Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy.

BACKGROUND: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks. OBJECTIVE: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy. STUDY DESIGN: Hospitalized patients with hypertensive disorders of pregnancy between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to January 2024 after the implementation of serum soluble fms-like tyrosine kinase-1/placental growth factor testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (placental growth factor and soluble fms-like tyrosine kinase-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines on the basis of biomarkers but made pragmatic management decisions independently. Results of soluble fms-like tyrosine kinase-1/placental growth factor tests were available to clinicians within 24 hours of venipuncture. The association between soluble fms-like tyrosine kinase-1/placental growth factor ≥40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. RESULTS: Of the 65 patient encounters, 36 had a soluble fms-like tyrosine kinase-1/placental growth factor <40 (55.4%). The rate of delivery for indications related to hypertensive disorders of pregnancy within 2 weeks was significantly lower among encounters with a low ratio vs high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted hazard ratio, 7.52; 95% confidence interval, 3.05-18.54; P<.001). A diagnosis of preeclampsia with severe features within 2 weeks of testing was also less likely among the encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 when compared with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (2/36 [5.6%] vs 23/29 [79.3%], P<.001; positive predictive value of 79% [95% confidence interval, 0.65-0.94] and negative predictive value of 0.94 [95% confidence interval, 0.87-1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within 2 weeks of testing were 6.13 and 0.09, respectively. Encounters with a soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 were less likely to experience a maternal or fetal adverse event as compared with encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], P=.01). Among 36 encounters involving low soluble fms-like tyrosine kinase-1/placental growth factor values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed on the basis of biomarkers, and none developed preeclampsia with severe features or adverse outcomes at 2 weeks. The median latency defined as days between biomarker measurement and delivery in patients with a low biomarker ratio was 33 (interquartile ratio, 23-47) vs 7 (interquartile ratio, 4-14) days among patients with a high ratio (P<.001). Corticosteroid use within 2 weeks was also significantly reduced in the low biomarker group when compared with the high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], P<.001). CONCLUSION: In this study, the incorporation of soluble fms-like tyrosine kinase-1/placental growth factor ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with hypertensive disorders of pregnancy in the United States. Among patients with a low ratio, pregnancy may be prolonged, which results in better neonatal outcomes without harm to the mother.

Family Perceptions of Virtual Family-Centered Rounds in a Quaternary Cardiac Intensive Care Unit.

Background: Family-centered rounds (FCR) reduce the risk of psychological comorbidities of family members and improve the quality of communication between providers and families. Materials and methods: We conducted a pilot quality improvement study analyzing family perceptions of virtual FCR. Family members of previously admitted cardiac ICU patients who participated in at least one session of virtual FCR between April 2020 and June 2021 at Massachusetts General Hospital were surveyed post-ICU discharge. Results: During the study, 82 family members enrolled and participated in virtual FCR with 29 completing the post-admission telephone survey. Many cardiac ICU patients were male (n = 53), and a majority were discharged home (43%) with the patient's wives being the most common respondents to the questionnaire (n = 18). Across all questions in the survey, more than 75% of the respondents perceived the highest level of care in trust, communication, relationship, and compassion with their provider. Participants perceived the highest level of care in trust (96%), explanation (88%), as well as care and understanding (89%). Conclusions: Family members of cardiac ICU patients positively rated the quality of communication and perceived a high level of trust and communication between their providers on the virtual format.

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.

Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study.

PURPOSE: We aimed to estimate the association of glucagon-like peptide 1 (GLP-1) receptor agonist therapy with the incidence of endoscopically visible gastric contents after preprocedural fasting. METHODS: We reviewed the records of esophagogastroduodenoscopy (EGD) performed at our institution between 2019 and 2023 and determined the presence of residual gastric contents from the procedure notes and saved images. We compared patients taking GLP-1 agonists at the time of the procedure (GLP group, 90 procedures) with patients who started GLP-1 agonist therapy within 1,000 days after undergoing EGD (control, 102 procedures). We excluded emergent procedures without fasting, combined EGD/colonoscopy procedures, and patients with known gastroparesis or previous gastric surgery. We estimated the association between GLP-1 agonist therapy and residual gastric contents with a confounder-adjusted generalized linear mixed effect model. RESULTS: Compared with controls, the GLP cohort had a higher age, American Society of Anesthesiologists' Physical Status, and incidence of nausea and diabetes mellitus. Body mass index and fasting duration were comparable between groups. Visible gastric content was documented in 17 procedures in the GLP group (19%) and in five procedures in the control group (5%), with an associated confounder adjusted odds ratio of 5.8 (95% confidence interval, 1.7 to 19.3; P = 0.004). There were five instances of emergent endotracheal intubation in the GLP group vs one case in control and one case of pulmonary aspiration vs none in control. CONCLUSIONS: In fasting patients, GLP-1 agonist therapy was associated with an increased incidence of residual gastric contents, potentially posing an additional risk of periprocedural pulmonary aspiration.

