Upper Airway Obstruction Induced by Warfarin Sodium MAJ Michael Leo
Lepore, MC, USA
\s=b\ I report a patient in whom warfarin sodium induced upper airway obstruction secondary to a spontaneous nontraumatic hemorrhage into the sublingual space. Treatment of this obstructive sublingual space hematoma with conservative medical management is reviewed. I discuss the role of warfarin sodium in coagulation and in the production of this pseudo-Ludwig
phenomenon. (Arch Otolaryngol 102:505-506, 1976) sodium is a derivative mol¬ of the ecule.1 In addition to warfarin so¬ dium, other clinically useful coumarins include dicumarol and ethyl biscoumacetate. Orally administered anticoagulants affect plasma coagulation. Activity of factors VII, IX, X, and thrombin and liver prothrombin are depressed by their action. Consequently, clot forma¬ tion is inhibited with a resulting state of hypocoaguability. Orally administered anticoagulants differ in rate of absorption, peak effect, and duration of effect.1 Hence, control of the potential hemorrhagic tendencies of these drugs is quite difficult. The action of the orally administered anticoagulants is in¬ fluenced, by many factors. Those factors and drugs potentiating their response are as follows: (1) change in dietary fat; (2) vitamin deficiency; (3) destruction of intestinal flora secondary to broad-spectrum antibiot¬ ics; (4) obstructive jaundice; (5) alco¬ holism; (6) renal insufficiency; (7)
Warfarin4-hydroxy-coumarin
(8) fever; (9) aspirin; (10) methyldopa; (11) guanethidine sul¬ fate; (12) reserpine (long-term use);
scurvy;
for publication April 13, 1976. From the Division of Otolaryngology, Walter Reed Army Medical Center, Washington, DC. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or reflecting the views of the Department of the Army, Navy, Air Force, or Defense. Reprint requests to Division of Otolaryngology, Walter Reed Army Medical Center, Washington, DC 20012 (MAJ Lepore).
Accepted
x-ray treatment; (14) radioactive substances. Factors that inhibit the anticoagu¬ lant response are as follows: (1) increased gastrointestinal motility; (2) chloral hydrate; (3) meprobamate;
(13)
(4) griseofulvin; (5) phénobarbital; (6) glutethimide (Doriden); (7) insecti¬ cides (chlorophenothane); and (8) reserpine (short-term use). Bleeding secondary to oral anti¬ coagulants is rare. Conn and Willis2
described major and minor varieties of bleeding. Commonly described loca¬ tions for bleeding were: (1) bleeding from traumatic or operative wounds; (2) bleeding of urologie origin with microscopic and macroscopic hematuria; (3) bleeding from the gastrointes¬ tinal tract; and (4) bleeding into the subcutaneous tissue with the forma¬ tion of subcutaneous hematomas.--3 Respiratory obstruction secondary to warfarin sodium is recorded in the literature. Owens et al described a case of respiratory obstruction sec¬ ondary to a retropharyngeal hema¬ toma that was induced by warfarin so¬ dium.4 A recent and unusual case of upper airway obstruction was observed. The
obstruction, secondary
to
a
sponta¬
nontraumatic sublingual hema¬ was induced by warfarin so¬ dium. It is believed to be the first recorded case of such an occurrence.
