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Thromboemboli, Acute Right Heart Failure and Disseminated Intravascular Coagulation After Intraoperative Application of a Topical Hemostatic Matrix

Ferschl, Marla B. MD; Rollins, Mark D. MD, PhD

doi: 10.1213/ane.0b013e31818d3f48
Cardiovascular Anesthesiology: Case Report
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Topical hemostatic agents are frequently used in spine surgeries to control or reduce bleeding. Although there are a number of commercially available products, at our institution, an absorbable gelatin powder (Surgifoam™) is mixed with bovine thrombin and used for this purpose. We report the case of a patient undergoing a posterior spinal fusion for scoliosis who developed acute right heart failure, cardiac arrest, and disseminated intravascular coagulation after probable intravascular hemostatic agent-induced emboli. Clinicians need to be aware of this potentially deadly complication associated with topical hemostatic agents.

IMPLICATIONS: We present a case of thromboemboli, acute right heart failure, and disseminated intravascular coagulation after the application of a topical hemostatic matrix during posterior spine fusion surgery. Clinicians need to be aware of this potentially deadly complication associated with topical hemostatic agent use in the operating room.

From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, California.

Accepted for publication June 30, 2008.

Reprints will not be available from the author.

Address correspondence to Mark D. Rollins, MD, PhD, 513 Parnassus Ave., S-455, Box 0464, San Francisco, CA 94143-0464. Address e-mail to rollinsm@anesthesia.ucsf.edu.

Topical hemostatic agents are frequently used to control intraoperative bleeding in surgery. These agents often consist of an absorbable gelatin matrix mixed with thrombin. When applied topically, they provide tamponade to sites of surgical bleeding and activate coagulation. To our knowledge, there have been no documented cases of unintentional intravascular hemostatic matrix application in the literature. We present the case of a patient undergoing a posterior spinal fusion for scoliosis who likely experienced thromboembolism induced by the intraoperative application of a mixture of Surgifoam™ absorbable gelatin powder and bovine thrombin at the surgical site.

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CASE DESCRIPTION

An otherwise healthy 18-yr-old 60-kg female underwent a 13-level spinal fusion for moderate scoliosis (Cobb angle = 72 degrees). She had normal preoperative laboratory values (Table 1) and was not taking any prescription medications. After an unremarkable anesthetic induction and tracheal intubation, two large-bore peripheral IVs, a left- sided radial arterial line, and a right internal jugular double-lumen central line were placed. The patient was positioned prone, anesthesia was maintained with fentanyl, low dose ketamine, a propofol infusion and inhaled desflurane (0.5 minimum alveolar anesthetic concentration), with motor and sensory evoked potentials monitored throughout. These four drugs are frequently used in combination at our institution during large spine surgeries to optimize neuromonitoring signals and improve postoperative pain control. Antifibrinolytic drugs were not used. About 1.5 h after incision, the patient had lost approximately 1000 mL of blood. At this time, a complete blood count showed a hematocrit of 25% and a platelet count of 204,000/μL. Two units of packed red blood cells were transfused. Also at this time, coagulation studies revealed a prothrombin time of 16.9 s, partial thromboplastin time of 41.6 s, International Normalized Ratio of 1.3 and fibrinogen of 202 mg/dL (Table 1). The patient remained stable until 30 min later, when she became acutely hypotensive and had a precipitous decrease in end-tidal carbon dioxide (from 35 mm Hg to 17 mm Hg). Ventricular tachycardia with progression to ventricular fibrillation and cardiac arrest immediately followed. One milligram of epinephrine was given, the surgical site rapidly packed and the patient promptly turned supine. Cardiopulmonary resuscitation was initiated and the patient defibrillated with a return to sinus rhythm. The patient remained severely hypotensive requiring multiple epinephrine boluses and an epinephrine infusion to maintain mean arterial blood pressures above 50 mm Hg. A transesophageal echocardiogram (TEE) probe was placed to differentiate occult hemorrhage from cardiac failure, as the surgeon described significant bleeding at the surgical site just before the event and was concerned there might have been significant vascular compromise. The TEE revealed increased right ventricular volume, reduced systolic function, a leftward septal bowing, a small left ventricle, and numerous mobile masses migrating from the right atrium to right ventricle (Figs. 1 and 2). A norepinephrine infusion and inhaled nitric oxide were initiated. Repeat laboratory studies reveled severe thrombocytopenia (platelets of 11,000/μL), coagulopathy (International Normalized Ratio 3.2, partial thromboplastin time >100 s) and a fibrinogen of 51 mg/dL (Table 1). During the resuscitation and discussion of the echocardiogram findings, the surgeon noted that, just before the event, brisk venous bleeding from a pedicle occurred at the L2 level. In order to provide more adequate hemostasis, 20 mL of a Surgifoam-thrombin mixture was applied into the pedicle hole and surrounding tissue using a syringe.

Table 1

Table 1

Figure 1

Figure 1

Figure 2

Figure 2

In response to the severe coagulopathy after the event, the patient was resuscitated with fresh frozen plasma, platelets, and cryoprecipitate. Though cell salvage was used, no salvaged blood was ever processed or returned to the patient at anytime during the case.

After stabilization, the patient was repositioned laterally for surgical wound approximation and transported to the intensive care unit. The patient was then started on a low-dose heparin infusion per recommendation of a hematology consult. She also underwent a chest computed tomography, which showed numerous filling defects throughout bilateral segmental and subsegmental pulmonary branches, evidence of right heart strain with flattening of the interventricular septum, and enlargement of the right ventricle (Figs. 3 and 4). Forty-eight hours later, she was taken back to the operating room for wound washout and formal closure. Over the next 2 days, she was weaned off vasopressors, and then underwent uneventful and definitive posterior spinal fusion. The patient was discharged and completed a 3-month period of anticoagulation with no permanent sequela.

Figure 3

Figure 3

Figure 4

Figure 4

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DISCUSSION

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.

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REFERENCES

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
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
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