naloxone and Asphyxia-Neonatorum

Studies in animal models have suggested that naloxone, a specific opiate antagonist, may improve outcomes for newborn infants with perinatal asphyxia.. In newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia: to assess the effects of naloxone versus placebo or no drug, and of single versus multiple doses of naloxone, on mortality, long term neurological problems, severity of hypoxic-ischaemic encephalopathy, and frequency of neonatal seizures.. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003), MEDLINE (1966 - August 2003), EMBASE (1980 - August 2003), conference proceedings, and previous reviews.. Randomised or quasi-randomised controlled trials comparing naloxone versus placebo, or no drug, or another dose of naloxone, in newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia.. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors. The pre-specified outcomes for this review were: death before hospital discharge, severe neurodevelopmental disability, severity of hypoxic-ischaemic encephalopathy, and seizures in the neonatal period.. We identified only one eligible randomised controlled trial. This study compared the use of naloxone with placebo in newborn infants with an Apgar score of six or less at one minute after birth. There were not any data on the pre-specified outcomes for this review.. There are insufficient data available to evaluate the safety and effectiveness of the routine use of naloxone for newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia. A further randomised controlled trial is needed to determine if naloxone benefits newborn infants with suspected perinatal asphyxia. Such a trial should assess clinically important outcomes such as mortality, and adverse short and long term neurological outcomes.

Topics: Asphyxia Neonatorum; Gestational Age; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Randomized Controlled Trials as Topic

Medication use during neonatal resuscitation is uncommon. The infrequent use of resuscitation medications has impeded rigorous investigations to determine the most effective agents and/or dosing regimens. The medications most commonly used during delivery room resuscitation include epinephrine, sodium bicarbonate, naloxone hydrochloride and volume expanders. The available evidence for each of these medications is reviewed in this article.

Topics: Asphyxia Neonatorum; Cardiopulmonary Resuscitation; Combined Modality Therapy; Epinephrine; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Plasma Substitutes; Sodium Bicarbonate; Vasoconstrictor Agents

Objectives were to identify and to evaluate controlled trials of interventions for term infants developing hypoxic-ischaemic encephalopathy. Five randomized trials concerning prophylactic anticonvulsant therapy for neonatal HIE were identified. There were methodological problems with all of them, and meta-analysis of barbiturate prophylaxis showed no significant effect on death or disability. One randomized trial of allopurinol showed short-term benfits, but was too small to test death or disability. One small randomized trial of hypothermia found no adverse effects, but was too small to examine death or disability. No adequate trials of dexamethasone, calcium channel blockers, magnesium sulphate, or naloxone have yet been completed, but pilot studies in infants have shown the risks of magnesium sulphate and calcium channel blockers.

Topics: Allopurinol; Anti-Inflammatory Agents; Anticonvulsants; Asphyxia Neonatorum; Calcium Channel Blockers; Dexamethasone; Diuretics, Osmotic; Fetal Hypoxia; Free Radical Scavengers; Humans; Hypothermia, Induced; Infant, Newborn; Magnesium Sulfate; Mannitol; Naloxone; Perinatal Care; Research Design; Treatment Outcome

The abrupt transition from intrauterine to extrauterine life represents a series of profound physiologic changes. This process puts the baby at risk for asphyxia. At birth, the newborn is, therefore, more frequently in need of resuscitation than at any other age. This article reviews the rationale for the sequence and process of neonatal resuscitation, emphasizing recent changes in recommendations.

Topics: Asphyxia Neonatorum; Atropine; Cardiopulmonary Resuscitation; Delivery Rooms; Epinephrine; Ethics, Medical; Humans; Infant, Newborn; Intensive Care, Neonatal; Meconium Aspiration Syndrome; Naloxone; Sodium Bicarbonate

Naloxone has enjoyed long-standing success as a safe and effective opioid antagonist and has been invaluable in defining the role of endogenous opioid pathways in the response to pathological states such as sepsis and hypovolemia. We look forward to exciting research to further elucidate these pathways and to improve outcome by modulating the patient's physiological response to these stresses.

Topics: Acute Disease; Adult; Animals; Asphyxia Neonatorum; Cerebrovascular Disorders; Child; Emergency Medicine; Humans; Infant, Newborn; Naloxone; Poisoning; Shock; Spinal Cord Injuries; Treatment Outcome

To determine whether endogenous opiates play a role in the pathogenesis of perinatal asphyxia, a blinded clinical trial of naloxone, a competitive opiate receptor blocker, was undertaken in infants with low 1-minute Apgar scores. Of 85 infants with 1-minute Apgar score 0 to 3, 44 received an injection of naloxone (approximately 0.4 mg/kg) and 41 received saline solution. In 108 infants with 1-minute Apgar score 4 to 6, 54 received naloxone and 54 saline solution. In neither group was there a significant effect of naloxone on respiratory frequency or heart rate up to 30 minutes after injection, nor at 24 hours of age. In both groups active muscle tone of upper and lower limbs was increased by naloxone, a response that may not be beneficial in the face of inadequate oxygen delivery to vital organs. We conclude that naloxone at this dose had no readily apparent benefit in the resuscitation of the asphyxiated newborn infant.