neous
toma,
REPORT OF A CASE
58-year-old man came to Walter Reed Army Medical Center with an initial, complaint of swelling in the floor of his mouth associated with minimal respiratory difficulty. There was no history of trauma. A
For the past five years, he had been treated for chronic thrombophlebitis in¬ volving his left leg. He had a long-standing history of hypertension. He had been receiving alternating doses of warfarin sodium, ranging from 10 to 15 mg daily, for the last six months. The patient was obese. Vital signs and respiratory rate were within normal limits. Examination of the oral cavity revealed a mucosal-covered blue mass in the floor of the mouth. It measured approximately
On palpation, the mass was both and tense. He had difficulty closing his mouth and speaking intelligibly. The fauces were obscured because of the obstructing tongue. Anteriorly, the neck was asymmetrical, the left side appearing larger than the right. When assuming the supine position, an increase in respiratory rate was noted. Due to the mild difficulty in breathing, the patient was unable to remain in the supine position for a long period of time. Several superficial ecchymotic areas were located on the anterior part of the abdomen. Results of the remaining portion of the examination were within normal limits. Several hours after admission, the patient's condition worsened. He was found sitting up in bed unable to lie down and was extremely anxious. His vital signs were stable. An increase in respiratory rate was noted. Auscultation of his chest posteriorly revealed expiratory wheezing. A roentgenogram of the chest taken at that time revealed normal findings. A lateral soft-tissue roentgenogram of the neck demonstrated almost total upper airway obstruction (Fig 1). There was marked swelling of the soft tissue of the anterior part of the neck. Severe epiglottic thickening, four times normal, was noted. A shadow of the thickened base of the tongue and soft palate were visible above the enlarged epiglottis. Retropharyngeal enlargement was also present. Almost total absence of the air column was noted at the point where the epiglottis and posterior pharyngeal wall meet. The partial thromboplastin time was 106 seconds (control, 32 seconds), and the prothrombin time was 39.5 seconds (con¬ trol, 13 seconds). He received 12 mg of dexamethasone and 10 mg of phytonadione 2x2
cm.
cystic
'
intravenously. The patient was transferred to the surgical intensive care unit. Under direct vision using a fiberoptic bronchoscope, a
7.0-mm soft-cuffed nasotracheal tube was passed to establish an airway.'"' The proce¬ dure was performed with the patient under local anesthesia using 4% topically applied cocaine. During the next 12 hours, two units of fresh frozen plasma, 20 mg of phytonadione, and 12 mg of dexametha¬ sone were administered intravenously in divided doses. The patient began prophy¬ lactic antibiotic therapy consisting of intravenous administration of ampicillin sodium, 500 mg every six hours. Within 24 hours, the sublingual hema¬ toma began resolving. After 48 hours, the partial thromboplastin time was 36.7 seconds (control, 28 seconds). The pro¬ thrombin time was 15.9 seconds (control, 12 seconds). A lateral soft-tissue roentgen¬ ogram of the neck demonstrated minimal decrease in size of the soft-tissue swelling of the anterior part of the neck. Adequate
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/24/2015
presentation was not imme¬ diately appreciated as a Ludwig variant. As the patient's clinical course progressed, it became quite evident what was occurring. This sublingual space hematoma caused displacement of the tongue upward clinical
and backward. As
Fig 1 .—Pretreatment. Lateral soft-tissue roentgenogram of neck demonstrating almost total airway obstruction.
Fig 2.—Posttreatment. Lateral soft-tissue roentgenogram of neck demonstrating restoration of patient's airway.
interpretation of the epiglottis was impos¬ sible due to placement of the nasotracheal tube. Indirect laryngoscopy was performed showing the epiglottis and the base of the
maxillary space is triangular in shape. It is bounded superiorly by the mandi¬ ble, inferoanteriorly by the anterior belly of the digastric muscle, and inferoposteriorly by the posterior bel¬ ly of the digastric and stylohyoid muscles. Both the mylohyoid and hyoglossus muscles make up the floor or medial plane of this triangular compartment. The sublingual and sub¬ maxillary spaces are in communica¬ tion with each other through the anatomical relationship of the sub¬ maxillary gland and its duct at the posterior aspect of the mylohyoid
to be normal in appearance and size. The nasotracheal tube was removed 72 hours postintubation. A lateral soft-tissue roentgenogram of the neck postextubation demonstrated a near normal airway with a decrease in thickness of the epiglottis and aryepiglottic folds (Fig 2). Moderate reso¬ lution of the soft-tissue swelling of the anterior part of the neck occurred. The remaining portion of the patients hospital course was uneventful. The patient contin¬ ued to improve and was discharged on the sixth hospital day to be seen by the depart¬ ment of medicine as an outpatient in one week.
