Pathophysiologic and clinical correlates of hypophosphatemia and the relationship with sepsis and outcome in postoperative patients after hepatectomy

Abstract

Hypophosphatemia in critically ill and postoperative (p.o.) patients is a multifactorial event, and is also related to severity of illness. This study was conducted to assess pathophysiologic correlates of hypophosphatemia and the simultaneous relationship with clinical events after hepatectomy. A total of 333 measurements were obtained in 59 patients: these were performed preoperatively and at p.o. days 1, 3, and 7 in all patients, and subsequently, until recovery or death, only in those with complications. Measurements included plasma phosphate together with a large number of additional blood chemistries, taking into account primary and associated diseases, events associated with the operation, doses of parenteral substrates, occurrence of sepsis or other p.o. complications, outcome, and a consistent set of complementary variables. Plasma phosphate decreased at p.o. days 1 and 3 (P < 0.001) and retumed to a level close to baseline at p.o. day 7. Regression analysis showed that phosphate was related simultaneously to patient age (inversely), levels of creatinine and potassium (directly), and dose of parenteral amino acids (inversely; P < 0.001 for all). Independently of covariation with these variables, there was a decrement in phosphate at p.o. days 1 and 3 that was related specifically to p.o. condition; this decrement had a general component common to all patients, an additional component related to duration of previous hepatic ischemia at surgery, and a further component predictive of the subsequent development of complications (in most cases, sepsis). Plasma phosphate at p.o. day 1 was related inversely to APACHE II score (r2 = 0.4, P < 0.001), and levels lower than 1.5 mg/dL were associated with an almost 4-fold increase in the rate of complications compared with cases with higher phosphate (P < 0.001). The best single variable bridging early evidence of hypophosphatemia to subsequent development of complications was plasma cholesterol, which fell significantly from p.o. day 3 onward in patients with complications compared with those recovering normally (P < 0.01), and in nonsurvivors compared with survivors (P < 0.01). Hypophosphatemia may anticipate clinical evidence of complications by reflecting an early stronger acute-phase response, with shift of phosphate from intra- to extravascular space, or true phosphorus deficiency, which may favor development of complications by impairing high-energy substrate availability for host defense and other cell functions.