naloxone and Apnea

A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed.

Topics: Apnea; Bradycardia; Chlorpromazine; Drug Therapy, Combination; Family; Female; Humans; Infant; Male; Meperidine; Naloxone; Phenothiazines; Promethazine; Urinary Tract Infections

When selecting the appropriate long-acting opioid to treat cancer pain, both analgesic efficacy and safety need consideration. Generally, opioids are well tolerated. However, of opioid-typical adverse events, respiratory depression is especially important because of the risk of a fatal outcome. Although all potent opioid analgesics act via the micro-opioid receptor system, they differ in how they affect respiratory control. Recently, the respiratory effects of fentanyl (1 7 microg/kg) and buprenorphine (0.7-9 microg g/kg) were compared in healthy opioid-naïve volunteers. Fentanyl produced dose-dependent depression of respiration with apnoea at doses > or = 3 microg/kg, while buprenorphine caused depression that levelled at approximately 50% of baseline with doses > or = 2 microg/kg. These findings indicate the occurrence of a ceiling in the respiratory depression induced by buprenorphine but not by fentanyl. Surprisingly few studies have addressed the clinically important ability to reverse the respiratory effects of opioids. A recent assessment of the naloxone dose required to reverse 0.2 mg intravenous buprenorphine-induced respiratory depression in healthy opioid-naïve volunteers, found that the accumulated naloxone dose causing 50% reversal of respiratory depression was 1.20 +/- 0.32 mg/70 kg (given in 30 min); 80% reversal was observed at 2.50 +/- 0.60 mg/70 kg (given in 30 min). At greater buprenorphine doses, full reversal is observed when the duration of naloxone infusion is increased. These findings indicate the need for a continuous rather than bolus administration of naloxone to reverse the respiratory effects of buprenorphine. In conclusion, buprenorphine is more favourable compared with fentanyl in respect to ventilatory control. Buprenorphine causes limited respiratory depression with a ceiling effect at higher doses, while fentanyl causes dose-dependent respiratory depression with apnoea at high dose levels. In the rare instance of respiratory depression, reversal is possible with a sufficient and continuous infusion of naloxone.

Topics: Analgesics, Opioid; Apnea; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Fentanyl; Humans; Naloxone; Narcotic Antagonists; Neoplasms; Pain; Respiratory Insufficiency

Opioid-induced respiratory depression can be partially antagonized in the preBötzinger Complex and Parabrachial Nucleus/Kölliker-Fuse Complex. We hypothesized that additional opioid antagonism in the caudal medullary raphe completely reverses the opioid effect.. In adult ventilated, vagotomized, decerebrate rabbits, we administrated remifentanil intravenously at "analgesic", "apneic", and "very high" doses and determined the reversal with sequential naloxone microinjections into the bilateral Parabrachial Nucleus/Kölliker-Fuse Complex, preBötzinger Complex, and caudal medullary raphe. In separate animals, we injected opioid antagonists into the raphe without intravenous remifentanil.. Sequential naloxone microinjections completely reversed respiratory rate depression from "analgesic" and "apneic" remifentanil, but not "very high" remifentanil concentrations. Antagonist injection into the caudal medullary raphe without remifentanil independently increased respiratory rate.. Opioid-induced respiratory depression results from a combined effect on the respiratory rhythm generator and respiratory drive. The effect in the caudal medullary raphe is complex as we also observed local antagonism of endogenous opioid receptor activation, which has not been described before.

Topics: Analgesics, Opioid; Animals; Apnea; Medulla Oblongata; Naloxone; Narcotic Antagonists; Rabbits; Remifentanil; Respiratory Insufficiency

