Publications by authors named "Koen P Dijkman"

18 Publications

  • Page 1 of 1

Survival and causes of death in extremely preterm infants in the Netherlands.

Arch Dis Child Fetal Neonatal Ed 2020 11 6. Epub 2020 Nov 6.

Department of Neonatology, Máxima Medical Centre, Veldhoven, The Netherlands.

Objective: In the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25 to 24 weeks' gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.

Design: National cohort study, using data from the Netherlands Perinatal Registry.

Patients: The study population included all 3312 stillborn and live born infants with a gestational age (GA) between 24 and 26 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.

Main Outcome Measures: Survival to discharge, as well as cause and timing of death.

Results: After guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks' GA (27%-69%, p<0.001), resulting in increased survival to discharge in 24-week live born infants (13%-34%, p<0.001). Top three causes of in-hospital mortality were necrotising enterocolitis (28%), respiratory distress syndrome (19%) and intraventricular haemorrhage (17%). A significant decrease in cause of death either complicated or caused by respiratory insufficiency was seen over time (34% in 2011-2014 to 23% in 2015-2017, p=0.006).

Conclusions: Implementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks' GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2020-318978DOI Listing
November 2020

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017.

Acta Ophthalmol 2021 Feb 23;99(1):97-103. Epub 2020 Jul 23.

Leiden University Medical Center, Leiden, Netherlands.

Purpose: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods.

Methods: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared.

Results: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599).

Conclusion: In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891652PMC
February 2021

Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.

Neonatology 2019 28;116(2):154-162. Epub 2019 Jun 28.

Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance.

Objectives: To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines.

Methods: Data were collected in the prospective multicentre PharmaCool study. In the present study, neonates treated with therapeutic hypothermia and receiving midazolam and/or phenobarbital were included. Plasma concentrations of phenobarbital and midazolam including its metabolites were determined in blood samples drawn on days 2-5 after birth. Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs.

Results: Data were available from 113 (phenobarbital) and 118 (midazolam) neonates; 68 were treated with both medications. Only clearance of 1-hydroxy midazolam was influenced by hypothermia. Phenobarbital co-administration increased midazolam clearance by a factor 2.3 (95% CI 1.9-2.9, p < 0.05). Anticonvulsant effectiveness was 65.5% for phenobarbital and 37.1% for add-on midazolam.

Conclusions: Therapeutic hypothermia does not influence clearance of phenobarbital or midazolam in (near-)term neonates with hypoxic-ischaemic encephalopathy. A phenobarbital dose of 30 mg/kg is advised to reach therapeutic concentrations. Phenobarbital co-administration significantly increased midazolam clearance. Should phenobarbital be substituted by non-CYP3A inducers as first-line anticonvulsant, a 50% lower midazolam maintenance dose might be appropriate to avoid excessive exposure during the first days after birth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000499330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878731PMC
May 2020

Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.

PLoS One 2019 14;14(2):e0211910. Epub 2019 Feb 14.

Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.

Objective: Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Study Design: Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.

Results: 244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C- 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C- 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.

Conclusions: Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.

Trial Registration: www.trialregister.nl NTR2529.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211910PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375702PMC
November 2019

Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis.

Neonatology 2019 12;115(2):127-133. Epub 2018 Nov 12.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands,

Background: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis.

Objectives: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis.

Methods: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome.

Results: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis.

Conclusion: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493358DOI Listing
December 2019

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BMC Pediatr 2018 08 4;18(1):262. Epub 2018 Aug 4.

Department of Paediatrics, Division of Neonatology, Radboud university medical centre Nijmegen, Radboud Institute for Health Sciences, Amalia Children's Hospital, Internal postal code 804, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.

Background: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking.

Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis.

Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks.

Trial Registration: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-018-1215-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090763PMC
August 2018

Evaluation of a System-Specific Function To Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia.

Antimicrob Agents Chemother 2018 04 27;62(4). Epub 2018 Mar 27.

Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.

