Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam

Background and objectives

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients.

Design, setting, participants, & measurements

We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001–2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay.

Results

There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001).

Conclusions

In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT.     

Low Systemic Oxygen Delivery and BP and Risk of Progression of Early AKI

Background and objectives

The optimal hemodynamic management of patients with early AKI is unknown. This study aimed to investigate the association between hemodynamic parameters in early AKI and progression to severe AKI and hospital mortality.

Design, setting, participants, & measurements

This study retrospectively analyzed the data of all patients admitted to the adult intensive care unit in a tertiary care center between July 2007 and June 2009 and identified those with stage 1 AKI (AKI I) per the AKI Network classification. In patients in whom hemodynamic monitoring was performed within 12 hours of AKI I, hemodynamic parameters in the first 12 hours of AKI I and on the day of AKI III (if AKI III developed) or 72 hours after AKI I (if AKI III did not develop) were recorded. Risk factors for AKI III and mortality were identified using univariate and multivariate logistic regression analyses.

Results

Among 790 patients with AKI I, 210 (median age 70 years; 138 men) had hemodynamic monitoring within 12 hours of AKI I; 85 patients (41.5%) progressed to AKI III and 91 (43%) died in the hospital. AKI progressors had a significantly higher Sequential Organ Failure Assessment score (8.0 versus 9.6; P<0.001), lower indexed systemic oxygen delivery (DO₂I) (median 325 versus 405 ml/min per m²; P<0.001), higher central venous pressure (16 versus 13; P=0.02), and lower mean arterial blood pressure (MAP) (median 71 versus 74 mmHg; P=0.01) in the first 12 hours of AKI I compared with nonprogressors. Multivariate analysis confirmed that raised lactate, central venous pressure, and Sequential Organ Failure Assessment score as well as mechanical ventilation were independently associated with progression to AKI III; higher DO₂I and MAP were independently associated with a lower risk of AKI III but not survival. The associations were independent of sepsis, heart disease, recent cardiac surgery, or chronic hypertension.

Conclusions

Higher DO₂I and MAP in early AKI were independently associated with a lower risk of progression.     

Validation of the Kidney Disease Improving Global Outcomes Criteria for AKI and Comparison of Three Criteria in Hospitalized Patients

Background and objectives

AKI is a major clinical problem and predictor of outcome in hospitalized patients. In 2013, the Kidney Disease: Improving Global Outcomes (KDIGO) group published the third consensus AKI definition and classification system after the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) working group systems. It is unclear which system achieves optimal prognostication in hospital patients.

Design, setting, participants, & measurements

A retrospective observational study using hospital laboratory, admission, and discharge databases was performed that included adult patients admitted to a teaching hospital in Tokyo, Japan between April 1, 2008, and October 31, 2011. AKI occurring during each hospital stay was identified, and discriminative ability of each AKI classification system based on serum creatinine for the prediction of hospital mortality was assessed. The receiver operating characteristic curve, a graphical measure of test performance, and the area under the curve were used to evaluate how classifications preformed on the study population.

Results

In total, 49,518 admissions were studied, of which 11.0% were diagnosed with RIFLE criteria and 11.6% were diagnosed with KDIGO criteria, but only 4.8% were diagnosed with AKIN criteria. Overall hospital mortality was 3.0%. AKI staging and hospital mortality were closely correlated in all systems. Discrimination for hospital mortality was similar for RIFLE and KDIGO criteria (area under the curve=0.77 versus 0.78; P=0.02), whereas AKIN discrimination was inferior (area under the curve=0.69 versus RIFLE [P<0.001] versus KDIGO [P<0.001]).

Conclusion

Among hospital patients, KDIGO and RIFLE criteria achieved similar discrimination, but the discrimination of AKIN was inferior.     

A Prospective International Multicenter Study of AKI in the Intensive Care Unit

Background and objectives

AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes.

Design, setting, participants, & measurements

This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours.

Results

Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P<0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75–5.0] days versus 0 [interquartile range, 0–5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only).

Conclusions

This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in care may explain these findings and should be considered in future trials.     

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Background and objectives

Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.

