Predictive modelling for postoperative acute kidney injury: big data enhancing quality or the Emperor's new clothes?

The increased availability of large clinical datasets together with increasingly sophisticated computing power has facilitated development of numerous risk prediction models for various adverse perioperative outcomes, including acute kidney injury (AKI). The rationale for developing such models is straightforward. However, despite numerous purported benefits, the uptake of preoperative prediction models into clinical practice has been limited. Barriers to implementation of predictive models, including limitations in their discrimination and accuracy, as well as their ability to meaningfully impact clinical practice and patient outcomes, are increasingly recognised. Some of the purported benefits of predictive modelling, particularly when applied to postoperative AKI, might not fare well under detailed scrutiny. Future research should address existing limitations and seek to demonstrate both benefit to patients and value to healthcare systems from implementation of these models in clinical practice.

Determinants and practice variability of oxygen administration during surgery in the U.S., a retrospective cohort study.

BACKGROUND: The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. We aimed to assess determinants of oxygen administration and its variability during surgery. METHODS: Using multivariable linear mixed-effects regression, we measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 minutes or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the U.S. participating in the Multicenter Perioperative Outcomes Group data registry. RESULTS: The sample included 367,841 cases (median [25 th, 75 th] age, 59 [47, 69] years; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25 th, 75 th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases <0.40 and 8.7% >0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced ASA classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (<1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5) of the variability in oxygen administration and procedure factors 4.4% (4.2 to 4.6). Anesthesiologist explained 7.7% (7.2 to 8.2) of the variability in oxygen administration, in-room anesthesia provider 8.1% (7.8 to 8.4), medical center 23.3% (22.4 to 24.2), and 53.0% (95% CI, 52.4 to 53.6) was unexplained. CONCLUSIONS: Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.

Effectiveness of Oral Iron Therapy in Anemic Inpatient Pregnant Women: A Single Center Retrospective Cohort Study.

Background and aim Oral iron therapy is effective in treating iron deficiency anemia in outpatient pregnant women but has not been studied in inpatient pregnant women. We aimed to evaluate the effect of oral iron therapy versus no therapy during hospitalization on maternal and neonatal outcomes in women with anemia who are hospitalized for pregnancy-related morbidities (i.e., preterm premature rupture of membranes, preterm labor, pre-eclampsia, abnormal placentation, or fetal monitoring). Methods A retrospective, single-center study was conducted in hospitalized pregnant women (2018 to 2020) with inpatient stays of more than three days. The primary outcome was a change in hemoglobin level from admission to delivery in women treated with oral iron compared with those left untreated. Secondary outcomes included the total amount of iron administered before delivery, the time interval from admission to delivery, and neonatal effects. Results Two hundred sixty-three women were admitted, 79 women had anemia, and 29 (36.7%) received at least one dose of oral iron. Baseline patient characteristics were similar between groups. The median (interquartile range) dose of iron in the oral iron group was 1185.0 (477.0, 1874.0) mg. Neither absolute hemoglobin before delivery (control group: 10.0±1.2 g/dL; iron group: 10.1±1.1 g/dL; p=0.774) nor change in hemoglobin from admission to delivery (control group: -0.1±1.1 g/dL vs. iron group: 0.4±1.1 g/dL; p=0.232) differed between groups. Women in the control group had shorter length of stay (LOS) median (IQR) than women in the iron group (control group: 7.1 (5.0, 13.7) days; iron group: 11.4 (7.4, 25.9) days; p=0.03). There were no differences in maternal mode of delivery, though each group had high rates of cesarean delivery (control group: 53.7%; iron group: 72.4%; p=0.181). There were no differences in estimated blood loss at delivery (control group: 559±401; iron group: 662.1±337.4;p=0.264) in either group. Neonatal birthweight (control group: 1.9±0.7 kg; iron group: 1.9±0.7 kg; p=0.901), birth hemoglobin (control group: 16.3±2.2 g/dL; iron group: 16±2.2 g/dL; p=0.569), neonatal intensive care unit (NICU) admission (control group: 93.3%; iron group: 84.8%;p=0.272 ), or neonatal death (control group: 8.9%; iron group: 3%; p=0.394) were not different between groups. Conclusions Oral iron administered to anemic inpatient pregnant women was not associated with higher hemoglobin concentrations before delivery. Lack of standardized iron regimens and short hospital stays may contribute to the inefficacy of oral iron for this inpatient pregnant population. The small sample size and retrospective nature of this study are limiting factors in drawing conclusive evidence from this study.

