Association of Acute Systemic Inflammation with Patient-Centric Postoperative Pulmonary Complications After Elective Cardiac Surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) occur frequently after cardiac surgery. Absolute postoperative values of biomarkers of inflammation (interleukin [IL]-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and alveolar epithelial injury (soluble receptor for advanced glycation end-products [sRAGE]) have been associated with hypoxia and prolonged ventilation. However, relationships between these biomarkers and PPCs, contextualized to preoperative inflammation and perioperative lung injury risk factors, are uncertain. We aimed to determine associations between perioperative increases in biomarkers of inflammation and alveolar epithelial injury with a patient-centric PPC definition in adult cardiac surgical patients, accounting for the influence of intraoperative risk factors for lung injury. METHODS: Adults undergoing elective cardiac surgery were eligible for this observational cohort study. Blood concentrations of IL-6, IL-8, TNF-α, and sRAGE were collected after anesthesia induction (baseline) and on postoperative day 1 (POD 1). The primary outcome was the occurrence of moderate or severe PPCs, graded using a validated scale, in POD 0 to 7. We estimated the association between POD 1 IL-6, IL-8, TNF-α, and sRAGE concentrations and moderate/severe PPC presence using separate logistic regression models for each biomarker, adjusted for baseline biomarker values and risk factors for postoperative lung injury (age, baseline PaO2/FiO2, left ventricle ejection fraction [LVEF], procedural type, cardiopulmonary bypass duration, and transfusions). Covariables were chosen based on relevance to lung injury and unadjusted between-group differences among patients with versus without PPCs. The secondary outcome was postoperative ventilation duration, which was log-transformed and analyzed using linear regression, adjusted using the same variables as the primary outcome. RESULTS: We enrolled 204 patients from 2016 to 2018. Biomarkers were analyzed in 2023 among 175 patients with complete data. In adjusted analyses, POD 1 IL-8 and IL-6 were significantly associated with moderate/severe PPCs. The odds ratio (OR) for developing a PPC for every 50 pg/mL increase in POD 1 IL-8 was 7.19 (95% confidence interval [CI], 2.13-28.53, P = .003) and 1.42 (95% CI, 1.13-1.93, P = .01) for every 50 pg/mL increase in POD 1 IL-6. In adjusted analyses, postoperative ventilation duration was significantly associated with POD 1 sRAGE; each 50 pg/mL increase in sRAGE was associated with a 25% (95% CI, 2%-52%, P = .03) multiplicative increase in hours of ventilation. TNF-α was not significantly associated with PPCs or ventilation duration. CONCLUSIONS: Acute systemic inflammation is significantly associated with PPCs after elective cardiac surgery in adults when taking into consideration preoperative inflammatory burden and perioperative factors that may influence postoperative lung injury.

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia.

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following. METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6). RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following  was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

Optimizing Perioperative Renal Replacement Therapy for Patients Undergoing Cardiac Surgical Procedures Requiring Cardiopulmonary Bypass.

Coronary artery disease is highly prevalent in patients with end-stage renal disease (ESRD), and cardiovascular complications remain the most common cause of death in this patient population. Accordingly, many cardiac surgical procedures requiring cardiopulmonary bypass support are performed on these patients each year, with morbidity and mortality rates far exceeding patients without ESRD. Anuric patients lack the normal renal homeostatic functions which typically allow for physiologic protection from challenges during the operation, such as volume overload, hyperkalemia, and acidemia. Careful preoperative planning and coordination to provide pre-, intra-, and postoperative renal replacement therapies for such patients are imperative. Many different strategies have been reported in the literature. Zero-balance ultrafiltration is a newer strategy which utilizes convective ultrafiltration much like pre-filter continuous renal replacement therapy and utilizes pre-existing connections on the cardiopulmonary bypass pump performed by the perfusion team. This allows for control of potassium concentration throughout the operation with existing personnel and minimal additional equipment. Here, we describe the unique challenges caring for patients receiving renal replacement therapy undergoing cardiac surgical procedures requiring cardiopulmonary bypass.

