Research Article: Fever as a Cause of Hypophosphatemia in Patients with Malaria

Date Published: December 26, 2007

Publisher: Public Library of Science

Author(s): Richard Haber, Warren Browner, Nicholas White.

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.

Partial Text: 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]–[3]. 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 ]). Patients with low serum phosphorus levels on admission had a significantly greater mean body temperature than those with normal levels (Table 1), and all 13 patients with temperatures ≥40.2°C had hypophosphatemia (Figure 1). There were also marginally significant differences in mean serum potassium and bicarbonate levels in those with and without hypophosphatemia (Table 1). Elevated body temperature is not listed as a cause of hypophosphatemia in reviews of this topic [1]–[3], nor has a linear relation between body temperature and serum phosphorus been reported previously. However, hypophosphatemia has been observed consistently in patients with conditions characterized by fever (altered hypothalamic set point) or hyperthermia (inability to dissipate a heat load), suggesting that the correlation between body temperature and serum phosphorus may not be unique to malaria. Whether the hypophosphatemia observed in these conditions is linearly related to body temperature has not been studied. Source:


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