Systematic review of hemostatic agents used in vascular surgery.

BACKGROUND: Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost. METHODS: A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study. RESULTS: We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient. CONCLUSIONS: Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

The effect of prophylactic hemoclips on the risk of delayed post-endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective cohort study.

BACKGROUND: Endoscopic mucosal resection (EMR) is a minimally invasive procedure used for the treatment of lesions in the gastrointestinal (GI) tract. There is increased usage of hemoclips during EMR for the prevention of delayed bleeding. This study aimed to evaluate the effect of hemoclips in the prevention of delayed bleeding after EMR of upper and lower GI tract lesions. METHOD: This is a retrospective cohort study using the Kaiser Permanente Southern California (KPSC) EMR registry. Lesions in upper and lower GI tracts that underwent EMR between January 2012 and December 2015 were analyzed. Rates of delayed bleeding were compared between the hemoclip and no-hemoclip groups. Analysis was stratified by upper GI and lower GI lesions. Lower GI group was further stratified by right and left colon. We examined the relationship between clip use and several clinically-relevant variables among the patients who exhibited delayed bleeding. Furthermore, we explored possible procedure-level and endoscopist-level characteristics that may be associated with clip usage. RESULTS: A total of 18 out of 657 lesions (2.7%) resulted in delayed bleeding: 7 (1.1%) in hemoclip group and 11 (1.7%) in no-hemoclip group (p = 0.204). There was no evidence that clip use moderated the effects of the lesion size (p = 0.954) or lesion location (p = 0.997) on the likelihood of delayed bleed. In the lower GI subgroup, clip application did not alter the effect of polyp location (right versus left colon) on the likelihood of delayed bleed (p = 0.951). Logistic regression analyses showed that the clip use did not modify the likelihood of delayed bleeding as related to the following variables: use of aspirin/NSAIDs/anti-coagulants/anti-platelets, pathologic diagnoses (including different types of colon polypoid lesions), ablation, piecemeal resection. The total number of clips used was 901 at a minimum additional cost of $173,893. CONCLUSION: Prophylactic hemoclip application did not reduce delayed post-EMR bleed for upper and lower GI lesions in this retrospective study performed in a large-scale community practice setting. Routine prophylactic hemoclip application during EMR may lead to significantly higher healthcare cost without a clear clinical benefit.

Effects of modification of trauma bleeding management: A before and after study.

OBJECTIVE: We hypothesised that the association of tranexamic acid (TXA) administration and thromboelastometry-guided haemostatic therapy (TGHT) with implementation of Damage Control Resuscitation (DCR) reduced blood products (BP) use and massive transfusion (MT). METHODS: Retrospective comparison of 2 cohorts of trauma patients admitted in a university hospital, before (Period 1) and after implementation of DCR, TXA (first 3-hours) and TGHT (Period 2). Patients were included if they received at least 1 BP (RBC, FFP or platelet) or coagulation factor concentrates (fibrinogen or prothrombin complex) during the first 24-hours following the admission. RESULTS: 380 patients were included. Patients in Period 2 (n = 182) received less frequently a MT (8% vs. 33%, P < 0.01), significantly less BP (RBC: 2 units [1-5] vs. 6 [3-11]; FFP: 0 units [0-2] vs. 4 [2-8]) but more fibrinogen concentrates (3.0 g [1.5-4.5] vs. 0.0 g [0.0-3.0], P < 0.01). Multivariate logistic regression analysis identified Period 1 as being associated with an increased risk of receiving MT (OR: 26.1, 95% CI: 9.7-70.2) and decreased survival at 28 days (OR: 2.0, 95% CI: 1.0-3.9). After propensity matching, the same results were observed but there was no difference for survival and a significant decrease for the cost of BP (2370 ± 2126 vs. 3284 ± 3812 €, P: 0.036). CONCLUSION: Following the implementation of a bundle of care including DCR, TGHT and administration of TXA, we observed a decrease to the use of blood products, need for MT and an improvement of survival.

