Pulmonary antioxidant concentrations and oxidative damage in ventilated premature babies.

OBJECTIVE: To determine the relation between lipid peroxidation and the antioxidants ascorbate, urate, and glutathione in epithelial lining fluid in ventilated premature babies, and to relate the biochemical findings to clinical outcome. DESIGN: A cohort study conducted between January 1999 and June 2001. SETTING: A NHS neonatal intensive care unit. PATIENTS: An opportunity sample of 43 ventilated babies of less than 32 weeks gestation. MAIN OUTCOME MEASURES: The duration of supplementary oxygen according to the definition of bronchopulmonary dysplasia (BPD; oxygen dependency at 36 weeks gestational age). METHODS: Epithelial lining fluid was sampled by bronchoalveolar lavage. Ascorbate, urate, glutathione, and malondialdehyde (a marker of lipid peroxidation) were measured. RESULTS: Babies who developed BPD had significantly lower initial glutathione concentrations (mean (SEM) 1.89 (0.62) v 10.76 (2.79) microM; p = 0.043) and higher malondialdehyde concentrations (mean (SEM) 1.3 (0.31) v 0.345 (0.09) microM; p < 0.05) in the epithelial lining fluid than those who were not oxygen dependent. These variables were poor predictors of the development of BPD. Gestational age, endotracheal infection, and septicaemia had good predictive power. The level of oxidative damage was associated with the presence of endotracheal infection/septicaemia rather than inspired oxygen concentration. CONCLUSIONS: Endotracheal infection, septicaemia, and gestational age, rather than antioxidant concentrations, are the most powerful predictors of the development of BPD.

Effect of morphine on respiratory drive in trigger ventilated pre-term infants.

The response to morphine (100 microgram (microg)/kg bolus, 10 microg/kg/h infusion) of 14 babies (median birth weight/gestation 1. 37 kg/30 weeks) trigger ventilated for hyaline membrane disease was compared to a group of 26 babies (median birth weight/gestation 1.1 kg/28 weeks) also trigger ventilated for hyaline membrane disease but not treated with morphine. The effect of morphine on triggered breath rate was very variable with no significant difference between the groups seen until 12 h after starting the infusion (mean [95% CI] difference=-17 [-33, -2] breaths/min). In those babies (n=11) who had plasma morphine levels measured there was no significant reduction in triggered rate over time despite significantly increasing plasma morphine levels. Babies who produced morphine-6-glucuronide at 12 h showed a significantly greater reduction in triggered breath rate than those who did not (median change -22 breaths/min compared to -4 breaths/min).

Delayed traumatic hemothorax on ticlopidine and aspirin for coronary stent.

A 64-year-old man presented with worsening dyspnea on exertion and hemothorax of the left chest 7 days after discharge from the hospital on ticlopidine and aspirin after coronary stent placement to his left circumflex artery. He had suffered traumatic rib fractures to the seventh, eighth, and ninth left ribs 28 days before this presentation and 21 days before starting the ticlopidine. Results of chest radiography at discharge 7 days earlier while on aspirin and after brief IV heparin had been negative except for minimal atelectasis and rib fractures barely visible on posteroanterior view. The delayed hemothorax had lowered the peripheral blood hematocrit to 23% and required tube thoracostomy drainage and blood transfusion. The delayed traumatic hemothorax in this case occurred on treatment with ticlopidine and did not recur with continuation of aspirin alone.

Stress response and mode of ventilation in preterm infants.

AIM: To assess the change in stress response in preterm babies changed from patient triggered ventilation (PTV) to conventional mandatory ventilation (CMV) and vice versa; to determine outcome in relation to stress hormone concentrations. METHODS: A randomised controlled study was conducted in two district general hospital neonatal intensive care units. Thirty babies, treated initially with CMV, were randomly assigned to remain on CMV or to change to PTV. A second group of 29 babies, treated initially with PTV, were randomly assigned to remain on PTV or to change to CMV. The babies were less than 32 weeks of gestation, ventilated within 72 hours of birth, with clinical and radiological features compatible with respiratory distress syndrome (RDS). Stress hormone concentrations and clinical distress score were measured before and 20 minutes after allocation of mode of ventilation. RESULTS: Babies changed from CMV to PTV had significantly reduced adrenaline concentrations (median change -0.4 nmol/l) compared with those who remained on CMV. There was no increase in adrenaline in babies changed from PTV to CMV. There were no significant changes in noradrenaline concentrations or clinical distress score. Babies who died had significantly higher adrenaline and noradrenaline concentrations than those who survived. CONCLUSION: A change in mode of ventilation significantly reduces adrenaline concentrations. Raised catecholamine values are associated with a poor outcome.

Congenital skin loss following Nd:YAG placental photocoagulation.

This is the first reported case of congenital skin loss following endoscopic placental laser coagulation, a new technique for the ante-natal treatment of twin-twin transfusion syndrome. The skin defect healed rapidly after birth with dressings alone, mimicking the spontaneous re-epithelialisation of a minor burn wound or aplasia cutis congenita.

Does change in skin perfusion provide a good index to monitor the sympathetic response to a noxious stimulus in preterm newborns?

Skin perfusion was measured using laser Doppler fluximetry (LDF) in 16 preterm babies undergoing a standardised heel prick procedure. Although there was a significant reduction in skin blood flow following the heel prick, this was variable and dependent on basal skin blood flow. This, together with loss of data due to movement artefact, makes this technique unreliable in quantifying the sympathetic response to a noxious stimulus in preterm infants.

