Characterizing the Relationship Between Arterial Carbon Dioxide Trajectory and Serial Brain Biomarkers with Central Nervous System Injury During Veno-Venous Extracorporeal Membrane Oxygenation: A Prospective Cohort Study.

BACKGROUND: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure of arterial carbon dioxide (PaCO2) following VV-ECMO initiation has been suggested as an etiological factor, but the challenges of diagnosing CNS injuries has made discerning a relationship between PaCO2 and CNS injury difficult. METHODS: We conducted a prospective cohort study of adult patients undergoing VV-ECMO for acute respiratory failure. Arterial blood gas measurements were obtained prior to initiation of VV-ECMO, and at every 2-4 h for the first 24 h. Neuroimaging was conducted within the first 7-14 days in patients who were suspected of having neurological injury or unable to be examined because of sedation. We collected blood biospecimens to measure brain biomarkers [neurofilament light (NF-L); glial fibrillary acidic protein (GFAP); and phosphorylated-tau 181] in the first 7 days following initiation of VV-ECMO. We assessed the relationship between both PaCO2 over the first 24 h and brain biomarkers with CNS injury using mixed methods linear regression. Finally, we explored the effects of absolute change of PaCO2 on serum levels of neurological biomarkers by separate mixed methods linear regression for each biomarker using three PaCO2 exposures hypothesized to result in CNS injury. RESULTS: In our cohort, 12 of 59 (20%) patients had overt CNS injury identified on head computed tomography. The PaCO2 decrease with VV-ECMO initiation was steeper in patients who developed a CNS injury (- 0.32%, 95% confidence interval - 0.25 to - 0.39) compared with those without (- 0.18%, 95% confidence interval - 0.14 to - 0.21, P interaction < 0.001). The mean concentration of NF-L increased over time and was higher in those with a CNS injury (464 [739]) compared with those without (127 [257]; P = 0.001). GFAP was higher in those with a CNS injury (4278 [11,653] pg/ml) compared with those without (116 [108] pg/ml; P < 0.001). The mean NF-L, GFAP, and tau over time in patients stratified by the three thresholds of absolute change of PaCO2 showed no differences and had no significant interaction for time. CONCLUSIONS: Although rapid decreases in PaCO2 following initiation of VV-ECMO were slightly greater in patients who had CNS injuries versus those without, data overlap and absence of relationships between PaCO2 and brain biomarkers suggests other pathophysiologic variables are likely at play.

Extracorporeal life support in trauma: Indications and techniques.

BACKGROUND: Clarity about indications and techniques in extracorporeal life support (ECLS) in trauma is essential for timely and effective deployment, and to ensure good stewardship of an important resource. Extracorporeal life support deployments in a tertiary trauma center were reviewed to understand the indications, strategies, and tactics of ECLS in trauma. METHODS: The provincial trauma registry was used to identify patients who received ECLS at a Level I trauma center and ECLS organization-accredited site between January 2014 and February 2021. Charts were reviewed for indications, technical factors, and outcomes following ECLS deployment. Based on this data, consensus around indications and techniques for ECLS in trauma was reached and refined by a multidisciplinary team discussion. RESULTS: A total of 25 patients underwent ECLS as part of a comprehensive trauma resuscitation strategy. Eighteen patients underwent venovenous ECLS and seven received venoarterial ECLS. Nineteen patients survived the ECLS run, of which 15 survived to discharge. Four patients developed vascular injuries secondary to cannula insertion while four patients developed circuit clots. On multidisciplinary consensus, three broad indications for ECLS and their respective techniques were described: gas exchange for lung injury, extended damage control for severe injuries associated with the lethal triad, and circulatory support for cardiogenic shock or hypothermia. CONCLUSION: The three broad indications for ECLS in trauma (gas exchange, extended damage control and circulatory support) require specific advanced planning and standardization of corresponding techniques (cannulation, circuit configuration, anticoagulation, and duration). When appropriately and effectively integrated into the trauma response, ECLS can extend the damage control paradigm to enable the management of complex multisystem injuries. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Hypoxemia During One-Lung Ventilation: Does It Really Matter?

