Effects of Morphine and Midazolam on Sleep-Wake Cycling in Amplitude-Integrated Electroencephalography in Post-Surgical Neonates ≥32 Weeks of Gestational Age

Abstract

Background: Studies of children who undergo major non-cardiac surgery in the neonatal period are needed so that subsequent abnormal neurodevelopment can be better understood. Objective:It was the aim of our study to describe the influence of analgesic and sedative medication on the predominant background pattern and the development of sleep-wake cycling (SWC), as measured on amplitude-integrated electroencephalography (aEEG), in newborn infants born ≥32 weeks’ gestation after major non-cardiac surgery. Methods:This prospective 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. Data on morphine and midazolam given after surgery were recorded and the BrainZ Monitor was applied post-operatively. The maximum levels of morphine and midazolam were assessed as predictors of time to aEEG outcomes using linear regression. Results: Forty-seven eligible infants were included. Emergence of SWC was observed at a mean of 13 h after surgery. The maximum dose of morphine or midazolam was not predictive of time to either any or developed SWC. Conclusions: Despite high doses of morphine and midazolam, SWC was observed on aEEG in neonates ≥32 weeks’ gestational age soon after major non-cardiac surgery. The aEEG background pattern was not affected by the maximum dose of either morphine or midazolam.

The power of N‐PASS, aEEG, and BIS in detecting different levels of sedation in neonates: A preliminary study

“…This observation is confirmed by studies investigating the effect of sufentanil, boluses of morphine, and pethidine on preterm infants brain activity . As reported by Olischar et al, sleep‐wake‐cycling were not dramatically affected by increasing use of sedative and analgesic drugs. In general, we observed less sleep cycles but with a longer duration in deeply sedated patients.…”

“…Also, neurophysiological methods react to the administration of sedative and analgesic drugs . Both amplitude‐integrated electroencephalography (aEEG) and Bispectral Index (BIS) are useful tools to monitor the brain activity at the bedside . aEEG is being used for the recognition of maturational features, classification of hypoxic‐ischemic encephalopathy and detection of seizures in preterm and term neonates .…”

Amplitude-Integrated EEG in Newborns With Critical Congenital Heart Disease Predicts Preoperative Brain Magnetic Resonance Imaging Findings

“…Ten of 15 infants (67%) with an abnormal aEEG had no sedative medications during the recording compared to 5 of 9 infants (56%) with a normal aEEG, so medications may not have contributed much to the findings. 25 Our infants also did not have hypoglycemia during the aEEG (Table 1). The infants with an abnormal aEEG may also have been more clinically unstable based on lower Apgar scores and later surgery due to time needed to stabilize them.…”

Pain Assessment and Measurement in Neonates

“…41 Moreover, painful procedures are often followed by prolonged periods of non-rapid-eye-movement sleep, 42 increased wakefulness 43 and agitation, 44 and immature sleep-wake cycling. 45,46 These findings suggest that painful procedures may have prolonged effects on the neurologic and psychosocial development of infants. Behavioral states are also assessed and included in many pain tools as contextual factors of pain.…”