scholarly journals Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yasser Sakr ◽  
◽  
Michael Bauer ◽  
Axel Nierhaus ◽  
Stefan Kluge ◽  
...  
Keyword(s):  
Septic Shock ◽  
Multicentre Study ◽  
Replacement Therapy ◽  
Dropout Rate ◽  
Human Albumin ◽  
Expected Improvement ◽  
Size Estimation ◽  
Usual Practice ◽  
Randomized Controlled ◽  
First Choice

Abstract Background Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. Methods/design The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2–3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40–80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. Discussion The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease. Trial registration ClinicalTrials.gov NCT03869385. Registration on 18 July 2019. Protocol version: Final 3.0.

Vitamin C, Thiamine, and Hydrocortisone in the Treatment of Sepsis: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

2021 ◽  
pp. 088506662098780
Author(s):  
Yazan Zayed ◽  
Bashar N. Alzghoul ◽  
Momen Banifadel ◽  
Hima Venigandla ◽  
Ryan Hyde ◽  
...  
Keyword(s):  
Septic Shock ◽  
Length Of Stay ◽  
Vitamin C ◽  
Sofa Score ◽  
Sequential Analysis ◽  
Trial Sequential Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Icu Length Of Stay ◽  
Significant Difference

Background: There is a conflicting body of evidence regarding the benefit of vitamin C, thiamine, and hydrocortisone in combination as an adjunctive therapy for sepsis with or without septic shock. We aimed to assess the efficacy of this treatment among predefined populations. Methods: A literature review of major electronic databases was performed to include randomized controlled trials (RCTs) evaluating vitamin C, thiamine, and hydrocortisone in the treatment of patients with sepsis with or without septic shock in comparison to the control group. Results: Seven studies met our inclusion criteria, and 6 studies were included in the final analysis totaling 839 patients (mean age 64.2 ± 18; SOFA score 8.7 ± 3.3; 46.6% female). There was no significant difference between both groups in long term mortality (Risk Ratio (RR) 1.05; 95% CI 0.85-1.30; P = 0.64), ICU mortality (RR 1.03; 95% CI 0.73-1.44; P = 0.87), or incidence of acute kidney injury (RR 1.05; 95% CI 0.80-1.37; P = 0.75). Furthermore, there was no significant difference in hospital length of stay, ICU length of stay, and ICU free days on day 28 between the intervention and control groups. There was, however, a significant difference in the reduction of SOFA score on day 3 from baseline (MD −0.92; 95% CI −1.43 to −.41; P < 0.05). In a trial sequential analysis for mortality outcomes, our results are inconclusive for excluding lack of benefit of this therapy. Conclusion: Among patients with sepsis with or without septic shock, treatment with vitamin C, thiamine, and hydrocortisone was not associated with a significant reduction in mortality, incidence of AKI, hospital and ICU length of stay, or ICU free days on day 28. There was a significant reduction of SOFA score on day 3 post-randomization. Further studies with a larger number of patients are needed to provide further evidence on the efficacy or lack of efficacy of this treatment.

scholarly journals Hydroxyethyl starch 130/0.4 for volume replacement therapy in surgical patients: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xu ◽  
Siying Wang ◽  
Leilei He ◽  
Hong Yu ◽  
Hai Yu
Keyword(s):  
Replacement Therapy ◽  
Meta Analysis ◽  
Postoperative Mortality ◽  
Kidney Injury ◽  
Volume Replacement ◽  
Surgical Patients ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Volume Replacement Therapy ◽  
Type Of Surgery

Abstract Background The safety of perioperative intravenous hydroxyethyl starch (HES) products, specifically HES 130/0.4, continues to be the source of much debate. The aim of this meta-analysis was to update the existing evidence and gain further insight into the clinical effects of HES 130/0.4 on postoperative outcomes for volume replacement therapy in surgical patients. Methods MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2020 for relevant randomized controlled trials (RCTs) on perioperative use of HES 130/0.4 in adult surgical patients. The primary outcome was postoperative mortality and secondary outcomes were the incidence of acute kidney injury (AKI) and requirement for renal replacement therapy (RRT). The analysis was performed using the random-effects method and the risk ratio (RR) with a 95% confidence interval (CI). We performed the risk-of-bias assessment of eligible studies and assessed the overall quality of evidence for each outcome. Results Twenty-five RCTs with 4111 participants were finally included. There were no statistical differences between HES 130/0.4 and other fluids in mortality at 30 days (RR 1.28, 95% CI 0.88 to 1.86, p = 0.20), the incidence of AKI (RR 1.23, 95% CI 0.99 to 1.53, p = 0.07), or requirement for RRT (RR 0.75, 95% CI 0.37 to 1.53, p = 0.43). Overall, there was a moderate certainty of evidence for all the outcomes. There was no subgroup difference related to the type of surgery (p = 0.17) in the incidence of AKI. As for the type of comparator fluids, however, there was a trend that was not statistically significant (p = 0.06) towards the increased incidence of AKI in the HES 130/0.4 group (RR 1.22, 95% CI 0.97 to 1.54) compared with the crystalloid group (RR 1.21, 95% CI 0.27 to 3.91). Subgroup analyses according to the type of surgery demonstrated consistent findings. Conclusions This systematic review and meta-analysis suggests that the use of HES 130/0.4 for volume replacement therapy compared with other fluids resulted in no significant difference in postoperative mortality or kidney dysfunction among surgical patients. Given the absent evidence of confirmed benefit and the potential trend of increased kidney injury, we cannot recommend the routine clinical use of HES 130/0.4 for volume replacement therapy in surgical patients from the perspective of benefit/risk profile. However, the results need to be interpreted with caution due to the limited sample size, and further well-powered RCTs are warranted. Trial registration PROSPERO registry reference: CRD42020173058

scholarly journals Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricardo Castro ◽  
Eduardo Kattan ◽  
Giorgio Ferri ◽  
Ronald Pairumani ◽  
Emilio Daniel Valenzuela ◽  
...  
Keyword(s):  
Septic Shock ◽  
Randomized Controlled Trial ◽  
Fluid Resuscitation ◽  
Controlled Trial ◽  
Tissue Perfusion ◽  
Capillary Refill Time ◽  
Capillary Refill ◽  
Randomized Controlled ◽  
Microcirculatory Flow ◽  
The Impact

Abstract Background Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. Results Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375–2625] vs. 1500 [1000–2000], p = 0.3), or balances (982[249–2833] vs. 15,800 [740–6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. Conclusions CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)

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