Ilse Ceelie

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (9)58.73 Total impact

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    ABSTRACT: From a previously validated paediatric population pharmacokinetic model, it was derived that non-linear morphine maintenance doses of 5 μg/kg(1.5)/h, with a 50 % dose reduction in neonates with a postnatal age (PNA) <10 days, yield similar morphine and metabolite concentrations across patients younger than 3 years. Compared with traditional dosing, this model-derived dosing regimen yields significantly reduced doses in neonates aged <10 days. Concentration predictions of the population model were prospectively evaluated in postoperative term neonates and infants up to the age of 1 year who received morphine doses according to the model-derived algorithm. The efficacy of this dosing algorithm was evaluated using morphine rescue medication and actual average infusion rates. Morphine and metabolite concentrations were accurately predicted by the paediatric pharmacokinetic morphine model. With regard to efficacy, 5 out of 18 neonates (27.8 %) with a PNA of <10 days needed rescue medication versus 18 of the 20 older patients (90 %) (p = 0.06). The median (interquartile range [IQR]) total morphine rescue dose was 0 (0-20) μg/kg in younger patients versus 193 (19-362) μg/kg in older patients (p = 0.003). The median (IQR) actual average morphine infusion rate was 4.4 (4.0-4.8) μg/kg/h in younger patients versus 14.4 (11.3-23.4) μg/kg/h in older patients (p < 0.001). Morphine paediatric dosing algorithms corrected for pharmacokinetic differences alone yield effective doses that prevent over-dosing for neonates with a PNA <10 days. The fact that many neonates and infants with a PNA ≥10 days still required rescue medication warrants pharmacodynamic studies to further optimize the dosing algorithm for these patients.
    Clinical Pharmacokinetics 02/2014; 53. DOI:10.1007/s40262-014-0135-4 · 5.49 Impact Factor
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    ABSTRACT: Continuous morphine infusion as standard postoperative analgesic therapy in young infants is associated with unwanted adverse effects such as respiratory depression. To determine whether intravenous paracetamol (acetaminophen) would significantly (>30%) reduce morphine requirements in neonates and infants after major surgery. Single-center, randomized, double-blind study conducted in a level 3 pediatric intensive care unit in Rotterdam, The Netherlands. Patients were 71 neonates or infants younger than 1 year undergoing major thoracic (noncardiac) or abdominal surgery between March 2008 and July 2010, with follow-up of 48 hours. All patients received a loading dose of morphine 30 minutes before the end of surgery, followed by continuous morphine or intermittent intravenous paracetamol up to 48 hours postsurgery. Infants in both study groups received morphine (boluses and/or continuous infusion) as rescue medication on the guidance of the validated pain assessment instruments. Primary outcome was cumulative morphine dose (study and rescue dose). Secondary outcomes were pain scores and morphine-related adverse effects. The cumulative median morphine dose in the first 48 hours postoperatively was 121 (interquartile range, 99-264) μg/kg in the paracetamol group (n = 33) and 357 (interquartile range, 220-605) μg/kg in the morphine group (n = 38), P < .001, with a between-group difference that was 66% (95% CI, 34%-109%) lower in the paracetamol group. Pain scores and adverse effects were not significantly different between groups. CONCLUSION AND RELEVANCE: Among infants undergoing major surgery, postoperative use of intermittent intravenous paracetamol compared with continuous morphine resulted in a lower cumulative morphine dose over 48 hours. trialregister.nl Identifier: NTR1438.
