Sedation of Mechanically Ventilated Newborn Infants

Publication: 22/11/2010  --
Last review: 31/03/2020  
Next review: 31/03/2023  
Clinical Protocol
CURRENT 
ID: 2322 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2020  

 

This Clinical Protocol is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Sedation of Mechanically Ventilated Newborn Infants

Background

Mechanical ventilation for newborn infants, especially those born less than 28 weeks gestation is commonplace. It is potentially a painful and stressful experience for the infant.

Pain and stress has been shown to increase

  • Heart rate
  • Respiratory rate
  • Blood pressure
  • Oxygen consumption/saturation
  • Intracranial pressure

These changes in turn may cause clinical instability and in turn may lead to complications such as intraventricular haemorrhage (IVH). Historically, pain in neonates has been under recognised. However, awareness is improving. Evidence supporting the routine use of sedation, in particular opioids, is lacking.

Systematic review and metaanalysis has been carried out on the use of opioid sedation versus placebo in this group. There is a wide variation in the studies analysed and therefore the results are difficult to interpret. There were no significant differences found between the 2 groups of babies. There appeared to be an increased time to tolerating enteral feeds in the treatment group and of hypotension in the very preterm treated group. Only one study reported on long term neurodevelopmental outcome. Whilst this showed no significant difference between the groups, clearly more work is needed in this area.

Sedation with benzodiazepines is increasingly used for sedation when morphine alone is inadequate for relief of stress/discomfort. Studies have shown it to increase sedation but one study raised concerns over increased rates of intraventricular haemorrhage.

Back to top

MORPHINE

Indications Morphine infusion for sedation and analgesia for mechanically ventilated infants should be considered when

  • an infant is expected to be ventilated for longer than 24 hours
  • a ventilated infant is judged to be in pain, as measured by a validated pain score

It is not necessary to routinely sedate all ventilated infants All infants in neonatal intensive care should have their pain and distress measured routinely with a validated pain score.

Dose

  • Starting loading dose 100 micrograms/kg intravenous infusion (i.v.i.) over 1 hour for a total of 1 hour only.
  • Continue with an i.v.i. of 10-20 micrograms/kg/hr
  • Morphine i.v.i. may be increased if the baby is judged to be in pain up to a maximum of 40 micrograms/kg/hour.
  • If pain /distress is controlled with this dose consider reducing infusion rate
  • If pain is not controlled on morphine infusion or the baby has an unusual painful condition add paracetamol (see formulary) then consider referral to pain team for specialist advice

Cautions

  • Infants less than 26 weeks: It is not always necessary to sedate these infants. If considered necessary to use sedation in these infants it should be used with caution due to the risk of hypotension. The lowest appropriate dose should be used. If hypotension occurs consider reducing the morphine infusion.
  • Pre-existing hypotension is exacerbated by morphine infusion and therefore morphine should only be used if absolutely necessary.

Ceasing morphine infusions
As with older children and adults neonates can become tolerant to morphine.

  • If an infant has had less than 1 weeks treatment with morphine it can be turned off without weaning.
  • If an infant has received 7-14 days sedation the infusion can be halved every 24 hours until infusion is running at 10micrograms/kg/hr then stopped. Infants should always be monitored for signs of withdrawal even after short periods of morphine treatment.
  • If treatment has continued for more than 2 weeks weaning should be considered. Withdrawal symptoms are more likely to occur when high doses or a prolonged duration of sedation has been used.
  • If morphine is being weaned symptoms of withdrawal must be measured using the Leeds opiate withdrawal scoring sheet.
  • Oral bioavailability of morphine is approximately 50%.

To convert an intravenous infusion does to an oral dose,  multiply the total daily intravenous dose by 2 to obtain the total daily oral dose. Divide this by 6 for 4 hourly dosing.

  • Morphine should be weaned according to the Neonatal Abstinence Syndrome Guideline
    • Calculate average score for previous 24 hours (omitting highest and lowest scores). Adjust dose depending on average score as follows:
      8+ same dose or increase by 10%
      6-8 decrease dose by 10% 24 hrly
      3-5 decrease dose by 25% 24 hrly
      0-2 decrease dose by 50% 24 hrly

These are only guidelines; each infant is unique and MUST be treated according to its own need. Some infants may become dependent more quickly than others, and vice versa.

