Purpose
To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.
Methods
We systematically reviewed randomised clinical trials (RCTs) comparing low-dose ...corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.
Results
There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 95% confidence interval (CI) 0.89–1.08,
p
= 0.71. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91–1.02,
p
= 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90–1.02,
p
= 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03–2.70,
p
= 0.04,
I
2
= 78%). No trials reported quality of life outcomes. Duration of shock mean difference (MD) −1.52 days; 95% CI −1.71 to −1.32,
p
< 0.0001, duration of mechanical ventilation (MD −1.38 days; 95% CI −1.96 to −0.80,
p
< 0.0001), and ICU stay (MD −0.75 days; 95% CI −1.34 to −0.17,
p
= 0.01) were shorter with corticosteroids versus placebo.
Conclusions
In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced.
PROSPERO registration no. CRD42017084037.
A lingua franca for guidelines—or a Tower of Babel? Laake, Jon Henrik; Møller, Morten Hylander
Acta anaesthesiologica Scandinavica,
August 2023, 2023-08-00, 20230801, Letnik:
67, Številka:
7
Journal Article
Patients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium ...in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis.
A post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database.
Most patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P < 0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31).
In our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis.
Clinicaltrials.gov number: NCT00962156. Registered 13 July 2009.
Objective
There is a widespread use of buffered crystalloid solutions in clinical practice. However, guidelines do not distinguish between specific types of buffered solutions and clinical equipoise ...exists. We aimed to assess the desirable and undesirable effects of acetate‐ versus lactate‐buffered solutions in hospitalised patients.
Methods
We conducted a systematic review with meta‐analysis and trial sequential analysis of randomised clinical trials assessing the use of acetate‐ versus lactate‐buffered solutions for intravenous administration in hospitalised adults and children. The primary outcome was all‐cause short‐term mortality. We adhered to our published protocol, the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement, the Cochrane Handbook and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.
Results
We included five RCTs enrolling 390 patients. We found no statistically significant difference in short‐term mortality (random effects, risk ratio RR 0.29; 95% confidence interval CI 0.06–1.51, p = .14, I2 = 0%) or hospital length of stay (LOS) (random effects, mean difference MD—1.31, 95% CI −3.66 to 1.05, p = .28, I2 = 0%) between acetate‐ versus lactate‐buffered solutions. The quality of evidence was very low. Data regarding intensive care unit LOS were reported by three trials and duration of vasopressor treatment by one trial; none of these data allowed for pooling in meta‐analyses. No trials reported data on long‐term mortality, health‐related quality of life, adverse events, duration of mechanical ventilation or renal replacement therapy.
Conclusion
In this systematic review, we found very low quantity and quality of evidence on the use of acetate‐ versus lactate‐buffered solutions in hospitalised patients.
Background
Thrombocytopenia is frequent in intensive care unit (ICU) patients and may be associated with adverse outcomes. We aimed to assess the incidence, risk factors, and outcomes associated with ...thrombocytopenia in adult ICU patients.
Methods
We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Review and Meta‐analyses extension for Scoping Reviews (PRISMA‐ScR) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included study reports on adult ICU patients with thrombocytopenia and assessed patient‐important outcomes, including mortality and health‐related quality‐of‐life.
Results
We included a total of 70 studies comprising a total of 215 098 patients; 57 were cohort studies. The incidence of thrombocytopenia varied from 8 to 56 per 100 admissions (very low quality of evidence). We identified several risk factors including age, sepsis, and higher disease severity (low quality of evidence). Thrombocytopenia was associated with bleeding, use of life support, length of stay in the ICU, and increased mortality (low/very low quality of evidence). Data on platelet transfusion before invasive procedures and transfusion thresholds were limited. No studies assessed the benefits and harms of thromboprophylaxis in ICU patients with thrombocytopenia.
Conclusions
Thrombocytopenia is common and associated with increased morbidity and mortality in adult ICU patients. Several risk factors for thrombocytopenia exists, but the evidence‐base on management strategies, including transfusion thresholds and thromboprophylaxis in ICU patients is very limited.
Severe gastrointestinal bleeding is frequent and associated with use of blood products and endoscopic and invasive procedures, including emergency surgery, which increases the risk of mortality.1 ...Interventions to stop bleeding include the use (often in an escalating manner) of proton-pump inhibitors, transfusion of blood products, therapeutic endoscopy, endovascular coiling, and open laparotomy.1,2 Tranexamic acid is also used in some patients in an attempt to inhibit blood clot breakdown by fibrinolysis that can occur in some cases.3 The use of tranexamic acid is supported by data from randomised trials and systematic reviews in patient groups with other conditions, including major trauma,4 post-partum haemorrhage,5 and surgery,6 in whom the use of tranexamic acid reduces mortality or bleeding with few adverse events. In patients with severe gastrointestinal bleeding, the evidence for the benefit of tranexamic acid has been unclear because existing data have come from few and small randomised trials, most of which had a high risk of bias.7 In The Lancet, the HALT-IT Trial Collaborators8 report the results of a randomised, double-blind, placebo-controlled trial investigating the effects of tranexamic acid in 12 009 adults (4266 35·5% female, 7743 64·5% male) with severe gastrointestinal bleeding, the majority of whom had signs of upper gastrointestinal bleeding. Patients were given a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h. Death due to bleeding within 5 days (primary outcome) occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio RR 0·99, 95% CI 0·82–1·18).
IMPORTANCE: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in ...hospitalized patients with COVID-19 who required respiratory support. OBJECTIVE: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. EXPOSURES: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). MAIN OUTCOMES AND MEASURES: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. RESULTS: A total of 1703 patients (median age, 60 years interquartile range, 52-68 years; 488 29% women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 95% CI, 0.53-0.82; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo. CONCLUSIONS AND RELEVANCE: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
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