We propose the etiology of this event was the unintended intravascular introduction of the Surgifoam- thrombin hemostatic agent resulting in numerous thromboemboli, right heart failure, and disseminated intravascular coagulation (DIC). Surgifoam is a porcine gelatin absorbable sponge intended for hemostatic use. At our institution, 2 g of Surgifoam powder is mixed with 10,000 IU bovine topical thrombin in saline, placed into a 20 mL syringe and applied with a 9 French applicator tip to control surgical bleeding. Surgifoam-thrombin is one of the many types of topical hemostatic agents that are commercially available. Some others include FloSeal™, Tisseel™, CoSeal™, and Gelfoam®. Though our patient’s cardiac arrest was linked to Surgifoam-thrombin, it is likely that any topical hemostat inadvertently introduced into the vascular space could cause a similar clinical event. Because these topical hemostatic agents are used routinely in the operating room, the possibility of inadvertent intravascular injection is an important consideration for all practitioners.
The Surgifoam sponge was approved by the Food and Drug Administration for clinical use in 1999. In 2002, the product was approved in a powdered form, known as Surgifoam powder, and in 2004, the product was approved for mixture with thrombin for improved topical hemostasis. Though no randomized, controlled trials have been published that compare Surgifoam-thrombin to other hemostatic agents, the Surgifoam sponge was compared to a control sponge in an unpublished trial of 281 patients (142 received the Surgifoam sponge versus 139 who received a control absorbable gelatin sponge) and found to have equivalent hemostasis, with no severe adverse events attributed to Surgifoam.1
The method of hemostasis with a Surgifoam-thrombin mixture is multifactorial.2,3 The gelatin granules in Surgifoam swell and conform to tissue surfaces upon wound contact providing some tamponade. The gelatin also initiates the intrinsic coagulation cascade through contact activation of Factor XII. Simultaneously, bovine thrombin initiates the coagulation cascade by activating Factors V, VII, and XIII. Thrombin also activates specific receptors on the platelet membrane and enhances aggregation. Importantly, thrombin directly converts local fibrinogen into fibrin, and the fibrin monomers then polymerize to form a fibrin clot.2 Once applied, Surgifoam can be molded to a bleeding surface, and excess can be removed with gentle irrigation or suction.3
In normal coagulation, thrombin is localized to the site of tissue injury. In clinical DIC, however, there is unregulated and excessive thrombin production, leading to both acute intravascular thromboses as well as bleeding.4 It is therefore plausible that bovine thrombin, when inadvertently injected intravascularly, could lead to clinical DIC. This would deplete platelets and fibrinogen as seen in our patient.
In swine studies, intravascular bovine thrombin, in doses of 60 U per kilogram, has been shown to lead to DIC and death.5 Even lower doses (30 U/kg) were associated with hypotension and histologic evidence of DIC.5 Interestingly, bovine thrombin, when compared to human thrombin, seems to cause a greater degree of hypotension and DIC.5 The Food and Drug Administration has received 4 reports since 1987 regarding the results of improper administration of topical bovine thrombin.6,7 Two patients were administered topical thrombin injected through dialysis access sites, one patient received thrombin injected directly into splenic tissue, and one patient was administered topical thrombin via nasogastric tube.6,7 Three of the four cases resulted in patient death. Unlike the cases in these reports, our case does not contain an obvious product misadministration. It is also important to note that exposure to bovine thrombin products has been reported to lead to an acquired Factor V inhibitor even after a single use.8 This presents the increased risk of possible future coagulopathy and warrants further hematologic follow-up.
The timing, echocardiographic findings, and laboratory studies from our case all suggest an embolic event related to inadvertent intravascular transfer of hemostatic matrix as the most likely diagnosis. It is unlikely that our patient’s embolic event was not related to the hemostatic agent. She was ambulatory before her surgery, was not taking oral contraceptives, had no known medical or surgical history, and had no known underlying hypercoaguable state. Her embolic event occurred <4 h after the induction of anesthesia and immediately followed the application of a large volume (20 mL) of topical hemostatic agent. Finally, her laboratory values after the event were consistent with DIC, a likely effect of intravascular thrombin.5 It is unlikely that either an air embolism or a fat embolism would lead to such a rapid decrease in platelet count and fibrinogen level or result in the demonstrated TEE and computed tomography findings.
We believe topical hemostatic agents have the potential to cause a severe thromboembolic event if introduced into the intravascular space. Additionally, because they activate the coagulation cascade and deplete fibrinogen, hemostatic matrices, if inadvertently transferred intravascularly, can cause DIC. Though our patient survived, prompt diagnosis and timely treatment are essential. It is important for clinicians to realize the potential of unintended intravascular injection and thromboembolic events after topical hemostatic agent application in the operating room.
1. Surgifoam™ Absorbable Gelatin Powder, package insert. Somerville, NJ: Johnson and Johnson, 2004
2. Oz MC, Rondinone JF, Shargill NS. FloSeal Matrix: new generation topical hemostatic sealant. J Card Surg 2003;18:486–93
3. Sabel M, Stummer W. The use of local agents: surgicel and surgifoam. Eur Spine J 2004;13:S97–S101
4. Levi M. Disseminated Intravascular Coagulation. Crit Care Med 2007;35:2191–4
5. Pusateri AE, Holcomb JB, Bhattacharyya SN, Harris RA, Gomez RR, MacPhee MJ, Enriquez JI, Delgado AV, Charles NC, Hess JR. Different hypotensive responses to intravenous bovine and human thrombin preparations in swine. J Trauma 2001;50:83–90
6. Gabay M. Absorbable hemostatic agents. Am J Health Syst Pharm 2006;63:1244–53
7. Gershon SK, Chang AC, Purvis WV, Salive M. Misadministration of topical bovine thrombin. JAMA 1999;282:1919
© 2009 International Anesthesia Research Society
8. Kajitani M, Ozdemir A, Aguinaga M, Jazieh AR, Flick JT, Antakli T. Severe hemorrhagic complication due to acquired factor V inhibitor after single exposure to bovine thrombin product. J Card Surg 2000;15:378–82