Vasoplegia is a ubiquitous phenomenon in all advanced shock states, including septic, cardiogenic, hemorrhagic, and anaphylactic shock. Its pathophysiology is complex, involving various mechanisms in ...vascular smooth muscle cells such as G protein-coupled receptor desensitization (adrenoceptors, vasopressin 1 receptors, angiotensin type 1 receptors), alteration of second messenger pathways, critical illness-related corticosteroid insufficiency, and increased production of nitric oxide. This review, based on a critical appraisal of the literature, discusses the main current treatments and future approaches. Our improved understanding of these mechanisms is progressively changing our therapeutic approach to vasoplegia from a standardized to a personalized multimodal treatment with the prescription of several vasopressors. While norepinephrine is confirmed as first line therapy for the treatment of vasoplegia, the latest Surviving Sepsis Campaign guidelines also consider that the best therapeutic management of vascular hyporesponsiveness to vasopressors could be a combination of multiple vasopressors, including norepinephrine and early prescription of vasopressin. This new approach is seemingly justified by the need to limit adrenoceptor desensitization as well as sympathetic overactivation given its subsequent deleterious impacts on hemodynamics and inflammation. Finally, based on new pathophysiological data, two potential drugs, selepressin and angiotensin II, are currently being evaluated.
Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their ...effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock.
Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality.
When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.
Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who ...remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns.
Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1-H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases.
Esmolol was infused 9 (6.4-11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34-0.83) to 0.78 (0.3-1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110-125) to 100 (92-103) beats/min and a decrease in cardiac index from 4.2 (3.1-4.4) to 2.9 (2.5-3.7) l/min/m
. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients.
In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).
Background
The COVID-19 sanitary crisis inflicted different challenges regarding the reorganization of the human and logistic resources, particularly in intensive care unit (ICU). Interdependence ...between regional pandemic burden and individual outcome remains unknown. The study aimed to assess the association between ICU bed occupancy and case fatality rate of critically ill COVID-19 patients.
Methods
A cross-sectional study was performed in France, using the national hospital discharge database from March to May, 2020. All patients admitted to ICU for COVID-19 were included. Case fatality was described according to: (i) patient’s characteristics (age, sex, comorbid conditions, ICU interventions); (ii) hospital’s characteristics (baseline ICU experience assessed by the number of ICU stays in 2019, number of ICU physicians per bed), and (iii) the regional outbreak-related profiles (workload indicator based on ICU bed occupancy). The determinants of lethal outcome were identified using a logistic regression model.
Results
14,513 COVID-19 patients were admitted to ICU; 4256 died (29.3%), with important regional inequalities in case fatality (from 17.6 to 33.5%). Older age, multimorbidity and clinical severity were associated with higher mortality, as well as a lower baseline ICU experience of the health structure. Regions with more than 10 days with ≥ 75% of ICU occupancy by COVID-19 patients experienced an excess of mortality (up to adjusted OR = 2.2 1.9–2.6 for region with the highest occupancy rate of ICU beds).
Conclusions
The regions with the highest burden of care in ICU were associated with up to 2.2-fold increase of death rate.
Objective
Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present ...study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients.
Design
We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.
Measurements and results
Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17–76%) and short-term mortality rate was 49% (21–69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR CI = 3.3 2.8–3.9) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (
n
= 1227) (adjusted OR = 4.7 3.4–6.4). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 3.0–6.0).
Conclusions
In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.
Acute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of ...oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF.
In this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF.
The STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180.
Among the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF.
Rapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies STRONG-HF; NCT03412201)
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Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also ...indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock.
Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg
.h
), CLP + E-5 (esmolol: 5 mg.kg
.h
), CLP + E-18 (esmolol: 18 mg.kg
.h
). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting.
CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hypo-responsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18.
In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.
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