The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now. A system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature-induced changes in amoxicillin clearance (CL) in the same patient study population was incorporated into a population PK model of benzylpenicillin with birthweight (BW)-based allometric scaling. Pediatric population covariate models describing the developmental changes in drug elimination may constitute system-specific information and may therefore be incorporated into PK models of drugs cleared through the same pathway. The performance of this system-specific model was compared to that of a reference model. Furthermore, Monte-Carlo simulations were performed to evaluate the optimal dose. The system-specific model performed as well as the reference model. Significant correlations were found between CL and postnatal age (PNA), gestational age (GA), body temperature (TEMP), urine output (UO; system-specific model), and multiorgan failure (reference model). For a typical patient with a GA of 40 weeks, BW of 3,000 g, PNA of 2 days (TEMP, 33.5°C), and normal UO (2 ml/kg/h), benzylpenicillin CL was 0.48 liter/h (interindividual variability [IIV] of 49%) and the volume of distribution of the central compartment was 0.62 liter/kg (IIV of 53%) in the system-specific model. Based on simulations, we advise a benzylpenicillin i.v. dose regimen of 75,000 IU/kg/day every 8 h (q8h), 150,000 IU/kg/day q8h, and 200,000 IU/kg/day q6h for patients with GAs of 36 to 37 weeks, 38 to 41 weeks, and ≥42 weeks, respectively. The system-specific model may be used for other drugs cleared through the same pathway accelerating model development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02311-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914006PMC
April 2018

Using benchmarking to identify inter-centre differences in persistent ductus arteriosus treatment: can we improve outcome?

Cardiol Young 2017 Oct 12;27(8):1488-1496. Epub 2017 Apr 12.

1Department of Neonatology,Máxima Medical Centre,Veldhoven,The Netherlands.

Objective: The aim of this study was to identify inter-centre differences in persistent ductus arteriosus treatment and their related outcomes. Materials and methods We carried out a retrospective, multicentre study including infants between 24+0 and 27+6 weeks of gestation in the period between 2010 and 2011. In all centres, echocardiography was used as the standard procedure to diagnose a patent ductus arteriosus and to document ductal closure.

Results: In total, 367 preterm infants were included. All four participating neonatal ICU had a comparable number of preterm infants; however, differences were observed in the incidence of treatment (33-63%), choice and dosing of medication (ibuprofen or indomethacin), number of pharmacological courses (1-4), and the need for surgical ligation after failure of pharmacological treatment (8-52%). Despite the differences in treatment, we found no difference in short-term morbidity between the centres. Adjusted mortality showed independent risk contribution of gestational age, birth weight, ductal ligation, and perinatal centre.

Conclusions: Using benchmarking as a tool identified inter-centre differences. In these four perinatal centres, the factors that explained the differences in patent ductus arteriosus treatment are quite complex. Timing, choice of medication, and dosing are probably important determinants for successful patent ductus arteriosus closure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S104795111700052XDOI Listing
October 2017

Severe hypercapnia causes reversible depression of aEEG background activity in neonates: an observational study.

Arch Dis Child Fetal Neonatal Ed 2017 Sep 27;102(5):F383-F388. Epub 2017 Jan 27.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

Introduction: Elevated carbon dioxide (CO) blood levels have a depressant effect on the central nervous system and can lead to coma in adults. Less is known about the effect of CO on the neurological function of infants.

Objective: To describe the effect of acute severe hypercapnia (PaCO >70 mm Hg) on amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation in newborn infants.

Study Design: Observational study of full-term and preterm infants with acute severe hypercapnia (identified by arterial blood gas measurements), monitored with aEEG. Visual analysis of the aEEG was performed in all infants. In preterm infants <32 weeks postmenstrual age (PMA), analysis of two-channel EEG was performed. Mean spontaneous activity transients (SAT) rate (SATs/min), interval between SATs (ISI in seconds) and the ISI percentage (ISP) were calculated for 10-min periods before, during and after hypercapnia. Mean regional cerebral oxygen saturation (rScO) and fractional tissue oxygen extraction (FTOE) measured with near-infrared spectroscopy were also calculated for these periods.

Results: Twenty-five infants (21 preterm, 4 full-term) comprising 32 episodes of acute severe hypercapnia were identified. Twenty-seven episodes were accompanied by a transient aEEG depression. Twenty-two episodes in 15 preterm infants <32 weeks PMA were quantitatively analysed. During hypercapnia, SAT rate decreased and ISI and ISP increased significantly. No significant change occurred in rScO or FTOE during hypercapnia.

