Critical bleeding requiring massive transfusion is associated with significant mortality and morbidity 1. Many complications of massive transfusion and critical bleeding are interrelated and may perpetuate one another. It is clear that preventing the 'vicious cycle' of coagulopathy, hypothermia and acidosis is pivotal in the survival of patients with critical bleeding requiring massive transfusion 1-3. Calcium is an important cation in the body and has a fundamental role as a co-factor in enzymatic reactions, transmembrane ion flux, muscle contraction, neuronal activity, coagulation cascade, platelet aggregation, regulation of vasomotor tone and cardiac contractility 4,5. Hypocalcaemia may occur in patients with critical bleeding requiring massive transfusion, leading to worsening coagulopathy 6,7 and prolonged QT interval and ventricular arrhythmias in the presence of co-existing hypomagnesaemia 8. The minimum acceptable ionised calcium concentration during critical bleeding remains controversial and uncertain. Although an in vitro study demonstrated that ionised calcium concentrations >0.56 mmol/l would be adequate for clot formation 9 , clinical studies indicate that ionised calcium concentrations <0.90 mmol/l during critical bleeding are associated with worse outcomes, although it is not clear that this is through an effect on coagulation 2. Citrate toxicity has been suggested as the mechanism of hypocalcaemia during massive transfusion 6,10. However, recent evidence suggests that intravenous colloid solutions and ischaemiareperfusion can also cause hypocalcaemia and exacerbate hypocalcaemia-induced coagulopathy 11,12 .

Optimal nutritional support, both in terms of route and formulation, in the critically ill remains controversial 1,2 . Apart from ensuring adequate caloric and protein intake, supplementation of micronutrients such as omega-3 fatty acids, glutamine, selenium and antioxidant vitamins has also been suggested to be important 3,4 . The rationale behind such practice is based on observational data in the critically ill.Oxidant stress is radically increased in critical illness and antioxidant capacity is consumed 5 .Circulatory antioxidant deficiency appears to be common in high acuity illnesses 6,7 and may contribute to patient mortality [8][9][10] . Serum concentrations of antioxidant vitamins are often transiently depressed as part of the acute phase response in critical illness 11,12 , particularly Vitamins A and E, whose concentrations are almost unrecordable in septic shock 5 and burns >20% of body surface area 13 . Major fluid shifts, diarrhoea, dialysis, diuresis and burn exudates contribute to substantial losses of watersoluble vitamins and trace elements 8 . Older studies suggested that deficiencies of the B vitamins were associated with complications and poor outcome in patients with critical illness 14,15 .While it may seem intuitive to supplement vitamins in all critically ill patients, the results of studies assessing the effects of antioxidant supplementation remain inconsistent 16 . Although studies employing supplementation of these vitamins have confirmed increases in plasma concentrations 9,10,17,18 , a consistent effect upon antioxidant defences 9 or outcome has not yet been convincingly demonstrated 10,18,19 . Furthermore, many of these studies did not measure the concentrations

This review aims to summarise the physiology of C-reactive protein (CRP), its possible roles and limitations as an inflammatory and infective marker in intensive care medicine, and also the emerging roles of CRP in the pathogenesis of cardiovascular and autoimmune diseases. Observational and animal studies on uses of CRP were retrieved from the PubMed database without any language restrictions. Quantitative data were not pooled because of the heterogeneity of patient characteristics and disparate ways in which CRP was studied. Serum CRP concentrations are determined by the synthetic rate of its production in the liver regulated predominantly by interleukin-6. It has a half-life of 19 hours and is relatively slow in its onset and offset in response to an acute inflammatory process when compared to procalcitonin. It has some favourable properties and limitations as an inflammatory marker. An elevated CRP concentration is not specific to infections and the absolute CRP concentrations cannot be used to differentiate between bacterial, fungal and severe viral infections. The dynamic response of CRP to therapy that aims to modify the underlying inflammatory process and the clinical context of a patient are of pivotal importance when CRP concentrations are interpreted. CRP is found to be a significant partaker and prognostic factor in a wide range of cardiovascular and chronic diseases. In summary, CRP concentration is an important prognostic factor of many acute and chronic diseases. Serial CRP measurements may be useful to reflect a patient's response to therapy that aims to modify the underlying inflammatory process.