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High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial
Garbero E, Livigni S, Ferrari F, Finazzi S, Langer M, Malacarne P, Meca MCC, Mosca S, Olivieri C, Pozzato M, et al
Intensive care medicine. 2021
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Editor's Choice
Abstract
PURPOSE This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.
PICO Summary
Population
Patients aged 14 or more with septic shock, enrolled in the COMPACT-2 multicentre trial (n= 115).
Intervention
High dose coupled plasma filtration-adsorption (CPFA), (n= 63).
Comparison
Standard care (n= 52).
Outcome
The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards. An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure; a dose-response relationship was observed between treated plasma volume and mortality. The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock.
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Therapeutic Plasma Exchange Protects Patients with Sepsis-Associated Disseminated Intravascular Coagulation by Improving Endothelial Function
Weng J, Chen M, Fang D, Liu D, Guo R, Yang S
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2021;27:10760296211053313
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Abstract
The mortality rate of sepsis-associated disseminated intravascular coagulation (DIC) is high. This study aimed to explore the efficacy of therapeutic plasma exchange (TPE) in sepsis-associated DIC patients by improving endothelial function. A total of 112 sepsis-associated DIC patients were randomly divided into the TPE group (n = 40), the heparin (HP) group (n = 36), and the SHAM group (n = 36). The SHAM group received conventional treatment; the HP group was treated with HP based on conventional treatment; and the TPE group received conventional treatment plus TPE. The differences in thromboelastogram (TEG), platelet (PLT), coagulation function, and the endothelial cell (EC) injury biomarkers at 6 h, 24 h, 48 h, 72 h, and 7 days after TPE were compared among the three groups, and the three groups were compared in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-Related Organ Failure Assessment (SOFA) score, the length of intensive care unit (ICU) hospitalization, 28-day mortality rate, 28-day cumulative survival rate, the incidence of bleeding events, the incidence of acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS). The efficacy of TPE is superior to the HP in increasing PLT, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of ICU hospitalization, 28-day mortality, and the incidence of bleeding events, AKI, and ARDS with statistically significant differences (P < .05). Moreover, the effect of TPE outperforms HP on the EC injury biomarkers with statistically significant differences (P < .05). Our results suggest that TPE may be more effective than HP in the treatment of patients with sepsis-associated DIC. The possible mechanism is via improving endothelial function.
PICO Summary
Population
Patients with sepsis-associated disseminated intravascular coagulation (DIC), (n= 112).
Intervention
Therapeutic plasma exchange (TPE), (n= 40).
Comparison
Heparin (HP), (n= 36); conventional treatment (n= 36).
Outcome
The efficacy of TPE was superior to the HP in increasing platelet, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of intensive care unit hospitalization, 28-day mortality, and the incidence of bleeding events, acute kidney injury and acute respiratory distress syndrome with statistically significant differences. The effect of TPE outperformed HP on the endothelial cell injury biomarkers with statistically significant differences.
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Sepsis-related anemia in a pediatric intensive care unit: transfusion-associated outcomes
Elshinawy M, Kamal M, Nazir H, Khater D, Hassan R, Elkinany H, Wali Y
Transfusion. 2020;60 Suppl 1:S4-s9
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Abstract
BACKGROUND Pediatric patients with sepsis in intensive care units are at high risk of developing anemia, which might have adverse effects on their prognosis. This study aimed to evaluate the impact of red blood cell (RBC) transfusion on the outcomes of patients admitted to a pediatric intensive care unit (PICU) with sepsis. METHODS We conducted a prospective randomized clinical trial, enrolling 67 children, aged 2 to 144 months who were admitted to a PICU with a new episode of sepsis from November 2017 to April 2018. Patients were allocated randomly to two groups: Group 1, liberal transfusion strategy group, including 33 patients who had initial hemoglobin (Hb) between 7 or greater and less than 10 g/dL and received an RBC top-up transfusion to 12 g/dL; and Group 2, restrictive strategy group, including 34 patients who had the same Hb range and did not receive RBCs. Patients with Hb less than 7 or greater than 10 g/dL were excluded. RESULTS Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%). CONCLUSIONS Compared to the restrictive transfusion strategy, liberal transfusion might be associated with a worse outcome. However, the possible role of other known and unknown confounding factors and minor protocol violations should be taken into consideration. We recommend minimizing factors worsening anemia in PICU patients to reduce the need for transfusion.
PICO Summary
Population
Children admitted to a pediatric intensive care unit (PICU) with new episode of sepsis (n= 67).
Intervention
Liberal transfusion strategy group, (Group 1) received an red blood cell (RBC) top-up transfusion to 12 g/dL (n=33).
Comparison
Restrictive strategy group, (Group 2) did not receive RBCs. (n= 34).
Outcome
Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%).
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Heterogenous treatment effects of transfusion thresholds by patient age: post-hoc analysis of the TRISS trial
Jonsson AB, Granholm A, Rygard SL, Holst LB, Moller MH, Perner A
Acta anaesthesiologica Scandinavica. 2019
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Editor's Choice
Abstract
BACKGROUND Use of a lower haemoglobin (Hb) threshold to guide red blood cell (RBC) transfusion is now generally recommended in critically ill patients, but uncertainty remains regarding the optimal HB-threshold for RBC transfusion in patients of different ages. METHODS We conducted a post-hoc analysis of 998 patients with septic shock and anaemia randomised to RBC transfusion at a Hb-threshold of 7 g/dl [4.3 mmol/l] vs. 9 g/dl [5.6 mmol/l] in the Transfusion Requirements in Septic Shock (TRISS) trial. We assessed if there were heterogeneous effects between the allocated Hb-threshold and patient age categorised and on the continuous scale. The primary outcome was 1-year mortality; the secondary outcome was 90-day mortality. Both outcomes were analysed using logistic regression models and in sensitivity analyses with additional adjusting for site of enrolment, presence of haematological malignancy and the Sequential Organ Failure Assessment (SOFA) score. The secondary analyses were Kaplan-Meier curves with corresponding log-rank tests. RESULTS We found no heterogeneity between patient age and the allocated Hb-thresholds for RBC transfusion for 1-year mortality or 90-day mortality in the primary analyses. The sensitivity analyses suggested heterogeneity between age groups regarding 90-day mortality, however, this was not consistent for 1-year mortality or when assessing age on the continuous scale. CONCLUSION In this post-hoc study of ICU patients with septic shock, we found no reliable heterogeneous effects of transfusion at a Hb-threshold of 7 vs. 9 g/dl according to patient age on mortality. However, due to low power, this study should only be considered as hypothesis-generating.
PICO Summary
Population
Patients with septic shock and anaemia, (n=998) who had not previously been transfused in the intensive care unit (ICU).
Intervention
Lower threshold group: RBC transfusion at a lower Hb-threshold of 7 g/dl [4.3 mmol/l], (n=502).
Comparison
Higher threshold group: RBC transfusion at a higher Hb-threshold of 9 g/dl [5.6 mmol/l], (n=496).
Outcome
No heterogeneity between patient age and the allocated Hb-thresholds for RBC transfusion for 1-year mortality or 90-day mortality in the primary analyses. The sensitivity analyses suggested heterogeneity between age groups regarding 90-day mortality, however, this was not consistent for 1-year mortality or when assessing age on the continuous scale.