RéSUMé: OBJECTIF: Notre objectif était d'estimer l'association d'un traitement par agonistes des récepteurs du peptide-1 de type glucagon (glucagon-like peptide 1, GLP-1) avec l'incidence de contenu gastrique visible par endoscopie malgré le jeûne préopératoire. MéTHODE: Nous avons examiné les dossiers des œsophagogastroduodénoscopies (OGD) réalisées dans notre établissement entre 2019 et 2023 et déterminé la présence de contenu gastrique résiduel à partir des notes d'intervention et des images enregistrées. Nous avons comparé les patient·es prenant des agonistes du GLP-1 au moment de l'intervention (groupe GLP, 90 procédures) avec les patient·es qui ont commencé un traitement par agonistes du GLP-1 dans les 1000 jours suivant l'OGD (groupe témoin, 102 procédures). Nous avons exclu les procédures d'urgence sans jeûne, les procédures combinées OGD/coloscopie et les patient·es présentant une gastroparésie connue ou une chirurgie gastrique antérieure. Nous avons estimé l'association entre le traitement par agonistes du récepteur GLP-1 et le contenu gastrique résiduel à l'aide d'un modèle linéaire généralisé à effets mixtes ajusté en fonction des facteurs de confusion. RéSULTATS: Par rapport aux témoins, la cohorte GLP était plus âgée, de statut physique selon l'American Society of Anesthesiologists plus élevé et présentait une incidence plus élevée de nausées et de diabète. L'indice de masse corporelle et la durée du jeûne étaient comparables entre les groupes. Du contenu gastrique visible a été documenté dans 17 procédures dans le groupe GLP (19 %) et dans cinq procédures dans le groupe témoin (5 %), avec un rapport de cotes ajusté associé de 5,8 (intervalle de confiance à 95 %, 1,7 à 19,3; P = 0,004). Il y a eu cinq cas d'intubation endotrachéale urgente dans le groupe GLP vs un cas dans le groupe témoin et un cas d'aspiration pulmonaire vs aucun dans le groupe témoin. CONCLUSION: Chez la patientèle à jeun, le traitement par agonistes des récepteurs du GLP-1 a été associé à une incidence accrue de contenu gastrique résiduel, ce qui pourrait entraîner un risque supplémentaire d'aspiration pulmonaire périprocédurale.

Patient perceptions of remote patient monitoring program for hypertensive disorders of pregnancy.

PURPOSE: The utilization of remote patient monitoring (RPM) with home blood pressure monitoring has shown improvement in blood pressure control and adherence with follow-up visits. Patient perceptions regarding its use in the obstetric population have not been widely studied. The aim of this study was to assess patients' knowledge about hypertensive disorders of pregnancy and perceptions and satisfaction of the RPM program. METHODS: Descriptive analysis of survey responses of patients with PPHTN enrolled into the RPM program for 6 weeks after delivery between October 2021 and April 2022. Surveys were automatically administered at 1-, 3-, and 6-week postpartum. Responses were further compared between Black and non-Black patient-reported race. RESULTS: 545 patients received the RPM program. Of these, 306 patients consented to data collection. At 1 week, 88% of patients that responded reported appropriately that a blood pressure greater than 160/110 is abnormal. At 3 weeks, 87.4% of patients responded reported they were "very" or "somewhat" likely to attend their postpartum follow-up visits because of RPM. At 6 weeks, 85.5% of the patients that responded were "very" or "somewhat" satisfied with the RPM program. Responses were not statistically different between races. CONCLUSIONS: Majority of postpartum patients enrolled in the RPM program had correct knowledge about hypertension. In addition, patients were highly satisfied with the RPM program and likely to attend postpartum follow-up based on responses. Further research is warranted to validate these findings and to address any barriers for patients who did not utilize the program.