Opioids suppress breathing through actions in the brainstem, including respiratory-related areas of the dorsolateral pons, which contain multiple phenotypes of respiratory patterned neurons. The discharge identity of dorsolateral pontine neurons that are impacted by opioids is unknown. To address this, single neuronal units were recorded in the dorsolateral pons of arterially perfused in situ rat preparations that were perfused with an apneic concentration of the opioid agonist fentanyl, followed by the opioid antagonist naloxone (NLX). Dorsolateral pontine neurons were categorized based on respiratory-associated discharge patterns, which were differentially affected by fentanyl. Inspiratory neurons and a subset of inspiratory/expiratory phase-spanning neurons were either silenced or had reduced firing frequency during fentanyl-induced apnea, which was reversed upon administration of naloxone. In contrast, the majority of expiratory neurons continued to fire tonically during fentanyl-induced apnea, albeit with reduced firing frequency. In addition, pontine late-inspiratory and postinspiratory neuronal activity were absent from apneustic-like breaths during the transition to fentanyl-induced apnea and the naloxone-mediated transition to recovery. Thus, opioid-induced deficits in respiratory patterning may occur due to reduced activity of pontine inspiratory neurons, whereas apnea occurs with loss of all phasic pontine activity and sustained tonic expiratory neuron activity.

Topics: Analgesics, Opioid; Animals; Apnea; Fentanyl; Naloxone; Neurons; Pons; Rats; Respiration

The role of the different components of the respiratory network in the mediation of opioid-induced respiratory depression is still unclear. We investigated the contribution of the preBötzinger Complex (preBötC) and the neighbouring Bötzinger Complex (BötC) and inspiratory portion of the ventral respiratory group (iVRG) in anesthetized, vagotomized, paralyzed and artificially ventilated adult rabbits making use of bilateral microinjections (30-50 nl) of the μ-opioid receptor agonist [D-Ala

Topics: Analgesics, Opioid; Animals; Apnea; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Medulla Oblongata; Microinjections; Naloxone; Narcotic Antagonists; Neurons; Phrenic Nerve; Rabbits; Receptors, Opioid, mu; Respiratory Center; Respiratory Insufficiency

The supply of unregulated "new psychoactive substances" (NPS) has shown a steady increase over the past six years. This report from the Swedish STRIDA project describes analytically confirmed non-fatal intoxications involving butyrfentanyl (butyrylfentanyl) or 4-fluorobutyrfentanyl (para-fluorobutyrfentanyl), two fentanyl analogues recently introduced as NPS opioids.. Observational case series of consecutive patients with suspected acute NPS exposure and requiring hospital care from all over Sweden.. From May 2014 to January 2015, blood and urine samples were obtained from four intoxication cases involving butyrfentanyl and one case involving 4-fluorobutyrfentanyl (men, 19-30 years) presenting in emergency departments (ED) or intensive care units (ICU). Laboratory analysis of serum and/or urine samples was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during consultations with the Poisons Information Centre and retrieved from medical records.. Of the five patients, two were discharged home from the ED and three were admitted to the ICU, of whom two required intubation and mechanical ventilation. Clinical features included typical opioid symptoms such as unconsciousness, respiratory depression, and apnea. In one case, naloxone successfully countered the effects. All patients were discharged the same or the following day. Butyrfentanyl was detected in two serum (0.6 and 0.9 ng/mL) and three urine (2.0-65.6 ng/mL) samples from three of four cases; three cases also contained fentanyl. In the 4-fluorobutyrfentanyl case, the substance was detected in serum (∼15 ng/mL) and urine (∼10 ng/mL). In four cases, other NPS and/or classical drugs were also detected. Analysis of two "butyrfentanyl" NPS products (nasal spray and powder) brought to hospital by patients showed that the 10-fold more potent fentanyl was the main active ingredient (∼7.5-10-fold higher amount) in both.. Typical and potentially life-threatening opioid toxicity was seen in acute intoxications involving butyrfentanyl, 4F-butyrfentanyl, and fentanyl. The incorrect labelling of butyrfentanyl NPS products which instead mainly contained fentanyl is alarming, given the narrow range between a safe and a lethal dose for opioids.

