Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients - an economic evaluation.

BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25-0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.

Economic aspects of intraoperative coagulation management targeting higher fibrinogen concentrations during major craniosynostosis surgery.

BACKGROUND: Results of a previously published study demonstrated a significant decrease in transfusion requirements and calculated blood loss for pediatric major craniosynostosis surgery, if a ROTEM(®) FIBTEM trigger of <13 mm (early substitution group) was applied as compared to a trigger of <8 mm (conventional group). The aim of this study was a posthoc analysis of the costs for this coagulation management. METHODS: The total volume as well as the number of units or bags for all transfused blood products and coagulation factors were recorded for each case. The number of laboratory and point-of-care coagulation tests was also analyzed. Total blood product costs were calculated according to the local prices per unit. RESULTS: The total cost for all transfused/administered blood products/coagulation factors per patient was a median of 1023EUR (IQR 850EUR-1058EUR) in the early substitution group as compared to a median of 910EUR (IQR 719EUR-1351EUR) in the conventional group (P = 0.81). No difference in the number of coagulation tests performed was observed. CONCLUSION: In this study, the use of a higher fibrinogen trigger was not linked to a significant increase in total costs for transfused blood products and coagulation factors, and may offer an economically equivalent approach to coagulation management.

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.

Cryoprecipitate therapy.

Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr. However, cryoprecipitate is no longer administered according to its original purpose, and is now most commonly used to replenish fibrinogen levels in patients with acquired coagulopathy, such as in clinical settings with haemorrhage including cardiac surgery, trauma, liver transplantation (LT), or obstetric haemorrhage. Cryoprecipitate is a pooled product that does not undergo pathogen inactivation, and its administration has been associated with a number of adverse events, particularly transmission of blood-borne pathogens and transfusion-related acute lung injury. As a result of these safety concerns, along with emerging availability of alternative fibrinogen preparations, cryoprecipitate has been withdrawn from use in a number of European countries. Compared with the plasma from which it is prepared, cryoprecipitate contains a high concentration of coagulation factor VIII, coagulation factor XIII, and fibrinogen. Cryoprecipitate is usually licensed by regulatory authorities for the treatment of hypofibrinogenaemia, and recommended for supplementation when plasma fibrinogen levels decrease below 1 g litre(-1); however, this threshold is empiric and is not based on solid clinical evidence. Consequently, there is uncertainty over the appropriate dosing and optimal administration of cryoprecipitate, with some guidelines from professional societies to guide clinical practice. Randomized, controlled trials are needed to determine the clinical efficacy of cryoprecipitate, compared with the efficacy of alternative preparations. These trials will allow the development of evidence-based guidelines in order to inform physicians and guide clinical practice.

The use fibrinogen/thrombin-coated equine collagen patch in children requiring reoperations for congenital heart disease. A single center clinical experience.

AIM: The aim of this study was to evaluate the efficacy and cost-effectiveness of fibrinogen/thrombin-coated collagen patch (FTCCP)(TachoSil®) during intraoperative hemostasis in patients with congenital heart disease, who required a reoperation during childhood. METHODS: We reviewed data on the intraoperative blood product requirements and hospital costs of children (age <16 years) who underwent a reoperation for treating their congenital heart disease between January 2009 and December 2011. RESULTS: One-hundred and seventeen patients were included. Median age at surgery was 2.1 years (range 3 days-14.1 years). Main causes of intraoperative bleeding were: 1) reinforcement of suture lines (106 patients, 90.6%); 2) lung lesions (5 patients, 4.2%); 3) epicardial lesions (3 patients, 2.6%); and 4) chest wall lesions (3 patients, 2.6%). At logistic regression the amount of packed red blood cells (PRBC) requirement was significantly higher in patients with preoperative cyanosis (P=0.008, OR=3.85) and in patients who required the use of cardiopulmonary bypass (P=0.005, OR=21.19). The use of FTCCP (N.=90 patients) as first line treatment was significantly associated with a lower PRBC requirement (P=0.0003, OR=0.1) which in addition to the avoidance of other hemostatic/sealant agents, leads to lower hospital cost. CONCLUSION: FTCCP is an effective hemostatic agent which can be safely used during the hemostasis of children requiring reoperations for their congenital heart malformations. When used as first line treatment, with specific indications, FTCCP limited the intraoperative PRBC requirement and the use of other hemostatic/sealant agents thus reducing hospital costs.

Recombinant activated factor VII use in critically ill infants with active hemorrhage.

