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Biomedical subjects

Joke H Kok

Publications and source records attributed to Joke H Kok.

15 recordsLinked to original sources

Fluid resuscitation in neonatal and pediatric hypovolemic shock: a Dutch Pediatric Society evidence-based clinical practice guideline.

OBJECTIVE: To develop a clinical practice guideline that provides recommendations for the fluid, i.e. colloid or crystalloid, used for resuscitation in critically ill neonates and children up to the age of 18 years with hypovolemia. METHODS: The guideline was developed through a comprehensive search and analysis of the pediatric literature. Recommendations were formulated by a national multidisciplinary committee involving all stakeholders in neonatal and pediatric intensive care and were based on research evidence from the literature and, in areas where the evidence was insufficient or lacking, on consensus after discussions in the committee. RESULTS: Because of the lack of evidence in neonates and children, trials conducted in adults were considered. We found several recent meta-analyses that show excess mortality in albumin-treated groups, compared with crystalloid-treated groups, and one recent large randomized controlled trial that found evidence of no mortality difference. We found no evidence that synthetic colloids are superior to crystalloid solutions. CONCLUSIONS: Given the state of the evidence and taking all other considerations into account, the guideline-developing group and the multidisciplinary committee recommend that in neonates and children with hypovolemia the first-choice fluid for resuscitation should be isotonic saline.

Child↗

Neonatal thyroxine supplementation for transient hypothyroxinemia of prematurity : beneficial or detrimental?

Extremely low birth-weight newborns (<1000g) experience low levels of thyroid hormone that vary inversely with the severity of neonatal illness and the extent of developmental immaturity with levels reaching a nadir at approximate, equals7 days after birth; this phenomenon can persist for several weeks. In the absence of transplacental passage, 30-50% of these neonates cannot generate sufficient quantities of thyroid hormone to meet postnatal demands, placing them at an increased risk for developmental delay and cerebral palsy. Population surveys and interventional trials suggest that a therapeutic opening exists during a 'window of opportunity' corresponding to this period of diminished capacity. Variables to consider before intervention focus on the consideration that supplementation of both the substrate thyroxine and the active hormone triiodothyronine may be necessary in quantities that do not suppress thyroid-stimulating hormone release, yet overcome the persistence of increased conversion to 3,3'5'-triodo-L-thyronine, terminal deiodination, and activity of the sulfation inactivation pathways, as well as the diminished capacity of the newborn to accommodate postnatal physiologic changes. Single daily replacement doses may suppress levels of converting enzymes in the brain, suggesting that physiologic 'mimicry' provided by a constant infusion may be the preferred dosing option. Properly powered clinical trials targeting long-term developmental outcomes are needed to discern whether these interventions will do more than simply elevate blood levels of thyroid hormones to the target values of either the fetus or developing neonate. Identifying the appropriate indications for supplementation may alleviate individual pain and distress due to disability for several hundred extremely low birth-weight neonates each year in the US alone, and save society a pro-rated lifetime cost of nearly $US1 million per child.

Humans↗

Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile.

In preterm infants, both hypo- and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis. In 25 preterm infants, glucose production and gluconeogenesis were measured using stable isotope techniques during a 6-h infusion of glucose only, glucose plus glycerol, or glucose plus an intravenous lipid emulsion. Two lipid emulsions differing in FFA composition were used: Intralipid ( approximately 60% polyunsaturated FFA) and Clinoleic (approximately 60% monounsaturated FFA). The rate of glucose infusion was 22 micromol x kg(-1) x min(-1) in all groups. During the study infusion, the FFA concentrations were higher in both lipid groups vs. the glycerol group (P < 0.001). Compared with baseline, the glucose production rate increased in the Intralipid group, whereas it decreased in the other groups (P = 0.002) due to a significant increase in gluconeogenesis in the Intralipid group (P = 0.016). The plasma glucose concentration was significantly higher during Intralipid infusion vs. the other groups (P = 0.046). Our conclusion was that Intralipid enhanced glucose production by increasing gluconeogenesis in preterm infants. This can be ascribed to the stimulatory effect of FFA in addition to any effect of glycerol alone. The lack of stimulation of gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different classes of fatty acids exert different effects on glucose kinetics in preterm infants.