Logistical Considerations and Clinical Outcomes Associated With Converting Operating Rooms Into an Intensive Care Unit During the Coronavirus Disease 2019 Pandemic in a New York City Hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a public health crisis that disrupted normal patterns of health care in the New York City metropolitan area. In preparation for a large influx of critically ill patients, operating rooms (ORs) at NewYork-Presbyterian/Columbia University Irving Medical Center (NYP-Columbia) were converted into a novel intensive care unit (ICU) area, the operating room intensive care unit (ORICU). METHODS: Twenty-three ORs were converted into an 82-bed ORICU. Adaptations to the OR environment permitted the delivery of standard critical care therapies. Nonintensive-care-trained staff were educated on the basics of critical care and deployed in a hybrid staffing model. Anesthesia machines were repurposed as critical care ventilators, with accommodations to ensure reliable function and patient safety. To compare ORICU survivorship to outcomes in more traditional environments, we performed Kaplan-Meier survival analysis of all patients cared for in the ORICU, censoring data at the time of ORICU closure. We hypothesized that age, sex, and obesity may have influenced the risk of death. Thus, we estimated hazard ratios (HR) for death using Cox proportional hazard regression models with age, sex, and body mass index (BMI) as covariables and, separately, using older age (65 years and older) adjusted for sex and BMI. RESULTS: The ORICU cared for 133 patients from March 24 to May 14, 2020. Patients were transferred to the ORICU from other ICUs, inpatient wards, the emergency department, and other institutions. Patients remained in the ORICU until either transfer to another unit or death. As the hospital patient load decreased, patients were transferred out of the ORICU. This process was completed on May 14, 2020. At time of data censoring, 55 (41.4%) of patients had died. The estimated probability of survival 30 days after admission was 0.61 (95% confidence interval [CI], 0.52-0.69). Age was significantly associated with increased risk of mortality (HR = 1.05, 95% CI, 1.03-1.08, P < .001 for a 1-year increase in age). Patients who were ≥65 years were an estimated 3.17 times more likely to die than younger patients (95% CI, 1.78-5.63; P < .001) when adjusting for sex and BMI. CONCLUSIONS: A large number of critically ill COVID-19 patients were cared for in the ORICU, which substantially increased ICU capacity at NYP-Columbia. The estimated ORICU survival rate at 30 days was comparable to other reported rates, suggesting this was an effective approach to manage the influx of critically ill COVID-19 patients during a time of crisis.

Frailty in Critical Care Medicine: A Review.

Traditional approaches to clinical risk assessment utilize age as a marker of increased vulnerability to stress. Relatively recent advancements in the study of aging have led to the concept of the frailty syndrome, which represents a multidimensional state of depleted physiologic and psychosocial reserve and clinical vulnerability that is related to but variably present with advancing age. The frailty syndrome is now a well-established clinical entity that serves as both a guide for clinical intervention and a predictor of poor outcomes in the primary and acute care settings. The biological aspects of the syndrome broadly represent a network of interrelated perturbations involving the age-related accumulation of molecular, cellular, and tissue damage that leads to multisystem dysregulation, functional decline, and disproportionately poor response to physiologic stress. Given the complexity of the underlying biologic processes, several well-validated approaches to define frailty clinically have been developed, each with distinct and reasonable considerations. Stemming from this background, the past several years have seen a number of observational studies conducted in intensive care units that have established that the determination of frailty is both feasible and prognostically useful in the critical care setting. Specifically, frailty as determined by several different frailty measurement tools appears associated with mortality, increased health care utilization, and disability, and has the potential to improve risk stratification of intensive care patients. While substantial variability in the implementation of frailty measurement likely limits the generalizability of specific findings, the overall prognostic trends may offer some assistance in guiding management decisions with patients and their families. Although no trials have assessed interventions to improve the outcomes of critically ill older people living with frailty, the particular vulnerability of this population offers a promising target for intervention in the future.

Off-Pump Versus On-Pump Coronary Artery Bypass Grafting-A Systematic Review and Analysis of Clinical Outcomes.

