Midazolam sedation in mechanically ventilated newborns: a double blind randomized placebo controlled trial. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. An RCT pilot study to test the effects of intravenous midazolam as a conscious sedation technique for anxious children requiring dental treatment--an alternative to general anaesthesia. Subhypnotic doses of midazolam prevent nausea and vomiting during spinal anesthesia for cesarean section. A double-blind randomized comparison of midazolam alone and midazolam combined with ketamine for sedation of pediatric dental patients. Midazolam premedication in children: a pilot study comparing intramuscular and intranasal administration. A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane. A double blind randomized comparison of oral trimeprazine-methadone and ketamine-midazolam for sedation of pediatric dental patients for oral surgical procedures.
To determine efficacy of midazolam as a sedative in mechanically ventilated newborns.
                Double blind randomized placebo controlled trial.
                Neonatal Unit of Tertiary Hospital.
                Sedation over 48 h of observation.
                Neonates with birth weight less than 2000 g who were mechanically ventilated within 7 days of life were randomly assigned to midazolam and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg) followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48 hours. Hemodynamic variables, ventilatory variables, complications and side effects of treatments were also recorded.
                Thirty-three neonates were enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for birth weights and gestation. The midazolam group had significantly better sedation from 18-24 hours after enrollment compared to placebo group. At 48 h there were no significant differences in proportion of infants with adequate sedation between midazolam and placebo group. The two groups were comparable with respect to heart rate, perfusion, ventilatory indices and blood gas parameters. None of the infants were noted to have hypotension on loading with midazolam or placebo. Seizures were noted in 2 neonates in placebo group 24 hours after enrollment (insignificant statistically).
                Sedation provided by continuous infusion of midazolam and morphine appears to be comparable to morphine alone in newborn babies on mechanical ventilation, with no significant adverse effects. The course of mechanical ventilation is not influenced by use of midazolam. Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo.
                To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis.
                Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.
                No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group.
                This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial. Although midazolam is used for sedation of mechanically ventilated newborn babies, this treatment has not been evaluated in a randomised trial. We have done a prospective placebo-controlled study of the effects of midazolam on haemodynamic variables and sedation as judged by a five-item behaviour score. 46 newborn babies on mechanical ventilation for respiratory distress syndrome were randomly assigned to receive midazolam (n = 24) or placebo (n = 22) as a continuous infusion. Doses of midazolam were calculated to obtain plasma concentrations between 200 and 1000 ng/mL within 24 h of starting treatment and to maintain these values throughout the study. Haemodynamic and ventilatory variables were noted every hour, as were complications and possible side-effects of treatment. Mean (SD) duration of inclusion was 78.7 (30.9) h. 1 patient in the treatment group and 7 in the placebo group were withdrawn because of inadequate sedation (p < 0.05). Midazolam gave a significantly better sedative effect than placebo, as estimated by the behaviour score (p < 0.05). Heart rate and blood pressure were reduced by treatment but remained within the normal range for gestational age and there was no effect on ventilatory indices. The incidence of complications was similar in the two groups. No midazolam-related side-effects were noted. Continuous infusion of midazolam at doses adapted to gestational age induces effective sedation in newborn babies on mechanical ventilation, with positive effects on haemodynamic variables. The course of the respiratory distress syndrome was not influenced by this treatment. Midazolam was given over only a few days and the limited effects on heart rate and blood pressure that we report should not encourage long-term administration. To add to the evidence base for acceptable and effective paediatric conscious sedation techniques in dental primary care.
                To compare three conscious sedation techniques for primary care as an alternative to dental general anaesthesia (DGA) in children. To assess the feasibility and practicality of running the trial in general dental practice. To form the basis for sample size calculations and assess scales of measurement.
                Single centre, randomised control trial (RCT).
                Queensway Anxiety Management Clinic (QAMC). A primary care based general and referral dental practice for the management of anxious patients.