Fat Emulsions, Intravenous↗

Ten-year follow-up of children born at <30 weeks' gestational age supplemented with thyroxine in the neonatal period in a randomized, controlled trial.

BACKGROUND: Thyroid hormones are essential for brain development. We conducted a randomized, controlled trial with thyroxine (T4) supplementation in infants <30 weeks' gestation and with the last neurodevelopmental follow-up moment at the age of 5.5 years. T4 supplementation was associated with improved outcome of infants <28 weeks' gestation and worse outcome of infants of 29 weeks' gestation. We studied gestational age-dependent effects of T4 supplementation at the mean age of 10.5 years in children participating in our randomized, controlled trial. METHODS: Questionnaires regarding school outcome, behavior, quality of life, motor problems, and parental stress were sent to the parents and children and their teachers at the same time point for all surviving children (9-12 years of age). RESULTS: Seventy-two percent of the families responded to our questionnaires. Nonrespondents had more sociodemographic risk factors and worse development until 5.5 years. At the mean age of 10.5 years, T4 supplementation was associated with better school outcome in those who were <27 weeks' gestation and better motor outcome in those who were <28 weeks' gestation, whereas the reverse was true for those who were born at 29 weeks' gestation. No other gestational age-dependent outcomes were found. CONCLUSIONS: Gestation-dependent effects of T4 supplementation remain stable over time. These effects do not prove beneficial effects of T4 in infants <28 weeks but should be the background for a new randomized, controlled trial with thyroid hormone in this age group.

Brain↗

Very preterm birth is associated with disabilities in multiple developmental domains.

OBJECTIVE: Follow-up studies in very preterm children usually present outcome for separate developmental domains. Presence of disabilities in more than one developmental domain will show a more serious outcome picture for extreme preterm infants and may be related to a different degree of perinatal problems. METHODS: At 5.5 years corrected age, outcome in the neurological, motor, cognitive, and behavioral domain was studied in 157 children born < 30 weeks gestation. The children were divided into a normal, a single, or a multiple disability group. Group differences in background, clinical characteristics, and neurodevelopmental outcome at 2 years were evaluated. RESULTS: Thirty-nine percent had a normal developmental outcome, 17% had a single disability, and 44% had multiple disabilities. Multiple disabilities were associated with lower birth weight, BPD, and difficulties according to neurodevelopmental assessments at 2 years. CONCLUSION: Assessments of different developmental domains show that most very preterm children had multiple disabilities.

Achievement↗

Transient hypothyroxinemia in severe hypertensive disorders of pregnancy.

OBJECTIVE: Assess whether and to what extent thyroid function is affected in pregnant women with early and severe hypertensive disorders and in their newborns. METHODS: Patients were 80 women with preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome or gestational hypertension combined with fetal growth restriction in the 24th to 34th week of singleton pregnancies. Maternal thyroid hormone levels and thyroid peroxidase antibodies were determined at admission and 3 months postpartum. Neonatal levels were determined from cord blood at delivery. Maternal hypothyroxinemia was defined as free T(4) (fT(4)) value below 9 pM. RESULTS: At admission 26 (33%) women in the study group had fT(4) levels below 9 pM, with spontaneous normalization during pregnancy. There were no statistically significant differences between thyroid hormone values in women in the study group and 10 normotensive pregnant women in their third trimester. Three months postpartum, 97.5% of patients had normal thyroid hormone levels. Thyroid peroxidase antibodies were elevated in 10% of women postpartum. Their infants, born at a median gestational age of 30 6/7 weeks, had lower cord blood fT(4) and thyroid-stimulating hormone values compared with preterm infants of the comparison group, appropriate for gestational age. Cord blood fT(4) had no correlation with gestational age or maternal fT(4), but there was a significant correlation of cord blood fT(4) with umbilical artery pH. CONCLUSION: Women with severe hypertensive disorders of pregnancy may have transiently lower fT(4) levels, without evidence of a thyroid disorder. Their neonates have lower fT(4) levels at birth unrelated to maternal fT(4), but related to prenatal acidosis. LEVEL OF EVIDENCE: II-2.

Adult↗

Reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia.

Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on bacterial growth and translocation in a piglet model of Group B streptococcal pneumonia. After creating surfactant deficiency by whole lung lavage, intratracheal instillation of bacteria induced severe pneumonia with bacterial translocation into the blood stream, resulting in a mortality rate of almost 80%. Treatment with 300 mg/kg of exogenous surfactant before instillation of streptococci attenuated both bacterial growth and translocation and prevented clinical deterioration. This goal was also achieved by reversing atelectasis in lavaged animals via open lung ventilation. Combining both exogenous surfactant and open lung ventilation prevented bacterial translocation completely, comparable to Group B streptococci instillation into healthy animals. We conclude that exogenous surfactant and open lung ventilation attenuate bacterial growth and translocation in experimental pneumonia and that this attenuation is at least in part mediated by a reduction in atelectasis. These findings suggest that minimizing alveolar collapse by exogenous surfactant and open lung ventilation may reduce the risk of pneumonia and subsequent sepsis in ventilated patients.

Animals↗

Hypothyroxinaemia and thyroid function after preterm birth.

The concentration of thyroid hormone in preterm infants is lower than that in term infants. This phenomenon is referred to as transient hypothyroxinaemia of prematurity. Low thyroid hormone levels after very preterm birth are associated with worse developmental outcome in childhood, but only one randomized controlled trial has been carried out in the surfactant era to find out whether thyroid hormone supplementation is beneficial for developmental outcome. More studies are required to find out whether thyroid hormone supplementation is beneficial, and if so, for which preterm group.

Drug Administration Schedule↗

Open lung ventilation improves gas exchange and attenuates secondary lung injury in a piglet model of meconium aspiration.

OBJECTIVE: Previous studies failed to show clear benefits of high-frequency ventilation compared with conventional positive pressure ventilation (PPV(CON)) in experimental meconium aspiration syndrome. However, none of these studies applied an open lung ventilation strategy (OLC), which aims to reduce intrapulmonary shunt due to alveolar collapse. We hypothesized that, if combined with an open lung strategy, both high-frequency oscillatory ventilation (HFOV(OLC)) and positive pressure ventilation (PPV(OLC)) would improve gas exchange and attenuate ventilator-induced lung injury in experimental meconium aspiration syndrome. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a large university. SUBJECTS: Forty-two newborn piglets. INTERVENTIONS: Thirty minutes after intratracheal meconium instillation, 36 newborn piglets were assigned to one of three ventilation groups-PPV(OLC), HFOV(OLC), or PPV(CON)-and ventilated for 5 hrs. In both OLC groups, collapsed alveoli were actively recruited and thereafter stabilized using the lowest possible airway pressures. During PPV(CON), ventilator settings were adjusted to prevent critical hypoxia (Pao2 <60 torr [8 kPa]). Six animals served as saline controls. MEASUREMENTS AND MAIN RESULTS: Compared with the PPV(CON) group, arterial oxygenation and lung mechanics were superior in both OLC groups and the saline controls. Analysis of the bronchoalveolar lavage fluid obtained after 5 hrs of ventilation showed increased myeloperoxidase activity in the PPV(CON) group compared with both OLC groups and saline controls. Alveolar protein influx was not different between the groups. Histologic analysis revealed a higher lung injury score in the PPV(CON) group compared with the PPV(OLC) and the HFOV(OLC) groups. CONCLUSIONS: Application of the OLC during PPV and HFOV is feasible in experimental meconium aspiration syndrome and results in superior oxygenation and less ventilator-induced lung injury compared with PPV(CON).

Animals↗

Response to exogenous surfactant is different during open lung and conventional ventilation.