Surgical coronary artery bypass grafting (CABG) is the standard of care for revascularization of left main or three-vessel coronary artery disease. The off-pump coronary artery bypass graft (OPCAB) procedure avoids the use of cardiopulmonary bypass. Theoretically, OPCAB may improve long-term outcomes by reducing the rates of perioperative myocardial injury, stroke, neurocognitive impairment, and cardiac-related mortality. Several high-quality clinical trials have been conducted since OPCAB became popular in the 1990s and have demonstrated no benefit of OPCAB over traditional CABG with respect to these outcomes despite favorable short-term reductions in transfusion requirements and other postoperative complications. Ultimately, OPCAB is associated with less effective myocardial revascularization and does not entirely prevent complications traditionally associated with cardiopulmonary bypass. This article reviews major high-quality trials of OPCAB versus traditional CABG with respect to both short- and long-term clinical outcomes.

Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy.

Vasoplegic syndrome, characterized by low systemic vascular resistance and hypotension in the presence of normal or supranormal cardiac function, is a frequent complication of cardiovascular surgery. It is associated with a diffuse systemic inflammatory response and is mediated largely through cellular hyperpolarization, high levels of inducible nitric oxide, and a relative vasopressin deficiency. Cardiopulmonary bypass is a particularly strong precipitant of the vasoplegic syndrome, largely due to its association with nitric oxide production and severe vasopressin deficiency. Postoperative vasoplegic shock generally is managed with vasopressors, of which catecholamines are the traditional agents of choice. Norepinephrine is considered to be the first-line agent and may have a mortality benefit over other drugs. Recent investigations support the use of noncatecholamine vasopressors, vasopressin in particular, to restore vascular tone. Alternative agents, including methylene blue, hydroxocobalamin, corticosteroids, and angiotensin II, also are capable of restoring vascular tone and improving vasoplegia, but their effect on patient outcomes is unclear.

Frontal Electroencephalography Findings in Critically Ill COVID-19 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) negatively impacts the central nervous system, and studies using a full montage of electroencephalogram (EEG) electrodes have reported nonspecific EEG patterns associated with coronavirus disease 2019 (COVID-19) infection. The use of this technology is resource-intensive and limited in its implementation. In this descriptive pilot study, we report neurophysiological patterns and the potential prognostic capability of an abbreviated frontal EEG electrode montage in critically ill COVID-19 patients. MATERIALS AND METHODS: Patients receiving mechanical ventilation for SARS-CoV-2 respiratory failure were monitored with Sedline Root Devices using EEG electrodes were placed over the forehead. Qualitative EEG assessments were conducted daily. The primary outcome was mortality, and secondary outcomes were duration of endotracheal intubation and lengths of intensive care and hospitalization stay. RESULTS: Twenty-six patients were included in the study, and EEG discontinuity was identified in 22 (84.6%) patients. The limited sample size and patient heterogeneity precluded statistical analysis, but certain patterns were suggested by trends in the data. Survival was 100% (4/4) for those patients in which a discontinuous EEG pattern was not observed. The majority of patients (87.5%, 7/8) demonstrating activity in the low-moderate frequency range (7 to 17 Hz) survived compared with 61.1% (11/18) of those without this observation. CONCLUSIONS: The majority of COVID-19 patients showed signs of EEG discontinuity during monitoring with an abbreviated electrode montage. The trends towards worse survival among those with EEG discontinuity support the need for additional studies to investigate these associations in COVID-19 patients.

Use of 90-day mortality does not change assessment of hospital quality after coronary artery bypass grafting in New York State.

