Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.
BACKGROUND
Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants.


OBJECTIVE
To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants.


METHODS
11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design.


RESULTS
Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV.


CONCLUSIONS
Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.
van Alfen-van der Velden
A A E M
AA
Subdivision Neonatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. janvanalfen@wxs.nl
Hopman
J C W
JC
Klaessens
J H G M
JH
Feuth
T
T
Sengers
R C A
RC
Liem
K D
KD
D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D002534:Hypoxia, Brain; D007231:Infant, Newborn; D007234:Infant, Premature; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects*; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000032:analysis; D012121:Respiration, Artificial; D019265:Spectroscopy, Near-Infrared
D006454:Hemoglobins; D006993:Hypnotics and Sedatives; D010108:Oxyhemoglobins; D009020:Morphine; C100003:deoxyhemoglobin; D008874:Midazolam; D010100:Oxygen