Reevaluation of rectal ketamine premedication in children: comparison with rectal midazolam

BACKGROUND: Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines. Therefore, the authors reevaluated the efficacy of rectally administered ketamine in comparison with 1 mg/kg rectal midazolam. METHODS: Sixty-six infants and children (age, 7-61 months) who were American Society of Anesthesiologists physical status I and who were undergoing minor surgeries as in-patients were randomized to receive 5 mg/kg ketamine (n = 16), 7 mg/kg ketamine (n = 16), 10 mg/kg ketamine (n = 17), or 1 mg/kg midazolam (n = 17) via rectum. A blinded observer scored sedation 45 min and 15 min after administration of ketamine and midazolam, respectively, when children were separated from parent(s) for inhalational induction. All children underwent standardized general anesthesia with sevoflurane, nitrous oxide, and oxygen with endotracheal intubation. Blood pressure, heart rate, and oxyhemoglobin saturation were determined before, during, and after anesthesia. Postoperative recovery characteristics and incidence of adverse reactions were also assessed. RESULTS: Most children (88%) who received rectally 10 mg/kg ketamine or 1 mg/kg midazolam separated easily from their parents compared with those (31%) who received 7 or 5 mg/kg rectal ketamine (P < 0.05). Similarly, more children who received 10 mg/kg ketamine or 1 mg/kg midazolam underwent mask induction without struggling or crying compared with those who received 7 or 5 mg/kg ketamine (P < 0.05). There were no clinically significant changes in blood pressure, heart rate, and oxyhemoglobin saturation after administration of either drug. Immediately after surgery, more children receiving midazolam or 5 mg/kg ketamine were agitated compared with 7 or 10 mg/kg ketamine. Ketamine, 7 and 10 mg/kg, provided postoperative analgesia, but the largest dose of ketamine was associated with delayed emergence from general anesthesia. CONCLUSIONS: The results indicate that rectally administered ketamine alone produces dose-dependent sedative effects in children, when evaluated at its predicted peak plasma concentration. Ketamine, 10 mg/kg, has a delayed onset but is as effective as 1 mg/kg midazolam for sedating healthy children before general anesthesia. However, 10 mg/kg rectal ketamine is not recommended for brief surgeries because of prolonged postoperative sedation.     

Reevaluation of Rectal Ketamine Premedication in Children: Comparison with Rectal Midazolam

Background: Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines. Therefore, the authors reevaluated the efficacy of rectally administered ketamine in comparison with 1 mg/kg rectal midazolam.

Methods: Sixty-six infants and children (age, 7-61 months) who were American Society of Anesthesiologists physical status I and who were undergoing minor surgeries as in-patients were randomized to receive 5 mg/kg ketamine (n = 16), 7 mg/kg ketamine (n = 16), 10 mg/kg ketamine (n = 17), or 1 mg/kg midazolam (n = 17) via rectum. A blinded observer scored sedation 45 min and 15 min after administration of ketamine and midazolam, respectively, when children were separated from parent(s) for inhalational induction. All children underwent standardized general anesthesia with sevoflurane, nitrous oxide, and oxygen with endotracheal intubation. Blood pressure, heart rate, and oxyhemoglobin saturation were determined before, during, and after anesthesia. Postoperative recovery characteristics and incidence of adverse reactions were also assessed.

Results: Most children (88%) who received rectally 10 mg/kg ketamine or 1 mg/kg midazolam separated easily from their parents compared with those (31%) who received 7 or 5 mg/kg rectal ketamine (P < 0.05). Similarly, more children who received 10 mg/kg ketamine or 1 mg/kg midazolam underwent mask induction without struggling or crying compared with those who received 7 or 5 mg/kg ketamine (P < 0.05). There were no clinically significant changes in blood pressure, heart rate, and oxyhemoglobin saturation after administration of either drug. Immediately after surgery, more children receiving midazolam or 5 mg/kg ketamine were agitated compared with 7 or 10 mg/kg ketamine. Ketamine, 7 and 10 mg/kg, provided postoperative analgesia, but the largest dose of ketamine was associated with delayed emergence from general anesthesia.     