Topics: Adult; Apgar Score; Asphyxia Neonatorum; Clinical Trials as Topic; Delivery, Obstetric; Female; Heart Rate; Humans; Infant, Newborn; Injections, Intramuscular; Labor, Obstetric; Male; Maternal Age; Naloxone; Pregnancy; Respiration; Resuscitation

Both early post-ischaemic blood-brain barrier disruption and enhanced brain endogenous opioid system activity have been implicated in the pathogeneses of ischaemic neuronal damage; however, their roles in neonatal asphyxia have not been evaluated. Under alpha-Chloralose anaesthesia, 17 newborn lambs were asphyxiated until their mean arterial pressures were < or = 25 mmHg. They were then immediately resuscitated, and assigned to two groups. Group I, but not group II lambs received IV bolus of 10 mg kg-1 Naloxone within 5 min of resuscitation. The infusion was continued at the same dose hourly until sacrificed 24 h post-asphyxia. Arterial pH/gases, intracranial/arterial pressures, and rectal temperature were monitored. Neurological examinations were performed on both groups prior to sacrifice, and the blood-brain barrier integrity was assessed by Evans blue. Despite aggressive resuscitation, 5 lambs died during asphyxia, but 12 survived and were assigned according to the protocol. There were no significant group differences in the magnitude of asphyxia, arterial and intracranial pressures. However, blood-brain barrier disruption was observed in 5 out of 6 untreated, and in only 1 of the 6 lambs treated with Naloxone (p < 0.05). Severe neurological abnormalities were observed in 75% of lambs with disrupted, but in none of the animals with intact blood-brain barrier (p < 0.05). Our study suggests that post-asphyxia blood-brain barrier disruption is causally related to poor neurological outcome, and that Naloxone prevents both the disruption, and the neurological dysfunction among those survivors with intact blood-brain barrier.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Blood Pressure; Blood-Brain Barrier; Body Temperature; Brain; Humans; Infant, Newborn; Intracranial Pressure; Naloxone; Neurologic Examination; Reference Values; Resuscitation; Sheep

The Neonatal Resuscitation Programme, sponsored by the Canadian Heart and Stroke Foundation and by the American Heart Association, is a structured learning package and workshop for all individuals who provide resuscitation for newborns. The emphasis is on rapid, decisive action using algorithms based on clearly stated criteria. This CME article serves as an introduction to the NRP and discusses some of the new guidelines regarding concurrent ventilation and chest compressions, tracheal suction for meconium and the use of medications. The author encourages readers who find this article helpful to register in an accredited NRP course to receive the extensive illustrated textbook and to benefit from the "hands-on" nature of the workshop.

Topics: Asphyxia Neonatorum; Body Temperature; Cyanosis; Education, Medical, Continuing; Epinephrine; Heart Rate; Humans; Infant, Newborn; Intubation, Intratracheal; Laryngoscopy; Masks; Meconium; Naloxone; Plasma Substitutes; Positive-Pressure Respiration; Practice Guidelines as Topic; Respiration; Respiration, Artificial; Resuscitation; Suction

Topics: Animals; Asphyxia Neonatorum; Cerebrovascular Circulation; Humans; Infant, Newborn; Naloxone

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Topics: Acidosis; Animals; Animals, Newborn; Asphyxia Neonatorum; Bradycardia; Cardiac Output, Low; Disease Models, Animal; Endorphins; Heart Ventricles; Humans; Hydrochloric Acid; Infant, Newborn; Naloxone; Sheep; Stroke Volume

Previous studies have shown that severe neonatal asphyxia and hypoxia lead to a redistribution of cerebral blood flow (CBF) with a preferential perfusion of the brain stem. The present study shows that this mechanism is operative also in moderately hypoxic newborn lambs (oxygen saturation 32.7-65.2) with a threshold of about 25% reduction in oxygen saturation. In hypoxia, the mean increase in total CBF, brain stem and telencephalic blood flow was 44%, 68% and 43%, respectively (five lambs). We found that naloxone reverses this redistribution, and that the effects of naloxone on telencephalic perfusion and cerebral metabolic rate of oxygen (CMRO2) were proportional. In hypoxia + naloxone (1 mg/kg), a further increase in total CBF, brain stem, and telencephalic blood flow of 30%, 7% and 31% was noted. We therefore suggest that the redistribution of CBF is an important opioid-mediated homeostatic mechanism, which diminishes the metabolic requirements of the newer part of the brain in hypoxia and allows a preferential perfusion of the vital structures of the brain stem.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Brain Stem; Cerebrovascular Circulation; Endorphins; Homeostasis; Hypoxia, Brain; Naloxone; Receptors, Opioid; Sheep