    JAMA The Journal of the American Medical Association 01/2013; 309(2):149-54. DOI:10.1001/jama.2012.148050 · 30.39 Impact Factor
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    ABSTRACT: The American Academy of Pediatrics states that ongoing assessment of pain is essential for adequate pain treatment. Pain assessment by means of the COMFORT behaviour scale and the Numeric Rating Scale is therefore an important component of the post-operative pain treatment protocol for neonates and infants in our intensive care unit (ICU). The study aims to determine degrees of staff compliance with this protocol. This retrospective chart review concerned post-surgical patients under the age of 3 years admitted to our level III ICU over a 1-year period. The degree of compliance to the post-operative pain protocol was measured by the frequency of deviations from protocol-dictated drug treatment and pain assessments. Records of 200 children with a median age at surgery of 98 days (interquartile range 6-320) were analysed. A mean of 11 assessments in the first 72  h post-operatively per patient had been recorded. A total of 2103 pain assessments were retrieved, of which 1675 (79.7%) suggested comfort. Compliance to the protocol (reassessment and correct medication) was provided in 66 (15.4%) of the 428 assessments suggesting pain or distress. The post-operative pain protocol applied in our ICU appears to be effective; however, full compliance to the protocol was marginal, possibly leading to under-treatment of pain.
    European journal of pain (London, England) 05/2012; 16(5):760-6. DOI:10.1002/j.1532-2149.2011.00056.x · 3.22 Impact Factor
  • Pediatric Critical Care Medicine 07/2011; 12(4):484-5. DOI:10.1097/PCC.0b013e3182196ec0 · 2.33 Impact Factor
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    ABSTRACT: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Retrospective analysis. Level III pediatric intensive care unit. Two pediatric patients with myopathies and acute liver failure. CLINICAL INVESTIGATIONS: We determined acetaminophen protein adduct levels, in combination with a literature review and systematic evaluation of the cases, using the Roussel Uclaf Causality Assessment Method for drug-induced liver injury to assess causality between recommended acetaminophen dosing and acute liver failure in two children with myopathies. The serum adduct levels were consistent with the values previously reported in children with acute liver injury following acetaminophen overdose. We found four similar cases of acute liver failure in pediatric and adult patients with myopathies following recommended acetaminophen doses in the literature (n = 3) and personal communication (n = 1). The Roussel Uclaf Causality Assessment Method suggested a probable relationship between acetaminophen use at recommended doses and acute liver failure in our myopathy patients. Our data suggest that some patients with myopathies who are receiving recommended doses of acetaminophen may be at increased risk for the development of toxicity resulting in acute liver failure. More studies are needed to corroborate these findings. In the meantime, we would advise physicians to be alert in these patients while taking acetaminophen, especially when critically ill or postoperative.
    Critical care medicine 04/2011; 39(4):678-82. DOI:10.1097/CCM.0b013e318206cc8f · 6.15 Impact Factor
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    ABSTRACT: Minimal access surgery (MAS) in adults is associated with less postoperative pain in comparison to conventional 'open' surgery. It is not known whether this holds true for neonates as well. Less pain would imply that opioid consumption can be reduced, which has a beneficial effect on morbidity. To evaluate potential differences in' opioid consumption between neonates undergoing thoracoscopic minimal access surgery or conventional surgery of esophageal atresia (EA) and congenital diaphragmatic hernia (CDH). In this retrospective cohort study we included two controls for each MAS patient, matched on diagnosis, sex and age at surgery. Opioid dose titration was based on validated pain scores (VAS and COMFORT behaviour), applied by protocol. Cumulative opioid doses at 12, 24, 48 h and 7 days postoperatively were compared between groups with the Mann-Whitney test. The study group consisted of 24 MAS patients (14 EA; 10 CDH). These were matched to 48 control patients (28 EA; 20 CDH). At none of the time points cumulative opioid (median in mg/kg (IQR)) doses significantly differed between MAS patients and controls, both with CDH and EA. For example at 24 h postoperative for CDH patients cumulative opioid doses were [0.84(0.61-1.83) MAS vs. 1.06(0.60-1.36) p=1.0] controls, For EA patients at 24 h the cumulative opioid doses were [0.48(0.30-0.75) MAS vs. 0.49(0.35-0.79) p=0.83] controls. This held true for the postoperative pain scores as well. Minimal access surgery for the repair of esophageal atresia or congenital diaphragmatic hernia is not associated with less cumulative opioid doses.
