Hydroxyethyl starch (HES) corrected is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.
In ...this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.
Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval CI, 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.
Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).
Purpose
New-onset atrial fibrillation (NOAF) is common and associated with increased morbidity and mortality. However, its clinical importance and management in critically ill patients are not well ...described. The aim of this scoping review is to assess the epidemiology and management strategies of NOAF during critical illness.
Method
The review was conducted in accordance with the PRISMA extension for scoping reviews. We searched PubMed, EMBASE and the Cochrane Library for studies assessing the incidence, outcome and management strategies of NOAF in adult critically ill patients. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Results
A total of 99 studies were included, of which 79 were observational and 20 were interventional. The incidence of NOAF varied from 1.7% to 43.9% with considerable inter-population variation (very low quality of evidence). Commonly identified risk factors for NOAF included higher age, cardiovascular comorbidities and sepsis. The occurrence of NOAF was associated with adverse outcomes, including stroke, prolonged length of stay and mortality (very low quality of evidence). We found limited data on the optimal management strategy with no evidence for firm benefit or harm for any intervention (very low/low quality of evidence).
Conclusions
The definition and incidence of NOAF in critically ill patients varied considerably and many risk factors were identified. NOAF seemed to be associated with adverse outcomes, but data were very limited and current management strategies are not evidence-based.
Abstract Purpose The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and ...coagulopathy in septic patients. Materials and methods Septic patients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation. Results Sixty-seven patients were included, of whom 14 turned out to receive noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n = 53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P < .05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P < .05), and 28- and 90-day mortality ( P < .05). Conclusions In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood.
Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in ...clinical practice. We aimed to evaluate associations between hospital and patient characteristics and fluid resuscitation volumes in ICU patients with severe sepsis.
We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume and secondary outcome total fluid input administered from 24 hours before randomisation until the end of day 3 post-randomisation. We performed multivariate analyses with hospital and patient baseline characteristics as covariates to assess associations with fluid volumes given.
We included 654 patients who were in the ICU for 3 days and had fluid volumes available. Individual trial sites administered significantly different volumes of fluid resuscitation and total fluid input after adjusting for baseline variables (P<0.001). Increased lactate, higher cardiovascular and renal SOFA subscores, lower respiratory SOFA subscore and surgery were all independently associated with increased fluid resuscitation volumes.
Hospital characteristics adjusted for patient baseline values were associated with differences in fluid resuscitation volumes given in the first 3 days of severe sepsis. The data indicate variations in clinical practice not explained by patient characteristics emphasizing the need for RCTs assessing fluid resuscitation volumes fluid in patients with sepsis.
Abstract Purpose The aim of this study was to assess associations between consecutive thrombelastography (TEG) profiles and standard coagulation tests and disease severity and mortality in patients ...with severe sepsis. Materials and Methods This was a prospective observational study of adults with severe sepsis admitted to the intensive care unit (ICU). Clinical scores/variables, infection, TEG, biochemistry, therapy, and overall mortality were recorded. Results Fifty patients (60% men, median age 62 years, 28-day mortality 24%) were included. At admission, 22%, 48%, and 30% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (maximum amplitude MA), respectively. Hypocoagulable patients had higher Sequential Organ Failure Assessment and disseminated intravascular coagulation scores compared with hypercoagulable patients and higher 28-day mortality compared with normocoagulable patients (all P < .05). Most patients (73%-91%) displayed a TEG MA comparable with the admission profile during the initial 4 ICU days or until death/discharge. Patients progressing to hypocoagulable MA had a high early mortality (80%) and hypocoagulable MA independently predicted 28-day mortality (adjusted odds ratio, 4.29 95% confidence interval, 1.35-13.65, P = .014). In hypocoagulable and hypercoagulable patients, only fibrinogen ( P = .041 and P < .001, respectively) contributed independently to clot strength, whereas both platelets ( P < .001) and fibrinogen ( P < .001) contributed independently to clot strength in normocoagulable patients. Conclusions The ICU admission TEG MA remained constant for several days in patients with severe sepsis and hypocoagulable MA independently predicted 28-day mortality.