Back to top

MIDAZOLAM

Indications Midazolam infusion for sedation and analgesia for mechanically ventilated infants should be considered when

  • an infant is already on a morphine infusion
  • increasing the morphine infusion dose has not achieved adequate sedation
  • the ventilated infant is judged to be in pain or distress, as measured by a validated pain score

It is not necessary to routinely sedate all ventilated infants All infants in neonatal intensive care MUST have their pain and distress measured routinely with a validated pain score.

Dose

  • No loading dose is needed
  • Continuous intravenous infusion
    • 31+6 weeks gestation or less: 30 micrograms/kg/hour adjusted according to response
    • 32+0weeks gestation or more: 60 micrograms/kg/hour adjusted according to response
    • Doses may be gradually increased up to 150 micrograms/kg/hour.
    • Note this dosing regime is different to the use of midazolam as an anticonvulsant
  • If pain /distress is controlled with this dose consider reducing infusion rate

Cautions

  • Avoid prolonged use and abrupt withdrawal as tolerance can develop.

Ceasing midazolam infusions
As with older children and adults neonates can become tolerant to midazolam. It is unclear from the literature how long it takes to become tolerant but the suggestion is that it can happen quickly.

  • If an infant has had less than 5 days treatment with midazolam it can be turned off without weaning.
  • If an infant has received more than 5 days of midazolam the dose should be reduced by
    • 25% initially then
    • By approximately 10% every 12 hours depending on patient response. These are only guidelines; each infant is unique and MUST be treated according to its own need. Some infants may become dependent more quickly than others, and vice versa.

Clonidine

To be considered for use when an infant develops a tolerance to strong opioids, such as morphine or oxycodone.

Clonidine should be used with caution as there is limited data regarding the use in preterm neonates. It should only be used in neonates >2kg and >32 weeks gestation.

Dose

  • 32 to 36 weeks corrected gestation or less than 4 weeks of age- Start at 0.5 micrograms/kg/hr., increase to 1 microgram/kg/hr if necessary.
  • Infants > 36 weeks corrected gestation and > 4 weeks of age- Start at 0.5 micrograms/kg/hr., increase by 0.5 microgram/kg/hr increments up to 2 micrograms/ kg/hr. if necessary.

Cautions

Blood pressure and pulse must be monitored on initiating treatment and after each dosage increase.

Ceasing clonidine infusions

  • If a patient is weaning from other opiate infusions wean the clonidine last as clonidine can help with opiate withdrawal.
  • If used for less than 7 days clonidine can be halved and then stopped after 12-24 hours.
  • If used for more than 7 days reduce daily over at least 5 days.
  • Blood pressure must be monitored at least every 6 hours when weaning clonidine due to the risk of rebound hypertension.

These are only guidelines; each infant is unique and MUST be treated according to its own need. Some infants may become dependent more quickly than others, and vice versa.

Provenance

Record: 2322
Objective:
  • To achieve safe and adequate sedation in the newborn infants
  • To minimise side effects of sedation
  • To amalgamate the practice of sedation for ventilation across the newborn service.
Clinical condition:

Mechanically ventilated newborns

Target patient group: Neonates
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

  1. Hall RW, Shbarou RM. Drugs of choice for sedation and analgesia in the neonatal ICU. Clin Perinatol. 2009 Mar;36(1):15-26.
  2. van Dijk M et al. The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants. Pain 84 (2000) 367±377
  3. Anand KJS for the NEOPAIN Investigators Group. Effects Of Morphine Analgesia In Ventilated Preterm Infants: Primary Outcomes Form The NEOPAIN Randomised Trial. Lancet 2004;363:9422
  4. Bellù R, de Waal K, Zanini R Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2010 Apr 13. [Epub ahead of print]
  5. Bellù R, de Waal KA, Zanini R. Opioids for neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004212.
  6. Guy’s and St. Thomas’, King’s College and University Lewisham Hospitals. Paediatric Formulary 7th Edition, 2005.
  7. M Bennett, H King, A Wignell, C Silvestre. Sedation and analgesia withdrawal on PICU. Nottingham Children’s Hospital. Online accessed March 2020. https://www.nuh.nhs.uk/download.cfm?doc=docm93jijm4n4534.pdf&ver=8801

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 2.0

Related information

Not supplied

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.