S(+)-ketamine for rectal premedication in children

Our purpose for this prospective, randomized, and double-blinded study was to evaluate the anesthetic efficacy of S(+)-ketamine, an enantiomer of racemic ketamine, compared with a combination of S(+)-ketamine and midazolam, and plain midazolam for rectal premedication in pediatric anesthesia. Sixty-two children, ASA physical status I and II, scheduled for minor surgery, were randomly assigned to be given rectally one of the following: 1.5 mg/kg preservative-free S(+)-ketamine, a combination of 0.75 mg/kg preservative-free S(+)-ketamine and 0.75 mg/kg midazolam, or 0.75 mg/kg midazolam. Preoperative anesthetic efficacy was graded during a period of 20 min by using a five-point scale from 1 = awake to 5 = asleep. Tolerance during anesthesia induction via face mask was graded by using a four-point scale from 1 = very good to 4 = bad. A sufficient anesthetic level (> or = 3) after rectal premedication was reached in 86% in midazolam/S(+)-ketamine premedicated children, in 75% in midazolam premedicated children, but only in 30% in S(+)-ketamine premedicated children (P < 0.05 S(+)-ketamine versus midazolam/S(+)-ketamine and midazolam groups). The incidence of side effects after rectal premedication was rare. Whereas the mask acceptance score was comparable in the three study groups, a 25% rate of complications during anesthesia induction via face was observed in the S(+)-ketamine study group (P < 0.05 versus other study groups). Our conclusions are that S(+)-ketamine for rectal premedication in the dose we chose shows a poor anesthetic effect and a frequent incidence of side effects during induction of anesthesia via face mask compared with the combination of midazolam/S(+)-ketamine and plain midazolam. Dose-response studies of S(+)-ketamine for rectal premedication in pediatric anesthesia may be warranted.     

Oral midazolam in children: effect of time and adjunctive therapy.

The purpose of this study was to determine the influence of timing and concomitant administration of atropine and/or meperidine on the perioperative effects of oral midazolam in children. In 154 healthy children, 1-8 yr old, we studied six oral preanesthetic medication regimens according to a randomized, double-blind protocol. Group A (placebo) received 5 mL of apple juice. The other five groups received medication with apple juice to a total volume of 5 mL, 20-60 min before induction of anesthesia. Group B received atropine (0.02 mg/kg); group C received midazolam (0.5 mg/kg); group D received midazolam (0.5 mg/kg) and atropine (0.02 mg/kg); group E received meperidine (1.5 mg/kg) and atropine (0.02 mg/kg); and group F received meperidine (1.5 mg/kg), atropine (0.02 mg/kg), and midazolam (0.5 mg/kg). The sedative effect of midazolam was maximal 30 min after oral administration. Ninety-five percent of the children who were separated from their parents within 45 min after oral midazolam administration (with or without atropine) had satisfactory separation scores (vs 66% of those separated after 45 min; P less than 0.02). Midazolam-treated patients were more cooperative with a mask induction of anesthesia compared with non-midazolam-treated children (83% vs 56%). Neither atropine nor meperidine appeared to significantly improve the effectiveness of oral midazolam. No preoperative changes in heart rate, respiratory rate, or hemoglobin oxygen saturation were noted in any of the treatment groups. Finally, oral midazolam did not prolong recovery even after outpatient procedures lasting less than 30 min. In conclusion, midazolam (0.5 mg/kg) given orally 30-45 min before induction of anesthesia is safe and effective without delaying recovery after ambulatory surgery.     

