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1.  Pharmacological therapy for analgesia and sedation in the newborn 
Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non‐steroidal anti‐inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence‐based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long‐term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non‐pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long‐term clinical outcomes.
PMCID: PMC2672765  PMID: 17056842
2.  Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial 
BJA: British Journal of Anaesthesia  2008;101(5):680-689.
Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates.
Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 µg kg−1), morphine infusions [23–26 weeks postmenstrual age (PMA) 10 µg kg−1 h−1; 27–29 weeks 20 µg kg−1 h−1; and 30–32 weeks 30 µg kg−1 h−1] were established for a maximum of 14 days. Open-label morphine (20–100 µg kg−1) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20–28 and 70–76 h after starting the drug infusion and at 10–14 h after discontinuation of the study drug. The concentration–effect response was investigated using non-linear mixed effects models.
A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat50) and increased from 2.05 litre h−1 70 kg−1 at 24 weeks PMA to 6.04 litre h−1 70 kg−1 at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg−1 (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0–440 µg litre−1) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile.
A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.
PMCID: PMC2733178  PMID: 18723857
anaesthesia, paediatric; anaesthetic–analgesic regimens; analgesics opioid, morphine; model, pharmacodynamic; model, pharmacokinetic
3.  Aspirin and Reye's syndrome — do parents know? 
Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (P<0.001); only one parent chose to ignore the advice. The media, particularly television, is again shown to be a potent means of publicity. Despite the very high response to the advice about aspirin none of the parents mentioned Reye's syndrome as the reason.
PMCID: PMC1711069  PMID: 3505289
4.  Transplantation of the heart and both lungs 
Thorax  1969;24(4):391-398.
It is estimated that an unknown, yet possibly large, number of patients would benefit from transplantation of the heart and both lungs if technically, physiologically, and immunologically feasible. In this paper we attempt to explore the main non-immunological areas in which we feel that cardiopulmonary transplantation requires further evaluation. A technique is described by which the heart and lungs, as one unit, can be removed from a donor animal, and viability of these organs can be maintained for several hours by autoperfusion (circulation being through the coronary and pulmonary vessels) with positive pressure ventilation via the trachea. This simple heart-lung preparation preserves the organs concerned for sufficient time to allow preparation of the recipient, transport of the donor organs, and tissue typing to be carried out. Our technique of implanting these donor organs into the recipient is also described. We have carried out this operation on approximately 100 dogs and have been impressed by the good cardiac function obtained, but spontaneous respiratory function has been either absent or inadequate to sustain life for more than a few hours. It would appear that dogs cannot tolerate bilateral pulmonary denervation, and our findings are discussed in the light of other work on this subject. Work on primates suggests that man would be able to undergo this procedure successfully. The organizational and ethical problems involved in cardiac and cardiopulmonary transplantation are briefly discussed.
PMCID: PMC472001  PMID: 4894051
British Medical Journal  1914;1(2790):1384-1385.
PMCID: PMC2301351
6.  Optimal location for a helicopter in a rural trauma system: prediction using discrete-event computer simulation. 
A discrete-event computer simulation was developed using the C programming language to determine the optimal base location for a trauma system helicopter in Maine, a rural area with unevenly distributed population. Ambulance run reports from a one-year period provided input data on the times and places where major injuries occurred. Data from a statewide trauma registry were used to estimate the percentage of cases which would require trauma center care and the locations of functional trauma centers. Climatic data for this region were used to estimate the likelihood that a helicopter could not fly due to bad weather. The incidence of trauma events was modeled as a nonstationary Poisson process, and location of the events by an empirical distribution. For each simulated event, if the injuries were sufficiently severe, if weather permitted flying, if the occurrence were not within 20 miles of a center or outside the range of the helicopter, and if the helicopter were not already in service, then it was used for transportation. 35 simulated years were run for each of 4 proposed locations for the helicopter base. One of the geographically intermediate locations was shown to produce the most frequent utilization of the helicopter. Discrete-event simulation is a potentially useful tool in planning for emergency medical services systems. Further refinements and validation of predictions may lead to wider utilization.
PMCID: PMC2247741  PMID: 7950052

Results 1-6 (6)