Perioperative Acute Renal Injury: Revisiting Pathophysiology.

BACKGROUND: Acute renal dysfunction and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is upregulated early (within 1 to 3 h) after murine renal injury and in pediatric acute renal dysfunction after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing acute renal dysfunction after cardiac surgery compared with patients without acute renal dysfunction. METHODS: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. Acute renal dysfunction was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. RESULTS: Sixteen of 81 patients (20%) developed postoperative acute renal dysfunction, and the mean urinary NGAL concentrations in patients who developed acute renal dysfunction were significantly higher early after surgery (after 1 h, mean ± SD, 4,195 ± 6,520 vs. 1,068 ± 2,129 ng/ml; P < 0.01) compared with patients who did not develop acute renal dysfunction. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with acute renal dysfunction. In contrast, urinary NGAL in patients without acute renal dysfunction decreased rapidly after cardiac surgery. CONCLUSIONS: Patients developing postoperative acute renal dysfunction had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of acute renal dysfunction after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.

Determinants of Professional Fulfillment and Burnout Among Intensivists: A National Survey by the Society of Critical Care Anesthesiologists in 2022.

BACKGROUND: Increased burnout and decreased professional fulfillment among intensive care physicians is partly due to intensive care unit (ICU) workload. Although the SARS-CoV-2 (COVID-19) pandemic increased ICU workload, it also may have increased feelings of personal fulfillment due to positive public perceptions of physicians caring for COVID patients. We surveyed critical care anesthesiologists to identify the effect of provider demographics, ICU workload, and COVID-19-related workload, on professional fulfillment and burnout. METHODS: We performed an exploratory survey of 606 members of the Society of Critical Care Anesthesiologists (SOCCA) in January and February 2022. We used the Stanford Professional Fulfillment Index (PFI) to grade levels of professional fulfillment and markers of burnout (ie, work exhaustion and disengagement). Univariable and multivariable models were used to identify associations between provider demographics and practice characteristics and professional fulfillment and work exhaustion. RESULTS: One hundred and seventy-five intensivists (29%) responded. A total of 65% were male and 49% were between 36 and 45 years old. The overall median PFI score-0 (none) to 24 (most professional fulfillment)-was 17 (IQR, 1-24), with a wide distribution of responses. In multivariable analysis, factors associated with higher professional fulfillment included age >45 years ( P =.004), ≤15 weeks full-time ICU coverage in 2020 ( P =.02), role as medical director ( P =.01), and nighttime home call with supervision of in-house ICU fellows ( P =.01). CONCLUSIONS: Professional fulfillment and work exhaustion in this cross-sectional survey were associated with several demographic and practice characteristics but not COVID-19-related workload, suggesting that COVID-19 workload may not have either positive or negative perceptions on professional fulfillment.

The Impact of Glucagon-Like Peptide-1 Agonists on Hip and Knee Arthroplasty and Perioperative Considerations.

Glucagon-Like Peptide agonists have traditionally been used for glycemic control in diabetic patients. However, there has been a dramatic rise in their utilization for weight loss management. As such, arthroplasty surgeons will encounter an increasing number of patients on these medications, and therefore it is important to understand the implications of their use in the perioperative period. This review will describe the pharmacological actions of these medications as well as the impact on hip and knee arthroplasty patients, and considerations for perioperative management. Because of the rapid adaption and utilization of these drugs, the science is evolving at a fast pace. More and longer-term studies are needed to truly understand the impact of these medications on total joint arthroplasty utilization and in management of these patients in the perioperative period.

Postdischarge Functional Capacity, Health-Related Quality of Life, Depression, Anxiety, and Post-traumatic Stress Disorder in Patients Receiving a Long-term Left Ventricular Assist Device.