Comparison of rectal to intramuscular administration of midazolam and atropine for premedication of children

The effectiveness of midazolam and atropine as anaesthetic premedication was investigated, comparing rectal to intramuscular administration. A total of 202 children varying in age from 10 months to 9 years, who had been admitted to the Day Surgery Department for short ENT procedures, were assigned to one of two groups on a random basis. The first group (n = 102) was given 0.5 mg/kg midazolam and 0.05 mg/kg atropine as a rectal solution 30 to 75 min prior to induction, while the second group (n = 100) was given 0.15 mg/kg midazolam and 0.02 mg/kg atropine as an intramuscular injection 20 to 60 min prior to induction. The levels of sedation and salivation were compared, as was the degree of tolerance to intravenous induction. The parents of children older than 3 years of age were given a questionnaire designed to determine the degree of amnesia. We found this combination of drugs to be effective in the relief of anxiety, the inhibition of salivary secretion and the promotion of memory loss, regardless of the route of administration. We feel that rectal administration is preferable because it is not associated with pain or anxiety.     

Oral ketamine or midazolam or low dose combination for premedication in children

This randomized controlled trial was designed to evaluate whether the combination of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg) provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6 mg/kg). Seventy-eight children of ASA physical status I or II scheduled for elective ophthalmic surgery were randomly divided into three groups and given premedication in the holding area 30 minutes before surgery. Two subjects from each group vomited the medication and were excluded, leaving 72 subjects for further analysis. The onset of sedation was earlier in the combination group than the other two groups. At 10 minutes after premedication 12.5% in the combination group had an acceptable sedation score compared with none in the other two groups. After 20 minutes 54% in the combination group had an acceptable sedation score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There were no significant differences in the parental separation score, response to induction and emergence score. The mean time for best parental separation score was significantly less in the combination group (19+/-8 min) than either the midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier in the combination group, as the time required to reach a modified Aldrete score of 10 was significantly less in the combination group (22+/-5 min) than in the oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of excessive salivation was significantly higher in the ketamine alone group (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in children.     

Better acceptance of measures for induction of anesthesia after rectal premedication with midazolam in children. Comparison of results of an open and placebo-controlled study

The rectal administration of midazolam for premedication of children before induction of anesthesia by mask was investigated in two clinical studies. In 62 children aged between 2 and 10 years, midazolam was given by open design at various dosages (0.15 mg.kg-1, 0.25 mg.kg-1, 0.30 mg.kg-1, 0.35 mg.kg-1, 0.40 mg.kg-1) to evaluate the most effective dose for optimal acceptance of the mask and gas mixture. An additional 40 children between 3 and 9 years received 0.2 mg midazolam.kg-1 body weight or placebo in a double-blind design to estimate the lower limit of efficacy of midazolam. All children were classified as ASA I and had to undergo a surgical procedure. Within the two studies the children were not different with respect to their general data, age, weight, and sex. In both studies more boys than girls were included. Parameters of efficacy were the degree of sedation before and at 10, 20, and 30 min after midazolam as well as acceptance of the mask and the gas mixture at induction of anesthesia. In all groups, including placebo, a sedative and tranquilizing effect of the premedication was found. The rectal administration of 0.35-0.4 mg midazolam.kg-1 is most suitable for the preoperative medication of children between 2 and 10 years. Due to the degree of sedation and the relief of anxiety toward the surroundings and the operation, the induction of anesthesia is optimally accepted by the child. In contrast, the effect of a dose around 0.2 mg midazolam.kg-1 body weight is not much different from that of placebo and is not sufficient for effective premedication.     

Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children.

