Opioid treatment for opioid withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodevelopmental disability. There was low certainty evidence for no difference in days hospitalisation or days treatment. This study did not report adverse events. Opioid versus diazepam: there was a reduction in treatment failure from use of an opioid (RR 0.43, 95% CI 0.23 to 0.80; 2 studies, 86 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study of 34 infants comparing methadone versus diazepam reported no difference in days hospitalisation or days treatment (very low certainty evidence). Adverse events were not reported. Opioid versus phenobarbital: there was a reduction in treatment failure from use of an opioid (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants; moderate certainty evidence). Subgroup analysis found a reduction in treatment failure in trials titrating morphine to ≧ 0.5 mg/kg/day (RR 0.21, 95% CI 0.10 to 0.45; 3 studies, 230 infants), whereas a single study using morphine < 0.5 mg/kg/day reported no difference compared to use of phenobarbital (subgroup difference P = 0.05). Neonatal or infant mortality and neurodevelopmental disability were not reported. A single study (111 infants) of paregoric versus phenobarbital reported seven infants with seizures in the phenobarbital group, whereas no seizures were reported in two studies (170 infants) comparing morphine to phenobarbital. There was no difference in days hospitalisation or days treatment. A single study (96 infants) reported no adverse events in either group. Opioid versus chlorpromazine: there was a reduction in treatment failure from use of morphine versus chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants; moderate certainty evidence). No seizures were reported in either group. There was low certainty evidence for no difference in days treatment. This trial reported no adverse events in either group. None of the included studies reported time to control of NAS. Data for duration and severity of NAS were limited, and we were unable to use these data in quantitative synthesis. AUTHORS' CONCLUSIONS: Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Aggressive intensive care treatment of very elderly patients with tetanus is justified.

Tetanus is now rare in industrialized countries, occurring mainly in elderly patients. To assess whether aggressive therapy of these patients in the intensive care unit is justified, we retrospectively studied all patients with tetanus hospitalized in our institution between 1968 and 1989. Patients over the age of 70 years fared as well as those under 70 years and recovered without sequelae. These results favor aggressive treatment of elderly patients with tetanus in the intensive care unit.

Anesthetic management of conray toxicity.

Conray (meglumine iothalamate), the contrast media frequently used in shuntograms for diagnosing malfunctioning ventriculo-peritoneal shunts, will occasionally cause severe muscular spasms and seizures. In this article, the authors describe anesthetic and critical care management of a case with this complication.

The neonatal narcotic abstinence syndrome: a brief review.

Because substance abuse experts are not available in many institutions, the consulting psychiatrist is required to diagnose and manage conditions such as the neonatal narcotic abstinence syndrome, which is readily recognized and treated. The authors discuss morbidity due to this syndrome in neonates born to narcotic addicted mothers. The clinical usefulness of neonatal narcotic abstinence scales is reviewed, with special reference to their application in treatment. The dosing of various drugs currently in use is also discussed.

[7 years' experience with neonatal tetanus in Yucatan]. / Experiencia de siete años con tétanos neonatal en Yucatán.

Forty-six patients with neonatal tetanus (NT) were studied to identify factors for poor prognosis which could be used to select a therapeutic regimen with intravenous diazepam or neuromuscular blockade (NB) with pancuronium. Nine patients with NT grades II and III were successfully treated with diazepam; none of them died. Of the patients with NT grades IV and V, 27 received diazepam and ten received pancuronium. The mortality rate in these groups was 55% and 100%, respectively. Factors predicting poor prognosis among patients treated with diazepam were apneas (P = 0.01), and an age on admission of seven days or less (P = 0.0002). Patients who received diazepam and died, generally presented a rapidly fatal course (mean of four days); in this group tetanus was the main cause of death (73%). Patients treated with pancuronium survived a comparably longer period (mean = 15.7 days, P = 0.05), but generally died from nosocomial infections (70%, P = 0.04). On the basis of our results we propose that NT grades IV and V with the aforementioned factors for poor prognosis be treated with NB. In hospitals with limited resources and high rates of nosocomial infection, we suggest that NT grades IV and V without such factors initially be managed with diazepam, reserving NB for therapeutic failures. Finally, NT grades I-III may be effectively treated with diazepam alone.

Comparative double-blind trial of mianserin hydrochloride (Organon GB94) and diazepam in patients with depressive illness.

1. The antidepressant action of mianserin was tested in a double-blind clinical trial lasting 6 weeks. Forty-six patients with moderate to severe degrees of depression were treated at random with mianserin or diazepam. Patients who failed to improve by week 3 were taken out of the trial. 2. Mianserin was more effective than diazepam in reducing scores on the Hamilton Rating Scale for depression. Fewer patients allocated to mianserin had to be withdrawn from the trial on account of failure to improve. Mianserin was more effective than diazepam in reducing symptoms of 'retarded depression' and as effective as diazepam in reducing symptoms of 'anxious depression'. 3. Mianserin did not cause any more side-effects than diazepam, very few side-effects being encountered with either drug. 4. The design of this trial on antidepressant drugs is commended on ethical grounds.