Electrical Impedance Tomography Identifies Evolution of Regional Perfusion in a Porcine Model of Acute Respiratory Distress Syndrome.

BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.

The additive role of angiogenic markers for women with confirmed preeclampsia.

BACKGROUND: Hypertension complicates 2% to 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality globally. Given the prognostic role that angiogenic markers play in evaluation of patients with "suspected preeclampsia," the International Society for the Study of Hypertension in Pregnancy incorporated angiogenic imbalance into the 2021 definition of preeclampsia. As women with "suspected preeclampsia" are a heterogeneous group, with some already meeting the diagnostic criteria for preeclampsia, we evaluated whether the soluble fms-like tyrosine kinase-1/placental growth factor ratio adds prognostic value among these women. OBJECTIVE: This study aimed to assess the additive value of soluble fms-like tyrosine kinase-1/placental growth factor ratio when the diagnostic criteria for preeclampsia have already been met. STUDY DESIGN: This was a secondary analysis of a prospective cohort study of patients presenting to obstetrical triage with suspected preeclampsia at ≥20+0 weeks' gestation from July 2009 to June 2012 in Boston, United States. Clinicians were masked to soluble fms-like tyrosine kinase-1/placental growth factor ratio results. Clinical records were reviewed for maternal and neonatal care and outcomes. The value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio (≤38, >38, or >85) was assessed for identifying women at low or high risk of evolving into preeclampsia with severe features within 2 weeks of the triage visit, with preeclampsia with severe features being defined by the American College of Obstetricians and Gynecologists (2013 definition). Based on information in obstetrical triage, preeclampsia among triage patients was defined either by: (1) The International Society for the Study of Hypertension in Pregnancy "restrictive" criteria (ie, new-onset hypertension and proteinuria at ≥20 weeks), or (2) The International Society for the Study of Hypertension in Pregnancy "broad" maternal criteria (ie, new-onset hypertension with proteinuria or one/more relevant maternal end-organ complications). RESULTS: Of 1043 patients included, 459 presented at 20+0 to 34+6 weeks and 584 at ≥35+0 weeks. In triage, 25.8% of women with "suspected preeclampsia" already met the preeclampsia criteria based on the International Society for the Study of Hypertension in Pregnancy broad criteria and 22.0% based on the restrictive criteria. In separate multivariable analyses adjusted for gestational age, a soluble fms-like tyrosine kinase-1/placental growth factor ratio >38 was independently associated with preeclampsia with severe features within 2 weeks even after adjusting for preeclampsia diagnosis in obstetrical triage, whether that preeclampsia were defined restrictively (odds ratio, 15.62; 95% confidence interval, 8.91-27.40) or broadly (odds ratio, 14.56; 95% confidence interval, 8.30-25.56). A soluble fms-like tyrosine kinase-1/placental growth factor ratio ≤38 was good at ruling out development of preeclampsia with severe features within 2 weeks among all patients and among those meeting the restrictive or broad definitions of preeclampsia (negative likelihood ratios, ≤0.16), driven by performance of the ratio before 35 weeks (ie, negative likelihood ratio ≤0.12). A soluble fms-like tyrosine kinase-1/placental growth factor ratio >85 was good at ruling-in preeclampsia with severe features within 2 weeks among women with suspected preeclampsia, either before (positive likelihood ratio, 8.20) or after 35 weeks (positive likelihood ratio, 6.00) and fair at ruling-in preeclampsia with severe features within 2 weeks when preeclampsia had already been confirmed in patients at <35 weeks (restrictively positive likelihood ratio, 3.48, or broadly positive likelihood ratio, 3.40). CONCLUSION: Our findings support the prognostic value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio among patients with confirmed preeclampsia, particularly to identify those both likely and unlikely to progress toward the development of severe features in the next 2 weeks and those who may be most appropriate for expectant and potentially outpatient care. Our findings support the incorporation of angiogenic imbalance into the definition of preeclampsia, particularly at 20-34+0 weeks.