We studied the effect of oral premedication with midazolam on the recovery characteristics of sevoflurane anesthesia in small children. In a randomized, double-blinded study, 60 children (1-3 yr, ASA physical status I or II) undergoing ambulatory adenoidectomy received either midazolam 0.5 mg/kg (Group M) or placebo (Group P) PO approximately 30 min before the induction of anesthesia. All children received atropine 0.01 mg/kg IV and alfentanil 10 microg/kg IV before the induction of anesthesia with sevoflurane up to 8 vol% inspired concentration in N2O 67% in O2. Tracheal intubation was facilitated with mivacurium 0.2 mg/kg. Anesthesia was continued with sevoflurane adjusted to maintain hemodynamic stability. In the postanesthesia care unit, predetermined recovery end points (emergence, recovery, discharge) were recorded. A pain/ discomfort scale was used to determine the quality of recovery. A postoperative questionnaire was used to evaluate the well-being of the patient at home 24 h after surgery. Emergence (spontaneous eye opening), recovery (full points on the modified Aldrete scale), and discharge were achieved later in Group M than in Group P (15+/-6 vs. 11+/-3 min [P = 0.002], 25+/-17 vs. 16+/-6 min [P = 0.01], and 80+/-23 vs. 70+/-23 min [P = 0.03]). Side effects, postanesthetic excitement, and analgesic treatment did not differ significantly between groups. At home, more children in Group P (30%) experienced disturbed sleep during the night compared with those in Group M (4%) (P = 0.007). IMPLICATIONS: In this randomized, double-blinded, placebo-controlled study, premedication with midazolam 0.5 mg/kg PO delayed recovery in children 1-3 yr of age after brief (<30 min) sevoflurane anesthesia. Except for more peaceful sleep at home, premedication did not affect the quality of recovery.     

Effectiveness of preoperative sedation with rectal midazolam, ketamine, or their combination in young children.

To determine which of three types of rectal sedation was most effective preoperatively in facilitating parental separation and intravenous cannulation in young children, 100 children 3.0 +/- 1.7 (mean +/- SD) yr of age were randomly assigned to four equal groups. One group (M-K-A) received rectal midazolam (0.5 mg/kg), ketamine (3 mg/kg), and atropine (0.02 mg/kg). The other sedation groups received the same doses of midazolam and atropine (M-A) or ketamine and atropine (K-A) alone, and the control group (A) received only rectal atropine. Most children in either the M-K-A (100%) or M-A (92%) groups separated easily from their parents without struggling or crying, significantly more than in the K-A (60%) or A (64%) groups. However, more children in the M-K-A group (44%) were asleep during separation than in the M-A group (8%; P < 0.05). Only 20% of the children in the M-A or M-K-A groups cried during intravenous catheter placement, significantly less than in the K-A (56%) or A (92%) groups. Intravenous catheter placement was also successful significantly more often in the M-A (80%) and M-K-A (84%) groups than in the K-A (48%) or A (40%) groups. Complications were similar among the groups, but there was evidence that midazolam prolonged recovery time in some patients. Rectal midazolam with or without ketamine is a useful technique when intravenous catheter placement before induction of anesthesia is desired.     

Rectal premedication with midazolam in children. A comparative clinical study

Anesthetic premedication by injection is usually poorly accepted by children, especially those under 10 years of age. Less disturbing for the child is oral premedication, but this increases the risk of aspiration and must be administered 1.5-2 h before anesthetic induction. This double-blind study was performed in children to investigate the efficacy, acceptance, and general safety of midazolam given rectally. METHOD. Rectal premedication was administered to a total of 80 healthy children between 2 and 10 years of age undergoing elective operations. The children were divided randomly into two groups: group I received 0.4 mg/kg and group II 0.5 mg/kg midazolam with the addition of 0.015-0.02 mg/kg atropine. Premedication was carried out on the pediatric ward. The calculated dose was drawn from the ampule and diluted to 8-10 ml with distilled water. This dose was instilled immediately behind the anal sphincter using a suitable plastic applicator (Stanylan). The following parameters were recorded: immediate reaction to the rectal medication, sedative-hypnotic signs, and acceptance of the anesthetic mask. Heart rate and blood pressure were measured before premedication and before the induction of anesthesia. Observations were made for 5 h post-operatively. Any unusual side effects of the treatment were also noted. The existence of any anterograde amnesia was investigated in 20 children (10 in each group) between 6 and 10 years of age. RESULTS. There was no significant difference between the children allocated to the two groups with regard to age, body weight, sex, type of operation, and duration of anesthesia (Table 2). Of the total of 80 children, 66 (82.5%) accepted the rectal instillation well, 12 (15%) moderately well, and 2 (2.5%) poorly. Signs of respiratory depression or allergic reaction to midazolam were not observed in any case. The observations made before induction of anesthesia are presented in Table 3. The children in group II exhibited significantly greater (P less than 0.05) slurred speech than those in group I. A low incidence of hiccup was seen in both groups. Most of the children (27 in group I, 67.5%; 37 in group II, 92.5%: P less than 0.05) were delivered to the operating room lying down, whereas the others were sitting up in bed but showed no desire to get up. Between 10 and 55 min after the premedication, a total of 5 children (12.5%) in group I and 2 (5%) in group II were restless or crying on arrival in the induction room. Most, however, were quiet to tired/drowsy. The optimal sedative-hypnotic action was observed after 20-30 min (Fig. 1). At this time 21.7% of the children in group I were tired/drowsy, whereas 50% in group II were tired/drowsy and 9.1% were asleep but easy to arouse. This effect was significantly greater in group II (P less than 0.01). Acceptance of the mask was comparable in both groups (Table 4) and was tolerated well to very well by 92-97% of the children. (ABSTRACT TRUNCATED AT 400 WORDS)     

