Biomedical subjects

Dick Tibboel

Publications and source records attributed to Dick Tibboel.

At least 37 records · Page 2Linked to original sources

PubMed2006

Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane oxygenation in neonates.

OBJECTIVE: To examine morphine metabolite serum concentrations in neonates undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to quantify clearance differences between these neonates and those subjected to noncardiac major surgery. PATIENTS AND METHODS: This was an observational study in level III referral centre. Fourteen neonates (< 7 days old) undergoing ECMO were included. Morphine and concomitant medications were given by protocol, adapted to the clinical conditions of the neonates. Pharmacokinetic findings were compared with those from a previous study in infants after noncardiac major surgery. Nonlinear mixed-effect modelling was used. Parameter estimates were standardised to a 70 kg person using allometric modeling RESULTS: Morphine-3-glucuronide (M3G) was the predominant metabolite. Formation clearance to M3G at the start of ECMO on day 1 was lower than those in postoperative children, but matured more rapidly. After 10 days formation clearances of M3G in neonates on ECMO equalled those of postoperative children. Higher ECMO flows were associated with reduced formation clearances. Elimination clearances of M3G, but not morphine-6-glucuronide (M6G), were lower in the ECMO neonates; this was attributable to reduced renal clearance. These elimination clearances were correlated positively with ECMO flow and negatively with dopamine dose. Haemofiltration cleared M3G and M6G, but not morphine. CONCLUSION: Formation clearance to M3G, the predominant metabolite, is reduced during the first 10 days of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance. ECMO flow had a small effect on metabolite clearance. Higher flows were associated with decreased formation clearances, possibly reflecting illness severity. Dopamine dose reflected decreased renal clearance.

Adult↗

PubMed2005

Iroquois genes influence proximo-distal morphogenesis during rat lung development.

Lung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox (Irx) genes have been implicated in the patterning and specification of several Drosophila and vertebrate organs, including the heart. Herein, we investigated whether the Irx genes play a role in lung morphogenesis. We found that Irx1-3 and Irx5 expression was confined to the branching lung epithelium, whereas Irx4 was not expressed in the developing lung. Antisense knockdown of all pulmonary Irx genes together dramatically decreased distal branching morphogenesis and increased distention of the proximal tubules in vitro, which was accompanied by a reduction in surfactant protein C-positive epithelial cells and an increase in beta-tubulin IV and Clara cell secretory protein positive epithelial structures. Transmission electron microscopy confirmed the proximal phenotype of the epithelial structures. Furthermore, antisense Irx knockdown resulted in loss of lung mesenchyme and abnormal smooth muscle cell formation. Expression of fibroblast growth factors (FGF) 1, 7, and 10, FGF receptor 2, bone morphogenetic protein 4, and Sonic hedgehog (Shh) were not altered in lung explants treated with antisense Irx oligonucleotides. All four Irx genes were expressed in Shh- and Gli(2)-deficient murine lungs. Collectively, these results suggest that Irx genes are involved in the regulation of proximo-distal morphogenesis of the developing lung but are likely not linked to the FGF, BMP, or Shh signaling pathways.

Animals↗

PubMed2005

Hormone levels in children during the first week of ICU-admission: is there an effect of adequate feeding?

BACKGROUND & AIMS: To evaluate the course of hormonal parameters in relation to clinical parameters, illness severity and nutritional intake in children admitted to the pediatric ICU during the first week of admission. METHODS: Prospective, observational study. Levels of triiodothyronine (T3), reverse T3 (rT3), ratio T3/rT3 and insulin-like growth factor I (IGF-1) were evaluated in 84 critically ill children (50 term neonates and 34 children aged 32 d-15 yr) admitted to our multidisciplinary tertiary pediatric intensive care unit within 24 h after admission, on days 4 and 6 after admission. Changes in hormones levels over time were related to illness severity, C-reactive protein-levels and the adequacy of feeding. RESULTS: For both age groups IGF-1 levels remained low until day 4, but at day 6 IGF-1 levels were significantly higher than admission level. In 88% and 89% of the older children, T3 levels remained below normal at days 4 and 6, respectively. In both age groups, rT3 levels declined significantly over time, whereas the ratio T3/rT3 increased. The increases in IGF-1, T3 and ratio T3/rT3 and decrease in rT3 were significantly associated with decreases in CRP-levels. No significant relations were found between changes in IGF-1 and thyroid hormone levels during admission and the adequacy of energy and protein intake. CONCLUSIONS: During the first week of ICU-admission, abnormalities in levels of IGF-1, T3 and rT3 were frequently observed in critically ill children, especially in the children aged >1 month. The adequacy of feeding did not seem to affect the normalization of IGF-1 and thyroid hormone levels.

