What Are the Real Issues in Providing Extracorporeal Membrane Oxygenation (ECMO) Support: A Survey.

INTRODUCTION: By using a novel survey our study aimed to assess the challenges ECMO and Critical Care (CC) teams face when initiating and managing patient's ECMO support. METHODS: A qualitative survey-based observational study was performed of members of 2 Critical Care Medicine organizations involved in decision-making around the practice of Extracorporeal Membrane Oxygenation (ECMO). The range of exploratory questions covered ethical principles of informed consent, autonomy and goals of care discussions, beneficence, non-maleficence (offering life-sustaining treatments in end-of-life care), and justice (insurance-related limitations of treatment). Questions also covered pragmatic practice and quality improvement areas, such as exploring whether palliative care or ethics teams were involved in such decision-making. RESULTS: 305 members received the survey links, and a total of 61 completed surveys were received, for an overall response rate of 20% among all eligible members. Only 70% of the participants who manage ECMO patients are involved in the ECMO initiation decision process. The majority do not involve Ethics or Palliative care at the initial ECMO initiation decision step. Of the ethical and moral dilemmas reported, the majority revolved around 1. Prognostication of patients receiving VV and VA ECMO support, 2. Lack of knowledge of patient's wishes and goals, 3. Disconnect between expectations of families and outcomes and 4. Staff moral distress around when to stop ECMO in case of futility. CONCLUSION: Our survey highlights areas of distress and dilemma which have been stressed before in the initiation, management, and outcomes of ECMO patients, however with the increasing use of this modality of cardiopulmonary mechanical support being offered, the survey results can offer a guidance using sound ethical principles.

Epidemiology, Resistance Profiles, and Outcomes of Bloodstream Infections in Community-Onset Sepsis in the United States.

OBJECTIVES: To describe frequency of positive blood cultures, patterns of pathogens' characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. DESIGN: Retrospective cohort study. SETTING: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. SUBJECTS: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales /extended-spectrum ß-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85-0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78-0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa , methicillin-sensitive Staphylococcus aureus , and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli , Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. CONCLUSIONS: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

Association Between Gabapentinoids and Postoperative Pulmonary Complications in Patients Undergoing Thoracic Surgery.

OBJECTIVE: Perioperative gabapentinoids in general surgery have been associated with an increased risk of postoperative pulmonary complications (PPCs), while resulting in equivocal pain relief. This study's aim was to examine the utilization of gabapentinoids in thoracic surgery to determine the association of gabapentinoids with PPCs and perioperative opioid utilization. DESIGN: A multicenter retrospective cohort study. SETTING: Hospitals in the Premier Healthcare Database from 2012 to 2018. PARTICIPANTS: A total of 70,336 patients undergoing elective open thoracotomy, video-assisted thoracic surgery, and robotic-assisted thoracic surgery. INTERVENTIONS: Propensity score analyses were used to assess the association between gabapentinoids on day of surgery and the primary composite outcome of PPCs, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, and noninvasive and invasive ventilation. Secondary outcomes included invasive and noninvasive ventilation, hospital mortality, length of stay, opioid consumption on day of surgery, and average daily opioid consumption after day of surgery. RESULTS: Overall, 8,142 (12%) patients received gabapentinoids. The prevalence of gabapentin on day of surgery increased from 3.8% in 2012 to 15.9% in 2018. Use of gabapentinoids on day of surgery was associated with greater odds of PPCs (odds ratio [OR] 1.19, 95% CI 1.11-1.28), noninvasive mechanical ventilation (OR 1.30, 95% CI 1.16-1.45), and invasive mechanical ventilation (OR 1.14, 95% CI 1.02-1.28). Secondary outcomes indicated no clinically meaningful associations of gabapentinoid use with opioid consumption, hospital mortality, or length of stay. CONCLUSIONS: Perioperative gabapentinoid administration in elective thoracic surgery may be associated with a higher risk of PPCs and no opioid-sparing effect.