Serum potassium after enflurane-succinylcholine induction of anesthesia in children receiving rectal midazolam as premedication.

The administration of succinylcholine causes an increase in serum potassium (K+) concentrations in healthy patients. The purpose of this study was to investigate serum K+ changes following intravenous succinylcholine in children and to evaluate the effect of rectal midazolam pretreatment on these changes. Forty healthy children between the ages of 2 and 7 yr, and who were to undergo oral surgical procedures under general anesthesia were randomly assigned to receive either placebo (saline) or 0.25, 0.35, or 0.45 mg/kg midazolam administered rectally as premedication 30 min before induction of inhalational anesthesia. Blood was drawn after induction with enflurane and at 1, 2, 3, 4, and 5 min after administration of 1 mg/kg succinylcholine to determine changes in serum K+. Although the results indicate a significant increase in serum K+ after succinylcholine in all groups, midazolam pretreatment failed to cause any observable attenuation in the hyperkalemic response.     

Dexmedetomidine Premedication Attenuates Ketamine-induced Cardiostimulatory Effects and Postanesthetic Delirium

Background: Dexmedetomidine is a new potent and highly selective alpha2 -adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulalory effects and attenuating the adverse central nervous system effects of ketamine.

Methods: A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micro gram/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according t clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.

Results: Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra and postoperative bradycardia.     

Atropine prevents midazolam-induced core hypothermia in elderly patients.

STUDY OBJECTIVE: To test the hypothesis that core temperature is well preserved when atropine and midazolam are combined. DESIGN: Randomized, blinded study. SETTING: Department of Anesthesia, Yamanashi Medical University. PATIENTS: 40 elderly, ASA physical status I and II patients (aged more than 60 years). INTERVENTIONS: Patients were randomly assigned (n = 10 per group) to premedication with: 1) saline control; 2) midazolam 0.05 mg/kg; 3) atropine 0.01 mg/kg; and 4) midazolam 0.05 mg/kg combined with atropine 0.01 mg/kg. All premedication was given on the ward at approximately 8:30 am, approximately 30 minutes before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Core temperatures were measured at the right tympanic membrane. Mean skin temperature was calculated as 0.3 x (T(chest) + T(arm)) + 0.2 x (T(thigh) + T(calf)). Fingertip perfusion was evaluated using forearm minus fingertip and calf minus toe, skin-surface temperature gradients. Temperatures were evaluated at the time of premedication and 30 minutes later, just before induction of anesthesia. Core temperature remained nearly constant in the control patients (0.1 +/- 0.2 degrees C; mean +/- SD), whereas it decreased significantly in the patients given midazolam alone (-0.3 +/- 0.1 degrees C). Atropine alone increased core temperature (0.3 +/- 0.2 degrees C), although the increase was not statistically significant. The combination of midazolam and atropine attenuated the hypothermia induced by midazolam alone (0.0 +/- 0.2 degrees C). Initial skin-temperature gradients exceeded 0 degrees C in all groups, indicating that the patients were vasoconstricted. The gradients were unchanged by premedication with saline or atropine. Midazolam significantly decreased the gradient (-1.8 +/- 1.1 degrees C), as did the combination of midazolam and atropine (-1.4 +/- 0.9 degrees C). CONCLUSIONS: The thermoregulatory effects of benzodiazepine receptor agonist and cholinergic inhibitors oppose each other, and the combination leaves core temperature unchanged.     

