Perioperative Organ Injury Research Articles

Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery

Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury. To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery. This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center. Adult patients (>18 years) presenting for elective open cardiac surgery without preoperative oxygen requirement, acute coronary syndrome, carotid stenosis, or dialysis were included. Of 3919 patients assessed, 2501 were considered eligible and 213 provided consent. Of these, 12 were excluded prior to randomization and 1 following randomization whose surgery was cancelled, leaving 100 participants in each group. Participants were randomly assigned to hyperoxia (1.00 fraction of inspired oxygen [FiO2]) or normoxia (minimum FiO2 to maintain oxygen saturation 95%-97%) throughout surgery. Participants were assessed for oxidative stress by measuring F2-isoprostanes and isofurans, for acute kidney injury (AKI), and for delirium, myocardial injury, atrial fibrillation, and additional secondary outcomes. Participants were monitored for 1 year following surgery. Two hundred participants were studied (median [IQR] age, 66 [59-72] years; 140 male and 60 female; 82 [41.0%] with diabetes). F2-isoprostanes and isofurans (primary mechanistic end point) increased on average throughout surgery, from a median (IQR) of 73.3 (53.1-101.1) pg/mL at baseline to a peak of 85.5 (64.0-109.8) pg/mL at admission to the intensive care unit and were 9.2 pg/mL (95% CI, 1.0-17.4; P = .03) higher during surgery in patients assigned to hyperoxia. Median (IQR) change in serum creatinine (primary clinical end point) from baseline to postoperative day 2 was 0.01 mg/dL (-0.12 to 0.19) in participants assigned hyperoxia and -0.01 mg/dL (-0.16 to 0.19) in those assigned normoxia (median difference, 0.03; 95% CI, -0.04 to 0.10; P = .45). AKI occurred in 21 participants (21%) in each group. Intraoperative oxygen treatment did not affect additional acute organ injuries, safety events, or kidney, neuropsychological, and functional outcomes at 1 year. Among adults receiving cardiac surgery, intraoperative hyperoxia increased intraoperative oxidative stress compared to normoxia but did not affect kidney injury or additional measurements of organ injury including delirium, myocardial injury, and atrial fibrillation. ClinicalTrials.gov Identifier: NCT02361944.

Chronic obstructive pulmonary disease affects outcome in surgical patients with perioperative organ injury: a retrospective cohort study in Germany

BackgroundThe impact of chronic obstructive pulmonary disease (COPD) on outcome in perioperative organ injury (POI) has not yet been investigated sufficiently.MethodsThis retrospective cohort study analysed data of surgical patients with POI, namely delirium, stroke, acute myocardial infarction, acute respiratory distress syndrome, acute liver injury (ALI), or acute kidney injury (AKI), in Germany between 2015 and 2019. We compared in-hospital mortality, hospital length of stay (HLOS) and perioperative ventilation time (VT) in patients with and without COPD.ResultsWe analysed the data of 1,642,377 surgical cases with POI of which 10.8% suffered from COPD. In-hospital mortality was higher (20.6% vs. 15.8%, p < 0.001) and HLOS (21 days (IQR, 12–34) vs. 16 days (IQR, 10–28), p < 0.001) and VT (199 h (IQR, 43–547) vs. 125 h (IQR, 32–379), p < 0.001) were longer in COPD patients. Within the POI examined, AKI was the most common POI (57.8%), whereas ALI was associated with the highest mortality (54.2%). Regression analysis revealed that COPD was associated with a slightly higher risk of in-hospital mortality (OR, 1.19; 95% CI:1.18–1.21) in patients with any POI.ConclusionsCOPD in patients with POI is associated with higher mortality, longer HLOS and longer VT. Especially patients suffering from ALI are susceptible to the detrimental effects of COPD on adverse outcome.

