A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]
Journal of hepatology. 2022
BACKGROUND AND AIM The choice of resuscitation fluid in cirrhosis patients with sepsis-induced hypotension (SIH) is unclear. 5% albumin has been superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties with plasmalyte in reversing SIH. METHODS Critically-ill cirrhosis(CIC) patients underwent open-label randomization to receive either 20% albumin [0.5-1.0gm/kg over 3 hours; n=50] or plasmalyte (30ml/kg over 3 hours, n=50). The primary end-point of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at three hours. RESULTS Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate(mmol/L) [6.16±3.18 vs. 6.38±4.77; p=0.78), MAP (mmHg) [51.4±6.52 vs. 49.9±4.45; p=0.17] and SOFA score [10.8±2.96 vs. 11.1±4.2; p=0.68] respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat (ITT) analysis, albumin was superior to plasmalyte in achieving the primary end-point (62% vs. 22%; p<0.001). A rapid decline in arterial lactate (P=0.03), a lesser proportion of dialysis [48% vs. 62%; p=0.16], and a higher time to initiation of dialysis (in hours) [68.13±47.79 vs. 99.7± 63.4; p=0.06] was seen with albumin. However, the 28-day mortality was not different (58% vs. 62%, p=0.57). Patients in the albumin group required discontinuation of therapy in 11 (22%) patients due to adverse effects compared to none in plasmalyte group. CONCLUSION In patients with cirrhosis and SIH, 20% albumin transiently improves the hemodynamics with early lactate clearance than plasmalyte but needs monitoring as it is more often attended with pulmonary complications. Both fluids provide comparable 28 days survival. NCT02721238 LAY SUMMARY The current randomized controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores hemodynamics but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in deaths at 28-days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.
Prospective Comparison of Functional and Radiological Outcomes of Arthroscopic Anterior Cruciate Ligament Reconstruction by Hamstring Graft Alone and Platelet-Rich Plasma Added to the Hamstring Graft
AIMS AND OBJECTIVES To measure the additional effect of platelet-rich plasma (PRP) on functional outcome of anterior cruciate ligament tear managed by augmenting anterior cruciate ligament (ACL) reconstruction with PRP. METHODS The present study was conducted on patients with ACL tear admitted in the department of orthopaedics, King George's Medical University, Lucknow wherein a total of 70 subjects were assigned into two groups of 35 patients each randomly, viz Group 1 in which the patients were treated by quadruple hamstring graft alone and Group 2 in which the patients were treated with augmented hamstring graft with PRP. The standardized anterior drawer test, Lachman's test, Lysholm knee score were quantified both preoperatively and postoperatively at different follow-ups and also tibial tunnel widening was measured postoperatively at different follow-ups. RESULT The present study had 70 patients with ACL tears. The mean age of patients in non-PRP groups was 29.71 ±2.99 years while that in the PRP group was 28.34±4.32 years. On comparing the improvement in grades at pre-op, immediate postop, 6 weeks, and 3 months follow-ups, there was no statistically significant difference between the two groups. The tibial tunnel widening also showed no significant difference between the two groups. CONCLUSION In our study, it was found that both the groups showed improvements in grades of anterior drawer test and Lachman's test postoperatively but the difference between both the groups was not significant. Similarly, while comparing the improvements in Lysholm knee score and tibial tunnel widening among both the groups, the difference was not significant. Follow up of 3 months was a limiting factor in our study. This technique needs further clinical evaluation to assess the long-term results.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
The New England Journal of Medicine. 2021
BACKGROUND Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
Critically ill patients with severe COVID-19 (n= 1,098).
Therapeutic-dose anticoagulation with heparin (n= 534).
Usual-care pharmacologic thromboprophylaxis (n= 564).
The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis. The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.
Standard-volume plasma-exchange improves outcomes in patients with acute liver failure - A Randomized Controlled Trial
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021
BACKGROUND High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS ALF patients [aged 31.5±12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15±1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p=0.02), amelioration of SIRS (84% vs. 26%; P=0.02), reduction in ammonia levels [(221.5±96.9) vs.(439±385.6) μg/dl, P=0.02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P=0.001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P=0.04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079).
