Although previous studies have indicated that hypophosphatemia is associated with worse clinical outcomes in critically ill patients [14, 20], few studies have been carried out to investigate the association between the serum phosphorus levels at admission and the outcomes of general ICU population. Whether hypophosphatemia itself causes higher mortality or is a marker of illness severity remains unclear.
Earlier evidence has revealed that episodes of hypophosphatemia during the ICU stay is associated with higher mortality in the ICU population [10, 15,16,17]. After the adjustments for confounding factors, Marcus Broman [15] found that when compared with normal phosphate group, patients with hypophosphatemia episodes had higher risk of death (HR = 1.2, 98.3% CI = 1.0–1.5, P = .0089). However, they defined hypophosphatemia as phosphate levels < 0.7 mmol/L and no phosphate levels > mmol/L during the ICU stay. A retrospective study was conducted by Yi Yang [17] on patients who had developed hypophosphatemia during the CVVH therapy period. They divided the patients into two groups, the ratio of hypophosphatemia to total CVVH therapy days lower than 0.58 defined as low ratio group, and the other as high ratio group. They found that, compared to the low ratio group, the high ratio group had a 1.451-fold in 28-day mortality rate (95% CI 1.103–1.910, P = 0.008). Renana Shor [16] reported that sever hypophosphatemia indicated a higher mortality than those without severe hypophosphatemia (80.8% VS 34.5%, P = 0.001). But unlike our study, they selected septic patients for study subjects, with a small population size. On the other hand, Dominik [21] and Satoshi [20] found that hypophosphatemia was associated with a longer hospital stay, but was not an independent predictor of mortality in the ICU population. The association between serum phosphate abnormalities and the clinical prognosis is still debatable. We conducted the study in the general ICU, most of our patients admitted to ICU for post-operation monitoring and sepsis. We found that hypophosphatemia at ICU admission was related to longer ICU and hospital stays, and hypophosphatemia was associated with higher mortality. The results of the multivariable logistic regression analysis showed that hypophosphatemia (< 0.80 mmol/L) can predict 28-day mortality in ICU.
We found that male sex, APACHE II scores, serum albumin level and hypophosphatemia were associated with 28-day mortality in the general ICU population. Then, we examined whether the association between phosphorus levels and 28-day mortality were related to the illness severity and the nutritional status. Even after adjustment for APACHE II scores and serum albumin, and the gender, hypophosphatemia (< 0.80 mmol/L) was still associated with increased 28-day mortality. This indicates that hypophosphatemia (< 0.80 mmol/L) was associated with the 28-day mortality regardless of the illness severity and nutritional status in the general ICU.
In the present investigation, we established that hypophosphatemia was associated with an increased duration of mechanical ventilation. As Christopher [22] reported, the duration of ventilation in the hypophosphatemia group was 3.0 [1.7–5.9] days, whereas in the normophosphatemia group it was 4.8 [2.3–10.5] days. Phosphorus is a source of ATP (adenosine triphosphate) required for neurologic functions and muscular contraction. Phosphate supply disturbance can lead to multiple organ system dysfunctions, included respiratory failure [3, 4]. As established in our study, the patients in the hypophosphatemia group required more intensive and prolonged mechanical ventilation.
Our study showed that the hypophosphatemia group had a higher proportion of RRT than that in the normophosphatemia group (8.8% VS 18.7%, P = 0.00), and the former had a longer duration of RRT time. Renal replacement therapy (RRT) has been recommended for severe renal failure in critically-ill patients, such as those patients with sepsis shock and complicated with acute renal failure (ARF). RRT is also used in patient with chronic renal failure in the situation of hemodynamic instability. In our study population, although there was no difference between the two groups in the reasons for ICU admission, but the number of septic shock patients complicated with acute renal insufficiency and received RRT therapy in hypophosphatemia group is higher than that in the control group (22.4% VS 36.5%, P = 0.01).
Hypophosphatemia may lead to a multitude of complications in critically ill patients [2, 10] since numerous cellular mechanisms require phosphates. Hypophosphatemia is associated with cardiac, respiratory, immunologic, and hematologic disorders, which is a subsequence of the impaired energy metabolism. Hypophosphatemia can be asymptomatic but may as well be accompanied by fatal clinical complications, leading to poor outcomes in critically ill patients.
Some important limitations to our study should be acknowledged. First, this investigation was retrospective and performed at a single medical center. Second, we identified only the baseline measurements of the plasma phosphate level, which hindered the evaluation of plasma phosphate values over time. Phosphate replacement [22] is recommended in symptomatic hypophosphatemia and phosphate levels < 0.32 mmol/L. Whether maintenance of normal plasma phosphate level and correction of the hypophosphatemia in critically -ill-patients can improve outcome is currently unknown. Further randomized controlled trials are required to assess the benefit when the patients are treated with hypophosphatemia. Finally, we did not have information on the other confounders, such as fluid therapy, but we had a large number of other confounding variables for adjustment. Therefore, further studies in larger populations are required to confirm our findings.
