Low dose calcium administration increases mortality during septic peritonitis in rats

Calcium is essential for normal cellular function. However, increases in cell calcium are also involved in cellular dysfunction and death by activating destructive enzymatic processes such as proteases, nucleases, and lipases. Since ionized hypocalcemia is common during sepsis, calcium is often administered in an attempt to normalize circulating levels. Previous studies using endotoxin and large amounts of calcium demonstrated increased mortality in calcium-treated animals. This study extends these preliminary data to endogenous sepsis (cecal ligation) and low dose calcium therapy. Sprague Dawley rats (n = 9 per group) had jugular catheters placed and their cecums ligated. They were randomized to an infusion of D5W at 1 ml/hr, calcium chloride at 4 mg/ml/hr (Low Ca), or calcium chloride at 6 mg/ml/hr (High Ca) for 24 hr. An additional group of animals received calcium chloride at 6 mg/ml/hr but had no surgery. Animals were followed for 24 hr survival. A separate group of animals (n = 6 per group) was prepared in a similar manner. Blood was obtained 6 hr following cecal ligation for circulating endotoxin concentrations, and animals were sacrificed. Calcium infusion increased ionized calcium levels slightly (low Ca, 1.12 ± .06 to 1.21 ± .09; high Ca, 1.06 ± .04 to 1.16 ± .05; P < 0.05). Survival (24 hr) was 100% in the nonseptic controls and D5W septic animals, 67% in the low Ca septic group, and 44% (P < 0.05) in the high Ca septic group. Endotoxin levels were 3 ± 1 ng/ml in the nonseptic controls, 245 ± 42 ng/ml in the D5W septic animals, 317 ± 56 ng/ml in the low Ca septic animals, and 652 ± 140 ng/ml (P < 0.05) in the high Ca septic group. We conclude that calcium administration decreases survival and increases circulating endotoxin levels in an experimental model of sepsis.