Objective Hyperchloremia is frequently observed in critically ill patients in the intensive care unit (ICU). Our study aimed to examine the association of serum chloride (Cl) levels with hospital mortality in septic ICU patients. Design Retrospective cohort study. Setting Urban academic medical center ICU. Patients ICU adult patients with severe sepsis or septic shock who had Cl measured on ICU admission were included. Those with baseline estimated glomerular filtration rate < 15 ml/min/1.73 m2 or chronic dialysis were excluded. Intervention: None. Measurements and Main Results Of 1940 patients included in the study, 615 (31.7%) had hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission. All-cause hospital mortality was the dependent variable. Cl on ICU admission (Cl0), Cl at 72 h (Cl72), and delta Cl (ΔCl = Cl72 – Cl0) were the independent variables. Those with Cl0 ≥ 110 mEq/L were older and had higher cumulative fluid balance, base deficit, and sequential organ failure assessment scores. Multivariate analysis showed that higher Cl72 but not Cl0 was independently associated with hospital mortality in the subgroup of patients with hyperchloremia on ICU admission [adjusted odds ratio (OR) for Cl72 per 5 mEq/L increase = 1.27, 95% CI (1.02–1.59), P = 0.03]. For those who were hyperchloremic on ICU admission, every within-subject 5 mEq/L increment in Cl72 was independently associated with hospital mortality [adjusted OR for ΔCl 5 mEq/L = 1.37, 95% CI [1.11–1.69], P = 0.003]. Conclusions In critically ill septic patients manifesting hyperchloremia (Cl ≥110 mEq/L) on ICU admission, higher Cl levels and within-subject worsening hyperchloremia at 72 h of ICU stay were associated with all-cause hospital mortality. These associations were independent of base deficit, cumulative fluid balance, acute kidney injury, and other critical illness parameters.

There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity.

Objective Incident acute kidney injury (AKI) and prevalent chronic kidney disease (CKD) are commonly encountered in septic patients. We examined the differential effect of AKI and CKD on the association between cumulative fluid balance (CFB) and hospital mortality in critically ill septic patients. Design Retrospective cohort study. Setting Urban academic medical center ICU. Patients ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 h of ICU admission. Patients with estimated glomerular filtration rate <15 mL/min/1.73m2 or receiving chronic dialysis were excluded. Interventions None. Measurements and Main Results 2632 patients, 1211 with CKD, were followed until hospital death or discharge. AKI occurred in 1525 (57.9%), of whom 679 (44.5%) had CKD. Hospital mortality occurred in 603 (22.9%) patients. Every 1 L increase in CFB at 72 h of ICU admission was independently associated with hospital mortality in all patients, adjusted odds ratio (aOR) 1.06, 95% CI (1.04–1.08), p <0.001, and in each AKI/CKD subgroup: aOR 1.06 (1.03–1.09) for AKI+/CKD+; 1.09 (1.05–1.13) for AKI−/CKD+; 1.05 (1.03–1.08) for AKI+/CKD−; and 1.07 (1.02–1.11) for AKI−/CKD−. There was a significant interaction between AKI and CKD on CFB, p =0.005, such that different CFB cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for AKI+/CKD+; 3.8 L for AKI−/CKD+; 4.3 L for AKI+/CKD−; and 1.5 L for AKI−/CKD−. The addition of CFB to the admission SOFA score had increased prognostic utility for hospital mortality when compared to SOFA alone, particularly in patients with AKI. Conclusions Higher CFB at 72 h of ICU admission was independently associated with hospital mortality regardless of AKI or CKD presence. We characterized CFB cut-offs associated with hospital mortality based on AKI/CKD status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

BackgroundHyperchloremia is common in critically ill septic patients. The impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not well studied. We investigated the association between hyperchloremia and AKI within the first 72 h of intensive care unit (ICU) admission.Methods6490 ICU adult patients admitted with severe sepsis or septic shock were screened for eligibility. Exclusion criteria included: AKI on admission, baseline estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, chronic renal replacement therapy, absent baseline serum creatinine data, and absent serum chloride data on ICU admission.ResultsA total of 1045 patients were available for analysis following the implementation of eligibility criteria: 303 (29%) had hyperchloremia (Cl0 ≥ 110 mEq/L) on ICU admission, 561 (54%) were normochloremic (Cl0 101–109 mEq/L) and 181 (17%) were hypochloremic (Cl0 ≤ 100 mEq/L). AKI within the first 72 h of ICU stay was the dependent variable. Chloride on ICU admission (Cl0) and change in Cl by 72 h (ΔCl = Cl72 – Cl0) were the independent variables. The odds for AKI were not different in the hyperchloremic group when compared to the normochloremic group [adjusted odds ratio (OR) =0.80, 95% confidence interval [CI] (0.51–1.25); p = 0.33] after adjusting for demographics, comorbidities, baseline kidney function, drug exposure and critical illness indicators including cumulative fluid balance and base deficit. Furthermore, within the subgroup of patients with hyperchloremia on ICU admission, neither Cl0 nor ΔCl was associated with AKI or with moderate/severe AKI (KDIGO Stage ≥2).ConclusionsHyperchloremia occurs commonly among critically ill septic patients admitted to the ICU, but does not appear to be associated with an increased risk for AKI within the first 72 h of admission.

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