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1.
Eur Heart J ; 45(18): 1613-1630, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38596850

ABSTRACT

BACKGROUND AND AIMS: Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe. METHODS: In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis. RESULTS: Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments. CONCLUSIONS: In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.


Subject(s)
Positron Emission Tomography Computed Tomography , Humans , Female , Male , Middle Aged , Prognosis , Positron Emission Tomography Computed Tomography/methods , Aged , Europe/epidemiology , Cardiovascular Diseases/mortality , Brain/diagnostic imaging , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Heart/diagnostic imaging
2.
N Engl J Med ; 384(14): 1301-1311, 2021 04 08.
Article in English | MEDLINE | ID: mdl-33471452

ABSTRACT

BACKGROUND: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONS: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).


Subject(s)
Oxygen Inhalation Therapy/methods , Oxygen/administration & dosage , Oxygen/blood , Respiratory Insufficiency/therapy , Aged , Female , Humans , Hypoxia/blood , Hypoxia/etiology , Hypoxia/therapy , Intensive Care Units , Kaplan-Meier Estimate , Male , Middle Aged , Respiration, Artificial/methods , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/blood , Respiratory Insufficiency/complications , Respiratory Insufficiency/mortality
3.
Crit Care ; 28(1): 61, 2024 02 26.
Article in English | MEDLINE | ID: mdl-38409034

ABSTRACT

BACKGROUND: To assess the frequency, risk factors, consequences, and prevention of violence against healthcare workers in intensive care units. METHODS: PubMed, Scopus, Google Scholar, EMBASE, Cochrane, and Web of Science were searched for studies on violence against healthcare workers in adult intensive care units. Risk factors, patient characteristics, and implications for healthcare workers were collected. Study quality, bias, and level of evidence were assessed using established tools. RESULTS: Seventy-five studies with 139,533 healthcare workers from 32 countries were included. The overall median frequency of violence was 51% (IQR 37-75%). Up to 97% of healthcare workers experienced verbal violence, and up to 82% were victims of physical violence. Meta-analysis of frequency revealed an average frequency of 31% (95% CI 22-41%) for physical violence, 57% for verbal violence (95% CI 48-66%), and 12% for sexual violence (95% CI 4-23%). Heterogeneity was high according to the I2 statistics. Patients were the most common perpetrators (median 56%), followed by visitors (median 22%). Twenty-two studies reported increased risk ratios of up to 2.3 or odds ratios of up to 22.9 for healthcare workers in the ICU compared to other healthcare workers. Risk factors for experiencing violence included young age, less work experience, and being a nurse. Patients who exhibited violent behavior were often male, older, and physically impaired by drugs. Violence was underreported in up to 80% of cases and associated with higher burnout rates, increased anxiety, and higher turnover intentions. Overall the level of evidence was low. CONCLUSIONS: Workplace violence is frequent and underreported in intensive care units, with potential serious consequences for healthcare workers, calling for heightened awareness, screening, and preventive measures. The potential risk factors for violence should be further investigated. SYSTEMATIC REVIEW REGISTRATION: The protocol for this review was registered with Prospero on January 15, 2023 (ID CRD42023388449).


Subject(s)
Health Personnel , Workplace Violence , Adult , Humans , Male , Workplace Violence/prevention & control , Aggression , Intensive Care Units , Delivery of Health Care
4.
Crit Care ; 28(1): 209, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937819

ABSTRACT

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations. METHODS: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022. RESULTS: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17). CONCLUSION: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.


Subject(s)
Intensive Care Units , Organ Dysfunction Scores , Sepsis , Shock, Septic , Humans , Female , Male , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Middle Aged , Aged , Retrospective Studies , Sepsis/classification , Sepsis/physiopathology , Sepsis/diagnosis , Sepsis/mortality , Shock, Septic/physiopathology , Shock, Septic/mortality , Shock, Septic/classification , Shock, Septic/diagnosis , Switzerland/epidemiology , Sex Factors , Prospective Studies , Adult
5.
Euro Surveill ; 29(2)2024 Jan.
Article in English | MEDLINE | ID: mdl-38214079

ABSTRACT

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.


