thiopental and Asphyxia-Neonatorum

Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in order to prevent seizures. However, barbiturate therapy may adversely affect neurodevelopment leading to concern regarding aggressive use in neonates.. To determine the effect of administering prophylactic barbiturate therapy on death or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia.. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCT) and quasi-RCTs.. We included all RCTs or quasi-RCTs of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures compared to controls following perinatal asphyxia.. Three review authors independently selected, assessed the quality of, and extracted data from the included studies. We assessed methodologic quality and validity of studies without consideration of the results. The review authors independently extracted data and performed meta-analyses using risk ratios (RR) and risk differences (RD) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI). For significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH).. In this updated review, we identified nine RCTs of any barbiturate therapy in term and late preterm infants aged less than three days old with perinatal asphyxia without evidence of seizures. Eight of these studies compared prophylactic barbiturate therapy to conventional treatment (enrolling 439 infants) and one study compared barbiturate therapy to treatment with phenytoin (enrolling 17 infants). Prophylactic barbiturate therapy versus conventional treatment: one small trial reported a decreased risk of death or severe neurodevelopmental disability for barbiturate therapy (phenobarbital) versus conventional treatment (RR 0.33, 95% CI 0.14 to 0.78; RD -0.55, 95% CI -0.84 to -0.25; NNTB 2, 95% CI 1 to 4; 1 study, 31 infants) (very low quality evidence).Eight trials comparing prophylactic barbiturate therapy with conventional treatment following perinatal asphyxia demonstrated no significant impact on the risk of death (typical RR 0.88, 95% CI 0.55 to 1.42; typical RD -0.02, 95% CI -0.08 to 0.05; 8 trials, 429 infants) (low quality evidence) and the one small trial noted above reported a significant decrease in the risk of severe neurodevelopmental disability (RR 0.24, 95% CI 0.06 to 0.92; RD -0.43, 95% CI -0.73 to -0.13; NNTB 2, 95% CI 1 to 8; 1 study, 31 infants) (very low quality evidence).A meta-analysis of the six trials reporting on seizures in the neonatal period demonstrated a statistically significant reduction in seizures in the prophylactic barbiturate group versus conventional treatment (typical RR 0.62, 95% CI 0.48 to 0.81; typical RD -0.18, 95% CI -0.27 to -0.09; NNTB 5, 95% CI 4 to 11; 6 studies, 319 infants) (low quality evidence). There were similar results in subgroup analyses based on type of barbiturate and Sarnat score. Prophylactic barbiturate therapy versus other prophylactic anticonvulsant therapy: one study reported on prophylactic barbiturate versus prophylactic phenytoin. There was no significant difference in seizure activity in the neonatal period between the two study groups (RR 0.89, 95% CI 0.07 to 12.00; 1 trial, 17 infants).. We found only low or very low quality evidence addressing the use of prophylactic barbiturates in infants with perinatal asphyxia. Although the administration of prophylactic barbiturate therapy to infants following perinatal asphyxia did reduce the risk of seizures, there was no reduction seen in mortality and there were few data addressing long-term outcomes. The administration of prophylactic barbiturate therapy for late preterm and term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice. If used at all, barbiturates should be reserved for the treatment of seizures. The results of the current review support the use of prophylactic barbiturate therapy as a promising area of research. Future studies should be of sufficient size and duration to detect clinically important reductions in mortality and severe neurodevelopmental disability and should be conducted in the context of the current standard of care, including the use of therapeutic hypothermia.

Topics: Anticonvulsants; Asphyxia Neonatorum; Barbiturates; Humans; Infant; Infant, Newborn; Infant, Premature; Neurodevelopmental Disorders; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Thiopental

The pharmacokinetic properties of thiopental were studied in 10 asphyxiated neonates (mean +/- SE; birth weight, 3,244 +/- 212 g; gestational age, 40 +/- 1 weeks) as part of a randomized, controlled trial which tested the ability of barbiturate therapy to decrease central nervous system damage secondary to perinatal asphyxia. Therapy was begun at a mean age of 2.3 h in all and was initially given as a loading dose of 15 mg/kg over 30 min followed by a constant infusion. The mean steady-state thiopental concentration was 13.4 +/- 3.7 micrograms/ml (mean +/- SD) and the average time to reach steady state was 7 +/- 5 h. Mean elimination half-life, plasma clearance and volume of distribution for thiopental were 39 h (range 26-70), 66 ml/(h x kg) (range 31-172), and 3.6 liters/kg (range 1.1-6.7), respectively. Arterial blood pressure support was required in 8 of 10 patients. While it appears feasible to give thiopental to the asphyxiated neonate at the reported infusion rates, the risk-benefit ratio is increased by the frequent associated hypotension and need for pharmacologic blood pressure support.

