André Léké

Effect of Domperidone on QT Interval in Neonates

OBJECTIVES To determine whether oral domperidone is associated with QT interval prolongation and ventricular arrhythmia and to identify factors that can influence these effects. STUDY DESIGN An electrocardiogram was performed before and after oral administration of domperidone in 31 neonates or infants classified into 3 groups according to gestational age. RESULTS Oral domperidone is associated with QTc prolongation except in infants with a gestational age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On univariate analysis, oral domperidone-induced QTc prolongation was correlated with gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after adjustment for gestational age, serum potassium was the only factor independently associated with interval QT prolongation during treatment. No ventricular arrhythmias were observed. CONCLUSIONS This study shows a significant association between oral domperidone therapy and QTc prolongation. Two risk factors were identified: advanced gestational age and serum potassium at the upper limit of normal. It is recommended that measurement of the QT interval be done before and after oral domperidone therapy.

Échanges thermiques et thermorégulation chez le nouveau-né

The newborns energy expenditure is used in order of priority for: (i) basic metabolism; (ii) body temperature regulation and (iii) body growth. Thermal regulation is an important part of energy expenditure, especially for low birth-weight infants or preterm newborns. The heat exchanges with the environment are greater in the infant than in the adult, explaining the increased risk of body hypo- or hyperthermia. The newborn infant is a homeotherm, but over a long period of time, he cannot maintain the thermal processes. Further developments are expected to improve the infants thermal environment, with assessment of the various heat exchange mechanisms by conduction, convection, radiation and evaporation. The quantification of the respective parts of these exchanges would improve nursing care through clinical procedures or equipment used to ensure the control of the optimal thermohygrometric conditions in incubators, especially when the likelihood of excessive body cooling is high. The present review focuses on the various body heat exchange mechanisms, the thermoregulation processes of the newborn, and their implications in clinical usage and limitations in the neonatal intensive care unit.

Ventilatory response to a hyperoxic test is related to the frequency of short apneic episodes in late preterm neonates.

Chemoreception is frequently involved in the processes underlying apnea in premature infants. Apnea could result from a decrease in carotid body effectiveness. However, increased carotid body activity could also initiate apnea through hypocapnia following hyperventilation when the receptors are stimulated. The aim of this study was to analyze the relationship between carotid body effectiveness and short apneic episodes in older preterm neonates. Carotid body effectiveness was assessed at thermoneutrality in 36 premature neonates (2.07 ± 0.26 kg) by performing a 30-s hyperoxic test during sleep, the oxygen inhalation involving a ventilation decrease. Blood O2 saturation (Spo2) and ventilatory parameters were monitored before and during the hyperoxic test. Short episodes of apnea (frequency and mean duration) were recorded during the mornings 3-h interfeeding interval. Pretest Spo2 was not related to any of the measured respiratory parameters. A higher frequency of short apneic episodes was linked to a greater ventilation decrease in response to the hyperoxic test (ρ = −0.32; p = 0.01). Increased carotid body response is correlated with greater apneic episodes frequency, even in the absence of concomitant oxygen desaturation. Fetal or early postnatal hypoxemia could have increased peripheral chemoreceptor activity, which could initiate a “overshoot/undershoot” situation, which in turn could induce a critical Po2/Pco2 combination and apnea.

(1–3)-β-D-glucan levels in candidiasis infections in the critically ill neonate

Introduction: The diagnosis of neonatal invasive Candida infections (ICIs) is problematic because the clinical signs are not specific and blood cultures are rarely positive. Hence, new diagnostic markers are needed. Objective: To assess the contribution of serum (1–3)-β-d-glucan (BDG) levels to the diagnosis of neonatal ICIs and to analyse the change in this parameter during antifungal therapy. Methods: This retrospective study (December 2010-March 2012) was performed at Amiens University Medical Center (Amiens, France). We included newborns in whom a BDG assay was performed for a suspected ICI and classified as infected (n = 18) or non-infected (n = 43). Results: Sixty-one patients (median (IQR) gestational age: 28.5 weeks (26.7–30.6); birth weight: 1000 g (910–1440)) were included. The BDG level was higher in the infected group (364 pg/ml (131–976) vs. 89 pg/ml (30–127); p < 0.001). The optimal BDG cut-off for distinguishing between non-infected and infected patients was 125 pg/ml (Se = 84%, Sp = 75%). The BDG level fell over the course of antifungal therapy. Conclusion: Our study results suggest that BDG levels were increased in neonatal invasive Candida infections (cut-off for BDG positivity > 125 pg/ml). The change in the serum BDG levels may be of value in evaluating the efficacy of antifungal therapy.

Effects of warm and cool thermal conditions on ventilatory responses to hyperoxic test in neonates

Body temperature interacts with respiratory control, but it is unclear what sites or mechanisms mediate those interactions. We hypothesized that warm and cool thermal conditions affect the decrease in ventilation (VE) seen during the hyperoxic test (HT), a breathing response believed to reflect the strength of the peripheral chemoreceptor drive. A breath-by-breath analysis during a 30 s HT was performed in eight premature neonates (postconceptional age: 36 +/- 1 weeks) under neutral, warm, and cool thermal conditions. Quiet sleep (QS) and active sleep (AS) were scored by neurophysiological criteria. The VE fall was higher in AS than in QS, and warm and cool conditions significantly enhanced the response only in AS (-24.2 +/- 6.0, -39.1 +/- 9.1, and -37.5 +/- 14.1% in neutral, warm, and cool conditions, respectively). Central control mechanisms of the respiratory chemoreflex may explain the increase in peripheral chemoreceptor drive during AS in response to thermal challenges, which may produce increased breathing instability leading to apnea in early life.

Interindividual differences in the thermoregulatory response to cool exposure in sleeping neonates.