Subject(s)
COVID-19 , Female , Humans , Male , Adult , Middle Aged , COVID-19/epidemiology , Post-Acute COVID-19 Syndrome , Switzerland/epidemiology , Prospective Studies , SARS-CoV-2 , Disease Progression
6.
JAMA ; 331(14): 1185-1194, 2024 04 09.
Article in English | MEDLINE | ID: mdl-38501214

ABSTRACT

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.


Subject(s)
COVID-19 , Adult , Humans , Male , Aged , Female , COVID-19/therapy , COVID-19/etiology , Oxygen , Respiration, Artificial , Oxygen Inhalation Therapy/methods , Hypoxia/etiology , Hypoxia/therapy
7.
Crit Care ; 27(1): 14, 2023 01 12.
Article in English | MEDLINE | ID: mdl-36635740

ABSTRACT

BACKGROUND: Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland. METHODS: Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019. RESULTS: Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (- 6.4% in women versus - 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10-1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94-1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85-0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94-1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions. CONCLUSION: Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed.


Subject(s)
Myocardial Infarction , Stroke , Male , Humans , Female , Retrospective Studies , Hospital Mortality , Myocardial Infarction/therapy , Stroke/therapy , Critical Care , Sex Factors
8.
Crit Care ; 27(1): 308, 2023 08 05.
Article in English | MEDLINE | ID: mdl-37543625

ABSTRACT

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.


Subject(s)
Status Epilepticus , Male , Humans , Adult , Female , Retrospective Studies , Treatment Outcome , Status Epilepticus/epidemiology , Status Epilepticus/drug therapy , Patients , Academic Medical Centers , Anticonvulsants/therapeutic use
9.
J Clin Monit Comput ; 37(1): 179-188, 2023 02.
Article in English | MEDLINE | ID: mdl-35665876

ABSTRACT

In vitro studies have thoroughly documented age-dependent impact of storage lesions in packed red blood cells (pRBC) on erythrocyte oxygen carrying capacity. While studies have examined the effect of pRBC age on patient outcome only few data exist on the microcirculation as their primary site of action. In this secondary analysis we examined the relationship between age of pRBC and changes of microcirculatory flow (MCF) in 54 patients based on data from the Basel Bedside assessment Microcirculation Transfusion Limit study (Ba2MiTraL) on effects of pRBC on sublingual MCF. Mean change from pre- to post-transfusion proportion of perfused vessels (∆PPV) was + 8.8% (IQR - 0.5 to 22.5), 5.5% (IQR 0.1 to 10.1), and + 4.7% (IQR - 2.1 to 6.5) after transfusion of fresh (≤ 14 days old), medium (15 to 34 days old), and old (≥ 35 days old) pRBC, respectively. Values for the microcirculatory flow index (MFI) were + 0.22 (IQR - 0.1 to 0.6), + 0.22 (IQR 0.0 to 0.3), and + 0.06 (IQR - 0.1 to 0.3) for the fresh, medium, and old pRBC age groups, respectively. Lower ∆PPV and transfusion of older blood correlated with a higher Sequential Organ Failure Assessment (SOFA) score of patients upon admission to the intensive care unit (ICU) (p = 0.01). However, regression models showed no overall significant correlation between pRBC age and ∆PPV (p = 0.2). Donor or recipient sex had no influence. We detected no significant effect of pRBC on microcirculation. Patients with a higher SOFA score upon ICU admission might experience a negative effect on the ∆PPV after transfusion of older blood.


