The Cause And Prognostic Value Of Hyperchloremia In Critically Ill Stroke Patients

BackgroundCritically ill stroke refers to cerebrovascular diseases that lead to neurotoxic impairment and respiratory,circulatory or other systems severe disorders,mainly includes acute ischemic stroke and intracerebral hemorrhage,which accounting for the major part of patients who required neurocritcal care.These diseases heavily burden the family and society,making the treatment and outcome prediction particularly important.Fluid management aiming at maintaining adequate cerebral blood flow and oxygenation plays a crucial role in the management of neurocritically ill patients.However,the most frequently used solution in critically ill patients today,namely the normal saline(0.9%NaCl solution),is neither normal nor physiological.Previous researches have demonstrated large-volume saline infusion could result in hyperchloremia.Chlorine is an important constant element in human body and mainly exists in the form of chloride(Cl-)combined with sodium and potassium.Chloride is the most abundant anion in the extracellular fluid,constituting approximately one third of plasma tonicity,and plays an essential role in various body functions including the regulation of body fluids,electrolyte balance,acid-base status,muscular activity,osmosis,and immunomodulation.Hyperchloremia is an electrolytic abnormality which is easy to be ignored in the neurointensive care unit(NCU).However,hyperchloremia has been reported to be associated with increased hospital mortality and negative outcome in critically ill patients.In this study,we aimed to investigate the incidence of hyperchloremia,to identify risk factors that related to the development of hyperchloremia in critically ill stroke patients,with particular focus to the infusion of normal saline.The influence of hyperchloremia and chloride fluctuation on 30-day mortality and 6-month functional prognosis in patients with critically ill stroke patients were evaluated as well.MethodWe conducted a retrospective study of a prospective database of consecutive adult patients with first-ever acute ischemic stroke or intracerebral hemorrhage admitted to the NCU of Nanfang hospital,a university-affiliated academic hospital,between Jan 2013 and Dec 2016.A total of 509 critically ill stroke patients were screened and patients were excluded if they younger than 18 or older than 85,admitted beyond 72 hours of the onset,required neurocritical care for less than 72 hours,used hypertonic saline(3%or 10%)or other types of crystalloids except 0.9%saline during the first 72 hours of NCU admission,had premorbid disability(modified Rankin Scale,mRS>1)or end-stage renal disease requiring hemodialysis or creatinine clearance less than 15 mL/min.Finally,405 patients satisfied inclusion and exclusion criteria.Hyperchloremia was defined as[Cl-]?110 mmol/L,we defined the[Cl-]at the time of NCU admission as[Cl-]?(baseline chloride)and the following maximum[Cl-]in the first 72 hours as[Cl-]max.Patients with normal[Cl-]at the time of NCU admission but who developed hyperchloremia in the first 72 hours of NCU stay were defined as new-onset hyperchloremia.The increase in the first 72 hours of serum chloride(?[Cl-],?[Cl-]=[Cl-]max-[Cl-]0)was calculated and grouping based on 5 mmol/L,?[Cl-]?5 mmol/L was regarded as a moderate increase in chloride.Baseline demographics and clinical characteristics of new-onset hyperchloremia and non-new-onset hyperchloremia groups,?[Cl-]?5 mmol/L and?[Cl-]<5 mmol/L groups in the first 72 hours of NCU admission were compared and analyzed.All analyses were performed using SPSS,version 23.0(SPSS,Chicago,IL),categorical variables were compared using the two-sided chi-square test and continuous data were compared by Student's t-test or Mann-Whitney U test,as appropriate.Univariable and multivariable logistic regression analysis were conducted to assess the risk factors of hyperchloremia,30-day mortality and 6-month poor outcome(mRS>3).ResultOf 405 patients were finally eligible for the study,250(61.7%)patients were diagnosed with acute ischemic stroke and 155(38.3%)were intracerebral hemorrhage.There were 35(8.6%)patients with hyperchloremia at NCU admission([Cl-]0?110 mmol/L),and the number increased to 69(17.0%)within 72 hours after admission([Cl-]max?110 mmol/L).Of note,38(9.4%)patients had new-onset hyperchloremia and 367 patients had non-new-onset hyperchloremia in the first 72 hours after NCU admission.The patients with new-onset hyperchloremia had lower Glasgow Coma Scale(GCS)score,higher National Institutes of Health Stroke Scale(NIHSS)and Sequential Organ Failure Assessment(SOFA)scores.Moreover,these patients required more vasopressors and mechanical ventilation when compared with those without new-onset hyperchloremia within 72 hours of NCU admission.However,neither total fluid input nor cumulative fluid balance(CFB)had significant association with new-onset hyperchloremia.In terms of A[Cl-],110(27.1%)patients had moderate increase in chloride(A[Cl-]?5 mmol/L)in the first 72 hours after admission.Univariate and multivariate logistic regression analysis showed that the SOFA score was an independent risk factor both for new-onset hyperchloremia and A[Cl-]?5 mmol/L.During follow up,61(15.1%)patients died within 30 days after admission.Results showed that patients with new-onset hyperchloremia were associated with a 158%increase in odds for 30-day mortality and each 5 mmol/L increase in[Cl-]0,[Cl-]max,and A[Cl-]was associated with a 50%,66%,and 55%increase in odds for 30-day mortality,respectively.In terms of 6-month functional outcome,new-onset hyperchloremia,[Cl-]max and ?[CI-]were all associated with increased risk of poor outcome.Nevertheless,these indicators were not independently related to 30-day mortality and 6-month poor outcome in multivariate models,where SOFA score was also an independent risk factor of 30-day mortality and 6-month poor outcome.ConclusionHyperchloremia is not rare after critically ill stroke and it tends to occur in more severe critically ill acute ischemic stroke and intracerebral hemorrhage patients.While no independent association was found,new-onset hyperchloremia and every 5 mmol/L increment in A[Cl-]within 72 hours of NCU admission were related to an increased odds of all cause 30-day mortality and 6-month poor prognosis in critically ill stroke patients.