Bihari, Shailesh

Key Points The Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI trial found that starting dialysis earlier for AKI resulted in a 74% higher risk of still receiving dialysis at 90 days. Among patients who likely would have started dialysis under usual practice, the risks of dialysis dependence were similar. This suggests much of the risk observed may have been due to starting dialysis (versus never starting) rather than starting slightly earlier. Background The Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI Trial showed that among critically ill patients with AKI, an accelerated KRT initiation strategy resulted in more KRT dependence at 90 days, as compared with a standard strategy. However, it is unclear whether this difference exists among participants who likely would have been treated with KRT in usual practice. Methods Secondary analysis of the Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI randomized controlled trial, analyzing participants who received more than the median number of days of KRT, which served as a proxy for high probability of requiring KRT under usual practice. Two sensitivity analyses redefined the cohort as ( 1 ) those with ≥24 hours of oliguria who received KRT and ( 2 ) those who received any KRT. Using the same statistical approach as the original trial, we calculated unadjusted relative risks with 95% confidence intervals (CIs) for the exposure of randomized KRT initiation strategy (accelerated versus standard) on the outcome of KRT dependence at 90 days among survivors. Results Among the 1184 participants who received ≥6 days of KRT (670 and 514 in the accelerated and standard arms, respectively), baseline characteristics remained balanced between treatment arms. The relative risk of KRT dependence at 90 days was attenuated and nonsignificant: 1.21 (95% CI, 0.84 to 1.78), compared with 1.74 (95% CI, 1.24 to 2.43) in the overall trial. The results were similar in sensitivity analyses. Conclusions Among patients who likely would have been treated with KRT in usual practice, there was no significant difference in 90-day KRT dependence among survivors between those randomized to the accelerated and standard KRT initiation strategies. These results suggest that the harm of long-term KRT dependence may be largely due to KRT initiation (versus never initiation) rather than earlier initiation. Clinical Trial registry name and registration number: NCT02568722.

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], –11.3%; 95% CI, –17.7% to –4.8%; p < 0.001 and for ANZ vs. North America: RD, –10.3%; 95% CI, –17.5% to –3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

Abstract ObjectivePrevious studies suggested that hypernatremia or hyperosmolarity may have protective effects in lung injury. We hypothesized that hypernatremia and/or hyperosmolarity would prevent ARDS in those at risk of lung injury and associated with favorable outcomes in ARDS patients.SubjectsAll admissions at medical, surgical, and multidisciplinary intensive care units in Mayo Clinic, Rochester from the year of 2009 to 2019.DesignRetrospective cohort study. The occurrence of ARDS was identified using a validated computerized search strategy. The association between serum sodium/osmolarity and the occurrence of ARDS was analyzed using a multivariable logistic regression model. The relationship between serum sodium/osmolarity and outcomes of ARDS was analyzed using linear and logistic regression models.ResultsAmong 50,498 patients, the serum sodium level on admission did not have a significant association with the occurrence of ARDS, with an adjusted odds ratio of 0.95 [95% CI (0.86, 1.05)]. There was no significant association between calculated serum osmolarity and the occurrence of ARDS, with an adjusted odds ratio of 1.03 [95% CI (1.00, 1.07)]. 1560 patients developed ARDS during the ICU stay. Their serum sodium level did not have a significant association with their outcomes [adjusted estimated difference in 28-day ICU-free days, 0.08 days, 95% CI (-0.85, 1.02), adjusted estimated difference in 28-day ventilator-free days, -0.02, 95% CI (-0.62, 0.58), adjusted odds ratio of 28-day mortality 1.02, 95%CI (0.84, 1.24)]. There was no significant association between their calculated serum osmolarity and their outcomes [adjusted estimated difference in 28-day ICU-free days, -0.26, 95% CI, (-0.63, 0.12); adjusted estimated difference in 28-day ventilator-free days, -0.05, 95% CI (-0.28, 0.19); adjusted odds ratio of 28-day mortality, 1.07, 95% CI (0.99, 1.15)].ConclusionsAdmission serum sodium or serum osmolarity were not associated with the occurrence or outcomes of ARDS in ICU.

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Abstract Rationale Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. Methods The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. Conclusions NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).