Adolescent↗

PubMed2005

Agenesis of the trachea: phenotypic expression of a rare cause of fatal neonatal respiratory insufficiency in six patients.

Tracheal agenesis is a rare congenital malformation, which is usually fatal in the newborn period. Its incidence is approximately 1 in 50,000 births. Presentation is with respiratory insufficiency and no audible cry. Other anomalies are found in most cases. Six cases of tracheal agenesis were seen in our hospital since 1988. Their medical records were reviewed. Three of our cases classify as Floyd's type III, two as Floyd's type II and one as Floyd's type I. Associated anomalies were found in five cases. The classification of tracheal agenesis, associated anomalies and potential therapeutic options are discussed.

Bronchoscopy↗

PubMed2005

Nonselective cyclo-oxygenase inhibitors and glomerular filtration rate in preterm neonates.

The adverse effects of nonselective cyclo-oxygenase (COX) inhibitors on the immature kidney have been described in newborn rabbits, but it is much more laborious and difficult to study its relative impact on renal function in human neonates. Amikacin clearance was therefore used as surrogate marker to study the impact of nonselective COX-inhibitors on glomerular filtration rate. Clinical characteristics and amikacin clearance of infants on respiratory support were retrospectively collected. Results in neonates in whom either ibuprofen-lysine or acetylsalicylic acid was administered prophylactically to induce closure of a patent asymptomatic ductus arteriosus were compared to infants not cotreated with any COX-inhibitor (Mann-Whitney U-, chi-square tests). Amikacin clearance was calculated in 142 infants, of whom 50 were cotreated with ibuprofen and 33 with acetylsalicylic acid. There were no significant differences in clinical characteristics between the three groups. Compared to controls (0.52, range 0.09-2.33 ml/kg/min), a significant similar decrease in amikacin clearance in infants cotreated with ibuprofen (0.38, range 0.13-0.80 ml/kg/min, p<0.01) or acetylsalicylic acid (0.38, range 0.13-0.78 ml/kg/min, p<0.01) was demonstrated. Using amikacin clearance as marker, a significant and similar reduction in glomerular filtration rate was documented in preterm infants cotreated with ibuprofen or acetylsalicylic acid.

Amikacin↗

PubMed2005

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample.

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population.

Adolescent↗

PubMed2005

The role of initial monitoring of routine biochemical nutritional markers in critically ill children.

AIMS: The objectives of this study were to determine whether abnormal values of routine laboratory parameters at admission predict outcome and changes in anthropometric parameters in critically ill children during intensive care unit (ICU) stay and to discuss the clinical implications of abnormalities. STUDY DESIGN: This is a prospective descriptive study in a tertiary multidisciplinary pediatric ICU. Serum urea, albumin, triglycerides and magnesium were measured in samples obtained from 105 children (age, 7 days-16 years) within the first 24 h after their admission. The prevalences of abnormalities in these parameters as well as their possible association with outcome (length of stay, days on mechanical ventilation) and changes in nutritional status (changes in S.D. scores for weight, mid upper arm circumference and calf circumference) between admission and discharge were assessed. RESULTS: Prevalences of hypomagnesemia, hypertriglyceridemia, uremia and hypoalbuminemia were 20%, 25%, 30% and 52%, respectively, with no significant associations between the different disorders. Except for uremia, no significant association was found between abnormalities in biochemical parameters and changes in S.D. scores of anthropometric measurements. Children with uremia showed larger declines in S.D. scores for weight and arm circumference between admission and discharge than children without uremia did. Children with hypertriglyceridemia had longer ventilator dependence (P<.01) and length of stay (P<.001) than children with normal triglyceride levels upon admission had. CONCLUSIONS: Abnormalities in routine nutritional laboratory parameters were frequently noted in critically ill children at admission. Detection of abnormalities was not predictive of changes in anthropometric parameters during ICU admission but can be important in individualizing nutritional support.

Adolescent↗

PubMed2005

Illness severity and parental permission for clinical research in a pediatric ICU population.

