.07)% in the control group) (p <0.001). We conclude that clonidine 5 μg.kg⁻¹ orally administered pre-operatively reduces sevoflurane requirements for anaesthesia and hypnosis.     

Oral ketamine premedication for paediatric cardiac surgery--a comparison with intramuscular morphine (both after oral trimeprazine)

In a single-blind controlled study, forty children with congenital heart disease were premedicated with oral trimeprazine 3 mg/kg and either intramuscular morphine 0.1 mg/kg or oral ketamine 10 mg/kg. Cardiovascular and respiratory effects of premedication and degree of sedation induced were similar in the two groups of patients. Oral ketamine is a safe and effective premedicant in this group of patients.     

A comparison of propofol and other sedative use in paediatric intensive care in the United Kingdom

The retrospective study was designed to examine the safety of propofol against other sedative agents when used by infusion for the sedation of children requiring mechanical ventilation. One-hundred-and-ninety-eight patients were recruited. One-hundred-and-six received propofol and 92 received other sedative agents for durations of 30 min to 156 days and 13 min to 11 days respectively. The mean infusion rate of propofol was 3.39 mg·kg⁻¹·h⁻¹. Sixty-one of the 92 patients in the nonpropofol group received midazolam at a mean infusion rate of 0.4 mg·kg⁻¹·h⁻¹. Forty-one patients developed clinical metabolic acidosis with five falling into the pathological range as defined. Seventeen received propofol and 24 another sedative agent. Seventy-eight percent of patients that became acidotic were under the age of three. No patient who became acidotic was noted to have lipaemic serum. Three of four patients were recorded as having lipaemic serum received propofol, however two of these patients along with the patient that received midazolam also received Intralipid. Overall mortality was similar in both sedation groups with 27 deaths being recorded. Thirteen patients received propofol. Five nonfatal adverse events occurred, three in patients that had received propofol. The findings of the survey suggest that propofol compares favourably with other sedative agents when used for sedating children in a paediatric intensive care unit.     

Injectable midazolam as oral premedicant in pediatric neurosurgery

In a randomized, double blind, placebo controlled study; the acceptability, efficacy and safety of injectable midazolam as oral premedicant in children was evaluated. One hundred children (ASA 1,2) aged 6 months to 6 years, undergoing elective neurosurgical operations, like meningomyelocele, meningo-encephalocele, ventriculo peritoneal and other shunts and craniotomies for tumour decompression etc., were included in the study. The patients were randomly assigned to one of four groups (A, B, C, D) receiving respectively saline or 0.50, 0.75 and 1.0 mg/kg midazolam in honey, 45 min before separation from parents. All received identical general anesthesia (GA). Age, sex, weight, heart rate, blood pressure, respiratory rate, saturation (SaO2), reaction to parent's separation, sedation score and duration of anesthesia, recovery conditions and side effects were noted.We found no difference in age, sex, weight, patient acceptability vomiting after ingestion and duration of anesthesia between groups. Even though many children resisted the placement of premedicant in the mouth, only three children spat it out and none vomited after swallowing. The reaction to separation from parents was better after midazolam premedication. However, on reaching the operating room, 24% children (placebo-60%) were found anxious after 0.50 mg/kg, but 12% were deeply sedated after a dose of 1.0 mg/kg. Recovery was similar in groups A, B and C except that more (48%) patients were anxious in group A. Recovery, however was delayed in 16% patients of group D. Though, fewer complications were reported during recovery after midazolam than placebo premedication, they were minimal in the 0.75 mg/kg group.We concluded that giving injectable midazolam orally as premedication in pediatric age group scheduled for neurosurgical operations is acceptable, effective and safe in 0.75 mg/kg dose. While 0.50 mg/kg is less effective, 1.0 mg/kg does not offer any additional benefit over 0.75 mg/kg but does delay recovery and may compromise safety.     

A comparison of oral midazolam solution with temazepam as a day case premedicant.

Seventy-five women undergoing elective day case gynaecological surgery were randomised into one of three groups to receive an oral formulation of midazolam IV solution 10 mg, temazepam 20 mg or placebo for premedication. The two treatment groups showed a significant reduction in anxiety score compared with placebo (P less than 0.002 and P less than 0.04 for placebo compared with temazepam and midazolam respectively). Similarly the treatment groups showed a significantly greater sedation score compared with placebo. Recovery as assessed by letter deletion and memory tests was no worse for the treatment groups than for placebo. Patient acceptance of the two treatment groups was significantly greater than that of placebo. There was no significant difference between treatment groups with respect to anxiolysis, sedation or recovery. As a day case premedicant, midazolam IV solution 10 mg orally was found to be as effective as temazepam 20 mg and superior to placebo, in terms of anxiolysis and sedation, but did not offer any clinical advantage over temazepam in this setting.     

Pre-operative forced-air warming as a method of anxiolysis

We tested the hypothesis that pre-operative forced-air warming is as effective for anxiolysis as intravenous midazolam, using a blinded, placebo controlled factorial design. One hundred and twenty patients were randomly assigned to cotton blanket and saline injection ( n  =   30), forced-air warmer and saline injection ( n  =   30), midazolam 30 μg.kg⁻¹ and cotton blanket ( n  =   30), and forced-air warmer and midazolam 30 μg.kg⁻¹ ( n  =   30). Patients completed visual analogue scales for anxiety and thermal comfort, and the State-Trait Anxiety Inventory, at baseline and after 20 min. The estimated effect of midazolam on visual analogue scores for anxiety was −10 (95% CI −3 to −18; p = 0.007) and on state anxiety was −5 (95% CI −7 to −4; p = 0.03). Warming had no influence on visual analogue scores for anxiety (p = 0.50) or state anxiety (p = 0.33), but its estimated effect on thermal comfort was +23 (95% CI 19–27; p < 0.0001). There was no interaction between midazolam and warming. Pre-operative warming was not equivalent to midazolam for anxiolysis and cannot be recommended solely for this purpose.