"Signs and Symptoms Tell All"-Pseudoaneurysm as a Cause of Postoperative Bleeding after Orthognathic Surgery-Report of a Case and a Systematic Review of Literature
Journal of maxillofacial and oral surgery. 2021;20(3):345-355
PURPOSE Pseudoaneurysms are one of the rare complications that can be encountered after the orthognathic surgery. We are presenting a new case of pseudoaneurysm of bilateral sphenopalatine artery after Bijaw Surgery in a young male and a systematic review of all the cases in the literature emphasizing on signs and symptoms, epistaxis or bleeding episodes and treatment outcomes. METHODS A systematic research strategy was planned according to the PRISMA guidelines, and articles were taken from 1986 to September, 2019. A total of 899 articles were selected for screening, out of which only 26 articles met our inclusion and exclusion criteria. These were included in the study for qualitative analysis. RESULTS Most PAs were associated with Lefort I osteotomy (69.7%), followed by sagittal split osteotomy (24.24%). Average intraoperative blood was 635 ml. Maximum number of episodes of epistaxis/swelling or bleeding occurred in second week. Mean bleeding episodes were 2.58 ± 0.996. The arteries commonly affected were internal maxillary artery (42%), sphenopalatine artery (27.27%), facial artery (15.15%), descending palatine artery (12.12%), internal carotid artery (9.09%) and infraorbital artery (3.03%). Embolization was treatment of choice in 81.81% cases. CONCLUSION If a patient has recurrent epistaxis or swelling after orthognathic surgery, it is advisable to go for diagnostic imaging like angiography without any delay. In recent times, advanced techniques and expertise are readily available for early diagnosis and management of pseudoaneurysm.
Perioperative blood loss after embolization of hypervascular musculoskeletal tumors outside of the spine: A single-center ten year experience and systematic review of the literature
Clinical imaging. 2021;79:24-29
PURPOSE To evaluate outcomes following trans-arterial embolization of hypervascular appendicular bony tumors in patients undergoing orthopedic resection by performing a systematic review including data from the authors' institution. MATERIALS AND METHODS From April 2008 to August 2018, 73 patients (59 males, mean age 58.1 years) with musculoskeletal tumors presented for embolization for preoperative devascularization prior to orthopedic surgery. A retrospective chart review was performed to identify demographic, procedural and surgical data. A systematic review of the Pubmed, Medline, and Web of Science databases was performed to identify studies in which pre-operative embolization was performed of appendicular MSK tumors, and with measurements of estimated blood loss. All the variables listed above were recorded. A patient level analysis was performed to determine average estimated blood loss. RESULTS 58 patients (47 men, 11 women, range 21-84 years) were included in our institutional analysis. The median EBL was 500 mL (range 100-3000). There was no difference in EBL between RCC (719.6 ± 626.1) and non-RCC groups (855.6 ± 657.5); p = 0.44. The median intra-operative transfusion requirement was 1.0 unit (range 0-8 ± 2.06). From 1984 to 2015, 9 studies were identified that provided data for a total of 118 patients (46 males, 42 females, range 10-82 years). The mean and median post-surgical EBL across all patients was 976.9 ± 78.5 (SE) and 725 mL (range 10-7000), respectively. There were no complications related to non-target embolization. CONCLUSION Preoperative trans-arterial embolization of hypervascular MSK neoplasms appears to be safe and effective in minimizing peri- and post-operative bleeding while keeping transfusion requirements low.
Efficacy of Tranexamic Acid in Reducing Blood Loss in Lower Segment Cesearean Section: A Randomised Controlled Study
Journal of obstetrics and gynaecology of India. 2020;70(6):479-484
OBJECTIVES To determine the efficacy of tranexamic acid in decreasing blood loss in elective/emergency LSCS. MATERIALS AND METHODS A prospective randomised case control study was done in 200 pregnant women undergoing elective/emergency LSCS in the Department of Obstetrics and Gynaecology, at a tertiary care teaching hospital in Mysuru, from December 2018 to September 2019. Women in the age group of 18-35 years were included in the study. Those with anaemia (Hb < 10 gm%), hypertension in pregnancy, bleeding diathesis, GDM on insulin, polyhydramnios, oligohydramnios, cardiac and chronic liver disorders were excluded from the study. Two hundred women undergoing emergency/elective LSCS were divided into case (group 1) or control (group 2) groups using a computer-generated random number table. Tranexamic acid (10 mg/Kg) was given in 100 ml Normal Saline 10 mins prior to skin incision to women in the first group, along with routine care (10 Units of Oxytocin IM soon after extraction of the baby). Routine care, as per institutional protocol, was followed in the second group. The primary outcome was to estimate the intraoperative blood loss. Blood loss was measured by weighing pads, mops, drapes before and after surgery and blood in the suction container after surgery. Two separate suction catheters and containers were used, in order to minimise mixing of blood and amniotic fluid. Total blood loss was calculated as the difference in the weight of the pads, mops and drapes before and after surgery and the sum of the amount of blood in suction container. The difference between the pre-operative and post-operative haemoglobin and haematocrit was compared. The pre-operative, intra-operative and post-operative hemodynamics were also compared. RESULTS Statistical analysis was done using MS Excel and R-3.5.1 software. Unpaired and paired t test were used. In our study, there was a significant decrease in intraoperative bleeding in women receiving tranexamic acid. Women in the control group had a significant fall in the postoperative hemoglobin when compared to women who received tranexamic acid. Also, women who received tranexamic acid did not develop any significant hemodynamic changes during or immediately after the surgery. CONCLUSION Tranexamic acid can be safely used as a prophylactic agent to reduce bleeding during elective and emergency LSCS.