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort.

BACKGROUND: Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence. METHODS: A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables. RESULTS: Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI. CONCLUSIONS: Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk-benefit ratio of these drugs in the perioperative period.

Poor Agreement Between Preoperative Transthoracic Echocardiography and Intraoperative Transesophageal Echocardiography for Grading Diastolic Dysfunction.

BACKGROUND: Guidelines for the evaluation and grading of diastolic dysfunction are available for transthoracic echocardiography (TTE). Transesophageal echocardiography (TEE) is used for this purpose intraoperatively but the level of agreement between these 2 imaging modalities for grading diastolic dysfunction is unknown. We assessed agreement between awake preoperative TTE and intraoperative TEE for grading diastolic dysfunction. METHODS: In 98 patients undergoing cardiac surgery, key Doppler measurements were obtained using TTE and TEE at the following time points: TTE before anesthesia induction (TTEawake), TTE following anesthesia induction (TTEanesth), and TEE following anesthesia induction (TEEanesth). The primary endpoint was grade of diastolic dysfunction categorized by a simplified algorithm, and measured by TTEawake and TEEanesth, for which the weighted κ statistic assessed observed agreement beyond chance. Secondary endpoints were peak early diastolic lateral mitral annular tissue velocity (e'lat) and the ratio of peak early diastolic mitral inflow velocity (E) to e'lat (E/e'lat), measured by TTEawake and TEEanesth, were compared using Bland-Altman limits of agreement. RESULTS: Disagreement in grading diastolic dysfunction by ≥1 grade occurred in 43 (54%) of 79 patients and by ≥2 grades in 8 (10%) patients with paired measurements for analysis, yielding a weighted κ of 0.35 (95% confidence interval [CI], 0.19-0.51) for the observed level of agreement beyond chance. Bland-Altman analysis of paired data for e'lat and E/e'lat demonstrated a mean difference (95% CI) of 0.51 (-0.06 to 1.09) and 0.70 (0.07-1.34), respectively, for measurements made by TTEawake compared to TEEanesth. The percentage (95% CI) of paired measurements for e'lat and E/e'lat that lay outside the [-2, +2] study-specified boundary of acceptable agreement was 36% (27%-48%) and 39% (29%-51%), respectively. Results were generally robust to sensitivity analyses, including comparing measurements between TTEawake and TTEanesth, between TTEanesth and TEEanesth, and after regrading diastolic dysfunction by the American Society of Echocardiography (ASE)/European Association of CardioVascular Imaging (EACVI) algorithm. CONCLUSIONS: There was poor agreement between TTEawake and TEEanesth for grading diastolic dysfunction by a simplified algorithm, with disagreement by ≥1 grade in 54% and by ≥2 grades in 10% of the evaluable cohort. Future studies, including comparing the prognostic utility of TTEawake and TEEanesth for clinically important adverse outcomes that may be a consequence of diastolic dysfunction, are needed to understand whether this disagreement reflects random variability in Doppler variables, misclassification by the changed technique and physiological conditions of intraoperative TEE, or the accurate detection of a clinically relevant change in diastolic dysfunction.

Effects of Postoperative Blood Pressure Management on Delirium Among Patients in the Intensive Care Unit After Cardiac Surgery: An Observational Cohort Study.

OBJECTIVES: This study aimed to determine whether blood pressure control in the early postoperative period was associated with postoperative delirium in the cardiovascular intensive care unit (ICU). DESIGN: Observational cohort study. SETTING: Single large academic institution with a high volume of cardiac surgery. PARTICIPANTS: Cardiac surgery patients admitted to the cardiovascular ICU after surgery. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: A total of 517 cardiac surgery patients had mean arterial pressure (MAP) data recorded minute-by-minute for 12 postoperative hours. The time spent in each of the 7 prespecified blood pressure bands was calculated, and the development of delirium was recorded in the ICU. A multivariate Cox regression model was developed using the least absolute shrinkage and selection operator approach to identify associations between time spent in each MAP range band and delirium. Compared with the reference band of 60-to-69 mmHg, longer durations spent in 3 bands were independently associated with a lower risk of delirium: 50-to-59 mmHg band (adjusted hazard ratio [HR] 0.907 [per 10 minutes]; 95% CI 0.861-0.955); 70-to-79 mmHg band (adjusted HR 0.923 [per 10 minutes]; 95% CI 0.902-0.944); 90-to-99 mmHg band (adjusted HR 0.898 [per 10 minutes]; 95% CI 0.853-0.945). CONCLUSIONS: The MAP range bands above and below the authors' reference band of 60-to- 69 mmHg were associated with decreased risk of ICU delirium development; however, this was difficult to reconcile with a plausible biologic mechanism. Therefore, the authors did not find a correlation between early postoperative MAP control and increased risk of the development of ICU delirium after cardiac surgery.