Echocardiogram Utilization Patterns and Association With Mortality Following Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury (TBI) can result in left ventricular dysfunction, which can lead to hypotension and secondary brain injuries. Although echocardiography is often used to examine cardiovascular function in multiple clinical settings, its use and association with outcomes following severe TBI are not known. To address this gap, we used the National Trauma Data Bank (NTDB) to describe utilization patterns of echocardiography and examine its association with mortality following severe TBI. METHODS: A retrospective cohort study was conducted using a large administrative trauma registry maintained by the NTDB from 2007 to 2014. Patients >18 years with isolated severe TBI, and without concurrent severe polytrauma, were included in the study. We examined echocardiogram utilization patterns (including overall utilization, factors associated with utilization, and variation in utilization) and the association of echocardiography utilization with hospital mortality, using multivariable logistic regression models. RESULTS: Among 47,808 patients, echocardiogram was utilized as part of clinical care in 2548 patients (5.3%). Clinical factors including vascular comorbidities and hemodynamic instability were associated with increased use of echocardiograms. Nearly half (46.0%, 95% confidence interval [CI], 40.3%-51.7%) of the variation in echocardiogram utilization was explained at the individual hospital level, above and beyond patient and injury factors. Exposure to an echocardiogram was associated with decreased odds of in-hospital mortality following severe TBI (adjusted odds ratio [OR] = 0.77; 95% CI, 0.69-0.87; P < .001). CONCLUSIONS: Echocardiogram utilization following severe TBI is relatively low, with wide variation in use at the hospital level. The association with decreased in-hospital mortality suggests that the information derived from echocardiography may be relevant to improving patient outcomes but will require confirmation in further prospective studies.

Associations Between Perioperative Crystalloid Volume and Adverse Outcomes in Five Surgical Populations.

BACKGROUND: Optimal administration of fluids is an important part of enhanced recovery after surgery (ERAS) protocols. We sought to examine the relationship between perioperative crystalloid volume and adverse outcomes in five common types of surgical procedures with ERAS fluid guidelines in place where large randomized controlled trials have not been conducted: breast reconstruction, bariatric, major urologic, gynoncologic, and head and neck oncologic procedures. METHODS: This retrospective cohort study included patients who had undergone any one of the aforementioned procedures within any facility in a large multihospital alliance (Premier, Inc, Charlotte, NC) between 2008 and 2014. We used multivariable generalized additive models to examine relationships between the total crystalloid volume (TCV) on the day of surgery and a composite adverse outcome of prolonged (>75th percentile) hospital or intensive care unit stay or in-hospital mortality. Models were constructed separately within each surgical category and adjusted for demographic, clinical, and hospital characteristics. Informed consent requirements were waived because deidentified data were used. RESULTS: We identified 83,685 patients within 312 US hospitals undergoing breast reconstruction (n = 8738), bariatric surgery (n = 8067), major urologic surgery (n = 28,654), gynoncologic surgery (n = 34,559), and head/neck oncology surgery (n = 3667). There was significant patient-independent variation in TCV. Probabilities of adverse outcomes increased at a TCV below 3 L and above 6 L for all types of surgeries except bariatric surgery, where larger volumes were associated with progressively better outcomes. CONCLUSIONS AND RELEVANCE: Relationships between TCV and adverse outcomes were generally J shaped with higher volumes (>6 L) associated with increased risk. As per current ERAS guidelines, it is important to avoid excessive crystalloid volume in most surgical procedures except for bariatric surgery.

Effects of Acetaminophen, NSAIDs, Gabapentinoids, and Their Combinations on Postoperative Pulmonary Complications After Total Hip or Knee Arthroplasty.

OBJECTIVE: Multimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic combinations are lacking. DESIGN: A retrospective study using the Premier Healthcare Database (2009-2014). SUBJECTS: Adults who underwent elective primary THA or TKA. METHODS: We categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs). RESULTS: Among 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI] = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery. CONCLUSIONS: Gabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.

COVID-Activated Emergency Scaling of Anesthesiology Responsibilities Intensive Care Unit.