BACKGROUND: There is a paucity of data on depression, anxiety and post-traumatic stress disorder after left ventricular assist device (LVAD) implantation. We designed an observational study to integrate these with functional capacity and health-related quality of life (HR-QOL) in surviving LVAD patients. METHODS AND RESULTS: Consenting patients between 1 month and 9 years after LVAD implantation (n = 121) were screened for functional capacity (World Health Organization Disability Assessment Schedule 2.0 [WHODAS 2.0)]); HR-QOL (European Quality of Life [EQ-5D] and Visual Assessment Scales [EQ-VAS]), depression (Patient Health Questionnaire [PHQ-9], anxiety (Generalized Anxiety Disorder Scale [GAD-7]) and post-traumatic stress disorder (Impact of Event Scale Revised [IES-R]). Of the 94% of patients who consented, 34.7% reported impaired functional capacity (WHODAS 2.0 score of ≥25%), 23.1%-34.7% HR-QOL problems (domain EQ-5D of ≥3), 10.7% "poor health" (EQ-VAS of ≤40), 14.9% depression (PHQ-9 of >14), 11.7% suicidal ideation and 17.5% anxiety (GAD-7 of >10). Among these patients, 23.5% had a positive screen for post-traumatic stress disorder (IES-R of ≥24). An EQ-VAS of 80 or greater predicted good functional capacity (P < .001). CONCLUSIONS: One-third of discharged LVAD patients reported impaired function, HR-QOL, and psychological issues. A standardized evaluation before and after LVAD implantation could facilitate psychologic prehabilitation, inform decision-making, and identify indications for mental health intervention.

Frailty in the End-Stage Lung Disease or Heart Failure Patient: Implications for the Perioperative Transplant Clinician.

The syndrome of frailty for patients undergoing heart or lung transplantation has been a recent focus for perioperative clinicians because of its association with postoperative complications and poor outcomes. Patients with end-stage cardiac or pulmonary failure may be under consideration for heart or lung transplantation along with bridging therapies such as ventricular assist device implantation or venovenous extracorporeal membrane oxygenation, respectively. Early identification of frail patients in an attempt to modify the risk of postoperative morbidity and mortality has become an important area of study over the last decade. Many quantification tools and risk prediction models for frailty have been developed but have not been evaluated extensively or standardized in the cardiothoracic transplant candidate population. Heightened awareness of frailty, coupled with a better understanding of distinct cellular mechanisms and biomarkers apart from end-stage organ disease, may play an important role in potentially reversing frailty related to organ failure. Furthermore, the clinical management of these critically ill patients may be enhanced by waitlist and postoperative physical rehabilitation and nutritional optimization.

New Innovations in Circulatory Support With Ventricular Assist Device and Extracorporeal Membrane Oxygenation Therapy.

The past decade has seen an exponential increase in the application and development of durable long-term as well as nondurable short-term mechanical circulatory support for cardiogenic shock and acute or chronic heart failure. Support has evolved from bridge-to-transplant to destination therapy, bridge to rescue, bridge to decision making, and bridge to a bridge. Notable trends include device miniaturization, minimally invasive and/or percutaneous insertion, and efforts to superimpose pulsatility on continuous flow. We can certainly anticipate that innovation will accelerate in the months and years to come. However, despite-or perhaps because of-the enhanced equipment now available, mechanical circulatory support is an expensive, complex, resource-intensive modality. It requires considerable expertise that should preferably be centralized to highly specialized centers. Formidable challenges remain: systemic inflammatory response syndromes and vasoplegia after device insertion; postoperative sepsis; optimal anticoagulation regimens to prevent device-induced thrombosis and cerebral thromboembolism; wound site, intracranial, and gastrointestinal bleeding; multisystem injury and failure; patient dissatisfaction (even when providers consider the procedure a "success"); and ethical decision making in conditions of futility.