Topics: Adult; Analgesics, Opioid; Apnea; Chromatography, Liquid; Dose-Response Relationship, Drug; Emergency Service, Hospital; Fentanyl; Humans; Illicit Drugs; Intensive Care Units; Male; Mass Spectrometry; Naloxone; Respiratory Insufficiency; Retrospective Studies; Sweden; Unconsciousness; Young Adult

Topics: Aged; Anesthesia; Anesthetics, Intravenous; Apnea; Humans; Male; Naloxone; Narcotic Antagonists; Piperidines; Remifentanil; Ventriculoperitoneal Shunt

To give new insights into how an infant responded to naloxone, given after acquiring a maternal opiate by recording the breathing pattern directly after birth.. A respiratory recording is presented of an infant during resuscitation in the delivery room after receiving naloxone for respiratory depression, resulting from maternal remifentanyl use.. The infant was born apneic and bradycardic. Normal resuscitation manoeuvres had no effect on the respiratory drive. Directly after administration of naloxone, a tachypneic breathing pattern with sporadic expiratory breaking manoeuvres was observed.. The immediate tachypnoea is most likely a direct effect of the naloxone causing an immediate 'rebound response' after the release of the opiate-induced inhibition of the respiratory drive.

Topics: Analgesics, Opioid; Anesthetics, Intravenous; Apnea; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Naloxone; Narcotic Antagonists; Piperidines; Pregnancy; Remifentanil; Respiratory Rate

Topics: Administration, Oral; Apnea; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Imidazoles; Infant, Newborn; Infusions, Intravenous; Male; Naloxone; Nonprescription Drugs; Risk Assessment; Treatment Outcome

Topics: Analgesics, Opioid; Apnea; Bile Ducts; Humans; Infant; Lung; Magnetic Resonance Imaging; Male; Naloxone; Narcotic Antagonists; Piperidines; Remifentanil; Tomography, X-Ray Computed

A young, healthy adult man exhibited naloxone-reversible, prolonged apnea after a 4-hour infusion of remifentanil, which was used as the opioid component of a general endotracheal anesthetic. Clinical experience and pharmacokinetic simulations indicate that the apnea was clearly atypical.

Topics: Adult; Analgesics, Opioid; Anesthesia, General; Apnea; Craniotomy; Humans; Male; Naloxone; Narcotic Antagonists; Piperidines; Postoperative Complications; Remifentanil; Time Factors

Topics: Adult; Anesthetics, Intravenous; Anesthetics, Local; Apnea; Bupivacaine; Drug Combinations; Humans; Injections, Spinal; Male; Naloxone; Narcotic Antagonists; Oxygen; Positive-Pressure Respiration; Pruritus; Sleep Stages; Sufentanil

To present a case of respiratory arrest following the use of intrathecal sufentanil and bupivacaine for combined spinal-epidural anaesthesia in a healthy labouring parturient.. A 20-yr-old term parturient received 10 micrograms sufentanil and 2.5 mg bupivacaine intrathecally as part of a combined spinal-epidural technique for labour analgesia. She had received no previous analgesics. Twenty-three minutes after the intrathecal injection she became unresponsive and suffered a respiratory arrest. Resuscitation included manual bag/mask ventilation with oxygen and intravenous naloxone.. Respiratory arrest is a rare but potentially life-threatening complication associated with the use of intrathecal opioids for labour analgesia. Vigilance in post-procedure patient monitoring is imperative.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Apnea; Bupivacaine; Female; Humans; Injections, Intravenous; Injections, Spinal; Naloxone; Narcotic Antagonists; Pregnancy; Respiration, Artificial; Resuscitation; Sufentanil

The activation of the laryngeal chemoreflex may be a pathogenic mechanism in apnoea, apparent life threatening events, and SIDS. Infants with apnoea and increased levels of beta-endorphin immunoreactivity in CSF have been successfully treated with naloxone. Beta-endorphin may induce respiratory depression, and naloxone is a beta-endorphin antagonist. We therefore wanted to measure beta-endorphin levels in CSF before and after the chemoreflex induced apnoea. This study includes 13 piglets, 5-10 days of age, treated with and without naloxone. Respiration, blood pressure, and heart rate were monitored. CSF was sampled before and after the laryngeal chemoreflex induced apnoea. We found a shorter duration of apnoea in the piglets which had received naloxone than in those which did not (p = 0.02). The beta-endorphin immunoreactivity levels in CSF increased after apnoea, and the increased levels correlated positively with the duration of the apnoea in the piglets which had not received naloxone (r = 0.94, p = 0.02), but not in those pretreated with naloxone (r = 0.1, p = 0.8). The median amount of beta-endorphin immunoreactivity in CSF after apnoea in the naloxone-treated piglets was not significantly different from that in the non-treated piglets: 615 +/- 589 (n = 7) fmol/ml CSF and 984 +/- 851 (n = 6) fmol/ml CSF, respectively. The beta-endorphin immunoreactivity levels measured before the apnoea were less than 4.3 fmol/ml CSF.. The laryngeal chemoreflex induced apnoea may possible be partly mediated by beta-endorphin.