Topics: Asphyxia Neonatorum; Humans; Infant, Newborn; Random Allocation; Thiopental

The possible cerebral sparing effect of thiopental was evaluated in 32 severely asphyxiated neonates randomly assigned to either a thiopental treatment or control group. All infants had neurologic manifestations of asphyxia and required assisted ventilation. Thiopental was begun at a mean age of 2.3 hours and was given as a constant infusion that delivered 30 mg/kg over 2 hours. Treatment was continued at a lower dose for 24 hours. Seizure activity occurred in 76% of infants given thiopental and 73% of control infants at a mean age of 1.5 and 2.5 hours, respectively. Although initial arterial blood pressure was similar in both groups, hypotension occurred in 88% of treated and 60% of control infants. The amount of blood pressure support required was significantly greater (P less than 0.005) in the thiopental treatment group. Three infants died in the control group, and five in the treatment group. Developmental assessment was performed at a minimum of 12 months of age in 22 infants. There were no significant differences in neurologic, cognitive, or motor outcome between groups. Deteriorating performance over time was a consistent trend in both groups. These findings indicate that treatment of severe perinatal asphyxia with thiopental does not appear to have a cerebral sparing effect and may be associated with significant arterial hypotension.

Topics: Apgar Score; Asphyxia Neonatorum; Brain; Brain Ischemia; Child Development; Clinical Trials as Topic; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infusions, Parenteral; Intracranial Pressure; Neurologic Examination; Outcome and Process Assessment, Health Care; Random Allocation; Seizures; Thiopental

The aim of this study was to determine the feasibility of inducing a prolonged coma in severely asphyxiated newborn babies by the infusion of high dose thiopentone. In six severely asphyxiated babies the electroencephalograph (EEG) and blood pressure were monitored continuously. Thiopentone was infused at a rate sufficient to suppress completely the EEG providing the mean blood pressure remained above 35 mm Hg; it was continued until there was no evidence of cerebral oedema for 24 hours. In two the infusion was stopped prematurely because of hypotension that was unresponsive to treatment. In the other four a deep coma was maintained for a median duration of 127 hours. All developed pharmacodynamic tolerance to the thiopentone and showed non-linear elimination kinetics. Three babies died; the three survivors have moderate to severe handicap. It was concluded that with full intensive care it is possible to induce a deep coma; the outcome does not seem to be improved, however, and the incidence of complications was high.

Topics: Asphyxia Neonatorum; Coma; Feasibility Studies; Female; Humans; Infant, Newborn; Kinetics; Male; Thiopental

Arterial blood pressures were taken by the Doppler ultrasound method in 134 unselected mature neonates (birthweights 2,600-3,900 grams) who were managed in the same manner after birth. Blood pressures were measured at 3-5, 10 and 30 minutes of life and, if indicated, intermittently during the next 24-48 h. Left and right arm pressures were identical or differed by only 1-2 mm Hg. Lower than normal blood pressures were found in 4 groups of infants: those born by cesarean section, those recovering from intrauterine asphyxia, those exposed to maternal anti-hypertensive therapy, and those whose mothers received thiopental within four minutes of delivery. Return of the low pressures to within the normal range was fastest following thiopental induction in the absence of fetal asphyxia and slowest after antihypertensive therapy.

Topics: Antihypertensive Agents; Asphyxia Neonatorum; Birth Weight; Blood Pressure; Blood Pressure Determination; Cesarean Section; Female; Fetal Distress; Humans; Hypotension; Infant, Newborn; Pregnancy; Thiopental; Time Factors; Ultrasonography

Topics: Anesthesia, Obstetrical; Apgar Score; Asphyxia Neonatorum; Cesarean Section; Female; Humans; Infant, Newborn; Pregnancy; Thiopental

Topics: Asphyxia Neonatorum; Female; Humans; Infant, Newborn; Labor, Induced; Obstetric Labor Complications; Oxytocin; Pregnancy; Thiopental

Topics: Adolescent; Adult; Anesthesia, General; Anesthesia, Obstetrical; Asphyxia Neonatorum; Cesarean Section; Cyclopropanes; Female; Hexobarbital; Humans; Infant, Newborn; Nitrous Oxide; Pregnancy; Sodium; Thiopental

Topics: Anesthesia, Obstetrical; Asphyxia Neonatorum; Cesarean Section; Energy Transfer; Female; Fetus; Humans; Infant, Newborn; Pregnancy; Propanidid; Thiopental

Topics: Adult; Asphyxia Neonatorum; Female; Fetal Death; Humans; Infant, Newborn; Labor, Induced; Oxytocin; Pregnancy; Thiopental

Topics: Anesthesia, Obstetrical; Asphyxia Neonatorum; Female; Fetus; Humans; Hydroxybutyrates; Infant, Newborn; Thiopental

Topics: Anesthesia; Anesthesia, General; Anesthesia, Inhalation; Asphyxia Neonatorum; Barbiturates; Cesarean Section; Cyclopropanes; Ether; Female; Humans; Infant Mortality; Infant, Newborn; Muscle Relaxants, Central; Nitrous Oxide; Pregnancy; Thiopental; Toxicology