OBJECTIVE: Previous studies have shown that the efficacy of exogenous surfactant is dose-dependent during conventional positive pressure ventilation (PPVCON). The present study aimed to determine whether this dose-dependent relationship is also present during open lung (OLC) ventilation. We also explored the effect of exogenous surfactant on the ventilation pressures applied during ventilation. DESIGN: Animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Seventy-two newborn piglets. INTERVENTIONS: After repeated whole lung lavage, animals were randomly allocated to two surfactant groups receiving either 100 mg/kg surfactant (S100) or 25 mg/kg surfactant (S25) or to a control group receiving a bolus of air. Within each group, animals were randomly assigned to either PPVCON, open lung PPV (PPVOLC), or open lung high-frequency oscillatory ventilation (HFOVOLC) and ventilated for 5 hrs. MEASUREMENTS AND MAIN RESULTS: The ventilation pressures decreased in a dose-dependent way, showing the largest reduction in the S100 group. In both OLC groups, oxygenation, lung mechanics, and polymorphonuclear neutrophils analyzed in bronchoalveolar lavage were independent of the surfactant dose. In the PPVCON group, however, there was a clear dose-dependency, resulting in a deterioration of oxygenation and lung mechanics and an increase in polymorphonuclear neutrophils as the surfactant dose decreased. Although comparable between the three ventilation groups, bronchoalveolar lavage interleukin-8 concentrations significantly increased in all ventilation groups as the surfactant dose increased. Alveolar protein influx and conversion of large to small aggregate surfactant were higher during PPVCON compared with both OLC groups. There were no differences in the surfactant treatment response between PPVOLC and HFOVOLC. CONCLUSION: Exogenous surfactant enables a reduction in ventilation pressures. Compared with PPVCON, the efficacy of surfactant treatment is less dose-dependent during open lung ventilation. Surfactant conversion during open lung ventilation is reduced compared with PPVCON. Exogenous surfactant seems to up-regulate bronchoalveolar lavage interleukin-8 concentrations, independent of the ventilation strategy.

Analysis of Variance↗

A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects.

A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T(3) (0.5 microg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T(3) levels were comparable between the groups. T(4), free T(4), and reverse T(3) were increased in groups A and B during the period of T(4) administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T(3) and T(4) administration did not have any effect on cortisol levels. We did not find any effects of T(3) or of T(4) administration on the cardiovascular system. A single injection of T(3) (0.5 microg/kg) given 22-26 h after birth only leads to a 2-d increase of T(3) levels and does not have effects on the cardiovascular system. This study does not support the use of T(3) according to our regimen in preterm infants.

Drug Therapy, Combination↗

Application of the open-lung concept during positive-pressure ventilation reduces pulmonary inflammation in newborn piglets.

It has been shown that application of the open-lung concept (OLC) during high-frequency oscillatory ventilation (HFOV) attenuates pulmonary inflammation. We hypothesized that this attenuation could also be achieved by applying the OLC during positive-pressure ventilation (PPV). After repeated whole-lung lavage, newborn piglets were assigned to one of three ventilation groups: (1) PPV(OLC); (2) HFOV(OLC), or (3) conventional PPV (PPV(CON)). After a ventilation period of 5 h, analysis of bronchoalveolar lavage fluid showed a reduced influx of polymorphonuclear neutrophils, interleukin 8, and thrombin activity in both OLC groups as compared with the PPV(CON) group. There were no differences in tumor necrosis factor alpha levels. We conclude that application of the OLC during PPV reduces pulmonary inflammation as compared with conventional PPV and that the magnitude of this reduction is comparable to that of HFOV.

Animals↗

Positive pressure ventilation with the open lung concept optimizes gas exchange and reduces ventilator-induced lung injury in newborn piglets.

Previous studies demonstrated that high-frequency oscillatory ventilation using the open lung concept (OLC) resulted in superior gas exchange and a reduction in ventilator-induced lung injury (VILI). We hypothesized that these beneficial effects could also be achieved by applying the OLC during positive pressure ventilation. After repeated whole-lung-lavage, newborn piglets were assigned to either OLC positive pressure ventilation (PPV(OLC)), OLC high-frequency oscillatory ventilation (HFOV(OLC)), or conventional positive pressure ventilation (PPV(CON)) and ventilated for 5 h. In both OLC groups, collapsed alveoli were actively recruited and thereafter stabilized using the lowest possible airway pressures. In the PPV(CON) group, ventilator settings were adjusted to prevent critical hypoxia. Airway pressure, blood gas analysis, pressure-volume curve, and alveolar protein infiltration was recorded. A lung injury score was used for histologic comparison. Mean airway pressures were comparable in the three ventilation groups over time (1.2-1.5 kPa). Arterial oxygenation increased to mean values above 60 kPa in both OLC groups compared with 10 kPa in the PPV(CON) group (p < 0.001). Maximal lung compliance was superior in both OLC groups (PPV(OLC): 91 +/- 23; HFOV(OLC): 90 +/- 31 mL/kPa/kg, p < 0.01) compared with the PPV(CON) group (39 +/- 14 mL/kPa/kg). Alveolar protein infiltration was significantly reduced in the PPV(OLC) group (0.33 +/- 0.10 mg/mL, p < 0.01) and the HFOV(OLC) group (0.40 +/- 0.13 mg/mL, p < 0.01) compared with the PPV(CON) group (0.70 +/- 0.15 mg/mL). Lung injury scores were significantly higher in the PPV(CON) group (33.5 +/- 9.5, p < 0.01) compared with both OLC groups (PPV(OLC): 10.5 +/- 2.6; HFOV(OLC): 11 +/- 2.2). There were no differences between the two OLC groups. We conclude that, in surfactant-depleted newborn piglets, application of the OLC during PPV is feasible and results in superior gas exchange and a reduction in VILI compared with conventional PPV. These beneficial effects are comparable to HFOV.

