A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery.

Chronic postoperative pain is common after breast cancer surgery. Peri-operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large-scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double-blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5 mg.kg-1 ) and infusion (2 mg.kg-1 .h-1 ) intra-operatively, and a subcutaneous infusion (1.33 mg.kg-1 .h-1 ) postoperatively for up to 12 h on a standard surgical ward, with novel safety monitoring tools in place. The co-primary outcomes were: in-hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long-term data capture. In-hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74-2.83 [1.12-6.06]) µg.ml-1 , n = 41) and subcutaneous (1.52 (1.28-1.83 [0.64-2.85]) µg.ml-1 , n = 48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥ 99% capture of outcomes at 3 and 6 months. The adjusted odds ratio (95%CI) for postoperative pain at 6 months in the lidocaine arm was 0.790 (0.370-1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger-scale trial is planned.

Preparation and characterization of ruthenium(II) monophosphaferrocene complexes. Reactivity, dynamic solution behavior, and X-ray structure of [RuH(2)(eta(2)-H(2))(PCy(3))2(2-phenyl-3,4-dimethylphosphaferrocene)].

The bis(dihydrogen) complex RuH(2)(H(2))(2)(PCy(3))(2) (1) reacts with 2-phenyl-3,4-dimethylphosphaferrocene (L(1)) to give RuH(2)(H(2))(PCy(3))(2)(L(1)) (2). This dihydride-dihydrogen complex has been characterized by X-ray crystallography and variable-temperature (1)H and (31)P NMR spectroscopy. The exchange between the dihydrogen ligand and the two hydrides is characterized by a DeltaG() of 46.2 kJ/mol at 263 K. H/D exchange is readily observed when heating a C(7)D(8) solution of 2 (J(H-D) = 30 Hz). The H(2) ligand in 2 can be displaced by ethylene or carbon monoxide leading to the corresponding ethylene or carbonyl complexes. The reaction of 1 with 2 equiv of 3,4-dimethylphosphaferrocene (L(2)) yields the dihydride complex RuH(2)(PCy(3))(2)(L(2))(2) (5).