Background:  Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri‐operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri‐operative management in infants and children. Later publications also support the use of clonidine for premedication (3–6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children.

Rectal premedication with clonidine was associated with a significant reduction of pain in the early postoperative period compared to midazolam and was also associated with moderately increased sedation during the first 24 postoperative hours. The sedative effect of clonidine is in agreement with the unambiguous finding of a parental preference for a calm and sedated child during the first 24 postoperative hours.

Opioid use is costly to society, and the costs vary with OIC severity. OIC is discomforting, affects the QoL of patients, and can limit an effective pain therapy.

Coinduction with clonidine significantly increased the number of PONV-free patients after breast cancer surgery with general anesthesia.

Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg·l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults.

Midazolam the most commonly used drug for paediatric premedication worldwide. Despite having a number of beneficial effects it is far from an ideal premedicant, especially concerning its effect on cognition/amnesia, confusion and long-term behavioural disturbances. Clonidine lacks the majority of the negative effects associated with midazolam and is associated with a number of beneficial perioperative effects. Our clinical experience of replacing midazolam with clonidine as premedicant in children, including also outpatients, has been favourable.

Background The use of clonidine as an adjunct to epidural administration of local anesthetics in children has been reported to substantially improve the duration and quality of postoperative analgesia. The aims of the present study were to determine the pharmacokinetic profile and to investigate the interaction between postoperative sedation and analgesia after epidurally administered clonidine in children. Methods: Plasma levels of clonidine (0-10 h postop) and assessment of postoperative analgesia and sedation (0-24 h postop) were performed at predetermined intervals following lumbar epidural administration of bupivacaine 2.0 mg /kg and clonidine 2 mg/kg in 8 children undergoing ureteral re-implantation surgery using general anesthesia (age range: 1-9 yr, weight range: 9 4 1 kg). Plasma levels of clonidine were analyzed by radioimmunoassay, and sedation and analgesia were assessed by previously described scoring systems. Results: The venous plasma pharmacokinetics of clonidine following epidural administration showed a considerable interindividual variation. C, , , and T, , , values of clonidine were found to be within the 0.45-0.77 ng/mL and 48-193 min range, respectively. The time to absorb 95% of the clonidine dose from the epidural space into plasma varied between 36 min and 7.6 h. In 6 of the 8 patients postoperative analgesia substantially outlasted the duration of sedation ( 2 2 h). Sedation could not be detected in any patients at plasma concentrations below 0.3 ng/ mL. Conclusions: The pharmacokinetic profile associated with epidural clonidine administration in children (1-9 y) was similar to that previously reported in adults. The postoperative analgesia seen after administration of epidural bupivacaine-clonidine during general anesthesia in children cannot only be explained by residual postoperative sedation.

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