The ED50 of dexmedetomidine administered over 5 s without significant hemodynamic compromise is 0.49 mcg·kg(-1). Further work is needed to determine the 'safe' (ED5 or less) and effective dose for desired perioperative clinical outcomes.

Oral morphine 200 mcg·kg then 100 mcg·kg 4 h or 150 mcg·kg 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses.

A mother brought her nine-month-old baby girl into hospital, concerned that she was unusually sleepy and not feeding. Apart from mild coryza, the baby had been well when she left for work but now seemed irritable and disinterested in her surroundings. The father said she had been unsettled during the day and had vomited twice. She had not experienced any diarrhoea, fevers, rash or breathing difficulties. On arrival, her saturations were 92% in room air and her respiratory rate was 20 breaths per minute. She was warm and well perfused, with a blood pressure of 95/45 mm Hg, a heart rate of 110 beats per minute and had an axillary temperature of 36.5°C. Her pupils were 3 mm and sluggish to react, and she would only respond to painful stimulus. Her fontanelle was full and she appeared hypotonic. Intravenous access was difficult to obtain and after multiple failed attempts, an intraosseous needle was sited. She was given 20 mL/kg of 0.9% saline and 80 mg/kg ceftriaxone intravenously (IV). She subsequently had a generalised tonicclonic seizure, which terminated after 0.1 mg/kg IV lorazepam was administered; however, she required continuous bag-mask ventilation due to poor respiratory effort. A capillary blood gas revealed a pH of 7.05, pCO 2 10 kPa, HCO 3 -20 mmol/L, base excess -4 mmol/L, lactate 2 mmol/L, glucose 4 mmol/L, Na 132 mmol/L, K 4.1 mmol/L, Hb 10 g/dL. Her right pupil was now fixed and dilated. The paediatric consultant called the paediatric intensive care (PIC) retrieval team while the anaesthetic team prepared for intubation. Neuroprotective strategies, a dose of IV mannitol and an urgent CT head were advised. The post-intubation chest X-ray (CXR) showed a correctly placed endotracheal tube (ETT) and old rib fractures. The CT scan demonstrated bilateral subdural haematomas and hydrocephalus. She was referred to neurosurgeons at the local neurosurgical centre, who, after reviewing the scans, requested that she be immediately transferred for an emergency craniotomy. This was organised by the local hospital and the parents accompanied the baby in the ambulance.Since the Department of Health Report 'Paediatric Intensive Care: A framework for the future' in 1997, paediatric intensive care services have been centralised and 24-hour retrieval services developed. However, all hospitals admitting critically ill children must be able to resuscitate and stabilise prior to retrieval, and occasionally undertake the 'timecritical' transfers themselves. This article reviews the clinical and organisational skills involved in the retrieval process, and also suggests ways in which knowledge and skills can be maintained.

This model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of other important covariates, such as phenotype, will add value and will help overcome the limitations of the presented population pharmacokinetic analysis.

In this study, a rapid bolus of dexmedetomidine transiently shortened corrected QT intervals. However, these effects are confounded by dexmedetomidine-induced bradycardia. These findings should be confirmed in pediatric studies without concomitant TIVA administration and with optimized correction of baseline HR.

Pharmacokinetic pharmacodynamic modeling is an important tool which uses statistical methodology to provide a better understanding of the relationship between concentration and effect of drugs such as analgesics and sedatives. Pharmacokinetic pharmacodynamic models also describe between‐subject variability that allows identification of subgroups and dose adjustment for optimal pain management in individual patients. This approach is particularly useful in the pediatric population, where most drugs have received limited evaluation and dosing is extrapolated from adult practice. In children, the covariates of weight and age are used to describe size‐ and maturation‐related changes in pharmacokinetics. It is important to consider both size and maturation in order to develop an accurate model and determine the optimal dose for different age groups. An adequate assessment of analgesic and sedative effect using pain scales or brain activity measures is essential to build reliable pharmacokinetic pharmacodynamic models. This is often challenging in children due to the multidimensional nature of pain and the limited sensitivity and specificity of some measurement tools. This review provides a summary of the pharmacokinetic and pharmacodynamic methodology used to describe the dose–concentration–effect relationship of analgesics and sedation in children, with a focus on the different pharmacodynamic endpoints and the challenges of pharmacodynamic modeling.

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