A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine. A double blind randomized comparison of oral trimeprazine-methadone and ketamine-midazolam for sedation of pediatric dental patients for oral surgical procedures.
To compare treatment of ongoing seizures using intramuscular (IM) midazolam versus intravenous (IV) diazepam.
                Controlled clinical trial.
                Children with motor seizures of at least 10 minutes' duration.
                Time to cessation of seizures.
                Twenty-four patients were enrolled (13 midazolam, 11 diazepam). Initial treatment with either midazolam or diazepam was successful in 22 of the 24 patients. One patient in each group failed therapy and eventually required endotracheal intubation and general anesthesia for convulsive status epilepticus lasting more than one hour. Patients in the midazolam group received medication sooner (3.3 +/- 2.0 vs 7.8 +/- 3.2 minutes, P = 0.001) and had more rapid cessation of their seizures (7.8 +/- 4.1 vs 11.2 +/- 3.6, P = 0.047) than patients randomized to receive diazepam.
                IM midazolam is an effective anticonvulsant for children with motor seizures. Compared to IV diazepam, IM midazolam results in more rapid cessation of seizures because of more rapid administration. The IM route of administration may be particularly useful in physicians' offices, in the prehospital setting, and for children with difficult IV access. To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures.
                Prospective randomised study.
                Paediatric emergency department in a general hospital.
                47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period.
                Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures: Time from arrival at hospital to starting treatment and cessation of seizures.
                Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7. 9 to 8.3). No significant side effects were observed in either group.
                Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home. In sub-Saharan Africa, rectal diazepam or intramuscular paraldehyde are commonly used as first-line anticonvulsant agents in the emergency treatment of seizures in children. These treatments can be expensive and sometimes toxic. We aimed to assess a drug and delivery system that is potentially more effective, safer, and easier to administer than those presently in use.
                We did an open randomised trial in a paediatric emergency department of a tertiary hospital in Malawi. 160 children aged over 2 months with seizures persisting for more than 5 min were randomly assigned to receive either intranasal lorazepam (100 microg/kg, n=80) or intramuscular paraldehyde (0.2 mL/kg, n=80). The primary outcome measure was whether the presenting seizure stopped with one dose of assigned anticonvulsant agent within 10 min of administration. The primary analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00116064.
                Intranasal lorazepam stopped convulsions within 10 min in 60 (75%) episodes treated (absolute risk 0.75, 95% CI 0.64-0.84), and intramuscular paraldehyde in 49 (61.3%; absolute risk 0.61, 95% CI 0.49-0.72). No clinically important cardiorespiratory events were seen in either group (95% binomial exact CI 0-4.5%), and all children finished the trial.
                Intranasal lorazepam is effective, safe, and provides a less invasive alternative to intramuscular paraldehyde in children with protracted convulsions. The ease of use of this drug makes it an attractive and preferable prehospital treatment option. Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs.
                A multicentre, randomised controlled trial was undertaken to compare buccal midazolam with rectal diazepam for emergency-room treatment of children aged 6 months and older presenting to hospital with active seizures and without intravenous access. The dose varied according to age from 2.5 to 10 mg. The primary endpoint was therapeutic success: cessation of seizures within 10 min and for at least 1 hour, without respiratory depression requiring intervention. Analysis was per protocol.
                Consent was obtained for 219 separate episodes involving 177 patients, who had a median age of 3 years (IQR 1-5) at initial episode. Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for rectal diazepam (percentage difference 29%, 95% CI 16-41). Analysing only initial episodes revealed a similar result. The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use of antiepileptic drugs, prior treatment, and length of seizure before treatment were adjusted for with logistic regression, buccal midazolam was more effective than rectal diazepam.
                Buccal midazolam was more effective than rectal diazepam for children presenting to hospital with acute seizures and was not associated with an increased incidence of respiratory depression. It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus.
                We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed.
                Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08).
                Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam. The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean +/- SD = 4.9 +/- 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P < .05). The maximum dose (mean +/- SD) of midazolam and diazepam required was 5.3 +/- 2.6 microg/kg/min and 0.04 +/- 0.02 mg/kg/min, respectively. About half of the patients needed mechanical ventilation and 40% had hypotension in both groups, but the mortality was higher in the midazolam group (38%) as compared to the diazepam group (10.5%, P < .1 > .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections. Lorazepam was compared with diazepam for the treatment of acute convulsions and status epilepticus in 102 children in a prospective, open, 'odd and even dates' trial. Convulsions were controlled in 76 per cent of patients treated with a single dose of lorazepam and 51 per cent of patients treated with a single dose of diazepam. Significantly fewer patients treated with lorazepam required additional anticonvulsants to terminate the seizure. Respiratory depression occurred in 3 per cent of lorazepam-treated patients and 15 per cent of diazepam-treated patients. No patient who received lorazepam required admission to the intensive care unit for either respiratory depression or persisting status epilepticus. Rectally administered lorazepam appeared to be particularly valuable (100 per cent efficacy) when venous access was not possible. Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia.
                The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg).
                The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups.
                We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine. 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.
The conclusions of this update have changed to suggest that intravenous lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions. Where intravenous access is unavailable there is evidence from one trial that buccal midazolam is the treatment of choice.