Design, setting, participants, & measurements

We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children’s Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.

Results

At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid–binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.

Conclusions

Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.     

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Background and objectives

AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness.

Design, setting, participants, & measurements

A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed.

Results

In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P<0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR<60 ml/min per 1.73 m² at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P<0.001).

Conclusion

Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings.     

Plasma Catalytic Iron,AKI, and Death among Critically Ill Patients

Background and objectives

Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.

Design, settings, participants, & measurements

A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.

Results

ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31–3.65] versus 0.29 µmol/l [0.22–0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r_s=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (r_s=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.

Conclusions

Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.     

AKI in Hospitalized Children: Comparing the pRIFLE,AKIN, and KDIGO Definitions

Background and objectives

Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.

Design, setting, participants, & measurements

Observational, electronic medical record–enabled study of 14,795 hospitalizations at the Lucile Packard Children’s Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov–Smirnov tests, respectively.

Results

AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%–1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.

Conclusions

Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.     

Predictors of morbidity and mortality after hepatectomy in elderly patients: analysis of 7621 NSQIP patients

Objectives

Increasingly, surgeons are performing hepatectomies in older patients. This study was designed to analyse the incidences of and risk factors for post-hepatectomy morbidity and mortality in elderly patients.

Methods

All elective hepatectomies for the period 2005–2010 recorded in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were evaluated. Factors associated with 30-day rates of morbidity and mortality were compared between patients aged ≥75 years and those aged <75 years.

Results

Elderly patients accounted for 894 of 7621 (11.7%) hepatectomies. These patients more frequently had comorbidities (diabetes, cardiovascular or lung disease, lower albumin, elevated creatinine, anaesthesia risk; all P < 0.05) and were more likely to undergo partial or left rather than right or extended hepatectomies (P = 0.013). Despite the lesser surgical magnitude of these procedures, elderly patients experienced higher rates of severe complications (23.9% versus 18.4%; P < 0.001) and overall postoperative mortality (4.8% versus 2.0%; P < 0.001). The occurrence of any severe complication was associated with a mortality rate of 20.1% in elderly patients and 10.8% in non-elderly patients (P < 0.001). This disparity in mortality was more pronounced in patients with two or more (31.7% versus 20.2%; P < 0.001) and three or more (46.3% versus 31.1%; P < 0.001) severe complications. Independent risk factors for severe complications and/or mortality included an albumin level of < 4 g/dl, lung disease, intraoperative transfusion, a concurrent intra-abdominal operation, and an operative time of >240 min (all P < 0.05).

Conclusions

Given their lower physiologic reserve, elderly patients are at much greater risk for mortality after severe complications. To improve outcomes, surgeons should balance age and preoperative comorbidities with magnitude of hepatectomy.     

AKI in Low-Risk versus High-Risk Patients in Intensive Care

Background and objectives

AKI in critically ill patients is usually part of multiorgan failure. However, nonrenal organ failure may not always precede AKI and patients without evidence of these organ failures may not be at low risk for AKI. This study examined the risk and outcomes associated with AKI in critically ill patients with and without cardiovascular or respiratory organ failures at presentation to the intensive care unit (ICU).

Design, setting, participants, & measurements

A large, academic medical center database, with records from July 2000 through October 2008, was used and the authors identified a low-risk cohort as patients without cardiovascular and respiratory organ failures defined as not receiving vasopressor support or mechanical ventilation within the first 24 hours of ICU admission. AKI was defined using Kidney Disease Improving Global Outcomes criteria. The primary end points were moderate to severe AKI (stages 2–3) and risk-adjusted hospital mortality.

Results

Of 40,152 critically ill patients, 44.9% received neither vasopressors nor mechanical ventilation on ICU day 1. Stages 2–3 AKI occurred less frequently in the low-risk patients versus high-risk patients within 24 hours (14.3% versus 29.1%) and within 1 week (25.7% versus 51.7%) of ICU admission. Patients developing AKI in both risk groups had higher risk of death before hospital discharge. However, the adjusted odds of hospital mortality were greater (odds ratio, 2.99; 95% confidence interval, 2.62 to 3.41) when AKI occurred in low-risk patients compared with those with respiratory or cardiovascular failures (odds ratio, 1.19; 95% confidence interval, 1.09 to 1.3); interaction P<0.001.