Animals↗

Neurodevelopmental outcome of children treated with antenatal thyrotropin-releasing hormone.

OBJECTIVE: To evaluate neurodevelopmental outcome until 2 years of age in children who participated in a multicenter antenatal thyrotropin-releasing hormone (TRH) trial to improve respiratory outcome and to lower mortality. METHODS: Neurodevelopmental outcome was studied in infants whose mothers were admitted to the Academic Medical Center and enrolled in the European Antenatal TRH trial. Mothers were treated for imminent preterm delivery (before 30 weeks) with corticosteroids plus either placebo (placebo-group) or TRH (TRH-group). TRH treatment consisted of 400 micro g every 8 hours up to 4 doses. Assessments included neurologic development at 12 months and psychomotor development at 12 and 24 months using the Bayley developmental scales. RESULTS: Sixty-two infants were included, 10 of whom died. Of the surviving infants, 24 received TRH and 28 received placebo. Ten infants were lost to follow-up. Each group consisted of 21 infants. Both groups were comparable regarding gestational age, birth weight, and time interval between trial medication and birth. However, in the TRH group, more respiratory problems, ventilator days, and chronic lung disease were found. Neurologic and motor outcome did not differ between the groups, but lower mental developmental index scores were found in the TRH group at both ages. CONCLUSIONS: Antenatal TRH treatment is associated with a delay in mental development. This study demonstrates the importance of long-term follow-up of perinatal intervention trials with possible consequences for neurodevelopmental outcome of the infant.

Child Development↗

Free thyroxine levels during the first weeks of life and neurodevelopmental outcome until the age of 5 years in very preterm infants.

BACKGROUND: We have conducted a randomized trial with thyroxine (T4) in 200 infants <30 weeks' gestation. T4 treatment was associated with better 5-year outcome in infants <29 weeks' gestation, but with worse outcome in infants of 29 weeks. These effects could be related to low, respectively high free thyroxine (FT4) levels METHODS: For each infant, the average FT4 of 5 scheduled measurements was calculated between day 3 and day 28. Infants of the placebo and the T4 group separately were divided in 2 groups. The placebo group consisted of a group of infants with average FT4 in the lowest quartile and a group in the upper 75%. The T4 group consisted of a group of infants with average FT4 in the upper quartile and a group in the lower 75%. Developmental outcome (mental/cognitive, motor, and neurologic) at 2 and 5.7 years was compared between high and low FT4 groups, and then compared separately for the T4 and placebo group. RESULTS: In the placebo group, low FT4 was associated with worse outcome on all domains at both time points. After correction for confounding variables, mental and neurologic outcome remained significantly different at 2 years, and motor outcome at 5 years. In the T4 group, high FT4 was not associated with worse outcome, neither at 2 nor at 5 years. CONCLUSIONS: In untreated infants, low FT4 values during the first 4 weeks after birth in infants born at <30 weeks' gestation are associated with worse neurodevelopmental outcome at 2 and 5 years. In T4-treated infants, high FT4 is not associated with worse outcome. Other factors than high FT4 concentrations must play a role in the worse outcome of the T4-treated group of 29 weeks' gestational age.

Child Development↗