OBJECTIVE: Research in child subjects requires parental permission. We examined whether parental authorization of involvement in a clinical study is influenced by the child's severity of illness at the time of the consent decision. DESIGN AND SETTING: Observational study in a multidisciplinary tertiary pediatric and neonatal intensive care. PATIENTS AND PARTICIPANTS: Parents of 421 children (age range from preterm to 18 years) were asked to consent for participation in a study focusing on measuring their child's nutritional status within 24 h after admission to the ICU. Over 20% of the parents (n=88) refused consent, most of them because they expected the study to be too burdensome for their child. MEASUREMENTS AND RESULTS: Patient and disease characteristics were comparable in the children for whom consent had or had not been obtained. A higher illness severity score did not decrease the probability of obtaining informed consent, but parents of children with a history of disease were 3.2 times less likely to consent. CONCLUSIONS: Parents of children with higher illness severity scores are not more likely to decline permission to include their child in clinical observational research on the ICU. History of disease and subjectively perceived burden to the child are important factors that must be considered.

Adolescent↗

PubMed2005

Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems.

We identified, by homozygosity mapping, a novel locus on 10q21.3-q22.1 for Goldberg-Shprintzen syndrome (GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect. Furthermore, since bilateral generalized polymicogyria was diagnosed in all patients in this family, this feature might also be considered a key feature of the syndrome. We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development.

Abnormalities, Multiple↗

PubMed2005

Expression of glucocorticoid, retinoid, and thyroid hormone receptors during human lung development.

CONTEXT: Although glucocorticoid hormone, thyroid hormone, and retinoic acid play important roles in fetal development, the expression of their receptors in human lung is still unknown. OBJECTIVE: The aim of this study was to investigate the ontogeny of glucocorticoid receptor (GR)alpha, thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and retinoid X receptors (RXRs) mRNA expression in human lungs. DESIGN: Lungs from human fetuses and neonates (13.5-41 wk gestation; n = 20) as well as adults (n = 5) were analyzed by real-time PCR to monitor the ontogeny of mRNA expression for each receptor. In addition, immunohistochemistry was performed to show the cellular distribution of the different receptors. RESULTS: The expression of GRalpha, TRs, RARs, and RXRs was already detected in the earliest developmental stages analyzed. There was no significant difference in mRNA expression between developmental groups for any of the genes studied. However, for fetal and neonatal samples, there were positive correlations between gestational age and mRNA expression for RARalpha (r = 0.665; P = 0.001), RXRalpha (r = 0.444; P = 0.050), and RXRgamma (r = 0.464; P = 0.039). Immunohistochemical studies showed the presence of GRalpha, TRs, RARs, and RXRs in the nuclei of both epithelial and mesenchymal cells, albeit more pronounced in epithelium of larger airways. CONCLUSIONS: The detection of GRalpha, TRs, RARs, and RXRs expression in human lung as early as 13.5 wk gestation implies an early potential for therapeutic or toxic effects by exogenous analogs or by excess of endogenous ligands.

Female↗

PubMed2005

Pharmacodynamics of chloral hydrate in former preterm infants.

UNLABELLED: The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycardic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively evaluated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (Mann Whitney U, Fischer's exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P < 0.01). A significant increase in the number of bradycardic events (<80/min: 38 to 82 events, of which < 70/min: 30 to 79 of which < 60/min: 15 to 45; at least P < 0.01) and in the duration of the most severe bradycardic event (8-12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (< 60/min) events ( n = 13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. CONCLUSION: Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.

Administration, Oral↗

PubMed2005

Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates.

OBJECTIVE: To study morphine pharmacokinetics in neonates undergoing venoarterial ECMO and to quantify differences between these neonates and neonates subjected to noncardiac major surgery. DESIGN AND SETTING: Observational study in a level III referral center. PATIENTS AND METHODS: Pharmacokinetic estimates from 14 neonates undergoing ECMO were compared with findings from a previous study in 0- to 3-year-olds after noncardiac major surgery using a nonlinear mixed effect model. A one-compartment linear disposition model with zero-order input (infusion) and first-order elimination was used to describe all data. RESULTS: Clearance in neonates (age <7 days) at the start of ECMO (2.2 l per hour per 70 kg) was lower than that in postoperative neonates (10.5 l per hour per 70 kg) but increased rapidly (maturation half-life 30 and 70 days, respectively) and equaled that of the postoperative group after 14 days. Clearance was affected by size and age only. Exchange transfusion, when used, contributed only 1.1% (CV 46%) of total clearance. Distribution volume increased with age and was 2.5 times (CV 102%) greater in ECMO children than in postoperative children. The between-subject variability values for volume of distribution and clearance were 49.4% and 38.7%. Weight and age information explained 83% of the overall clearance variability and 60% of overall distribution volume variability. CONCLUSIONS: Morphine clearance is reduced in infants requiring ECMO, possibly reflecting severity of illness. Clearance maturation on ECMO is rapid and normalizes within 2 weeks. Initial morphine dosing may be guided by age and weight, but clearance and distribution volume changes (and their variability) during prolonged ECMO suggests that morphine therapy should be subsequently guided by clinical monitoring.