Anesthetic Preferences for Cardiac Anesthesia: A Survey of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Volatile anesthetics have been historically preferred for cardiac anesthesia, but the evidence for their superiority to intravenous agents is mixed. We conducted a survey to better understand the current state of practice and the rationale behind provider preferences for anesthesia for cardiac surgery with cardiopulmonary bypass. We hypothesized that anesthetic preference would vary considerably among surveyed providers without a clear majority, as would the rationale behind those preferences. METHODS: Email invitations were sent to members of the Society of Cardiovascular Anesthesiologists, who were asked to identify the anesthetics or sedatives they typically prefer to administer during induction, prebypass, bypass, postbypass, and postoperative periods and why they prefer those agents. Members' beliefs regarding the importance of anesthetics on postoperative outcomes were also assessed. RESULTS: Invitations were sent on 2 separate dates to 3328 and 3274 members, of whom 689 (21%) responded. The median (interquartile range [IQR]) respondent age was 45 (37-56) years, 79% were men, and 75% were fellowship trained. The most frequently chosen drug for induction was propofol (80%). Isoflurane was the most frequently selected primary agent for the prebypass (57%), bypass (62%), and postbypass periods (50%). Sevoflurane was the second most frequently selected (30%; 17%, and 24%, respectively). Propofol was the third most frequently selected agent for the bypass (14%) and postbypass periods (17%). Ease of use was the most frequently selected reason for administering isoflurane and sevoflurane for each period. During bypass, the second most frequently selected rationale for using isoflurane and sevoflurane was institutional practice. A total of 76% responded that the perfusionist typically delivers the bypass anesthetic. Ischemic preconditioning, organ protection, and postoperative cognitive function were infrequently selected as rationales for preferring the volatile anesthetics. Most respondents (73%) think that anesthetics have organ-protective properties, especially isoflurane (74%) and sevoflurane (59%), and 72% believed that anesthetic choice contributes to patient outcome. The median (IQR) agreement (0 = strongly disagree to 100 = strongly agree) was 72 (63-85) for the statement that "inhaled anesthetics are an optimal maintenance anesthetic for cardiac surgery." CONCLUSIONS: In a survey of cardiac anesthesiologists, a majority of respondents indicated that they prefer volatile anesthetics for maintenance of anesthesia, that anesthetic selection impacts patient outcomes, and that volatile anesthetics have organ-protective properties. The members' rationales for preferring these agents possibly reflect that practical considerations, such as ease of use, effectiveness, and institutional practice, also influence anesthetic selection during cardiac surgery in addition to considerations such as organ protection.

Nationwide Clinical Practice Patterns of Anesthesiology Critical Care Physicians: A Survey to Members of the Society of Critical Care Anesthesiologists.

BACKGROUND: Despite the growing contributions of critical care anesthesiologists to clinical practice, research, and administrative leadership of intensive care units (ICUs), relatively little is known about the subspecialty-specific clinical practice environment. An understanding of contemporary clinical practice is essential to recognize the opportunities and challenges facing critical care anesthesia, optimize staffing patterns, assess sustainability and satisfaction, and strategically plan for future activity, scope, and training. This study surveyed intensivists who are members of the Society of Critical Care Anesthesiologists (SOCCA) to evaluate practice patterns of critical care anesthesiologists, including compensation, types of ICUs covered, models of overnight ICU coverage, and relationships between these factors. We hypothesized that variability in compensation and practice patterns would be observed between individuals. METHODS: Board-certified critical care anesthesiologists practicing in the United States were identified using the SOCCA membership distribution list and invited to take a voluntary online survey between May and June 2021. Multiple-choice questions with both single- and multiple-select options were used for answers with categorical data, and adaptive questioning was used to clarify stem-based responses. Respondents were asked to describe practice patterns at their respective institutions and provide information about their demographics, salaries, effort in ICUs, as well as other activities. RESULTS: A total of 490 participants were invited to take this survey, and 157 (response rate 32%) surveys were completed and analyzed. The majority of respondents were White (73%), male (69%), and younger than 50 years of age (82%). The cardiothoracic/cardiovascular ICU was the most common practice setting, with 69.5% of respondents reporting time working in this unit. Significant variability was observed in ICU practice patterns. Respondents reported spending an equal proportion of their time in clinical practice in the operating rooms and ICUs (median, 40%; interquartile range [IQR], 20%-50%), whereas a smaller proportion-primarily those who completed their training before 2009-reported administrative or research activities. Female respondents reported salaries that were $36,739 less than male respondents; however, this difference was not statistically different, and after adjusting for age and practice type, these differences were less pronounced (-$27,479.79; 95% confidence interval [CI], -$57,232.61 to $2273.03; P = .07). CONCLUSIONS: These survey data provide a current snapshot of anesthesiology critical care clinical practice patterns in the United States. Our findings may inform decision-making around the initiation and expansion of critical care services and optimal staffing patterns, as well as provide a basis for further work that focuses on intensivist satisfaction and burnout.

