BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P = 0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P = 0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P = 0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P = 0.60). CONCLUSIONS Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)

Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

BACKGROUND Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P = 0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P = 0.01). CONCLUSIONS Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline.

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.Objectives: To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.Methods: This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer's solution or PlasmaLyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.Measurements and Main Results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P , 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).Conclusions: An electronic health record-embedded, clusterrandomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt.Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Their use is likely even higher than estimated due to an increase in the number of PPIs available without a prescription. Appropriate indications for PPI use include Helicobacter pylori infection, erosive esophagitis, gastric ulcers, and stress ulcer prevention in high-risk critically ill patients. Unfortunately, PPIs are often used off-label for extended periods of time. This increase in PPI usage over the past two decades has called into question the long-term effects of these medications. The association between PPI use and infection, particularly Clostridium difficile and pneumonia, has been the subject of several studies. It’s proposed that the alteration in gastrointestinal microflora by PPIs produces an environment conducive to development of these types of infections. At least one study has suggested that long-term PPI use increases the risk of dementia. Drug interactions are an important and often overlooked consideration when prescribing any medication. The potential interaction between PPIs and antiplatelet agents has been the subject of multiple studies. One of the more recent concerns with PPI use is their role in the development or progression of chronic kidney disease. There is also some literature suggesting that PPIs contribute to the development of various micronutrient deficiencies. Most of the literature examining the potential adverse effects of PPI use is composed of retrospective, observation studies. There is a need for higher quality studies exploring this relationship.

APPROXIMATELY 300,000 patients undergo cardiac surgical procedures each year in the United States. More than 80% of routine cardiac surgical procedures are performed using cardiopulmonary bypass (CPB).1 Acute kidney injury (AKI; previously referred to as acute renal failure) after CPB is a well-known, yet incompletely understood, entity that has significant implications on both short-and long-term outcomes. The development of AKI after CPB is associated with a significant increase in infectious complications, an increase in length of hospital stay, and greater mortality when compared with patients without AKI-CPB.2 The incidence of AKI-CPB averages 20 -30%, depending on the definition used and the duration of the postoperative period studied.3,4 Furthermore, more patients with AKI-CPB who require dialysis remain dialysis dependant. For all patients undergoing CPB, the risk of AKI-CPB is the least in those who undergo coronary artery bypass grafting (CABG) only; the risk increases for patients undergoing valve replacement surgery; and the risk is the greatest after combined CABGvalve procedures. 4 There has not been a significant reduction in mortality, despite many recent advances in our understanding of the causative pathophysiology and pharmacotherapeutics of AKI-CPB. Furthermore, advances in renal replacement therapies (RRTs) have not significantly altered the overall mortality associated with AKI-CPB.In this review, we will focus on the current definitions of AKI, pathophysiologic features, and risk factors for developing AKI-CPB. We will also discuss perioperative strategies and emerging concepts that add to our understanding of this complex entity to help better manage patients at risk for AKI-CPB. Defining AKIAKI is a complex diagnosis and has been described using several definitions and diagnostic criteria, ranging from a 25% increase in baseline serum creatinine (sCr) to the need for hemodialysis.3,4 The requirement for a consensus definition addressing early detection and grading of severity of AKI led to the development of the Risk-Injury-Failure-Loss-End stage kidney disease (RIFLE) classification by the Acute Dialysis Quality Initiative. 5 To further refine the scoring, the Acute Kidney Injury Network (AKIN) proposed a modification of the RIFLE classification, known as the AKIN classification. 6 The RIFLE and AKIN classifications have been used and validated in prospective studies 7 in patients with AKI after cardiac surgery.The differences between RIFLE and AKIN staging criteria are subtle. Stage 1 in the AKIN classification has been broadened to include patients with an increase in sCr of at least 26.5 M (0.3 mg/dl) greater than baseline because there is accumulating evidence that even minor increments in sCr concentration are associated with adverse outcomes. 6 In contrast, the "risk" stage of RIFLE classification requires a 50% increase in sCr over baseline. Urine output over time is retained in both classification systems because it may precede the increase in sCr, especially in critically ill ...

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Acute kidney injury is common among critically ill adults and is associated with increased mortality and morbidity. The Major Adverse Kidney Events by 30 days (MAKE30) composite of death, new renal replacement therapy, or persistent renal dysfunction is recommended as a patient-centered outcome for pragmatic trials involving acute kidney injury. Accurate electronic detection of the MAKE30 endpoint using data within the electronic health record (EHR) could facilitate the use of the EHR in large-scale kidney injury research. In an observational study using prospectively collected data from 200 admissions to a single medical intensive care unit, we tested the performance of electronically-extracted data in identifying the MAKE30 composite compared to the reference standard of two-physician manual chart review. The incidence of MAKE30 on manual-review was 16 %, which included 8.5 % for in-hospital mortality, 3.5 % for new renal replacement therapy, and 8.5 % for persistent renal dysfunction. There was strong agreement between the electronic and manual assessment of MAKE30 (98.5 % agreement [95 % CI 96.5–100.0 %]; kappa 0.95 [95 % CI 0.87–1.00]; P < 0.001), with only three patients misclassified by electronic assessment. Performance of the electronic MAKE30 assessment was similar among patients with and without CKD and with and without a measured serum creatinine in the 12 months prior to hospital admission. In summary, accurately identifying the MAKE30 composite outcome using EHR data collected as a part of routine care appears feasible.