Stemland, Christopher J.; Witte, Jurgen; Colquhoun, Douglas A.; Durieux, Marcel E.; Langman, Loralie J.; Balireddy, Ravi; Thammishetti, Swapna; Abel, Mark F.; Anderson, Brian J. Author Information
Abstract Background Despite the significant healthcare impact of acute kidney injury, little is known regarding prevention. Single-center data have implicated hypotension in developing postoperative acute kidney injury. The generalizability of this finding and the interaction between hypotension and baseline patient disease burden remain unknown. The authors sought to determine whether the association between intraoperative hypotension and acute kidney injury varies by preoperative risk. Methods Major noncardiac surgical procedures performed on adult patients across eight hospitals between 2008 and 2015 were reviewed. Derivation and validation cohorts were used, and cases were stratified into preoperative risk quartiles based upon comorbidities and surgical procedure. After preoperative risk stratification, associations between intraoperative hypotension and acute kidney injury were analyzed. Hypotension was defined as the lowest mean arterial pressure range achieved for more than 10 min; ranges were defined as absolute (mmHg) or relative (percentage of decrease from baseline). Results Among 138,021 cases reviewed, 12,431 (9.0%) developed postoperative acute kidney injury. Major risk factors included anemia, estimated glomerular filtration rate, surgery type, American Society of Anesthesiologists Physical Status, and expected anesthesia duration. Using such factors and others for risk stratification, patients with low baseline risk demonstrated no associations between intraoperative hypotension and acute kidney injury. Patients with medium risk demonstrated associations between severe-range intraoperative hypotension (mean arterial pressure less than 50 mmHg) and acute kidney injury (adjusted odds ratio, 2.62; 95% CI, 1.65 to 4.16 in validation cohort). In patients with the highest risk, mild hypotension ranges (mean arterial pressure 55 to 59 mmHg) were associated with acute kidney injury (adjusted odds ratio, 1.34; 95% CI, 1.16 to 1.56). Compared with absolute hypotension, relative hypotension demonstrated weak associations with acute kidney injury not replicable in the validation cohort. Conclusions Adult patients undergoing noncardiac surgery demonstrate varying associations with distinct levels of hypotension when stratified by preoperative risk factors. Specific levels of absolute hypotension, but not relative hypotension, are an important independent risk factor for acute kidney injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
It is not my purpose to advocate any particular model for drug action as being the truth. And, a fortiori the particular values of parameters used here in numerical examples are chosen for illustration only, though they are chosen to be not grossly incompatible with experimental results (see p. 163). My intention is merely to discuss the extent to which some new observations are compatible with the substantial body of quantitative evidence that is consistent with the classical ideas about drug action. These new observations suggest that some form of cooperative step is involved in the response to certain agonists, whereas no cooperativity was postulated in the classical ideas about drug action.
Surgical procedures performed on patients with recent exposure to COVID-19 infection have been associated with increased mortality risk in previous studies. Accordingly, elective surgery is often delayed after infection. The study aimed to compare 30-day hospital mortality and postoperative complications (acute kidney injury, pulmonary complications) of surgical patients with a previous COVID-19 infection to a matched cohort of patients without known previous COVID-19. The authors hypothesized that COVID-19 exposure would be associated with an increased mortality risk.
Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications.
The coagulopathy of end-stage liver disease results from a complex derangement in both anticoagulant and procoagulant processes. With even minor insults, cirrhotic patients experience either inappropriate bleeding or clotting, or even both simultaneously. The various phases of liver transplantation along with fluid and blood product administration may contribute to additional disturbances in coagulation. Thus, anesthetic management of patients undergoing liver transplantation to improve hemostasis and avoid inappropriate thrombosis in the perioperative environment can be challenging. To add to this challenge, traditional laboratory tests of coagulation are difficult to interpret in patients with end-stage liver disease. Viscoelastic coagulation tests such as thromboelastography (Haemonetics Corporation, Braintree, MA) and rotational thromboelastometry (TEM International, Munich, Germany) have helped to reduce transfusion of allogeneic blood products, especially fresh frozen plasma, but have also lead to the increased use of fibrinogen-containing products. In general, advancements in surgical techniques and anesthetic management have led to significant reduction in blood transfusion requirements during liver transplantation. Targeted transfusion protocols and pharmacologic prevention of fibrinolysis may further aid in the management of the complex coagulopathy of end-stage liver disease.
