Hospital-administered ECPR for out-of-hospital cardiac arrest: an observational cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a treatment method for refractory out-of-hospital cardiac arrest (OHCA) requiring a complex chain of care. METHODS: All cases of OHCA between 1 January 2016 and 31 December 2021 in the Helsinki University Hospital catchment area in which the ECPR protocol was activated were included in the study. The protocol involved patient transport from the emergency site with ongoing mechanical cardiopulmonary resuscitation (CPR) directly to the cardiac catheterisation laboratory where the implementation of extracorporeal membrane oxygenation (ECMO) was considered. Cases of hypothermic cardiac arrest were excluded. The main outcomes were the number of ECPR protocol activations, duration of prehospital and in-hospital time intervals, and whether the ECPR candidates were treated using ECMO or not. RESULTS: The prehospital ECPR protocol was activated in 73 cases of normothermic OHCA. The mean patient age (SD) was 54 (±11) years and 67 (91.8%) of them were male. The arrest was witnessed in 67 (91.8%) and initial rhythm was shockable in 61 (83.6%) cases. The median ambulance response time (IQR) was 9 (7-11) min. All patients received mechanical CPR, epinephrine and/or amiodarone. Seventy (95.9%) patients were endotracheally intubated. The median (IQR) highest prehospital end-tidal CO2 was 5.5 (4.0-6.9) kPa.A total of 37 (50.7%) patients were treated with venoarterial ECMO within a median (IQR) of 84 (71-105) min after the arrest. Thirteen (35.1%) of them survived to discharge and 11 (29.7%) with a cerebral performance category (CPC) 1-2. In those ECPR candidates who did not receive ECMO, 8 (22.2%) received permanent return of spontaneuous circulation during transport or immediately after hospital arrival and 6 (16.7%) survived to discharge with a CPC 1-2. CONCLUSIONS: Half of the ECPR protocol activations did not lead to ECMO treatment. However, every fourth ECPR candidate and every third patient who received ECMO-facilitated resuscitation at the hospital survived with a good neurological outcome.

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.

This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of 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 cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24-76 yr old) with complete echocardiography were included in this study. INTERVENTIONS: Patients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia. MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (-9.0% ± 3.8% vs -8.1% ± 3.6%; p = 0.555) but better in xenon than 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 in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups. CONCLUSIONS: Among comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone.

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.

Current Use and Impact on 30-Day Mortality of Pulmonary Artery Catheter in Cardiogenic Shock Patients: Results From the CardShock Study.

BACKGROUND: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). METHODS: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. RESULTS: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices (P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. CONCLUSIONS: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.

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.

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.

Mechanical compression devices for cardiac arrest: report of three cases.

Mechanical compression devices enable transportation of patients with cardiac arrest to the catheterization laboratory. Coronary angiography and coronary interventions can be performed while the patients are being resuscitated with these devices. In this report, we describe three cases in whom resuscitation with mechanical compression devices and rapid transportation to the catheterization laboratory resulted in favorable cardiac and neurological outcome.

Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The Xe-Hypotheca Trial.

BACKGROUND: The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). OBJECTIVES: A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. METHODS: A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. RESULTS: Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS: Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T.

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.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892.

Early hemodynamic variables and outcome in severe acute pancreatitis: a retrospective single-center cohort study.

