Colchicine reduces lung injury in experimental acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Rats were treated with colchicine (1 mg/kg) or placebo for three days prior to intravenous oleic acid-induced ALI (150 mg/kg). Four hours later they were studied and compared to a sham group. Colchicine reduced the area of histological lung injury by 61%, reduced lung edema, and markedly improved oxygenation by increasing PaO2/FiO2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO2 and respiratory acidosis. Lung neutrophil recruitment, assessed by myeloperoxidase immunostaining, was greatly increased after injury from 1.16 ± 0.19% to 8.86 ± 0.66% and significantly reduced by colchicine to 5.95 ± 1.13%. Increased lung NETosis was also reduced by therapy. Circulating leukocytosis after ALI was not reduced by colchicine therapy, but neutrophils reactivity and CD4 and CD8 cell surface expression on lymphocyte populations were restored. Colchicine reduces ALI and respiratory failure in experimental ARDS in relation with reduced lung neutrophil recruitment and reduced circulating leukocyte activation. This study supports the clinical development of colchicine for the prevention of ARDS in conditions causing ALI

A Delphi-Based Consensus Statement on the Management of Anticoagulated Patients With Botulinum Toxin for Limb Spasticity.

Objective To create a consensus statement on the considerations for treatment of anticoagulated patients with botulinum toxin A (BoNTA) intramuscular injections for limb spasticity. Design We used the Delphi method. Setting A multiquestion electronic survey. Participants Canadian physicians (N=39) who use BoNTA injections for spasticity management in their practice. Interventions After the survey was sent, there were e-mail discussions to facilitate an understanding of the issues underlying the responses. Consensus for each question was reached when agreement level was ≥75%. Main Outcome Measures Not applicable. Results When injecting BoNTA in anticoagulated patients: (1) BoNTA injections should not be withheld regardless of muscles injected; (2) a 25G or smaller size needle should be used when injecting into the deep leg compartment muscles; (3) international normalized ratio (INR) level should be ≤3.5 when injecting the deep leg compartment muscles; (4) if there are clinical concerns such as history of a fluctuating INR, recent bleeding, excessive or new bruising, then an INR value on the day of injection with point-of-care testing or within the preceding 2-3 days should be taken into consideration when injecting deep compartment muscles; (5) the concern regarding bleeding when using direct oral anticoagulants (DOACs) should be the same as with warfarin (when INR is in the therapeutic range); (6) the dose and scheduling of DOACs should not be altered for the purpose of minimizing the risk of bleeding prior to BoNTA injections. Conclusions These consensus statements provide a framework for physicians to consider when injecting BoNTA for spasticity in anticoagulated patients. These consensus statements are not strict guidelines or decision-making steps, but rather an effort to generate common understanding in the absence of evidence in the literature