“Let’s step outside to settle this.” While this pugilistic phrase is most commonly seen in Hollywood movies, it is rarely heard in the professional confines of an operating room. However, just a decade ago, one of us found themselves uttering it during a dialogue with a new orthopedic surgeon recommending the use of tranexamic acid for an elective hip replacement. This was a medication the anesthesiologist knew well from their liver transplant patient population but had never administered for a joint replacement. It seemed inappropriate to have this discussion in front of an awake patient. While only 4% of patients undergoing elective lower extremity joint replacement in 2011 received tranexamic acid,1 nearly three quarters were receiving it in 2016,2 and it is now recommended routine practice in consensus guidelines.3In this issue of Anesthesiology, Poeran et al.2 advance our knowledge in a critically understudied area: tranexamic acid administration in “high-risk” lower extremity arthroplasty patients. These data demonstrate three important concepts for the readers of this journal: (1) lower extremity arthroplasty patients with a history of myocardial infarction, atrial fibrillation, or renal disease that receive tranexamic acid had a lower rate of transfusion without a measurable difference in adverse events than patients who did not receive the medication; (2) robust analyses of rigorously collected and validated observational data can advance daily practice beyond clinician bias and preference when we lack randomized controlled trial data; and (3) anesthesiologists must become facile at assessing the quality of a variety of study data, methods, interpretations, and conclusions.Tranexamic acid has been identified by the World Health Organization as an essential medicine given its ability to treat life-threatening hemorrhage in trauma, traumatic brain injury, and obstetrics.4–6 The agent was developed and reported in 1962 by Utako Okamoto and has found renewed interest across a range of surgeries. Early literature using national administrative data from hundreds of hospitals evaluated the association of transfusion and tranexamic acid administration in lower extremity arthroplasty.1 However, very few high-risk patients with a history of coronary artery disease, congestive heart failure, or neurologic disorders received tranexamic acid due to concerns of adverse events. As a result, while the overall population did not demonstrate a risk of adverse events associated with tranexamic acid administration, the issue of high-risk patients and their risk/benefit balance remained unanswered because this group has been systematically understudied.In the current work, Poeran et al.2 extend their previous analyses and evaluate the risk/benefit of tranexamic acid administration in three distinct high-risk patient groups receiving tranexamic acid compared to similar high-risk patients not receiving the drug: (1) more than 12,000 patients with a history of myocardial infarction; (2) more than 22,000 patients with a history of renal disease; and (3) more than 22,000 patients with a history of atrial fibrillation. In each of these groups, there was a nearly 70% adjusted relative reduction in transfusion from a baseline of more than 15 to 23% to 5 to 9%. In addition, there was no measurable increase in venous thromboembolism, myocardial infarction, ischemic stroke, or transient ischemic attack. These data suggest that previous concerns about administration of tranexamic acid in these high-risk populations may be overstated. Administration of tranexamic acid was associated with a lower rate of erythrocyte transfusions, which have their own risks and costs. However, no single study is definitive. In contrast to the large number of patients with myocardial infarction, renal disease, or atrial fibrillation, relatively few patients with other comorbidities in this data set received tranexamic acid and were available for study (only 178 patients with a history of deep venous thrombosis, 52 patients with pulmonary embolism, 83 patients with ischemic stroke, and 614 patients with seizures). These high-risk patients remain an importantly understudied population with no reliable evidence to guide practice. We must continue to cautiously observe and reevaluate the use of tranexamic acid in these patients; the current data cannot be used to establish safety in these populations. Ideally, high-quality prospective randomized controlled trials of tranexamic acid in these populations will be performed. Perioperative clinicians must ensure we do not repeat the mistakes of the aprotinin era, plagued by the absence of high-quality unbiased evidence and a lack of data transparency.7 However, combined with a recently published meta-analysis of tranexamic acid randomized controlled trials in many different surgical groups,8 the data presented by Poeran et al.2 do provide a degree of reassurance that current patterns of use of tranexamic acid in specific high-risk lower extremity arthroplasty patients are not associated with harm.When left with individual clinician biases due to the absence of randomized controlled trial data, prospective registries and administrative data can be used to advance the perioperative medicine evidence base if collected and analyzed with transparent declarations of their limitations. Many essential perioperative clinical trials evaluating choice of fluid resuscitation, fluid balance, anesthetic adjuncts, and anesthesia technique inform daily care.9–12 However, many questions remain unanswered. In joint arthroplasty, observational data can inform the role of tranexamic acid, the risk of concurrent bilateral knee replacements, the benefits of home discharge, and identify specific implants at high risk of failure. One such collaborative quality initiative and data registry is the Michigan Arthroplasty Registry Collaborative Quality Initiative. The registry has abstracted standardized and validated patient comorbidities, operative information, implant data, and outcomes since 2012 for nearly 50,000 lower extremity joint replacements a year. Rigorously validated, highly scrutinized data overcome some of the limitations and concerns of retrospective cohort studies.We must use the full breadth of reliable, reproducible, and peer-reviewed data to advance care. In many situations, we must be ready to shed our biases or historical practices when new evidence is presented. Through collaborative efforts across surgery and anesthesiology, we can collect data, evaluate practice, and disseminate information.3 Robust trials and subsequent meta-analyses of such studies remain the pinnacle of trusted evidence. However, in the absence of such evidence, the anesthesiologist is left weighing retrospective cohort studies against expert opinions and their own biases; these opinions and biases are less reliable than well-conducted retrospective cohort studies, which use rigorously collected and validated data. The work by Poeran et al.2 in this issue highlight one such situation. The reality is that we cannot be mesmerized by any one article. We must demand reproducible science, regardless of the underlying methods. As scientists trained in the field of anesthesiology, we must adhere to words often ascribed to Keynes: “When the facts change, I change my mind. What do you do?”Dr. Hallstrom and Dr. Kheterpal’s institution receives salary support funding from Blue Cross Blue Shield of Michigan/Blue Care Network (Detroit, Michigan) as part of the Blue Cross Blue Shield of Michigan/Blue Care Network Value Partnerships program to lead the Michigan Arthroplasty Registry Collaborative Quality Initiative and the Anesthesiology Performance Improvement and Reporting Exchange (the quality improvement arm of the Multicenter Perioperative Outcomes Group), respectively. Although Blue Cross Blue Shield of Michigan/Blue Care Network and the authors work collaboratively, the opinions, beliefs, and viewpoints expressed by the authors do not necessarily reflect the opinions, beliefs, and viewpoints of Blue Cross Blue Shield of Michigan/Blue Care Network or any of its employees. Dr. Colquhoun discloses research support paid to the University of Michigan from Merck & Co. (Kenilworth, New Jersey) unrelated to the presented work.
Introduction Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. Methods and analysis This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. Ethics and dissemination This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. Trial registration number NCT05346588 .
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