Roland Hentschel

Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea.

Objective. Methylxanthines are among the most commonly prescribed drugs in neonatal intensive care. This study evaluates the effect of caffeine on oxygen consumption and metabolic rate in premature infants with idiopathic apnea. Methods. Eighteen preterm infants at gestational ages from 28 to 33 weeks and birth weights of 890 to 1680 g were enrolled in the study. Nine preterm infants received caffeine therapy, and 9 served as a control group. Oxygen consumption and energy expenditure were examined before, during, and after caffeine treatment. Results. Oxygen consumption increased significantly from 7.0 ± 0.9 before caffeine to 8.8 ± 0.7 mL/kg/min after 48 hours of caffeine therapy, and energy expenditure increased from 2.1 ± 0.3 to 3.0 ± 0.2 kcal/kg/hour. During the observation period of 4 weeks of caffeine treatment, oxygen consumption increased significantly in the caffeine group compared with the control patients. In the caffeine group, a lower environmental temperature was sufficient to maintain a normal body temperature. With similar caloric intake in both groups during the study period, daily weight gain in the control group was significantly higher (21 ± 4 vs 42 ± 2 g/d). None of the other parameters recorded changed during caffeine therapy. Conclusion. Long-term administration of caffeine in preterm infants is associated with an increase in oxygen consumption and with a reduction of weight gain. This may have implications for clinical practice as nutritional regimens need to be adjusted during this therapy.

Neonatal outcome in small for gestational age infants: do they really better?

Abstract Background: There still is a controversy as to the neonatal outcome of small for gestational age (SGA) infants compared to a appropriate for gestational age (AGA) preterm infants. As a part of a randomized multicenter trial on timing of bovine surfactant therapy, we aimed at investigating short-term outcome variables in SGA-infants compared with AGA-infants. Methods: SGA-infants were classified weighing below the 10th percentile at birth and were compared to AGA-infants in terms of prenatal and neonatal characteristics and neonatal outcome. Results: A total of 317 infants were enrolled, 59 SGA-and 258 AGA-infants. Both groups did not differ in gestational age, however, SGA-infants had a lower birth weight. Preterm premature rupture of fetal membranes was observed more frequently in AGA-, preeclampsia in SGA-infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary airleaks and days on the ventilator did not differ between both groups. However prolonged nasal CPAP, supplemental oxygen therapy and chronic lung disease at 28 days and 36 weeks was diagnosed more often in SGA-infants. Furthermore mortality was significantly higher in SGA-infants as well as total NICU and total hospital days. Conclusion: As SGA-infants have an increased mortality rate and an increased risk for developing chronic lung disease, further studies should focus on prevention of intrauterine growth restriction and its complications.

Cord Blood Levels of Interleukin-6 and Interleukin-8 for the Immediate Diagnosis of Early-Onset Infection in Premature Infants

Background: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. Patients and Methods: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite®). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. Results: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5–95% confidence interval 308–4,660 pg/ml); group B, 50 (15–102) pg/ml; group C, 21 (12–71) pg/ml, and group D, 8 (6–11) pg/ml. For IL-8, median levels for groups A–D were 289 (226–514) pg/ml, 87 (40–107) pg/ml, 44 (33–98) pg/ml and 21 (16–25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). Conclusion: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.

Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants

In a prospective study hemodynamic effects of dobutamine or dopamine (10 micrograms/kg/min) were investigated in 20 preterm infants who had protracted arterial hypotension refractory to volume therapy. Doppler ultrasonography of the superior mesenteric artery (SMA) was applied to verify intestinal perfusion and blood pressure was recorded in parallel. Mean arterial pressure (MAP) raised significantly in both groups (from 31.0 +/- 6.8 to 37.7 +/- 9.8 mm Hg during dobutamine and from 27.7 +/- 3.6 to 36.0 +/- 9.3 mm Hg during dopamine). Mean blood flow velocity increased from 25.8 +/- 13.5 to 31.5 +/- 16 cm/s with dobutamine and from 16.3 +/- 5.0 to 19.0 +/- 6.0 cm/s with dopamine (significant for dobutamine). Vascular resistance of SMA (indicated by resistance index; RI) decreased from 0.81 +/- 0.07 to 0.74 +/- 0.11 for dobutamine and from 0.89 +/- 0.06 to 0.79 +/- 0.07 for dopamine (significant for both groups). These data indicate that in the dose tested here both catecholamines are equally effective in raising MAP and lead to a significant increase of intestinal perfusion. Thus, a negative impact on mesenteric blood supply, predisposing to necrotizing enterocolitis, is not probable.

Continuous calculation of intratracheal pressure in the presence of pediatric endotracheal tubes.

