Hemodynamics and outcome of septic shock

Septic shock is a common killer in intensive care units (ICU). The most crucial issue concerning the outcome is the early and aggressive start of treatment aimed at normalization of hemodynamics and the early start of antibiotics during the very first hours. The optimal targets of hemodynamic treatment, or impact of hemodynamic treatment on survival after first resuscitation period are less known. The objective of this study was to evaluate different aspects of the hemodynamic pattern in septic shock with special attention to prediction of outcome. In particular components of early treatment and monitoring in the ICU were assessed. A total of 401 patients, 218 with septic shock and 192 with severe sepsis or septic shock were included in the study. The patients were treated in 24 Finnish ICUs during 1999-2005. 295 of the patients were included in the Finnish national epidemiologic Finnsepsis study. We found that the most important hemodynamic variables concerning the outcome were the mean arterial pressures (MAP) and lactate during the first six hours in ICU and the MAP and mixed venous oxygen saturation (SvO2) under 70% during first 48 hours. The MAP levels under 65 mmHg and SvO2 below 70% were the best predictive thresholds. Also the high central venous pressure (CVP) correlated to adverse outcome. We assessed the correlation and agreement of SvO2 and mean central venous oxygen saturation (ScvO2) in septic shock during first day in ICU. The mean SvO2 was below ScvO2 during early sepsis. Bias of difference was 4.2% (95% limits of agreement 8.1% to 16.5%) by Bland-Altman analysis. The difference between saturation values correlated significantly to cardiac index and oxygen delivery. Thus, the ScvO2 can not be used as a substitute of SvO2 in hemodynamic monitoring in ICU. Several biomarkers have been investigated for their ability to help in diagnosis or outcome prediction in sepsis. We assessed the predictive value of N-terminal pro brain natriuretic peptide (NT-proBNP) on mortality in severe sepsis or septic shock. The NT-proBNP levels were significantly higher in hospital nonsurvivors. The NT-proBNP 72 hrs after inclusion was independent predictor of hospital mortality. The acute cardiac load contributed to NTproBNP values at admission, but renal failure was the main confounding factor later. The accuracy of NT-proBNP, however, was not sufficient for clinical decision-making concerning the outcome prediction. The delays in start of treatment are associated to poorer prognosis in sepsis. We assessed how the early treatment guidelines were adopted, and what was the impact of early treatment on mortality in septic shock in Finland. We found that the early treatment was not optimal in Finnish hospitals and this reflected to mortality. A delayed initiation of antimicrobial agents was especially associated with unfavorable outcome.Septisessä sokissa määritelmän mukaisesti potilaalla todetaan infektion aiheuttamana yleinen tulehdusreaktio sekä sepsikseen liittyen matala verenpainetaso ja riittämätön verenkierto nestehoidosta huolimatta. Kuolleisuus septiseen sokkiin on suuri, 30 60% ja se on eräs yleisimmistä kuolinsyistä teho-osastoilla. Väitöstutkimuksen tavoiteena oli arvioida eri näkökohtia septisen sokin hemodynamiikkaan, hoitoon ja ennusteeseen liittyen suomalaisilla potilailla. Väitöstutkimus koostuu yhdestä retrospektiivisestä ja kolmesta prospektiivisesta kohorttitutkimuksesta. Kaksi tutkimuksista oli kansallisen sepsistutkimuksen Finnsepsiksen osatöitä. Tutkimuksissa oli yhteensä 401 potilasta 24:ltä suomalaiselta teho-osastolta vuosina 1999-2005. 218:lla potilaista todettiin septinen sokki ja 192:lla vaikea sepsis. Hemodynamiikan hoidon tavoitteista septisessä sokissa on useita erilaisia suosituksia, joiden ennusteellinen merkitys on puutteellisesti tunnettu. Tässä tutkimuksessa arvioitiin yleisesti mitattujen ja monitoroitujen hemodynaamisten muuttujien ennusteellista vaikutusta. Totesimme, että keskiverenpaine (MAP) ja sekoittuneen laskimoveren happisaturaatio (SvO2) ovat ennusteellisesti erittäin merkityksellisiä. Nykyisin yleisesti käytetyt tavoiterajat (MAP>65mHg, SvO2>70%) ovat ennusteen kannalta optimaaliset. Korkea keskuslaskimopaine viittaa potilaan huonontuneeseen ennusteeseen. Kansainvälisessä sepsiksen hoitosuosituksessa keskuslaskimon happisaturaatio (ScvO2) ja SvO2 rinnastetaan vertailukelpoisiksi toisiinsa nähden. Väitöstutkimus selvensi että saturaatioiden rinnastaminen ei kuitenkaan ole suositeltavaa septisessä sokissa näiden huomattavan vaihtelun ja eroavaisuuden vuoksi. Useista biomarkkereista on odotettu diagnostista tai ennusteellista apua sepsiksessä. Me selvitimme sydämen erittämän hormonin, natriureettisen peptidin (NT-proBNP) ennustevaikutusta vaikeassa sepsiksessä ja septisessä sokissa. Havaintomme mukaan NT-proBNP ennustaa merkittävästi mortaliteettia mutta ei ole riittävän luotettava biomarkkeri hoitopäätöksiä ajatellen. Varhainen tehokas ja riittävä antibioottihoito, verenkierron nestehoito sekä infektion kirurginen saneeraus tarvittaessa on oleellisia toimia sepsispotilaiden ennusteen parantamiseksi. Tutkimuksessa selvitimme septisen sokin varhaisen hoidon onnistumista Suomessa. Totesimme, että varhainen hoito ei toteudu optimaalisesti. Puutteellinen alkuhoito ja erityisesti antibioottihoidon viivästyminen lisää kuolleisuutta. Päivystyspoliklinikalla vietetty aika ennen teho-osastolle siirtoa korreloi varhaisen hoidon toteutumiseen sekä antibioottihoidon aloitusviiveeseen. Sepsiksen ennustetta voidaan tulevaisuudessa parantaa tehostamalla sepsiksen tunnistamista, diagnostiikkaa ja kehittämällä paikalliset hoitoketjut toimiviksi potilaan ensikontaktista alkaen