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic and the potential need for physicians to provide critical care services, the American Society of Anesthesiologists (ASA) has collaborated with the Society of Critical Care Anesthesiologists (SOCCA), the Society of Critical Care Medicine (SCCM), and the Anesthesia Patient Safety Foundation (APSF) to develop the COVID-Activated Emergency Scaling of Anesthesiology Responsibilities (CAESAR) Intensive Care Unit (ICU) workgroup. CAESAR-ICU is designed and written for the practicing general anesthesiologist and should serve as a primer to enable an anesthesiologist to provide limited bedside critical care services.

Association 'Between Gabapentinoids on the Day of Colorectal Surgery and Adverse Postoperative Respiratory Outcomes.

OBJECTIVE: The aim of this study was to determine the association between gabapentinoids on the day of surgery and adverse postoperative outcomes in patients undergoing colorectal surgery in the United States. BACKGROUND: Gabapentinoids, gabapentin and pregabalin, are recommended in multimodal analgesia protocols for acute postoperative pain management after colorectal surgery. However, current literature focuses on the efficacy in reducing opioid consumption, but provides limited information about adverse risks. METHODS: This was a retrospective study including 175,787 patients undergoing elective colorectal surgery using the Premier database between 2009 and 2014. Multilevel regression models measured associations of receipt of gabapentinoids with naloxone use after surgery, non-invasive ventilation (NIV), invasive ventilation (IMV), hospital length of stay (LOS), and parental morphine equivalents (PMEs) on the day of surgery and on the day before discharge. RESULTS: Overall, 4677 (2.7%) patients received gabapentinoids on the day of surgery, with use doubling (1.7% in 2009 to 4.3% in 2014). Compared with patients who were unexposed to ganapentinoids, gabapentinoid exposure was associated with lower PMEs on the day of surgery [-2.7 mg; 95% confidence interval (CI), -5.2 to -0.0 mg], and with higher odds of NIV [odds ratio (OR) 1.22, 95% CI, 1.00-1.49] and receipt of naloxone (OR 1.58, 95% CI, 1.11-2.26). There was no difference between the groups with respect to IMV or PMEs on the day before discharge. CONCLUSIONS: Although use of gabapentinoids on the day of surgery was associated with slightly lower PMEs on the day of surgery, it was associated with higher odds of NIV and naloxone use after surgery.

Perioperative Anesthetic and Transfusion Management of Veno-Venous Extracorporeal Membrane Oxygenation Patients Undergoing Noncardiac Surgery: A Case Series of 21 Procedures.

OBJECTIVES: To analyze the perioperative management of veno-venous extracorporeal membrane oxygenation (VV ECMO) in patients undergoing major noncardiac surgical procedures, which is poorly described in the literature. In doing so, perioperative challenges related to hemodynamic instability, impaired gas exchange, bleeding, and coagulopathy will be quantified. DESIGN: Retrospective, nonrandomized, observational study. SETTING: A single, university-affiliated, quaternary medical center. PARTICIPANTS: Fourteen patients who underwent 21 noncardiac surgical procedures during the period of January 1, 2014, through April 1, 2016. Approval for this study was obtained from the Duke University Medical Center Institutional Review Board (study Pro00072723). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty percent of subjects were alive at 1 year after ECMO cannulation. Anesthetic type was variable with an inhaled anesthetic utilized in 71.4% of events, a presurgical continuous sedative was continued in 81.0% of cases, fentanyl was utilized in 100% of encounters, and midazolam was utilized in 71.4% of encounters. Intraoperatively, 50% of encounters resulted in an oxygen desaturation with a peripheral oxygen saturation assessed by pulse oximetry (SpO2)<90%, and 15% of procedures resulted in a SpO2 <80%. A vasopressor, most commonly epinephrine, was used during 66.7% of procedures. Intraoperatively, blood was administered in 52.4% of procedures, fresh frozen plasma was administered in 23.8% of procedures, and platelets were administered in 28.6% of procedures. Hemoglobin levels remained stable throughout the perioperative period, averaging 9.5 g/dL preoperatively, 9.7 g/dL immediately postoperatively, and 9.5 g/dL 24 hours after surgery. CONCLUSIONS: VV ECMO patients can be anesthetized using either inhalational or intravenous anesthetics. Patient hemodynamics, oxygenation, and decarboxylation require frequent interventions, but can typically be optimized to meet clinically acceptable thresholds.

