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  • Malik AK
  • Amer AO
  • Tingle SJ
  • Thompson ER
  • White SA
  • et al.
Cochrane Database Syst Rev. 2023 Aug 8;8(8):CD010872 doi: 10.1002/14651858.CD010872.pub2.

Adults undergoing liver resection (22 randomised controlled trials, n= 2,945).


Fibrin-based haemostatic agents (FBHAs).


No intervention. Non-FBHAs.


FBHAs vs. no intervention (6 RCTs, 1,001 participants): It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58; 95% CI [0.89, 7.44] 4 trials), serious adverse events (RR 0.96; 95% CI [0.88, 1.05] 4 trials), postoperative transfusion (RR 1.04; 95% CI [0.77, 1.40] 5 trials), reoperation (RR 2.92, 95% CI [0.58, 14.61] 2 trials), or postoperative bile leak (RR 1.00; 95% CI [0.67, 1.48] 4 trials), as the certainty of evidence was very low for all these outcomes. FBHAs vs. non-FBHAs (16 RCTs, 1,944 participants): It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03; 95% CI [0.62, 1.72] 11 trials), postoperative transfusion (RR 0.92; 95% CI [0.68, 1.25] 7 trials), reoperation (RR 0.48; 95% CI [0.25, 0.90] 3 trials), or postoperative bile leak (RR 1.15; 95% CI [0.60, 2.21] 9 trials), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99; 95% CI [0.95, 1.03] 9 trials, low-certainty evidence).


Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use.


To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection.


We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials.


We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery.


Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables.


We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence).


The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

  • Phung LC
  • Farrington EK
  • Connolly M
  • Wilson AN
  • Carvalho B
  • et al.
Am J Obstet Gynecol. 2021 Sep;225(3):250.e1-250.e38 doi: 10.1016/j.ajog.2021.04.258.

To compare the available evidence on intravenous oxytocin dosing regimens for the prevention of postpartum hemorrhage following cesarean delivery.


We searched Ovid MEDLINE, Embase, Global Index Medicus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Controlled Register of Trials, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for eligible studies published until February 2020.


We included any randomized or nonrandomized study published in peer-reviewed journals that compared at least 2 different dosing regimens of intravenous oxytocin for postpartum hemorrhage prevention in women undergoing cesarean delivery.


Two authors independently assessed the eligibility of studies, extracted the data, and assessed the risk of bias. The primary outcome was incidence of postpartum hemorrhage ≥1000 mL. Other review outcomes included use of additional uterotonics, blood loss, and adverse maternal events. Data were analyzed according to the type of intravenous administration (bolus only, infusion only, or bolus plus infusion) and total oxytocin dose. A meta-analysis was performed on randomized trials and the results were reported as risk ratios or mean differences with 95% confidence intervals. The Grading of Recommendations, Assessment, Development, and Evaluations scale was used to rate the certainty of evidence. Findings from dose-finding trials and nonrandomized studies were reported narratively.


A total of 35 studies (7333 women) met our inclusion criteria and included 30 randomized trials and 5 nonrandomized studies. There were limited data available from the trials for most outcomes, and the results were not conclusive. Compared with bolus plus infusion regimens, bolus only regimens probably result in slightly higher mean blood loss (mean difference, 52 mL; 95% confidence interval, 0.4-104 mL; moderate certainty). Among the bolus plus infusion regimens, initial bolus doses <5 IU may reduce nausea (risk ratio, 0.26; 95% confidence interval, 0.11-0.63; low certainty) when compared with doses of 5-9 IU. Total oxytocin doses of 5-9 IU vs total doses of 10-19 IU may increase the use of additional uterotonics (risk ratio, 13.00; 95% confidence interval, 1.75-96.37; low certainty). Effects on other outcomes were generally inconclusive.


There are limited data available for comparisons of IV oxytocin regimens for postpartum hemorrhage prevention following cesarean delivery. Bolus plus infusion regimens may lead to minor reductions in mean blood loss and initial bolus doses of <5 IU may minimize nausea. Bolus only regimens of 10 IU vs bolus only regimens of 5 IU may decrease the need for additional uterotonics, however, further comparative trials are required to understand the effects on other key outcomes, particularly hypotension.

  • Ganio C
  • Tenewitz FE
  • Wilson RC
  • Moyles BG
J Foot Ankle Surg. 1993 May-Jun;32(3):263-8.

The treatment of chronic, nonhealing wounds is discussed. The authors have successfully utilized locally acting growth factors as an adjunct to aggressive, comprehensive management in a clinical setting. At the Holmes Regional Wound Care Center, wounds with an average duration of 75 weeks at presentation were 100% epithelialized in an average of 10 weeks of therapy. The use of topical PROCUREN, or autologous platelet-derived wound healing factors (PDWHF) is introduced to the podiatric literature.