INTRODUCTION: Recombinant activated factor VII (rFVIIa) is infrequently used off-label in infants despite a paucity of data in this population. We report a retrospective review of rFVIIa use in infants focusing on safety and efficacy. METHOD: Between 2002 and 2007, 32 critically ill nonhemophiliac infants less than 1 year old received rFVIIa at our institution. Indications of rFVIIa and post-rFVIIa venous thrombosis were reviewed. Transfusion requirements were calculated 8 hours before and after rFVIIa administration. RESULTS: Infants received on average 2 doses of rFVIIa at a mean dosage of 90 microg/kg. Active hemorrhage was the indication for rFVIIa in 24 infants, which included postoperative bleeding in 16 and nonsurgical bleeding in 8. The remaining 8 infants had preoperative coagulopathy. Thrombosis was noted in 4 infants (13%) and was not related to transfusion requirements, the number of doses, or dosage of rFVIIa. For infants who had active hemorrhage, rFVIIa was able to significantly reduce the requirements of packed red blood cells by 36.17 mL/kg (P < .005), platelets by 10.31 mL/kg (P < .01), and cryoprecipitates by 2.19 mL/kg (P < .05). CONCLUSION: This is the first large case series demonstrating the efficacy of rFVIIa in critically ill infants with active hemorrhage by reducing their transfusion requirements. Furthermore, venous thrombosis was not associated with increase in either the number of doses or dosage of rFVIIa.

[A medical and economic study about use of hemostatic glues in cardiac surgery]. / Etude médicoéconomique en chirurgie cardiaque : application aux colles hémostatiques.

INTRODUCTION: The impact of the use of biological and synthetic glues in cardiac surgery was assessed by an economic and medical study. MATERIAL AND METHODS: The observational prospective study had duration of three months. All the patients undergoing cardiac surgery were included in the study. The end points were medical (blood transfusion) and economic (duration and cost of the stay in hospital). There were 2 groups: treated or not by glues. STATISTICAL ANALYSIS: T Student tests. RESULTS: Among 154 patients, the 2 principal indications were valvular replacement (48%) and coronary artery bypass grafting (37%). Fifty seven (37%) patients received a glue. The number of transfused globular units and the duration of the stay in the intensive care unit were significantly higher (p<0.05) by treated patients. CONCLUSION: Not only the use of glues did not decrease the post-operative bleedings but it increased also the cost of the stay in hospital. Guidelines were validated by the hospital Commission on drugs.

Do the benefits of shorter hospital stay associated with the use of fleece-bound sealing outweigh the cost of the materials?

OBJECTIVES: To compare the cost of materials and hospitalization for standard techniques (suturing, stapling and electrocautery) for sealing the lung after pulmonary resection with those for a fleece-bound sealing procedure. METHODS: This cost comparison analysis uses as its basis a prospective randomised clinical trial involving 152 patients with pulmonary lobectomy/segmentectomy (standard technique group: 77 patients; fleece-bound sealing group: 75 patients). The cost comparison was performed from the economic perspective of Austrian and German hospitals, taking into consideration the cost of materials for the two alternatives as well as the mean time to hospital discharge. RESULTS: The clinical study found significantly smaller postoperative air leaks in the fleece-bound sealing group. The mean times to chest drain removal and to hospital discharge were also significantly reduced after application of fleece-bound sealing [5.1 vs. 6.3 days (P=0.022) and 6.2 vs. 7.7 days (P=0.01), respectively]. The cost of materials for sealing air leaks amounted to euro47 per patient in the standard technique group and euro410 per patient in the fleece-bound sealing group. The 1.5-day reduction in the length of hospital stay associated with fleece-bound sealing represents a saving of euro462 per patient. CONCLUSIONS: There was an overall saving of euro99 for the fleece-bound sealing procedure compared to standard techniques for sealing the lung following pulmonary resection.

An economic model of haemophilia in Mexico.

A model was developed to assess the lifetime costs and outcomes associated with haemophilia in Mexico. A retrospective chart review of 182 type A haemophiliacs was conducted for patients aged 0-34 years receiving one of three treatments: (i) cryoprecipitate at clinic; (ii) concentrate at home; or (iii) concentrate at clinic. Patients treated at home experienced 30% less joint damage, used 13-54% less factor VIII, had four times fewer clinic visits, and utilized half as many hospital days than those treated at a clinic. For cryoprecipitate at clinic patients, the annual incidence rates of HCV and HIV were calculated to be 3.6% and 1.4% respectively. The life expectancy for patients receiving cryoprecipitate and those receiving concentrate was estimated to be 49 years and 69 years respectively, with 58% of cryoprecipitate patients predicted to die of AIDS before age 69. Across the lifespan, the average annual cost of care was US$11,677 (MN$110,464) for cryoprecipitate at clinic patients, US$10,104 (M$95,580) for concentrate at home patients and US$18,819 (MN$178,027) for concentrate at clinic patients. Using a 5% discount rate, the incremental lifetime cost per year of life added for treatment with concentrate at home compared with cryoprecipitate at a clinic was US$738 (MN$6981). Rank order stability analysis demonstrated that the model was most sensitive to the cost of fVIII. These results indicate that treatment with concentrate at home compared with cryoprecipitate at a clinic substantially improves clinical outcomes at reduced annual cost levels.