Pharmacokinetic studies following intravenous and rectal administration of midazolam in children

In children, rectal midazolam is being used increasingly for premedication, as this substance is reported to have a short half-life and rapid action. Above all it is the only known diazepam derivative with a good correlation of plasma concentration and clinical action despite its receptor binding capacity. As pharmacokinetic data in children are lacking and different dose regimens for rectal premedication exist, we studied plasma concentrations in 3 groups of children. METHODS. After obtaining informed parental consent we studied children aged 3-7 years (15-30 kg body weight) ASA I status scheduled for minor elective surgery. Group 1 (n = 6) received 0.1 mg/kg midazolam i.v. for induction of anesthesia. Group 2 (n = 10) was premedicated with 0.35 mg/kg midazolam, instilled just behind the anal sphincter; group 3 (n = 5) received 0.5 mg/kg midazolam rectally. Blood samples were drawn up to 120 min after application. The anesthesia technique consisted of N2O/O2, enflurane, intubation and the use of muscle relaxants, if necessary. Midazolam plasma levels were measured by HPLC. RESULTS. There were no differences with respect to age or body weight. Group 1: half-life in children was shorter than in adults, Vdss was smaller and clearance identical. Group 2: Rectal midazolam 0.35 mg/kg has a remarkably short onset of action with peak plasma concentrations (71 ng/ml) in the range of sedative levels in adults occurring in 7.5 min. After 2 h they reached levels of 30 ng/ml. Group 3 patients had peak levels of midazolam of 246 ng/ml after 12.5 min, falling to an average concentration of 120 ng/ml after 2 h. The bioavailability of rectal midazolam, comparing the area under the median curves, is 4.7% in group 2 and 16.1% in group 3. CONCLUSIONS: The pharmacokinetics of midazolam in our patients showed a shorter half-life, probably due to the higher hepatic clearance based on the high CI in children, as midazolam is known to have a first-pass effect of 30-70%. The increased metabolic transformation and the smaller amount of fatty tissue accounts for the smaller Vdss in children compared to adults. Rectal midazolam has a remarkably short onset and especially in a dose of 0.5 mg/kg prolonged action due to ongoing resorption from the rectum as demonstrated by the clinically relevant plasma concentrations. This fact must be taken into consideration in the overall anesthesia management.(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes in the auditory evoked potentials index by induction doses of four different intravenous anesthetics

BACKGROUND: Many studies have investigated the electroencephalographic changes during the induction and maintenance of anesthesia. However, no comparative studies have been performed on the effects of intravenous anesthetics on the auditory evoked potentials index (AAI). The present study was performed to compare the changes in AAI caused by induction doses of thiopental, propofol, midazolam and ketamine. METHODS: Eighty females, aged 30-70 years, referred for mastectomy, had anesthesia induced with thiopental 4 mg/kg, propofol 2 mg/kg, midazolam 0.1 mg/kg or ketamine 1 mg/kg (each 20 patients). The response to verbal command and the AAI were measured every minute for 5 min. RESULTS: The AAI decreased to less than 40 within 1 min with thiopental and propofol. The AAI increased after 3 min with thiopental, but remained low with propofol. The AAI gradually decreased to less than 40 within 4 min with midazolam, but was higher than the AAI with propofol or thiopental. The AAI increased significantly with ketamine. The AAIs at the loss of verbal command were 19 +/- 7 with thiopental, 21 +/- 8 with propofol, 31 +/- 10 with midazolam and 92 +/- 2 with ketamine. CONCLUSION: The AAI correlated with changes in hypnotic level, as measured by the response to verbal command, with induction doses of thiopental, propofol and midazolam, but not with ketamine. The AAI decreased to lower levels with propofol and thiopental than with midazolam at the induction of anesthesia.     