Prognostic impact of baseline and residual SYNTAX scores in cardiogenic shock

Objectives The aim was to assess the extent of coronary artery disease and revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was evaluated and assessed for additive value over clinical risk scores. Background bSS and rSS have been proven to be useful in risk stratification in stable coronary artery disease as well as in acute coronary syndromes, but they have not been studied in STEMI related CS. Methods Patients from a multinational prospective study of CS were analyzed. The study population was divided into tertiles according to bSS. The Cox regression and receiver operating characteristic (ROC) curves were used to assess the predictive power of SS. Results Of the 61 studied patients, 85% were male and the mean age was 67 years. Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10). However, additive value over clinical risk scores was limited. rSS was not associated with mortality, whereas post-percutaneous coronary intervention (PCI) TIMI flow 3 of infarct-related artery (IRA) predicted better survival. Conclusions In STEMI related CS, the added value of bSS and rSS over clinical assessment and risk scores is limited. Our results suggest that while immediate PCI in order to restore blood flow to the IRA is essential, deferring the treatment of residual lesions does not seem to be associated with worse prognosis.Peer reviewe

Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock : results from the CardShock Study

Aims Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. [GRAPHICS] .Peer reviewe

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality

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.Peer reviewe

Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest—A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial

OBJECTIVES: This explorative substudy aimed at determining the effect ofinhaled xenon on left ventricular function by echocardiography in comatose survivorsof out-of-hospital cardiac arrest.DESIGN: A randomized two-group single-blinded phase 2 clinical drug trial.SETTING: A multipurpose ICU in two university hospitals.PATIENTS: Of the 110 randomized comatose survivors after out-of-hospital cardiacarrest with a shockable rhythm in the xenon in combination with hypothermiaafter cardiac arrest trial, 38 patients (24–76 yr old) with complete echocardiographywere included in this study.INTERVENTIONS: Patients were randomized to receive either inhaled xenoncombined with hypothermia (33 C) for 24 hours or hypothermia treatment alone.Echocardiography was performed at hospital admission and 24 4 hours afterhypothermia.MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection fraction,myocardial longitudinal systolic strain, and diastolic function were analyzedblinded to treatment. There were 17 xenon and 21 control patients in whom echocardiographywas completed. Clinical characteristics did not differ significantlybetween the groups. At admission, ejection fraction was similar in xenon and controlpatients (39% 10% vs 38% 11%; p = 0.711) but higher in xenon thancontrol patients after hypothermia (50% 10% vs 42% 10%; p = 0.014).Global longitudinal systolic strain was similar in xenon and control patients atadmission (–9.0% 3.8% vs –8.1% 3.6%; p = 0.555) but better in xenonthan control patients after hypothermia (–14.4.0% 4.0% vs –10.5% 4.0%;p = 0.006). In patients with coronary artery disease, longitudinal strain improved inthe nonischemic myocardial segments in xenon patients. There were no changesin diastolic function between the groups.</p

Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest-A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial

Peer reviewe

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. (C) 2019 The Authors. Published by Elsevier B.V.Peer reviewe

Acute coronary syndromes and acute heart failure:a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients