SWC on aEEG in Post-surgical Neonates on Morphine and Midazolam
Condition: Neurology; Newborn; Analgesia; Sedation; Surgery
Study type: Observational

Summary: 
      Objectives: Sleep characteristics have been used for prediction of neuro-developmental
      outcome. The aim of our study was to evaluate the influence of morphine and midazolam on the
      development of SWC in newborns > 32 weeks' gestational age after major non-cardiac surgery.

      Study design: This prospective aEEG study included infants > 32+0 weeks' gestation admitted
      to the Neonatal Intensive Care Unit at The Royal Children's Hospital in Melbourne who were
      undergoing major non-cardiac surgery. The BrainZ Monitor (BRM2, Version 8.0, BrainZ
      Instruments, New Zealand) was applied post-operatively. The time of onset and quality of SWC
      and the maximum levels of morphine and midazolam as predictors of time to SWC were then
      assessed.

      Results: Forty-seven eligible infants were included. Emergence of SWC was observed at a mean
      of 13 hours post-surgery. The maximum dose of morphine or midazolam was not predictive of
      time to SWC.

      Conclusions: Despite high doses of continuous infusions of morphine and midazolam SWC was
      observed on aEEG in neonates > 32 weeks' gestational age soon after major non-cardiac
      surgery. The main type of aEEG background pattern was not affected by the maximum dose of
      either morphine or midazolam. Abnormalities in aEEG in post-surgical patients are not always
      drug related.
    

Detailed description: 
      There is increasing evidence of neurodevelopmental impairment in survivors of non-cardiac
      surgery (1,2,3,4). Psychosocial maldevelopment and emotional problems have been reported to
      occur more commonly in children with repaired abdominal wall defects, and routine assessment
      of survivors of non-cardiac surgery has been recommended throughout later childhood (5,6).
      These reports also emphasize the need for further study of children who undergo major
      non-cardiac surgery in the neonatal period so that the neurological substrate for subsequent
      abnormal neurodevelopment can be better understood.

      Amplitude-integrated electroencephalography (aEEG) is being increasingly used to monitor
      cerebral activity at the bedside in the neonatal intensive care unit (NICU) (7). Widely used
      scoring systems for aEEG incorporate consideration of background activity, presence of sleep
      wake cycling (SWC) and seizures (8). There are several aEEG reports indicating that analgesic
      and sedative agents routinely used in neonates suppress amplitude and therefore alter
      background activity (9,10,11,12,13) and it is believed that interpretation of aEEG in sedated
      patients is unreliable. Most of these studies have been conducted investigating pre-term
      infants or infants with hypoxic-ischaemic encephalopathy.

      Sleep characteristics have been reported as predictors of neurodevelopmental outcome
      (14,15,16) and there is general agreement that indices of stability in SWC over time are
      positively correlated with improved clinical outcomes. SWC is described as smooth sinusoidal
      variations, mostly in the minimum amplitude. Phases with broader bandwidth represent
      discontinuous background activity during quiet sleep, whilst the phases with narrower
      bandwidth correspond to the more continuous activity during wakefulness and active sleep. SWC
      develops with increasing maturation of the child. From 31 to 32 weeks' gestational age, quiet
      sleep periods are clearly discernable in the aEEG trace as distinct periods with increased
      bandwidth. At term-equivalent age these periods represent trace alternant
      electroencephalography (EEG) patterns (17). The average duration of quiet sleep periods is 24
      to 28 minutes for infants between 32 and 36 weeks' gestational age. These periods are
      slightly longer at night but are otherwise relatively stable and are not affected by
      incubator covers or developmental care interventions (18). The internal trigger for SWC is
      located in the brainstem and the presence of SWC in healthy term newborns is considered a
      sign of brain stem integrity (19,20). In newborns with hypoxic-ischemic encephalopathy sleep
      organization can be altered and the presence of SWC on aEEG is considered to be a good
      prognostic sign (21). Timing of onset of SWC has been shown to predict neurodevelopmental
      outcome based on whether the SWC returns before or after 36 hours of a presumed hypoxic
      insult (22).

      There are several reports indicating that analgesic and sedative agents routinely used in
      neonates may lead to amplitude depression on aEEG. However, to our knowledge there are
      currently no reports of aEEG studies and SWC in newborn infants requiring major non-cardiac
      surgery during the neonatal period. Studying background activity and emergence of SWC on aEEG
      in neonates requiring major non-cardiac surgery may provide useful information about the
      relationship of analgesia and sedation and cerebral function in the post-operative infant.
      Knowledge of the effects of drugs that may modify cerebral activity is important to the
      interpretation of aEEG's in critically ill neonates requiring high doses of analgesics and
      sedatives.

      The aim of this prospective observational aEEG study was to describe the influence of
      analgesic and sedative medication on background pattern and the development of SWC in newborn
      infants born > 32 weeks' gestation after major non-cardiac surgery.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        newborns > 32 weeks' gestational age post abdominal surgery