Improvement of hemostasis in open and laparoscopically performed partial nephrectomy using a gelatin matrix-thrombin tissue sealant (FloSeal)

Material and methods 

Between January 2001 and April 2002, 25 consecutive patients with renal cell carcinoma were treated by partial nephrectomy using a two-component tissue sealant (FloSeal). The median age was 54 years (range 42 to 71). The follow-up time was 1 to 12 months (median 3.5). The tumor diameter ranged from 2 to 5 cm (median 2.8). Fifteen cases were performed by open retroperitoneal surgery, and 10 cases were performed laparoscopically using a transperitoneal approach (Table I). The decision to perform laparoscopic versus partial nephrectomy among these 25 consecutive cases was made by the individual surgeon. No statistically significant difference in tumor size (median tumor size 3.0 versus 2.7 cm, respectively) was present between the open and laparoscopically performed procedures. All tumors were exophytic and not centrally located. The laparoscopic resection of the renal tumor was carried out using the UltraCision device (Ethicon). Vascular control was achieved by temporary occlusion of the renal vasculature, both artery and vein, before resection of the tumor. The clamping time ranged from 0 to 30 minutes. The kidney was not cooled down in each of the cases. The collecting system was not entered.

TABLE I. Patient demographics, tumor characteristics, and surgical approach

	Patient demographics
	Men (n)	16
	Women (n)	9
	Age (yr)
	Median	53
	Range	42–71
	Tumor characteristics
	Tumor size (cm)
	Median	2.8
	Range	2–5
	Tumor size in open partial nephrectomy	3 (2.5–5)
	Tumor size in laparoscopic partial nephrectomy	2.7 (2–5)
	Procedures
	Total (n)	25
	Laparoscopic partial nephrectomy (n)	10
	Retroperitoneal open partial nephrectomy (n)	15
	Clamping time (min)
	Median	18
	Range	0–30

Numbers in parentheses are the range.

The two-component tissue sealant (consisting of a gelatin matrix granula component and a thrombin component) was applied after resection of the tumor and before perfusion of the kidney. After mixing the two components, the slurry was pushed through the applicator or, in the open cases, directly onto the resected surface. Pressure with a moist sponge stick was applied for 1 to 2 minutes. No additional methods of hemostasis, such as bipolar coagulation or ligation sutures, were applied.

The following parameters were recorded: time until complete hemostasis was achieved; decrease in postoperative hemoglobin level; postoperative bleeding; and presence or absence of a perirenal hematoma 24 hours and 10 days postoperatively by ultrasonography.

Results 

Application of the tissue sealant and hemostasis 

After application of the tissue sealant for 1 to 2 minutes to the moist resection site with a sponge stick, hemostasis was almost immediate in all cases (Fig. 1). The average time to complete hemostasis was 116 seconds for all cases combined. The assessment of the length of time needed to apply the tissue sealant until hemostasis was complete was made by the operating surgeon and was dependent on the tumor size and location. No statistically significant difference was noted in the time until complete hemostasis was achieved between the laparoscopically performed cases and the open partial nephrectomies (110 ± 22 seconds versus 122 ± 35 seconds, respectively). During the laparoscopically performed partial nephrectomies, a laparoscopic applicator was used to avoid wasting the tissue sealant within the dead space of the instrument (Fig. 2). When reperfusion of the kidney was established, hemostasis was maintained without further need for coagulation or surgical closure of the resection site. No case of rebleeding occurred after the hilum was unclamped.

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FIGURE 1. Tissue sealant applied to the resection site after partial nephrectomy.

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FIGURE 2. Laparoscopic applicator for the tissue sealant (FUSION [now Baxter]).

Hemoglobin levels, intraoperative blood loss 

The estimated intraoperative blood loss, as determined by the amount of blood in the suction collector, was 118 ± 33 mL for the retroperitoneal partial nephrectomies and 109 ± 53 mL for the laparoscopically performed partial nephrectomies. The difference in intraoperative blood loss between the open and partial nephrectomies was not statistically significant.