tongue
COMMENT A
pseudo-Ludwig phenomenon
was
observed resulting from a sublingual space hematoma. In the classical
example of Ludwig angina, described
in 1836, a gangrenous induration of the neck had been observed.7 In the vast majority of cases, underlying dental pathological features are pres¬ ent. In approximately 80% of the cases, an infectious process begins in the apex of a tooth and rapidly spreads to involve adjacent anatom¬ ical structures." The sublingual and submaxillary spaces and their con¬ tents are frequently involved sites. Anatomically, the two spaces are separated by the mylohyoid muscle. The sublingual space lies above and the submaxillary space lies below this muscle. The sublingual space is bounded medially by the genioglossus muscle, laterally by the mandible, superiorly by mucous membrane of the floor of the mouth, and inferiorly by the mylohyoid muscle. The sub-
muscle. Due to the accumulation of inflam¬ matory products into the sublingual space, the tongue is thrust upward and backward. With just involvement of the sublingual space, the fauces are visualized. Once the process extends to the submaxillary space, visualization of the fauces is difficult or impossible. Thus, visualization of the fauces is an important clinical sign, for it implies that the pathological features still lie above the mylohyoid muscle. With extension to the submaxillary space, the preceding conditions are further aggravated. The tongue is noted to be pushed even further upward and back¬ ward, with resulting obstruction to faucial view. At this stage, odynophagia and dysphagia are present. Respiratory difficulty with associated dyspnea is also present. Rapid pro¬ gression to total upper airway ob¬ struction is frequently encountered. In our patient, a hemorrhage into the sublingual space was noted to produce a similar clinical picture. Because of the noninfectious nature of the pathological features, the initial
noted, the fauces
initially were visualized, but with difficulty. The difficulty encountered could be explained by the gradual shift of the hemorrhagic substance into the submaxillary space. In essence, the process
was now below the mylohyoid muscle. With the grad¬ ual involvement of the remaining portion of the submaxillary space, the patient's condition worsened. He was noted to be sitting up in bed, anxious, and unable to lie down. This, as in Ludwig angina, implies that the pathological process had extended toward the base of the tongue. At this point, complete respiratory obstruc¬ tion is possible. Once this stage is reached, management is one of rapid recognition and establishment of an
adequate upper airway. It is vital that otolaryngologists
be of such atypical clinical presen¬ tations of upper airway obstruction. It is also interesting to note that the impending obstructive problem was secondary to a commonly used anti¬ coagulant, warfarin sodium. aware
Nonproprietary Name and Trademarks of Drug Warfarin sodium-Coumadin, Prothromadin.
Panwarfin,
References 1. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics, ed 4. New York, Macmillan Co, 1451-1463, 1965. 2. Conn WW, Willis PW: Hemorrhagic complications of anticoagulant therapy. Arch Intern Med 133:386-392, 1974. 3. Reussi C, Schiavi JE, Altman R, et al: Unusual complications in the course of anticoagulant therapy. Am J Med 46:460-463, 1969. 4. Owens DE, Calcaterra TC, Aarstad RA: Retropharyngeal hematoma: A complication of therapy with anticoagulants. Arch Otolaryngol 101:565-568, 1975. 5. Murphy P: A fiber-optic endoscope used for nasal intubation. Anaesthesia 22:489-491, 1967. 6. Prithvi Raj P, Forestner J, Watson T, et al: Technics for fiberoptic laryngoscopy in anesthesia. Anesth Analg 53:708-713, 1975. 7. McCaskey CH: Ludwig's angina. Arch Otolaryngol 36:467-472, 1942. 8. Paparella MM, Shumrick DA: Otolaryngology. Philadelphia, WB Saunders Co, 1973, vol 3; pp 330-340.