Is venepuncture in neonatal research ethical?

AIM: To determine whether venepuncture accords with the accepted (BPA) criteria of not causing more than minimal physical or psychological distress during non-therapeutic research. METHODS: Ninety two venepunctures were carried out in 69 neonates between days 6 and 10 of life, and in some cases, on day 28. Parents were fully informed of the need for the procedure and allowed to attend while it was performed. Ninety parents and 87 doctors completed questionnaires to assess the levels of perceived parental and child distress and anxiety before and after the procedure. RESULTS: Only three parents were very upset, and 47% reported the test as being better than they expected, compared with 10% who thought it worse than expected. Seven babies were recorded as being very upset. Doctors tended to underestimate the degree of anxiety before the procedure and the level of distress afterwards. CONCLUSIONS: Venepuncture in neonates seems to be acceptable to most parents and is associated with a favourable risk: benefit ratio using semiquantitative assessment of risk and benefit.

Development of morphine glucuronidation in premature neonates.

In premature neonates (25-34 weeks gestation) who were given morphine intravenously during the first 24 h of life, only morphine, and morphine-3-glucuronide (M3G) were detected in plasma obtained after a 2-hour loading infusion, but morphine-6-glucuronide (M6G) could also be quantified following 24 h of continuous infusion. M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight. However, the M6G/M3G plasma concentration ratio decreased with increasing birth weight (and gestational age), thus providing the first indication in vivo of the differential development of uridinediphosphate glucuronosyltransferases in humans.

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Which central venous catheter for neonatal use?

Complications in 100 percutaneous central venous catheters used for parenteral nutrition were monitored prospectively in patients on a regional neonatal medical and surgical unit. Infants were randomly allocated to receive either a Vygon Epicutaneous catheter or Dow Corning silastic tubing. The majority of lines -63 - were removed electively when parenteral feeding was no longer required. The most common serious complication was catheter sepsis for which 11 lines were removed; all patients made a complete recovery. Minor mechanical complications were encountered with 17 catheters. There was no difference in performance or complication rate comparing the two types of catheter. Percutaneous central venous catheters provide a suitable and safe means of administration of parenteral nutrition to preterm infants over an extended period of time.

Effect of morphine and pancuronium on the stress response in ventilated preterm infants.

Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.

Cerebral arterial and venous flow-velocity measurements in post-haemorrhagic ventricular dilatation and hydrocephalus.

Simultaneous anterior cerebral artery (ACA) and internal cerebral vein (ICV) flow-velocities were measured in 18 babies with post-haemorrhagic ventricular dilatation (PHVD) and hydrocephalus (PHH). Compared with a control group matched for post-conceptional age, the resistance index of the ACA was increased. This was shown to occur at an early stage of PHVD in a longitudinal study of seven of the babies. There were no significant changes in ACA or ICV time-averaged velocities. Eight babies with PHH had ventricular taps on 18 occasions to relieve raised intracranial pressure. There was a significant decrease in the resistance index of the ACA, accompanied by an increase in the ACA time-averaged velocity, but no change in the ICV time-averaged velocity.

Middle cerebral artery pulsatility in children with blocked cerebrospinal fluid shunts.

The application of transcranial Doppler ultrasound to the diagnosis of blocked ventriculo-peritoneal shunts was studied in 63 children. Thirty two of these required shunt revision, whereas in 31 children symptoms resolved without surgery. The group of children requiring shunt revision had a significantly higher mean Gosling pulsatility index, than both the group of children whose symptoms resolved and a group of age-matched controls (p less than 0.001). Those with a raised pulsatility index were more likely to have higher intracranial pressure. There was no correlation between CT scan changes and the pulsatility index.

Intraventricular haemorrhage after aspiration of ventricular reservoirs.

A previously unrecognised complication of aspirating ventricular reservoirs is described. Four infants developed fresh bleeding into the cerebrospinal fluid after reservoir taps; ultrasound confirmed intraventricular blood clot in one case. The technique for aspirating the reservoir may have an important bearing on the incidence of this complication.

The Doppler pulsatility index as a screening test for blocked ventriculo-peritoneal shunts.

Doppler ultrasound studies have demonstrated a raised Gosling pulsatility and Pourcelot resistance index in untreated hydrocephalus. The application of transcranial Doppler ultrasound to the diagnosis of blocked ventriculoperitoneal shunts was studied by comparing the Gosling pulsatility indices of 63 children with symptoms of shunt malfunction with a reference range derived from 248 asymptomatic shunted children. An abnormally raised pulsatility index predicted a blocked shunt with a sensitivity of 56% and a specificity of 97%. The pulsatility index correlated with intracranial pressure in patients with confirmed shunt blockage.

Morbidity and outcome of shunted hydrocephalus.

Over an eighteen month period 50 children with hydrocephalus of different aetiologies were treated with a ventriculo-peritoneal shunt during the first year of life. The morbidity associated with their shunts and their outcome were reviewed after 10 years. During the 10 year follow-up period 82% required a shunt revision. The number of hospitalisations varied widely (range 0-13, median 3). 28% suffered from a shunt infection at some time during the 10 years. Shunt revisions and shunt infections had no significant effect on long-term outcome. 72% of the infants had a good outcome and the sub-group of infants with post-haemorrhagic hydrocephalus fared as well as the rest.