Conclusion: Profound depression of brain activity due to severe hypercapnia is also seen in infants. It can be recognised by an acute depression of the aEEG, without clinically detectable changes in cerebral oxygenation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2016-311770DOI Listing
September 2017

The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia.

Pediatr Neurol 2016 07 1;60:49-53. Epub 2016 Apr 1.

Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands. Electronic address:

Background: The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed.

Objective: The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia.

Methods: The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied.

Results: Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8).

Conclusion: The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated newborns. A score ≥12 is associated with adverse outcomes (death before discharge and development of severe epilepsy). The Thompson encephalopathy score is not associated with the development of multiple organ failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2016.03.014DOI Listing
July 2016

Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia.

Br J Clin Pharmacol 2016 06 10;81(6):1067-77. Epub 2016 Mar 10.

Department of Pharmacy, Academic Medical Center, Amsterdam.

Aim(s): Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients

Methods: Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the ‘PharmaCool Study’) were collected. A non-linear mixed-effects regression analysis (nonmem®) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model.

Results: A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3 kg, GA 40 weeks, 2 days post-natal age (PNA)) was 0.06 l kg−1 h−1 (inter-individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46 l kg−1 (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (>96 h PNA).

Conclusions: This study describes the PK of gentamicin in neonates undergoing controlled hypothermia. The 29% higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred. Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 36–40 weeks and GA 42 weeks, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876193PMC
June 2016

A simple quantitative method analysing amikacin, gentamicin, and vancomycin levels in human newborn plasma using ion-pair liquid chromatography/tandem mass spectrometry and its applicability to a clinical study.

J Chromatogr B Analyt Technol Biomed Life Sci 2014 Mar 30;951-952:110-8. Epub 2014 Jan 30.

Department of Pharmacy, Academic Medical Centre, Amsterdam, The Netherlands.

Neuroprotective controlled therapeutic hypothermia is the standard of care for newborns suffering perinatal asphyxia. Antibiotic drugs, such as amikacin, gentamicin, and vancomycin are frequently administered during controlled hypothermia, which possibly alters their pharmacokinetic (PK) and pharmacodynamic (PD) profiles. In order to examine this effect an LC-MS/MS method for the simultaneous quantification of amikacin, the major gentamicin components (gentamicin C, C1a and C2), and vancomycin in plasma was developed. In 25μL plasma proteins were precipitated with trichloroacetic acid (TCA) and detection of the components was achieved using ion-pair reversed phase chromatography coupled with electrospray ionization tandem mass spectrometry. The chromatographic runtime was 7.5min per sample. Calibration standards were prepared over a range of 0.3-50mgL(-1) for amikacin and gentamicin and 1.0-100mgL(-1) for vancomycin. At LLOQ accuracy was between 103 and 120% and imprecision was less than 19%. For concentrations above LLOQ accuracy ranged from 98% to 102% and imprecision was less than 6%. Process efficiency, ionization efficiency, and recovery were acceptable. Samples and stock solutions were stable during the time periods and at the different temperatures examined. The applicability of the method was shown by analysing plasma samples from 3 neonatal patients. The developed method allows accurate and precise simultaneous quantification of amikacin, gentamicin, and vancomycin in a small volume (25μL) of plasma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2014.01.035DOI Listing
March 2014

Introduction of hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders.

Neonatology 2013 23;104(1):15-21. Epub 2013 Apr 23.

Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database.

Objectives: The aim of this study was to analyse complications and outcome after implementation.

Methods: Data were retrieved from an online database to which all centres had contributed.

Results: In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials.

Conclusions: The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000348823DOI Listing
January 2014

Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study.

BMC Pediatr 2012 May 22;12:45. Epub 2012 May 22.

Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.

Background: In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of the 180-185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care.

Methods/design: Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE) resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM). It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance.

Discussion: On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The results of this study will lead to an evidence based drug treatment of hypothermic neonatal patients. Results will be published in a national web based evidence based paediatric formulary, peer reviewed journals and international paediatric drug references.

Trial Registration: NTR2529.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2431-12-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358232PMC
May 2012

[Procedural sedation with propofol in non-painful interventions in children].

