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Naloxone for opiate-exposed newborn infants

  1. Thirimon Moe-Byrne1,
  2. Jennifer VE Brown1,
  3. William McGuire2,*

Editorial Group: Cochrane Neonatal Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 31 JUL 2012

DOI: 10.1002/14651858.CD003483.pub2


How to Cite

Moe-Byrne T, Brown JVE, McGuire W. Naloxone for opiate-exposed newborn infants. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003483. DOI: 10.1002/14651858.CD003483.pub2.

Author Information

  1. 1

    Centre for Reviews and Dissemination, University of York, York, UK

  2. 2

    Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK

*William McGuire, Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK. William.McGuire@hyms.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Bonta 1979

MethodsRandomised controlled trial


Participants43 normal term newborn infants whose mothers had received routine narcotic analgesia within 6 hours of delivery. Infants delivered in breech presentation or by Caesarean section, and infants with Apgar score less than 6 at 1 minute, were excluded


Interventions1. Intramuscular naloxone (0.02 mg/kg body weight): n = 22
2. Placebo (normal saline): n = 21


OutcomesApgar score at 5 minutes, capillary blood gas values at 1, 2 and 4 hours of life, neurobehavioural assessment at 1, 4, and 24 hours


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom sequence generated in pharmacy to produce sequentially numbered ampoules containing either naloxone or placebo

Allocation concealment (selection bias)Low riskSequentially numbered ampoules (unable to predict whether naloxone or placebo)

Blinding (performance bias and detection bias)
All outcomes
Low riskOutcome assessors blinded (placebo-controlled)

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete ascertainment of outcomes

Brice 1979a

MethodsRandomised controlled trial


Participants50 term newborn infants whose mothers had received intramuscular pethidine within 4 hours of delivery


Interventions1. Naloxone administered via the umbilical vein (0.01 or 0.02 mg/kg body weight): n = 26

2. No drug: n = 24


OutcomesTime to sustained respiration, expired carbon dioxide output and alveolar ventilation up to 24 hours of life, Brazelton Neonatal Behavioral Assessment Score and Scanlon Behavioral Score within the first 24 hours of life


NotesBlinding of outcome measurement for Scanlon Behavioral Score only


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
Low riskAssessors blinded for Scanlon developmental assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Dick 1978a

MethodsRandomised controlled trial


Participants40 newborn infants, of unspecified gestation, whose mothers had been given intravenous pethidine in labour


Interventions1. Naloxone, via the umbilical vein (0.02 mg/kg): n = 10

2. Naloxone (0.03 mg/kg): n = 10

3. Naloxone (0.04 mg/kg): n = 10

4. No drug: n = 10


OutcomesCapillary blood gas pH and partial pressure of carbon dioxide and of oxygen at 1, 5, 10, 30, 60 and 120 minutes of life


NotesReceived naloxone immediately after birth


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Dick 1978b

MethodsRandomised controlled trial


Participants30 newborn infants, of unspecified gestation, whose mothers had been given intravenous pethidine in labour


Interventions1. Naloxone, via the umbilical vein (either 0.04 mg/kg or 0.04 mg total): n = 20
2. Placebo: n = 10


OutcomesCapillary blood gas pH, partial pressure of carbon dioxide and of oxygen, and calculated base excess at 1, 5, 10, 30, 60 and 120 minutes of life


NotesReceived naloxone immediately after birth


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
Low risk"Double-blind"

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Evans 1976

MethodsRandomised controlled trial


Participants44 newborn infants, of gestation 38-42 weeks, delivered spontaneously or by forceps, whose mothers had been given pethidine in labour


Interventions1. Naloxone administered via the umbilical vein at 1 minute of age (0.04 mg total): n = 20

2. No drug: n = 24


OutcomesTime to first breath, time to onset of sustained respiration, Apgar score at 5 minutes, alveolar carbon dioxide tension, alveolar ventilation, and ventilation rate at 10 minutes and 30 minutes of life


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Gerhardt 1977

MethodsRandomised controlled trial


Participants20 term newborn infants, born vaginally, whose mothers had received intravenous pethidine within 3 hours of delivery


Interventions1. Intramuscular naloxone at 30 minutes of life (0.01 mg/kg): n = 14