OBJECTIVES: The aim of this study was to assess the association of hemodynamic factors with 90-day mortality in critically ill patients with severe acute pancreatitis (SAP). METHODS: One hundred fifty-nine consecutive patients with SAP admitted to the intensive care units between January 2005 and December 2008 were included in study. We assessed the association of hemodynamic variables during the first 24 hours in the intensive care unit with 90-day mortality using multivariate analysis for all patients with SAP and for a subgroup with circulatory shock. RESULTS: Advanced age (odds ratio [OR], 1.09; 95% confidence interval, 1.04-1.15 per year), higher serum creatinine (OR, 1.01; 95% confidence interval, 1.00-1.02 per unit), and lower mean arterial pressure (OR, 0.92; 95% confidence interval, 0.86-0.99 per mm Hg) were independently associated with 90-day mortality. In the subgroup of SAP with shock, higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.15; 95% confidence interval, 1.00-1.32 per point), higher central venous pressure (OR, 1.25; 95% confidence interval, 1.03-1.52 per mm Hg), and lower cardiac index (OR, 0.33; 95% confidence interval, 0.11-0.98 per L/min per m²) were independent risk factors for 90-day mortality. CONCLUSIONS: Advanced age, higher serum creatinine, and lower mean arterial pressure are associated with 90-day mortality in patients with SAP. In the subgroup of patients with SAP and shock, higher Acute Physiology and Chronic Health Evaluation II score, higher central venous pressure, and lower cardiac index predicted 90-day mortality.

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance.

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45 years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P < 0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P < 0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.

Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.

Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.

Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome.

PURPOSE: To assess the clinical utility of a recently developed highly sensitive cardiac troponin T (hs-cTnT) assay for providing prognostic information on patients with sepsis. METHODS: cTnT levels were measured by the novel hs-cTnT assay at two time points (inclusion and 72 h thereafter) in a subgroup of patients from the FINNSEPSIS study and associations with clinical outcomes were examined. Results for the hs-cTnT assay were compared to those of the established fourth-generation cTnT assay. RESULTS: cTnT measured by the fourth-generation and hs-cTnT assay was detectable in 124 (60%) and 207 (100%) patients, respectively, on inclusion in this study. hs-cTnT levels on inclusion correlated with several indices of risk in sepsis, including the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores. The level of hs-cTnT on inclusion was higher in hospital non-survivors (n = 47) than survivors (n = 160) (median 0.054 [Q1-3, 0.022-0.227] versus 0.035 [0.015-0.111] µg/L, P = 0.047), but hs-cTnT level was not an independent predictor of in-hospital mortality. hs-cTnT levels on inclusion were also higher in patients with septic shock during the hospitalization (0.044 [0.024-0.171] versus 0.033 [0.012-0.103] µg/L, P = 0.03), while this was not the case for the fourth-generation cTnT assay or NT-proBNP levels. CONCLUSIONS: Circulating hs-cTnT is present in patients with severe sepsis and septic shock, associates with disease severity and survival, but does not add to SAPS II score for prediction of mortality. hs-cTnT measurement could still have a role in sepsis as an early marker of shock.

[Cardiogenic shock--severe complication of myocardial infarction]. / Kardiogeeninen sokki--sydäninfarktin vakava komplikaatio.

Cardiogenic shock is the most common fatal complication of acute myocardial infarction. The conception of an extensive irreparable myocardial injury underlying the cardiogenic shock has changed especially with the results of the SHOCK study. In addition to the infarction injury, an acute inflammatory reaction, neurohumoral activation as well as improving myocardial stunning influence the development of shock. Mortality is high at the initial stage, whereas subsequent prognosis is equivalent to that seen in other infarction patients. Essential therapy consists in a prompt revascularization of the infarcted area and optimization of hemodynamics, if necessary by applying mechanical supportive therapies.

Heme oxygenase 1 polymorphisms and plasma concentrations in critically ill patients.