                Sixty five children too anxious for management with relative analgesia, requiring invasive dental procedure for which dental general anaesthesia (DGA) will be required if an alternative cannot be found.
                Group 1 (n = 20) - A combination of inhaled medical air and titrated intravenous midazolam. Group 2 (n = 22) - A combination of inhaled 40% nitrous oxide in oxygen and titrated intravenous midazolam. Group 3 (n = 23) - A combination of an inhaled mixture of 0.3% sevoflurane and 40% nitrous oxide in oxygen with titrated intravenous midazolam.
                Successful completion of the intended dental treatment with a child who is co-operative and responsive to verbal commands.
                Fifty per cent (ten children) successfully completed treatment in Group 1, 73% (16 children) in Group 2 and 83% (19 children) in Group 3. This difference was not significant at a 5% level (chi(2) = 5.53, df = 2, P = 0.07) Of the total of 20 failures, eight children in Group 1 and one child in Group 2 were successfully treated with the addition of sevoflurane and nitrous oxide in oxygen. Only two children required referral to a hospital setting for DGA and the remaining nine children were managed with an alternative conscious sedation technique.
                This pilot shows that intravenous midazolam especially in combination with the addition of inhaled nitrous oxide or sevoflurane and nitrous oxide were promising safe and effective techniques, sufficient to justify progression to a definitive RCT with appropriate methods. We aimed to evaluate the efficacy of subhypnotic doses of midazolam and propofol for peripartum nausea and vomiting during regional anesthesia for elective cesarean section in order to prevent emesis in at least 50% of patients.
                A prospective, double blind, placebo-controlled study was carried out. Patients were randomly allocated to one of three groups to receive placebo (saline, N=28), propofol (20 mg bolus and 1.0 mg x kg(-1) x h(-1) infusion, N=30), and midazolam (1 mg bolus and 1.0 mg x h(-1) infusion, N=30) at subhypnotic doses intravenously (i.v.) immediately after the umbilical cord was clamped. Bupivacaine hydrochloride (8-10 mg) and fentanyl (10 microg) were injected into the intervertebral space for spinal anesthesia. Blood pressure was monitored at 2 min intervals and intraoperative postdelivery emetic episodes and ephedrine consumption were recorded. The study was carried out at the Anesthesiology Department, Hacettepe University, Turkey, hospitalized care. We included 90 parturients with ASA physical status I and II between the ages of 20 and 38 years undergoing spinal anesthesia for elective cesarean delivery to evaluate the efficacy of subhypnotic doses of propofol and midazolam and, in particular, the incidence of nausea, retching, and vomiting intraoperatively.
                The incidence of nausea, retching, and vomiting was significantly higher in the control group, compared to the propofol and midazolam groups. Total ephedrine consumption was significantly higher in the control group compared to the propofol and midazolam groups.
                A subhypnotic dose of midazolam (1 mg x h(-1)) was as effective as the subhypnotic dose of propofol (1 mg x kg(-1) x h(-1)) for the prevention of nausea and vomiting in parturients undergoing cesarean section under spinal anesthesia. The safety and efficacy of a new sedation technique for children having dental procedures under local anesthesia were evaluated.
                One hundred children between the ages of 2 and 7 years who required sedation for dental procedures were administered either a combination of midazolam (0.35 mg/kg) and ketamine (5 mg/kg) or midazolam alone (1 mg/kg) rectally 30 minutes before removal to the dental chair. Pulse rate, respiratory rate, arterial pressure, oxygen saturation, adverse reactions, postoperative recovery, and behavior were recorded.
                Satisfactory sedation and anxiolysis were achieved with both drugs used in the study. When evaluating postoperative recovery, statistically significantly more children receiving midazolam alone were fully awake on admission to the recovery room and 30 minutes later. Results of physiologic monitoring, behavioral ratings, and adverse effects are reported. Excessive salivation occurred in 26% of children receiving the combination of drugs, compared with 14% receiving midazolam alone. Seven (14%) of the children receiving the combination of drugs hallucinated, compared with 21 (42%) receiving midazolam alone. Both drug groups had reliably good anxiolysis and sedation without loss of respiratory drive or protective airway reflexes.