Oxygen administration during surgery and postoperative organ injury: observational cohort study.

OBJECTIVE: To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury. DESIGN: Observational cohort study. SETTING: 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. PARTICIPANTS: Adult patients undergoing surgical procedures ≥120 minutes' duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018. INTERVENTION: Supraphysiological oxygen administration, defined as the area under the curve of the fraction of inspired oxygen above air (21%) during minutes when the hemoglobin oxygen saturation was greater than 92%. MAIN OUTCOMES: Primary endpoints were acute kidney injury defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin >0.04 ng/mL within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes. RESULTS: The cohort comprised 350 647 patients with median age 59 years (interquartile range 46-69 years), 180 546 women (51.5%), and median duration of surgery 205 minutes (interquartile range 158-279 minutes). Acute kidney injury was diagnosed in 19 207 of 297 554 patients (6.5%), myocardial injury in 8972 of 320 527 (2.8%), and lung injury in 13 789 of 312 161 (4.4%). The median fraction of inspired oxygen was 54.0% (interquartile range 47.5%-60.0%), and the area under the curve of supraphysiological inspired oxygen was 7951% min (5870-11 107% min), equivalent to an 80% fraction of inspired oxygen throughout a 135 minute procedure, for example. After accounting for baseline covariates and other potential confounding variables, increased oxygen exposure was associated with a higher risk of acute kidney injury, myocardial injury, and lung injury. Patients at the 75th centile for the area under the curve of the fraction of inspired oxygen had 26% greater odds of acute kidney injury (95% confidence interval 22% to 30%), 12% greater odds of myocardial injury (7% to 17%), and 14% greater odds of lung injury (12% to 16%) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations. CONCLUSIONS: Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded. TRIAL REGISTRATION: Open Science Framework osf.io/cfd2m.

Translating evidence into practice: still a way to go.

Chiu and colleagues report a retrospective analysis describing the 5-yr trend in both intraoperative fluid and vasopressor administration in 32 250 patients undergoing elective abdominal surgery within the Multicenter Perioperative Outcomes Group (MPOG) database from 2015 to 2019, and exploring the association between these two factors and acute kidney injury. Modelling predicted the lowest risk for acute kidney injury when the administered crystalloid volume was 15-20 ml kg-1 h-1, and an 80% increase in risk for acute kidney injury as intraoperative vasopressor use increased from 0 to 0.04 µg kg-1 min-1 of norepinephrine equivalents. Although these results are consistent with those of a large, randomised trial (REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery [RELIEF]) published in 2018, the mean intraoperative volume of crystalloid administered in the current study declined monotonically through every year included, from 6.4 ml kg-1 h-1 in 2015 to 5.5 ml kg-1 h-1 in 2019. These new findings support the broad generalisability of the RELIEF trial; highlight the complexity of the relationship between intravenous crystalloid volume infused, arterial pressure, and acute kidney injury; and demonstrate the ongoing challenge of translating high-quality evidence into clinical practice.

Is an Acute Perioperative Increase in Creatinine Production Rate a Potential Mechanism for an Early Creatinine-Based Signal of Renal Injury After Cardiac Surgery?

