British journal of anaesthesia
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The human p.G2434R variant of the RYR1 gene is most frequently associated with malignant hyperthermia (MH) in the UK. We report the phenotype of a knock-in mouse that expresses the RYR1 variant p.G2435R, which is isogenetic with the human variant. ⋯ RYR1 pG2435R mice demonstrated gene dose-dependent in vitro and in vivo responses to pharmacological and environmental stressors that parallel those seen in patients with the human RYR1 variant p.G2434R.
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Prothrombin complex concentrate (PCC) is increasingly used to correct acquired coagulopathy in trauma and surgery. Dosing of PCC is guided by the prothrombin time, which only reflects the onset of thrombin generation, but does not account for variations in intrinsic pathway coagulation factors, including factor IX (FIX). We hypothesised that FIX contained in PCC could strongly influence thrombin generation patterns. ⋯ FIX derived from PCC strongly enhances tissue factor-triggered thrombin generation in the presence of elevated FVIII activity. Haemodilution further enhances procoagulant effects of FIX and FVIII by slowing down inhibition of procoagulant enzymes. Dosing of PCC per prothrombin time may underestimate PCC's procoagulant potential because it does not account for intrinsic tenase or antithrombin activity.
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Placement of local anaesthetic within the adductor canal using ultrasonography is an alternative to femoral nerve blocks for postoperative pain relief after knee joint replacement surgery. However, the effect of an inflated thigh tourniquet on the distribution of local anaesthetic within the adductor canal is unknown. The aim of this cadaveric study was to compare the distribution of radio-opaque dye within the adductor canal in the presence or absence of an inflated thigh tourniquet. ⋯ Application and inflation of thigh tourniquets significantly increased the combined superior-inferior dye distribution within the adductor canal of cadaveric limbs. There was insufficient evidence to suggest significant proximal spread of 25 ml of local anaesthetic to involve the motor branches of the femoral nerve. In some patients, the local anaesthetic may reach the popliteal fossa in close approximation to the sciatic nerve.