Heme oxygenase 1 (HO-1) is a cytoprotective enzyme upregulated by various critical illness-related stress stimuli. We investigated the association of HO-1 gene polymorphisms and plasma concentrations with the outcome of critically ill patients in a prospective cohort study of 231 critically ill patients admitted to tertiary care medical and medical-surgical intensive care units. Blood samples were collected on days 1, 2, and 3 to 4 in the intensive care unit. The HO-1 plasma concentration was measured in serial samples, and HO-1 single nucleotide polymorphisms, -413A/T and +99G/C, and HO-1 promoter GTn repeat length polymorphism were determined. The +99C and long GTn alleles were in perfect linkage disequilibrium, and the -413T/GT(L)/+99C haplotype had significant independent effect on first-day HO-1 plasma concentrations in linear regression analysis (P = 0.03) and associated with lower HO-1 plasma levels. Furthermore, -413T/GT(L)/+99C haplotype associated with a lower frequency of multiple-organ dysfunction compared with other haplotypes (P = 0.017). The HO-1 plasma concentrations of study patients were significantly higher than the values of healthy controls at all time points (P < 0.001), and the first-day plasma HO-1 levels were independently associated with the Sequential Organ Failure Assessment score (P = 0.001). In conclusion, the HO-1 -413T/GT(L)/+99C haplotype is associated with HO-1 plasma levels and the frequency of multiple-organ dysfunction in critically ill patients. The HO-1 plasma concentrations are significantly increased among critically ill patients and associated with the degree of organ dysfunction.

Are small hospitals with small intensive care units able to treat patients with severe sepsis?

PURPOSE: To find out whether mortality from sepsis is influenced by the size of the hospital and of the intensive care unit (ICU). METHODS: In the Finnsepsis study, 470 patients with severe sepsis were identified. The present study is a retrospective subgroup analysis of the Finnsepsis study. Eighteen patients were excluded because of treatment in more than one ICU. We divided the 24 units into three groups based on hospital size and academic status. RESULTS: There were no significant differences between the ICU groups in terms of severity of illness. Overall, the hospital mortality rate was 29.2%. In post-operative patients, the hospital mortality rate was 22.9% for patients treated in large ICUs (including university and large non-university hospital ICUs) but 42.3% for patients treated in small ICUs (p = 0.045). In medical patients, no differences in outcomes were found. CONCLUSIONS: Treatment of surgical patients with severe sepsis in small ICUs was associated with increased mortality. Because of the relatively small sample size, further studies are needed to confirm or refute this association.

Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation.

Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P < 0.01 for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034, respectively). Receiver operating characteristic curves showed that MCF, CFT and alpha angle discriminated patients with overt DIC moderately (area under curve 0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

Free cortisol in sepsis and septic shock.

BACKGROUND: Severe sepsis activates the hypothalamopituitary axis, increasing cortisol production. In some studies, hydrocortisone substitution based on an adrenocorticotropic hormone-stimulation test or baseline cortisol measurement has improved outcome. Because only the free fraction of cortisol is active, measurement of free cortisol may be more important than total cortisol in critically ill patients. We measured total and free cortisol in patients with severe sepsis and related the concentrations to outcome. METHODS: In a prospective study, severe sepsis was defined according the American College of Chest Physicians/Society of Critical Care Medicine criteria. Blood samples were drawn within 24 h of study entry. Serum cortisol was analyzed by electrochemiluminescence immunoassay. The Coolens method was used for calculating serum free cortisol concentrations. RESULTS: Blood samples were collected from 125 patients, of whom 62 had severe sepsis and 63 septic shock. Hospital mortality was 21%. Calculated free serum cortisol correlated well with serum total cortisol (r = 0.90, P < 0.001). There was no difference in the total cortisol concentrations in patients with sepsis and septic shock (728 +/- 386 nmol/L vs 793 +/- 439 nmol/L, P = 0.44). Nonsurvivors had higher calculated serum free (209 +/- 151 nmol/L) and total (980 +/- 458 nmol/L) cortisol concentrations than survivors (119 +/- 111 nmol/L, P = 0.002, and 704 +/- 383 nmol/L, P = 0.002). Depending on the definition, the incidence of adrenal insufficiency varied from 8% to 54%. CONCLUSIONS: Clinically, calculation of free cortisol does not provide essential information for identification of patients who would benefit from corticoid treatment in severe sepsis and septic shock.

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock.

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis. METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene. RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis. CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.