Esko Ruokonen

University of Eastern Finland, Kuopio, Northern Savo, Finland

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Publications (97)543.81 Total impact

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    ABSTRACT: Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting it may reduce ICU resource needs and thus lower ICU costs. Based on resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation. The total ICU costs associated with each study sedative were calculated based on total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline towards discharge, reflecting the observed reduction in mean daily TISS points between the periods. A number of additional sensitivity analyses were performed, including one where the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only. Based on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of 2,656 in the median (interquartile range) total ICU costs ( 11,864 (7,070 - 23,457) versus 14,520 (7,871 - 26,254)), and 1,649 in the mean total ICU costs. Compared to propofol or midazolam, the median (mean) total ICU costs with dexmedetomidine were 1,292 ( 747) and 3,573 ( 2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those where only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared to pooled standard care was 91.0% (72.4% versus propofol, 98.0% versus midazolam). From an economic point of view, dexmedetomidine appears to be a preferable option compared to standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation. ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).
    Full-text · Article · Dec 2015 · Critical Care
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    ABSTRACT: Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24h or more after the onset of anesthetic therapy. We defined the incidence and outcome of SRSE in adults in Finland. We analyzed retrospectively the Finnish Intensive Care Consortium database in order to identify adult patients with SRSE treated in ICUs in Finland during a three-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating refractory SE (RSE) with general anesthesia in the intensive care unit (ICU). We included consecutive adult (16years or older) patients with RSE and identified those who had SRSE. Patients with postanoxic etiologies were excluded. All five university hospitals and 10/15 of the central hospitals participated. The adult referral population of the study hospitals is 3.9 million, representing 91% of the total adult population of Finland. We identified 395 patients with ICU-treated RSE, 87 (22%) of whom were classified as having SRSE. This corresponds to an annual incidence of SRSE of 0.7/100,000 (95% confidence interval [CI]: 0.6-0.9). The one-year mortality rates were 36% (95% CI: 26-46%) for patients with SRSE and 22% (95% CI: 17-27%) for patients with RSE. Mortality was highest (63%) in patients with SRSE aged over 75years. Approximately 20% of patients with RSE treated in Finnish ICUs progressed to having SRSE. The incidence of SRSE, 0.7/100,000, is about 5-10% of the incidence of SE. The mortality of patients with SRSE, 36%, was comparable to earlier studies and twofold higher than the mortality of patients with RSE. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Epilepsy & Behavior
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    ABSTRACT: Aim of the study To study plasma concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and S-100B during intensive care after out-of-hospital cardiac arrest from ventricular fibrillation (OHCA-VF), and their associations with the duration of ischemia, organ dysfunction and long-term neurological outcome. Materials and methods A 12-month prospective observational multicenter study conducted in 21 Finnish intensive care units in 2011. IL-6, hs-CRP and S-100B were measured at 0-6 h, 24 h, 48 h and 96 h hours after ICU admission. Associations with the time to return of spontaneous circulation (ROSC), Sequential Organ Failure Assessment (SOFA) scores divided into tertiles and 12-month Cerebral Performance Category (CPC) were tested. Results Of 186 OHCA-VF patients included in the study, 110 (59.1%) patients survived with good neurological outcome (CPC 1-2) 12 months after cardiac arrest. Admission plasma concentrations of IL-6 but not hs-CRP were higher with prolonged time to ROSC (p < 0.001, 0.203, respectively), in patients with subsequent higher SOFA scores (p < 0.001, 0.069) and poor long-term neurological outcome (CPC 3-5) (p < 0.001, 0.315). S-100B concentrations over time were higher in patients with CPC of 3-5 (p < 0.001). The area under the curve for prediction of poor 12-month outcome for admission levels was 0.711 IL-6, 0.663 for S-100B and 0.534 for hs-CRP. With multivariate logistic regression analysis only admission IL-6 (p = 0.046, OR 1.006, 95% CI 1.000-1.011/ng/l) was an independent predictor of poor neurological outcome. Conclusion Admission high IL-6, but not hs-CRP or S-100B, is associated with extra-cerebral organ dysfunction and along with age and time to ROSC are independent predictors for 12-month poor neurologic outcome (CPC 3-5).