Chi-Square Distribution↗

PubMed2005

The co-occurrence of congenital diaphragmatic hernia, esophageal atresia/tracheoesophageal fistula, and lung hypoplasia.

BACKGROUND: Two severe birth defects, congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with or without tracheoesophageal fistula (TEF), have traditionally been analyzed separately in epidemiological studies. Lung hypoplasia (LH), part of the CDH spectrum, is not usually associated with EA/TEF, yet both are foregut malformations. METHODS: We conducted an epidemiological study of two combinations of the defects in the population of 3,318,966 live births and stillbirths monitored from 1983 to 1996 by the California Birth Defects Monitoring Program (CBDMP). RESULTS: A total of 433 cases had a Bochdalek type CDH/LH (0.13 per 1000 births), 893 had EA/TEF (0.27 per 1000 births), and 646 had LH (0.19 per 1000 births). Among them, 18 cases had CDH/LH with EA/TEF (0.005 per 1000 births), and 53 had EA/TEF and LH (0.02 per 1000 births); both prevalences are significantly higher than expected. Sixteen of 17 cases of CDH/LH with EA/TEF, and 34 of 40 cases of EA/TEF with LH were stillborn or died; 72% and 74%, respectively, had an autopsy. The male to female sex ratios were 1.43 and 1.13, respectively. In both groups, infants had similar proportions of additional severe defects, except for genitourinary and anal defects and syndromes/associations, which were more prevalent in the EA/TEF with LH group. We reviewed human studies and experimental animal models for factors reported to cause any combination of the defects. CONCLUSIONS: Several genetic and environmental factors could affect the significant co-occurrence of the defects. Future studies should include storage of patients' biological materials for DNA analysis, karyotyping, and environmental exposure evaluation.

Esophageal Atresia↗

PubMed2005

Anesthesia and analgesia during and after surgery in neonates.

BACKGROUND: Historically, the use of anesthetics and analgesics in neonates and infants has been based on extrapolations from studies performed in adults and older children. Over the past 20 years, there has been a growing body of research on the clinical pharmacology and clinical outcomes of these agents in neonates and infants. OBJECTIVE: This article summarizes clinical pharmacology and clinical outcomes studies of opioids, opioid antagonists, sedative-hypnotics, nonsteroidal anti-inflammatory drugs and acetaminophen, and local anesthetics in neonates and infants to highlight gaps in the available knowledge, review some concerns about study design, and identify drugs that should receive high priority for future study. METHODS: Relevant studies were identified through a search of MEDLINE and a review of textbooks, conference proceedings, and abstracts. The available literature was subjected to expert committee-based review. CONCLUSIONS: There is a growing body of information on analgesic and anesthetic pharmacokinetics, pharmacodynamics, and clinical outcomes in neonates and infants, permitting safe and effective use in some clinical settings. Major gaps in knowledge persist, however. Future research may involve a combination of clinical trials and preclinical studies in suitable infant animal surrogate models.

Analgesia↗

PubMed2005

Alveolar capillary dysplasia: a logical approach to a fatal disease.

PURPOSE: The aim of the study was to review the authors' experience with alveolar capillary dysplasia (ACD), a cause of persistent pulmonary hypertension of the neonate (PPHN) caused by decreased alveolar units, dilated anomalous pulmonary veins, thick-walled arterioles, and thickened interalveolar septa. METHODS: The records of all neonates with ACD were reviewed from Children's Hospital, Columbus, Ohio, and Sophia's Children's Hospital, Rotterdam, The Netherlands. The clinical characteristics and pathological findings are discussed. RESULTS: Eight neonates were diagnosed with ACD from 1994 to 2002. Twenty-five percent (2/8) experienced respiratory distress immediately after birth, whereas 75% (6/8) had normal Apgar scores but deteriorated 1.5 hours to 30 days after birth. All infants required conventional ventilation initially; 50% (4/8) were placed on high-frequency oscillating ventilation and 87% (7/8) on extracorporeal membrane oxygenation. A premorbid diagnosis was established in 3 patients by open lung biopsy. The diagnosis of ACD was confirmed at autopsy in all patients. CONCLUSIONS: ACD is a fatal disease that should be suspected in all neonates with respiratory failure and PPHN who fail conventional therapy. Prompt diagnosis helps to avoid prolongation of costly treatment modalities in a uniformly fatal disease. An algorithm is proposed in which neonates with PPHN who fail treatment with extracorporeal membrane oxygenation are managed by open lung biopsy.

