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Case report: Management of life-threatening oropharyngeal bleeding with recombinant factor VIIa

[Une présentation de cas : le traitement de graves saignements oropharyngiens avec le facteur VIIa recombinant]

Sheila Riazi, MD^*, Keyvan Karkouti, MD^*, and Jane Heggie, MD^*

^* From the Department of Anesthesia, and the
Department of Health Policy, Management, and Evaluation,University of Toronto, University Health Network, Toronto, Ontario, Canada.

Address correspondence to: Dr. Keyvan Karkouti, Toronto General Hospital, University Health Network, Department of Anesthesia, 3 Eaton North, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. Phone: 416-340-5164; Fax: 416-340-3698; E-mail: keyvan. karkouti{at}uhn.on.ca

	Abstract

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Purpose: To report the use of recombinant factor VIIa (rFVIIa) for management of profuse oropharyngeal bleeding in a cirrhotic patient that nearly resulted in a ‘cannot intubate, cannot ventilate’ scenario.

Clinical features: A 42-yr-old woman with end-stage liver disease presented for orthotopic liver transplantation. She was dialysis dependent and had marked coagulopathy [international normalized ratio (INR) = 3.1], without evidence of active bleeding. Following uneventful induction of anesthesia, routine airway manipulation for tracheal intubation caused profuse upper airway bleeding making visualization of her airway by direct laryngoscopy impossible. Moreover, several further attempts at tracheal intubation along with the bleeding made manual ventilation progressively more difficult, nearly resulting in a ‘cannot intubate, cannot ventilate’ scenario. In an attempt to control the bleeding, rFVIIa 4.8 mg iv was administered. Within five minutes, her INR had decreased to 1.1, bleeding was markedly reduced, the vocal cords were successfully visualized using an anterior commissure laryngoscope, and intubation of the trachea was achieved with the use of a gum-elastic bougie. Postintubation examination of the airway showed several abrasions along the right oropharyngeal wall with minimal bleeding. The remainder of surgery and postoperative airway management were uneventful.

Conclusions: This report demonstrates that in the relatively uncommon setting of upper airway hemorrhage in a patient with pre-existing coagulopathy, rFVIIa can be effective in gaining rapid control of bleeding to facilitate visualization of the vocal cords and securing of the airway.

	Introduction

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PATIENTS with cirrhosis have varying degrees of coagulopathy that may elevate their risk of bleeding events. Bleeding in such patients may occur spontaneously, or in association with minor trauma as well as major surgery. This case report describes a cirrhotic coagulopathic patient in whom routine airway manipulation following induction of general anesthesia for liver transplantation caused profuse upper airway bleeding that nearly led to a ‘cannot intubate, cannot ventilate’ scenario. The uncontrolled bleeding was managed successfully with recombinant factor VIIa (rFVIIa). The patient gave informed consent for review of her medical records and publication of this case.

	Clinical report

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A 42-yr-old woman (51 kg) with end-stage liver disease secondary to autoimmune hepatitis presented for total recipient hepatectomy and orthotopic liver transplantation. She had a history of deteriorating liver function for one year, and one episode of esophageal variceal bleeding four months previously, which was band-ligated. One month prior to surgery, she underwent upper gastrointestinal endoscopy as part of the transplant protocol, which showed grade II esophageal varices, with no active bleeding. Her only previous surgery was for a duodenal ulcer, which was performed uneventfully three years previously. Her renal function deteriorated during the month prior to surgery, to the stage where she required hemodialysis. By the time of surgery, the patient was encephalopathic and drowsy. Her preoperative airway examination was unremarkable – mouth opening, oropharyngeal view, thyromental distance, and neck movement were all normal. She did not have any active bleeding prior to surgery, despite her marked coagulopathy. The results of the preoperative blood tests are presented in Table I. During the three hours prior to surgery, the patient received two units of fresh frozen plasma (FFP), but coagulation tests were not repeated.

Two more units of FFP were rapidly transfused with no noticeable effect on bleeding. Given the critical and progressive nature of the situation, priority was given to obtaining rapid control of the bleeding by rFVIIa. Approval was obtained via consultation with a hematologist, and 4.8 mg of rFVIIa (Novoseven®, Novo Nordisk, Mississauga, ON, Canada) was administered intravenously over one minute. Within five minutes there was a marked reduction in the bleeding, and the otorhinolaryngologist was able to visualize the vocal cords with the anterior commissure laryngoscope. A bougie was advanced through the cords, and an endotracheal tube was railroaded over the bougie to secure the airway.

Approximately 30 to 45 min elapsed from anesthetic induction to securing of the airway. Post-intubation examination of the airway showed several abrasions along the right oropharyngeal wall with minimal bleeding. Fibreoptic bronchoscopy revealed that considerable blood had been aspirated, but there were no clots and the airways were patent. Post-rFVIIa hematological variables are presented in Table I, and pre- and post-intubation arterial blood gas values are presented in Table II.

