PROSPECTIVE RANDOMIZED TRIAL OF HIGH-DOSE BOLUS VERSUS LOW-DOSE TISSUE-PLASMINOGEN ACTIVATOR INFUSION IN THE MANAGEMENT OF ACUTE LIMB ISCHEMIA

Introduction Accelerated thrombolysis with high-dose bolus tissue plas minogen activator (tPA) may enable patients with more severe acute leg ischaemia to be treated without recourse to surgery. This study was a randomized comparison of two thrombolytic regimens. Methods One hundr ed patients with acute leg ischaemia of less than 30 days' duration we re randomized to receive either high-dose bolus tPA (three doses of 5 mg over 30 min, then 3.5 mg/h for up to 4 h, then 0.5-1.0 mg/h) or con ventional low-dose tPA (0.5-1.0 mg/h). The groups were well matched fo r age, cardiovascular risk factors, duration and severity of ischaemia , site, cause and length of arterial occlusion. Results The median dur ation of infusion in the high-dose group was 4.0 (range 0.25-46) h com pared with 20 (range 2-46) h for low-dose infusion (P < 0.0001). Succe ssful thrombolysis was achieved in 45 of 49 high-dose and 39 of 44 low -dose infusions but significantly more adjunctive procedures were requ ired following high-dose bolus infusion (26 versus 16 patients) (P = 0 .002), Thirty days after treatment was commenced, limb salvage was ach ieved in 39 of 49 patients in the high-dose group compared with 37 of 44 who had a low-dose infusion of tPA, Six and two patients respective ly required amputation, Four patients in the high-dose group and five in the low-dose group died. Three patients in each group suffered a ma jor haemorrhage and one in the low-dose group had a stroke. Conclusion High-dose bolus therapy significantly accelerated thrombolysis with t PA without compromising outcome. Some 50 per cent of patients were tre ated within 4 h enabling thrombolysis to be used as primary therapy fo r patients with acute critical ischaemia.