The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median 0.7). None of the patients required blood transfusions (Table II). No cases of postoperative bleeding occurred, and no signs of infection were evident postoperatively.

TABLE II. Preoperative and postoperative hemoglobin levels and postoperative ultrasound findings 24 hours and 10 days postoperatively

		Average Blood Loss(mL)	Transfusion of Blood Products	Drop inHemoglobin(range)	Time UntilCompleteHemostasis(s)	Postoperative Ultrasound Findings
						24 hr	10 days
	Open partial nephrectomy(n = 15)	118 ± 33	None	0.8 (0.5–1.2)	122 ± 35	No perirenal hematoma	No perirenal hematoma
	Laparoscopic partialnephrectomy (n = 10)	109 ± 48	None	0.6 (0.3–1.0)	110 ± 22	No perirenal hematoma	No perirenal hematoma

Comment 

To expand the possibilities of the laparoscopic approach to nephron-sparing surgery, the achievement of a prompt and durable hemostasis is of paramount importance. Intracorporeal suturing of the renal parenchyma is time consuming and fraught with the risk of the surgical suture material cutting through the tissue.

Hemostasis by coagulation can be achieved laparoscopically but often does not provide a sufficient depth of coagulation to control the bleeding. Furthermore, the depth of coagulation is impossible to predict, and the occurrence of late bleeding caused by desquamation of the necrosed surface area has been described.

To achieve prompt and immediate hemostasis in the setting of laparoscopic nephrectomy, the tissue sealant (FloSeal) has been evaluated. It is a two-component product consisting of a thrombin component and a gelatin matrix granula component. Both parts are mixed in a syringe shortly before application, according to the manufacturer’s instructions (FUSION Medical, Fremont, Calif; now Baxter). The substance was approved by the Food and Drug Administration in 1999, after long series of testing proved its safety.1 As a protein product, it was tested with respect to the possibility of viral transmission, which was ruled out.1 The use of other local hemostatic agents, such as gelatin (Gelfoam, Pharmacia & Upjohn), thrombin, oxidized regenerated cellulose (Surgicel, Ethicon), microfibrillar collagen (Avitene, Davol), and fibrin glue (Tisseel, Oestereichisches Institut für Haemoderivate GES, MBH) has been fraught with difficulties in application, particularly in parenchymal bleeding sites without a dry surface, in difficult-to-reach locations, and by a lack of efficacy in anticoagulated patients. The FloSeal matrix, in contrast, activates the coagulation cascade while maintaining a hemostatic plug that is not easily displaced. During blood contact, the gelatin particles swell and tamponade bleeding.

The bulk of the gelatin matrix thrombin composite mechanically slows down bleeding and provides exposure to a high thrombin concentration, which accelerates the long-term hemostasis by clot formation. Since its introduction, it has been used successfully in a variety of procedures.

Reuthenbach et al.2 reported on vascular procedures, including 10 patients with abdominal aortic aneurysm repairs after implantation of a transfemoral endovascular prosthesis and one Y-graft, as well as endarterectomies of the carotid artery and embolectomies. FloSeal was used in cases of continuous profuse bleeding with intact coagulation mechanism, in bleeding despite the application of several hemostatic agents, and in difficulties during suturing of the arteries, because of inaccessibility or fragility of the tissues.2 Bleeding stopped in 15 of the cases (88%) with application of FloSeal alone. It took an average of 5.29 ± 2.7 minutes and 3.41 ± 0.21 mL of the sealant to achieve complete hemostasis. In the remaining 12% of cases, the bleeding was stopped by combining FloSeal with additional vascular sutures or local hemostatics (fibrin sponges).2, 3

Similar results have been reported in cardiac procedures. A prospective randomized trial, including 93 patients, was undertaken to compare FloSeal matrix with Gelfoam thrombin to control perioperative bleeding.4 FloSeal stopped the bleeding in 94% of patients within 10 minutes compared with 60% of the Gelfoam thrombin group and maintained hemostasis after 3 minutes in 72% of cases compared with only 23% in the control group.4

Additional use of the FloSeal matrix has been reported in head and neck surgery5 and spinal surgery.6 A multicenter, prospective, randomized trial comparing the FloSeal matrix with Gelfoam thrombin in spinal surgery including 127 patients has been conducted.6 The FloSeal matrix was able to stop the bleeding in 98% of the patients within 10 minutes compared with 90% of the controls. At 3 minutes, successful hemostasis had been achieved in 97% versus 71% of the control group.6 The occurrence of adverse events was not different between the groups.