Subject(s)
Critical Illness , Erythrocyte Transfusion , Humans , Retrospective Studies , Microcirculation , Mouth Floor , Intensive Care Units , Erythrocytes
10.
Br J Anaesth ; 129(5): 659-669, 2022 11.
Article in English | MEDLINE | ID: mdl-36184294

ABSTRACT

BACKGROUND: Portal vein Doppler ultrasound pulsatility measured by transoesophageal echocardiography is a marker of the haemodynamic impact of venous congestion in cardiac surgery. We investigated whether the presence of abnormal portal vein flow pulsatility is associated with a longer duration of invasive life support and postoperative complications in high-risk patients. METHODS: In this multicentre cohort study, pulsed-wave Doppler ultrasound assessments of portal vein flow were performed during anaesthesia before initiation of cardiopulmonary bypass (before CPB) and after separation of cardiopulmonary bypass (after CPB). Abnormal pulsatility was defined as portal pulsatility fraction (PPF) ≥50% (PPF50). The primary outcome was the cumulative time in perioperative organ dysfunction (TPOD) requiring invasive life support during 28 days. Secondary outcomes included major postoperative complications. RESULTS: 373 patients, 71 (22.0%) had PPF50 before CPB and 77 (24.9%) after CPB. PPF50 was associated with longer duration of TPOD (median [inter-quartile range]; before CPB: 27 h [11-72] vs 19 h [8.5-42], P=0.02; after CPB: 27 h [11-61] vs 20 h [8-42], P=0.006). After adjusting for confounders, PPF50 before CPB showed significant association with TPOD. PPF50 after CPB was associated with a higher rate of major postoperative complications (36.4% vs 20.3%, P=0.006). CONCLUSIONS: Abnormal portal vein flow pulsatility before cardiopulmonary bypass was associated with longer duration of life support therapy after cardiac surgery in high-risk patients. Abnormal portal vein flow pulsatility after cardiopulmonary bypass separation was associated with a higher risk of major postoperative complications although this association was not independent of other factors. CLINICAL TRIAL REGISTRATION: NCT03656263.


Subject(s)
Cardiac Surgical Procedures , Portal Vein , Humans , Portal Vein/diagnostic imaging , Prospective Studies , Cohort Studies , Cardiac Surgical Procedures/adverse effects , Ultrasonography, Doppler , Postoperative Complications/etiology
11.
Can J Anaesth ; 68(1): 130-136, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33063295

ABSTRACT

PURPOSE: Transcranial Doppler (TCD) ultrasound is a non-invasive monitor of cerebral blood velocity that can be used intraoperatively. The purpose of this report is to describe how different patterns seen on TCD can help identify the cause of cerebral desaturation when near-infrared spectroscopy (NIRS) oximetry is used concomitantly. CLINICAL FEATURES: A 69-yr-old male patient undergoing coronary revascularisation and aortic valve replacement developed perioperative complications that were detected using a combination of transtemporal TCD of the middle cerebral artery along with cerebral and somatic NIRS. Initial brain desaturation was secondary to hypocapnia during which TCD-derived blood velocity and somatic NIRS values remained unchanged. After the procedure, a second episode of brain desaturation occurred secondary to a technical issue with the aortic valve prosthesis requiring a return to cardiopulmonary bypass (CPB); there were no high-intensity transient signals (HITS) on TCD. Brain desaturation occurred a third time following the second attempt to separate from CPB at which time TCD detected a significant amount of HITS suggesting air emboli that were associated with acute right ventricular dysfunction; there was also a reduction in somatic NIRS. CONCLUSIONS: Combining TCD with cerebral NIRS allows for the rapid identification of three different mechanisms of brain desaturation. An algorithm is proposed to help identify the origin of NIRS cerebral desaturation. Prospective clinical trials are needed to investigate potential benefits of multimodal brain monitoring and its impact on short and/or long-term clinical outcomes.