Ned Tijdschr Geneeskd 2011 ;155(26):A2523

Máxima Medisch Centrum, afd. Kindergeneeskunde en Neonatologie, Veldhoven, the Netherlands.

Unlabelled: Propofol is the sedative of choice in our hospital for all procedural sedations in children older than 3 months. Data were collected from all patients who underwent PSA with propofol in the period from November 2007 to December 2009. The procedure was performed by a paediatrician experienced in airway management, sedation and paediatric IC, and a specialized nurse. Patient characteristics, American Society of Anesthesiologists (ASA) classification, vital parameters and propofol dosage were registered on specially designed forms. Patient data were analyzed and compared with data from a non-matched historical cohort of patients who in the past had undergone PSA with chloral hydrate.

Results: 204 procedural sedations with intravenous propofol were performed in 196 patients. The mean cumulative induction dose was 3.39 mg/kg (SD: 1.34) and the mean maintenance dose was 4.05 mg/kg/h (SD: 2.23). The success rate was 99.5%, compared to 88.6% in the cohort that had received PSA with chloral hydrate. 1 procedure was aborted because of desaturation due to an obstructed airway, for which a jaw thrust was performed. No complications were observed in 199 procedures (97.5%). In 4 procedures a mild and transient desaturation (85-89%) occurred.

Conclusion: The results suggest that propofol can be used safely and is effective for procedural sedation in selected children, provided that PSA is performed by experienced and trained staff.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2011

Failed resuscitation of a newborn due to congenital tracheal agenesis: a case report.

Cases J 2009 Jul 17;2:7212. Epub 2009 Jul 17.

Department of Neonatology, Máxima Medical Center, PO Box 7777, 5500 MB, Veldhoven, The Netherlands.

Tracheal agenesis is a rare congenital condition. It usually presents as an unexpected emergency during resuscitation of a newborn in the delivery room. The condition is almost always fatal in the resuscitation phase, but also when the neonate survives the long term prognosis remains poor. We present a case of tracheal agenesis, discuss its presenting symptoms and possibilities for antenatal diagnosis and review the therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4076/1757-1626-2-7212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740092PMC
July 2009

[Haematological abnormalities in premature babies due to placental mesenchymal dysplasia].

Ned Tijdschr Geneeskd 2010 ;154:A1040

Máxima Medisch Centrum, Veldhoven, afd. Kindergeneeskunde en Neonatologie, Veldhoven, The Netherlands.

Two premature babies were admitted separately to the Neonatal Intensive Care Unit. One patient, a girl, presented with severe anaemia and thrombocytopaenia, the other, another girl, showed isolated thrombocytopaenia. During both pregnancies, ultrasound showed abnormalities of the placenta. The first patient also had intra-uterine growth restriction. A postpartum pathological examination showed abnormalities of both placentae consistent with placental mesenchymal dysplasia. Placental mesenchymal dysplasia is a rare condition which is associated with intra-uterine growth restriction, intra-uterine mortality, prematurity and Beckwith-Wiedemann syndrome. Thrombocytopaenia and anaemia are less commonly described in literature and are caused by micro-angiopathic haemolysis in the placenta. Both children had unrestricted growth and development patterns at one year and 6 months follow-up, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2010

Vanishing spleen after Nissen fundoplication: a case report.

Eur J Pediatr 2009 Mar 3;168(3):355-7. Epub 2008 Jul 3.

Department of Paediatrics, Paediatric Intensive Care Unit, University Hospital Maastricht, Maastricht, The Netherlands.

Nissen fundoplication is a generally accepted treatment for severe gastro-oesophageal reflux after conservative management has failed. The surgical techniques and the complications that may develop following the operation have been well described. However, necrosis of the spleen is a rare complication. We report here a patient with Down syndrome with a vanishing spleen after a Nissen fundoplication, who died of overwhelming pneumococcal septic shock 7 months after the operation. Vascular anomaly in Down syndrome, inadvertent ligation of the splenic artery or volvulus of the spleen may have caused a compromised splenic arterial circulation.Conclusion Nissen fundoplication may be associated with vanishing spleen and, consequently, with devastating consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-008-0752-8DOI Listing
March 2009