A Comparative Efficacy Evaluation of Recombinant Topical Thrombin (RECOTHROM^®) With A Gelatin Sponge Carrier Versus Topical Oxidized Regenerated Cellulose (TABOTAMP^®/SURGICEL^®) In A Porcine Liver Bleeding Model

Figures & data

Table 1. The validated intraoperative bleeding scale (VIBe SCALE).

Grade	Visual presentation	Anatomic appearance	Qualitative description	Visually estimated rate of blood loss (mL/min)
0	No bleeding	No bleeding	No bleeding	≤1.0
1	Ooze or intermittent flow	Capillary-like bleeding	Mild	>1.0–5.0
2	Continuous flow	Venule and arteriolar-like bleeding	Moderate	>5.0–10.0
3	Controllable spurting and/or overwhelming flow	Noncentral venous- and arterial-like bleeding	Severe	>10.0–50.0
4	Unidentified or inaccessible spurting or gush	Central arterial- or venous-like bleeding	Life threatening*	>50.0

^* Systemic resuscitation is required (e.g., volume expanders, vasopressors, blood products, etc.).

The scale is designed and validated for use in clinical studies to generate labeling claims. The scale is a Likert-type scale, in which the user assigns a grade based on the overall agreement of the items listed.

This table was published in Surgery 161 (3): Lewis KM, Li Q, Jones DS, et al. Development and validation of an intraoperative bleeding severity scale for use in clinical studies of hemostatic agents. pp 771–781. Copyright Elsevier 2017.

Table 2. Initial bleeding rates in non-heparinized and heparinized animals.

	Without heparin		With heparin
All lesions with initial bleeding rates ≤10 g/min	rT + gelatin sponge carrier	ORC	rT + gelatin sponge carrier	ORC
Mean ± standard deviation	3.069 ± 1.928	3.140 ± 2.236	3.649 ± 1.810	4.326 ± 1.885
Median [interquartile range]	2.66	2.60	3.03	4.19
	[1.90–3.44]	[1.72–4.04]	[2.46–4.42]	[2.57–5.99]
Number of valid applications (n)	16	19	20	18

ORC, oxidized regenerated cellulose; rT, recombinant thrombin.

All data are g/min unless specified otherwise. Bleeding rates >10 g/min were excluded.

Figure 1. Comparison of time to hemostasis – all initial bleeding rates within intended range (≤10 g/min).

ORC, oxidized regenerated cellulose; rT, recombinant thrombin. Horizontal line and box represent the median and interquartile ranges; error bars represent maximum/minimum values.

Table 3. Time to hemostasis and number of applications by treatment in non-heparinized and heparinized animals.

	Without heparin		With heparin
All lesions with initial bleeding rates ≤10 g/min	rT + gelatin sponge carrier	ORC	rT + gelatin sponge carrier	ORC
Mean ± standard deviation	30 ± 0	200 ± 107	30 ± 0	248 ± 145
Median [interquartile range]	30	180	30	215
	[30, 30]	[120, 210]	[30, 30]	[135, 345]
Number of effective applications (n)	16	19	20	16
Number of failures (n)	0	0	0	2
Sub-set of lesions with initial bleeding rates ≤5 g/min
Mean ± standard deviation	30 ± 0	203 ± 117	30 ± 0	215 ± 156
Median [interquartile range]	30	188	30	175
	[30–30]	[105–263]	[30–30]	[108–290]
Number of effective applications (n)	15	16	17	10
Number of failures (n)	0	0	0	1
Sub-set of lesions with initial bleeding rates >5–10 g/min
Mean ± standard deviation	30	185 ± 9	30 ± 0	304 ± 116
Median [interquartile range]	–	180	30	285
	[180–195]	[30–30]	[225–394]
Number of effective applications (n)	1	3	3	6
Number of failures (n)	0	0	0	1

ORC, oxidized regenerated cellulose; rT, recombinant thrombin.

All data are time in seconds unless specified otherwise.

Figure 2. Proportion of active bleeding events over time – all initial bleeding rates within intended range (≤10 g/min).

ORC, oxidized regenerated cellulose; rT, recombinant thrombin.

Figure 3. Comparison of time to hemostasis – A. Initial bleeding rates ≤5 g/min (VIBe SCALE grade 1), and B. Initial bleeding rates >5–10 g/min (VIBe SCALE grade 2). A. B. ORC, oxidized regenerated cellulose; rT, recombinant thrombin. Horizontal line and box represent the median and interquartile ranges; error bars represent maximum/minimum values.

Figure 4. Test samples post application.

ORC, oxidized regenerated cellulose; rT, recombinant thrombin plus gelatin sponge on the left, ORC on the right, after 3 layers have been applied.

Figure 5. Martius, Scarlet and Blue staining of ORC (top) and rT plus gelatin sponge carrier (bottom).

ORC, oxidized regenerated cellulose; rT, recombinant thrombin.

Orange-yellow coloring represents fresh fibrin, red represents mature fibrin, erythrocytes are stained yellow, and connective tissue is shown in blue.

Liver tissue can be seen in the lower part of each picture with the patch material covering the superficial organ defect on top. Note the spongious structure of the gelatin sponge carrier that has been partially penetrated with blood in the lower regions, whereas ORC shows significant amounts of coagulated blood between the individual layers and blood penetration throughout the top layer.