The Risk Factors Of Hypophosphatemia And Its Association With Mortality In Neurocritical Patients

BackgroundPhosphorus is an essential element for all living cells.And it plays a key role in different kind of physiologic processes,such as energy storage and metabolism,genetic information storage and traslation,acid-base buffering,activation of enzymes and cell-signalling cascade.Normal range of the values of total serum inorganic phosphate(iP)level is 0.80 to 1.45mmol/L.Phosphorus is obtained from daily diet,absorbed by the intestine and excreted by the renal.The serum inorganic phosphate level is influenced by the dietary intake,intestine obsorption and renal excretion of phosphate and the internal redistribution of phosphate between intracellular and extracellular fluid.Hypophosphatemia is common in critically ill patients.And there are three different mechanisms of the incidence of hypophosphatemia:decreased intestinal absorption,increased renal excretion,or redistribution of phosphate into the intracellular space.Although most patients with mild hypophosphatemia are asymptomatic,life-threatening complications of hypophosphatemia have been described.The most common symptoms of hypophosphatemia include respiratory muscle dysfunction,decreased myocardial contractility and arrhythmia.The association between hypophosphatemia and poor outcome in critically ill patients has been described.It has been reported that in critical care unit patients with hypophosphatemia had higher mortality rates.However,most of studies on the association between hypophosphatemia and clinical outcome did not analyze the independent relationship between hypophosphatemia and outcome after the necessary adjustments for inllness severity.And whether hypophosphatemia is an independent risk factor of higher mortality among critically ill patient still remains controversial today.In addition,there are few studies which focused on the risk factors and the prognostic value of hypophosphatemia in neurocritical patients.The aim of this study was to assess the risk factors of hypophosphatemia and the association of phosphate concentration with the clinical outcome in neurocritical patients.MethodWe conducted a single-center,retrospective and observational investigation in the neurocritical care unit(NCU)of a university-affliated hospital.Adult patients who were admitted to NCU during the period from Jan 2013 to Dec 2016 and stayed for more than 72h in NCU were enrolled.We recorded the first serum phosphate value within 24 hours after NCU admission(iP0),the minimum phosphatemia value between 24 to 96 hours after NCU admission(iP1),and the minimum phosphate value within 96h after NCU admission(iPmin).The decrease of serum phosphate(△ P= iP0-iP1)was calculated and △ P≥0.25mmol/L was regarded as moderate increase in chloride.Univariable and multivariable logistic regression analysis were conducted to assess the risk factors of hypophosphatemia and 30-day mortality.ResultHypophosphatemia(defined as iP<0.81mmol/L)occurred in 18.84%patients within 24h after admission and 31.65%patients between 24 to 96 hours after admission.As for the risk factors of hypophosphatemia,in patients without hyperphosphatemia(defined as iP>1.45mmol/L),Glasgow Coma Scale(GCS)score,intracranial infection,pH of arterial blood and the level of serum C-reactive protein were independently associated with iP0.Acute physiology and chronic health evaluation II(APACHE II)score were independently associated with △P(OR= 1.090,95%CI 1.037-1.145,p=0.001).In patients with normal iP0(0.81 to 1.45mmol/L),26.77%of them developed hypophosphatemia between 24 to 96 hours after admission,which was defined as NCU acquired hypophosphatemia.APACHE II score were independently associated with the incidence of NCU acqueired hypophosphatemia(OR=1.073,95%CI 1.016-1.133,p=0.011).As for the relationship between hypophosphatemia and the mortality of patients without hyperphosphatemia,the average level of iPmin was significantly lower in patients who died within 30 days after admission,compared to those who survived(0.75±0.22 VS 0.84±0.22,p=0.017).In the univariable analyze of 30-day mortality,there was significant association between 30-day mortality and iPmin(OR=0.182,95%CI 0.044-0.752,p=0.019).And NCU acquired hypophosphatemia was also significantly associated with 30-day mortality(OR=2.703,95%CI 1.273-5.738,p=0.010).However,in the multivariable analyze,iPmin was not independently associated with 30-day mortality.APACHE II score was independently associated with 30-day mortality.As for the secondary outcome indicator 30-day modified Rankin scale(mRS)score,patients with hypophosphatemia had significantly higher mRS scores,compared to patients with normal serum phosphate(p=0.008).In patients with normal iP0 levels,patients who developed NCU acquired hypo-phospatemia had significantly higher mRS scores compared to patients without NCU acquired hypophosphatemia(p=0.002).And patients with △ P ≥ 0.25mmol/L had significantly higher mRS scores compared to patients with △ P<0.25mmol/L(p=0.009).ConclusionHypophosphatemia is common in neurocritical patients.The risk factors of hypophosphatemia within 24h after NCU admission included low GCS score,high C-reactive protein level,high pH level of arterial blood.Patients with normal phosphate level at admission may develop NCU acquired hypophosphatemia.The incidence of NCU acquired hypophosphatemia was related to the illness severity of patients.Thus,it is necessary to strictly monitor the phosphate level of NCU patients.Patients with hypophosphatemia turned out to have higher mortality and poor clinical outcome.However,serum phosphate level was not independently associated with mortality,suggesting that hypophosphatemia are likely a marker of illness severity rather than an independent contributor to mortality.