Evaluating tissue hypoxia and the response to fluid administration in septic shock patients: a metabolic cluster analysis.

BACKGROUND: The selection of adequate indicators of tissue hypoxia for guiding the resuscitation process of septic patients is a highly relevant issue. Current guidelines advocate for the use of lactate as sole metabolic marker, which may be markedly limited, and the integration of different variables seems more adequate. In this study, we explored the metabolic profile and its implications in the response to the administration of a fluid challenge in early septic shock patients. METHODS: Observational study including septic shock patients within 24 h of ICU admission, monitored with a cardiac output estimation system, with ongoing resuscitation. Hemodynamic and metabolic variables were measured before and after a fluid challenge (FC). A two-step cluster analysis was used to define the baseline metabolic profile, including lactate, central venous oxygen saturation (ScvO2), central venous-to-arterial carbon dioxide difference (PcvaCO2), and PcvaCO2 corrected by the difference in arterial-to-venous oxygen content (PcvaCO2/CavO2). RESULTS: Seventy-seven fluid challenges were analyzed. Cluster analysis revealed two distinct metabolic profiles at baseline. Cluster A exhibited lower ScvO2, higher PcvaCO2, and lower PcvaCO2/CavO2. Increases in cardiac output (CO) were associated with increases in VO2 exclusively in cluster A. Baseline isolated metabolic variables did not correlate with VO2 response, and changes in ScvO2 and PcvaCO2 were associated to VO2 increase only in cluster A. CONCLUSIONS: In a population of early septic shock patients, two distinct metabolic profiles were identified, suggesting tissue hypoxia or dysoxia. Integrating metabolic variables enhances the ability to detect those patients whose VO2 might increase as results of fluid administration.

Characterization of postintensive care syndrome in a prospective cohort of survivors of COVID-19 critical illness: a 12-month follow-up study.

PURPOSE: Studies integrating an exhaustive longitudinal long-term follow-up of postintensive care syndrome (PICS) in critically ill COVID-19 survivors are scarce. We aimed to 1) describe PICS-related sequelae over a 12-month period after intensive care unit (ICU) discharge, 2) identify relevant demographic and clinical factors related to PICS, and 3) explore how PICS-related sequelae may influence health-related quality of life (HRQoL) in critically ill COVID-19 survivors. METHODS: We conducted a prospective cohort study in adult critically ill survivors of SARS-CoV-2 infection that did or did not need invasive mechanical ventilation (IMV) during the COVID-19 pandemic in Spain (March 2020 to January 2021). We performed a telemedicine follow-up of PICS-related sequelae (physical/functional, cognitive, and mental health) and HRQoL with five data collection points. We retrospectively collected demographic and clinical data. We used multivariable mixed-effects models for data analysis. RESULTS: We included 142 study participants in the final analysis, with a median [interquartile range] age of 61 [53-68] yr; 35% were female and 59% needed IMV. Fatigue/dyspnea, pain, impaired muscle function, psychiatric symptomatology and reduced physical HRQoL were prominent sequelae early after ICU discharge. Over the 12-month follow-up, functionality and fatigue/dyspnea improved progressively, while pain remained stable. We observed slight fluctuations in anxiety symptoms and perception of cognitive deficit, whereas posttraumatic stress disorder (PTSD) and depressive symptoms improved, with a mild rebound at the end of the follow-up. Female sex, younger age, and the need for IMV were risk factors for PICS, while having higher cognitive reserve was a potential protective factor. Physical HRQoL scores showed a general improvement over time, whereas mental HRQoL remained stable. Shorter ICU stay, better functionality, and lower scores for fatigue/dyspnea and pain were associated with better physical HRQoL, while lower scores for anxiety, depression, and PTSD were associated with better mental HRQoL. CONCLUSIONS: Postintensive care syndrome was common in COVID-19 critical illness survivors and persisted in a significant proportion of patients one year after ICU discharge, impacting HRQoL. The presence of risk factors for PICS may identify patients who are more likely to develop the condition and who would benefit from more specific and closer follow-up after ICU admission. STUDY REGISTRATION: ClinicalTrials.gov ( NCT04422444 ); first submitted 9 June 2020.

