To cite this article: Carrier M, Le Gal G, Cho R, Tierney S, Rodger M, Lee AY. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost 2009; 7: 760À5. Summary. Background: Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE. Objectives: To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE. Patients and methods: This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period. Results: Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0À17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI 2.0À17.8%). Three patients (4.3%; 95% CI 1.5À11.9%), or 4.8 per 100 patient-years (95% CI 0.0À10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0À83.9 months). Conclusions: Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.

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BACKGROUND: Interscalene block (ISB) is the acute pain management technique of choice for shoulder surgery, but its undesirable respiratory side effects have prompted seeking alternatives. Supraclavicular block (SCB) is proposed as an ISB alternative, but evidence of comparative analgesic and respiratory-sparing effects is inconsistent. We compared the analgesic and respiratory effects of SCB and ISB for shoulder surgery. METHODS: Trials comparing ISB to SCB for shoulder surgery were sought. We decided a priori that SCB would be an acceptable alternative if it were noninferior for (1) postoperative 24-hour cumulative oral morphine equivalent consumption (primary outcome, noninferiority margin Δ = −25 mg) and (2) postoperative pain (secondary outcome, noninferiority margin Δ = 4.0 cm·hour–1); and superior for (3) postblock respiratory dysfunction (primary outcome). Opioid-related side effects and block-related complications were also evaluated. RESULTS: Fifteen studies (1065 patients) were analyzed. In single-injection blocks, SCB was noninferior to ISB for 24-hour morphine consumption (mean difference for SCB-ISB, MD [95% confidence interval {CI}] = −3.11 mg [−9.42 to 3.19], Δ = −25 mg); it was also noninferior for 24-hour pain scores (MD = 0.78 cm·hour–1 [0.07–1.49], Δ = 4.0 cm·hour–1); and decreased the odds of respiratory dysfunction (odds ratio [OR] [95% CI] = 0.08 [0.01–0.68]). Similarly, in continuous blocks, SCB was noninferior to ISB for 24-hour morphine consumption (MD = 0.46 mg [−6.08 to 5.15], Δ = −25 mg), and decreased the odds of respiratory dysfunction (OR = 0.22 [0.08–0.57]). SCB also decreased odds of minor block-related complications (OR = 0.36 [0.20–0.68] and OR = 0.25 [0.15–0.41] for single-injection and continuous blocks, respectively). Consequently, the null joint-hypothesis was rejected, and SCB can be considered an acceptable alternative to ISB. CONCLUSIONS: For acute pain control following shoulder surgery, high-quality evidence indicates that SCB can be used as an effective ISB alternative. SCB is noninferior for postoperative opioid consumption and acute pain, and it reduces the odds of postblock respiratory dysfunction.