Association Between Postoperative Delirium and Long-Term Subjective Cognitive Decline in Older Patients Undergoing Cardiac Surgery: A Secondary Analysis of the Minimizing Intensive Care Unit Neurological Dysfunction with Dexmedetomidine-Induced Sleep Trial.

OBJECTIVES: This study aimed to evaluate whether a measure of subjective cognitive decline (SCD), the Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities questionnaire, was associated with postoperative delirium. It was hypothesized that delirium during the surgical hospitalization would be associated with a decrease in subjective cognition up to 6 months after cardiac surgery. DESIGN: This was a secondary analysis of data from the Minimizing Intensive Care Unit Neurological Dysfunction with Dexmedetomidine-induced Sleep randomized, placebo-controlled, parallel-arm superiority trial. SETTING: Data from patients recruited between March 2017 and February 2022 at a tertiary medical center in Boston, Massachusetts were analyzed in February 2023. PARTICIPANTS: Data from 337 patients aged 60 years or older who underwent cardiac surgery with cardiopulmonary bypass were included. INTERVENTIONS: Patients were assessed preoperatively and postoperatively at 30, 90, and 180 days using the subjective PROMIS Applied Cognition-Abilities and telephonic Montreal Cognitive Assessment. MEASUREMENT AND MAIN RESULTS: Postoperative delirium occurred within 3 days in 39 participants (11.6%). After adjusting for baseline function, participants who developed postoperative delirium self-reported worse cognitive function (mean difference [MD] -2.64 [95% CI -5.25, -0.04]; p = 0.047) up to 180 days after surgery, as compared with nondelirious patients. This finding was consistent with those obtained from objective t-MoCA assessments (MD -0.77 [95% CI -1.49, -0.04]; p = 0.04). CONCLUSIONS: In this cohort of older patients undergoing cardiac surgery, in-hospital delirium was associated with SCD up to 180 days after surgery. This finding suggested that measures of SCD may enable population-level insights into the burden of cognitive decline associated with postoperative delirium.

Red blood cell distribution width predicts mortality of adult patients receiving veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Red blood cell distribution width (RDW) is a numerical measure of the variation in the size of circulating red blood cells. Recently, there is increasing interest in the role of RDW as a biomarker for inflammatory states and as a prognostication tool for a wide range of clinical manifestations. The predictive power of RDW on mortality among patients receiving mechanical circulatory support remains largely unknown. METHODS: A retrospective analysis of 281 VA-ECMO patients at a tertiary referral academic hospital from 2009 to 2019 was performed. RDW was dichotomized with RDW-Low <14.5% and RDW-High ≥14.5%. The primary outcome was all-cause mortality at 30 days and 1 year. Cox proportional hazards models were used to examine the association between RDW and the clinical outcomes after adjusting for additional confounders. RESULTS: 281 patients were included in the analysis. There were 121 patients (43%) in the RDW-Low group and 160 patients (57%) in the RDW-High group. Survival to ECMO decannulation [RDW-H: 58% versus RDW-L: 67%, p = 0.07] were similar between the two groups. Patients in RDW-H group had higher 30-days mortality (RDW-H: 67.5% vs RDW-L: 39.7%, p < 0.001) and 1 year mortality (RDW-H: 79.4% vs RDW-L: 52.9%, p < 0.001) compared to patients in the RDW-L group. After adjusting for confounders, Cox proportional hazards model demonstrated that patients with high RDW had increased odds of mortality at 30 days (hazard ratio 1.9, 95% CI 1.2-3.0, p < 0.01) and 1 year (hazard ratio 1.9, 95% CI 1.3-2.8, p < 0.01) compared to patients with low RDW. CONCLUSIONS: Among patients receiving mechanical circulatory support with VA-ECMO, a higher RDW was independently associated with increased 30-days and 1-year mortality. RDW may serve as a simple biomarker that can be quickly obtained to help provide risk stratification and predict survival for patients receiving VA-ECMO.

Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis.

BACKGROUND: Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption. METHODS: In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV). RESULTS: In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin. CONCLUSIONS: Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021232593.

