Stress, severity of illness, and outcome in ventilated preterm infants.

AIM: To determine physiological and hormonal stress responses in ventilated preterm infants. METHODS: Physiological and hormonal stress responses were studied in 47 ventilated preterm infants who were judged clinically to require sedation. The correlation between the stress response and severity of illness was examined, and responses were compared between infants with different clinical outcomes. RESULTS: Stress hormone concentrations were significantly correlated with severity of illness, assessed using the arterial: alveolar oxygen partial pressure ratio. Noradrenaline showed the strongest correlation, with an exponential pattern of increased secretion. Catecholamine concentrations before sedation were significantly higher among infants who subsequently died (n = 15, at a median age of 6 days) than among survivors: median noradrenaline 4.31 vs 2.16 nmol/l, median adrenaline 0.69 vs 0.31 nmol/l. The observed fall in noradrenaline with sedation was lower among those who died than survivors (median fall 2% vs 40%). CONCLUSION: Preterm infants are capable of hormonal stress responses appropriate for the severity of their illness. Extreme catecholamine responses, in the sickest infants, are associated with the worst outcome.

Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions.

1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 micrograms kg-1 or 200 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2. Following both the 50 micrograms kg-1 or 200 micrograms kg-1 loading doses the mean steady-state plasma concentration (+/- s.d.) of morphine, M3G and M6G were 86 +/- 52 ng ml-1, 703 +/- 400 ng ml-1 and 48 +/- 28 ng ml-1 respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min-1 kg-1. 3. M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min-1 kg-1. 4. M3G metabolite clearance was 0.46 +/- 0.60 ml min-1 kg-1, the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg-1. M6G metabolite clearance was 0.71 +/- 0.36 ml min-1 kg-1, the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg-1. 5. No significant effect of the loading dose (50 micrograms kg-1 or 200 micrograms kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults.

Capillary blood sampling: should the heel be warmed?

The hypothesis that capillary blood sampling is made easier by warming the heel was examined in a randomised, controlled trial of healthy newborn infants. Sampling was performed using an automated lancet with or without prior warming. The time taken to collect a standard volume of blood, the number of repeat procedures needed, and the infants' behavioural responses were measured. Eighty one procedures were studied in 57 infants. Warming produced a median rise in heel skin temperature of 4.7 degrees C. However, there were no significant differences between the warmed and unwarmed groups in any of the outcome measures. Heel skin temperature is not an important factor in capillary blood sampling. Attention should be directed towards improving sampling devices and technique.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

AIMS: To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS: Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS: Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS: Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Lignocaine ointment and local anaesthesia in preterm infants.

The ability of topically applied lignocaine ointment to produce surface anaesthesia was examined in 45 preterm infants (gestational age 25 to 35 weeks) at a median age of 2 days. Two strengths of ointment, 5% and 30%, were tested at 30 and 60 minutes after application to the dorsum of the foot. Anaesthesia was assessed by comparing the response to skin stimulation at the test and control sites, using von Frey hairs. In 84% of cases responses indicated that there was no surface anaesthesia. Topically applied lignocaine ointment is not an effective local anaesthetic in preterm infants, presumably due to poor absorption.

Exposure to invasive procedures in neonatal intensive care unit admissions.

The nature and numbers of invasive procedures were studied in 54 consecutive infants admitted to a neonatal intensive care unit. Over 3000 procedures were recorded, 74% in infants below 31 weeks of gestation. One infant (23 weeks' gestation, birth weight 560 g) underwent 488 procedures. Heel prick blood sampling was the most common procedure (56%), followed by endotracheal suction (26%) and intravenous cannula insertion (8%). Invasive procedures which would cause pain or distress to a child are frequently performed on infants admitted to the neonatal intensive care unit. A reduction in the number of procedures, modifying them, or providing adequate analgesia could relieve some of this pain and distress.

Heel blood sampling in preterm infants: which technique?

Preterm infants undergoing heel blood sampling were randomly allocated to specimen collection by heel puncture (Autolet II Clinisafe) or incision (Tenderfoot 'preemie'). A total of 187 procedures was observed in 47 infants. No significant difference was found in the infants' behavioural response, increase in heart rate, or in the frequency of specimen haemolysis. Collection times for small to medium sized samples were similar, but for large samples (> 1 ml) the Tenderfoot method was superior and fewer repeat procedures were necessary. Tenderfoot has the added advantage of improved safety, but it is too costly for routine use.

A career in paediatrics? A survey of paediatric senior house officers in England and Wales.

A telephone questionnaire was targeted at 189 paediatric senior house officers (SHOs) throughout England and Wales in order to evaluate their attitudes towards paediatrics and gain insight into methods by which recruitment could be improved in future years. A total of 152 senior house officers were interviewed. The group consisted mainly of general practice trainees, but included 51 career paediatricians. The majority were female (57%) and 44% were married. Our assessment revealed a perceived high work-load, but also showed that paediatrics remains a satisfying specialty. Training while in post was perceived as unsatisfactory by 32% of those questioned. Sixty per cent reported a decline in their social life since starting their post. Paediatrics was seen as the busiest of a number of specialties. This perception persisted, and in fact increased, between SHO and consultant grade. It is foreseen that this may lead to further problems in recruitment.