Conclusions

Patients admitted to ICU without respiratory or cardiovascular failure have a substantial likelihood of developing AKI. Although survival for low-risk patients is better than for high-risk patients, the relative increase in mortality associated with AKI is actually greater for low-risk patients. Strategies aimed at preventing AKI should not exclude ICU patients without cardiovascular or respiratory organ failures.     

Utilization of Small Changes in Serum Creatinine with Clinical Risk Factors to Assess the Risk of AKI in Critically lll Adults

Background and objectives

Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient''s clinical course. We set out to assess the performance of this combination approach.

Design, setting, participants, & measurements

A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1–0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit.

Results

Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001).

Conclusion

Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.     

Distinct predictors of pre- versus post-discharge venous thromboembolism after hepatectomy: analysis of 7621 NSQIP patients

Objectives

Hepatectomy patients are known to be at significant risk for venous thromboembolism (VTE), but previous studies have not differentiated pre- versus post-discharge events. This study was designed to evaluate the timing, rate and predictors of pre- (‘early’) versus post-discharge (‘late’) VTE.

Methods

All patients undergoing elective hepatectomy during 2005–2010 and recorded in the American College of Surgeons National Surgical Quality Improvement Program participant use file were identified. Perioperative factors associated with 30-day rates of early and late VTE were analysed.

Results

A total of 7621 patients underwent 4553 (59.7%) partial, 802 (10.5%) left, 1494 (19.6%) right and 772 (10.1%) extended hepatectomies. Event rates were 1.9% for deep venous thrombosis, 1.2% for pulmonary embolus and 2.8% for VTE. Of instances of VTE, 28.6% occurred post-discharge. The median time of presentation of late VTE was postoperative day 14. Multivariate analysis determined that early VTE was associated with age ≥75 years [odds ratio (OR) 1.92, P = 0.007], male gender (OR 1.87, P = 0.002), intraoperative transfusion (OR 2.49, P < 0.001), operative time of >240 min (OR 2.28, P < 0.001), organ space infection (OSI) (OR 2.60, P < 0.001), and return to operating room (ROR) (OR 3.25, P < 0.001). Late VTE was associated with operative time of >240 min (OR 2.35, P = 0.008), OSI (OR 3.78, P < 0.001) and ROR (OR 2.84, P = 0.011).

Conclusions

Late VTE events occur in patients with clearly identifiable intraoperative and postoperative risk factors. This provides a rationale for the selective use of post-discharge VTE chemoprophylaxis in high-risk patients.     

Urinary Elafin and Kidney Injury in Hematopoietic Cell Transplant Recipients

Background and objectives

Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury.

Design, setting, participants, & measurements

Urine was collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels and microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined using Cox proportional hazards or linear regression models. Available kidney biopsy specimens were processed for immunohistochemistry.

Results

Mean urinary elafin levels to day 100 were higher in patients with micro- or macroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a normal ACR (adjusted mean difference, 1295 pg/ml; P<0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P<0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro- or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P<0.01). Each increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to 1.13; P<0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P<0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules.

Conclusion

Higher urinary elafin levels are associated with an increased risk of micro- and macroalbuminuria, AKI and CKD, and death after HCT.     

False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

Background and objectives

Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false–positive rates because of inherent laboratory and biologic variabilities of creatinine.

Design, setting, participants, & measurements

We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false–positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient’s true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria.

Results

Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false–positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%–8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false–positive AKI diagnosis rate of 30.5% (interquartile range =30.1%–30.9%) versus 2.0% (interquartile range =1.9%–2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001).

Conclusions

Use of small serum creatinine changes to diagnose AKI is limited by high false–positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies.     

Neoadjuvant radiation therapy and its impact on complications after pancreaticoduodenectomy for pancreatic cancer: analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)

Objectives

This study investigated the impact of neoadjuvant radiation therapy (XRT) on postoperative outcomes following pancreaticoduodenectomy for pancreatic cancer.

