The effect of early vasopressin use on patients with septic shock: A systematic review and meta-analysis
The American journal of emergency medicine. 2021;48:203-208
BACKGROUND The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.
Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: a multi-center, open-label, randomized controlled trial
Journal of Thrombosis and Haemostasis : JTH. 2021
BACKGROUND Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. OBJECTIVE To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. METHODS We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight-adjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. RESULTS A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P=0.31 by chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33 to 1.37; P=0.28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. CONCLUSION In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.
Adults hospitalized with COVID-19 admitted to an intensive care unit (n= 176).
Enoxaparin intermediate dose (n= 88).
Enoxaparin standard dose (n= 88).
In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin. Unadjusted Cox proportional hazards modelling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin. Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm.
Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial
BMJ (Clinical research ed.). 2021;375:n2400
OBJECTIVE To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN Randomised controlled, adaptive, open label clinical trial. SETTING 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m(2). At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION ClinicalTrials.gov NCT04362085.
EXPRESS: Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Proof-of-Concept Randomized Controlled Trial
International journal of stroke : official journal of the International Stroke Society. 2021;:17474930211006580
Background Remote ischemic conditioning (RIC) can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage (ICH). Aims This study aimed to evaluate the safety and preliminary efficacy of RIC in patients with ICH.Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial ICH presenting within 24-48 hours of onset were randomly assigned to receive medical therapy plus RIC for consecutive 7 days or medical therapy alone. The primary safety outcome was neurological deterioration within 7 days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 d ([hematoma volume at 7 d â hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results The mean age was 59.3Â±11.7 years and hematoma volume was 13.9Â±4.5 mL. No subjects experienced neurological deterioration within 7 days of enrollment, and no subject died or experienced RIC-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19Â±5.07 mL in the control group and 13.55Â±3.99 mL in the RIC group, and they were 8.54Â±3.99 mL and 6.95Â±2.71 mL at 7 days after enrollment, respectively, not a significant difference (p>0.05 each). The hematoma resolution rate in the RIC group (49.25Â±9.17%) was significantly higher than in the control group (41.92Â±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015). The absolute PHE volume was 17.27Â±8.34 mL in the control group and 12.92Â±7.30 mL in the RIC group at 7 days after enrollment, not a significant between-group difference (p=0.087), but the relative PHE in the RIC group (1.77Â±0.39) was significantly lower than in the control group (2.02Â±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023). At 90-day follow-up, 13 subjects (65%) in the RIC group and 12 subjects (60%) in the control group achieved favorable functional outcomes (mRS scoreâ¤3), not a significant between-group difference (p=0.744).Conclusions Repeated daily RIC for consecutive 7 days was safe and well-tolerated in patients with ICH, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, effects RIC on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.
Oral vs intravenous tranexamic acid in total-knee arthroplasty and total hip arthroplasty: A systematic review and meta-analysis
BACKGROUND This study aimed to compare the efficacy and safety of oral tranexamic acid (TXA) with intravenous (IV) TXA in reducing perioperative blood loss in total-knee arthroplasty (TKA) and total-hip arthroplasty (THA). METHODS PubMed, Web of Science, Embase, and Cochrane Library were fully searched for relevant studies. Studies comparing the efficacy and safety of oral TXA with IV TXA in TKA and THA were included in this research. Odds ratio (OR) or risk difference (RD) was applied to compare dichotomous variables, while mean difference (MD) was used to compare continues variables. RESULTS A total of 7 studies (5 randomized controlled trials and 2 retrospective studies) were included into this study. As for patients undergoing TKA or THA, there were no obvious differences between oral TXA group and IV TXA group in hemoglobin (Hb) drop (MD = 0.06, 95% confidence interval [CI] = -0.01 to 0.13, P = .09), transfusion rate (OR = 0.78, 95% CI = 0.54-1.13, P = .19), total blood loss (MD = 16.31, 95% CI = -69.85 to 102.46, P = .71), total Hb loss (MD = 5.18, 95% CI = -12.65 to 23.02, P = .57), length of hospital stay (MD = -0.06, 95% CI = -0.30 to 0.18, P = .63), drain out (MD = 21.04, 95% CI = -15.81 to 57.88, P = .26), incidence of deep vein deep vein thrombosis (RD = 0.00, 95% CI = -0.01 to 0.01, P = .82) or pulmonary embolism (RD = 0.00, 95% CI = -0.01 to 0.01, P = .91). The sample size of this study was small and several included studies were with relatively low quality. CONCLUSION Oral TXA is equivalent to IV TXA in reducing perioperative blood loss and should be recommended in TKA and THA. More high-quality studies are needed to elucidate this issue.
Preoperative transfusion in patients with sickle cell disease to prevent perioperative complications: A systematic review and meta-analysis
Background Sickle cell disease (SCD) is associated with perioperative vascular (SCD-related) and non-vascular complications. To minimize perioperative complications during elective surgery, either exchange blood transfusion or simple blood transfusion can be used. We systematically reviewed the literature and meta-analyzed randomized and observational trials comparing exchange transfusion to simple transfusion, as well as studies comparing preoperative transfusion to no transfusion to assess the relative risk (RR) and benefit of each strategy in sickle cell patients undergoing surgery. Methods Medline, Embase, and the Cochrane-controlled trial register were searched to identify studies that evaluated exchange transfusion to simple transfusion, as well as studies comparing any form of blood transfusion with no transfusion. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Pooled RR was estimated using a random effects model. Results Three randomized trials and seven observational studies were included. We found there was no difference between exchange transfusion and simple transfusion for perioperative mortality, vascular, or non-vascular perioperative complications. However, transfusion-related complications (RR 2.41, 95% confidence interval (CI): 1.49-3.91) and the amount of blood transfused (mean difference 2.03, 95% CI: 1.23-2.83) were higher in those treated with exchange transfusion versus simple transfusion. Similarly, there was no difference in perioperative mortality, vascular, or non-vascular perioperative complications between those treated with preoperative transfusion strategy and no transfusion strategy. Conclusion Based on the current literature, neither preoperative exchange transfusion nor simple transfusion reduces perioperative complications in patients with SCD who are undergoing surgery; however, available studies were underpowered to detect a treatment effect.