Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study

被引:2
作者
Valkenburg, Abraham J. [1 ,2 ,3 ]
Goulooze, Sebastiaan C. [4 ]
Breatnach, Cormac, V [5 ]
Mathot, Ron A. A. [6 ]
Tibboel, Dick [2 ,3 ]
van Dijk, Monique [2 ,3 ,7 ]
Knibbe, Catherijne A. J. [4 ,8 ]
Peeters, Mariska Y. M. [8 ]
机构
[1] Erasmus MC, Dept Intens Care, Rotterdam, Netherlands
[2] Erasmus MC, Intens Care, Sophia Childrens Hosp, Rotterdam, Netherlands
[3] Erasmus MC, Dept Pediat Surg, Sophia Childrens Hosp, Rotterdam, Netherlands
[4] Leiden Univ, Leiden Acad Ctr Drug Res, Div Syst Biomed & Pharmacol, Leiden, Netherlands
[5] Our Ladys Childrens Hosp, Dept Anaesthesia & Crit Care Med, Dublin, Ireland
[6] Acad UMC, Dept Pharm, Amsterdam, Netherlands
[7] Erasmus MC, Dept Internal Med, Sect Nursing Sci, Rotterdam, Netherlands
[8] St Antonius Hosp, Dept Clin Pharm, Nieuwegein, Netherlands
关键词
cardiac surgical procedures; down syndrome; intensive care; midazolam; pharmacokinetics; sedation; PAIN; MORPHINE; INFANTS; SCALE;
D O I
10.1097/PCC.0000000000002580
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objectives: To compare the pharmacokinetics and pharmacodynamics of IV midazolam after cardiac surgery between children with and without Down syndrome. Design: Prospective, single-center observational trial. Setting: PICU in a university-affiliated pediatric teaching hospital. Patients: Twenty-one children with Down syndrome and 17 without, 3-36 months, scheduled for cardiac surgery with cardiopulmonary bypass. Interventions: Postoperatively, nurses regularly assessed the children's pain and discomfort with the validated COMFORT-Behavioral scale and Numeric Rating Scale for pain. A loading dose of morphine (100 mu g/kg) was administered after coming off bypass; thereafter, morphine infusion was commenced at 40 mu g/kg/hr. Midazolam was started if COMFORT-Behavioral scale score of greater than 16 and Numeric Rating Scale score of less than 4 (suggestive of undersedation). Plasma midazolam and metabolite concentrations were measured for population pharmacokinetic- and pharmacodynamic analysis using nonlinear mixed effects modeling (NONMEM) (Version VI; GloboMax LLC, Hanover, MD) software. Measurements and Main Results: Twenty-six children (72%) required midazolam postoperatively (15 with Down syndrome and 11 without; p = 1.00). Neither the cumulative midazolam dose (p = 0.61) nor the time elapsed before additional sedation was initiated (p = 0.71), statistically significantly differed between children with and without Down syndrome. Population pharmacokinetic and pharmacodynamics analysis revealed no statistically significant differences between the children with and without Down syndrome. Bodyweight was a significant covariate for the clearance of 1-OH-midazolam to 1-OH-glucuronide (p = 0.003). Pharmacodynamic analysis revealed a marginal effect of the midazolam concentration on the COMFORT-Behavioral score. Conclusions: The majority of children with and without Down syndrome required additional sedation after cardiac surgery. This pharmacokinetic and pharmacodynamic analysis does not provide evidence for different dosing of midazolam in children with Down syndrome after cardiac surgery.
引用
收藏
页码:E259 / E269
页数:11
相关论文
共 25 条
  • [1] Validation of the COMFORT Behavior Scale and the FLACC Scale for Pain Assessment in Chinese Children after Cardiac Surgery
    Bai, Jinbing
    Hsu, Lily
    Tang, Yan
    van Dijk, Monique
    [J]. PAIN MANAGEMENT NURSING, 2012, 13 (01) : 18 - 26
  • [2] Trends in Congenital Heart Defects in Infants With Down Syndrome
    Bergstrom, Sofie
    Carr, Hanna
    Petersson, Gunnar
    Stephansson, Olof
    Bonamy, Anna-Karin Edstedt
    Dahlstrom, Anders
    Halvorsen, Cecilia Pegelow
    Johansson, Stefan
    [J]. PEDIATRICS, 2016, 138 (01)
  • [3] Carnevale Franco A., 2002, Pediatr Crit Care Med, V3, P177, DOI 10.1097/00130478-200204000-00016
  • [4] Reducing Exposure to Opioid and Benzodiazepine Medications for Pediatric Cardiac Intensive Care Patients: A Quality Improvement Project
    Donnellan, Amy
    Sawyer, Jaclyn
    Peach, Anne
    Staveski, Sandra
    Nelson, David P.
    Pratap, J. Nick
    [J]. PEDIATRIC CRITICAL CARE MEDICINE, 2019, 20 (04) : 340 - 349
  • [5] Down JohnL., 1887, SOME MENTAL AFFECTIO
  • [6] Pharmacodynamic Analysis of Morphine Time-to-Remedication Events in Infants and Young Children After Congenital Heart Surgery
    Elkomy, Mohammed H.
    Drover, David R.
    Galinkin, Jeffery L.
    Hammer, Gregory B.
    Glotzbach, Kristi L.
    [J]. CLINICAL PHARMACOKINETICS, 2016, 55 (10) : 1217 - 1226
  • [7] Comparison of morphine requirements for sedation in Down's syndrome and non-Down's patients following paediatric cardiac surgery
    Gakhal, B
    Scott, CS
    MacNab, AJ
    [J]. PAEDIATRIC ANAESTHESIA, 1998, 8 (03): : 229 - 233
  • [8] Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery
    Goot, Benjamin H.
    Kaufman, Jon
    Pan, Zhaoxing
    Bourne, David W. A.
    Hickey, Francis
    Twite, Mark
    Galinkin, Jeffrey
    Christians, Uwe
    Zuk, Jeannie
    da Cruz, Eduardo M.
    [J]. PEDIATRIC CRITICAL CARE MEDICINE, 2018, 19 (05) : 459 - 467
  • [9] Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals
    Harris, Julia
    Ramelet, Anne-Sylvie
    van Dijk, Monique
    Pokorna, Pavla
    Wielenga, Joke
    Tume, Lyvonne
    Tibboel, Dick
    Ista, Erwin
    [J]. INTENSIVE CARE MEDICINE, 2016, 42 (06) : 972 - 986
  • [10] Cardiopulmonary bypass and edema: physiology and pathophysiology
    Hirleman, E.
    Larson, D. F.
    [J]. PERFUSION-UK, 2008, 23 (06): : 311 - 322