Topics: Animals; Animals, Newborn; Apnea; beta-Endorphin; Blood Pressure; Bradycardia; Female; Humans; Larynx; Male; Naloxone; Narcotic Antagonists; Radioimmunoassay; Random Allocation; Reflex; Swine; Time Factors

We previously reported that the electrical stimulation of gastrocnemius muscle nerve afferents given at a suprathreshold intensity for C-fiber afferents induces naloxone-reversible reflexive respiratory suppression ('after suppression'). The effects of kainic acid (KA) microinjections into the parabrachial area (nucleus parabrachialis lateralis: NPBL and nucleus parabrachialis medialis: NPBM) on (1) ongoing respiratory activity and (2) the 'after suppression' were studied in chloralose-urethane anesthetized, bivagotomized, paralyzed, and artificially ventilated cats. A large dose of KA (1.91 nmol in 0.1 microliters) microinjected into the unilateral NPBL induced significant long-lasting respiratory facilitation, while a subsequent KA injection into the ipsilateral NPBM induced significant, long-lasting respiratory depression. A small dose of KA (0.48 nmol in 0.1 microliters) into the unilateral NPBL (right side) induced significant respiratory facilitation, and the 'after suppression' effect was eliminated. A small dose into the unilateral NPBM (right side) caused initial transient respiratory facilitation followed by respiratory depression before 'after suppression' was restored. Subsequent KA injections into the NPBL on the other side (left side) significantly augmented respiration. The 'after suppression' effect was again eliminated after an injection of KA into the bilateral NPBL. It was concluded that NPBL may exhibit tonic inhibitory activities on respiration and play a critical role in the 'after suppression' effect, since an injection of KA into the NPBM counteracted both of these effects in the NPBL.

Topics: Animals; Apnea; Carbon Dioxide; Cats; Electric Stimulation; Kainic Acid; Microinjections; Naloxone; Neuromuscular Junction; Phrenic Nerve; Pons; Respiratory System

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.

Topics: Animals; Apnea; Blood Pressure; Brain; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Antagonism; Electrophysiology; Female; Humans; Maternal-Fetal Exchange; Morphine; Naloxone; Pregnancy; Respiration; Sheep

1. Respiratory depressant effects of five drugs of the fentanyl series have been studied in anaesthetised rats. 2. The potency ratios of the fentanyl drugs to produce apnea and depress minute volume were dissimilar. Further, in vivo naloxone pA2 values were identical for blockade of apnea for the fentanyl drugs but different for antagonism of minute volume. 3. Differences in agonist potency and in naloxone pA2 values were also seen in vagotomised rats where only depression of minute volume is observed. 4. The data suggests that multiple receptor interactions are involved in the respiratory depressant effects of these drugs; the apnea response is primarily mediated through peripheral mu receptors but minute volume depression involves both mu receptors and non-mu sites.

Topics: Alfentanil; Anesthesia; Animals; Apnea; Blood Gas Analysis; Fentanyl; Hemodynamics; In Vitro Techniques; Injections, Intraventricular; Male; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Respiration; Sufentanil; Vagotomy

Milk from breast or baby formula is the exclusive source of nutrition for newborn infants. Short chain opioid peptides such as beta-casomorphins have been isolated from breast milk as well as baby formula. These biologically active peptides are absorbed from the gastrointestinal tract. In infants predisposed to respiratory apnea because of abnormal autonomic nervous system development and respiratory control mechanisms, opioid peptides derived from milk might be one of the etiological factors for sudden infant death syndrome and near miss sudden infant death syndrome.

Topics: Animals; Apnea; Blood-Brain Barrier; Digestive System; Endorphins; Humans; Infant; Infant, Newborn; Milk; Milk, Human; Models, Biological; Naloxone; Respiration; Sudden Infant Death

We investigated the hypothesis that ketamine-induced respiratory depression might be mediated through the opiate system that can be eliminated by naloxone. The steady-state respiratory responses to i.v. ketamine (2 mg.ml-1.kg-1) and their antagonism by naloxone (0.4 mg.ml-1.kg-1) were studied in anesthetized, paralyzed, vagotomized, and artificially ventilated cats. We found that ketamine depressed central respiratory output, assessed from the phrenic nerve electroneurogram, leading to apneustic breathing, which was not antagonized by naloxone. The apneustic respiratory depression by ketamine was thus mediated through mechanism other than the opiate system.

Topics: Animals; Apnea; Cats; Ketamine; Naloxone; Receptors, Opioid; Respiration

The reflex effect elicited by mechanical stimulation of the glottis has been studied in dogs. The three components of the response--sudden apnea, constriction of the glottis and bradycardia--were modified by naloxone, although not in the same degree. These results suggest the existence of opioid interneurons between laryngeal afferent fibers and central inspiratory neurons.

Topics: Animals; Apnea; Carbon Dioxide; Dogs; Glottis; Heart Rate; Naloxone; Physical Stimulation; Receptors, Opioid; Respiration

Cerebrospinal fluid (CSF) beta-endorphin levels were determined in 16 patients with infant apnea syndrome and 34 control patients. A statistically significant difference (P less than or equal to .0001) was found with the infant apnea syndrome patients having beta-endorphin levels of 14.7 +/- 1.2 pmol/L (mean +/- SE) and the controls having levels of 6.9 +/- 0.6 pmol/L (mean +/- SE). To test whether these elevated CSF beta-endorphin levels were the result or the possible cause of the apneas, three patients with infant apnea syndrome and abnormal CSF beta-endorphin levels participated in a study to determine whether a continuous low-dose infusion (10 micrograms/kg/h) of the narcotic antagonist naloxone would reduce the occurrence of apneas and respiratory pauses during all-night polysomnogram recordings. A fourth patient with documented apneas but normal CSF beta-endorphin levels was also studied while on a regimen of naloxone. In the patients with infant apnea syndrome and abnormal CSF beta-endorphin levels, a significant (P less than or equal to .05) reduction in apneas and respiratory pauses occurred during naloxone infusion. There was no change in the occurrence of apneas or respiratory pauses during naloxone infusion in the patient with normal CSF endorphin levels. Abnormal CSF levels of endorphins may play a role in apneas of infancy and may be amenable to therapy with narcotic antagonists.

Topics: Apnea; Drug Evaluation; Endorphins; Female; Humans; Infant; Male; Naloxone; Spinal Puncture; Sudden Infant Death

The apneic laryngeal chemoreflex (QRL), elicited by water on the vocal cords and by mechanical stimulation (MRL) has been compared in dog. Both stimuli cause apnea, bradycardia, hypotension and constriction of the glottis. In QRL apnea predominates white in MRL bradycardia is more intense. All the components of the response decrease with naloxone at a 400 micrograms X kg-1 doses, suggesting that the reflex inhibition depends on endogenous opioids located in the respiratory centre.

Topics: Animals; Apnea; Bradycardia; Dogs; Hypotension; Larynx; Naloxone; Physical Stimulation; Reflex