Abstract Purpose The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. ...Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed to investigate associations between HES vs Ringer and changes in plasma biomarkers reflecting endothelial damage and coagulation impairment. Materials and methods Six biomarkers, including soluble thrombomodulin (sTM) and plasminogen activator inhibitor 1 (PAI-1), were assessed in a subgroup of 208 patients from the 6S trial. We analyzed differences in plasma concentration in the 2 intervention groups using linear or logistic regression models. Results The increase in plasma sTM was lower in the HES group (− 1.8 ng/mL; 95% confidence interval, − 2.9 to − 0.7; P = .002). The change was not statistically significant associated with mortality whereas increase in plasminogen activator inhibitor 1 was (odds ratio for 1-unit increase, 1.04; 95% confidence interval, 1.01-1.08; P = .01). Conclusions Resuscitation with HES vs Ringer decreased early endothelial damage. Although this finding should be interpreted with caution, it indicates that the increased mortality observed with HES in the 6S trial may not be explained by endothelial damage and it emphasizes the challenge of using surrogate markers as outcome.
Gone fishing in a fluid trial Hjortrup, Peter B; Haase, Nicolai; Wetterslev, Jørn ...
Critical Care and Resuscitation/aCritical care and resuscitation,
03/2016, Letnik:
18, Številka:
1
Journal Article
Odprti dostop
To maximise the yield of existing data by assessing the effect on mortality of being born under the zodiac sign Pisces in a trial of intravenous (IV) fluids.
A retrospective observational study, with ...no predefined hypothesis or statistical analysis plan, of 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation, randomised in the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial.
Ninety-day mortality.
We included all 798 randomised patients in our study; 70 (9%) were born under the sign of Pisces. The primary outcome (death within 90 days after randomisation) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03).
In a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.
Objective To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.Design Systematic review with meta-analyses and trial sequential ...analyses of randomised clinical trials.Data sources Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.Trial selection Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.Data extraction Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.Results 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference −1.43, 95% confidence interval −2.01 to −0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.Conclusions Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.Trial registration PROSPERO CRD42013004272.
Resuscitation with hydroxyethyl starch (HES) is controversial. In this review, we will present the current evidence for the use of HES solutions including data from recent high-quality randomized ...clinical trials.
Meta-analyses of HES vs. control fluids show clear signals of harm including adverse effects on kidney and haemostatic function, and trends towards increased mortality. These results are mainly based on recent large randomized clinical trials comparing tetrastarch (HES 130/0.4 and HES 130/0.42) vs. crystalloid in patients in the ICU. Trials in trauma and surgical patients cannot adequately assess safety issues and do not show clear benefit with the use of HES. There is currently no firm evidence that tetrastarch has better safety profile than the former HES solutions.
There is no evidence for an overall beneficial effect of HES in any subgroup of critically ill patients, but there are clear signs of harm. As safer alternatives exist, we recommend that HES is no longer used in critically ill patients.
Purpose
We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock.
Methods
...We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction group fluid boluses were permitted only if signs of severe hypoperfusion occurred, while in the standard care group fluid boluses were permitted as long as circulation continued to improve.
Results
The co-primary outcome measures, resuscitation fluid volumes at day 5 and during ICU stay, were lower in the fluid restriction group than in the standard care group mean differences −1.2 L (95 % confidence interval −2.0 to −0.4);
p
< 0.001 and −1.4 L (−2.4 to −0.4) respectively;
p
< 0.001. Neither total fluid inputs and balances nor serious adverse reactions differed statistically significantly between the groups. Major protocol violations occurred in 27/75 patients in the fluid restriction group. Ischaemic events occurred in 3/75 in the fluid restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08–1.27;
p
= 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23–0.92;
p
= 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36–1.40;
p
= 0.32).
Conclusions
A protocol restricting resuscitation fluid successfully reduced volumes of resuscitation fluid compared with a standard care protocol in adult ICU patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes.
Trial registration
NCT02079402.
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