	Discussion

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In coagulopathic patients, upper airway bleeding precluding visualization of the vocal cords for tracheal intubation is a critical event, particularly if it compromises the anesthesiologists’ ability to maintain adequate ventilation. This case demonstrates that rFVIIa can rapidly restore hemostasis in this setting, allowing for adequate visualization of the airway for tracheal intubation.

Coagulopathy is one of the main characteristics of cirrhosis, and is caused by low blood concentrations of coagulation proteins normally synthesized in the liver, as well as thrombocytopenia from hypersplenism, enhanced fibrinolysis due to decreased hepatic clearance of its inhibitors, and platelet dysfunction if there is accompanying renal dysfunction.¹ Consequently, even minor injuries can result in major bleeding events in cirrhotic patients.² In this case, routine airway manipulation resulted in profuse upper airway bleeding that precluded vocal cord visualization and tracheal intubation by direct laryngoscopy, and eventually compromised the ability of the anesthesiologist to maintain adequate ventilation.

Current standard of care for restoring hemostasis in cirrhotic patients with elevated international normalized ratio is by FFP transfusions.¹ Fresh frozen plasma transfusions, however, cannot restore hemostasis rapidly, and in fact are often ineffective in cirrhotic patients.¹ Owing to the grave condition of the patient and the impending ‘cannot intubate, cannot ventilate’ scenario, this case required rapid restoration of hemostasis.

Faced with an impending ‘cannot intubate, cannot ventilate’ scenario, practice guidelines recommend use of extraglottic devices such as the laryngeal mask airway as a temporizing measure to aid ventilation, or failing that, obtaining emergency invasive airway access by surgical or percutaneous tracheostomy or cricothyrotomy. ³ In this case, however, rapid restoration of hemostasis with rFVIIa made tracheal intubation possible, thereby avoiding the need for temporizing or invasive measures for securing the airway.

Activated recombinant factor VII is a synthetic analogue of human plasma factor VII with similar structure and activity. The mechanism of action of rFVIIa involves enhanced thrombin generation on thrombin- activated platelet surfaces, leading to increased platelet activation and clot formation at the site of injury.⁴ While the product was developed originally as an alternate therapy for hemophiliac patients with inhibitors against factor VIII and IX, there have been an increasing number of reports describing its successful application in a diverse range of clinical situations in non-hemophiliac patients.⁵ The ability of rFVIIa to increase thrombin generation has initiated numerous ‘off-label’ uses for rFVIIa either as a prophylactic agent against hemorrhage, or as rescue therapy for patients who have failed conventional hemostatic therapy, and there are successful reports of its use in various patient populations including cirrhotic, trauma, and cardiac surgical patients.^1,5–7

Use of rFVIIa for intractable oropharyngeal bleeding has been limited to hemophiliac patients undergoing tooth extraction.^8,9 This is the first reported case where rFVIIa was used to rapidly control profuse oropharyngeal bleeding in a non-hemophiliac coagulopathic patient, thereby helping to prevent an impending ‘cannot intubate, cannot ventilate’ scenario. Although rFVIIa is not part of the difficult airway algorithm, anesthesiologists should consider its use when faced with coagulopathic patients with intractable upper airway hemorrhage.

	Footnotes

 
Funding and conflicts of interest: Dr. K. Karkouti is supported in part by the Canadian Institutes of Health Research and the Canadian Blood Services. K. Karkouti has received an unrestricted research grant and consultant’s fees from Novo Nordisk.

Accepted for publication April 7, 2006. Revision accepted May 4, 2006.

	References

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2 Wiklund RA. Preoperative preparation of patients with advanced liver disease. Crit Care Med 2006; 32(Suppl.): S106–15.

3 American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Practice guidelines for management of the difficult airway. An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 2003; 98: 1269–77.[Medline]

4 Hedner U. Mechanism of action of recombinant activated factor VII: an update. Semin Hematol 2006; 43(Suppl 1): S105–7.[Medline]

5 Welsby IJ, Monroe DM, Lawson JH, Hoffmann M. Recombinant activated factor VII and the anaesthetist. Anaesthesia 2005; 60: 1203–12.[Medline]

6 Boffard KD, Riou B, Warren B, et al.; NovoSeven Trauma Study Group. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo- controlled, double-blind clinical trials. J Trauma 2005; 59: 8–15.[Medline]

7 Karkouti K, Beattie WS, Wijeysundera DN, et al. Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity-score matched casecontrol analysis. Transfusion 2005; 45: 26–34.[Medline]

8 Laguna P, Klukowska A. Management of oral bleedings with recombinant factor VIIa in children with haemophilia A and inhibitor. Haemophilia 2005; 11: 2–4.[Medline]

9 Morimoto Y, Yoshioka A, Shima M, Kirita T. Intraoral hemostasis using a recombinant activated factor VII preparation in a hemophilia A patient with inhibitor. J Oral Maxillofac Surg 2003; 61: 1095–7[Medline]

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