    Full-text · Article · Sep 2014 · Resuscitation
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    ABSTRACT: Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all). Conclusions Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure.
    Full-text · Article · May 2014 · BMC Infectious Diseases
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    ABSTRACT: The incidence of severe sepsis and septic shock requiring intensive care in Finnish adult population has increased to 0.60 11000 /y. Despite improved prognosis, hospital mortality related to severe sepsis and septic shock is high 24.1%. Key recommendations include prompt administration of antimicrobial therapy, optimally after blood cultures, quantitative fluid resuscitation and imaging studies to identify possible source of infection. Crystalloids are suitable for fluid resuscitation. Norepinephrine is the first-choice vasopressor in septic shock. Hydrocortisone should be considered only if fluid and vasopressor treatment does not restore hemodynamics.
    No preview · Article · Apr 2014 · Duodecim; lääketieteellinen aikakauskirja
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    ABSTRACT: Clinical trials in septic shock continue to fail due, in part, to inequitable and sometimes unknown distribution of baseline mortality risk between study arms. Investigators advocate that interventional trials in septic shock require effective outcome risk stratification. We derived and tested a multibiomarker-based approach to estimate mortality risk in adults with septic shock. Previous genome-wide expression studies identified 12 plasma proteins as candidates for biomarker-based risk stratification. The current analysis used banked plasma samples and clinical data from existing studies. Biomarkers were assayed in plasma samples obtained from 341 subjects with septic shock within 24 hours of admission to the ICU. Classification and regression tree analysis was used to generate a decision tree predicting 28-day mortality based on a combination of both biomarkers and clinical variables. The derived tree was first tested in an independent cohort of 331 subjects, then calibrated using all subjects (n = 672), and subsequently validated in another independent cohort (n = 209). Multiple ICUs in Canada, Finland, and the United States. Eight hundred eighty-one adults with septic shock or severe sepsis. None. The derived decision tree included five candidate biomarkers, admission lactate concentration, age, and chronic disease burden. In the derivation cohort, sensitivity for mortality was 94% (95% CI, 87-97), specificity was 56% (50-63), positive predictive value was 50% (43-57), and negative predictive value was 95% (89-98). Performance was comparable in the test cohort. The calibrated decision tree had the following test characteristics in the validation cohort: sensitivity 85% (76-92), specificity 60% (51-69), positive predictive value 61% (52-70), and negative predictive value 85% (75-91). We have derived, tested, calibrated, and validated a risk stratification tool and found that it reliably estimates the probability of mortality in adults with septic shock.
    Full-text · Article · Dec 2013 · Critical care medicine
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    ABSTRACT: Purpose: We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland. Methods: We included all adult OHCA patients admitted to 21 ICUs in Finland from March 1, 2010 to February 28, 2011 in this prospective observational study. Patients were followed (mortality and neurological outcome evaluated by Cerebral Performance Categories, CPC) within 1 year after cardiac arrest. Results: This study included 548 patients treated after OHCA. Of those, 311 patients (56.8%) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2%) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92%) patients were unconscious. TH was given to 241/281 (85.8%) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (CPC 3-4-5) in 42.0% with TH versus 77.5% without TH (p < 0.001). TH was given to 70/223 (31.4%) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3-4-5 in 80.6% (54/70) with TH versus 84.0% (126/153) without TH (p = 0.56). This lack of difference remained after adjustment for propensity to receive TH in patients with non-shockable rhythms. Conclusions: One-year unfavourable neurological outcome of patients with shockable rhythms after TH was lower than in previous randomized controlled trials. However, our results do not support use of TH in patients with non-shockable rhythms.