Neonatal abstinence syndrome, pharmacotherapy and developmental outcome.

The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmacotherapy for the treatment of withdrawal symptoms. Phenobarbital, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants born to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the neonatal abstinence scoring system. Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paragoric, phenobarbital (titration), phenobarbital (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were defined: paregoric (n = 21); phenobarbital (n = 17); more than one agent (n = 31); and no treatment (n = 16). Data for the phenobarbital loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in group III since diazepam as a single agent was not successful. Results of one way analysis of variance revealed no differences in developmental status between groups (p greater than 0.10, F = 0.25). Scores for all groups were well within the normal range of development.(ABSTRACT TRUNCATED AT 250 WORDS)

Midlatency auditory-evoked potentials in the assessment of sedation in cardiac surgery patients.

OBJECTIVES: Midlatency auditory-evoked potentials (MLAEPs) may provide an objective measure of depth of sedation. The aim of this study was to evaluate MLAEPs for measuring sedation in cardiac surgery patients. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PARTICIPANTS: Twenty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: MLAEPs were obtained at 5 time points: the day before surgery (baseline), 1 hour before surgery, after premedication, postoperatively during deep (Ramsay 6) and moderate (Ramsay 4) sedation, and the day after surgery. MEASUREMENTS AND MAIN RESULTS: The latency of the Nb MLAEP component increased from 44 ms (38-60 ms; median, range) at baseline to 49 ms (41-64 ms) after premedication (p = 0.03) and further to 63 ms (48-80 ms) during deep sedation after surgery (P < 0.01). Although a decreasing clinical level of sedation after rewarming was not associated with a significant change in Nb latency (61 ms [42-78 ms]), the MLAEP NaPa amplitude increased from 0.9 muV (0.4-1.6 microV) to 1.3 muV (0.8-3.9 microV; p = 0.01). Nb latency remained increased the day after surgery (49 ms [37-71 ms]) as compared with baseline (p < 0.01). CONCLUSIONS: MLAEP latencies can reflect subtle changes in auditory perception, while amplitudes seem to change with transition between deep levels of sedation.

Narcotic addiction in the newborn: differences in behavior generated by methadone and heroin.

The nutritive sucking performance of congenitally addicted infants undergoing narcotic withdrawal was used to provide objective measures of adaptive behavior in a series of 50 infants born to mothers addicted either to heroin or methadone. Sucking rates as well as average pressures developed during sucking were significantly reduced for the addicted infants relative to a control group born to normal mothers and a second control group born to toxemic mothers. The subgroup of infants born to methadone-addicted mothers was significantly more depressed with regard to sucking behavior than the infants of heroin-addicted mothers. Furthermore, infants treated with paregoric (an opiate) for symptoms of the narcotic withdrawal syndrome showed significantly less depression of the sucking response than those treated with sedatives such as phenobarbital.

Neonatal narcotic abstinence: Effects of pharmacotherapeutic agents and maternal drug usage on nutritive sucking behavior.

An uncoordinated and ineffectual sucking reflex is a major manifestation of neonatal narcotic abstinence and may have important consequences for the infant's subsequent well being. Measures of nutritive sucking were used to monitor the severity of neonatal narcotic abstinence in a series of infants born to narcotic-dependent mothers who were either attending the methadone clinic or else were "street addicts." In all these infants, sucking measures were significantly reduced relative to normal control subjects. Furthermore, the sucking behavior of infants born to mothers attending the methadone clinic was significantly more depressed than that of infants born to street addicts. In regard to the salutary effects of pharmacotherapy for neonatal narcotic abstinence, infants treated with paregoric approached normal control levels and showed significantly better sucking than those treated with phenobarbital or diazepam. The latter drug practically eliminated all spontaneous nutritive sucking behavior.

Anaesthetic experiences in three sets of conjoined twins in King Chulalongkorn Memorial Hospital.

We describe the anaesthetic management for magnetic resonance image scanning, angiography and surgical operations in three sets of conjoined twins (ischiopagus, throracopagus and pygopagus) in King Chulalongkorn Memorial Hospital during 1996-2002. The anaesthetic technique and associated problems are summarized.

Neonatal seizures associated with narcotic withdrawal.

Among 302 neonates passively addicted to narcotics, 18 had seizures that were attributed to withdrawal. Of those 18 infants, 10 were among the 127 infants exposed to methadone (7.8%), whereas only one of them was among the 83 infants exposed to heroin (1.2%). Generalized motor seizures and myoclonic jerks were the predominant convulsive manifestations. Paregoric was more effective than was diazepam in controlling and preventing these seizures once they occurred. Electroencephalograms were obtained on 13 neonates in the interictal period; 12 of these ECGs were normal. Three infants, two with myoclonic jerks, had paroxysmal brain wave activity at the time of the seizures.