OBJECTIVES: Publicly reported postoperative 30-day mortality rates are commonly used to compare hospital quality after coronary artery bypass grafting. We sought to determine whether 90-day mortality rates, which are not publicly reported but better capture postdischarge mortality, are a better determinant of hospital performance. METHODS: We performed a retrospective cohort analysis of 30- versus 90-day risk-standardized mortality rates at adult cardiac surgical centers in New York State from 2008 to 2014. Hospitals were classified as good or poor performing outliers at each time point based on the bounds of the 95% confidence interval around each hospital's predicted risk-standardized mortality rates determined via hierarchical models. The primary outcome was change in institutional performance via outlier classification from 30 to 90 days. RESULTS: During the study period, 72,398 adults underwent a coronary artery bypass grafting procedure at 1 of 42 institutions. The risk-standardized mortality rates increased from 30 to 90 days at all institutions, with a median 30-day risk-standardized mortality rate of 2.16% (interquartile range, 0.69%) and median 90-day risk-standardized mortality rate of 3.69% (interquartile range, 1.00%). In using a 90-day instead of a 30-day metric, 3 hospitals changed outlier status. One hospital improved to a good from as expected performer, and 2 worsened to as expected from good performers. CONCLUSIONS: In a cohort of patients who underwent coronary artery bypass grafting surgery from 2008 to 2014 in New York State, use of a 90-day mortality metric resulted in a change in hospital quality assessment for a minority of hospitals. The use of 90-day mortality may not provide additional value when evaluating institutional performance for this population.

Veno-venous extracorporeal membrane oxygenation allocation in the COVID-19 pandemic.

Rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant clinical illness, coronavirus disease 2019 (COVID-19), drove the World Health Organization to declare COVID-19 a pandemic. Veno-venous Extra-Corporeal Membrane Oxygenation (VV-ECMO) is an established therapy for management of patients demonstrating the most severe forms of hypoxemic respiratory failure from COVID-19. However, features of COVID-19 pathophysiology and necessary length of treatment present distinct challenges for utilization of VV-ECMO within the current healthcare emergency. In addition, growing allocation concerns due to capacity and cost present significant challenges. Ethical and legal aspects pertinent to triage of this resource-intensive, but potentially life-saving, therapy in the setting of the COVID-19 pandemic are reviewed here. Given considerations relevant to VV-ECMO use, additional emphasis has been placed on emerging hospital resource scarcity and disproportionate representation of healthcare workers among the ill. Considerations are also discussed surrounding withdrawal of VV-ECMO and the role for early communication as well as consultation from palliative care teams and local ethics committees. In discussing how to best manage these issues in the COVID-19 pandemic at present, we identify gaps in the literature and policy important to clinicians as this crisis continues.

Supporting the Geriatric Critical Care Patient: Decision Making, Understanding Outcomes, and the Role of Palliative Care.

Geriatric admissions to the intensive care unit (ICU) are common and require unique considerations for ICU clinicians. Admission to the ICU should be considered on an individual-patient basis. It is reasonable to consider a "trial of critical care" for many patients, even those who have uncertain chances of meaningful recovery. Quality of life and functional independence are especially important to older adults, and these outcomes should be considered when weighing the risks and benefits of admission or continuing ICU care.

Anesthesia for Kidney and Pancreas Transplantation.

Kidney transplants are the most common solid organ abdominal transplant and are occasionally performed simultaneously with pancreas transplants in diabetic patients. Preoperative evaluation of potential transplant recipients should focus on the potential for occult cardiovascular disease while also screening for other signs of end-organ dysfunction. Intraoperatively, it is of utmost importance to ensure adequate graft perfusion to limit the risk of postoperative graft dysfunction or rejection. Postoperative care of the kidney or pancreas transplant patient should focus on ensuring normalization of volume status, electrolyte concentrations, and glycemic control.

Mitochondrial Dysfunction in Atrial Tissue of Patients Developing Postoperative Atrial Fibrillation.