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/24/2015
Lepore, MC, USA
\s=b\ I report a patient in whom warfarin sodium induced upper airway obstruction secondary to a spontaneous nontraumatic hemorrhage into the sublingual space. Treatment of this obstructive sublingual space hematoma with conservative medical management is reviewed. I discuss the role of warfarin sodium in coagulation and in the production of this pseudo-Ludwig
phenomenon. (Arch Otolaryngol 102:505-506, 1976) sodium is a derivative mol¬ of the ecule.1 In addition to warfarin so¬ dium, other clinically useful coumarins include dicumarol and ethyl biscoumacetate. Orally administered anticoagulants affect plasma coagulation. Activity of factors VII, IX, X, and thrombin and liver prothrombin are depressed by their action. Consequently, clot forma¬ tion is inhibited with a resulting state of hypocoaguability. Orally administered anticoagulants differ in rate of absorption, peak effect, and duration of effect.1 Hence, control of the potential hemorrhagic tendencies of these drugs is quite difficult. The action of the orally administered anticoagulants is in¬ fluenced, by many factors. Those factors and drugs potentiating their response are as follows: (1) change in dietary fat; (2) vitamin deficiency; (3) destruction of intestinal flora secondary to broad-spectrum antibiot¬ ics; (4) obstructive jaundice; (5) alco¬ holism; (6) renal insufficiency; (7)
Warfarin4-hydroxy-coumarin
(8) fever; (9) aspirin; (10) methyldopa; (11) guanethidine sul¬ fate; (12) reserpine (long-term use);
scurvy;
for publication April 13, 1976. From the Division of Otolaryngology, Walter Reed Army Medical Center, Washington, DC. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or reflecting the views of the Department of the Army, Navy, Air Force, or Defense. Reprint requests to Division of Otolaryngology, Walter Reed Army Medical Center, Washington, DC 20012 (MAJ Lepore).
Accepted
x-ray treatment; (14) radioactive substances. Factors that inhibit the anticoagu¬ lant response are as follows: (1) increased gastrointestinal motility; (2) chloral hydrate; (3) meprobamate;
(13)
(4) griseofulvin; (5) phénobarbital; (6) glutethimide (Doriden); (7) insecti¬ cides (chlorophenothane); and (8) reserpine (short-term use). Bleeding secondary to oral anti¬ coagulants is rare. Conn and Willis2
described major and minor varieties of bleeding. Commonly described loca¬ tions for bleeding were: (1) bleeding from traumatic or operative wounds; (2) bleeding of urologie origin with microscopic and macroscopic hematuria; (3) bleeding from the gastrointes¬ tinal tract; and (4) bleeding into the subcutaneous tissue with the forma¬ tion of subcutaneous hematomas.--3 Respiratory obstruction secondary to warfarin sodium is recorded in the literature. Owens et al described a case of respiratory obstruction sec¬ ondary to a retropharyngeal hema¬ toma that was induced by warfarin so¬ dium.4 A recent and unusual case of upper airway obstruction was observed. The
obstruction, secondary
to
a
sponta¬
nontraumatic sublingual hema¬ was induced by warfarin so¬ dium. It is believed to be the first recorded case of such an occurrence.
