Antibiotic dosing in critically ill patients with acute kidney injury

A common cause of acute kidney injury (AKI) is sepsis, which makes appropriate dosing of antibiotics in these patients essential. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable within the critically ill population. The volume of distribution of hydrophilic agents can increase as a result of fluid overload and decreased binding of the drug to serum proteins, and antibiotic loading doses must be adjusted upwards to account for these changes. Although renal elimination of drugs is decreased in patients with AKI, residual renal function in conjunction with renal replacement therapies (RRTs) result in enhanced drug clearance, and maintenance doses must reflect this situation. Antibiotic dosing decisions should be individualized to take into account patient-related, RRT-related, and drug-related factors. Efforts must also be made to optimize the attainment of antibiotic pharmacodynamic goals in this population.     

The assessment of acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients and is associated with high morbidity and mortality. The availability of several biomarkers of kidney injury offers new tools for its early recognition and management. The early identification of high-risk patients provides an opportunity to develop strategies for the prevention, early diagnosis and treatment of AKI. Despite progress in critical care medicine over the past decade, the treatment strategies for AKI in critically ill patients, such as when to start renal replacement therapy, remain controversial. A recently proposed risk prediction score for AKI, based on routinely available clinical variables, presents a new means of identifying patients at high risk of AKI.     

Pre-existing chronic kidney disease and acute kidney injury among critically ill patients

BackgroundThe impact of pre-existing chronic kidney disease (CKD) and acute kidney injury (AKI) on health outcomes in critically ill patients is unclear. Yet, CKD complicated by AKI in critically ill patients is common.Objectives: To compare risk of death within one-month of admission in critically ill patients with and without pre-existing CKD who developed AKI.MethodsA multicenter retrospective comparative study using medical records review was conducted. Study participants consisted of 826 adult patients who received mechanical ventilation for at least 6 h in the critical care units from January 2012 to December 2017. Assessment of kidney function was established by serum creatinine. Severity and staging of AKI were defined using RIFLE criteria: Risk, Injury, Failure, Loss and End stage of renal disease. Chronic kidney disease was defined as eGFR > 60 ml/mg/1.73 m² on admission.ResultsPre-existing CKD was present in 55% of patients and 7% had AKI within 7 days of admission. The overall mortality rate among these patients was 87.3%. The mortality rate was highest in patients with CKD (70.1%) followed by that of patients without pre-existing CKD but with AKI (20.7%) and that of patients with pre-existing CKD (7.1%) and AKI. Risks associated with mortality were APACHE II score (1.03; 95% CI 1.02–1.05;(P<0.001) and AKI (1.68; 95% CI 1.12–2.5;P<0.01) in patients with pre-existing CKD. Only APACHI-II (1.03; 95% CI 1.0–1.1; p < 0.001) was predictive of death in patients without pre-existing CKD.Conclusion: Pre-existing comorbid CKD increases risks of death among critically ill patients compared to patients without CKD and regardless of whether they develop AKI or not. Early identification of CKD and recognition of the risk for mortality among these patients may result in earlier intervention that could reduce mortality.     

Sex-related differences in mortality,acute kidney injury,and respiratory failure among critically ill patients with COVID-19

Although the number of deaths due to coronavirus disease 2019 (COVID-19) is higher in men than women, prior studies have provided limited sex-stratified clinical data.We evaluated sex-related differences in clinical outcomes among critically ill adults with COVID-19.Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day in-hospital mortality, severe acute kidney injury (AKI requiring kidney replacement therapy), and respiratory failure occurring within 14 days of intensive care unit admission.A total of 4407 patients were included (median age, 62 years; 2793 [63.4%] men; 1159 [26.3%] non-Hispanic White; 1220 [27.7%] non-Hispanic Black; 994 [22.6%] Hispanic). Compared with women, men were younger (median age, 61 vs 64 years, less likely to be non-Hispanic Black (684 [24.5%] vs 536 [33.2%]), and more likely to smoke (877 [31.4%] vs 422 [26.2%]). During median follow-up of 14 days, 1072 men (38.4%) and 553 women (34.3%) died. Severe AKI occurred in 590 men (21.8%), and 239 women (15.5%), while respiratory failure occurred in 2255 men (80.7%) and 1234 women (76.5%). After adjusting for age, race/ethnicity and clinical variables, compared with women, men had a higher risk of death (OR, 1.50, 95% CI, 1.26–1.77), severe AKI (OR, 1.92; 95% CI 1.57–2.36), and respiratory failure (OR, 1.42; 95% CI, 1.11–1.80).In this multicenter cohort of critically ill adults with COVID-19, men were more likely to have adverse outcomes compared with women.     

