Derivation and Validation of Clinical Phenotypes of the Cardiopulmonary Bypass-Induced Inflammatory Response.

BACKGROUND: Precision medicine aims to change treatment from a "one-size-fits-all" approach to customized therapies based on the individual patient. Applying a precision medicine approach to a heterogeneous condition, such as the cardiopulmonary bypass (CPB)-induced inflammatory response, first requires identification of homogeneous subgroups that correlate with biological markers and postoperative outcomes. As a first step, we derived clinical phenotypes of the CPB-induced inflammatory response by identifying patterns in perioperative clinical variables using machine learning and simulation tools. We then evaluated whether these phenotypes were associated with biological response variables and clinical outcomes. METHODS: This single-center, retrospective cohort study used Cleveland Clinic registry data from patients undergoing cardiac surgery with CPB from January 2010 to March 2020. Biomarker data from a subgroup of patients enrolled in a clinical trial were also included. Patients undergoing emergent surgery, off-pump surgery, transplantation, descending thoracoabdominal aortic surgery, and planned ventricular assist device placement were excluded. Preoperative and intraoperative variables of patient baseline characteristics (demographics, comorbidities, and laboratory data) and perioperative data (procedural data, CPB duration, and hemodynamics) were analyzed to derive clinical phenotypes using K-means-based consensus clustering analysis. Proportion of ambiguously clustered was used to assess cluster size and optimal cluster numbers. After clusters were formed, we summarized perioperative profiles, inflammatory biomarkers (eg, interleukin [IL]-6 and IL-8), kidney biomarkers (eg, urine neutrophil gelatinase-associated lipocalin [NGAL] and IL-18), and clinical outcomes (eg, mortality and hospital length of stay). Pairwise standardized difference was reported for all summarized variables. RESULTS: Of 36,865 eligible cardiac surgery cases, 25,613 met inclusion criteria. Cluster analysis derived 3 clinical phenotypes: α, ß, and γ. Phenotype α (n = 6157 [24%]) included older patients with more comorbidities, including heart and kidney failure. Phenotype ß (n = 10,572 [41%]) patients were younger and mostly male. Phenotype γ (n = 8884 [35%]) patients were 58% female and had lower body mass index (BMI). Phenotype α patients had worse outcomes, including longer hospital length of stay (mean = 9 days for α versus 6 for both ß [absolute standardized difference {ASD} = 1.15] and γ [ASD = 1.08]), more kidney failure, and higher mortality. Inflammatory biomarkers (IL-6 and IL-8) and kidney injury biomarkers (urine NGAL and IL-18) were higher with the α phenotype compared to ß and γ immediately after surgery. CONCLUSIONS: Deriving clinical phenotypes that correlate with response biomarkers and outcomes represents an initial step toward a precision medicine approach for the management of CPB-induced inflammatory response and lays the groundwork for future investigation, including an evaluation of the heterogeneity of treatment effect.

Evaluation of psychological impact of COVID-19 on anesthesiology residents in the United States.

The aim of our study was to evaluate the impact of COVID-19 on the mental health of in-training anesthesiology residents in the United States. A link containing validated survey tools including the Depression-Anxiety-Stress-Scale (DASS-21), the Abbreviated Maslach Burnout Inventory (aMBI), and the Brief Resilient Coping Scale (BRCS) along with questions related to work environment, and additional personal factors were emailed to 159 Anesthesiology residency programs across the US. 143 responses were received of which 111 were complete. The prevalence of depression, anxiety, stress and burnout was 42%, 24%, 31% and 71% respectively. Emotional exhaustion, depersonalization, and reduced feelings of personal accomplishment were experienced by 80%, 53%, and 65% of respondents, respectively. The BRCS scale showed 33% of respondents with low, 44% with moderate and 22% with high coping scales. Logistic regression analyses indicated those with a prior mental health diagnosis were 3 times more likely to have a non-normal DASS depression score, 4 times more likely to have a non-normal DASS anxiety score, and 11.74 times more prone to emotional exhaustion. Increased work hours and higher training levels were associated with increased levels of stress. In our survey, prior mental health illness, gender and increased work hours were the main drivers of increased risk.

The Anesthetic Management of a Parturient With Osteogenesis Imperfecta Type I Undergoing Cesarean Delivery.

Osteogenesis imperfecta (OI) is a rare disorder of bone fragility caused by mutations in the COL1A1/2 genes, which encode type I procollagen. It commonly manifests with bone fractures, joint dislocations, and easy bruising. OI patients presenting for surgery may pose multiple challenges to the anesthesiologist such as management of a potentially difficult airway and heightened positional fracture risks. We present a case detailing the spinal anesthetic management of a 28-year-old woman with type I OI requiring cesarean delivery for a 32-week intrauterine pregnancy with fetal cardiac anomalies.

Real-time echocardiographic guidance for confirming septal placement of right ventricular leads: A pilot study.

INTRODUCTION: Accuracy of fluoroscopy in predicting septal placement of the right ventricular (RV) leads is poor. This pilot study evaluated the feasibility and impact of real-time transthoracic echocardiogram (TTE) during RV lead placement. METHOD: Consecutive patients undergoing transvenous RV lead placement and had a point of care ultrasound team available for TTE guidance were included in the study. TTE was performed to confirm or refute the septal position of RV lead initially positioned using fluoroscopy; leads were repositioned until a septal position was confirmed on TTE. The primary outcome measured was whether the use of TTE resulted in lead repositioning. RESULT: Among the 26 patients included in the study, real-time TTE during RV lead placement resulted in reposition of the lead to a septal position in 38.5% of patients. CONCLUSION: Use of real-time TTE guidance during fluoroscopic RV lead placement is feasible and can aid in confirming a septal position.

Perioperative Individualized Goal Directed Therapy for Cardiac Surgery: A Historical-Prospective, Comparative Effectiveness Study.

INTRODUCTION: Cardiac surgery patients are at increased risk for post-operative complications and prolonged length of stay. Perioperative goal directed therapy (GDT) has demonstrated utility for non-cardiac surgery, however, GDT is not common for cardiac surgery. We initiated a quality improvement (QI) project focusing on the implementation of a GDT protocol, which was applied from the immediate post-bypass period into the intensive care unit (ICU). Our hypothesis was that this novel GDT protocol would decrease ICU length of stay and possibly improve postoperative outcomes. METHODS: This was a historical prospective, QI study for patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Integral to the QI project was education towards all associated providers on the concepts related to GDT. The protocol involved identifying patient specific targets for cardiac index and mean arterial pressure. These targets were maintained from the post-CPB period to the first 12 h in the ICU. Statistical comparisons were performed between the year after GDT therapy was launched to the last two years prior to protocol implementation. The primary outcome was ICU length of stay. RESULTS: There was a significant decrease in ICU length of stay when comparing the year after the protocol initiation to years prior, from a median of 6.19 days to 4 days (2017 vs. 2019, p < 0.0001), and a median of 5.88 days to 4 days (2018 vs. 2019, p < 0.0001). Secondary outcomes demonstrated a significant reduction in total administered volumes of inotropic medication(milrinone). All other vasopressors demonstrated no differences across years. Hospital length of stay comparisons did not demonstrate a significant reduction. CONCLUSION: These results suggest that an individualized goal directed therapy for cardiac surgery patients can reduce ICU length of stay and decrease amount of inotropic therapy.