RéSUMé: OBJECTIF: L'échographie par Doppler transcrânien (DTC) est un moniteur non invasif de la vélocité sanguine cérébrale qui peut être utilisé en période peropératoire. L'objectif de ce compte rendu est de décrire comment différents tracés observés sur le DTC peuvent aider l'anesthésiologiste à identifier la cause de la désaturation cérébrale lorsque l'oxymétrie par spectroscopie proche infrarouge (SPIR) est utilisée de manière concomitante. ÉLéMENTS CLINIQUES: Un homme de 69 ans subissant une revascularisation coronarienne et un remplacement de valve aortique a présenté des complications périopératoires détectées grâce à la combinaison d'un DTC trans-temporal de l'artère cérébrale moyenne et d'une SPIR cérébrale et somatique. La désaturation cérébrale initiale était secondaire à une hypocapnie, pendant laquelle la vélocité sanguine dérivée du DTC et les valeurs de SPIR somatique sont demeurées inchangées. Après l'intervention, un deuxième épisode de désaturation cérébrale est survenu suite à un problème technique avec la prothèse de valve aortique, nécessitant un retour sous circulation extracorporelle (CEC); il n'y avait pas de signaux transitoires de haute intensité (HITS) sur le DTC. Il y a eu un troisième épisode de désaturation cérébrale suite à la deuxième tentative de sevrage de la CEC; à ce moment-là, le DTC a détecté une quantité significative de HITS, suggérant des embolies gazeuses associées à une insuffisance ventriculaire droite aiguë; une réduction de la SPIR somatique a également été observée. CONCLUSION: La combinaison du DTC à la SPIR cérébrale a permis d'identifier trois différents mécanismes de désaturation cérébrale. Un algorithme est proposé pour aider le clinicien à déterminer l'origine de la désaturation cérébrale sur la SPIR. Des études cliniques prospectives sont nécessaires afin d'explorer les avantages potentiels d'un monitorage cérébral multimodal et son impact sur les devenirs cliniques à court et à long terme.


Subject(s)
Cerebrovascular Circulation , Monitoring, Intraoperative , Algorithms , Humans , Male , Oximetry , Prospective Studies , Ultrasonography, Doppler, Transcranial
12.
Article in English | MEDLINE | ID: mdl-32641296

ABSTRACT

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.


Subject(s)
Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Hydroxychloroquine/pharmacokinetics , Lopinavir/pharmacokinetics , Pneumonia, Viral/drug therapy , Ritonavir/pharmacokinetics , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/blood , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Drug Administration Schedule , Drug Combinations , Female , Hospitals, University , Humans , Hydroxychloroquine/blood , Hydroxychloroquine/pharmacology , Length of Stay/statistics & numerical data , Lopinavir/blood , Lopinavir/pharmacology , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Ritonavir/blood , Ritonavir/pharmacology , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
13.
Can J Anaesth ; 67(10): 1393-1404, 2020 10.
Article in English | MEDLINE | ID: mdl-32440906

ABSTRACT

Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure.


RéSUMé: Les complications pulmonaires du coronavirus (COVID-19) constituent ses manifestations cliniques les plus fréquentes. De récentes observations cliniques ont fait émerger deux phénotypes : le phénotype à élastance faible ou type L (low), et le phénotype à élastance élevée, ou type H (high). La présentation clinique, la physiopathologie, les mécanismes pulmonaires, ainsi que les observations radiologiques et échographiques de ces deux différents phénotypes sont différents. L'approche thérapeutique variera par conséquent selon le phénotype des patients atteints de COVID-19 souffrant d'insuffisance respiratoire.


Subject(s)
Coronavirus Infections/complications , Lung/diagnostic imaging , Pneumonia, Viral/complications , Respiratory Insufficiency/diagnostic imaging , Ultrasonography , Acute Disease , Algorithms , COVID-19 , Coronavirus Infections/diagnostic imaging , Humans , Lung/physiopathology , Lung/virology , Oxygen/metabolism , Pandemics , Phenotype , Pneumonia, Viral/diagnostic imaging , Point-of-Care Systems , Respiratory Insufficiency/virology , Respiratory Rate/physiology
14.
Eur J Nucl Med Mol Imaging ; 46(10): 2032-2041, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31254034