PURPOSE OF REVIEW: Hypoxemia during one-lung ventilation, while decreasing in frequency, persists as an intraoperative challenge for anesthesiologists. Discerning when desaturation and resultant hypoxemia correlates to tissue hypoxia is challenging in the perioperative setting and requires a thorough understanding of the physiology of oxygen delivery and tissue utilization. RECENT FINDINGS: Oxygen delivery is not directly correlated with peripheral oxygen saturation in patients undergoing one-lung ventilation, emphasizing the importance of hemoglobin concentration and cardiac output in avoiding tissue hypoxia. While healthy humans can tolerate acute hypoxemia without long-term consequences, there is a paucity of evidence from patients undergoing thoracic surgery. Increasingly recognized is the potential harm of hyperoxic states, particularly in the setting of complex patients with comorbid diseases. SUMMARY: Anesthesiologists are left to determine an acceptable oxygen saturation nadir that is individualized to the patient and procedure based on an understanding of oxygen supply, demand, and the consequences of interventions.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

Vancouver General Hospital Pulmonary Embolism Response Team (VGH PERT): initial three-year experience.

PURPOSE: Clinical equipoise exists with the use of novel reperfusion therapies such as catheter-directed thrombolysis in the management of patients presenting to hospital with high risk pulmonary embolism (PE). Therapeutic options rely on clinical presentation, patient factors, physician preference, and institutional availability. We established a Pulmonary Embolism Response Team (PERT) to provide urgent assessment and multidisciplinary care for patients presenting to our institution with high-risk PE. METHODS: Data were retrospectively collected from PERT activations between January 2016 and December 2018. Chi square tests were used to determine differences in mortality across the three years of study. Logistic regression was used to evaluate 30- and 90-day mortality and occurrence of major bleeds between those receiving anticoagulation alone (AC) and those receiving advanced reperfusion therapy (ART). RESULTS: There were 128 PERT activations over three years, the majority originating from the emergency department. Eighty-five percent of activations were for submassive PE, with 56% of all activations assessed as submassive-high risk. Fifteen patients (12%) presented with massive PE. Advanced reperfusion therapy was used in 29 (23%) patients, of whom 25 (20%) received catheter-directed thrombolysis. There was an increased risk of major bleeding in the ART group compared with in the AC group (odds ratio [OR], 17.9; 95% confidence interval [CI], 4.1 to 125.0; P < 0.001), but no increased risk of mortality at 30 days (OR, 2.1; 95% CI, 0.4 to 9.1; P = 0.3). The 30-day mortality rate was 7.8%. CONCLUSION: We describe the first Canadian PERT, a multidisciplinary team aimed at providing urgent individualized care for patients with high-risk PE. Further research is necessary to determine whether a PERT improves clinical outcomes.

RéSUMé: OBJECTIF: Le concept d'équilibre clinique existe lors de l'utilisation de traitements innovants de reperfusion tels que la thrombolyse in situ (ou thrombolyse par cathéter) pour la prise en charge des patients se présentant à l'hôpital avec une embolie pulmonaire (EP) à haut risque. Les options thérapeutiques s'appuient sur la présentation clinique, les caractéristiques du patient, la préférence du médecin et la disponibilité institutionnelle. Nous avons mis sur pied une Équipe d'intervention en cas d'embolie pulmonaire (PERT - Pulmonary Embolism Response Team) afin de fournir une évaluation urgente et des soins multidisciplinaires aux patients se présentant dans notre institution avec une EP à haut risque. MéTHODE: Nous avons récolté rétrospectivement les données concernant les activations/alertes reçues par notre PERT entre janvier 2016 et décembre 2018. Des tests de chi carré ont été utilisés afin de déterminer les différences en matière de mortalité au cours des trois années de durée de l'étude. La régression logistique a été utilisée pour évaluer la mortalité à 30 et à 90 jours ainsi que la survenue de saignements majeurs entre les patients recevant uniquement un traitement anticoagulant (AC) et ceux recevant un traitement de reperfusion avancé (TRA). RéSULTATS: Il y a eu 128 alertes requérant l'activation de notre PERT en trois ans, la majorité provenant de l'urgence. Quatre-vingt-cinq pour cent des activations concernaient des EP submassives, et 56 % de toutes les activations ont été évaluées comme étant submassives à haut risque. Quinze patients (12 %) se sont présentés avec une EP massive. Un traitement de reperfusion avancé a été administré à 29 (23 %) patients, parmi lesquels 25 (20 %) ont reçu une thrombolyse in situ. Un risque accru de saignement majeur a été observé dans le groupe TRA par rapport au groupe AC (rapport de cotes [RC], 17,9; intervalle de confiance [IC] 95 %, 4,1 à 125,0; P < 0,001), mais il n'y avait pas de risque accru de mortalité à 30 jours (RC, 2,1; IC 95 %, 0,4 à 9,1; P = 0,3). Le taux de mortalité à 30 jours était de 7,8 %. CONCLUSION: Nous décrivons la première PERT canadienne, une équipe multidisciplinaire ayant pour but de prodiguer des soins personnalisés urgents aux patients avec embolie pulmonaire à haut risque. Des recherches supplémentaires sont nécessaires pour déterminer si une PERT améliore les pronostics cliniques.

