Abstract
Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = −0.62; P<0.0001), such that each 1°C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: −0.12 to −0.24 mmol/L [−0.37 to −0.74 mg/dL] per 1°C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia.
Highlights
Low serum phosphorus levels (,0.81 mmol/L [2.5 mg/dL]) are common in hospitalized patients [1]
Of the 76 adult patients who presented to San Francisco General Hospital with acute malaria in the initial 12-year period, 59 (78%) patients had serum phosphorus levels available for analysis, of whom 35 (59%) had low levels (,0.81 mmol/L [2.5 mg/dL]), including 5 (8%) with severe hypophosphatemia (,0.32 mmol/L [1.0 mg/dL ])
Serum phosphorus correlated inversely with temperature (Figure 1, r = 20.62; P,0.0001), such that each 1uC increase in body temperature was associated with a reduction of 0.18 mmol/ L [0.56 mg/dL] in the serum phosphorus level (95% confidence interval: 20.12 to 20.24 mmol/L [20.37 to 20.74 mg/dL] per uC)
Summary
Low serum phosphorus levels (,0.81 mmol/L [2.5 mg/dL]) are common in hospitalized patients [1]. When combined with chronic phosphate depletion, hypophosphatemia can result in serious neurologic, cardiopulmonary, musculoskeletal, hematological, and metabolic dysfunction [1,2,3]. Hypophosphatemia may occur in 40–60% of patients with acute malaria [4,5,6], its pathogenesis in this setting is not known. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. We analyzed a second sample of malaria patients during a subsequent 10-year period
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