Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis.

OBJECTIVES: Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014. PATIENTS: Adult critical ill patients with type 2 diabetes mellitus and sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35-0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62-0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22-0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42-12.1). CONCLUSIONS: Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis.

The impact of acute kidney injury by serum creatinine or urine output criteria on major adverse kidney events in cardiac surgery patients.

OBJECTIVES: Oliguria after cardiac surgery remains of uncertain clinical significance. Therefore, we investigated the relationship of acute kidney injury severity across urine output and creatinine domains with the risk for major adverse kidney events at 180 days. We aimed to determine the impact of acute kidney injury after cardiac surgery. METHODS: In a retrospective multicenter study, we investigated the relationship of acute kidney injury severity across urine output and creatinine categories with the risk for major adverse kidney events at 180 days-the composite of death, dialysis, and persistent renal dysfunction-using a large database of patients undergoing cardiac surgery at 1 of 5 hospitals within the regional medical system. We analyzed electronic records from 6637 patients treated between 2008 and 2014, of whom 5389 (81.2%) developed any acute kidney injury within 72 hours of surgery. We stratified patients by levels of urine output or serum creatinine according to Kidney Disease Improving Global Outcomes criteria for acute kidney injury. RESULTS: Major adverse kidney events at 180 days increased from 4.5% for no acute kidney injury to 61.3% for stage 3 acute kidney injury (P < .001). Death or dialysis by day 180 was 2.4% for those with no acute kidney injury and 46.7% for those with acute kidney injury stage 3 (P < .001). Isolated oliguria was common (42.6%), and isolated azotemia was rare (6.1%). Even stage 1 acute kidney injury by oliguria alone was associated with an increased risk of major adverse kidney events at 180 days (odds ratio, 1.76; 1.20-2.57; P = .004), mainly driven by persistent renal dysfunction (odds ratio, 2.01; 1.26-3.18; P = .003). CONCLUSIONS: Acute kidney injury is common in patients undergoing cardiac surgery, and even milder forms of acute kidney injury, including isolated stage 1 oliguria, are associated with adverse long-term consequences.

Effects of 5% Albumin Plus Saline Versus Saline Alone on Outcomes From Large-Volume Resuscitation in Critically Ill Patients.

OBJECTIVES: To compare 5% albumin with 0.9% saline for large-volume resuscitation (> 60 mL/Kg within 24 hr), on mortality and development of acute kidney injury. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 13 hospitals across Western Pennsylvania. We analyzed two independent cohorts, the High-Density Intensive Care databases: High-Density Intensive Care-08 (July 2000 to October 2008, H08) and High-Density Intensive Care-15 (October 2008 to December 2014, H15). PATIENTS: Total of 18,629 critically ill patients requiring large-volume resuscitation. INTERVENTIONS: Five percent of albumin in addition to saline versus 0.9% saline. MEASUREMENTS AND MAIN RESULTS: After excluding patients with acute kidney injury prior to large-volume resuscitation, 673 of 2,428 patients (27.7%) and 1,814 of 16,201 patients (11.2%) received 5% albumin in H08 and H15, respectively. Use of 5% albumin was associated with decreased 30-day mortality by multivariate regression in H08 (odds ratio 0.65; 95% CI 0.49-0.85; p = 0.002) and in H15 (0.52; 95% CI 0.44-0.62; p < 0.0001) but was associated with increased acute kidney injury in H08 (odds ratio 1.98; 95% CI 1.56-2.51; p < 0.001) and in H15 (odds ratio 1.75; 95% CI 1.58-1.95; p < 0.001). However, 5% albumin was not associated with persistent acute kidney injury and resulted in decreased major adverse kidney event at 30, 90, and 365 days. Propensity matched analysis confirmed similar associations with mortality and acute kidney injury. CONCLUSIONS: During large-volume resuscitation, 5% albumin was associated with reduced mortality and major adverse kidney event at 30, 90, and 365 days. However, a higher rate of acute kidney injury of any stage was observed that did not translate into persistent renal dysfunction.