2. Placebo: n = 10


OutcomesRespiratory rate, tidal volume, minute ventilation, end-tidal carbon dioxide tension, and the ventilatory response to inhalation of 4% carbon dioxide


NotesNaloxone given at 30 minutes of age


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Random number" selection

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
Unclear risk"Placebo-controlled", but unclear whether investigators aware of which group infants allocated to

Incomplete outcome data (attrition bias)
All outcomes
Low riskNear-complete follow-up but 2 infants in each group were excluded post-randomisation because "lung compliance values changed more than 25% between the two determinations"

Welles 1984

MethodsRandomised controlled trial


Participants27 newborn infants, of gestation 38-42 weeks, whose mothers had received pethidine during labour. Infants with Apgar scores less than 8 at 1 minute, or less than 9 at 5 minutes were not eligible for inclusion


Interventions1. Naloxone at about 1 hour of age (0.1 mg total): n = 14

2. Placebo (normal saline): n = 13


OutcomesBrazelton Neonatal Behavioral Assessment Score at 12-24 hours of life and after a further 48 hours, and the Broussard Neonatal Perception Inventory after the second Brazelton assessment


NotesThe route of administration of naloxone and placebo is presumed to be intramuscular, but this is not stated explicitly in the paper


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding (performance bias and detection bias)
All outcomes
Low riskOutcome assessor blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Wiener 1977a

MethodsRandomised controlled trial


Participants28 newborn infants, of gestation 38-42 weeks, whose mothers had been given pethidine in labour


Interventions1. Naloxone administered via the umbilical vein at 1 minute of age (0.04 mg total): n = 10

2. Normal saline placebo: n = 18


OutcomesAlveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour, and habituation to a sound-specific stimulus up to 48 hours of life


NotesNaloxone or normal saline were "chosen blind at random"


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom allocation in pharmacy

Allocation concealment (selection bias)Low riskCoded ampoules

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding (placebo-controlled)

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Wiener 1977b

MethodsRandomised controlled trial


Participants30 newborn infants, of gestation 38-42 weeks, whose mothers had been given pethidine in labour


Interventions1. Intramuscular naloxone at 1 minute of age (0.2 mg total): n = 15

2. Intramuscular normal saline placebo: n = 15


OutcomesAlveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour (mean sucking frequencies and pressures, and mean milk consumption), and habituation to a sound-specific stimulus up to 48 hours of life


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom allocation in pharmacy

Allocation concealment (selection bias)Low riskCoded ampoules

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding (placebo-controlled)

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Brice 1979bThis report of pharmacokinetic data in infants who received either intravenous or intramuscular naloxone is unlikely to be a randomised comparison

Martin 1972This report is unlikely to be a randomised controlled trial

 
Comparison 1. Naloxone versus placebo or no drug

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Expired carbon dioxide output (mL/kg/min)3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 At 15 minutes
150Mean Difference (IV, Fixed, 95% CI)1.30 [0.15, 2.45]

    1.2 At 30 minutes
3108Mean Difference (IV, Fixed, 95% CI)0.90 [0.39, 1.40]

    1.3 At 90 minutes
150Mean Difference (IV, Fixed, 95% CI)0.50 [-0.17, 1.17]

    1.4 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)0.86 [0.12, 1.59]

 2 Alveolar carbon dioxide tension (kPa)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 At 10 minutes
144Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.01, -0.19]

    2.2 At 30 minutes
3102Mean Difference (IV, Fixed, 95% CI)-0.87 [-1.16, -0.59]

    2.3 At about 35 minutes
120Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.90, 0.70]

    2.4 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)-0.87 [-1.25, -0.50]

 3 Alveolar ventilation (mL/kg/minute)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 At 10 minutes
144Mean Difference (IV, Fixed, 95% CI)13.0 [-16.88, 42.88]

    3.2 At 15 minutes
150Mean Difference (IV, Fixed, 95% CI)16.0 [-8.53, 40.53]

    3.3 At 30 minutes
4152Mean Difference (IV, Fixed, 95% CI)36.03 [21.92, 50.14]

    3.4 At 90 minutes
150Mean Difference (IV, Fixed, 95% CI)14.0 [-6.30, 34.30]

    3.5 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)55.30 [33.92, 76.69]