ABSTRACT

BACKGROUND: Although women with cardiovascular disease experience relatively worse outcomes as compared to men, substantial knowledge gaps remain regarding the unique female determinants of cardiovascular risk. Heart rate (HR) responses to vasodilator stress mirror autonomic activity and may carry important long-term prognostic information in women. METHODS AND RESULTS: Hemodynamic changes during adenosine stress were recorded in a total of 508 consecutive patients (104 women) undergoing clinically indicated 13N-ammonia Positron-Emission-Tomography (PET) at our institution. Following propensity matching, 202 patients (101 women, mean age 61.3 ± 12.6 years) were analyzed. During a median follow-up of 5.6 years, 97 patients had at least one cardiac event, including 17 cardiac deaths. Heart rate reserve (% HRR) during adenosine infusion was significantly higher in women as compared to men (23.8 ± 19.5 vs 17.3 ± 15.3, p = 0.009). A strong association between 10-year cardiovascular endpoints and a blunted HRR was observed in women, while this association was less pronounced in men. Accordingly, in women, but not in men, reduced HRR was selected as a strong predictor for adverse cardiovascular events in a Cox regression model fully adjusted for imaging findings and traditional risk factors (HR 2.41, 95% CI 1.23-4.75, p = 0.011). Receiver operating characteristics (ROC) curves revealed that a blunted HRR <21% was a powerful predictor for MACE in women with a sensitivity of 77% and a specificity of 68%. CONCLUSION: Blunted HRR to adenosine stress adds incremental prognostic value for long-term cardiovascular outcomes in women beyond that provided by traditional risk factors and imaging findings.


Subject(s)
Heart Diseases/diagnostic imaging , Heart Rate , Myocardial Perfusion Imaging/methods , Positron-Emission Tomography/methods , Adenosine/administration & dosage , Adenosine/pharmacology , Aged , Female , Heart/drug effects , Heart/physiopathology , Heart Diseases/diagnosis , Humans , Middle Aged , Myocardial Perfusion Imaging/standards , Nitrogen Radioisotopes , Radiopharmaceuticals , Sensitivity and Specificity , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacology
16.
J Cardiothorac Vasc Anesth ; 33(3): 651-660, 2019 03.
Article in English | MEDLINE | ID: mdl-30683595

ABSTRACT

OBJECTIVE: To report the authors' 12 years of experience with intratracheal milrinone administration and to assess the efficacy and limitations of intratracheal milrinone bolus administration for the treatment of unexpected acute right ventricular (RV) failure in patients undergoing cardiac surgery. DESIGN: Retrospective analysis. SETTING: Single-center university hospital. PARTICIPANTS: One hundred seventy-six patients (4.6%) undergoing on-pump cardiac surgery. INTERVENTIONS: Endotracheal tube administration of milrinone (5-mg bolus) after unexpected acute RV failure during separation from cardiopulmonary bypass (CPB) weaning. RV failure was defined as the simultaneous presence of all of the following criteria: (1) hemodynamic instability or difficult separation from CPB with associated elevated central venous pressure or abnormal RV pressure waveform, (2) >20% reduction of RV fractional area change from baseline evaluated by transesophageal echocardiography, and (3) anatomical visualization of impaired or absent RV wall motion by direct intraoperative visual inspection. MEASUREMENTS AND MAIN RESULTS: Intratracheal milrinone administration was found to improve RV failure in 109 patients (61.9%) whereas RV failure persisted in 67 patients (38.1%). Using a multiple logistic regression model, severely decreased left ventricular ejection fraction (<35% v >50%) (adjusted odds ratio [OR] 3.72; 95% confidence interval [CI] 1.2-11.3; p = 0.012), longer CPB time (adjusted OR 1.014; CI 1.01-1.02; p = 0.001) and elevated postoperative fluid balance (adjusted OR 1.39; CI 1.1-1.8; p = 0.02) were found to be significant predictors of persistent RV failure. CONCLUSION: Intratracheal instillation of milrinone was associated with clinical improvement of RV failure occurring during separation from CPB in almost two-thirds of patients. Factors limiting its therapeutic efficacy include severe left ventricular dysfunction, increased fluid balance, and long CPB time.