Primary graft dysfunction after heart transplantation: Incidence, trends, and associated risk factors.

Changes in heart transplantation (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society for Heart & Lung Transplantation (ISHLT)-defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time-trend analysis was performed over the study period. Three-hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD, or both, were observed in 99 patients (31%). Risk factors independently associated with PGD included ischemic time, recipient African American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence; however, there was an increase in the recipient pretransplantation use of amiodarone. The rate of 30-day mortality was significantly elevated in those with PGD versus those without PGD (6.06% vs 0.92%, P = .01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions.

Perioperative Management of the Adult Patient on Venovenous Extracorporeal Membrane Oxygenation Requiring Noncardiac Surgery.

The use of venovenous extracorporeal membrane oxygenation is increasing worldwide. These patients often require noncardiac surgery. In the perioperative period, preoperative assessment, patient transport, choice of anesthetic type, drug dosing, patient monitoring, and intraoperative and postoperative management of common patient problems will be impacted. Furthermore, common monitoring techniques will have unique limitations. Importantly, patients on venovenous extracorporeal membrane oxygenation remain subject to hypoxemia, hypercarbia, and acidemia in the perioperative setting despite extracorporeal support. Treatments of these conditions often require both manipulation of extracorporeal membrane oxygenation settings and physiologic interventions. Perioperative management of anticoagulation, as well as thresholds to transfuse blood products, remain highly controversial and must take into account the specific procedure, extracorporeal membrane oxygenation circuit function, and patient comorbidities. We will review the physiologic management of the patient requiring surgery while on venovenous extracorporeal membrane oxygenation.

Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa3 inhibition in rats: a proof of concept study.

PURPOSE: Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO2). In addition to StO2, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa3 (Cytox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cytox independent of changes in hemoglobin saturation. METHODS: In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O2 containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg-1 iv was injected in order to produce cytochrome aa3 reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa3 and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions. RESULTS: The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (-0.014 [-0.29 to -0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [-0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.015 [-0.020 to -0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (-0.17 [-0.22 to -0.15] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.04 [-0.06 to -0.03] AU; P < 0.001). CONCLUSION: Broadband NIRS can effectively measure the directionality of changes in both Cytox and StO2 by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia.

Peroxisome proliferator-activated receptor γ co-activator 1-α as a critical co-activator of the murine hepatic oxidative stress response and mitochondrial biogenesis in Staphylococcus aureus sepsis.

A key transcriptional regulator of cell metabolism, the peroxisome proliferator-activated receptor γ co-activator 1-α (PPARGC-1-α or PGC-1α), also regulates mitochondrial biogenesis, but its role in antioxidant gene regulation is not well understood. Here, we asked whether genetic heterozygosity of PGC-1α modulates gene expression for the mitochondrial antioxidant enzyme SOD-2 during hepatic inflammatory stress. Using Staphylococcus aureus peritonitis in mice, we found significant Sod2 gene induction in WT mice, whereas PGC-1α heterozygotes (PGC-1α(+/-)) failed to augment Sod2 mRNA and protein levels. Impaired Sod2 regulation in PGC-1α(+/-) mice was accompanied by oxidative stress shown by elevated mitochondrial GSSG/GSH and protein carbonyls. In silico analysis of the mouse proximal Sod2 promoter region revealed consensus binding sites for the Nfe2l2 (Nrf2) transcription factor. Chromatin immunoprecipitation demonstrated diminished Nfe2l2 protein binding to the antioxidant response element promoter site proximal to the Sod2 start site in PGC-1α heterozygous mice, implicating PGC-1α in facilitation of Nfe2l2 DNA binding. Nuclear protein co-immunoprecipitation demonstrated an interaction between hepatic Nfe2l2 and PGC-1α in WT mice that was greatly reduced in PGC-1α(+/-) mice. The data indicate that PGC-1α promotes mitochondrial antioxidant enzyme expression through Nfe2l2-mediated SOD-2 expression in sepsis. The presence of this new PGC-1α-dependent signaling axis indicates that PGC-1α opposes mitochondrial oxidative stress by means of selective induction of one or more antioxidant response element-driven genes. By implication, exploitation of this axis could lead to new pharmacological interventions to improve the antioxidant defenses during oxidative stress-induced mitochondrial damage.