Somatostatin (SRIF) (6 nmol) given intracisternally (i.c.) into the alpha-chloralose anaesthetized rat has recently been shown to cause apnoea with a latency of 5-10 minutes (Kalia et al. 1984a). The apnoea produced by SRIF is very rapid, irreversible and leads to the death of the animal. In view of the existence of SRIF nerve cell bodies and terminals in medullary respiratory nuclei such as the ventral and ventrolateral subnuclei of the nucleus of the tractus solitarius (nTS) (Kalia et al. 1984b, Johanson et al. 1984), we have proposed the existence of somatostatinergic mechanisms in the respiratory nuclei of the medulla oblongata involved in mediating apnoeic conditions (Kalia et al. 1984a). In the present study, we have analysed whether the SRIF induced apnoea could be counteracted by a previous i.c. administration of the highly selective alpha 2-adreno-receptor blocking agent RX 781094 (2-(2-(I,4 benzodioxanyl]2-imi-dazoline HCl) (Doxey et al. 1983), or an opiate receptor blocking agent such as naloxone. Thus, both alpha 2-adrenoreceptor agonists and opiates induce respiratory depression, and opiates in high doses cause apnoea (Bolme et al. 1974, Hassen et al. 1982, Sitsen et al. 1982). In addition, catecholamine (CA) and enkephalin immuno-reactive nerve terminal networks exist in high densities within the nucleus tractus solitarius (nTS) of the medulla oblongata and may therefore interact with somatostatin nerve terminals in regulation of respiratory activity (Kalia et al. 1984b).

Topics: Animals; Apnea; Brain; Cisterna Magna; Dioxanes; Idazoxan; Injections; Injections, Intravenous; Male; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Respiration; Somatostatin

Topics: Acute Disease; Adult; Anesthesia, General; Anesthetics; Apnea; Coma; Fentanyl; Humans; Male; Muscle Rigidity; Naloxone; Postoperative Complications; Respiratory Insufficiency; Sufentanil; Time Factors

Topics: Anesthesia, Inhalation; Apnea; Bradycardia; Endorphins; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Naloxone; Postoperative Complications; Pyloric Stenosis

This report describes the use of a naloxone infusion at a rate of 300 micrograms/h to provide constant antagonism of the respiratory depressant effects of a near fatal nor-methadone dose in a 2 year old boy. The terminal half-life for nor-methadone was calculated to be 13.5 h. The results indicate that a single dose of a narcotic antagonist with a short half-life (e.g. naloxone) will probably be inadequate to provide long lasting reversal of the effects of overdoses of long half-life narcotic agonists, and that continuous infusion may be the preferable to repeated bolus doses.

Topics: Apnea; Child, Preschool; Humans; Infusions, Parenteral; Male; Methadone; Naloxone

Topics: Apnea; Clonidine; Coma; Female; Humans; Infant; Naloxone

FK 33-824, a potent enkephalin analogue was administered systemically, 0.5-5 mg/kg to preterm neonatal rabbits. A marked decrease in respiratory frequency as well as irregular breathing and apneic spells was recorded at 5 mg/kg. Tidal volume was not affected. The enkephalin-induced respiratory depression was restored immediately after naloxone (10 mg/kg). Bases on the results it may be speculated upon whether brain stem enkephalin neurons are involved in the pathogenesis of neonatal transient apnea and irregular breathing.

Topics: Animals; Animals, Newborn; Apnea; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dose-Response Relationship, Drug; Endorphins; Enkephalins; Female; Naloxone; Pregnancy; Rabbits

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

Topics: Apnea; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levallorphan; Meperidine; Naloxone; Pregnancy

The newborn rabbit responds to acute anoxia, as a result of breathing nitrogen, with successive periods of dyspnoea, primary apnoea, gasping and terminal apnoea. Pethidine caused an increase in the period of primary apnoea and a decrease in the duration and rate of gasping. When nalorphine was combined with pethidine the period of primary apnoea was still increased although the duration and number of gasps were restored to control values. Naloxone, in contrast, acted as a mild respiratory stimulant, shown as a longer phase of dyspnoea. Also it completely abolished the respiratory depression produced by pethidine. Naloxone may be preferable to nalorphine as a drug to reverse the effects of pethidine immediately after birth.

Topics: Animals; Apnea; Dyspnea; Humans; Hypoxia; Infant, Newborn; Meperidine; Morphine; Nalorphine; Naloxone; Nitrogen; Rabbits; Respiration

Topics: Adult; Apnea; Humans; Male; Metoclopramide; Morphine; Naloxone; Preanesthetic Medication