Severity of acute gastrointestinal injury grade is a good predictor of mortality in critically ill patients with acute pancreatitis

BACKGROUND Gastrointestinal(GI)dysfunction is a common and important complication of acute pancreatitis(AP),especially in patients with severe AP.Despite this,there is no consensus means of obtaining a precise assessment of GI function.AIM To determine the association between acute gastrointestinal injury(AGI)grade and clinical outcomes in critically ill patients with AP.METHODS Patients with AP admitted to our pancreatic intensive care unit from May 2017 to May 2019 were enrolled.GI function was assessed according to the AGI grade proposed by the European Society of Intensive Care Medicine in 2012,which is mainly based on GI symptoms,intra-abdominal pressure,and feeding intolerance in the first week of admission to the intensive care unit.Multivariate logistic regression analysis was performed to assess the association between AGI grade and clinical outcomes in critically ill patients with AP.RESULTS Among the 286 patients included,the distribution of patients with various AGI grades was 34.62%with grade I,22.03%with grade II,32.52%with grade III,and 10.84%with grade IV.The distribution of mortality was 0%among those with grade I,6.35%among those with grade II,30.11%among those with grade III,and 61.29%among those with grade IV,and AGI grade was positively correlated with mortality(χ2=31.511,P<0.0001).Multivariate logistic regression analysis showed that age,serum calcium level,AGI grade,persistent renal failure,and persistent circulatory failure were independently associated with mortality.Compared with the Acute Physiology and Chronic Health Evaluation II score(area under the curve:0.739 vs 0.854;P<0.05)and Ranson score(area under the curve:0.72 vs 0.854;P<0.01),the AGI grade was more useful for predicting mortality.CONCLUSION AGI grade is useful for identifying the severity of GI dysfunction and can be used as a predictor of mortality in critically ill patients with AP.     

Risk factors for acute kidney injury in critically ill patients with torso injury: A retrospective observational single-center study

Acute kidney injury (AKI) is common in trauma patients and associated with poor outcomes. Identifying AKI risk factors in trauma patients is important for risk stratification and provision of optimal intensive care unit (ICU) treatment. This study identified AKI risk factors in patients admitted to critical care after sustaining torso injuries.We performed a retrospective chart review involving 380 patients who sustained torso injuries from January 2016 to December 2019. Patients were included if they were aged >15 years, admitted to an ICU, survived for >48 hours, and had thoracic and/or abdominal injuries and no end-stage renal disease. AKI was defined according to the Kidney Disease Improving Global Outcomes definition and staging system. Clinical and laboratory variables were compared between the AKI and non-AKI groups (n = 72 and 308, respectively). AKI risk factors were assessed using multivariate logistic regression analysis.AKI occurred in 72 (18.9%) patients and was associated with higher mortality than non-AKI patients (26% vs 4%, P < .001). Multivariate logistic regression analysis identified bowel injury, cumulative fluid balance >2.5 L for 24 hours, lactate levels, and vasopressor use (adjusted odds ratio: 2.953, 2.058, 1.170, and 2.910; 95% confidence interval: 1.410–6.181, 1.017–4.164, 1.019–1.343, and 1.414–5.987; P = .004, .045, .026, and .004, respectively) as independent risk factors for AKI.AKI in patients admitted to the ICU with torso injury had a substantial mortality. Recognizing risk factors at an early stage could aid risk stratification and provision of optimal ICU care.     

The association of interleukin 6 haplotype clades with mortality in critically ill adults