Acute kidney injury in cardiac surgery.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a long-recognized complication of cardiac surgery. It is a commonly encountered clinical syndrome that, in its most severe form, increases the odds of operative mortality three to eight-fold. The pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) is complex. No single intervention is likely to provide a panacea, and thus, the purpose of this review is to assess the wide breadth of emerging research into potential strategies to prevent, diagnose, and treat CSA-AKI. RECENT FINDINGS: Research in the field of CSA-AKI published within the last 18 months adds further layers of knowledge to many previously studied areas. These include its definition (Risk, Injury, Failure, Loss, End-stage kidney disease, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes criteria), diagnosis (biomarkers and intraoperative renal oximetry), prevention (statin therapy, acetylsalicylic acid, N-acetylcysteine, sodium bicarbonate, off-pump coronary revascularization, goal-directed hemodynamic therapy, and minimizing blood transfusion), and treatment (early initiation of renal replacement therapy). SUMMARY: Although there has been much high-quality research conducted in this field in recent years, preventing CSA-AKI by avoiding renal insults remains the mainstay of management. Although biomarkers have the potential to diagnose CSA-AKI at an earlier stage, efficacious interventions to treat established CSA-AKI remain elusive.

Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery.

INTRODUCTION: Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. METHODS: Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients' medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography. RESULTS: Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (α) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751. CONCLUSIONS: Our results indicate that preoperative ROTEM assays that include fibrin clot and platelet interaction may detect patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Future studies need to evaluate the clinical utility and cost effectiveness of preoperative ROTEM and better define the association between ROTEM values and specific hypercoagulable conditions.

Clevidipine compared with nitroglycerin for blood pressure control in coronary artery bypass grafting: a randomized double-blind study.

PURPOSE: We tested the hypothesis that clevidipine, a rapidly acting dihydropyridine calcium channel blocker, is not inferior to nitroglycerin (NTG) in controlling blood pressure before cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG). METHODS: In this double-blind study from October 4, 2003 to April 26, 2004, 100 patients undergoing CABG with CPB were randomized at four centres to receive intravenous infusions of clevidipine (0.2-8 µg·kg(-1)·min(-1)) or NTG (0.4 µg·kg(-1)·min(-1) to a clinician-determined maximum dose rate) from induction of anesthesia through 12 hr postoperatively. The study drug was titrated in the pre-CPB period with the aim of maintaining mean arterial pressure (MAP) within ± 5 mmHg of a clinician-predetermined target. The primary endpoint was the area under the curve (AUC) for the total time each patient's MAP was outside the target range from drug initiation to the start of CPB, normalized per hour (AUCMAP-D). The predefined non-inferiority criterion for the primary endpoint was a 95% confidence interval (CI) upper limit no greater than 1.50 for the geometric means ratio between clevidipine and NTG. RESULTS: Total mean [standard deviation (SD)] dose pre-bypass was 4.5 (4.7) mg for clevidipine and 6.9 (5.4) mg for NTG (P < 0.05). The geometric mean AUCMAP-D for clevidipine was 283 mmHg·min·hr(-1) (n = 45) and for NTG was 292 mmHg·min·hr(-1) (n = 48); the geometric means ratio was 0.97 (95% CI 0.74 to 1.27). The geometric mean AUCMAP-D during aortic cannulation was 357.7 mmHg·min·hr(-1) for clevidipine compared with 190.5 mmHg·min·hr(-1) for NTG. Mean (SD) heart rate with clevidipine was 76.0 (13.8) beats·min(-1) compared with 81.5 (14.4) beats·min(-1) for NTG. There were no clinically important differences between groups in adverse events. CONCLUSION: During CABG, clevidipine was not inferior to NTG for blood pressure control pre-bypass.

Heart and lung transplantation.

PURPOSE OF REVIEW: Every year, thousands of heart and lung transplants are performed worldwide. As experience and clinical acumen advance, both fields are continually evolving. This review elucidates and describes many of the recent changes in practice and future directions of heart and lung transplantation. Preoperative, intraoperative and postoperative developments are presented with supporting evidence in these continually evolving fields. RECENT FINDINGS: The field of heart transplantation is continually adapting to the growing use of mechanical circulatory support devices as bridge to transplant and for postoperative support. Recent modifications in surgical technique have contributed to improved outcomes.Lung transplantation advancements include the increasing use of extracorporeal membrane oxygenation during the perioperative period. Lobar transplantation and ex-vivo lung perfusion techniques may aid in providing successful lung grafts to those with potentially long wait list times.Rates of rejection continue to decline in both fields as immunosuppression regimens are improved and modified. SUMMARY: This review investigates and summarizes the recent changes and advancements in heart and lung transplantation. Mechanical circulatory support and extracorporeal membrane oxygenation are increasingly used in the perioperative setting, and continuing research will evaluate their safety profiles. Optimizing and tailoring immunosuppression regimens for transplant recipients continue to be the subject of ongoing investigation.

Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes.

OBJECTIVES: Consensus definitions represent an important step toward defining the epidemiology of acute kidney injury (AKI). However, the oliguric component of these definitions remains of uncertain impact and utility after cardiac surgery. The authors sought to define the specific impact of oliguric criteria, both alone and in combination with serum creatinine criteria, on the observed incidence of AKI and associated adverse outcomes following adult cardiac surgery. DESIGN: Retrospective observational study over a 1-year period. SETTING: Academic medical institution. PARTICIPANTS: A total of 311 adult patients undergoing elective valve and/or coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: No interventions were performed as part of the study. MEASUREMENTS AND MAIN RESULTS: Hourly urine output and daily serum creatinine were recorded in the 2 days following surgery. AKI was defined by Acute Kidney Injury Network oliguric and serum creatinine criteria. Defined by serum creatinine criteria alone, the incidence of AKI was 17.7% and was associated strongly with in-hospital mortality (odds ratio 6.6, 95% confidence interval 1.4-30.5, p = 0.02) and renal replacement therapy (odds ratio 12.7, 95% confidence interval 2.4-67.3, p = 0.003) as well as time to discharge from the intensive care unit and hospital. Defined by oliguric criteria alone through 48 hours following surgery, the incidence of AKI dramatically increased to 55.6% but was not associated with mortality, renal replacement therapy, or time to discharge. CONCLUSIONS: Acute Kidney Injury Network oliguric criteria applied over 48 hours after surgery dramatically increased the measured incidence of AKI after cardiac surgery, but was not associated with adverse outcomes.

Clinical and economic burden of postoperative pulmonary complications: patient safety summit on definition, risk-reducing interventions, and preventive strategies.

OBJECTIVE: Postoperative pulmonary complications are a major contributor to the overall risk of surgery. We convened a patient safety summit to discuss ways to enhance physician awareness of postoperative pulmonary complications, advance postoperative pulmonary complications as a substantive public health concern demanding national attention, recommend strategies to reduce the deleterious impact of postoperative pulmonary complications on clinical outcomes and healthcare costs, and establish an algorithm that will help identify patients who are at increased risk for postoperative pulmonary complications. DATA SOURCES: We conducted PubMed searches for relevant literature on postoperative pulmonary complications in addition to using the summit participants' experience in the management of patients with postoperative pulmonary complications. DATA SYNTHESIS: Postoperative pulmonary complications are common, are associated with increased morbidity and mortality, and adversely affect financial outcomes in health care. A multifaceted approach is necessary to reduce the incidence of postoperative pulmonary complications. Identifying a measurable marker of risk will facilitate the targeted implementation of risk-reduction strategies. CONCLUSIONS: The most practicable marker that identifies patients at highest risk for postoperative pulmonary complications is the need for postoperative mechanical ventilation of a cumulative duration >48 hrs.

Preventing acute kidney injury after cardiac surgery.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a serious complication that significantly increases morbidity, mortality and cost of care after cardiac surgery. In this review we identify the current literature that addresses strategies for renal protection and the prevention of AKI after cardiac surgery. RECENT FINDINGS: Even with aggressive medical care and renal replacement therapy (RRT) the morbidity, mortality and cost of postoperative AKI after cardiac surgery is substantial. An emphasis on preventive strategies would therefore appear to be the most cost-effective approach. Recent literature offers hope that as our understanding of the pathogenesis of AKI after cardiac surgery continues to improve, new directions for the prevention and amelioration of AKI will emerge. Approaches to the prevention of postoperative AKI include careful risk stratification of patients, allowing adequate recovery following a prior AKI, consideration of less extensive surgical procedures, avoidance of cardiopulmonary bypass, minimizing injury from radiocontrast dyes or other nephrotoxic agents, and optimizing cardiovascular function and oxygen delivery. Early identification of AKI and prompt, judicious application of RRT may also improve outcomes. Interest in pharmacologic renoprotection is currently directed toward statins and sodium bicarbonate. SUMMARY: Postoperative AKI is a serious complication after cardiac surgery. Therapeutic interventions and RRT have limited influence on the outcome of AKI, and a preventive strategy remains the mainstay to attenuate its impact.