    European journal of pain (London, England) 12/2010; 15(6):615-20. DOI:10.1016/j.ejpain.2010.11.010 · 3.22 Impact Factor
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    Monique van Dijk · Ilse Ceelie · Dick Tibboel
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    ABSTRACT: Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the effects of analgesic drugs. Here, we review current and promising new endpoints used in pediatric pain assessment studies.
    European Journal of Clinical Pharmacology 11/2010; 67 Suppl 1(S1):61-6. DOI:10.1007/s00228-010-0947-6 · 2.70 Impact Factor
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    ABSTRACT: To evaluate availability and reliability of pediatric drug dosing guidelines in selected formularies for intensive care patients. Most drugs used in the pediatric intensive care unit are prescribed off-label, often on the guidance of limited information from commonly used drug formularies. Availability of dosing information on prescribed drugs in a Dutch intensive care unit from January 1, 2005 to December 31, 2006 was compared among four selected formularies (Micromedex, Lexi-Comp, Drug Formulary for Children, Drug Doses). Reliability of dosing guidelines was assessed by evaluating labeling status and literature data for the three most (midazolam, acetaminophen, and amoxicillin/clavulanic acid) and the three least (bosentan, ketanserin, and iloprost) prescribed drugs. The selected formularies covered 68% to 86% of all 257 prescribed drugs. Guidelines differ widely on daily doses per kilogram, dose description, dosing regimen, and age ranges. For the three most prescribed and one of the least prescribed drugs (bosentan), dosing guidelines adequately reflected labeling status and existing (but scarce) literature. No dosing guidelines were available for iloprost, and only one dosing guideline was available for ketanserin. This study shows that four commonly used drug formularies give few and widely differing dosing guidelines for drugs prescribed in the intensive care unit. If guidelines exist, they seem to reflect labeling status (if present) and limited literature available. Findings from this study likely reflect the scarcity of drug studies in this population. Physicians should be aware of the limitations of these formularies for daily practice in this group of vulnerable patients.
    Pediatric Critical Care Medicine 03/2010; 12(1):e14-9. DOI:10.1097/PCC.0b013e3181d90228 · 2.33 Impact Factor
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    ABSTRACT: To describe a potentially fatal adverse drug event after administration of morphine to a term neonate. A 2-day-old term neonate experienced generalized muscle rigidity and laryngeal spasm resulting in acute respiratory failure on 2 separate occasions after morphine administration. The first occasion was after administration of bolus doses of fentanyl and morphine 100 microg/kg in the operating theater; administration of intravenous propofol 2 mg/kg resulted in relief of muscle rigidity. The second occasion occurred a few hours later, when the patient received a continuous infusion of morphine 4.4 microg/kg/h in the intensive care unit and experienced generalized muscle rigidity with respiratory compromise. The opioid antagonist naloxone 30 microg/kg was administered intravenously, which immediately resulted in a patent airway and spontaneous breathing. An objective causality assessment using the Naranjo probability scale revealed that the likelihood of morphine causing the patient's muscle rigidity on the second occasion was highly probable to definite. It is not clear whether the first occurrence of muscle rigidity was morphine-induced. We searched PubMed and EMBASE (through August 2009) for previous reports of morphine-related muscle rigidity and/or laryngeal spasm, using the search terms (muscle rigidity OR chest rigidity OR laryngeal spasm) AND (morphine OR fentanyl OR opioid). Sudden onset of muscle rigidity and laryngeal spasm is described in the literature as a rare but serious adverse event after infusion of fentanyl and similar opioids in both adults and young infants. However, there are no reports of this potentially fatal adverse event after administration of morphine. To our knowledge this is the first case reported of life-threatening muscle rigidity and laryngeal spasm after therapeutic doses of morphine in humans. A serious adverse event consisting of generalized muscle rigidity and laryngospasm can occur after bolus administration of morphine as well as during continuous infusion. Clinicians should be aware of this possibility.
    Annals of Pharmacotherapy 10/2009; 43(10):1724-6. DOI:10.1345/aph.1M268 · 2.92 Impact Factor