    Full-text · Article · Feb 2013 · Intensive Care Medicine
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    ABSTRACT: Objectives: Midlatency auditory-evoked potentials (MLAEPs) may provide an objective measure of depth of sedation. The aim of this study was to evaluate MLAEPs for measuring sedation in cardiac surgery patients. Design: Prospective study. Setting: Intensive care unit of a university hospital. Participants: Twenty-two patients scheduled for elective coronary artery bypass grafting. Interventions: MLAEPs were obtained at 5 time points: the day before surgery (baseline), 1 hour before surgery, after premedication, postoperatively during deep (Ramsay 6) and moderate (Ramsay 4) sedation, and the day after surgery. Measurements and Main Results: The latency of the Nb MLAEP component increased from 44 ms (38-60 ms; median, range) at baseline to 49 ms (41-64 ms) after premedication (p 0.03) and further to 63 ms (48-80 ms) during deep sedation after surgery (P < 0.01). Although a decreasing clinical level of sedation after rewarming was not associated with a sig-nificant change in Nb latency (61 ms [42-78 ms]), the MLAEP NaPa amplitude increased from 0.9 V (0.4-1.6 V) to 1.3 V (0.8-3.9 V; p 0.01). Nb latency remained increased the day after surgery (49 ms [37-71 ms]) as compared with baseline (p < 0.01). Conclusions: MLAEP latencies can reflect subtle changes in auditory perception, while amplitudes seem to change with transition between deep levels of sedation. © 2004 Elsevier Inc. All rights reserved. KEY WORDS: auditory-evoked potentials, intensive care unit, sedation, cardiac surgery
    Full-text · Dataset · Feb 2013
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    Full-text · Article · Jan 2013 · Intensive Care Medicine
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    ABSTRACT: Purpose: We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs. Methods: This prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients' AKI status and risk factors for up to 5 days. Results: We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5-41.1 %). The incidence was 17.2 % (15.8-18.6 %) for stage 1, 8.0 % (7.0-9.0 %) for stage 2 and 14.1 % (12.8-15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1-11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717-774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0-28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9-36.5 %). All AKIN stages were independently associated with 90-day mortality. Conclusions: The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.
    No preview · Article · Jan 2013 · Intensive Care Medicine
  • Jukka Takala · Stephan M. Jakob · Esko Ruokonen

    No preview · Article · Jun 2012 · JAMA The Journal of the American Medical Association
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    ABSTRACT: To assess the prognostic information of chromogranin A (CgA), a marker associated with adrenergic tone and myocardial function, in patients with severe sepsis. CgA levels were measured at the time of study inclusion and 72 h later in 232 patients with severe sepsis recruited from 24 ICUs in Finland (FINNSEPSIS study). Sixty-five patients (28%) died during the index hospitalization. CgA levels at inclusion and after 72 h correlated with several established indices of risk in sepsis. Patients who died during the hospitalization had higher baseline CgA levels than hospital survivors: 14.0 (Q1-3, 7.4-27.4) versus 9.1 (5.9-15.8) nmol/l, P = 0.002, and after 72 h: 16.2 (9.0-31.1) versus 9.8 (6.0-18.0) nmol/l, P = 0.001. Prior cardiovascular disease (P = 0.04) and cardiovascular SOFA levels on day 3 (P = 0.03) were associated with higher CgA levels after 72 h by linear regression. CgA levels on study inclusion and after 72 h were independently associated with hospital mortality by logistic regression: OR (logarithmically transformed CgA levels) 1.95 (95% CI 1.01-3.77), P = 0.046 and OR 2.03 (95% CI 1.18-3.49), P = 0.01, respectively. The prognostic accuracy was comparable for CgA measurements and SAPS II score, and the addition of CgA measurements to the SAPS II score improved risk stratification of the patients as assessed by the category-free net reclassification index. A CgA level >6.6 nmol/l on study inclusion was associated with septic shock during the hospitalization. CgA levels measured during hospitalization for severe sepsis are associated with cardiovascular dysfunction and may provide additional prognostic information in patients with severe sepsis.
    No preview · Article · Apr 2012 · Intensive Care Medicine
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    ABSTRACT: Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care. Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. clinicaltrials.gov Identifiers: NCT00481312, NCT00479661.
    Full-text · Article · Mar 2012 · JAMA The Journal of the American Medical Association
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    ABSTRACT: 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.
