Vancomycin-Related Acute Kidney Injury

Zasowski EJ, et al. Identification of Vancomycin Exposure-Toxicity Thresholds in Hospitalized Patients Receiving Intravenous Vancomycin. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01684-17.

Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum a posteriori probability Bayesian estimation. Vancomycin AUC and minimum-concentration (Cmin) thresholds most strongly associated with nephrotoxicity were identified via classification and regression tree (CART) analysis. Predictive performances of CART-derived and other candidate AUC thresholds was assessed through positive and negative predictive value and receiver operating characteristic curves. Poisson regression was used to quantify the association between exposure thresholds and nephrotoxicity while adjusting for confounders. Among 323 patients included, nephrotoxicity was significantly higher in patients with AUCs from 0 to 48 h (AUC0-48) of ≥1,218 mg · h/liter, AUC0-24 of ≥677 mg · h/liter, AUC24-48 of ≥683 mg · h/liter, and day 1 Cmin (Cmin24) of ≥18.8 mg/liter. Vancomycin exposure in excess of these thresholds was associated with a 3- to 4-fold-increased risk of nephrotoxicity in Poisson regression. The predictive performance of AUC for nephrotoxicity was maximized at daily AUC values between 600 and 800 mg · h/liter. Although these data support an AUC range for vancomycin-associated nephrotoxity rather than a single threshold, available evidence suggests that a daily AUC limit of 700 mg · h/liter is reasonable.

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Article of interest: Assessment of morbidity and mortality after esophagectomy using a modified frailty index

Hodari A, et al. Assessment of morbidity and mortality after esophagectomy using a modified frailty index. Ann Thorac Surg. 2013 Oct;96(4):1240-1245.

Full-text for Emory users.

Results: A total of 2,095 patients were included in the analysis. Higher frailty scores were associated with a statistically significant increase in morbidity and mortality. A frailty score of 0, 1, 2, 3, 4, and 5 had associated morbidity rates of 17.9% (142 of 795 patients), 25.1% (178 of 710 patients), 31.4% (126 of 401 patients), 34.4% (48 of 140 patients), 44.4% (16 of 36 patients), and 61.5% (8 of 13 patients), respectively. A frailty score of 0, 1, 2, 3, 4, and 5 had associated mortality rates of 1.8% (14 of 795 patients), 3.8% (27 of 710 patients), 4% (16 of 401 patients), 7.1% (10 of 140 patients), 8.3% (3 of 36 patients), and 23.1% (3 of 13 patients), respectively. When using multivariate logistic regression for mortality comparing age, functional status, prealbumin, emergency surgery, wound class, American Society of Anesthesiologists score, and sex, only age and frailty were statistically significant. The odds ratio was 31.84 for frailty (p = 0.015) and 1.05 (p = 0.001) for age.

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Article of interest: LekCheck: A Prospective Study to Identify Perioperative Modifiable Risk Factors for Anastomotic Leakage in Colorectal Surgery

Huisman DE, Reudink M, van Rooijen SJ, et al. LekCheck: A Prospective Study to Identify Perioperative Modifiable Risk Factors for Anastomotic Leakage in Colorectal Surgery. Ann Surg. 2020 Jun 4. [Epub ahead of print]

Full-text for Emory users.

Objective: To assess potentially modifiable perioperative risk factors for anastomotic leakage in adult patients undergoing colorectal surgery.

Summary background data: Colorectal anastomotic leakage (CAL) is the single most important denominator of postoperative outcome after colorectal surgery. To lower the risk of CAL, the current research focused on the association of potentially modifiable risk factors, both surgical and anesthesiological.

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Smoking and pancreatic disease

Yadav D, Hawes RH, Brand RE, et al. Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch Intern Med. 2009 Jun 8; 169(11):1035-45.

Free full-text.

Chronic pancreatitis_smoking

Figure 3. Distribution of self-reported smoking status (A) and amount (B) stratified by drinking categories. All proportions are based on effective numbers, and never smokers account for the proportions not reflected in the graphs. C indicates control group; CP, chronic pancreatitis group; RAP, recurrent acute pancreatitis group.

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The use of risk stratification tools for perioperative and postoperative morbidity and mortality

Havens JM, Columbus AB, Seshadri AJ, et al. Risk stratification tools in emergency general surgery. Trauma Surg Acute Care Open. 2018 Apr 29;3(1):e000160.

Free full-text.

The use of risk stratification tools (RST) aids in clinical triage, decision making and quality assessment in a wide variety of medical fields. Although emergency general surgery (EGS) is characterized by a comorbid, physiologically acute patient population with disparately high rates of perioperative morbidity and mortality, few RST have been explicitly examined in this setting. We examined the available RST with the intent of identifying a tool that comprehensively reflects an EGS patients perioperative risk for death or complication.