Pregnant women undergoing elective or emergency lower segment caesarean section (n= 200).
Tranexamic acid (10 mg/Kg) in 100 ml Normal Saline 10 mins prior to skin incision to along with routine care (n= 100).
Routine care, as per institutional protocol (n= 100).
There was a significant decrease in intraoperative bleeding in women receiving tranexamic acid. Women in the control group had a significant fall in the postoperative haemoglobin when compared to women who received tranexamic acid. Also, women who received tranexamic acid did not develop any significant hemodynamic changes during or immediately after the surgery.
Preoperative Intravenous Iron Therapy and Survival after Colorectal Cancer Surgery: Long Term Results from the IVICA Randomised Controlled Trial
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2020
AIM: Preoperative iron is frequently used for the correction of anaemia in colorectal cancer surgery. However, enteral iron intake may promote tumour growth and progression which could influence cancer recurrence and patient survival. We explore the long term outcomes of patients receiving either oral or intravenous iron replacement therapy as part of a previous randomised controlled trial. METHODS The IVICA trial randomised anaemic colorectal cancer patients to receive either oral (OI, control) or intravenous (IVI, treatment) iron prior to their elective operation. Follow up analysis of all patients recruited to this multicentre trial who underwent surgical resection with curative intent was performed. Kaplan-Meier survival estimates, and Cox proportional hazard models were used to compare groups. A pooled group multivariable analysis comparing patients who achieved resolution of anaemia preoperatively to those who did not was also undertaken. RESULTS 110 of the 116 patients previously enrolled were eligible for analysis (OI n=56, IVI n=54). Median overall follow up duration was 61 months (IQR 46-67). No significant difference in 5-year overall survival (HR 1.22, 95% CI 0.65-2.28 P=0.522) or disease free survival (HR 1.08, 95% CI 0.61-1.92 P=0.79) was observed between OI and IVI. Pooled analysis of treatment groups found that preoperative resolution of anaemia led to improved 5 year overall survival on multivariable analysis (HR 3.38 [1.07-11.56, P=0.044). CONCLUSION We recommend IVI for the preoperative correction of anaemia. Route of iron therapy did not significantly influence survival. Preoperative anaemia correction may lead to an overall survival advantage following elective colorectal cancer surgery.
Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): Study design and methodology for an international, adaptive Bayesian randomized controlled trial
Clinical Trials (London, England). 2020;:1740774520943846
BACKGROUND Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care. METHODS An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible. The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation or death. CONCLUSION Using an adaptive trial design, the Anti-Thrombotic Therapy To Ameliorate Complications of COVID-19 trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.
Endovascular Management of Hemarthrosis in Patients with Bleeding Diatheses: Systematic Review
Cardiovascular and interventional radiology. 2019
PURPOSE In this systematic review, we report the safety and efficacy of embolization for treating hemarthrosis in patients with bleeding diatheses with or without a history of prior arthroplasty. MATERIALS AND METHODS A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. A structured search was performed in PubMed, Web of Science, MEDLINE, and SCOPUS databases of patients undergoing embolization for hemarthrosis. Demographic data, clinical history, angiographic findings, interventions, and outcomes were extracted and tabulated. RESULTS The search identified 97 unique titles of which 15 were deemed relevant comprising 78 patients with coagulopathies undergoing 93 embolization procedures. Mean follow-up time was 29 months (range 3-116.5). In the 29 patients who underwent arthroplasty prior to embolization for hemarthrosis, there were 11 bleeding recurrences (37.9%). Of these patients who experienced recurrences, 10 underwent repeat embolization as coagulation factor replacement was not sufficient to address the re-bleeding. In the 49 patients with bleeding diatheses who underwent embolization for hemarthrosis with no history of prior arthroplasty, there were 11 recurrences (22.4%) and 4 of these patients underwent repeat embolization with favorable results. There were four major procedure-related complications. CONCLUSION Transarterial embolization is safe and effective in addressing recurrent hemarthrosis in patients with bleeding diatheses with or without a history of arthroplasty of the affected joint.