Association Between Body Mass Index and Outcomes in Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The association between obesity, or elevated body mass index (BMI), and outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been well established. Recent studies in patients receiving venovenous ECMO did not detect an association between obesity and increased mortality. The purpose of this retrospective observational study is to evaluate the association between BMI and survival in patients receiving VA-ECMO for cardiogenic shock. METHODS: All patients >18 years of age supported on VA-ECMO for refractory cardiogenic shock in a single academic center between 2009 and 2019 were included. ECMO outcomes, including successful ECMO decannulation and 30-day survival, were analyzed after stratification according to BMI. Multivariable and univariate logistic regression were used to assess the association between BMI and VA-ECMO outcomes. RESULTS: Of the total patients (n = 355) cannulated for VA-ECMO, 61.7% of the patients survived to ECMO recovery/decannulation, 45.5% of the patients survived to 30 days after ECMO decannulation, and 38.9% of the patients survived to hospital discharge with no statistically significant differences among the BMI groups. Multivariable logistic regression did not reveal any associations between obesity as defined by BMI and survival to ECMO decannulation (odds ratio [OR] 1.07 per 5 unit increase in BMI, 95% confidence interval [CI], 0.86-1.33; P = .57), 30-day survival (OR = 0.91, 95% CI, 0.73-1.14; P = .41) or survival to hospital discharge (OR = 0.95, 95% CI, 0.75-1.20; P = .66). CONCLUSIONS: Despite potential challenges to cannulation and maintaining adequate flow during ECMO, this single centered, retrospective observational study did not detect association between BMI and survival to ECMO decannulation, 30-day survival, or survival to hospital discharge for patients requiring VA-ECMO for refractory cardiogenic shock. These data suggest that obesity alone should not exclude candidacy for VA-ECMO.The primary outcome in this retrospective study was survival of the ECMO therapy (survival to ECMO decannulation), defined as surviving >24 hours after decannulation without a withdrawal of care. Secondary outcomes included survival at 30 days and survival to hospital discharge.

Inhaled Pulmonary Vasodilator Utilization and Cost Following Initiation of a Protocol in a Quaternary Academic Heart Center Intensive Care Unit.

OBJECTIVES: To examine the use of inhaled nitric oxide (iNO) and inhaled epoprostenol (iPGI2) before and after implementation of an iPGI2-preferential protocol and the associated cost differences after rollout. DESIGN: A single-center, retrospective analysis. SETTING: A quaternary university hospital. PARTICIPANTS: All patients admitted to the Heart Center Intensive Care Unit (HCICU) who required inhaled pulmonary vasodilator use between December 2017 and November 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The HCICU comprised 84% of hospital-wide iNO utilization and 59% of hospital-wide iPGI2 use across the entire study period. There was no significant difference in postsurgical HCICU admission rates across the study period. There was a significant decrease in iNO mean monthly use from 578 ± 230 to 69 ± 71 hours, and a significant concurrent increase in iPGI2 from 756 ± 443 to 1,210 ± 547 hours after the implementation of a protocol. There were no changes in the average length of ICU stay between the 2 time periods. The protocol implementation led to a projected annual savings of roughly $1,180,000. CONCLUSIONS: These findings showed that multidisciplinary protocol development and implementation can have a substantial impact on medication utilization and lead to significant reductions in cost.

Preliminary Study of Serum Biomarkers Associated With Delirium After Major Cardiac Surgery.

