Intravenous Doses Of Diazepam Research Articles

Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting

BackgroundAnesthesia in lactating women is frequently indicated for time-sensitive procedures such as postpartum tubal ligation. Ketamine and diazepam are two of the most commonly used anesthetic agents in low resource settings, but their safety profile in lactating women has not been established.MethodsMedical records of post-partum tubal ligations between 2013 and 2018 at clinics of the Shoklo Malaria Research Unit were reviewed for completeness of key outcome variables. Logistic regression identified presence or absence of associations between drug doses and adverse neonatal outcomes: clinically significant weight loss (≥95th percentile) and neonatal hyperbilirubinemia requiring phototherapy.ResultsOf 358 records reviewed, 298 were lactating women with singleton, term neonates. There were no severe outcomes in mothers or neonates. On the first postoperative day 98.0% (290/296) of neonates were reported to be breastfeeding well and 6.4% (19/298) had clinically significant weight loss. Phototherapy was required for 13.8% (41/298) of neonates. There was no association between either of the outcomes and increasing ketamine doses (up to 3.8 mg/kg), preoperative oral diazepam (5 mg), or increasing lidocaine doses (up to 200 mg). Preoperative oral diazepam resulted in lower doses of intraoperative anesthetics. Doses of intravenous diazepam above 0.1 mg/kg were associated with increased risk (adjusted odds ratio per 0.1 mg/kg increase, 95%CI) of weight loss (1.95, 95%CI 1.13–3.35, p = 0.016) and jaundice requiring phototherapy (1.87, 95%CI 1.11–3.13, p = 0.017).ConclusionsIn resource-limited settings ketamine use appears safe in lactating women and uninterrupted breastfeeding should be encouraged and supported. Preoperative oral diazepam may help reduce intraoperative anesthetic doses, but intravenous diazepam should be used with caution and avoided in high doses in lactating women.

Opisthotonos and midazolam

A 3-year-child, weighing 11.4 kgs, was admitted in the accident and emergency ward in status epilepticus of more than one hour duration. He was administered diazepam suppository followed by 3 doses of intravenous diazepam. When diazepam failed to control the status epilepticus a loading dose of phenytoin sodium 200 mg (18 mg per kg) was given. This too failed to control the status hence, an additional dose of 5 mg per kg of phenytoin sodium was administered. As the child continued to have seizures, he was shifted to the pediatric intensive care unit and an intravenous bolus of midazolam at 0.1 mg per kg was given followed by increasing doses by infusion, from 1 μg/kg/minute to 5 μg/kg/ minute, which controlled the status. In addition, a dose of mannitol, at 0.5 g/kg and dexamethosone 0.15 mg per kg was given. After the status was controlled abnormal retractions of head and arching of back was observed. This worsened on examining. This posture was noted when the child was in the lateral posture, which reduced when supine. After the seizures control for 4 hours, a tapering of midazolam was started. With 1 μg/kg/minute there was no opisthotonos. Midazolam was continued for 24 hours and then tapered off. Phenytoin sodium was continued at 5 mg/kg, 12 hourly intravenous for the next 5 days. Midazolam is a water-soluble benzodiazepine with sedative and anesthetic properties (1). Several side effects are associated with midazolam which include central nervous system effects like hypoxia, apnea, headache, confusion, tremor, vertigo, ataxia and systemic side effects like hypotension, blood disorders and jaundice (2,3). Opisthotonos was recently reported in two children administered midazolam for non-neurological indications (e.g. imaging) (4). Flumazenil given to antagonize side effect of midazolam was reported producing opisthotonos (5). What is the underlying mechanism for the production of opisthotonos with midazolam is not clear. We could postulate it to be related to high dose, as opisthotonos disappeared on reducing the dose. The precise correlation needs further studies.

Amnestic Effects of Intravenous Diazepam in Healthy Young Men

Changes in a test of memory performance were evaluated in 103 healthy young men after challenges with placebo and two different doses of intravenous diazepam (0.12 and 0.20 mg/kg). Both diazepam doses significantly impaired free recall in a dose-dependent manner. Within each dose challenge there was no significant correlation between the average serum diazepam or desmethyldiazepam levels and the average number of words recalled across the time points. The data expand our current understanding of the amnestic effects of benzodiazepines and suggest that patients abusing these drugs in large doses may develop profound degrees of memory impairment.

Interaction of diazepam with famotidine and cimetidine, two H2-receptor antagonists.

Famotidine is currently under investigation as an H2-receptor antagonist. Eleven healthy male volunteers received a single 10 mg intravenous dose of diazepam on three occasions: once during coadministration of famotidine 40 mg bid, once during coadministration of cimetidine 300 mg qid, and once without other drug treatment (control). Multiple blood samples were drawn during the seven days after each diazepam dose. Diazepam and desmethyldiazepam plasma concentrations were measured by electron capture gas chromatography. There were no significant differences among the three treatment conditions in diazepam central compartment volume or total volume of distribution. During the cimetidine as compared with the control treatment, diazepam elimination half-life was significantly increased (72 vs 55 hr, P less than .05), total area under the curve (AUC) increased (11.8 vs 9.8 hr-micrograms/mL, P less than .05), and total clearance reduced (0.20 vs 0.28 mL/min/kg, P less than .05). Seven-day AUC for desmethyldiazepam also increased (4.6 vs 3.8 hr-micrograms/mL, P less than .05). However, there were no significant differences between famotidine and control treatment conditions in diazepam elimination half-life (53 vs 55 hr), total AUC (9.5 vs 9.8 hr-micrograms/mL), or total clearance (0.28 vs 0.28 mL/min/kg) or in seven-day AUC for desmethyldiazepam (3.9 vs 3.8 hr-micrograms/mL). Thus, therapeutic doses of cimetidine significantly impair the clearance of diazepam and desmethyldiazepam. Therapeutic doses of famotidine do not impair diazepam and desmethyldiazepam kinetics, suggesting that there is no significant kinetic interaction when diazepam and famotidine are administered concurrently in clinical practice.