Rectal administration of midazolam as an adjuvant in the premedication of infants

In a randomized, double-blind study of premedication in 69 infants aged between 13 and 48 months the effects of 0.82 mg/kg midazolam or diazepam rectally plus 2.0 mg/kg ketamine i.m., or the administration of 2.4 mg/kg ketamine i.m. alone was studied. A satisfying result of 94.1% following the premedication with midazolam/ketamine, of 82.9% with diazepam/ketamine and of 81.3% with ketamine alone was observed. Premedication with midazolam/ketamine was the best one in the review of vigilance, agitation, and behaviour of defence against the mask at the beginning of anaesthesia. The amnestic action of midazolam extinguished the infants' memory of the i.m.-injection. The dose of midazolam/ketamine is suitable as an effective and positive method for premedication of infants within 20 min.     

Ketamine and midazolam is an inappropriate preinduction combination in uncooperative children undergoing brief ambulatory procedures

BACKGROUND: We prospectively studied the effects of intramuscular (i.m.) ketamine alone, or combined with midazolam, on mask acceptance and recovery in young children who were uncooperative during induction of anaesthesia. METHODS: The Institutional Review Board (IRB) approval was obtained to study 80 children, 1-3 years, scheduled for bilateral myringotomies and tube insertion (BMT). Mask induction was attempted in all the children. Those who were uncooperative were randomly assigned to one of the four preinduction treatment groups: group I, ketamine 2 mg.kg(-1); group II, ketamine 2 mg.kg(-1) combined with midazolam 0.1 mg.kg(-1); group III, ketamine 2 mg.kg(-1) with midazolam 0.2 mg.kg(-1); or group IV, ketamine 1 mg.kg(-1) with midazolam 0.2 mg.kg(-1). Anaesthesia was continued with nitrous oxide and halothane by facemask. RESULTS: Children in all treatment groups achieved satisfactory sedation in less than 3 min following the administration of the preinduction drug(s). Compared with patients who received halothane induction (comparison group), the use of ketamine alone did not significantly (P > 0.0167, a Bonferroni corrected significance level) delay recovery and discharge times (18.8 +/- 2.5 and 82.5 +/- 30.7 min vs 12.6 +/- 4.6 and 81.0 +/- 33.8 min, P = 0.030 and P = 0.941, respectively). Patients who received ketamine/midazolam combinations, however, had significantly longer recovery and discharge times vs halothane (32.3 +/- 14.0 and 128.0 +/- 36.6 min, P = 0.001, P = 0.007, respectively). These times were so clinically unacceptable, that the study had to be terminated with only 17 patients receiving study drugs. CONCLUSIONS: It is concluded that ketamine/midazolam combination is not appropriate for preinduction of anaesthesia in paediatric ambulatory patients because of unacceptably prolonged recovery and delayed discharge times.     

Premedication with midazolam in young children: a comparison of four routes of administration

BACKGROUND: We undertook a study to determine the effects of four routes of administation on the efficacy of midazolam for premedication. METHODS: In a randomized double-blind study, 119 unmedicated children, ASA I-II, aged 1.5-5 years, who were scheduled for minor elective surgery and who had been planned to received midazolam as a premedicant drug, were randomly assigned to one of four groups. Group I received intranasal midazolam 0.3 mg.kg-1; group II, oral midazolam 0.5 mg x kg(-1); group III, rectal midazolam 0.5 mg x kg(-1); and group IV, sublingual midazolam 0.3 mg x kg(-1). A blinded observer assessed the children for sedation and anxiolysis every 5 min prior to surgery. Quality of mask acceptance for induction, postanaesthesia care unit behaviour and parents' satisfaction were evaluated. Thirty patients were enrolled in each of groups I, III and IV. Twenty-nine patients were enrolled in group II. RESULTS: There were no significant differences in sedation and anxiety levels among the four groups. Average sedation and anxiolysis increased with time, achieving a maximum at 20 min in group I and at 30 min in groups II-IV. Patient mask acceptance was good for more than 75% of the children. Although the intranasal route provides a faster effect, it causes significant nasal irritation. Seventy-seven percent of the children from this group cried after drug administration. Most parents in all groups (67-73%) were satisfied with the premedication. CONCLUSIONS: Intranasal, oral, rectal and sublingual midazolam produces good levels of sedation and anxiolysis. Mask acceptance for inhalation induction was easy in the majority of children, irrespective of the route of drug administration.     