In renal surgery, only a few studies, none of them prospective and randomized, have tried to evaluate the efficacy of tissue sealants—fibrin sealant in particular.7, 8, 9, 10 Kram et al.8 applied fibrin sealant to treat 14 renal lacerations. The sealant was sprayed over the lacerated renal parenchyma. The method required a nearly dry parenchymal surface. Deep penetrating injuries posed a problem. In these cases, fibrin was injected deep into the wound, creating a fibrin plug. No renal loss, infection, urinary fistula, or delayed bleeding resulted. Urlesberger et al.9 used fibrin sealant, consisting of fibrinogen cryoprecipitate, thrombin, factor VIII, and a proteinase inhibitor in 33 partial nephrectomies, 9 nephrotomies, and 4 renal lacerations. Sutures had to be placed in the renal parenchyma, and a collagen patch was applied in cases of renal trauma.9 The parenchymal surface had to be dry. The investigators, following this protocol, found no delayed hemorrhage, but 5 cases of urinary fistula occurred that closed spontaneously. Levinson et al.10 used fibrin sealant in seven partial nephrectomies. Provided that the cut surface showed only slow venous oozing, the hemostasis achieved by the tissue sealant was effective.

A relatively dry parenchymal surface is essential before application of conventional fibrin sealants. If it can be achieved, minor venous oozing can be stopped. Furthermore, a number of these investigations that addressed the effectiveness of fibrin sealant used one or more additional methods of hemostasis, such as suturing or argon beam coagulation.

The evolution of laparoscopic surgery in partial nephrectomy makes hemostasis a crucial and challenging part of the procedure. Janatschek et al.11 reported about their favorable experience in nephron-sparing surgery for small renal tumors. They used a variety of methods to achieve sufficient hemostasis of the renal parenchyma. Jeschke et al.12 reported recently about their experience of laparoscopic nephron-sparing surgery using bipolar coagulation and fibrin glue-coated cellulose for hemostasis in 51 cases. The mean blood loss was 282 mL (range 70 to 300) compared with 109 ± 48 mL in our group of laparoscopic partial nephrectomies with similar tumor sizes and locations. An interesting experimental approach for hemostasis in partial nephrectomy has been presented by Cornum et al.13 The investigators used a fibrin adhesive bandage, consisting of lyophilized fibrinogen and thrombin on a Vicryl mesh, in female pigs and achieved a stable and durable clot formation.

Our experience with the tissue sealant in partial nephrectomies has been encouraging. Almost immediate hemostasis was achieved and maintained after the kidney was reperfused. Significant perirenal hematoma was not evident 24 hours postoperatively. No cases of delayed bleeding occurred, and perirenal hematomas were not evident 10 days postoperatively.

Furthermore, the administration of blood products was not needed. After the evaluation of FloSeal in open partial nephrectomy, we used it for laparoscopically performed nephron-sparing surgery. Therefore, the design of a special applicator was necessary to avoid the loss of the sealant within the instrument (Fig. 2).

The experience in laparoscopy confirmed the efficacy of the sealant during nephron-sparing surgery. Conversion to an open procedure was not necessary. Furthermore, the administration of blood products intraoperatively or postoperatively was not required. As demonstrated by ultrasonography, significant perirenal hematomas 24 hours and 10 days postoperatively were not observed.

Conclusions 

The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopically performed partial nephrectomies. In contrast to other tissue sealants, it does not require a dry parenchymal surface at the time of application. The immediate and durable hemostasis achieved by the tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.