neous
toma,
REPORT OF A CASE
58-year-old man came to Walter Reed Army Medical Center with an initial, complaint of swelling in the floor of his mouth associated with minimal respiratory difficulty. There was no history of trauma. A
For the past five years, he had been treated for chronic thrombophlebitis in¬ volving his left leg. He had a long-standing history of hypertension. He had been receiving alternating doses of warfarin sodium, ranging from 10 to 15 mg daily, for the last six months. The patient was obese. Vital signs and respiratory rate were within normal limits. Examination of the oral cavity revealed a mucosal-covered blue mass in the floor of the mouth. It measured approximately
On palpation, the mass was both and tense. He had difficulty closing his mouth and speaking intelligibly. The fauces were obscured because of the obstructing tongue. Anteriorly, the neck was asymmetrical, the left side appearing larger than the right. When assuming the supine position, an increase in respiratory rate was noted. Due to the mild difficulty in breathing, the patient was unable to remain in the supine position for a long period of time. Several superficial ecchymotic areas were located on the anterior part of the abdomen. Results of the remaining portion of the examination were within normal limits. Several hours after admission, the patient's condition worsened. He was found sitting up in bed unable to lie down and was extremely anxious. His vital signs were stable. An increase in respiratory rate was noted. Auscultation of his chest posteriorly revealed expiratory wheezing. A roentgenogram of the chest taken at that time revealed normal findings. A lateral soft-tissue roentgenogram of the neck demonstrated almost total upper airway obstruction (Fig 1). There was marked swelling of the soft tissue of the anterior part of the neck. Severe epiglottic thickening, four times normal, was noted. A shadow of the thickened base of the tongue and soft palate were visible above the enlarged epiglottis. Retropharyngeal enlargement was also present. Almost total absence of the air column was noted at the point where the epiglottis and posterior pharyngeal wall meet. The partial thromboplastin time was 106 seconds (control, 32 seconds), and the prothrombin time was 39.5 seconds (con¬ trol, 13 seconds). He received 12 mg of dexamethasone and 10 mg of phytonadione 2x2
cm.
cystic
'
intravenously. The patient was transferred to the surgical intensive care unit. Under direct vision using a fiberoptic bronchoscope, a
7.0-mm soft-cuffed nasotracheal tube was passed to establish an airway.'"' The proce¬ dure was performed with the patient under local anesthesia using 4% topically applied cocaine. During the next 12 hours, two units of fresh frozen plasma, 20 mg of phytonadione, and 12 mg of dexametha¬ sone were administered intravenously in divided doses. The patient began prophy¬ lactic antibiotic therapy consisting of intravenous administration of ampicillin sodium, 500 mg every six hours. Within 24 hours, the sublingual hema¬ toma began resolving. After 48 hours, the partial thromboplastin time was 36.7 seconds (control, 28 seconds). The pro¬ thrombin time was 15.9 seconds (control, 12 seconds). A lateral soft-tissue roentgen¬ ogram of the neck demonstrated minimal decrease in size of the soft-tissue swelling of the anterior part of the neck. Adequate
Downloaded From: http://archotol.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/24/2015
presentation was not imme¬ diately appreciated as a Ludwig variant. As the patient's clinical course progressed, it became quite evident what was occurring. This sublingual space hematoma caused displacement of the tongue upward clinical
and backward. As
Fig 1 .—Pretreatment. Lateral soft-tissue roentgenogram of neck demonstrating almost total airway obstruction.
Fig 2.—Posttreatment. Lateral soft-tissue roentgenogram of neck demonstrating restoration of patient's airway.
interpretation of the epiglottis was impos¬ sible due to placement of the nasotracheal tube. Indirect laryngoscopy was performed showing the epiglottis and the base of the
maxillary space is triangular in shape. It is bounded superiorly by the mandi¬ ble, inferoanteriorly by the anterior belly of the digastric muscle, and inferoposteriorly by the posterior bel¬ ly of the digastric and stylohyoid muscles. Both the mylohyoid and hyoglossus muscles make up the floor or medial plane of this triangular compartment. The sublingual and sub¬ maxillary spaces are in communica¬ tion with each other through the anatomical relationship of the sub¬ maxillary gland and its duct at the posterior aspect of the mylohyoid
to be normal in appearance and size. The nasotracheal tube was removed 72 hours postintubation. A lateral soft-tissue roentgenogram of the neck postextubation demonstrated a near normal airway with a decrease in thickness of the epiglottis and aryepiglottic folds (Fig 2). Moderate reso¬ lution of the soft-tissue swelling of the anterior part of the neck occurred. The remaining portion of the patients hospital course was uneventful. The patient contin¬ ued to improve and was discharged on the sixth hospital day to be seen by the depart¬ ment of medicine as an outpatient in one week.