BACKGROUND: Mitochondria are the major site of cellular oxidation. Metabolism and oxidative stress have been implicated as possible mechanisms for postoperative atrial fibrillation (POAF) after cardiac operations. Establishing the precise nature of mitochondrial dysfunction as an etiologic factor for oxidative stress-related cell death and apoptosis could further the understanding of POAF. To establish this relationship, mitochondrial function was studied in patients undergoing cardiac operations that developed POAF and compared it with patients without POAF. METHODS: Right atrial tissue and serum samples were collected from 85 patients before and after cardiopulmonary bypass. Microarray analysis (36 patients) and RNA sequencing (5 patients) were performed on serum and atrial tissues, respectively, for identifying significantly altered genes in patients who developed POAF. On the basis of these results, Western blot was performed in 52 patients for the genes that were most altered, and functional pathways were established. RESULTS: POAF developed in 30.6% (n = 26) of patients. Serum microarray showed significant fold changes in the expression of 49 genes involved in inflammatory response, oxidative stress, apoptosis, and amyloidosis (p < 0.05) in the POAF group. Similarly, RNA sequencing demonstrated an increased expression of genes associated with inflammatory response, fatty acid metabolism, and apoptosis in the POAF group (false discovery rate > 0.05). Immunoblotting showed a significant increase in TNFAIP6 (tumor necrosis factor, α-induced protein 6; p = 0.02) and transforming growth factor-ß (p = 0.04) after cardiopulmonary bypass in the POAF group. There was a significant decrease in PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α; p = 0.002) and CPT1 (carnitine palmitoyltransferase I; p < 0.0005) in the POAF group after cardiopulmonary bypass. CONCLUSIONS: Compared with patients without POAF, those with POAF demonstrated mitochondrial dysfunction at various levels that are suitable for potential pharmacotherapy.

Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials.

BACKGROUND: Traumatic brain injury (TBI) is a worldwide health concern associated with significant morbidity and mortality. In the United States, severe TBI is managed according to recommendations set forth in 2007 by the Brain Trauma Foundation (BTF), which were based on relatively low quality clinical trials. These guidelines prescribed the use of hypothermia for the management of TBI. Several randomized controlled trials (RCTs) of hypothermia for TBI have since been conducted. Despite this new literature, there is ongoing controversy surrounding the use of hypothermia for the management of severe TBI. METHODS: We searched the PubMed database for all RCTs of hypothermia for TBI since 2007 with the intent to review the methodology outcomes of these trials. Furthermore, we aimed to develop evidence-based, expert opinions based on these recent studies. RESULTS: We identified 8 RCTs of therapeutic hypothermia published since 2007 that focused on changes in neurologic outcomes or mortality in patients with severe TBI. The majority of these trials did not identify improvement with the use of hypothermia, though there were subgroups of patients that may have benefited from hypothermia. Differences in methodology prevented direct comparison between studies. CONCLUSIONS: A growing body of literature disfavors the use of hypothermia for the management of severe TBI. In general, empiric hypothermia for severe TBI should be avoided. However, based on the results of recent trials, there may be some patients, such as those in Asian centers or with focal neurologic injury, who may benefit from hypothermia.

Whole-brain proton MR spectroscopic imaging in Parkinson's disease.

BACKGROUND AND PURPOSE: To examine the distributions of proton magnetic resonance spectroscopy (MRS) observed metabolites in Parkinson's disease (PD) throughout the whole brain. METHODS: Twelve PD patients and 18 age-matched controls were studied using neuropsychological testing, MRI and volumetric MR spectroscopic imaging. Average values of signal normalized metabolite values for N-acetyl-aspartate, total-creatine, and total-choline (NAA, total-Cre, total-Cho, respectively) and their ratios were calculated for gray matter (GM) and white matter (WM) in each lobar brain region. RESULTS: Analyses revealed altered metabolite values in PD subjects relative to controls within the GM of the temporal lobe (right: elevated Cre, P = .027; decreased NAA/Cre, P = .019; decreased Cho/Cre, P = .001 and left: decreased NAA/Cre; P = .001, decreased Cho/Cre, P = .007); the right occipital lobe (decreased NAA, P = .032 and NAA/Cre, P = .016); and the total cerebrum GM (decreased NAA/Cre, P = .029). No meaningful correlations were obtained between abnormal metabolite values and the neuropsychological measures. CONCLUSIONS: PD is associated with widespread alterations of brain metabolite concentrations, with a primary finding of increased creatine. Higher creatine values in our PD sample may reflect greater neuronal energy expenditure early in the disease process that is compensatory. This is the first whole brain MRS study of PD that has examined metabolite changes across a large fraction of the brain volume, including the cortical mantle.