On paediatric regional anaesthesia : the use of paravertebral blockade, aspects on plasma protein binding, and systemic toxicity of local anaesthetics

Abstract: Paediatric regional anaesthesia has gained widespread popularity during recent years because of an excellent potential for intra- and postoperative pain relief and reduction of the surgically induced stress response. The aim of the present thesis was to adapt and develop the technique of paravertebral blockade (PVB) for the safe use in paediatric patients and also to investigate aspects on plasma protein binding and toxicity of local anaesthetic drugs which might be of importance in the special settings of paediatric anaesthesia. The optimal landmarks for puncture of the thoracic paravertebral space (PVS) was derived from computed tomography and clinical measurements and were found to correlate well with patient weight (r = 0.94-0.95). The lateral distance from the spinous process and the depth from the skin to the PVS can be calculated from the equations: lateral distance (mm) = 0.12kg + 10.2 and depth (mm) = 0.53 kg + 21.2. Retrospective data indicate that the PVB is capable of providing similar postoperative pain relief in children undergoing renal surgery withan unilateral incision compared to lumbar epidural blocks. In a prospective multi-centre study the failure rate and complications associated with PVB were studied in a mixed population ofadult and paediatric patients and PVB was found comparable in these aspects to other established alternative regional techniques. Plasma concentrations of lidocaine after bolusinjection (5 mg . kg-1 ) and subsequent infusion (2.5 mg .kg-1 h-1 ) of lidocaine with adrenalineinto the PVS were found to be well below the levels associated with side effects or toxicity. In vitro studies of the effects of hypothermia and haemodilution on the plasma proteinbinding (PPB) of lidocaine, assessed by ultrafiltration, were carried out on blood collectedfrom healthy, medication free, adult volunteers. A significant reduction in PPB could beobserved between 37 and 24 ¡C but a further decrease in temperature did not cause anyaddition reduction in PPB. Even moderate degrees of dilution of the plasma phase of the bloodwill cause a decrease in PPB but the PPB was not found to be affected by changes in haemotocrit. In order to confirm a clinical impression of side effects or even early signs of central nervous system toxicity in ex-premature infants undergoing awake caudal anaesthesia, unblinded assessments of behavioural changes before and twenty minutes after the performanceof a caudal block with bupivacaine (3.1 mg . kg-1) were compared with blinded evaluations of simultaneously performed EEG recordings. An integrated evaluation of the findings support the occurrence of systemic side effects and signs of early CNS toxicity at plasma concentrations of bupivacaine within the 0.56-1.62 . mg ml-1 range. The current thesis delineate the use of paravertebral blockade in paediatric patients and has also elucidated some aspects of plasma protein binding and toxicity of local anaesthetic drugs that are of special interest in paediatric regional anaesthesia.