The applications and challenges of combined monitoring of macro/micro-circulation and mitochondrial homeostasis in early warning of perioperative organ injury

Perioperative organ injury is a leading risk factor for mortality in surgical patients. Given the current limitations in the timeliness and accuracy of markers for perioperative organ injury, this article proposes a comprehensive early-warning assessment system that jointly monitors the macro-circulation, micro-circulation, and mitochondrial homeostasis. Macro-circulation monitoring allows for real-time evaluation of key indicators such as blood pressure and cardiac output, while micro-circulation monitoring aids in assessing the status of microvascular perfusion. Monitoring of mitochondrial homeostasis provides timely insights into cellular energy metabolism. These three facets are interconnected and collectively determine the balance between tissue oxygenation and energy supply and demand. This article will elucidate commonly used monitoring methods and clinically valuable assessment models within this system, offering theoretical and technical guidance to deepen our understanding of the pathological processes of perioperative organ injury, enhance surgical safety and success rates, and improve patient prognosis and quality of life.

Nitric Oxide in Cardiac Surgery: A Review Article.

Perioperative organ injury remains a medical, social and economic problem in cardiac surgery. Patients with postoperative organ dysfunction have increases in morbidity, length of stay, long-term mortality, treatment costs and rehabilitation time. Currently, there are no pharmaceutical technologies or non-pharmacological interventions that can mitigate the continuum of multiple organ dysfunction and improve the outcomes of cardiac surgery. It is essential to identify agents that trigger or mediate an organ-protective phenotype during cardiac surgery. The authors highlight nitric oxide (NO) ability to act as an agent for perioperative protection of organs and tissues, especially in the heart-kidney axis. NO has been delivered in clinical practice at an acceptable cost, and the side effects of its use are known, predictable, reversible and relatively rare. This review presents basic data, physiological research and literature on the clinical application of NO in cardiac surgery. Results support the use of NO as a safe and promising approach in perioperative patient management. Further clinical research is required to define the role of NO as an adjunct therapy that can improve outcomes in cardiac surgery. Clinicians also have to identify cohorts of responders for perioperative NO therapy and the optimal modes for this technology.

Perioperative acute kidney injury: Current knowledge and the role of anaesthesiologists

Background Among the different types of perioperative organ injury, acute kidney injury (AKI) occurs frequently and is consistently associated with increased rates of mortality and mortality. Despite development of many clinical trials to assess perioperative interventions, reliable means to prevent or reverse AKI are still lacking. Objectives This narrative review discusses recent literature on modifiable risk factors, current approaches to prevention and potential directions for future research. Methods A Pubmed search with the relevant keywords was done for articles published in the last 10 years. Results New insights into preoperative identification and optimisation, intraoperative strategies, including the choice of anaesthetic, haemodynamic and fluid management, have been made, with the aim of preventing perioperative AKI. Conclusion A patient-centric multidisciplinary approach is essential to protect kidney function of patients going for surgery. Much can be done by anaesthesiologists perioperatively, to reduce the risk of development of AKI, especially in susceptible patients. There is a need for further multicentred trials to enhance the currently generic perioperative recommendations.

Impact of cesarean versus vaginal delivery on the risk of postpartum acute kidney injury: A retrospective database controlled study in 116,876 parturients

Study objectiveThe rate of cesarean delivery is increasing globally but the risk of perioperative organ injury associated with cesarean delivery is not well defined. The objective of this study was to determine the risk of postpartum acute kidney injury, a peripartum complication defined by an acute decrease in kidney function, associated with cesarean delivery compared to vaginal delivery. SettingPopulation-based discharge database. PatientsThe Optum Clinformatics® Data Mart was queried for parturients that underwent cesarean or vaginal delivery between January 2016 to January 2018. Using a propensity score model based on 27 antepartum characteristics, we generated a final matched cohort of 116,876 parturients. Intervention/ExposureCesarean delivery as the mode of delivery. MeasurementsThe risk of acute kidney injury associated with each delivery mode and the effect of acute kidney injury on the length of hospital stay for parturients. Main resultsThe matched cohort consisted of 116,876 deliveries, with 58,438 cases in each group. In the cesarean delivery group, the incidence of postpartum acute kidney injury was 24.5 vs. 7.9 per 10,000 deliveries in the vaginal delivery group (adjusted odds ratio = 3; 95% CI, 2.13–4.22; P < .001). The median of the length of hospital stay [interquartile range] was longer by 50% in parturients who developed postpartum acute kidney injury after vaginal delivery (3 [2–4] days vs. those who did not, 2 [2, 3] days; P < .001) and by 67% after cesarean delivery (5 [4–7] days vs. 3 [3, 4] days; P < .001). ConclusionsCesarean delivery is associated with a significantly increased risk of postpartum acute kidney injury as compared to vaginal delivery. The development of postpartum acute kidney injury is associated with prolonged length of hospital stay.