Gelatin Paste as an Alternative Cost-Effective Hemostatic Agent in Cranial Surgery: Doing More with Less.

OBJECTIVE: To present an alternative cost-effective hemostatic agent (HA) for cranial surgery and to describe the technique to produce it. METHODS: This HA has been used in 3 reference centers over the last year during 230 procedures, including different types of pathology, such as skull base, oncology, vascular, and trauma, either for endoscopic or open approaches. This agent was made from a low-cost and worldwide-available gelatin foam which was mixed with saline solution in 2 syringes and connected by a 3-way stopcock, making a useful hemostatic paste. RESULTS: The cost was 16 and 28 times less than SURGIFLO and FLOSEAL, respectively. The mean time to prepare the mix was 4 minutes. It was very effective for venous and low-flow bleeding. CONCLUSIONS: The presented technique offers a reliable and cost-effective way of achieving hemostasis in cranial surgery, therefore allowing hospitals with limited resources to perform advanced procedures in a safer way.

Safety of a condom uterine balloon tamponade (ESM-UBT) device for uncontrolled primary postpartum hemorrhage among facilities in Kenya and Sierra Leone.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone. METHODS: Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study. Three expert maternal health investigator physicians analyzed each complication/adverse event and developed consensus on whether there was a potential causal relationship associated with use of the ESM-UBT device. Adverse events/complications specifically investigated included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis. RESULTS: Of the 201 women treated with an ESM-UBT device in Kenya and Sierra Leone, 189 (94.0%) survived. Six-week or longer follow-up was recorded in 156 of the 189 (82.5%). A causal relationship between use of an ESM-UBT device and one death, three perineal injuries and one case of mild endometritis could not be completely excluded. Three experts found a potential association between these injuries and an ESM-UBT device highly unlikely. CONCLUSION: The ESM-UBT device appears safe for use in women with uncontrolled PPH. TRIAL REGISTRATION: Trial registration was not completed as data was collected as a quality assurance measure for the ESM-UBT kit.

Same-day discharge after coronary stenting and femoral artery device closure: A randomized study in stable and low-risk acute coronary syndrome patients.

OBJECTIVE: To compare same-day (SD) vs. delayed hospital discharge (DD) after single and multivessel coronary stenting facilitated by femoral closure device in patients with stable angina and low-risk acute coronary syndrome (ACS). METHODS: University of Southern California patients were screened and coronary stenting was performed in 2480 patients. Four hundred ninety-three patients met screening criteria and consented. Four hours after percutaneous coronary intervention, 100 were randomized to SD (n=50) or DD (n=50). Patients were followed for one year; outcomes-, patient satisfaction-, and cost analyses were performed. RESULTS: Groups were well distributed, with similar baseline demographic and angiographic characteristics. Mean age was 58.1±8.8years and 86% were male. Non-ST-elevation myocardial infarction and unstable angina were the clinical presentations in 30% and 44% of the SD and DD groups, respectively (p=0.2). Multivessel stenting was performed in 36% and 30% of SD and DD groups, respectively (p=0.14). At one year, two patients from each group (4%) required unplanned revascularization and one patient in the SD group had a gastrointestinal bleed that required a blood transfusion. Six SD and four DD patients required repeat hospitalization (p=0.74). There were no femoral artery vascular complications in either group. Patient satisfaction scores were equivalent. SD discharge was associated with $1200 savings per patient. CONCLUSIONS: SD discharge after uncomplicated single and multivessel coronary stenting of patients with stable, low-risk ACS, via the femoral approach facilitated by a closure device, is associated with similar clinical outcomes, patient satisfaction, and cost savings compared to overnight (DD) hospital stay.

A Cost-Effective Delivery System for FloSeal During Endoscopic and Microscopic Brain Surgery.

