ANCROD PROPHYLAXIS AFTER SURGERY FOR FRACTURED NECK OF FEMUR: A STUDYOF FATAL PULMONARY EMBOLISM

Abstract

A pilot multi-centre randomized controlledtrial was carried out to compare ancrod (Arvin, Knoll) versus no medical treatment in 453 patients having surgery for fractured neck of femur to assess prevention of fatal post-operative pulmonary embolism (PE).Ancrod was given subcutaneously by 5 daily injections starting immediately post-operatively; initially 4u/kg bw were given followed by 4 injections of 1u/kg bw, to reduce fibrinogen levels to 80mg/dl. The primary objective of the study was to record mortality due to PE, as shown by the DeathCertificate, within 3 months after surgery.Death Certificates were analysed by 2 medical assessors, unaware of the patient treatment group. Of 239 control patients, not given ancrod, there were 5 deaths due to PE and 2 deaths where PE may have been contributory. Total deaths were 30 (12.5%). In 214 ancrod treated patients there were 2 deaths due to PE and a further 3 where it may have been contributory. Total deaths were 31 (14.5%), not significantly different from the control group. Deaths from PE occurred between16 and 66 days after surgery. Although in this study there was abeneficial tendency for ancrod to reduce fatal PE it is likely that at least 6,000 patients would be needed to demonstrate that any drug significantly reduces by 50% the incidence of fatal PE compared to the control group. Wound infection was recorded in 16 patients in both groups. Wound haematomas were seen in 26 ancrod patients compared to 6 controls (p<0.02) but were not sufficiently serious to warrant re-exploration or prolonged hospital stay. The low mortality due to PE in our patients with fractured neck of femur (2%) is contrasted with the figures of Sevitt & Gallagher, 1959(8%). The low incidence of fatal PE in thehigh risk group studied here should be taken into account when assessing future antithrombotic prophylaxis after surgery. Advances in anaesthetics, surgery and rehabilitation may have contributed to the decline in fatal post-operative PE. Effective assessment of drugs for prophylaxis against post-operative venous thrombosis is best carried out by large scale simple controlled trials using fatal PE a the primary end point. Collaborative Centres were located in Portsmouth, Cape Town, Glasgow, Belfast and Leeds.