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Prognostic factors in splanchnic vein thromboses

Ageno W, et al. Long-term Clinical Outcomes of Splanchnic Vein Thrombosis: Results of an International Registry. JAMA Intern Med. 2015 Sep;175(9):1474-80. doi: 10.1001/jamainternmed.2015.3184.

Full-text for Emory users.

RESULTS: Of the 604 patients (median age, 54 years; 62.6% males), 21 (3.5%) did not complete follow-up. The most common risk factors for SVT were liver cirrhosis (167 of 600 patients [27.8%]) and solid cancer (136 of 600 [22.7%]); the most common sites of thrombosis were the portal vein (465 of 604 [77.0%]) and the mesenteric veins (266 of 604 [44.0%]). Anticoagulation was administered to 465 patients in the entire cohort (77.0%) with a mean duration of 13.9 months; 175 of the anticoagulant group (37.6%) received parenteral treatment only, and 290 patients (62.4%) were receiving vitamin K antagonists. The incidence rates (reported with 95% CIs) were 3.8 per 100 patient-years (2.7-5.2) for major bleeding, 7.3 per 100 patient-years (5.8-9.3) for thrombotic events, and 10.3 per 100 patient-years (8.5-12.5) for all-cause mortality. During anticoagulant treatment, these rates were 3.9 per 100 patient-years (2.6-6.0) for major bleeding and 5.6 per 100 patient-years (3.9-8.0) for thrombotic events. After treatment discontinuation, rates were 1.0 per 100 patient-years (0.3-4.2) and 10.5 per 100 patient-years (6.8-16.3), respectively. The highest rates of major bleeding and thrombotic events during the whole study period were observed in patients with cirrhosis (10.0 per 100 patient-years [6.6-15.1] and 11.3 per 100 patient-years [7.7-16.8], respectively); the lowest rates were in patients with SVT secondary to transient risk factors (0.5 per 100 patient-years [0.1-3.7] and 3.2 per 100 patient-years [1.4-7.0], respectively).

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The Child-Pugh score and its impact on surgical morbidity and mortality (check out the references if nothing else)

One discussion this week involved the impact of the Child-Pugh scoring system. A special thank you to Dr. Sellers for providing the wealth of original documents for this post. We love hearing you talk about liver disease and portal hypertension!


Cheung A., Cheung A. The Child-Pugh score: prognosis in chronic liver disease and cirrhosis [Classics Series]. 2 Minute Medicine, The Classics in Medicine: Summaries of the Landmark Trials. 2013 Jul 16. Retrieved May 17, 2019 from

Garrison RN, et al. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Annals of Surgery. 1984 Jun;199(6):648-655.

Malinchoc M, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000 Apr;31(4):864-871.

Mansour A, et al. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery. 1997 Oct;122(4):730-735. discussion 735-736.

Pugh RN, et al. Transection of the oesophagus for bleeding oesophageal varices. The British Journal of Surgery. 1973 Aug;60(8):646-649.

Teh SH, et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology. 2007 Apr;132(4):1261-1269.

Summary: The Child-Pugh score consists of five clinical features and is used to assess the prognosis of chronic liver disease and cirrhosis. It was originally developed in 1973 to predict surgical outcomes in patients presenting with bleeding esophageal varices. It has since been modified, refined, and become a widely used tool to assess prognosis in patients with chronic liver disease and cirrhosis.

The score considers five factors, three of which assess the synthetic function of the liver (i.e., total bilirubin level, serum albumin, and international normalized ratio, or INR) and two of which are based on clinical assessment (i.e., degree of ascites and degree of hepatic encephalopathy). Critics of the Child-Pugh score have noted its reliance on clinical assessment, which may result in inconsistency in scoring. Others have suggested that its broad classifications of disease are impractical when determining priority for liver transplantation; nevertheless, it remains widely used.

child pugh

In their 1997 study, Mansour et al found the mortality in Child’s class A was 10%, compared to 30% in Class B and 82% in Class C patients.

The Model for End-Stage Liver Disease (MELD) is a newer scoring system that has been developed to address some of the concerns with the Child-Pugh score, and the two systems are often used in conjunction to determine liver transplantation priority.

The utility of the Model for End-stage Liver Disease (MELD) in predicting mortality after surgery other than liver transplantation is unknown. In determining the risk factors for postoperative mortality in patients with cirrhosis, Teh et al (2007) found that only MELD score, American Society of Anesthesiologists class, and age predicted mortality at 30 and 90 days, 1 year, and long-term, independently of type or year of surgery. Emergency surgery was the only independent predictor of duration of hospitalization postoperatively. Thirty-day mortality ranged from 5.7% (MELD score, <8) to more than 50% (MELD score, >20). The relationship between MELD score and mortality persisted throughout the 20-year postoperative period.