    No preview · Article · Jul 2011 · Pharmacological Research
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    ABSTRACT: Microvascular flap surgery is a common technique in reconstructive surgery. The wide indications and variable patients provide challenge also for anesthesiologist. Both hypotension and hypoperfusion can be harmful to the flap. Hypotensive patients are treated with fluid resuscitation and vasopressors (e.g., norepinephrine), if needed. As vasoconstrictors, vasopressors might impair microvascular flap perfusion. In this experimental pig model we studied the effect of sevoflurane-induced hypotension on the perfusion of microvascular and superiorly pedicled rectus abdominis myocutaneous flaps. In addition, we evaluated the effect of norepinephrine on flap perfusion when it was used for correction of hypotension. Microdialysis (MD) was used to detect metabolic changes, as it is a sensitive method to detect early changes of tissue metabolism and ischemia in different tissue components of soft tissue flaps. The main finding of this study was that moderate degree of normovolemic hypotension or the use of norepinephrine for the correction of this hypotension did not affect flap perfusion as assessed by MD. More studies are clearly needed to confirm the safety of norepinephrine in clinical use in microsurgery.
    No preview · Article · Jun 2011 · Journal of Reconstructive Microsurgery
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    ABSTRACT: Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome. A multicenter, randomized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007. A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit (ICU) were randomized to receive either non-invasive cardiac output monitoring for 24 hrs (minimally invasive cardiac output/MICO group; n = 201) or usual care (control group; n = 187). The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study. The number of hemodynamic instability criteria at baseline (MICO group mean 2.0 (SD 1.0), control group 1.8 (1.0); P = .06) and severity of illness (SAPS II score; MICO group 48 (18), control group 48 (15); P = .86)) were similar. At 6 hrs, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (mean difference 5%; 95% confidence interval of the difference -3 to 14%; P = .24). Hemodynamic support with fluids and vasoactive drugs, and pulmonary artery catheter use (MICO group: 19%, control group: 26%; P = .11) were similar in the two groups. The median length of ICU stay was 2.0 (interquartile range 1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The hospital mortality was 26% in the MICO group and 21% in the control group (P = .34). Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome. Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output--especially their impact on the process of care--before any large-scale outcome studies are attempted. The study was registered at ClinicalTrials.gov (Clinical Trials identifier NCT00354211).
    Full-text · Article · Jun 2011 · Critical care (London, England)
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    ABSTRACT: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. ClinicalTrials.gov: NCT00962156.
    Full-text · Article · Jan 2011 · Trials
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    ABSTRACT: This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care. PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later. The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = < 0.001). Patients with septic shock had higher PCT concentrations than patients without (P = 0.02). PCT concentrations did not differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99, respectively), but mortality was lower in patients whose PCT concentration decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007). PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.
    Full-text · Article · Nov 2010 · Critical care (London, England)
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    ABSTRACT: The aim of this survey was to investigate clinicians' current approach to the haemodynamic management and resuscitation endpoints in septic shock. This cross-sectional, self-reported questionnaire-based survey was sent to the clinical director of selected ICUs in 16 European countries. The questionnaire consisted of two parts and 25 questions. The first part retrieved general information on the hospital and ICU, and the second part of the questionnaire collected detailed information on the approach to haemodynamic management of septic shock. Of 481 clinicians invited to participate, 237 (49.3%) responded. Ninety-two questionnaires were excluded because of more than 20% missing responses, rendering 145 (30.1%) for statistical analysis. Administration of albumin (P = 0.007), gelatine preparations (P = 0.002), Ringer's solution (P = 0.02) and isotonic saline (P = 0.001) for fluid resuscitation varied between respondents from different countries. Further differences between respondents from different countries were observed for the choice of the first-line inotropic drug (P < 0.001), use of supplementary vasopressin (P = 0.02), supplementary fludrocortisone (P = 0.05) and measurement of cardiac output with the transpulmonary thermodilution (P = 0.001), lithium dilution (P = 0.004) and oesophageal Doppler (P = 0.005) technique. Mean arterial blood pressure (87%), central venous oxygen saturation (65%), central venous pressure (59%), systolic arterial blood pressure (48%), mixed venous oxygen saturation (42%) and cardiac index (42%) were the six haemodynamic variables most commonly claimed to be used as resuscitation endpoints. The current approach to the haemodynamic management of septic shock patients in a selected cohort of European ICU clinicians is in agreement with the Surviving Sepsis Campaign guidelines with the exception of the haemodynamic goals.
    No preview · Article · Nov 2010 · European Journal of Anaesthesiology
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    ABSTRACT: 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. 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. 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. 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.
    Full-text · Article · Oct 2010 · Intensive Care Medicine