Objective: To measure the pressure‐flow relationship of pediatric endotracheal tubes (ETTs) in trachea models, to mathematically describe this relationship, and to evaluate in trachea/lung models a method for calculation of pressure at the distal end of the ETT (Ptrach) by subtracting the flow‐dependent pressure drop across the ETT from the airway pressure measured at the proximal end of the ETT. Design: Trachea models and trachea/lung models. Setting: Research laboratory in a university medical center. Interventions: The pressure‐flow relationship of pediatric ETTs (inner diameter, 2.5‐6.5 mm) was determined using a physical model consisting of a tube connector, an anatomically curved ETT, and an artificial trachea. The model was ventilated with sinusoidal gas flow (12‐60 cycles/min). The coefficients of an approximation equation considering ETT resistance and inertance were fitted separately to the measured pressure‐flow curves for inspiration and expiration. Calculated Ptrach was compared with directly measured Ptrach in mechanically ventilated physical trachea/lung models. Measurements and Main Results: The pressure‐flow relationship was considerably nonlinear and showed hysteresis around the origin caused by the inertia of accelerated gas. ETT inertance ranged from 0.1 to 0.4 cm H2O/L·sec2 (inner diameter, 6‐2.5 mm). The abrupt change in cross‐sectional area at the tube connector caused an inspiration‐to‐expiration asymmetry. Calculated and measured Ptrach were within ± 1 cm H2O. Correspondence between measured and calculated Ptrach is improved even further when the ETT inertance is taken into account. Conclusions: Ptrach can continuously be monitored in the presence of pediatric ETT by combining ETT coefficients and the flow and airway pressure continuously measured at the proximal end of the ETT.

Efficacy, recovery, and safety of RBCs from autologous placental blood: clinical experience in 52 newborns.

BACKGROUND:  In the present study, the efficacy, recovery, and safety of RBCs from autologous placental blood (PB‐RBCs) were investigated.

Pressure support ventilation combined with volume guarantee versus synchronized intermittent mandatory ventilation: a pilot crossover trial in premature infants in their weaning phase.

Objective: To compare pressure support ventilation combined with volume guarantee (PSV-VG) to synchronized intermittent mandatory ventilation (SIMV) regarding safety, course of blood gases, and infant-ventilator interaction in premature infants. Design: Prospective, two-treatment, crossover pilot study. Setting: Tertiary care neonatal unit. Patients: Twenty-five ventilated premature infants: median (range) gestational age 26.1 wks (23.1–35.7), birth weight 765 g (450–3170), age at study 5 days (2–27), in their weaning phase. Interventions: Infants were studied for three 30-min periods, starting from SIMV, followed by PSV-VG, and back again to SIMV. After concluding the last period, all infants were switched back to PSV-VG. On the next day, infants were studied in the opposite direction. During each period, vital parameters, ventilation parameters, degree of physical activity, duration of rhythmic breathing, and the number of vital signs monitor alarms were recorded. Measurements and Main Results: Nineteen infants (84%) could be successfully ventilated with PSV-VG till the next day. PSV-VG achieved a similar oxygenation level as SIMV but with significantly lower ventilation pressures. Comparable ventilation was achieved, but infants with strong respiratory drive were more liable to hyperventilation episodes during PSV-VG. Although infants breathed more rhythmically during PSV-VG, suggesting better infant-ventilator synchrony, the infants’ behavioral state and the fluctuations in blood gases did not differ. Conclusions: The potentials of PSV-VG to improve infant-ventilator synchrony and to decrease pressure needed to ventilate premature lungs are promising, even though the changes were small. However, its benefits during acute illness and on the final outcome remain to be proven.

Continuous Infusion of Clonidine in Ventilated Newborns and Infants: A Randomized Controlled Trial

Objectives: To assess the influence of an infusion of clonidine 1 &mgr;g/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. Design: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. Setting: Twenty-eight level 3 German PICUs/neonatal ICUs. Patients: Ventilated newborns and infants: stratum I (1–28 d), stratum II, (29–120 d), and stratum III (121 d to 2 yr). Interventions: Patients received clonidine 1 &mgr;g/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. Measurements and Main Results: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 &mgr;g/kg/hr, placebo: 3.2 ± 3.1 &mgr;g/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 &mgr;g/kg/hr, placebo: 180.2 ± 204.0 &mgr;g/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. Conclusions: Clonidine 1 &mgr;g/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

Acute side effects of surfactant treatment.

Abstract There is increasing evidence from studies on animals and humans that surfactant administration may have a great impact on cerebral perfusion. These effects may result from direct pulmonary or hemodynamic changes (or a combination of both), but may also be due to rapid alterations of blood gases. Type of surfactant and mode of administration seem to play an important role. Results from the pertinent literature are summarised with a special emphasis on how to avoid potentially harmful side effects of surfactant therapy in preterm infants.

Treatment of respiratory failure with inhaled nitric oxide and high- frequency ventilation in an infant with respiratory syncytial virus pneumonia and bronchopulmonary dysplasia.

In a 7-month-old infant with bronchopulmonary dysplasia and respiratory syncytial virus (RSV) pneumonia, we have shown an additive effect of high-frequency ventilation (HFV) and inhaled nitric oxide (iNO) in terms of improved oxygenation and the avoidance of extracorporeal membrane oxygenation. Apparently, the combined therapy of HFV and iNO is superior to either therapeutic modality alone in the treatment of hypoxemic respiratory failure due to RSV pneumonia. The mechanism of increased lung expansion and alveolar recruitment appears to be responsible for a favorable clinical outcome. We conclude that the combined therapy of HFV and iNO should be considered in hypoxemic respiratory failure in pediatric patients.