OBJECTIVE: To share our experience with a new delivery system for the flowable hemostatic matrix, FloSeal, in endoscopic and microscopic skull base surgery. METHODS: We prospectively analyzed the use of FloSeal with a hemostatic delivery system in transnasal endoscopic and microscopic skull base procedures performed at the authors' institution from January 1, 2015, to June 30, 2015. In all cases the number of aliquots was noted for the entire operation, and the total number of FloSeal ampules of 5 mL was also recorded. RESULTS: Our device allowed controlled application of small amounts (0.5-1 mL) of FloSeal to the site of bleeding. This controlled application resulted not only in increased visibility during its application, but it also reduced the amount of FloSeal required during the procedure. We were able to use 5-10 applications per 5-mL ampule of FloSeal within an individual procedure. No procedure required more than one 5-mL ampule of FloSeal. Therefore, the use of our device results in a reduction of costs. Prior to the use of our device, we were often only able to use 1 vial of 5 ml of material for 1 or 2 applications, especially in transnasal endoscopic procedures when working along a deep corridor. CONCLUSIONS: Our results indicate that our delivery device of FlowSeal can effectively control hemostasis by applying small amounts of FlowSeal to the site of bleeding. This results in increased visibility during hemostasis and a reduction of cost.

Cost of Bleeding in Trauma and Complex Cardiac Surgery.

PURPOSE: Trauma and complex cardiac surgery are associated with a high risk of bleeding complications. The difference in costs between patients who require bleeding control measures and those who do not is poorly understood. Our goal was to assess the cost of care and outcomes for patients in these settings. METHODS: Patients >18 years of age, who were discharged between January 2010 and December 2012, were retrospectively identified in the Premier Hospital Database based on International Classification of Disease, Ninth Revision codes. These patients were categorized as having received blood products ("bleeding patients") or not ("nonbleeding patients"). Patients with costs and length of stay (LOS) of zero were excluded. Differences in treatment costs and outcomes were assessed using univariate analysis and multivariate modeling. FINDINGS: Bleeding trauma patients (n = 8800) had a 150% higher total cost of care (P < 0.001; 146% after excluding costs of agents used for bleeding control, P < 0.001), an 81.3% longer hospital LOS (P < 0.001), and a 65.2% longer intensive care unit (ICU) LOS (P < 0.001) than nonbleeding patients (n = 53,727). Bleeding complex cardiac surgery patients (n = 82,832) had a 133.2% higher total cost of care (P < 0.001; 128.7% after excluding costs of agents used for bleeding control, P < 0.001), a 155.6% longer hospital LOS (P < 0.001), and an 89.3% longer ICU LOS (P < 0.001) than nonbleeding patients (n = 380,902). IMPLICATIONS: Trauma and cardiac surgery patients who experienced bleeding and received allogeneic blood product transfusions had significantly worse outcomes, including longer LOS, greater inpatient mortality, and higher costs of care (even when excluding costs of agents used for bleeding control) than those who did not.

Economic and outcomes consequences of TachoSil®: a systematic review.

BACKGROUND: TachoSil(®) is a medicated sponge coated with human fibrinogen and human thrombin. It is indicated as a support treatment in adult surgery to improve hemostasis, promote tissue sealing, and support sutures when standard surgical techniques are insufficient. This review systematically analyses the international scientific literature relating to the use of TachoSil in hemostasis and as a surgical sealant, from the point of view of its economic impact. METHODS: We carried out a systematic review of the PubMed literature up to November 2013. Based on the selection criteria, papers were grouped according to the following outcomes: reduction of time to hemostasis; decrease in length of hospital stay; and decrease in postoperative complications. RESULTS: Twenty-four scientific papers were screened, 13 (54%) of which were randomized controlled trials and included a total of 2,116 patients, 1,055 of whom were treated with TachoSil. In the clinical studies carried out in patients undergoing hepatic, cardiac, or renal surgery, the time to hemostasis obtained with TachoSil was lower (1-4 minutes) than the time measured with other techniques and hemostatic drugs, with statistically significant differences. Moreover, in 13 of 15 studies, TachoSil showed a statistically significant reduction in postoperative complications in comparison with the standard surgical procedure. The range of the observed decrease in the length of hospital stay for TachoSil patients was 2.01-3.58 days versus standard techniques, with a statistically significant difference in favor of TachoSil in eight of 15 studies. CONCLUSION: This analysis shows that TachoSil has a role as a supportive treatment in surgery to improve hemostasis and promote tissue sealing when standard techniques are insufficient, with a consequent decrease in postoperative complications and hospital costs.