Effects of Fentanyl and Diazepam in Dogs Deprived of Autonomic Tone

In contrast to reports of the untoward hemodynamic effects of fentanyl and diazepam in intact organisms, we found that neither a bolus of 100 micrograms/kg fentanyl nor the addition of intravenous doses of diazepam, up to and including 1 mg/kg (cumulative dose 2 mg/kg) caused cardiovascular depression in 13 anesthetized dogs after elimination of their sympathetic and parasympathetic tone. There were no significant changes in mean arterial blood pressure, cardiac output, heart rate, peak left ventricular dP/dt, cardiac filling pressures, or systemic vascular resistance. Rapid bolus injection of 3 mg/kg diazepam (cumulative dose 5 mg/kg) caused a significant (P less than 0.05) but transient (time to 50% recovery less than 2 min) decrease in systemic vascular resistance, blood pressure, and dP/dt. When corrected for pressure changed (dP/dt divided by simultaneous left ventricular pressure), the decrease in dP/dt did not attain statistical significance, nor did changes in cardiac output or filling pressures, even after this large dose of diazepam. We conclude that previously reported decreases in hemodynamic function in subjects with intact autonomic function after fentanyl alone, or after the combination of fentanyl and diazepam, are indirect in nature, that is, are caused by a centrally mediated decrease in vasoregulatory (mainly sympathetic) outflow from the central nervous system.

Absolute bioavailability and effect of food and antacid on diazepam absorption from a slow-release preparation.

A series of healthy volunteers received a single 7.5-mg intravenous dose of diazepam on one occasion and a single 15-mg oral dose of slow-release diazepam (DZ-SR) on another occasion. Diazepam concentrations were measured by gas chromatography in multiple plasma samples drawn during seven days after each dose. Absorption of diazepam from DZ-SR was slow, with mean +/- S.E. peak concentrations attained at 3.8 +/- 0.5 hours after dosage. Absolute bioavailability of DZ-SR averaged 0.98 +/- 0.06. In two other studies, diazepam absorption from DZ-SR was evaluated when coadministered with a standard breakfast or with an antacid preparation (Maalox). Neither food nor antacid altered the rate of diazepam absorption and did not impair the completeness of absorption. Higher peak total plasma diazepam concentrations occurred in the postprandial as opposed to the fasting state, but this was an artifact of reduced protein binding (increased free fraction) due to fasting. Thus, diazepam absorption from DZ-SR is slow and essentially complete.

Cardiopulmonary Arrest Following Small Intravenous Doses of Diazepam (Valium)

Cardiopulmonary Arrest Following Small Intravenous Doses of Diazepam (Valium)

Clearance of diazepam can be impaired by its major metabolite desmethyldiazepam

The pharmacokinetics of a single intravenous dose of diazepam 0.1 mg/kg was studied in 6 healthy volunteers, in random order under controlled conditions and following pretreatment with its major metabolite, desmethyldiazepam (20 mg/kg/day) for one week. In the two subjects with the highest plasma concentration of desmethyldiazepam (990 and 1100 ng/ml, respectively), total plasma clearance (Cl) of diazepam was reduced after desmethyldiazepam, by 31% and 54%, respectively. In three individuals there was a moderate decrease of 14% to 21%, and no effect was seen in one volunteer. Cl was significantly reduced (11.5 +/- 1.8 vs. 9.1 +/- 3.3 ml/min; p = 0.015) and elimination half-life tended to be prolonged (38.5 +/- 10.4 vs. 65.8 +/- 67.1 h; p = 0.15). It is concluded that high concentrations of desmethyldiazepam can influence the elimination of its parent drug diazepam by product inhibition.

Intravenous diazepam for psychiatric reactions following open-heart surgery.

The present study, based on a series of 79 consecutive unselected patients undergoing open-heart surgery with extracorporeal circulation at the Quebec Institute of Cardiology, was undertaken to determine the occurrence and severity of postoperative psychiatric complications, to discuss some of the factors involved in their pathogenesis, and to test the effectiveness of intravenous diazepam in their prevention and control. The 79 patients were divided into two groups: a control group of 37 subjects and a treatment group of 42 subjects. In the treatment group only, the usual postoperative analgesic medication was completed by intravenous doses of diazepam 2.5 to 5 mg. six times a day given between the doses of narcotics. Both groups were comparable as to the age, sex, height, weight, anaesthetic risk, degree of hypothermia, bypass time, duration of anaesthesia, and type of cardiac lesion. Our results are as follows: (a) The incidence of psychiatric complications was 35.1 per cent (13 cases) in the control group and 4.7 per cent (two cases) in the treatment group, (b) There were eight minor and five major reactions in the control group in comparison to two minor and no major disturbances in the treatment group, (c) Postoperative mechanical ventilatory support was carried out more frequently in the treatment group (92.0%) than in the control group (62.1%), yet the occurrence of psychiatric reactions was 5.1 per cent in the treatment group as compared to 56.5 per cent in the control group. It is concluded that the postoperative use of intravenous diazepam as an adjunct to the usual analgesic medication has markedly reduced the incidence and severity of psychiatric complications after intracardiac surgery with cardiopulmonary bypass. In the treatment group, the use of intravenous diazepam has resulted in better patient behaviour, and an improved patient-nurse and patient-doctor relationship. Because of the amnesic properties of this drug, the I.C.U. is no longer described as a “torture chamber” to prospective patients.