Acute Kidney Injury in Critically Ill Patients After Noncardiac Major Surgery: Early Versus Late Onset.

OBJECTIVES: Acute kidney injury is a common complication of major surgery. However, acute kidney injury occurring within the first 48 hours after surgery (early acute kidney injury) and therefore likely related to the surgery itself is possibly different from acute kidney injury occurring after 48 hours (late acute kidney injury). The aim of this study was to describe the epidemiology and identify differences in risk factors and outcomes between early and late acute kidney injury following major surgery. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Patients admitted to ICU following noncardiac major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data from 3,499 patients and defined acute kidney injury according to full Kidney Disease: Improving Global Outcomes criteria and classified as early (48 hr or less) or late (> 48 hr to 7 d) based on time from surgery. Separate multivariable logistic regression models were fit to identify risk factors of early acute kidney injury compared with no acute kidney injury and risk factors of late acute kidney injury compared with no acute kidney injury. Overall 41.7% (1,459/3,499) developed early acute kidney injury versus 14.4% (504/3,499) late acute kidney injury. Most acute kidney injury occurred within 48 hours following surgery and 12 hours was the peak interval. Risk factors for early acute kidney injury included increased age, body mass index, decreased estimated glomerular filtration rate, and anemia, whereas late acute kidney injury cases were closely associated with postoperative factors, like sepsis, mechanical ventilation, positive fluid balance, blood transfusions and exposure to diuretics, vasopressors, and nonsteroidal anti-inflammatory drugs. After adjusting for age, body mass index, estimated glomerular filtration rate, comorbidities, surgery type, both early acute kidney injury (odds ratio [95% CI], 1.84 [1.50-2.27]) and late acute kidney injury (odds ratio [95% CI], 1.42 [1.09-1.85]) were associated with higher 1-year mortality compared with patients without acute kidney injury. We found similar results in a validation cohort of 10,723 patients admitted between 2008 and 2014. CONCLUSIONS: Most surgery-related acute kidney injury occurred within 48 hours of surgery. Acute kidney injury occurring within the first 48 hours was associated with underlying health, whereas acute kidney injury occurring after 48 hours was related to postoperative complications or drugs. Design of clinical and experimental interventions for acute kidney injury in this population should consider these differences.

Intensive Monitoring of Urine Output Is Associated With Increased Detection of Acute Kidney Injury and Improved Outcomes.

BACKGROUND: Urine output (UO) is a vital sign for critically ill patients, but standards for monitoring and reporting vary widely between ICUs. Careful monitoring of UO could lead to earlier recognition of acute kidney injury (AKI) and better fluid management. We sought to determine if the intensity of UO monitoring is associated with outcomes in patients with and those without AKI. METHODS: This was a retrospective cohort study including 15,724 adults admitted to ICUs from 2000 to 2008. Intensive UO monitoring was defined as hourly recordings and no gaps > 3 hours for the first 48 hours after ICU admission. RESULTS: Intensive monitoring for UO was conducted in 4,049 patients (26%), and we found significantly higher rates of AKI (OR, 1.22; P < .001) in these patients. After adjustment for age and severity of illness, intensive UO monitoring was associated with improved survival but only among patients experiencing AKI. With or without AKI, patients with intensive monitoring also had less cumulative fluid volume (2.98 L vs 3.78 L; P < .001) and less fluid overload (2.49% vs 5.68%; P < .001) over the first 72 hours of ICU stay. CONCLUSIONS: In this large ICU population, intensive monitoring of UO was associated with improved detection of AKI and reduced 30-day mortality in patients experiencing AKI, as well as less fluid overload for all patients. Our results should help inform clinical decisions and ICU policy about frequency of monitoring of UO, especially for patients at high risk of AKI or fluid overload, or both.