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Hypercalcemia remains a poorly recognized cause of acute renal failure in patients with major burns that occurs as early as 3 weeks after injury [62]. The triad of hypercalcemia, arterial hypertension and acute renal failure is well known in other critical illnesses [40, 77], while the association of hypercalcemia and renal failure in patients with major burns is much less reported in the literature. In a recent retrospective study, hypercalcemia was shown to occur in 19 % of the burned patients with hospital lengths of stay of more than 28 days, and was noted to be associated with an increased mortality [88].

In our own setting, 30% of patients developed hypercalcemia: median time to the first hypercalcemia value was 21 days [88]. Hypercalcemia may also occur in patients with smaller burns requiring a stay of more than 20 days in the ICU. Ionized calcium determination enabled earlier detection, while using total calcium determination ‘with albumin correction’ was only slightly sensitive, as shown by normal corrected values in 15 cases with ionized hypercalcemia.

Treatment of hypercalcemia includes hydration, volume expansion and early mobilization. As most causes of severe hypercalcemia depend on increased osteoclast activation, drugs that decrease bone turnover are effective [50]. The treatment of choice in cases that do not resolve with the simple measures relies on the bisphosphonates, pamidronate disodium and zoledronic acid, which are available in intravenous forms [37]. In burned children, acute intravenous pamidronate administration has been shown to help to preserve bone mass [60], achieving a sustained therapeutic effect on bone [81]. An alternative treatment of the latter in burns includes anabolic agents such as oxandrolone [61]. The bisphosphonates have been advocated in the prevention of heterotrophic ossification, a complication that occurs in 1.2% of burn patients.

Bone demineralization and osteoporosis

Due to the substantial alterations of calcium and phosphorus metabolism and bone formation is reduced both in adults and children when burns exceed 40% TBSA. Bone mineral density is significantly lower in burned children compared with the same

age normal children. Girls have improved bone mineral content and percent fat compared with boys [52]. The consequences are increased risk of fractures, decreased growth velocity and stunting [11]. The bone is affected by various means: alteration of mineral metabolism, elevated cytokine and corticosteroid levels, decreased growth hormone (GH), nutritional deficiencies, and intra-operative immobilization. Cytokines contribute to the alterations, particularly interleukin-1(and interleukin-6, both of which are greatly increased in burns and stimulate osteoblast-mediated bone resorption. The increased cortisol production in thermal injury, leads to decreased bone formation, and the low GH levels fail to promote bone formation [59], further exacerbating the situation. Various studies suggest that immobilization plays a significant role in the pathogenesis of burn-associated bone disease [58]. Alterations of magnesium and calcium homeostasis constitute another cause. Hypocalcemia and hypomagnesemia are constant findings, and ionized calcium levels remain low for weeks [97]. The alterations are partly explained by large exudative magnesium and phosphorus losses [11] A close monitoring of ionized calcium, magnesium, and inorganic phosphate levels is mandatory, since burn patients usually require substantial supplementation by intravenous or enteral routes.

Micronutrients and antioxidants

Critically ill burned patients are characterized by a strong oxidative stress, an intense inflammatory response, and a hyper-metabolic state that can last months. Trace element (TE) deficiencies have repeatedly been described. The complications observed in major burns such as infections and delayed wound healing, can be partly attributed to TE deficiencies [16]. Plasma TE concentrations are low as a result of TE losses in biological fluids, low intakes, dilution by fluid resuscitation, and redistribution from plasma to tissues mediated by the inflammatory response. The large exudative losses cause negative TE balances. Intravenous supplementation trials show that early substitution improves recovery (IV doses: Cu 3.5 mg/d, Se 400–500 mcg/d, Zn 40 mg/d), reduces infectious complications (particularly noso-

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comial pneumonia) [14], normalize thyroid function, improve wound healing and shorten hospital length of stay [16]. The mechanisms underlying these improvements are a combination of antioxidant effects (particularly of selenium through restoration of glutathione peroxidase activity), but also immune (Cu, Se, Zn) and anabolic effects (Zn particularly).

High vitamin C requirements after major burns were identified already in the 40s, and have been confirmed since. Very interesting studies by Dubick et al. [34] and Tanaka et al. [99] have demonstrated that high doses of vitamin C administered during the first 24 hours after a major injury reduced the capillary leak, probably through antioxidant mechanisms, resulting in significant reductions in fluid resuscitation requirements. This has not yet become standard of clinical practice, but might do so in the coming years.

Thrombosis prophylaxis

Hematological alterations observed after burns are complex and can last for several months and can be summarized as follows:

uring the early phase after burns, fibrin split products increase.

Dilution and consumption explain the early low PT values.

The coagulation cascade is activated.

Fibrin, factors V and VIII increase as part of acute phase response.

Antithrombin deficiency is frequent [64, 72].

Thrombocytosis develops when wounds are closing.

The risk of deep venous thrombosis and of pulmonary embolism is at least as high as in any other surgical condition [38]. In our CHUV experience, 13% of patients develop some form of thrombotic complication. Specific risk factors include central venous lines, prolonged bed-rest and an intense inflammatory state. Prophylaxis should be started from admission. Interruptions for surgery should be reduced to minimum and discussed with the surgical team.

Conclusion

The critical care of the thermally injured patient, is complex and challenging for all involved. The result are however rather rewarding. The field has evolved tremendously over the last few decades and will continue to improve in-order to provide these challenging patients with the best care possible. Many questions remain in the etiology and thus treatment of these patients. Many of these can only be answered by the ongoing research in the field. This brief chapter highlights some of the important aspects of the care, and serves simply as a guide to the care of these patients.

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