Good Practice in Postoperative and Procedural Pain Management ...

undergoes hepatic biotransformation to an activemetabolite norketamine and is excreted mainly in theurine as metabolites. Subanesthetic doses of ketamineproduce analgesia. Oral administration has been utilizedfor sedation/premedication. Caudal/epiduraladministration of ketamine produces analgesia butconcern has been expressed regarding potential neurotoxicity.ClonidineClonidine is an alpha2-adrenergic agonist and has sedative,anxiolytic, and analgesic properties. As a result,potential perioperative benefits include use for premedication,reduction in general anesthetic requirements,analgesia, and management of opioid withdrawalsymptoms. Clonidine can be given orally, transdermally,intravenously, or epidurally. Clonidine is rapidlyabsorbed. After oral administration, about 50% ismetabolized in the liver, and it is excreted in the urineas unchanged drug and metabolites. Clearance in neonatesis about one-third of adult levels. The eliminationhalf-life has been variously reported to rangebetween 6 and 24 h, and extended up to 41 h inpatients with renal impairment. Clonidine crosses theplacenta and is distributed into breast milk. The hypotensiveeffect of clonidine may be enhanced by diuretics,other antihypertensives, and drugs that causehypotension. The sedative effect of clonidine may beenhanced by CNS depressants. Clonidine has beenassociated with impaired atrioventricular conduction ina few patients, although some of these may have hadunderlying conduction defects and had previouslyreceived digitalis, which may have contributed to theircondition.(ii) DosesKetamineFor anesthesia, 2 mgÆkg )1 given intravenously over60 s usually produces surgical anesthesia within 30 s ofthe end of the injection and lasting for 5–10 min.Addition of ketamine 0.25–0.5 mgÆkg )1 to caudallocal anesthetic (compared with a local anestheticalone) prolongs the time to first analgesia and reducespostoperative rescue analgesia requirements.ClonidineClonidine is rapidly absorbed after oral administrationand doses of 4 mcgÆkg )1 have been used for premedication.Clonidine has an established role as a spinaladjuvant analgesic in pediatric practice, and clonidinevia the intrathecal or caudal/epidural route has agreater effect than the same dose intravenously. Additionof 1–2 mcgÆkg )1 clonidine to caudal local anestheticprolongs analgesia and reduces postoperativeanalgesic requirements, when compared to local anestheticalone. Sensitivity to side effects (apnea, oxygendesaturation, and bradycardia) is greater in neonates,and cardiovascular and sedative side effects have beenreported following doses of 5 lgÆkg )1 caudal clonidinein children. Epidural clonidine 0.08–0.12 lgÆkg )1 Æh )1produces dose-dependent analgesia when added tolocal anesthetic infusion, and higher doses of clonidinealone (0.2 lgÆkg )1 Æh )1 preceded by bolus of 2 lgÆkg )1 )provide analgesia at rest following abdominal surgery.(iii) NeuroxicitySevere complications following pediatric regional techniquesare rare, but the incidence is higher in neonatesand infants (0.4% vs 0.1% for all regional blocks or1.1% vs 0.49% for epidural blocks alone). Rates ofneurological injury following neuraxial analgesia rangefrom 0.13 to 0.4 per 1000 in large series, with higherrates following epidural catheter techniques than singleshot caudals. Issues relating to the potential neurotoxicityof some spinally administered drugs and the ethicaluse of unlicensed routes of administration havebeen debated for many years.General anesthetics with NMDA antagonist and/orGABA agonist activity increase neuronal apoptosis inthe developing brain in rodents and primates and haveled to a number of clinical studies evaluating neurocognitiveoutcomes following exposure to general anesthesiain early life. The potential for additional developmentallyregulated spinal toxicity has been the impetus forstudies assessing histopathology and apoptosis in thespinal cord following intrathecal drugs in neonatalrodent models. Intrathecal bupivacaine produces densespinal analgesia but does not increase apoptosis in thebrain or spinal cord of neonatal and infant rats. Systemicallyadministered opioids have not been associated withincreased apoptosis in the brain, and similarly intrathecalmorphine did not increase apoptosis or produce histopathologyin the neonatal or infant spinal cord.Ketamine: In adult models, spinal cord toxicity hasbeen demonstrated following intrathecal administrationof ketamine in adult swine, rabbits, and dogs. Althoughsome studies have attributed changes to the preservative,administration of preservative-free S-ketamine for7 days produced necrotizing lesions with cellularª 2012 Blackwell Publishing Ltd, Pediatric Anesthesia, 22 (Suppl. 1), 1–79 71