OBJECTIVES: Previous studies report a creatinine-based signal of injury within hours after cardiac surgery, which is sooner than expected based on creatinine kinetic modelling. A plausible mechanism for such an early signal has not been established, but might be explained by an acute perioperative increase in creatinine production rate (Crprod-rate). The authors sought to test the hypothesis that perioperative Crprod-rate increases from baseline in patients undergoing cardiac surgery. DESIGN: Prospective cohort study. SETTING: Academic medical center. PARTICIPANTS: Fifty adult male patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on the principle of conservation of mass, precisely timed serial measurements of patient weight, plasma and urine creatinine concentration, and urine volume were used to calculate Crprod-rate over 3 consecutive periods: a baseline period immediately before surgery (period 0), the 24-hour period starting from induction of anesthesia (period 1), and again from 24 to 48 hours after induction of anesthesia (period 2). The primary outcome was change in Crprod-rate from period 0 to period 1 (∆Crprod-rate0-1). Median Crprod-rate0 was 5.4 (interquartile range [IQR], 4.7-5.7) µmol/kg/h at baseline and increased to 6.1 (IQR, 5.6-6.5) µmol/kg/h during period 1, a median increase of 14% (95% CI, 8%-27%; p = 0.002). ∆Crprod-rate0-1 ranged from -58% to +129%, with an increase above baseline in 25 patients (76%) and an increase by ≥30% above baseline in 10 patients (30%). CONCLUSIONS: Perioperative Crprod-rate increased from baseline in patients undergoing cardiac surgery. This may represent a mechanism for an earlier creatinine-based signal of renal injury than previously thought possible.

Society of Cardiovascular Anesthesiologists Clinical Practice Update for Management of Acute Kidney Injury Associated With Cardiac Surgery.

Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.

Predicting acute kidney injury after cardiac surgery: much work still to be done.

Accurate preoperative risk prediction for perioperative complications such as acute kidney injury (AKI) may serve to better inform patients and families of risk before surgery, assist with resource requirement planning, and aid with cohort enrichment for enrolment into clinical trials. Where a specific risk factor is modifiable, it may offer a potential therapeutic target for risk reduction. The report by Wang and colleagues describes the modest incremental benefit of N-terminal pro brain natriuretic peptide levels when added to almost 20 other variables for the preoperative prediction of AKI after cardiac surgery. This is consistent with previous smaller studies, but there are important additional questions still to be answered before this biomarker might be used for this purpose in clinical practice.

Potential Renoprotective Strategies in Adult Cardiac Surgery: A Survey of Society of Cardiovascular Anesthesiologists Members to Explore the Rationale and Beliefs Driving Current Clinical Decision-Making.

OBJECTIVES: The authors sought to (1) characterize the rationale underpinning anesthesiologists' use of various perioperative strategies hypothesized to affect renal function in adult patients undergoing cardiac surgery, (2) characterize existing belief about the quality of evidence addressing the renal impact of these strategies, and (3) identify potentially renoprotective strategies for which anesthesiologists would most value a detailed, evidence-based review. DESIGN: Survey of perioperative practice in adult patients undergoing cardiac surgery. SETTING: Online survey. PARTICIPANTS: Members of the Society of Cardiovascular Anesthesiologists (SCA). INTERVENTIONS: None. MEASUREMENTS & MAIN RESULTS: The survey was distributed to more than 2,000 SCA members and completed in whole or in part by 202 respondents. Selection of target intraoperative blood pressure (and relative hypotension avoidance) was the strategy most frequently reported to reflect belief about its potential renal effect (79%; 95% CI: 72-85). Most respondents believed the evidence supporting an effect on renal injury of intraoperative target blood pressure during cardiac surgery was of high or moderate quality. Other factors, including a specific nonrenal rationale, surgeon preference, department- or institution-level decisions, tradition, or habit, also frequently were reported to affect decision making across queried strategies. Potential renoprotective strategies most frequently requested for inclusion in a subsequent detailed, evidence-based review were intraoperative target blood pressure and choice of vasopressor agent to achieve target pressure. CONCLUSIONS: A large number of perioperative strategies are believed to variably affect renal injury in adult patients undergoing cardiac surgery, with wide variation in perceived quality of evidence for a renal effect of these strategies.

Peak Serum Chloride and Hyperchloremia in Patients Undergoing Cardiac Surgery Is Not Explained by Chloride-Rich Intravenous Fluid Alone: A Post-Hoc Analysis of the LICRA Trial.