Algorithms↗

PubMed2005

Congenital diaphragmatic hernia in a patient with tetrasomy 9p.

Tetrasomy of the short arm of chromosome 9 constitutes a rare condition resulting in a well clinically recognized syndrome. In our case, in addition to the characteristic phenotype at birth, the existence of a hernia-type Bochdalek diaphragmatic defect was found. Cytogenetic analysis revealed a nonmosaic case of an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm: 47, XX, +i (9p). Because chromosome 9 contains several gene locus for enzymes and receptors of the retinoid pathway, this case potentially contributes to retinoid hypothesis in the etiology of congenital diaphragmatic hernia.

Adult↗

PubMed2005

Adequate feeding and the usefulness of the respiratory quotient in critically ill children.

OBJECTIVE: We determined incidences of underfeeding and overfeeding in children who were admitted to a multidisciplinary tertiary pediatric intensive care and evaluated the usefulness of the respiratory quotient (RQ) obtained from indirect calorimetry to assess feeding adequacy. METHODS: Children 18 y and younger who fulfilled the criteria for indirect calorimetry entered our prospective, observational study and were studied until day 14. Actual energy intake was recorded, compared with required energy intake (measured energy expenditure plus 10%), and classified as underfeeding (<90% of required), adequate feeding (90% to 110% of required), or overfeeding (>110% of required). We also evaluated the adequacy of a measured RQ lower than 0.85 to identify underfeeding, and an RQ higher than 1.0 to identify overfeeding. RESULTS: Ninety-eight children underwent 195 calorimetric measurements. Underfeeding, adequate feeding, and overfeeding occurred on 21%, 10%, and 69% of days, respectively. An RQ lower than 0.85 to identify underfeeding showed low sensitivity (63%), high specificity (89%), and high negative predictive value (90%). An RQ higher than 1.0 to indicate overfeeding showed poor sensitivity (21%), but a high specificity (97%) and a high positive predictive value (93%). Food composition, notably high-carbohydrate intake, was responsible for an RQ exceeding 1.0 in the overfed group. CONCLUSION: Children admitted to the intensive care unit receive adequate feeding on only 10% of measurement days during the first 2 wk of admission. The usefulness of RQ to monitor feeding adequacy is limited to identifying (carbohydrate) overfeeding and excluding underfeeding.

Adolescent↗

PubMed2005

Does neonatal surgery lead to increased pain sensitivity in later childhood?

Does pain or tissue damage in early life lead to hyperalgesia persisting into childhood? We performed a cross-sectional study in 164 infants to investigate whether major surgery within the first 3 months of life increases pain sensitivity to subsequent surgery and to elucidate whether subsequent surgery in the same dermatome or in a different dermatome leads to differences in pain sensitivity. All infants received standard intraoperative and postoperative pain management, with rescue analgesia guided by a treatment algorithm. Differences in pain sensitivity during surgery were assessed by the intraoperative fentanyl intake and by (nor)epinephrine plasma concentrations. Differences in postoperative pain sensitivity were assessed by the observational pain measures COMFORT and VAS, and by morphine intake and (nor)epinephrine plasma concentrations. Infants previously operated upon in the same dermatome needed more intraoperative fentanyl, had higher COMFORT and VAS scores, had greater (nor)epinephrine plasma concentrations, and needed also more morphine than did infants with no prior surgery. In contrast, infants who previously underwent surgery in another dermatome had only significant higher postoperative analgesic requirements and norepinephrine plasma concentrations in comparison with infants with no prior surgery. These preliminary differences may indicate the occurrence of spinal and supraspinal changes following neonatal surgery. We conclude that the long-term consequences of surgery in early infancy are greater in areas of prior tissue damage and that these effects may portend limited clinical but important neurobiological differences.

Analgesics, Opioid↗