Recent reports suggest that naloxone, an opiate antagonist, may adversely affect the asphyxiated fetus. We found that naloxone exacerbated hypoxic-ischemic brain injury in the 7-day-old rat subjected to unilateral common carotid artery ligation and hypoxia. Moreover, there was no amelioration of systemic acidosis or brain edema in naloxone-treated animals compared to animals treated with saline solution. High doses of naloxone may reduce the resistance of the fetus to hypoxic stress.

Topics: Animals; Asphyxia Neonatorum; Brain; Female; Humans; Infant, Newborn; Male; Naloxone; Rats; Rats, Inbred Strains; Sodium Chloride

Pregnant near-term rabbits were given an intravenous dose of saline or the opiate antagonist naloxone and then asphyxiated. The fetuses were delivered by cesarean section and evaluated for respiration, color, muscle tone, response to stimulation, and general activity at 1, 3, 5, 10, 15, and 30 minutes of age. The naloxone-treated pups had significantly better scores during the first 15 minutes after birth than the saline-treated pups. Naloxone did not adversely affect the scores of nonasphyxiated pups. These data suggest that endogenous opiates worsen the neonatal depression caused by intrauterine asphyxia and that this effect can be reversed by naloxone.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Depression; Disease Models, Animal; Humans; Infant, Newborn; Naloxone; Rabbits

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Endorphins; Female; Humans; Infant, Newborn; Naloxone; Pregnancy; Rabbits

This case report of fetal asphyxia and related studies suggest that fetal endorphins play a role in fetal pain tolerance and cardiovascular asphyctic responses. Elevated fetal endorphin levels may, like narcotics, produce abnormally "flat" fetal heart rate patterns intrapartum and fetal tolerance to pain. Although naloxone hydrochloride was used with some success to return flat fetal heart rate patterns to "normal," the unopposed antagonism of fetal endorphins by naloxone in times of fetal distress may be detrimental.

Topics: Adult; Asphyxia Neonatorum; Endorphins; Female; Fetal Distress; Fetal Heart; Heart Rate; Humans; Infant, Newborn; Injections, Intramuscular; Naloxone; Pregnancy

Naloxone, a specific opiate antagonist with no agonist properties, in doses of 0.4 and 4.0 mg/kg was found to markedly reduce the duration of primary apnea in asphyxiated newborn rabbits. There was no effect on the duration of the hyperpneic phase (time to primary apnea) or on survival time (time to last gasp). It is suggested that endogenous opiate-like peptides are released during asphyxia and are the major factor in the suppression of medullary inspiratory neuronal discharge during primary apnea.

Topics: Animals; Apnea; Asphyxia Neonatorum; Humans; Infant, Newborn; Naloxone; Rabbits; Respiration; Sodium Chloride

The obstetrical problematic of intrapartal infant death following administration of Dolantin were discussed with the help of both of the cases described in the article by Riegel et al. At the same time, the question of analgesia during delivery with pethidine in combination with a respiratory depressant antidote was examined. Lorfalgyl, according to current opinion, cannot compensate the antidepressive effect of pethidine. Instead, the application of pure pethidine is recommended for obstetric analgesia in the first stage of labor. Today, naloxone used as antidote is particularly suitable before delivery or can be injected into the umbilical vein of the child after delivery. A plan of treatment for pathidine therapy during the first stage of labor in combination with the antidepressant was suggested.

Topics: Anesthesia, Obstetrical; Asphyxia Neonatorum; Depression, Chemical; Female; Fetal Heart; Humans; Infant, Newborn; Meperidine; Naloxone; Pregnancy; Respiration

Topics: Analgesia; Analgesics; Anesthesia, Obstetrical; Asphyxia Neonatorum; Female; Fetus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Meperidine; Morphine; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Oxymorphone; Pregnancy; Substance-Related Disorders

Topics: Asphyxia Neonatorum; Female; Fetus; Humans; Infant, Newborn; Injections, Intravenous; Maternal-Fetal Exchange; Naloxone; Narcotics; Poisoning; Pregnancy; Respiratory Insufficiency; Substance-Related Disorders