OBJECTIVES: With the exception of 0.9% saline, little is known about factors that may contribute to increased serum chloride concentration (SCl-) in patients undergoing cardiac surgery. For the present study, the authors sought to characterize the association between administered chloride load from intravenous fluid and other perioperative variables, with peak perioperative SCl-. DESIGN: Secondary analysis of data from a previously published controlled clinical trial in which patients were assigned to a chloride-rich or chloride-limited perioperative fluid strategy (NCT02020538). SETTING: Academic medical center. PARTICIPANTS: The study comprised 1,056 adult patients with normal preoperative SCl- undergoing cardiac surgery. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Peak perioperative SCl- and hyperchloremia, defined as peak SCl- >110 mmol/L, were selected as co-primary endpoints. Regression modeling identified factors independently associated with these endpoints. Mean (standard deviation) peak perioperative SCl- was 114 (5) mmol/L, and hyperchloremia occurred in 824 (78.0%) of the cohort. In addition to administered volume of 0.9% saline, multivariate linear and logistic regression modeling consistently associated preoperative SCl- (regression coefficient 0.5; 95% confidence interval [CI] 0.4-0.6 mmol/L; odds ratio 1.60; 95% CI 1.41-1.82 per 1 mmol/L increase) and cardiopulmonary bypass duration (regression coefficient 0.1; 95% CI 0.1-0.2 mmol/L; odds ratio 1.12; 95% CI 1.06-1.19 per 10 minutes) with both co-primary outcomes. Multivariate modeling only explained approximately 50% of variability in peak SCl-. CONCLUSIONS: The present study's data identified an association for both 0.9% saline administration and other nonfluid variables with peak perioperative SCl- and hyperchloremia. Stand-alone strategies to limit administration of chloride-rich intravenous fluid may have limited ability to prevent hyperchloremia in this setting.

Perioperative Clinical Trials in AKI.

To characterize current evidence and current foci of perioperative clinical trials, we systematically reviewed Medline and identified perioperative trials involving 100 or more adult patients undergoing surgery and reporting renal end points that were published in high-impact journals since 2004. We categorized the 101 trials identified based on the nature of the intervention and summarized major trial findings from the five categories most applicable to perioperative management of patients. Trials that targeted ischemia suggested that increasing perioperative renal oxygen delivery with inotropes or blood transfusion does not reliably mitigate acute kidney injury (AKI), although goal-directed therapy with hemodynamic monitors appeared beneficial in some trials. Trials that have targeted inflammation or oxidative stress, including studies of nonsteroidal anti-inflammatory drugs, steroids, N-acetylcysteine, and sodium bicarbonate, have not shown renal benefits, and high-dose perioperative statin treatment increased AKI in some patient groups in two large trials. Balanced crystalloid intravenous fluids appear safer than saline, and crystalloids appear safer than colloids. Liberal compared with restrictive fluid administration reduced AKI in a recent large trial in open abdominal surgery. Remote ischemic preconditioning, although effective in several smaller trials, failed to reduce AKI in two larger trials. The translation of promising preclinical therapies to patients undergoing surgery remains poor, and most interventions that reduced perioperative AKI compared novel surgical management techniques or existing processes of care rather than novel pharmacologic interventions.

Importance of intraoperative oliguria during major abdominal surgery: findings of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery trial.

BACKGROUND: The association between intraoperative oliguria during major abdominal surgery and the subsequent development of postoperative acute kidney injury (AKI) remains poorly defined. We hypothesised that, in such patients, intraoperative oliguria would be an independent predictor of subsequent AKI. METHODS: We performed a post hoc analysis of data from the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial of conservative vs liberal fluid therapy during and after major abdominal surgery. We used χ2, logistic regression, and fractional polynomials to study the association between intraoperative oliguria defined as a urinary output <0.5 ml kg-1 h-1 and the development of postoperative AKI defined by the Kidney Disease Improving Global Outcomes consensus criteria. RESULTS: We included 2444 of 2983 patients from the RELIEF trial in this study. A total of 889 patients (36%) met oliguric criteria intraoperatively. Oliguria occurred in 35% of those without AKI, and 44%, 48%, and 45% of those who developed postoperative AKI Stages 1-3, respectively (P<0.001 for trend). Intraoperative oliguria was associated with an increased risk of AKI, risk ratio: 1.38 (95% confidence interval: 1.14-1.44; P<0.001), but greater intensity of oliguria (urine output <0.3 ml kg-1 h-1) did not increase this risk further. Most patients with oliguria did not develop AKI; the positive predictive value of oliguria was 25.5%, and the negative predictive value was 81.6%. CONCLUSIONS: Intraoperative oliguria, defined as urine output <0.5 ml kg-1 h-1, was relatively common and was associated with postoperative AKI. However, the predictive utility of oliguria for AKI was low, whilst its absence had a good predictive value for an AKI-free postoperative course. CLINICAL TRIAL REGISTRATION: NCT01424150.

Combining Novel Renal Injury Markers with Delta Serum Creatinine Early after Cardiac Surgery and Risk-Stratification for Serious Adverse Outcomes: An Exploratory Analysis.