Dexmedetomidine in the care of critically ill patients from 2001 to 2007: an observational cohort study.

BACKGROUND: Dexmedetomidine is a novel sedative agent that causes anxiolysis without respiratory depression in critically ill patients. We sought to examine patient and hospital variation in dexmedetomidine use and adoption patterns of dexmedetomidine over time. METHODS: We performed a retrospective cohort study of all patients who received intravenous infusion sedation in 174 intensive care units contributing data to Project IMPACT from 2001 through 2007. Sedation use was defined as having received an intravenous sedative infusion (dexmedetomidine, midazolam, lorazepam, or propofol) for any period during the intensive care stay. The primary outcome was use of dexmedetomidine in the intensive care unit. RESULTS: Of 58,391 patients who received intravenous infusion sedation, 2,535 (4.3%, 95% confidence interval [CI], 4.2-4.5) received dexmedetomidine. Overall use was highest in cardiac surgery patients (11.7%, 10.8-12.7) and was similar in other surgical patients (4.3%, 4.0-4.6) and medical patients (3.4%, 3.2-3.6, P < 0.001). Use of dexmedetomidine increased from 2.0% (1.6-2.4) of patients receiving intravenous infusion sedation in 2001 to 7.2% (6.6-7.9) in 2007 (P < 0.001), primarily because of an increase in use in cardiac surgery patients (1.4%, 0.0-2.8, in 2001 vs. 20.2%, 17.6-22.8 in 2007, P < 0.001). Of the patients who received dexmedetomidine, 31.5% (29.6-33.3) received the infusion for more than 1 day, and 10.9% were not mechanically ventilated. CONCLUSION: Use of dexmedetomidine in critically ill patients has increased over time, primarily as a result of an increase in use among cardiac surgery patients. A substantial portion of dexmedetomidine was administered outside of the regulatory approval guidelines at the time.

Treatment of acute postoperative hypertension in cardiac surgery patients: an efficacy study of clevidipine assessing its postoperative antihypertensive effect in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Acute postoperative hypertension is a well-known complication of cardiac surgery and is associated with postoperative morbidity. Clevidipine, an ultrashort-acting, third-generation dihydropyridine calcium channel blocker, exerts vascular-selective, arterial-specific vasodilation to decrease arterial blood pressure without negatively impacting cardiac function. In this double-blind, placebo-controlled trial, we examined the efficacy and safety of clevidipine in treating postoperative hypertension in cardiac surgery patients. METHODS: Two hundred six patients undergoing cardiac surgery were randomized preoperatively. Of these, 110 met postrandomization inclusion criteria for the study [systolic blood pressure (SBP) >or=140 mm Hg within 4 h of admission to a postoperative setting, and clinically assessed as needing SBP reduction by >or=15% from baseline]. Patients received an infusion of either clevidipine (0.4-8.0 microg kg(-1) min(-1)) or 20% lipid emulsion (placebo) for 30 min to a maximum of 1 h unless treatment failure occurred sooner. The primary end point was the incidence of treatment failure, defined as the inability to decrease SBP by >or=15% from baseline, or the discontinuation of study treatment for any reason within the 30-min period after study drug initiation. RESULTS: Clevidipine-treated patients had a significantly lower incidence of treatment failure than placebo patients [8.2% (5 of 61) vs 79.6% (39 of 49), P < 0.0001]. Treatment success was achieved in 91.8% of clevidipine-treated patients. Median time to target SBP with clevidipine was 5.3 min (95% confidence interval, 4-7 min). No clinically significant increase in heart rate from baseline was observed. Adverse event rates were similar for both treatment groups. CONCLUSIONS: Clevidipine is effective and safe in the rapid treatment of acute postoperative hypertension after cardiac surgery.