Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography

To document the range and the most common strategies for the management of the parturient with inadvertent dural puncture (DP) during labour epidural analgesia. A confidential survey form was mailed to 46 academic units in Canada and USA. The responses were compiled into Canadian, US and joint North American databases. Thirty-six centres (78%) responded, representing 137,250 annual deliveries. The reported incidence of DP was 0.04-6%. The most common initial response to DP was resiting the catheter at another level. Most centres made little change in routine practice regarding epidural top-ups and infusion rates after DP. Unrestricted mobilisation was advocated by 86% of centres following delivery; enhanced oral hydration was encouraged by 61%. Prophylactic epidural blood patch (PEBP) was recommended by 37% of centres, with twice as many US as Canadian centres doing so. In the presence of PDPH, EBP was offered most commonly at or within 24 hr of diagnosis. Complications were common after EBP: 86% of centres reported patch failures; 44% reported persistent headache after > or = 2 EBP. Despite this, centres remained optimistic about EBP success, quoting cure rates > 90% in 58% of centres. There is little difference between the practices reported by Canadian or US centres. The expressed optimism regarding the efficacy of EBP is not supported by the evidence available and may be unwarranted. More research is needed to define the issue better.

Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing preclinical evaluation. Cross-over studies with i.v. levobupivacaine and bupivacaine were conducted in two groups of seven conscious sheep. Doses were chosen to avoid convulsions (smaller dose 6.25-37.5 mg/min) or to be potentially toxic (larger dose 75-200 mg/3 min). In subconvulsive doses, both drugs produced similar time- and dose-dependent depression of left ventricular systolic contractility (dP/dt(max)). Convulsions occurred consistently with > or = 75 mg of bupivacaine and > or = 100 mg of levobupivacaine, producing an abrupt reversal of dP/dt(max) depression. Subconvulsive doses produced minor cardiovascular effects on heart rate and blood pressure, whereas both were increased by convulsions. Cardiac output and myocardial blood flow were decreased with larger doses of both drugs. Doses > 75 mg of bupivacaine or > 100 mg of levobupivacaine induced QRS widening and ventricular arrhythmias, but significantly fewer and less deleterious arrhythmias were induced by levobupivacaine. Three animals died after 150, 150, and 200 mg of bupivacaine from the sudden onset of ventricular fibrillation. These doses of levobupivacaine produced nonfatal arrhythmias that automatically returned to sinus rhythm. We conclude that levobupivacaine could offer a greater margin of clinical safety than bupivacaine. Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. Local anesthetics can cause toxicity to the cardiovascular and central nervous systems. As a part of a preclinical evaluation of levobupivacaine, this study compared the toxic effects of levobupivacaine and bupivacaine in sheep.