Utilization of electroencephalogram post cardiac arrest in the United States: A nationwide retrospective cohort analysis.

OBJECTIVE: The use of electroencephalogram (EEG) has been demonstrated to have diagnostic and prognostic value in cardiac arrest patients. The use of this modality across the United States in this population is unknown. METHODS: The Nationwide Inpatient Sample (NIS) is a federal database capturing 20% of all US hospital admissions. A cohort of patients who suffered both in and out of hospital cardiac arrests from the 2006 to 2012 NIS datasets was created. RESULTS: The records of 55,208,382 hospitalizations were analyzed, of which 207,703 patients suffered a cardiac arrest. There were 2952 (1.42%) patients who also had an EEG. Patients who had an EEG compared to those who did not were: younger (62.2 years SD 16.6 vs 66.9 years SD 16.2, p<0.01), were less likely to have insurance coverage (89.9% vs 91.6%, p=0.03) and had significantly longer length of stay (8.6days IQR 3.7-17.1 vs 4.1days IQR 1.0-10.5, p<0.01). Patients treated at urban teaching hospitals were more likely to receive an EEG than patients treated at urban non-teaching and rural hospitals (p<0.01). The rate of EEG in survivors of cardiac arrest increased from 1.03% in 2006 to 2.16% in 2012, a relative increase of 110% (p<0.02). The median time to performance of an EEG was 1.6days IQR 0.33-4.53 days. CONCLUSION: EEG is performed on approximately 2% of patients who suffer cardiac arrest in the United States. The treatment hospital and patient characteristics of those who received an EEG different from those who did not.

Impact of hospital case-volume on subarachnoid hemorrhage outcomes: A nationwide analysis adjusting for hemorrhage severity.

OBJECTIVE: There have been suggestions that patients with subarachnoid hemorrhage (SAH) have a better outcome when treated in high-volume centers. Much of the published literature on the subject is limited by an inability to control for severity of SAH. METHODS: This is a nationwide retrospective cohort analysis using the Nationwide Inpatient Sample (NIS). The NIS Subarachnoid Severity Scale was used to adjust for severity of SAH in multivariate logistic regression modeling. RESULTS: The records of 47 911 414 hospital admissions from the 2006-2011 NIS samples were examined. There were 11 607 patients who met inclusion criteria for the study. Of these, 7787 (67.0%) were treated at a high-volume center compared with 3820 (32.9%) treated at a low-volume center. Patients treated at high-volume centers compared with low-volume centers were more likely to receive endovascular aneurysm control (58.5% vs 51.2%, P=.04), be transferred from another hospital (35.4% vs 19.7%, P<.01), be treated in a teaching facility (97.3% vs 72.9%, P<.01), and have a longer length of stay (14.9 days [interquartile range 10.3-21.7] vs 13.9 days [interquartile range, 8.9-20.1], P<.01). After adjustment for all baseline covariates, including severity of SAH, treatment in a high-volume center was associated with an odds ratio for death of 0.82 (95% confidence interval, 0.72-0.95; P<.01) and a higher odds of a good functional outcome (odds ratio, 1.16; 95% confidence interval, 1.04-1.28; P<.01). CONCLUSION: After adjustment for severity of SAH, treatment in a high-volume center was associated with a lower risk of in-hospital mortality and a higher odds of a good functional outcome.

An adaptation study of internal and external features in facial representations.

Prior work suggests that internal features contribute more than external features to face processing. Whether this asymmetry is also true of the mental representations of faces is not known. We used face adaptation to determine whether the internal and external features of faces contribute differently to the representation of facial identity, whether this was affected by familiarity, and whether the results differed if the features were presented in isolation or as part of a whole face. In a first experiment, subjects performed a study of identity adaptation for famous and novel faces, in which the adapting stimuli were whole faces, the internal features alone, or the external features alone. In a second experiment, the same faces were used, but the adapting internal and external features were superimposed on whole faces that were ambiguous to identity. The first experiment showed larger aftereffects for unfamiliar faces, and greater aftereffects from internal than from external features, and the latter was true for both familiar and unfamiliar faces. When internal and external features were presented in a whole-face context in the second experiment, aftereffects from either internal or external features was less than that from the whole face, and did not differ from each other. While we reproduce the greater importance of internal features when presented in isolation, we find this is equally true for familiar and unfamiliar faces. The dominant influence of internal features is reduced when integrated into a whole-face context, suggesting another facet of expert face processing.