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Background Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. Methods The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Results Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p  = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p  = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Conclusion Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

Background Sepsis is the result of a dysregulated immune response to infection and is associated with acute organ dysfunction. The syndrome’s complexity is contingent upon the underlying pathology and individual patient characteristics, including their immune response. The involvement of multiple organs and physiological functions adds complexity, with “organ cross-talk” emerging as a pivotal pathophysiological and clinical aspect. This narrative review to evaluate the rationale and available clinical evidence supporting the use of extracorporeal blood purification therapies as adjunctive therapy in patients with sepsis and septic shock. Main body A search of the PubMed, Embase, Web of Science and Scopus databases for relevant literature from August 2002 to May 2024 has been conducted. The search was performed using the terms: 1) “blood purification” or “hemadsorption” or “plasma exchange” AND 2) “sepsis” or “septic shock”. Therefore the authors have focused our discussion on several key areas such as conducting well-designed trials, developing more personalized protocols, ensuring optimal management and monitoring. Conclusions Given the heterogeneity of patients with sepsis, conducting traditional randomized clinical trials in this domain can be a daunting task. However, statistical techniques such as Bayesian methods, propensity score analysis, and emulated clinical trials using clinical databases hold promise for enhancing comparability between the study groups. Indeed, to comprehend the clinical efficacy of extracorporeal blood purification techniques in patients with sepsis, it is imperative to assemble homogeneous groups of patients receiving uniform treatments. Clinical strategies should be individualized, signaling the end of the “one size fits all” approach in sepsis therapy and the need for personalized treatments. Graphical abstract Current suggested best practice for use of cytokine hemadsorption in sepsis.

Infusion failure may have severe consequences for critical care patients, particularly if the medications are critical short half-life infusions. Interruptions to infusions, and infusions not running ‘to time’ can also lead to subtherapeutic management of patients receiving medications that require therapeutic monitoring. We aimed to identify determinants of longevity of infusions in critical care delivered by syringe driver and by volume pump, and to create, and test models for predicting the likelihood of successful infusion longevity. Data from 2,341,456 syringe pump and 3,498,279 large volume pump infusions were examined with a dependent variable of Infusion Longevity with explanatory variables of Medication Type, Concentration, Infusion Rate, and type of Critical Care Unit. Explanatory variables were added and removed from the core explanatory variables with each addition of explanatory ability being assessed against change in the adjusted goodness of fit (F-Score) within five statistical models. The study showed that ‘Infusion-Rate’ had the highest importance among other predictors of interruption. Eliminating this variable caused a 4.13% decrease in the F-Score. Following that, the ‘Care-Unit’ (3.45%), ‘Medication’ (2.75%), and ‘Concentration/Dose’ (1.41%). In 86% of the infusions, Random Forest was the most successful prediction model; in the remaining 14%, XGBoost was a better predictor. ANOVA confirms the statistical significance of F-Score reductions. t-tests were performed to check the significance of the F-Scores before and after the elimination of each predictor. The model identified and ranked predictive factors of longevity for infusions. This information can inform critical care clinicians of which types of infusion warrant more intense observation or proactive intravenous access management, in which kinds of care unit infusion failure is more likely, and what is the average length of uninterrupted infusion that can be expected in these care areas. We found that final medication concentration and medication type were of less significance to infusion longevity than rate and care unit. Optimizing rate settings to improve infusion longevity for continuous infusions through compounding to create customized concentrations for individual patients may be possible in the light of the results. Explanatory variables of added interest included pump occlusion pressure settings, and deployed syringe size and brand. A ‘sweet spot’ of infusion delivery rate for low flow infusions giving acceptable occlusion detection and shortened time-to-alarm by the pump along with extended infusion longevity was detected at 0.5–0.8 ml/h.

The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.). Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

There is limited data on the cardiovascular effects of norepinephrine (NE) in neonates. Our objective was to describe the clinical responses in neonates treated with NE infusion. This retrospective cohort study included neonates with evidence of shock and those who received NE infusion. Primary outcome: changes in mean blood pressure (MBP) at 6, 12, and 24 h post-initiation of NE. Secondary outcomes: Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24 h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4 mm Hg (SD: 6.6) at baseline to 39.4 mm Hg (SD: 10.5, p < 0.001) at 6 h, to 39.6 mm Hg (SD: 12.1, p = 0.002) at 12 h and to 40.4 mm Hg (SD: 15.5, p = 0.004) at 24 h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24 h. Urine output improved within 24 h [1.5 ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24 h; p = 0.04]. Oxygen requirement decreased after NE initiation.Conclusion: The use of NE appears to be effective and safe for treating systemic hypotension in neonates. Trial registration: Being a retrospective study, trial registration was not considered.What is known:• Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension.• Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonatesWhat is new:• Mean blood pressure improved significantly at 6, 12, and 24 h with reduction in vasoactive infusion score at 12 and 24 h after norepinephrine infusion.• No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

PurposeTo compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction.SourceWe conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality.Principal findingsWe included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis.ConclusionThe results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding.Study registrationCenter for Open Science (https://osf.io/ky2gr); registered 10 November 2020

Heart failure (HF) is a major cause of mortality, hospitalizations, and reduced quality of life and a major burden for the healthcare system. The number of patients that progress to an advanced stage of HF is growing. Only a limited proportion of these patients can undergo heart transplantation or mechanical circulatory support. The purpose of this review is to summarize medical management of patients with advanced HF. First, evidence‐based oral treatment must be implemented although it is often not tolerated. New therapeutic options may soon become possible for these patients. The second goal is to lessen the symptomatic burden through both decongestion and haemodynamic improvement. Some new treatments acting on cardiac function may fulfil both these needs. Inotropic agents acting through an increase in intracellular calcium have often increased risk of death. However, in the recent Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial, omecamtiv mecarbil was safe and effective in the reduction of the primary outcome of cardiovascular death or HF event compared with placebo (hazard ratio, 0.92; 95% confidence interval, 0.86–0.99; P = 0.03) and its effects were larger in those patients with more severe left ventricular dysfunction. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit, whereas patients without severe HF did not (P = 0.005 for interaction). Lastly, clinicians should take care of the end of life with an appropriate multidisciplinary approach. Medical treatment of advanced HF therefore remains a major challenge and a wide open area for further research.

This is a focused review looking at the pharmacological support in cardiogenic shock. There are a plethora of data evaluating vasopressors and inotropes in septic shock, but the data are limited for cardiogenic shock. This review article describes in detail the pathophysiology of cardiogenic shock, the mechanism of action of different vasopressors and inotropes emphasizing their indications and potential side effects. This review article incorporates the currently used specific risk-prediction models in cardiogenic shock as well as integrates data from many trials on the use of vasopressors and inotropes. Lastly, this review seeks to discuss the future direction for vasoactive medications in cardiogenic shock.

Background Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. Methods Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. Results Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73–1.27; P  = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18–0.95; P  = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. Conclusions BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165