Abstract The responses of the thermoregulatory effectors vary greatly among neonates. Therefore, we assume that a small decrease in air temperature from thermoneutrality induces various thermoregulatory responses within neonates that represent an energy cost due to the cold defence processes. To determine the importance of this variability in nursing, 26 neonates were explored at thermoneutrality and in a cool environment (−1.5 °C from thermoneutrality) similar to that which occurs currently in clinical procedure. Oxygen consumption (V˙O2), oesophageal and skin temperatures, as well as sleep parameters were recorded continuously in both conditions. Analysis of all of the data from all of the neonates revealed that the cool exposure induced thermal and sleep disturbances, but V˙O2 did not increase and was not negatively correlated to body temperature (as might be expected). Analyses of individual data showed large variability in body temperature regulation: the neonates could be assigned to one of three groups according to the direction of the individual slopes of V˙O2 versus oesophageal or skin temperature. The groups also differed according to the sleep changes recorded in the cool condition. The results show that the definition of thermoneutrality should be revised by incorporating non only changes in the body temperature, but also the sleep disturbances (increased wakefulness and active sleep, decreased quiet sleep), which are criteria that are more sensitive to mild cool exposure. Thermoneutrality should be defined for each individual, since the results stress that the variability does not help to predict a general pattern of thermoregulatory responses in cool-exposed neonates.

In Utero Exposure to Smoking and Peripheral Chemoreceptor Function in Preterm Neonates

OBJECTIVE: We aimed to assess the involvement of peripheral chemoreceptor tonic activity in the ventilatory pattern during sleep in preterm neonates exposed in utero to maternal smoking. PATIENTS AND METHODS: Peripheral chemoreceptor activity was measured at thermoneutrality in neonates (postmenstrual age: 36.1 ± 1.2 weeks) born to nonsmoking (n = 21) or smoking (n = 16) mothers by performing a 30-second hyperoxic test during active and quiet sleep. Blood oxygen saturation, baseline ventilatory parameters, and central apnea were monitored. RESULTS: Prenatal smoking exposure did not modify baseline ventilation. It was interesting to note that prenatal smoking exposure decreased the peripheral chemoreceptor tonic activity during active sleep and increased the response time during quiet sleep. These changes could explain the increase in the time spent in apnea (both with and without blood oxygen desaturation) and in the mean duration of apneic episodes with desaturation found in neonates exposed to smoking in utero. The involvement of a change in the chemoreceptor function is supported by the fact that the peripheral chemoreceptor tonic activity was negatively correlated with the mean duration of apneic episodes with desaturation in the control group only. CONCLUSIONS: To our knowledge, this is the first study to reveal that prenatal smoking exposure does not directly modify baseline ventilatory parameters in the neonate but has a negative impact on peripheral chemoreceptor tonic activity. These alterations may increase the risk of sleep respiratory disorders, especially via apnea with desaturation.

Relationship Between Functional Residual Capacity and Oxygen Desaturation During Short Central Apneic Events During Sleep in “Late Preterm” Infants

Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O2-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O2-desaturation during short central apneic events (>3 s) in “late-preterm” infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 ± 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O2-desaturation (drop in SpO2 >5% from the baseline, lowest SpO2 during apnea: 91.4 ± 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O2-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.

Thermal acclimation of neonates to prolonged cool exposure as regards sleep stages

The thermal responses of neonates during a cool acclimation period were studied with regard to sleep stages. Sleep stages, body temperatures and metabolic rate (o2) were studied for seven neonates nursed in incubators and exposed to a cool temperature (thermoneutrality minus 2 °C) for 75 h. Each recording session lasted 3 h in the morning: firstly under thermoneutral baseline conditions, then during the first and last 3‐h periods of the cool acclimation and finally during the last 3 h of a 24‐h recovery period. Sleep structure was modified during the initial hours of cool exposure: the percentage of active sleep increased (AS: +13%, P = 0.028) at the expense of quiet sleep (QS: −11%, P = 0.043). This alteration in sleep structure persisted at the end of the acclimation period. Metabolic heat production only increased in the later period of cool acclimation. Throughout the cool exposure, o2 increased more (P = 0.040) in QS (+33%) than in AS (+20%) so that by the end of the cool period, o2 levels were similar in both sleep stages. During cool acclimation, the maintenance of homeothermy is related not only to a change in sleep organization but also to modifications in the thermoregulatory processes in both sleep stages. Considering the importance of AS/QS patterns in the neurobehavioral development of neonates, the present results could have clinical implications for the thermal management of neonates.

Effects of medium‐ and long‐chain triglycerides on sleep and thermoregulatory processes in neonates

Sleep processes and body temperature regulation of neonates are never taken into account in the evaluation of nutrients, although these functions are implicated in the regulation of energy metabolism and are influenced by the nutritional state and its metabolic consequences. Medium‐chain triglycerides (MCT) are currently used in paediatric units during the first weeks of because they are considered to be a rapid source of energy, easy to assimilate for growing premature infants, whose digestive function is immature. However, no study has described the thermic effect of these nutrients on body temperature regulation and sleep. The present study aimed at analysing the influence of three feeding formulas with different content of MCT on sleep processes and on thermoregulation of neonates fed until desired intake was reached. Whatever the thermal conditions (thermal equilibrium or cool environment), the MCT‐fed groups had higher body temperatures and than groups fed without MCT, for whom total sleep time was reduced at thermal equilibrium. In this group, the large amount of quiet sleep seems to favour a strategy of conserving energy. Higher energy expenditure in MCT‐fed groups is not harmful to growth rate since nutritional efficiency is even better reflected by a larger body mass gain. The thermic effect of MCT contributes to lessening the vulnerability of neonates exposed to low incubator temperatures.