OBJECTIVE: To evaluate the prognostic utility of multiple novel urinary biomarkers of renal injury when used alone, in pair-wise combination with an early delta serum creatinine (ΔSCr) term, and combined as a broad biomarker panel for the prediction of serious adverse outcomes that may reflect AKI in patients undergoing cardiac surgery. DESIGN: Post-hoc analysis of prospective observational study. SETTING: Academic medical center. PARTICIPANTS: 603 adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urinary cystatin-c, kidney injury molecule-1, chemokine (C-C motif) ligand 2 and interleukin-18 were measured at baseline and <1 hour, 3 hours and 18-24 hours after separation from cardiopulmonary bypass (CPB). ΔSCr-initial was defined as the difference in SCr from baseline to first postoperative measure. The primary outcome of hospital mortality or renal replacement therapy occurred in 25 patients. Concordant elevation of any urinary biomarker measured 3 hours after CPB together with ΔSCr-initial ≥0 mg.dL-1 provided excellent early risk stratification for the primary outcome (OR ≥15.1, 95% CI 4.1-55.4). Combining four urinary biomarkers together with ΔSCr-initial and neutrophil gelatinase-associated lipocalin, previously reported from the same cohort, to provide a 6-point AKI risk score enabled early identification of patients reaching the primary outcome (ROCAUC 0.86, 95% CI 0.79-0.92) with potentially useful sensitivity and specificity at varied cut-points. CONCLUSIONS: Combining novel urinary biomarkers of renal injury with a creatinine-based metric soon after cardiac surgery provided excellent prognostic utility for serious adverse outcomes. Future studies are required to confirm these findings and determine optimal biomarker combinations for cost-effective risk stratification.

Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia.

OBJECTIVE: To evaluate 'days at home up to 30 days after surgery' (DAH30) as a patient-centred outcome measure. DESIGN: Prospective cohort study. DATA SOURCE: Using clinical trial data (seven trials, 2109 patients) we calculated DAH30 from length of stay, readmission, discharge destination and death up to 30 days after surgery. MAIN OUTCOME: The association between DAH30 and serious complications after surgery. RESULTS: One or more complications occurred in 263 of 1846 (14.2%) patients, including 19 (1.0%) deaths within 30 days of surgery; 245 (11.6%) patients were discharged to a rehabilitation facility and 150 (7.1%) were readmitted to hospital within 30 days of surgery. The median DAH30 was significantly less in older patients (p<0.001), those with poorer physical functioning (p<0.001) and in those undergoing longer operations (p<0.001). Patients with serious complications had less days at home than patients without serious complications (20.5 (95% CI 19.1 to 21.9) vs 23.9 (95% CI 23.8 to 23.9) p<0.001), and had higher rates of readmission (16.0% vs 5.9%; p<0.001). After adjusting for patient age, sex, physical status and duration of surgery, the occurrence of postoperative complications was associated with fewer days at home after surgery (difference 3.0(95% CI 2.1 to 4.0) days; p<0.001). CONCLUSIONS: DAH30 has construct validity and is a readily obtainable generic patient-centred outcome measure. It is a pragmatic outcome measure for perioperative clinical trials.

Standardized Renal Endpoints for Perioperative Clinical Trials: The Standardized Endpoints in Perioperative Medicine Initiative.

Perioperative acute kidney injury is a common problem. While clinical trials seek to evaluate the impact of interventions on a variety of primary and secondary endpoints with the aim of implementing this knowledge to improve perioperative outcomes, the use of valid and relevant endpoints within clinical trials is of critical importance to achieving this goal. Suitable endpoints must be validated for the study population and in light of the clinical context under investigation while also considering regulatory requirements that govern the licensing of new therapeutic agents as well as the values of patients whose outcomes we seek to improve. Heterogeneity in perioperative clinical trial endpoints and their definitions limits the ability to compare and interpret differences in outcomes across studies or to pool outcomes from different studies in meta-analysis. The Standardized Endpoints in Perioperative Medicine (StEP) initiative is an international collaboration whose goal is to identify and recommend a suite of clearly and precisely defined endpoints across multiple domains, specifically suited for use in perioperative clinical trials. The current review describes the rationale, goals and the planned pathway of the StEP renal subgroup. Development of a set of standardized and core renal endpoints, valid and relevant for use in the perioperative context, precisely defined and yet with sufficient flexibility to encourage broad uptake and application should facilitate high-quality and practice-changing perioperative research into the future.