Cost-effectiveness of contemporary vascular closure devices for the prevention of vascular complications after percutaneous coronary interventions in an all-comers PCI population.

AIMS: The present observational case-control study assessed the cost-effectiveness of contemporary vascular closure devices (VCDs) for the prevention of vascular complications in an all-comers transfemoral percutaneous coronary intervention (PCI) population. METHODS AND RESULTS: A total of 8,292 consecutive PCI patients were enrolled from a single-centre prospective registry from January 2005 to December 2010. VCDs were available from July 2007 and, from that time point, VCDs were implanted in 1,780 of the 5,394 patients (33%). Vascular complications occurred in 221 (2.7%) patients. The use of VCDs was independently associated with a 53% risk reduction (OR 0.47, 95% CI: 0.3-0.7) in vascular complications (3.0% vs. 1.5%) and with a 65% risk reduction (IRR 0.37, 95% CI: 0.32-0.43) in the post-PCI length of hospital stay (LOS) (mean 2.8 vs. 1.5 days). Mainly due to the reduced LOS, the patients with VCDs accrued vascular direct medical costs (VCD, diagnosis and treatment of vascular complications, post-PCI LOS) that were on average 498€ less than those accrued by the non-VCD patients. The cost-effectiveness was present across all vascular risk profiles. CONCLUSIONS: In this large, all-comers transfemoral PCI population, the use of VCDs was independently associated with a reduction in the rate of vascular complications and the post-PCI length of hospital stay and proved to be cost-saving across all vascular risk profiles.

The cost-effectiveness analysis of video capsule endoscopy compared to other strategies to manage acute upper gastrointestinal hemorrhage in the ED.

STUDY OBJECTIVE: Acute upper gastrointestinal (GI) hemorrhage is a common presentation in hospital-based emergency departments (EDs). A novel diagnostic approach is to use video capsule endoscopy to directly visualize the upper GI tract and identify bleeding. Our objective was to evaluate and compare the relative costs and benefits of video capsule endoscopy compared to other strategies in low- to moderate-risk ED patients with acute upper GI hemorrhage. METHODS: We constructed a model using standard decision analysis software to examine the cost-effectiveness of 4 available strategies for a base-case patient who presents to the ED with either mild- or moderate-risk scenarios (by Glasgow-Blatchford Score) for requiring invasive hemostatic intervention (ie, endoscopic, surgical, etc) The 4 available diagnostic strategies were (1) direct imaging with video capsule endoscopy performed in the ED; (2) risk stratification using the Glasgow-Blatchford score; (3) nasogastric tube placement; and, finally, (4) an admit-all strategy. RESULTS: In the low-risk scenario, video capsule endoscopy was the preferred strategy (cost $5691, 14.69 quality-adjusted life years [QALYs]) and was more cost-effective than the remaining strategies including nasogastric tube strategy (cost $8159, 14.69 QALYs), risk stratification strategy (cost $10,695, 14.69 QALYs), and admit-all strategy (cost $22,766, 14.68 QALYs). In the moderate-risk scenario, video capsule endoscopy continued to be the preferred strategy (cost $9190, 14.56 QALYs) compared to nasogastric tube (cost $9487, 14.58 QALYs, incremental cost-effectiveness ratio $15,891) and more cost effective than admit-all strategy (cost, $22,584, 14.54 QALYs.) CONCLUSION: Video capsule endoscopy may be cost-effective for low- and moderate-risk patients presenting to the ED with acute upper GI hemorrhage.

An inexpensive device to treat postpartum hemorrhage: a preliminary proof of concept study of health provider opinion and training in Nepal.