                The use of a combination of midazolam and ketamine or midazolam alone is a safe, effective, and practical approach to managing children for minor dental procedures under local anesthesia. With this technique, advanced airway management proficiency is recommended. The purpose of this study was to compare the effectiveness of intramuscular and intranasal midazolam used as a premedication before intravenous conscious sedation. Twenty-three children who were scheduled to receive dental treatment under intravenous sedation participated. The patients ranged in age from 2 to 9 years (mean age, 5.13 years) and were randomly assigned to receive a dose of 0.2 mg/kg of midazolam premedication via either intramuscular or intranasal administration. All patients received 50% nitrous oxide and 50% oxygen inhalation sedation and local anesthetic (0.2 mL of 4% prilocaine hydrochloride) before venipuncture. The sedation level, movement, and crying were evaluated at the following time points: 10 minutes after drug administration and at the times of parental separation, passive papoose board restraint, nitrous oxide nasal hood placement, local anesthetic administration, and initial venipuncture attempt. Mean ratings for the behavioral parameters of sedation level, degree of movement, and degree of crying were consistently higher but not significant in the intramuscular midazolam group at all 6 assessment points. Intramuscular midazolam was found to be statistically more effective in providing a better sedation level and less movement at the time of venipuncture than intranasal administration. Our findings indicate a tendency for intramuscular midazolam to be more effective as a premedication before intravenous sedation. Failure of dental treatment due to anxiety is a common problem in children. The aim of this study was to establish whether the use of a combination of intravenous midazolam with inhalation agents (nitrous oxide alone or in combination with sevoflurane) was any more likely to result in successful completion of treatment than midazolam alone. A further aim was to evaluate the clinical viability of these techniques as an alternative to general anaesthesia. In total, 697 children too anxious for management with relative analgesia and requiring invasive dental procedure for which a general anaesthetic would usually be required, were recruited and randomly assigned to one of three groups given the following interventions: group 1 - a combination of inhaled medical air and titrated intravenous midazolam, group 2 - a combination of inhaled 40% nitrous oxide in oxygen and titrated intravenous midazolam, and group 3 - a combination of an inhaled mixture of sevoflurane 0.3% and nitrous oxide 40% in oxygen with titrated intravenous midazolam. The primary outcome measure was successful completion of the intended dental treatment with a co-operative child responsive to verbal commands. In group 1, 54% (94/174 children) successfully completed treatment. In group 2, 80% (204/256 children) and in group 3, 93% (249/267 children) completed treatment. This difference was significant at the 1% level. Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment. The safety and efficacy of an oral sedation technique for children having minor oral surgical procedures under local anesthesia were studied. One hundred healthy children between the ages of 2 and 7 yr received either a combination of midazolam (0.35 mg/kg) and ketamine (5 mg/kg) (Group A), or a combination of trimeprazine (3 mg/kg) and methadone (0.2 mg/kg) (Group B) 30 min preoperatively. Hemodynamic parameters, adverse reactions, postoperative recovery, and behavior were evaluated. More children were asleep, but rousable to verbal commands, 30 min after drug administration in Group A (40%) than in Group B (8%). Immediately before the dental procedure, 46% of children in Group A were asleep in contrast to 8% of children in group B. Significantly more children in Group A were awake, coughing, crying, and moving purposefully 30 and 60 min after admission to the recovery room. Two children (4%) in Group A vomited. Ten (20%) children in Group A hallucinated compared to none in Group B. The surgeon rated the procedure as good or very good in 94% of children in Group A compared to 78% in Group B. Our results show that the combination of midazolam and ketamine, administered orally, is a safe, effective, and practical approach to managing children for minor oral surgical procedures under local anesthesia.
There are insufficient data to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.