BACKGROUND: Interleukin 6 (IL-6) is a key proinflammatory cytokine in the systemic inflammatory response syndrome (SIRS). A G-->C polymorphism at position -174 of the IL-6 gene is associated with an adverse outcome in a number of inflammatory diseases, although its association with sepsis as an outcome remains unclear. We tested the hypothesis that specific haplotype clades of IL-6 may be associated with an outcome of SIRS. METHODS: We studied a cohort of 228 critically ill white patients who met at least 2 of 4 SIRS criteria. Clinical data were collected over 28 days after hospital admission. Haplotypes of IL-6 were inferred from publicly available data using PHASE (software for haplotype reconstruction and recombination rate estimation from population data), and cladistic structure was determined using Molecular Evolutionary Genetic Analyses (MEGA2) software. Then, a minimum set of "haplotype tag" single nucleotide polymorphisms (-174G/C, 1753C/G, and 2954G/C) that defined all 4 major haplotype clades of the IL-6 gene was chosen for further genotyping. RESULTS: Patients who had 2 copies of haplotypes from within the haplotype clades -174C/1753C/2954G (C/C/G), G/G/G, or G/C/C had a greater 28-day mortality compared with patients who carried 1 or no copies of these haplotypes (40.0% vs 26.0%; P = .02). These patients also had fewer days alive and free of multiple system organ dysfunction (P<.05). There were no associations between individual single nucleotide polymorphisms (including -174G/C) and survival or organ dysfunction. CONCLUSIONS: The C/C/G, G/G/G, and G/C/C haplotype clades of IL-6 were strongly associated with increased mortality and more organ dysfunction in a cohort of critically ill patients who had SIRS. Haplotype-based analysis succeeded in identifying this association, whereas individual single nucleotide polymorphism-based analysis failed.     

KDIGO和ICA标准诊断住ICU的肝硬化患者急性肾损伤效能研究

目的 急性肾损伤(AKI)在肝硬化患者中普遍存在,会导致病死率明显升高。改善全球肾脏病预后(KDIGO)标准具有很高的预后预测能力,但是最近国际腹水俱乐部(ICA)提出了一项新的诊断AKI标准。本研究比较了这两种标准诊断AKI及其预测预后的效能。 方法 回顾性分析2010年～2015年收治的245例入住ICU的肝硬化患者,收集临床资料。采用Logistic回归分析住院死亡的独立危险因素。应用受试者工作特征曲线下面积(AUROC)和Hosmer-Lemeshow检验评估不同AKI标准对预后的预测能力和拟合优度。结果 本组住院死亡156例(63.7%);根据KDIGO和ICA标准,AKI发生率分别为63.7%和58.4%;AKI和尿量是住院死亡的独立危险因素;KDIGO标准(OR=1.703)的OR值比ICA标准(OR=1.547)更高;KDIGO标准和ICA标准预测死亡的AUROC分别为0.762和0.708,差异显著(P=0.014)。 结论 KDIGO标准比ICA标准预测入住ICU的肝硬化患者住院死亡的能力更强。     

Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill,non-septic patients

Background

The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients.

Methods

Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T?=?0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, π- and α-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively.

Results

Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P?=?0.001 at T?=?-24 vs. non-AKI patients) and KIM-1 (P?<?0.0001 at T?=?0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas π- and α-GST peaked at T?=?-24 before AKI (P?=?0.006 and P?=?0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T?=?-24 prior to AKI were modest for π- and α-GST, whereas NGAL sufficiently predicted AKI at T?=?-24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC?=?0.79, P?<?0.0001). KIM-1 was a good discriminator at T?=?0 only (AUC?=?0.73, P?<?0.0001).

Conclusions

NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.

     

Cognitive impairment and depression predict mortality in medically ill older adults

BACKGROUND: Depression and cognitive impairment are common in medically ill older adults. Few studies, however, have investigated the roles of both in predicting mortality for medically ill older adults. METHODS: We used a cohort of consecutive patients aged 60 or older admitted to a rehabilitation hospital (N = 667) of whom 455 completed a standardized protocol measuring cognition (Dementia Rating Scale), depression (Geriatric Depression Scale), and disabilities (Functional Independence Measure). Burden of medical illnesses was measured with the Charlson Index. Vital status was assessed one year later. RESULTS: Those subjects who did not complete the screening were more likely to die (24% vs 17%; p = .02) during the one-year follow-up. Of those who completed the screening, male sex (odds ratio [OR] = 1.84), depression (mild OR = 1.64; moderate OR = 2.49), and more severe cognitive impairment (OR = 2.13) predicted mortality independent of age, medical illnesses, or disabilities. No interaction of cognitive impairment and depression was detected. In those subjects cognitively intact, moderate depression (OR = 4.95) and male sex (OR = 3.42) were independent risk factors for dying. In those subjects without depression, male sex (OR = 2.24) and elevated Charlson Index (OR = 1.42) predicted mortality. CONCLUSIONS: Depression and cognitive impairment are independent predictors of one-year mortality in this subgroup of medically ill older adults.     

