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Background There are limited data on the presentation of Takotsubo cardiomyopathy ( TTC ) in severe sepsis. Methods and Results This was a retrospective cohort study using the National Inpatient Sample database (2007–2013) of all adults with severe sepsis. TTC was identified in patients with severe sepsis using previously validated administrative codes. The primary outcome was in‐hospital mortality, and secondary outcomes included resource utilization and discharge disposition. Regression analysis was performed for the entire cohort and a propensity‐matched sample. An exploratory analysis was performed for predictors of TTC incidence and mortality in TTC . During this 7‐year period, in 7.1‐million hospitalizations for severe sepsis, TTC was diagnosed in 10 746 (0.15%) admissions. TTC was noted more commonly in whites, females, and among 65‐ to 79‐year‐old individuals. TTC was independently associated with lower in‐hospital mortality in severe sepsis (odds ratio, 0.58; 95% confidence interval, 0.51–0.65). This association was more prominent in females (odds ratio, 0.51; 95% confidence interval, 0.44–0.59]) compared with males (odds ratio, 0.69; 95% confidence interval, 0.55–0.85]). Presentation in later years of the study period, middle‐age, female sex, and white race were independent predictors for the diagnosis of TTC . Age ≥80 years, black race, greater comorbidity, and multiorgan dysfunction were independently associated with higher in‐hospital mortality among TTC admissions. Conclusions TTC is observed with increasing frequency in severe sepsis and was associated with a significantly lower in‐hospital mortality compared with patients without TTC . Presentation in later years of the study period, middle age, female sex, and white race were independent predictors for the diagnosis of TTC in severe sepsis.

AbstractBackgroundNephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal β-lactam/VAN combinations.MethodsThe study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal β-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.ResultsThe overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).ConclusionShort courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.

Study Objective Serum creatinine ( S c r ) concentration is used to calculate estimated glomerular filtration rate (e GFR ) for medication dosing. Serum cystatin C (CysC) concentration has been proposed as an adjunct or alternative to S cr . This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections. Design Retrospective analysis of prospectively collected data. Setting Large academic tertiary care medical center. Patients A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. Measurements and Main Results Standardized S c r and CysC measured at the time of antibiotic dosing were used to estimate GFR from the three Chronic Kidney Disease Epidemiology Collaborative ( CKD ‐ EPI ) equations using S c r (eGFR Cr ), CysC( eGFR CysC ), or a combination of S c r and CysC (eGFR Cr‐CysC ), and these values were compared with estimated creatinine clearance (eCl cr ) from the Cockcroft‐Gault equation (standard of care for drug dosage adjustments). The eGFR s were categorized into five common dosage adjustment strata (lower than 20, 20–49, 50–79, 80–130, and higher than 130 ml/min), and agreement between equations was tested with the weighted κ statistic. Recommended drug doses varied considerably between the eC l cr and the CKD ‐ EPI equations (weighted κ [95% confidence interval]: eGFR Cr 0.73 [0.68–0.79], eGFR CysC 0.42 [0.35–0.5], eGFR Cr‐CysC 0.65 [0.6–0.71]). If eGFR Cr, eGFR CysC , or eGFR Cr‐CysC were used instead of eC l cr to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower. Conclusion Significant discordance in drug doses was observed when the CKD ‐ EPI equations were used in place of eCl cr . When CysC was included in eGFR equations, recommended doses were often lower. Further study is needed to develop and test drug‐specific dosing guidelines that incorporate alternate renal biomarkers and/or more contemporary eGFR equations.

AbstractBackgroundAcute kidney injury (AKI) is common in hospitalized patients and is associated with increased morbidity, mortality, and cost. Currently, AKI is diagnosed after symptoms manifest; available diagnostic tests (e.g., serum creatinine, urine microscopy, urine output) have limited ability to identify subclinical AKI. Because of the lack of treatment strategies, AKI typically is managed with supportive measures. However, strategies exist that may prevent renal insults in critically ill patients; therefore, early recognition of AKI is crucial for minimizing damage propagation.ContentExperimental and clinical studies have identified biomarkers that may facilitate earlier recognition of AKI or even identify patients at risk of AKI. Such biomarkers might aid in earlier implementation of preventive strategies to slow disease progression and potentially improve outcomes. This review describes some of the most promising novel biomarkers of AKI, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (lL-18), liver-type fatty-acid-binding protein (L-FABP), insulin-like-growth-factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinase 2 (TIMP-2).SummaryWe discuss biomarker test characteristics, their strengths and weaknesses, and future directions of their clinical implementation.

Objectives: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. Design: Retrospective case series. Setting: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. Patients: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. Interventions: None. Measurements and Main Results: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50–74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58–87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p < 0.01), malignancy (p < 0.01), and solid organ transplantation (p = 0.04), whereas seizure disorder was more common in survivors (p = 0.02). After adjustment, serum ammonia level was not associated with increased mortality. Conclusions: Hyperammonemia occurs in a substantial minority of critically ill patients without liver failure. These patients have a poor prognosis, although ammonia level per se is not independently associated with mortality. Serum ammonia should be measured when risk factors are present, such as nutritional deficiencies and protein refeeding, treatment with valproic acid, high tumour burden, and known or suspected urea cycle abnormalities.

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.

AbstractBackgroundFrailty, including low muscle mass, is an emerging risk factor for poor outcomes after lung transplant. The sarcopenia index (SI)—(serum creatinine value/cystatin C value) × 100—is a novel blood test to approximate muscle mass. We sought to validate SI among lung transplant patients.MethodsWe retrospectively identified adult lung transplant recipients from 2000 through 2012 at our institution who underwent computed tomography within 1 year before transplant and had preserved blood samples. Creatinine and cystatin C values were measured using the samples and used to calculate SI. Muscle mass was estimated by computed tomographic measurement of skeletal muscle cross‐sectional surface area (SA) at the L1 to L3 vertebral levels. Correlation between SI and SA was evaluated.ResultsOf 28 patients meeting eligibility criteria, most were white (96%) and men (54%). Median (interquartile range) body mass index, SI, and SA were 25.9 (22‐30) kg/m2, 106 (91‐119), and 157 (113‐195) cm2, respectively. The Pearson correlation coefficient between SI and SA was significant at L2 (0.43; P = .02) and L3 (0.41; P = .03).ConclusionSarcopenia index is a potentially objective measure for estimating muscle mass that is noninvasive and less expensive. Sarcopenia index could be considered in lung transplant candidate selection following prospective validation in larger cohorts.