RéSUMé: OBJECTIF: Les études intégrant un suivi longitudinal exhaustif à long terme des syndromes post-soins intensifs (SPSI) chez les survivant·es gravement malades de la COVID-19 sont rares. Notre objectif était 1) de décrire les séquelles liées au SPSI sur une période de 12 mois après la sortie de l'unité de soins intensifs (USI), 2) d'identifier les facteurs démographiques et cliniques pertinents liés au SPSI, et 3) d'explorer comment les séquelles liées au SPSI peuvent influencer la qualité de vie liée à la santé (QVLS) chez les survivant·es gravement malades de la COVID-19. MéTHODE: Nous avons mené une étude de cohorte prospective chez des adultes gravement malades survivant·es d'une infection par le SRAS-CoV-2 qui ont eu ou non besoin d'une ventilation mécanique invasive (VMI) pendant la pandémie de COVID-19 en Espagne (mars 2020 à janvier 2021). Nous avons effectué un suivi par télémédecine des séquelles liées au SPSI (santé physique/fonctionnelle, cognitive et mentale) et à la QVLS avec cinq points de collecte de données. Nous avons rétrospectivement colligé des données démographiques et cliniques. Des modèles multivariés à effets mixtes ont été utilisés pour l'analyse des données. RéSULTATS: Nous avons inclus 142 participant·es à l'étude dans l'analyse finale, avec un âge médian [intervalle interquartile] de 61 [53-68] ans; 35 % étaient des femmes et 59 % avaient besoin de VMI. La fatigue/dyspnée, la douleur, l'altération de la fonction musculaire, la symptomatologie psychiatrique et la réduction de la QVLS physique étaient des séquelles importantes peu après la sortie de l'USI. Au cours du suivi de 12 mois, la fonctionnalité et la fatigue/dyspnée se sont améliorées progressivement, tandis que la douleur est restée stable. Nous avons observé de légères fluctuations des symptômes d'anxiété et de perception du déficit cognitif, tandis que le trouble de stress post-traumatique (ESPT) et les symptômes dépressifs se sont améliorés, avec un léger rebond à la fin du suivi. Le sexe féminin, un jeune âge et le besoin de VMI étaient des facteurs de risque de SPSI, tandis qu'une réserve cognitive plus élevée était un facteur potentiel de protection. Les scores physiques de la QVLS ont montré une amélioration générale au fil du temps, tandis que la QVLS mentale est restée stable. Un séjour plus court aux soins intensifs, une meilleure fonctionnalité et des scores plus faibles pour la fatigue/dyspnée et la douleur étaient associés à une meilleure QVLS physique, tandis que des scores plus faibles pour l'anxiété, la dépression et le ESPT étaient associés à une meilleure QVLS mentale. CONCLUSION: Le syndrome post-soins intensifs était fréquent chez les survivant·es d'une maladie grave de la COVID-19 et a persisté chez une proportion importante de patient·es un an après leur sortie de l'unité de soins intensifs, ce qui a eu un impact sur la QVLS. La présence de facteurs de risque de SPSI peut identifier les patient·es qui sont plus susceptibles de développer la maladie et qui bénéficieraient d'un suivi plus spécifique et plus étroit après leur admission aux soins intensifs. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT04422444 ); première soumission le 9 juin 2020.

Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge: the role of demographic, clinical, and emotional factors.

BACKGROUND: Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits. METHODS: Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively. RESULTS: Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment. CONCLUSIONS: One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021.

Central venous-to-arterial carbon dioxide difference combined with arterial-to-venous oxygen content difference is associated with lactate evolution in the hemodynamic resuscitation process in early septic shock.

INTRODUCTION: Since normal or high central venous oxygen saturation (ScvO2) values cannot discriminate if tissue perfusion is adequate, integrating other markers of tissue hypoxia, such as central venous-to-arterial carbon dioxide difference (PcvaCO2 gap) has been proposed. In the present study, we aimed to evaluate the ability of the PcvaCO2 gap and the PcvaCO2/arterial-venous oxygen content difference ratio (PcvaCO2/CavO2) to predict lactate evolution in septic shock. METHODS: Observational study. Septic shock patients within the first 24 hours of ICU admission. After restoration of mean arterial pressure, and central venous oxygen saturation, the PcvaCO2 gap and the PcvaCO2/CavO2 ratio were calculated. Consecutive arterial and central venous blood samples were obtained for each patient within 24 hours. Lactate improvement was defined as the decrease ≥ 10% of the previous lactate value. RESULTS: Thirty-five septic shock patients were studied. At inclusion, the PcvaCO2 gap was 5.6 ± 2.1 mmHg, and the PcvaCO2/CavO2 ratio was 1.6 ± 0.7 mmHg · dL/mL O2. Those patients whose lactate values did not decrease had higher PcvaCO2/CavO2 ratio values at inclusion (1.8 ± 0.8vs. 1.4 ± 0.5, p 0.02). During the follow-up, 97 paired blood samples were obtained. No-improvement in lactate values was associated to higher PcvaCO2/CavO2 ratio values in the previous control. The ROC analysis showed an AUC 0.82 (p < 0.001), and a PcvaCO2/CavO2 ratio cut-off value of 1.4 mmHg · dL/mL O2 showed sensitivity 0.80 and specificity 0.75 for lactate improvement prediction. The odds ratio of an adequate lactate clearance was 0.10 (p < 0.001) in those patients with an elevated PcvaCO2/CavO2 ratio (≥1.4). CONCLUSION: In a population of septic shock patients with normalized MAP and ScvO2, the presence of elevated PcvaCO2/CavO2 ratio significantly reduced the odds of adequate lactate clearance during the following hours.