Methods

The American College of Surgeons National Quality Improvement Program database was queried for the period 2005–2010 to assess complication rates following pancreaticoduodenectomy for pancreatic cancer. Two groups of patients were identified, comprising those who received neoadjuvant XRT and those who did not (control group).

Results

A total of 4416 patients were identified, including 200 in the XRT group and 4216 in the control group. There were differences in patient characteristics between the groups, including in age, hypertension and bilirubin level. Despite the fact that weight loss was more common, median operative time was longer (423 min versus 368 min; P < 0.001), and vascular reconstruction was more commonly required (20.5% versus 8.4%; P < 0.001) in the XRT group. In addition, the XRT group had a shorter median hospital stay than the control group (9 days versus 10 days; P = 0.005). Mortality (3.0% versus 2.7%; P = 0.818) and morbidity (40.5% versus 37.6%; P = 0.404) rates were not influenced by neoadjuvant XRT. Blood transfusion rates were increased in the XRT group (13.0% versus 7.4%; P = 0.003). Severe complications were influenced by age >70 years, American Society of Anesthesiologists (ASA) class >2, preoperative sepsis, dyspnoea, weight loss, impaired functional status, peripheral vascular disease and operative time of >8 h.

Conclusions

Neoadjuvant XRT is not associated with an increase in complications after pancreaticoduodenectomy.     

Plasma Urate and Risk of a Hospital Stay with AKI: The Atherosclerosis Risk in Communities Study

Background and objectives

Higher urate levels are associated with higher risk of CKD, but the association between urate and AKI is less established. This study evaluated the risk of hospitalized AKI associated with urate concentrations in a large population-based cohort. To explore whether urate itself causes kidney injury, the study also evaluated the relationship between a genetic urate score and AKI.

Design, setting, participants, & measurements

A total of 11,011 participants from the Atherosclerosis Risk in Communities study were followed from 1996–1998 (baseline) to 2010. The association between baseline plasma urate and risk of hospitalized AKI, adjusted for known AKI risk factors, was determined using Cox regression. Interactions of urate with gout and CKD were tested. Mendelian randomization was performed using a published genetic urate score among the participants with genetic data (n=7553).

Results

During 12 years of follow-up, 823 participants were hospitalized with AKI. Overall, mean participant age was 63.3 years, mean eGFR was 86.3 ml/min per 1.73 m², and mean plasma urate was 5.6 mg/dl. In patients with plasma urate >5.0 mg/dl, there was a 16% higher risk of hospitalized AKI for each 1-mg/dl higher urate (adjusted hazard ratio, 1.16; 95% confidence interval, 1.10 to 1.23; P<0.001). When stratified by history of gout, the association between higher urate and AKI was significant only in participants without a history of gout (P for interaction=0.02). There was no interaction of CKD and urate with AKI, nor was there an association between genetic urate score and AKI.

Conclusions

Plasma urate >5.0 mg/dl was independently associated with risk of hospitalized AKI; however, Mendelian randomization did not provide evidence for a causal role of urate in AKI. Further research is needed to determine whether lowering plasma urate might reduce AKI risk.     

Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre

Objectives

Mortality in pancreatic cancer has remained unchanged over the last 20–30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution.

Methods

Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990–1999 and 2000–2009). Predictors of survival were analysed using univariate and multivariate analyses.

Results

Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990–1999 and 2000–2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990–1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome.

Conclusions

Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.     

Evaluation of stapler hepatectomy during a laparoscopic liver resection

Methods

An international database of 1499 laparoscopic liver resections was analysed using multivariate and Kaplan–Meier analysis.

Results

In total, 764 stapler hepatectomies (SH) were compared with 735 electrosurgical resections (ER). SH was employed in larger tumours (4.5 versus 3.8 cm; P < 0.003) with decreased operative times (2.6 versus 3.1 h; P < 0.001), blood loss (100 versus 200 cc; P < 0.001) and length of stay (3.0 versus 7.0 days; P < 0.001). SH incurred a trend towards higher complications (16% versus 13%; P = 0.057) including bile leaks (26/764, 3.4% versus 16/735, 2.2%: P = 0.091). To address group homogeneity, a subset analysis of lobar resections confirmed the benefits of SH. Kaplan–Meier analysis in non-cirrhotic and cirrhotic patients confirmed equivalent patient (P = 0.290 and 0.118) and disease-free survival (P = 0.120 and 0.268). Multivariate analysis confirmed the parenchymal transection technique did not increase the risk of cancer recurrence, whereas tumour size, the presence of cirrhosis and concomitant operations did.