Temporal trends and current practice patterns for intraoperative ventilation at U.S. academic medical centers: a retrospective study.

BACKGROUND: Lung protective ventilation strategies utilizing lower tidal volumes per predicted body weight (PBW) and positive end-expiratory pressure (PEEP) have been suggested to be beneficial in a variety of surgical populations. Recent clinical studies have used control groups ventilated with high tidal volumes without PEEP based on the assumption that this reflects current clinical practice. We hypothesized that ventilation strategies have changed over time, that most anesthetics in U.S. academic medical centers are currently performed with lower tidal volumes, and that most receive PEEP. METHODS: Intraoperative data were pooled for adults undergoing general anesthesia with tracheal intubation. Median tidal volumes per kilogram of PBW were categorized as > 10, 8-10 and < 8 mL per kg of PBW. The percentages of cases in 2013 that were performed with median tidal volumes < 8 mL per kg of PBW and PEEP were determined. As a secondary analysis, a proportional odds model using institution, year, height, weight and gender determined the relative associations of these factors using categorical and interquartile odds ratios. RESULTS: 295,540 cases were analyzed from 5 institutions over a period of 10 years. In 2013, 59.3% of cases used median tidal volumes < 8 mL per kg of PBW, 83.3% used PEEP, and 51.0% used both. Of those cases with PEEP, 60.9% used a median pressure of ≥ 5 cmH2O. Predictors of lower categories of tidal volumes included height (odds ratio (OR) 10.83, 95% confidence interval [10.50, 11.16]), institution (lowest OR 0.98 [0.96, 1.00], highest OR 9.63 [9.41, 9.86]), year (lowest OR 1.32 [1.21, 1.44], highest OR 6.31 [5.84, 6.82]), male gender (OR 1.10 [1.07, 1.12]), and weight (OR 0.30 [0.29, 0.31]). CONCLUSION: Most general anesthetics with tracheal intubation at the institutions surveyed are currently performed with a median tidal volume < 8 mL per kg of PBW, most are managed with PEEP of ≥ 5 cmH2O and approximately half utilize both. Given the diversity of the institutions included, this is likely reflective of practice in U.S. academic medical centers. The utilization of higher tidal volumes without PEEP in control groups for clinical research studies should be reconsidered.

Predicting risk of postoperative lung injury in high-risk surgical patients: a multicenter cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients. METHODS: This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test were used to assess model performance. RESULTS: Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and ≥30 breaths/min), FIO2 greater than 35%, and SpO2 less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS: In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS.

Essential right heart physiology for the perioperative practitioner POQI IX: current perspectives on the right heart in the perioperative period.

As patients continue to live longer from diseases that predispose them to right ventricular (RV) dysfunction or failure, many more patients will require surgery for acute or chronic health issues. Because RV dysfunction results in significant perioperative morbidity if not adequately assessed or managed, understanding appropriate assessment and treatments is important in preventing subsequent morbidity and mortality in the perioperative period. In light of the epidemiology of right heart disease, a working knowledge of right heart anatomy and physiology and an understanding of the implications of right-sided heart function for perioperative care are essential for perioperative practitioners. However, a significant knowledge gap exists concerning this topic. This manuscript is one part of a collection of papers from the PeriOperative Quality Initiative (POQI) IX Conference focusing on "Current Perspectives on the Right Heart in the Perioperative Period." This review aims to provide perioperative clinicians with an essential understanding of right heart physiology by answering five key questions on this topic and providing an explanation of seven fundamental concepts concerning right heart physiology.

Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis.

RATIONALE: Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2-related factor-2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown. OBJECTIVES: To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis. METHODS: A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage. MEASUREMENTS AND MAIN RESULTS: Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2-dependent gene expression and nuclear accumulation of nuclear respiratory factor-1, -2α (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1α; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-α production. By contrast, Nrf2(-/-) and Akt1(-/-) mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis. CONCLUSIONS: We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy.