Effects of Midazolam and Morphine on Cerebral Oxygenation and Hemodynamics in Ventilated Premature Infantsvan Alfen-van der Velden A.A.E.M.b · Hopman J.C.W.c · Klaessens J.H.G.M.c · Feuth T.d · Sengers R.C.A.a · Liem K.D.b
aDepartment of Pediatrics, bSubdivision Neonatology and cClinical Physics, dDepartment of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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Background: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. Objectives: 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 (ΔcO2Hb) and deoxyhemoglobin (ΔcHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= ΔcO2Hb – ΔcHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (ΔctHb = ΔcO2Hb + ΔcHHb) represent changes in cerebral blood volume (ΔCBV). Changes in cerebral blood flow velocity (ΔCBFV) 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.
© 2006 S. Karger AG, Basel
- Dyke MP, Kohan R, Evans S: Morphine increases synchronous ventilation in preterm infants. J Paediatr Child Health 1995;31:176–179.
- Jacqz-Aigrain E, Daoud P, Burtin P, Desplanques L, Beaufils F: Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. Lancet 1994;344:646–650.
- Burtin P, Daoud P, Jacqz-Aigrain E, Mussat P, Moriette G: Hypotension with midazolam and fentanyl in the newborn. Lancet 1991;337:1545–1546.
- Van Straaten HL, Rademaker CM, de Vries LS: Comparison of the effect of midazolam or vecuronium on blood pressure and cerebral blood flow velocity in the premature newborn. Dev Pharmacol Ther 1992;19:191–195.
- Ng E, Klinger G, Shah V, Taddio A: Safety of benzodiazepines in newborns. Ann Pharmacother 2002;36:1150–1155.
- Van den Anker JN, Sauer PJJ: The use of midazolam in the preterm neonate. Eur J Pediatr 1992;151:152.
Adams MM, Hahn JS, Benitz WE: A series of neonatal patients with paradoxical seizure-like reactions to bolus intravenous injections of midazolam. Pediatr Res 1997;41:134A.
- Harte GJ, Gray PH, Lee TC, Steer PA, Charles BG: Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates. J Paediatr Child Health 1997;33:335–338.
- Tholl DA, Wager MS, Sajous CH, Myers TF: Morphine use and adverse effects in a neonatal intensive care unit. Am J Hosp Pharm 1994;51:2801–2803.
- Anand KJ, Hall RW, Desai N, Shephard B, Bergqvist LL, Young TE, Boyle EM, Carbajal R, Bhutani VK, Moore MB, Kronsberg SS, Barton BA: Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN Randomised Trial. Lancet 2004;363:1673–1682.
Sabatino G, Quartulli L, Di Fabio S, Ramenghi LA: Hemodynamic effects of intravenous morphine infusion in ventilated preterm babies. Early Hum Dev 1997;27:263–270.
Kollee LA, Schols WA, Peer PGM: Non-invasive blood pressure measurement in the neonate; in Rolfe P (ed): Neonatal Physiological Measurements. Proc 2nd Int Conf Fetal and Neonatal Physiological Measurements, 1986, pp 69–73.
- Jobsis FF: Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977;198:1264–1267.
Van der Sluijs MC, Colier WNJM, Houston RJF, Oeseburg B: A new and highly sensitive continuous wave near infrared spectrophotometer with multiple detectors. Proc SPIE Int Soc Opt Eng 1998; 194:S63– S72.
Wickramasinghe Y, Rolfe P: Modified NIR coefficients taking into account the wavelength dependence of the optical pathlength; in Bancroft J (ed): Newsletter EC Concerted Action Near Infrared Spectroscopy and Imaging of Biological Tissue, 1993;2:5.
- Cooper CE, Elwell CE, Meek JH, Matcher SJ, Wyatt JS, Cope M, Delpy DT: The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy. Pediatr Res 1996;39:32–38.
- Duncan A, Meek JH, Clemence M, Elwell CE, Fallon P, Tyszczuk L, Cope M, Delpy DT: Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy. Pediatr Res 1996;39:889–894.
- Liem KD, Hopman JC, Kollee LA, Oeseburg B: effects of repeated indomethacin administration on cerebral oxygenation and haemodynamics in preterm infants: combined near infrared spectrophotometry and Doppler ultrasound study. Eur J Pediatr 1994;153:504–509.
- Lammertsma AA, Brooks DJ, Beaney RP, Turton DR, Kensett MJ, Heather JD, Marshall J, Jones T: In vivo measurement of regional cerebral haematocrit using positron emission tomography. J Cereb Blood Flow Metab 1984;4:317–322.
- De Wildt SN, Kearns GL, Hop WC, Murry DJ, Abdel-Rahman SM, and van den Anker JN: Pharmacokinetics and metabolism of intravenous midazolam in preterm infants. Clin Pharmacol Ther 2001;70:525–531.
- Perlman JM, Goodman S, Kreusser KL, Volpe JJ: Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome. N Engl J Med 1985;1353–1357.
- Wyatt JS, Cope M, Delpy DT, Richardson CE, Edwards AD, Wray S, Reynolds EO: Quantitation of cerebral blood volume in human infants by near-infrared spectroscopy. J Appl Physiol 1990;68:1086–1091.
- Urlesberger B, Trip K, Ruchti JJI, Kerbl R, Reiterer F, Muller W: Quantification of cyclical fluctuations in cerebral blood volume in healthy infants. Neuropediatrics 1998;29:208–211.
- Recio L, Marin J, Reviriego J, Salaices M, Lopez-Rico M: Effect of morphine on the cat middle cerebral artery. Brain Res 1986;376:262–267.
- Fahnenstich H, Steffan J, Kau N, Bartmann P: Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Crit Care Med 2000;28:836–839.
- Anand KJ, Barton BA, McIntosh N, Lagercrantz H, Pelausa E, Young TE, Vasa R: Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN Trial. Neonatal outcome and prolonged analgesia in neonates. Arch Pediatr Adolesc Med. 1999;153:331–338.
- Burtin P, Jacqz-Aigrain E, Girard P, Lenclen R, Magny JF, Betremieux P, Tehiry C, Desplanques L, Mussat P: Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther 1994;56:615–625.
- Saarenmaa E, Neuvonen PJ, Rosenberg P, Fellman V: Morphine clearance and effects in newborn infants in relation to gestational age. Clin Pharmacol Ther 2000;68:160–166.
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