Thenar oxygen saturation (StO2) alterations during a spontaneous breathing trial predict extubation failure.

BACKGROUND: Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring the regional oxygenation status has shown promising results in predicting the tolerance to spontaneously breathe in the process of weaning from MV. Our aim was to determine whether changes in skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) on the thenar eminence during a vascular occlusion test (VOT) can be used to predict extubation failure from mechanical ventilation. METHODS: We prospectively studied 206 adult patients with acute respiratory failure receiving MV for at least 48 h from a 30-bed mixed ICU, who were deemed ready to wean by their physicians. Patients underwent a 30-min spontaneous breathing trial (SBT), and were extubated according to the local protocol. Continuous StO2 was measured non-invasively on the thenar eminence. A VOT was performed prior to and at 30 min of the SBT (SBT30). The rate of StO2 deoxygenation (DeO2), StO2 reoxygenation (ReO2) rate and StO2 hyperemic response to ischemia (HAUC) were calculated. RESULTS: Thirty-six of the 206 patients (17%) failed their SBT. The remainder 170 patients (83%) were extubated. Twenty-three of these patients (13.5%) needed reinstitution of MV within 24 h. Reintubated patients displayed a lower HAUC at baseline, and higher relative changes in their StO2 deoxygenation rate between baseline and SBT30 (DeO2 Ratio). A logistic regression-derived StO2 score, combining baseline StO2, HAUC and DeO2 ratio, showed an AUC of 0.84 (95% CI 0.74-0.91) for prediction of extubation failure. CONCLUSIONS: Extubation failure was associated to baseline and dynamic StO2 alterations during the SBT. Monitoring StO2-derived parameters might be useful in predicting extubation outcome.

Trends in the incidence and mortality of patients with community-acquired septic shock 2003-2016.

PURPOSE: To evaluate the incidence and mortality of adult patients with community-acquired septic shock (CASS) and the influence of source control (SC) and other risk factors on the outcome. MATERIAL AND METHODS: The study included patients with CASS admitted to the ICU at a university hospital (2003-2016). Multivariate analyses were performed to identify risk factors of ICU mortality. RESULTS: A total of 625 patients were included. The incidence showed an average annual increase of 4.9% and the mortality an average annual decrease of 1.4%. The patients who required SC showed a lower mortality (20.4%) than patients who did not require SC (31.3%) (p = 0.002). However, the evolution in mortality was different: Mortality decreased in patients who did not require SC (from 56.3% to 20%; p = 0.02), but did not differ in those who required SC (from 21.4% to 27.6%; p = 0.43). In the multivariate analysis, severity at admission, age, alcoholism, cirrhosis, ARDS, neutropenia and thrombocytopenia were associated with worse outcome, whereas appropriate antibiotic treatment and adequate SC were independently associated with better survival. CONCLUSIONS: The incidence of CASS increased and the ICU mortality decreased during the study period. The mortality was mainly due to a decrease in mortality in infections not requiring SC.

Thenar oxygen saturation and invasive oxygen delivery measurements in critically ill patients in early septic shock.

This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO2) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO2) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. Interventions included transient ischemic challenge on the forearm. After blood pressure normalization, hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO2 and its changes from ischemic challenge (deoxygenation and reoxygenation rates) were measured. Fifteen patients were studied. All the patients had a mean arterial pressure above 65 mmHg. The DO2 index (iDO2) range in the studied population was 215 to 674 mL O2/min per m. The mean mixed venous oxygen saturation value was 61% ± 10%, mean cardiac index was 3.4 ± 0.9 L/min per m, and blood lactate level was 4.6 ± 2.7 mmol/L. Steady-state StO2 significantly correlated with iDO2, arterial and venous O2 content, and O2 extraction ratio. A StO2 cutoff value of 75% predicted iDO2 below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO2 reflects extremely low iDO2. Steady-state StO2 does not correlate with moderately low iDO2, indicating poor sensitivity of StO2 to rule out hypoperfusion.