Treatment threshold for intra-operative hypotension in clinical practice-a prospective cohort study in older patients in the UK.

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure <65 mmHg; systolic blood pressure reduction >20%; systolic blood pressure <100 mmHg). Secondary outcomes included the treatment blood pressure threshold for vasopressors; incidence of acute kidney injury; myocardial injury; stroke; and in-hospital mortality. Additionally, anaesthetists providing care for included patients were asked to complete a survey assessing their intended treatment thresholds for hypotension. Data were collected from 4750 patients. Hypotension affected 61.0% of patients when defined as mean arterial pressure <65 mmHg, 91.3% of patients had >20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension.

Outcome of Organ Dysfunction in the Perioperative Period.

While intraoperative mortality has diminished greatly over the last several decades, the risk of death within 30 days of surgery remains stubbornly high and is ultimately related to perioperative organ failure. Perioperative strokes, while rare (<2% in noncardiac surgery), are associated with a more than 10-fold increase in mortality. Rapid identification and treatment are key to maximizing long-term outcomes. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are separate but related perioperative neurological disorders, both of which are associated with poor long-term outcomes. To date, there are few known interventions that can ameliorate the risk of perioperative central nervous system dysfunction. Major adverse cardiac events (MACE) are a major contributor to adverse clinical outcomes following surgical procedures. Recently, advances in diagnostic strategies (eg, high-sensitivity cardiac troponin [hs-cTn] assays) have improved our understanding of MACE. Recently, the dabigatran in patients with myocardial injury after noncardiac surgery (MINS; Management of myocardial injury After NoncArdiac surGEry) trial demonstrated that a direct thrombin inhibitor could improve outcomes following MINS. While the risk of acute respiratory distress syndrome (ARDS) after surgery is approximately 0.2%, other less severe complications (eg, pneumonia, reintubation) are closer to 2%. While intensive care unit (ICU) concepts related to ARDS have migrated into the operating room, whether or not adverse pulmonary outcomes impact long-term outcomes in surgical patients remains a matter of debate. The standardization of acute kidney injury (AKI) definition has improved the ability of clinicians to measure and study the incidence of this important source of perioperative morbidity. AKI is associated with increased mortality as well as nonrenal morbidity (eg, myocardial infarction) after major surgery. Gastrointestinal complications after surgery range from ileus (common in abdominal procedures and associated with an increased length of stay) to less common complications such as mesenteric ischemia and gastrointestinal bleeding, both of which are associated with very high mortality. Outside of cardiothoracic surgery, the incidence of perioperative hepatic injury is not well described but, in this population, is associated with worsened long-term outcomes. Hyperglycemia is a common perioperative complication and occurs in patients undergoing both cardiac and noncardiac surgery. Both hyper- and hypoglycemia are associated with worsened long-term outcomes in cardiac and noncardiac surgery. Better diagnosis and increased understanding of perioperative organ injury has led to an increased appreciation for the specific role that particular organ systems play in poor long-term outcomes and has set the stage for targeted therapeutic interventions.

Cocaine-Positive Patients Undergoing Elective Surgery: From Avoiding Case Cancellations to Treating Substance Use Disorders.

Cocaine-Positive Patients Undergoing Elective Surgery: From Avoiding Case Cancellations to Treating Substance Use Disorders.

Disease Mechanisms of Perioperative Organ Injury.

Despite substantial advances in anesthesia safety within the past decades, perioperative mortality remains a prevalent problem and can be considered among the top causes of death worldwide. Acute organ failure is a major risk factor of morbidity and mortality in surgical patients and develops primarily as a consequence of a dysregulated inflammatory response and insufficient tissue perfusion. Neurological dysfunction, myocardial ischemia, acute kidney injury, respiratory failure, intestinal dysfunction, and hepatic impairment are among the most serious complications impacting patient outcome and recovery. Pre-, intra-, and postoperative arrangements, such as enhanced recovery after surgery programs, can contribute to lowering the occurrence of organ dysfunction, and mortality rates have improved with the advent of specialized intensive care units and advances in procedures relating to extracorporeal organ support. However, no specific pharmacological therapies have proven effective in the prevention or reversal of perioperative organ injury. Therefore, understanding the underlying mechanisms of organ dysfunction is essential to identify novel treatment strategies to improve perioperative care and outcomes for surgical patients. This review focuses on recent knowledge of pathophysiological and molecular pathways leading to perioperative organ injury. Additionally, we highlight potential therapeutic targets relevant to the network of events that occur in clinical settings with organ failure.

Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury.

Cancer and organ injury-such as that occurring in the perioperative period, including acute lung injury, myocardial infarction, and acute gut injury-are among the leading causes of death in the United States and impose a significant impact on quality of life. MicroRNAs (miRNAs) have been studied extensively during the last two decades for their role as regulators of gene expression, their translational application as diagnostic markers, and their potential as therapeutic targets for disease treatment. Despite promising preclinical outcomes implicating miRNA targets in disease treatment, only a few miRNAs have reached clinical trials. This likely relates to difficulties in the delivery of miRNA drugs to their targets to achieve efficient inhibition or overexpression. Therefore, understanding how to efficiently deliver miRNAs into diseased tissues and specific cell types in patients is critical. This review summarizes current knowledge on various approaches to deliver therapeutic miRNAs or miRNA inhibitors and highlights current progress in miRNA-based disease therapy that has reached clinical trials. Based on ongoing advances in miRNA delivery, we believe that additional therapeutic approaches to modulate miRNA function will soon enter routine medical treatment of human disease, particularly for cancer or perioperative organ injury. SIGNIFICANCE STATEMENT: MicroRNAs have been studied extensively during the last two decades in cancer and organ injury, including acute lung injury, myocardial infarction, and acute gut injury, for their regulation of gene expression, application as diagnostic markers, and therapeutic potentials. In this review, we specifically emphasize the pros and cons of different delivery approaches to modulate microRNAs, as well as the most recent exciting progress in the field of therapeutic targeting of microRNAs for disease treatment in patients.

Perioperative Acute Kidney Injury.

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various pharmacologic or nonpharmacologic interventions, reliable means to prevent or reverse acute kidney injury are still lacking. Nevertheless, several recent randomized multicenter trials provide new insights into renal replacement strategies, composition of intravenous fluid replacement, goal-directed fluid therapy, or remote ischemic preconditioning in their impact on perioperative acute kidney injury. This review provides an update on the latest progress toward the understanding of disease mechanism, diagnosis, and managing perioperative acute kidney injury, as well as highlights areas of ongoing research efforts for preventing and treating acute kidney injury in surgical patients.

Impact of Anesthetics on Human Neutrophil Function.

Anesthetics are widely used drugs administered in a multitude of clinical settings. Their impacts on various functions of the immune system have been studied but are still not fully understood. Neutrophil granulocytes are a critical first-line host defense mechanism against infections and contribute to the inflammatory phase of wound healing, but dysregulated neutrophil activation can also precipitate perioperative organ injury. A better understanding of the interactions between common anesthetics and neutrophils may reveal considerations toward optimizing treatment of our most vulnerable patients in the intensive care unit and in the perioperative setting.

AUTHOR REPLY

If it were tracked by the CDC, mortality after non-cardiac surgery would rank among the top 4 causes of mortality in the United States. 1 Bartels K Karhausen J Clambey ET Grenz A Eltzschig HK Perioperative organ injury. Anesthesiology. 2013; 119: 1474-1489 Crossref PubMed Google Scholar The aim of our study was to assess the association between postoperative troponin levels, and both short- and intermediate- term mortality in urologic patients undergoing major operations. This baseline information was needed as background information for a quality project to assess the role of routine troponin screening in our department. As such, there are a few inherent biases that were pointed out in this excellent editorial highlighting the role that troponins may play as a biomarker to predict mortality in our surgical patients.

Targeting Hypoxia Signaling for Perioperative Organ Injury.