BACKGROUND: Obstetric hemorrhage remains the leading cause of maternal mortality in resource limited areas. An inexpensive pneumatic anti-shock garment was devised of bicycle tubes and tailored cloth which can be prepared from local materials in resource-limited settings. The main purposes of this study were: 1) to determine acceptability of the device by nurses and midwives and obtain suggestions for making the device more suitable for use in their particular work environments, 2) to determine whether a three hour training course provided adequate instruction in the use of this device for the application of circumferential abdominal pelvic pressure, and 3) determine production capability and cost in a resource-limited country. METHODS: Fifty-eight nurse and midwife participants took part in three sessions over eight months in Nepal. Correct device placement was assessed on non-pregnant participants using ultrasound measurement of distal aortic flow before and after device inflation, and analyzed using confidence intervals. Participants were surveyed to determine acceptability of the device, obtain suggestions for improvement, and to collect data on clinical use. RESULTS: Device placement achieved flow decreases with a mean of 39% (95% CI 25%-53%, p < 0.001) in the first session, 28% (95% CI 21%-33%, P < 0.001) after four months and 29% (95% CI 24%-34%, p < 0.001) at 8 months. All nurses and midwives thought the device would be acceptable for use in obstetric hemorrhage and that they could make, clean, and apply it. They quickly learned to apply the device, remembered how to apply it, and were willing and able to use the device clinically. Ten providers used the device, each on one patient, to treat obstetric hemorrhage after routine measures had failed; bleeding stopped promptly in all ten, two of whom were transported to the hospital. Production of devices in Kathmandu using local tailors and supplies cost approximately $40 per device, in a limited production setting. CONCLUSIONS: Preliminary data suggest that an inexpensive, easily-made device is potentially an appropriate addition to current obstetric hemorrhage treatment in resource-limited areas and that further study is warranted.

Safety and efficacy of LigaSure usage in pancreaticoduodenectomy.

BACKGROUND: Over recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques. METHODS: One hundred and forty-eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri-operative outcomes were compared. RESULTS: Vascular intra-operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra-operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73. CONCLUSION: LigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD.

Incidence and costs of bleeding-related complications in French hospitals following surgery for various diagnoses.

BACKGROUND: Limited information is available on the epidemiology and economics of bleeding during surgery in France. METHOD: The objective of this study was to examine the incidence, costs and length of stay (LOS) of bleeding-related complications during various surgical procedures. RESULTS: Amongst all 88 different surgical DRGs recognised by the French database 24 (totalling 321,657 hospitalisations) yielded WB rates ≥10% (range 10.3-25.3%). The highest DRG rates were for transplantations, cardiac and major orthopaedic surgery, vascular and solid organ surgery. CONCLUSIONS: The present study for France demonstrates a significant increase of hospital LOS and associated costs following post-surgical bleeding, supporting the need for blood conservation strategies.

Discomfort and costs in epistaxis treatment.

Epistaxis is a very common ENT event. Apart from the effectiveness of the different treatment options, the discomfort and the financial burden are of great importance. It has been the aim of this study to obtain data regarding the discomfort/pain of the epistaxis treatments and to calculate the financial burden. During the period between April 2010 and July 2011 epistaxis patients at our hospital had the opportunity to rate the discomfort/pain they experienced during their treatment on a 0-10 VAS scale. The costs of epistaxis treatments were calculated in an extended cohort. 84 VAS scores in 61 patients were acquired and the costs of treatment were calculated in 96 patients. The lowest VAS scores were found in chemical and electric coagulation with 1.5 and 2.0, respectively, followed by surgery (3.0), Rapid Rhino packing (6.0) and balloon pack (7.5). The costs of treatments depended on whether the treatment was in an out- or inpatient setting. Surgery was not significantly more expensive than packing methods in the inpatient setting. Anterior epistaxis could be managed by local coagulation with an acceptable impact/cost ratio. At our institution, surgery was the most cost effective and the least troublesome procedure in posterior bleedings, preceded by Rapid Rhino packing if required.

Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

OBJECTIVE: Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. METHODS: From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. RESULTS: In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P < .05) in patients who received factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. CONCLUSIONS: Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role.