Acute kidney injury in critically ill cirrhotic patients: a review

Acute kidney injury (AKI) is an important marker of morbidity and mortality in critically ill cirrhotic patients. The most common causes of AKI in cirrhotic patients include prerenal or hepatorenal syndrome (HRS). Diagnosis of AKI may be delayed by the lack of clinical, biochemical, and radiological markers with proven sensitivity and specificity in cirrhotic patients. In this review, we discuss the epidemiology, pathophysiology, diagnosis, and therapies for AKI in cirrhotic patients admitted to an intensive care unit (ICU).     

急性肾损伤诊断分期标准在老年危重病中的应用

目的对重症医学科（ICU）老年危重病患者应用急性肾损伤（AKI）诊断分期标准监测肾功能的变化并指导治疗,以期改善预后。方法 2007年8月至2008年8月收住ICU的老年危重病患者134例为对照组,2008年9月年2009年9月收住ICU的老年危重病患者170例为实验组。实验组引入AKI诊断分期标准监测肾功能的变化并指导治疗,其它支持治疗原则与对照组相同。记录两组患者ICU期间医院获得性急性肾损伤（HA-AKI）的发生及血液净化的应用状况,比较预后。结果对照组HA-AKI发病率、AKI 3期占HA-AKI比例、ICU住院时间、病死率分别是37.3%,34.0%,（10.2±3.2）d和40.3%,实验组分别为26.5%,15.6%,（8.2±2.8）d和26.5%,两者差异有统计学意义（P〈0.05）。实验组未发生HA-AKI患者125例,HA-AKI 1期9例、2期29例、3期7例,病死率分别是16.8%,33.3%,51.7%和85.7%,差异有统计学意义（P〈0.05）;未发生HA-AKI的患者与HA-AKI 1期、2期患者ICU住院时间分别为（7.3±2.3）,（10.4±3.2）和（13.2±3.7）d,差异有统计学意义（P〈0.05）。对照组HA-AKI患者行血液净化20例,占HA-AKI患者的40.0%,住院时间（8±3）d,病死率72.0%;实验组HA-AKI患者行血液净化29例,占HA-AKI患者的64.4%,住院时间（11±3）d,病死率51.1%,两组之间差异有统计学意义（P〈0.05）。结论 AKI诊断分期标准对老年危重病患者很重要,可以减少HA-AKI及AKI 3期的发生率。HA-AKI的发生及进展使预后恶化,早期血液净化治疗能改善老年HA-AKI患者的预后。     

Organ system failure scoring system can predict hospital mortality in critically ill cirrhotic patients

GOALS: This study was conducted to assess and compare the accuracy of Child-Pugh classification and organ system failure (OSF) scores, obtained on the first day of ICU admission, in predicting the hospital mortality in critically ill cirrhotic patients. BACKGROUND: Cirrhotic patients admitted to the medical intensive care unit (ICU) are associated with high mortality rates. The prognosis of critically ill cirrhotic patients is determined by the extent of hepatic and extrahepatic organ dysfunction. STUDY: A total of 111 patients diagnosed with liver cirrhosis were admitted to medical ICU from July 2001 to June 2002. Information considered necessary to compute the Child-Pugh and OSF scores on the first day of ICU admission was prospectively collected. RESULTS: The overall hospital mortality rate was 64.9%. Liver disease was most commonly attributed to hepatitis B viral infection. The OSF scores demonstrate a good fit using the Hosmer and Lemeshow goodness-of-fit test. Meanwhile, by using the areas under receiver operating characteristic (AUROC) curve, the OSF scores demonstrated an excellent discriminative power (AUROC 0.901), whereas the performance of Child-Pugh scores is clearly poorer (AUROC 0.748). CONCLUSION: This investigation confirms that the prognosis for cirrhotic patients admitted to ICU is grave. The OSF score is a simple, reproducible, and easily applied tool with excellent prognostic abilities that can provide objective information for patients' families and physicians and supplement the clinical judgment of prognosis.     

The kidney in the critically ill

Acute kidney injury (AKI) is a common and serious complication in the intensive care setting. It seldom occurs in isolation, but is mostly part of a multiple organ dysfunction syndrome. The pathogenesis is frequently multifactorial, with sepsis contributing to 50% of the cases.The development of AKI in critically-ill patients is "bad news": patients with AKI have a high morbidity and mortality. In addition, AKI, even in its mildest from, is not only a marker of illness severity but appears to be independently associated with mortality. Prevention of AKI is therefore a major goal to improve outcome of critically-ill patients. Treatment of established AKI is largely supportive. The optimal modality for renal replacement therapy in critically-ill patients still remains a matter of debate). The majority of survivors recover renal function.