OBJECTIVES: The objective of this study was to identify novel serum biomarkers specific to postoperative delirium after major cardiac surgery to provide insight into the pathologic processes involved in delirium and its sequelae. DESIGN: Nested, case-control study. SETTING: Cardiac surgical intensive care unit in a single-site hospital setting. PARTICIPANTS: The study comprised 24 older adults (aged >60 years) undergoing major cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a positive screen for delirium from postoperative days one through three based on criteria included in the long form of the Confusion Assessment Method. A multiplexed proteomic approach was applied using proximity extension assays to identify and quantify proteins found in serum collected on the day of surgery and postoperative day one in delirious and nondelirious patient cohorts. An increase in serum fibroblast growth factor (FGF)-21 levels was identified in the delirious cohort from a presurgery baseline of (mean ± standard deviation) 5.0 ± 1.1 log2 abundance (95% confidence interval [CI], 4.3-5.7) to 6.7 ± 1.6 log2 abundance (95% CI, 5.7-7.7; p = 0.01) postsurgery. A similar increase was identified in FGF-23 from a presurgery baseline of 1.7 ± 1.3 log2 abundance (95% CI, 0.8-2.5) to 3.4 ± 2.2 log2 abundance (95% CI, 2.0-4.8; p = 0.06) postsurgery. An increase in interleukin-6 serum levels also was identified in the delirious cohort from a presurgery baseline of 3.8 ± 1.1 log2 abundance (95% CI, 3.1-4.5) to 8.7 ± 1.9 log2 abundance (95% CI, 7.5-9.9; p < 0.0001) postsurgery. However, the increase in interleukin-6 serum levels of the nondelirious cohort also met the study's threshold for statistical significance (p < 0.0001). Finally, an increase in monocyte chemotactic protein-3 serum levels was identified in the delirious cohort from a presurgery baseline of 4.1 ± 0.9 log2 abundance (95% CI, 3.6-4.7) to 6.1 ± 2.0 log2 abundance (95% CI, 4.8-7; p = 0.009) postsurgery. CONCLUSIONS: FGF-21, FGF-23, interleukin-6, and monocyte chemotactic protein-3 serum levels were increased postoperatively in patients who developed delirium after major cardiac surgery. This study identified two members of the FGF family as potential putative systemic biomarkers for postoperative delirium after cardiac surgery, suggesting a possible role for metabolic recovery in the pathophysiologic mechanisms underlying neurocognitive dysfunction.

Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. DESIGN: Randomized controlled trial. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. MEASUREMENTS AND MAIN RESULTS: Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median [IQR] change, 17.24 [1.11-536.77] v 101.51 [1.47-402.84] pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median [IQR], 53.92 [34.5-55.91] v 66.92 [53.03-94.44] pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median [IQR], 174.59 [73.59-446.06] v 548.22 [193.15-852.39] pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 [94.44%] v 19/22 [86.36%], p = 0.39) and hypoxemia (16/18 [88.88%] v 22/22 [100%], p = 0.11). CONCLUSIONS: Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.

Intraoperative Oxygen Practices in Cardiac Surgery: A National Survey.

OBJECTIVE: To describe the current nationwide perspectives and practice regarding intraoperative oxygen titration in cardiac surgery. DESIGN: Prospective, observational survey. SETTING: Hospitals across the United States. PARTICIPANTS: Cardiovascular anesthesiologists and perfusionists. INTERVENTIONS: Expert- and consensus-derived electronic surveys were sent to perfusionists and cardiac anesthesiologists to evaluate the current intraoperative practices around oxygen administration. Providers were asked about individual intraoperative oxygen titration practices used at different stages of cardiac surgical procedures. Anonymous responses were collected in the Research Electronic Data Capture (REDCap). MEASUREMENTS AND MAIN RESULTS: A total of 3,335 providers were invited to participate, of whom 554 (317 anesthesiologists and 237 perfusionists) were included in the final analysis (17% response rate). During cardiopulmonary bypass (CPB), perfusionists reported a median (interquartile range [IQR]) target range from 150 (110-220)-to-325 mmHg (250-400), while anesthesiologists reported a significantly lower target range from 90 (70-150)-to-250 mmHg (158-400) (p values <0.0001 and 0.02, respectively). This difference was most pronounced at lower partial pressure of arterial oxygen (PaO2) ranges. The median PaO2 considered "too low" by perfusionists was 100 mmHg (IQR 80-125), whereas it was 60 mmHg (IQR 60-75) for anesthesiologists, who reported for both off and on bypass. The median PaO2 considered "too high" was 375 mmHg (IQR 300-400) for perfusionists and 300 mmHg (IQR 200-400) for anesthesiologists. Anesthesiologists, therefore, reported more comfort with significantly lower PaO2 values (p < 0.0001), and considered a higher PaO2 value less desirable compared with perfusionists (p < 0.0001). CONCLUSIONS: This survey demonstrated there was wide variation in oxygen administration practices between perfusionists and anesthesiologists. Hyperoxygenation was more common while on CPB.

Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Intraoperative Oxygen Concentration and Neurocognition after Cardiac Surgery.

BACKGROUND: Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. METHODS: A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. CONCLUSIONS: In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

BACKGROUND: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. METHODS: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. RESULTS: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = -0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. CONCLUSIONS: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. TRIAL REGISTRATION: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393.