Subject(s)
Cardiopulmonary Bypass/trends , Cardiotonic Agents/administration & dosage , Intubation, Intratracheal/trends , Milrinone/administration & dosage , Ventricular Dysfunction, Right/drug therapy , Ventricular Dysfunction, Right/surgery , Acute Disease , Aged , Echocardiography, Transesophageal/trends , Female , Heart Failure , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Ventricular Dysfunction, Right/diagnostic imaging
19.
Echocardiography ; 30(10): 1143-50, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23742210

ABSTRACT

BACKGROUND: The effect of age and gender on left ventricular (LV) size, muscle mass, and systolic function as determined by two-dimensional echocardiography has not yet been investigated in a large population. METHODS: Normal transthoracic two-dimensional echocardiography studies of 5307 subjects (47% males) performed between March 1990 and December 2011 were analyzed. LV end-diastolic volume index (LVEDVI), LV muscle mass index (LVMMI), LV ejection fraction (LVEF), and LV fractional shortening (LVFS) were compared in different age groups. RESULTS: LVMMI increased in females from 66.4 ± 1.3 g/m(2) (7-20 years) to 76.3 ± 0.9 g/m(2) (60-80 years; P < 0.0001) and in males from 81.9 ± 1.7 g/m(2) (7-20 years) to 94.6 ± 1.3 g/m(2) (60-80 years; P < 0.0001). LVEDVI decreased in females from 49.8 ± 0.9 mL/m(2) (7-20 years) to 42.8 ± 0.6 mL/m(2) (60-80 years; P < 0.0001) and in males from 56.6 ± 0.8 mL/m(2) (7-20 years) to 49.0 ± 0.7 mL/m(2) (60-80 years; P < 0.0001). A significant increase in LVEF was observed with age (P < 0.0001 for both genders), but it was more pronounced in females (62 ± 0.5% [age 7-20 years] vs. 65 ± 0.3% [age 60-80 years]) than in males (62 ± 0.5% [age 7-20 years] vs. 64 ± 0.3% [age 60-80 years]). Similarly, LVFS increased in females from 37.7 ± 0.5% (7-20 years) to 42.4 ± 0.4% (60-80 years; P < 0.001) and in males from 37.3 ± 0.5% (7-20 years) to 39.4 ± 0.5% (60-80 years; P < 0.001). CONCLUSIONS: LVEF, LVFS, and LVMMI increase with advancing age, in particular in females. In contrast, LVEDVI decreases with age. These findings indicate that the LV undergoes a lifelong remodeling.


Subject(s)
Aging/physiology , Heart Ventricles/diagnostic imaging , Heart Ventricles/growth & development , Systole/physiology , Ventricular Function, Left/physiology , Ventricular Remodeling/physiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cardiac Volume/physiology , Child , Echocardiography , Female , Humans , Male , Middle Aged , Myocardium/cytology , Reference Values , Retrospective Studies , Sex Characteristics , Stroke Volume/physiology , Young Adult
20.
Nat Rev Endocrinol ; 19(4): 217-231, 2023 04.
Article in English | MEDLINE | ID: mdl-36494595

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a clear sex disparity in clinical outcomes. Hence, the interaction between sex hormones, virus entry receptors and immune responses has attracted major interest as a target for the prevention and treatment of SARS-CoV-2 infections. This Review summarizes the current understanding of the roles of androgens, oestrogens and progesterone in the regulation of virus entry receptors and disease progression of coronavirus disease 2019 (COVID-19) as well as their therapeutic value. Although many experimental and clinical studies have analysed potential mechanisms by which female sex hormones might provide protection against SARS-CoV-2 infectivity, there is currently no clear evidence for a sex-specific expression of virus entry receptors. In addition, reports describing an influence of oestrogen, progesterone and androgens on the course of COVID-19 vary widely. Current data also do not support the administration of oestradiol in COVID-19. The conflicting evidence and lack of consensus results from a paucity of mechanistic studies and clinical trials reporting sex-disaggregated data. Further, the influence of variables beyond biological factors (sex), such as sociocultural factors (gender), on COVID-19 manifestations has not been investigated. Future research will have to fill this knowledge gap as the influence of sex and gender on COVID-19 will be essential to understanding and managing the long-term consequences of this pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Male , Female , Humans , Progesterone , Gonadal Steroid Hormones , Androgens , Receptors, Virus
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