tongue
COMMENT A
pseudo-Ludwig phenomenon
was
observed resulting from a sublingual space hematoma. In the classical
example of Ludwig angina, described
in 1836, a gangrenous induration of the neck had been observed.7 In the vast majority of cases, underlying dental pathological features are pres¬ ent. In approximately 80% of the cases, an infectious process begins in the apex of a tooth and rapidly spreads to involve adjacent anatom¬ ical structures." The sublingual and submaxillary spaces and their con¬ tents are frequently involved sites. Anatomically, the two spaces are separated by the mylohyoid muscle. The sublingual space lies above and the submaxillary space lies below this muscle. The sublingual space is bounded medially by the genioglossus muscle, laterally by the mandible, superiorly by mucous membrane of the floor of the mouth, and inferiorly by the mylohyoid muscle. The sub-
muscle. Due to the accumulation of inflam¬ matory products into the sublingual space, the tongue is thrust upward and backward. With just involvement of the sublingual space, the fauces are visualized. Once the process extends to the submaxillary space, visualization of the fauces is difficult or impossible. Thus, visualization of the fauces is an important clinical sign, for it implies that the pathological features still lie above the mylohyoid muscle. With extension to the submaxillary space, the preceding conditions are further aggravated. The tongue is noted to be pushed even further upward and back¬ ward, with resulting obstruction to faucial view. At this stage, odynophagia and dysphagia are present. Respiratory difficulty with associated dyspnea is also present. Rapid pro¬ gression to total upper airway ob¬ struction is frequently encountered. In our patient, a hemorrhage into the sublingual space was noted to produce a similar clinical picture. Because of the noninfectious nature of the pathological features, the initial
noted, the fauces
initially were visualized, but with difficulty. The difficulty encountered could be explained by the gradual shift of the hemorrhagic substance into the submaxillary space. In essence, the process
was now below the mylohyoid muscle. With the grad¬ ual involvement of the remaining portion of the submaxillary space, the patient's condition worsened. He was noted to be sitting up in bed, anxious, and unable to lie down. This, as in Ludwig angina, implies that the pathological process had extended toward the base of the tongue. At this point, complete respiratory obstruc¬ tion is possible. Once this stage is reached, management is one of rapid recognition and establishment of an
adequate upper airway. It is vital that otolaryngologists
be of such atypical clinical presen¬ tations of upper airway obstruction. It is also interesting to note that the impending obstructive problem was secondary to a commonly used anti¬ coagulant, warfarin sodium. aware
Nonproprietary Name and Trademarks of Drug Warfarin sodium-Coumadin, Prothromadin.
Panwarfin,
References 1. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics, ed 4. New York, Macmillan Co, 1451-1463, 1965. 2. Conn WW, Willis PW: Hemorrhagic complications of anticoagulant therapy. Arch Intern Med 133:386-392, 1974. 3. Reussi C, Schiavi JE, Altman R, et al: Unusual complications in the course of anticoagulant therapy. Am J Med 46:460-463, 1969. 4. Owens DE, Calcaterra TC, Aarstad RA: Retropharyngeal hematoma: A complication of therapy with anticoagulants. Arch Otolaryngol 101:565-568, 1975. 5. Murphy P: A fiber-optic endoscope used for nasal intubation. Anaesthesia 22:489-491, 1967. 6. Prithvi Raj P, Forestner J, Watson T, et al: Technics for fiberoptic laryngoscopy in anesthesia. Anesth Analg 53:708-713, 1975. 7. McCaskey CH: Ludwig's angina. Arch Otolaryngol 36:467-472, 1942. 8. Paparella MM, Shumrick DA: Otolaryngology. Philadelphia, WB Saunders Co, 1973, vol 3; pp 330-340.
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