Midazolam premedication delays recovery from propofol-induced sevoflurane anesthesia in children 1–3 yr

PURPOSE: To study the effect of midazolam premedication on the recovery characteristics of sevoflurane anesthesia induced with propofol in pediatric outpatients. METHODS: Sixty children, one to three years, presenting for ambulatory adenoidectomy were randomly assigned , in a double-blind fashion, to receive either 0.5 mg x kg(-1) midazolam (Group M) or placebo (Group P) p.o. 30 min before anesthesia. Anesthesia was induced with 10 microg x kg(-1) atropine, 10 microg x kg(-1) alfentanil, and 3-4 mg x kg(-1) propofol i.v.. Tracheal intubation was facilitated with 0.2 mg x kg(-1) mivacurium. Anesthesia was maintained with nitrous oxide/oxygen (FiO2 0.3) and sevoflurane with controlled ventilation. Recovery characteristics were compared using the modified Aldrete scoring system, the Pain/Discomfort scale and measuring specific recovery end-points (emergence, full Aldrete score, discharge). A postoperative questionnaire was used to evaluate the children's well-being at home until 24 hr after discharge. RESULTS: Emergence from anesthesia (22 +/- 9 vs 16 +/- 6 min (mean +/- SD), P = 0.005) and achieving full Aldrete scores (30 +/- 11 vs 24 +/- 16 min, P = 0.006) were delayed in patients receiving midazolam. Children in the placebo group were given postoperative analgesia sooner than those in the midazolam group (18 +/- 11 vs 23 +/- 8 min, P = 0.009). More children premedicated with midazolam suffered from arousal distress (20% vs 3%, P = 0.04) and scored higher on the Pain/Discomfort scale (P = 0.004) at 20 min after arrival in the recovery room. Discharge was not affected by premedication and well-being at home was similar in the groups. CONCLUSIONS: Oral premedication with midazolam delays early recovery but not discharge after ambulatory sevoflurane anesthesia induced with propofol in children one to three years. Midazolam did not improve the quality of recovery.     

Comparative evaluation of midazolam and ketamine with midazolam alone as oral premedication

BACKGROUND: Oral premedication with midazolam and ketamine is widely used in pediatric anesthesia to reduce emotional trauma and ensure smooth induction. However, various dosing regimens when used alone or in combination have variable efficacy and side effect profile. The aim of our study was to investigate and compare the efficacy of oral midazolam alone with a low-dose combination of oral midazolam and ketamine. METHODS: We performed a prospective randomized double-blind study in 100 children who were randomly allocated into two groups. Group M received 0.5 mg.kg(-1) oral midazolam and group MK received 0.25 mg.kg(-1) oral midazolam with 2.5 mg.kg(-1) oral ketamine. The preoperative sedation score, ease of parental separation and ease of mask acceptance were evaluated on a 4-point scale. The time to recovery from anesthesia and to achieve satisfactory Aldrete score was also noted. RESULTS: Uniform and acceptable sedation scores were seen in both the groups (group M 95.9%; group MK 97.96%), without any serious side effects. However, the combination offered significantly more children in an awake, calm and quiet state, who were easily separated from their parents (73.46% in MK vs 41% in group M). The induction scores were comparable between the groups. The recovery room characteristics and time to achieve satisfactory Aldrete score were also comparable between the two groups. CONCLUSIONS: Oral midazolam alone and a combination of midazolam with ketamine provide equally effective anxiolysis and separation characteristics. However, the combination provided more children in an awake, calm and quiet state who could be separated easily from parents.