Perioperative organ injury has a significant impact on surgical outcomes and presents a leading cause of death in the United States. Recent research has pointed out an important role of hypoxia signaling in the protection from organ injury, including for example myocardial infarction, acute respiratory distress syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target genes, which facilitates adaptive responses to low oxygen. In this review, we focus on current therapeutic strategies targeting hypoxia signaling in various organ injury models and emphasize potential clinical approaches to integrate these findings into the care of surgical patients. Conceptually, there are 2 options to target the HIF pathway for organ protection. First, drugs became recently available that promote the stabilization of HIFs, most prominently via inhibition of prolyl hydroxylase. These compounds are currently trialed in patients, for example, for anemia treatment or prevention of ischemia and reperfusion injury. Second, HIF target genes (such as adenosine receptors) could be activated directly. We hope that some of these approaches may lead to novel pharmacologic strategies to prevent or treat organ injury in surgical patients.

Adrenomedullin Is Associated With Surgical Trauma and Impaired Renal Function in Vascular Surgery Patients.

Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury. The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis. One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs. Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not directly correlate with adverse cardiac events. Consistently low levels of MR-proADM may identify a subgroup of patients with acceptable low risk to guide discharge from high-density care units.

Xenon anaesthesia for patients undergoing off-pump coronary artery bypass graft surgery: a prospective randomized controlled pilot trial

Off-pump coronary artery bypass (OPCAB) surgery carries a high risk for haemodynamic instability and perioperative organ injury. Favourable haemodynamic effects and organ-protective properties could render xenon an attractive anaesthetic for OPCAB surgery. The primary aim of this study was to assess whether xenon anaesthesia for OPCAB surgery is non-inferior to sevoflurane anaesthesia with regard to intraoperative vasopressor requirements. Forty-two patients undergoing elective OPCAB surgery were enrolled in this prospective, single-blind, randomized controlled pilot trial. Patients were randomized to either xenon (50-60 vol%) or sevoflurane (1.1-1.4 vol%) anaesthesia. Primary outcome was intraoperative noradrenaline requirements necessary to achieve predefined haemodynamic goals. Secondary outcomes included safety variables such as the occurrence of adverse events (intraoperatively and during a 6-month follow-up after surgery) and the perioperative cardiorespiratory and inflammatory profile. Baseline and intraoperative data did not differ between groups. Xenon was non-inferior to sevoflurane, as xenon patients required significantly less noradrenaline intraoperatively to achieve the predefined haemodynamic goals {geometric mean 428 [95% confidence interval (CI) 312, 588] vs 1702 [1267, 2285] µg, P<0.0001}. No differences were found for safety. Significantly more sevoflurane patients developed postoperative delirium (POD) (hazard ratio 4.2, P=0.044). The average arterial pressure was lower in the sevoflurane group {median75 [interquartile range (IQR) 6] vs 72 [4] mmHg, P=0.002}. No differences were found for other haemodynamic parameters, the respiratory profile and the perioperative release of inflammatory cytokines, troponin T, serum protein S-100β and erythropoietin. Compared with sevoflurane, xenon anaesthesia allows a significant reduction in vasopressor administration in OPCAB surgery. Moreover, xenon anaesthesia was associated with a lower risk for POD, a finding that has to be confirmed in larger studies. ClinicalTrials.gov (NCT01757106) and EudraCT (2012-002316-12).

Next generation of cardiovascular studies: transcriptional responses of the human myocardium during cardiac surgery.

Next generation of cardiovascular studies: transcriptional responses of the human myocardium during cardiac surgery.

Perioperative Organ Injury

Despite the fact that a surgical procedure may have been performed for the appropriate indication and in a technically perfect manner, patients are threatened by perioperative organ injury. For example, stroke, myocardial infarction, acute respiratory distress syndrome, acute kidney injury, or acute gut injury are among the most common causes for morbidity and mortality in surgical patients. In the current review, the authors discuss the pathogenesis of perioperative organ injury, and provide select examples for novel treatment concepts that have emerged over the past decade. Indeed, the authors are of the opinion that research to provide mechanistic insight into acute organ injury and identification of novel therapeutic approaches for the prevention or treatment of perioperative organ injury represent the most important opportunity to improve outcomes of anesthesia and surgery.

Targeting Purinergic Signaling for Perioperative Organ Protection

Targeting Purinergic Signaling for Perioperative Organ Protection