Sedation in paediatric intensive care
This study consisted of two stages. Stage 1 investigated the reproducibility and practicality of two observational sedation assessment scales for use in critically ill children. The two scales were different in design, the first being simple in design requiring a single assessment of the patient. The second was more complex in design requiring assessment of five patient parameters to obtain an overall sedation score. It was established that nursing staff preferred the second, more complex sedation scale mainly because it was perceived to give a more accurate assessment of level of sedation and anxiety rather than merely level of sedation. Stage 2 investigated the pharmacokinetics and pharmacodynamics of midazolam in critically ill children. 52 children, aged between 0 and 18 years were recruited to the study and 303 blood samples taken to analyse midazolam and its metabolites, 1-hydroxymidazolam (1-OH) and 4-hydroxymidazolam (4-OH). A significant correlation was found between midazolam plasma concentration and sedative effect (r=0.598, p=0.01). It was found that a midazolam plasma concentration of 223ng/ml (±31.9) achieved a satisfactory level of sedation. Only a poor correlation was found between dose of midazolam and plasma concentration of midazolam. Similarly only a poor correlation was found between sedative effect and dose of midazolam. Clearance of midazolam was found to be 6.3ml/kg/min (±0.36), which is lower than that reported in healthy children (9.11-13.3ml/kg/min). neonates produced the lowest clearance values (1.63ml/kg/min), compared to children aged 1 to 12 months (8.52ml/kg/min) who achieved the highest clearance values. Clearance was found to decrease after the age of 12 months to values of 5.34ml/kg/min in children aged 7 yeas and above. Patients with renal (n=5) and liver impairment (n=4) were found to have reduced midazolam clearance (1.37 and 0.74ml/kg/min respectively). Disease state was found to affect production of 1-OH. Patients with renal impairment (n=5) produced the lowest 1-OH midazolam plasma ratio (0.059) compared to patients with head injury (0.858).