Conclusions

A SH provides several advantages including: diminished blood loss, transfusion requirements and shorter operative times. In spite of the smaller surgical margins in the SH group, equivalent recurrence and survival rates were observed when matched for parenchyma and extent of resection.     

Actual 10-year survival following hepatectomy for hepatocellular carcinoma

Objectives

This study was conducted to compare 10-year survivors with patients who survived <10 years in a large Western series of patients submitted to hepatectomy for hepatocellular carcinoma (HCC).

Methods

A retrospective review of a series of hepatic resections conducted in a referral centre for HCC between January 1987 and October 2002 was conducted.

Results

A total of 176 patients were analysed. Twenty-eight patients survived ≥ 10 years (Group A) and were compared with the 148 patients who did not (Group B). Group A had smaller tumours (5.7 cm versus 8.2 cm; P = 0.001) and a lower incidence of microvascular invasion (18.5% versus 37.1%; P = 0.004). Recurrence did not differ significantly (Group A 18/28, 64.3% versus Group B 94/148, 63.5%). Median time to recurrence was longer in Group A (70 months versus 15 months; P < 0.0001), and more patients in Group A were able to undergo curative treatment for recurrence (88.8% versus 40.4%; P < 0.0001). Multivariate analysis showed that lack of vascular invasion (P = 0.020), absence of perioperative transfusion (P = 0.014), and recurrence at >2 years after primary resection (P = 0.045) were significantly associated with 10-year survival.

Conclusions

Ten-year survival after liver resection for HCC can be expected in approximately 15% of patients. Recurrence does not preclude longterm survival. Recurrence at >2 years after resection, absence of vascular invasion, and absence of perioperative transfusion are independently associated with 10-year survival.     

Peripheral Edema,Central Venous Pressure,and Risk of AKI in Critical Illness

Background and objectives

Although venous congestion has been linked to renal dysfunction in heart failure, its significance in a broader context has not been investigated.

Design, setting, participants, & measurements

Using an inception cohort of 12,778 critically ill adult patients admitted to an urban tertiary medical center between 2001 and 2008, we examined whether the presence of peripheral edema on admission physical examination was associated with an increased risk of AKI within the first 7 days of critical illness. In addition, in those with admission central venous pressure (CVP) measurements, we examined the association of CVPs with subsequent AKI. AKI was defined using the Kidney Disease Improving Global Outcomes criteria.

Results

Of the 18% (n=2338) of patients with peripheral edema on admission, 27% (n=631) developed AKI, compared with 16% (n=1713) of those without peripheral edema. In a model that included adjustment for comorbidities, severity of illness, and the presence of pulmonary edema, peripheral edema was associated with a 30% higher risk of AKI (95% confidence interval [95% CI], 1.15 to 1.46; P<0.001), whereas pulmonary edema was not significantly related to risk. Peripheral edema was also associated with a 13% higher adjusted risk of a higher AKI stage (95% CI, 1.07 to 1.20; P<0.001). Furthermore, levels of trace, 1+, 2+, and 3+ edema were associated with 34% (95% CI, 1.10 to 1.65), 17% (95% CI, 0.96 to 1.14), 47% (95% CI, 1.18 to 1.83), and 57% (95% CI, 1.07 to 2.31) higher adjusted risk of AKI, respectively, compared with edema-free patients. In the 4761 patients with admission CVP measurements, each 1 cm H₂O higher CVP was associated with a 2% higher adjusted risk of AKI (95% CI, 1.00 to 1.03; P=0.02).

Conclusions

Venous congestion, as manifested as either peripheral edema or increased CVP, is directly associated with AKI in critically ill patients. Whether treatment of venous congestion with diuretics can modify this risk will require further study.