History
A 12-year-old 13.8-kg (30.4-lb) castrated male Beagle was examined at the Veterinary Medical Teaching Hospital of Seoul National University for a cervical mass and hoarseness. The owner had observed the mass 1 year previously, and there had been no notable change in size; however, barking sounds were slightly harsh recently. Cytologic examination of a fine-needle aspirate of the mass performed by the referring veterinarian suggested a diagnosis of thyroid carcinoma. On physical examination at our hospital, an approximately 3-cmdiameter, round, firm, immobile, apparently nonpainful mass was palpated subcutaneously in the region of the right thyroid gland. No other abnormalities were detected on palpation of the cervical region, including the left thyroid gland, and superficial lymph nodes. The patient, although excited and panting, was bright, alert, and responsive. Indirect systolic blood pressure, measured twice by means of Doppler sphygmomanometrya with a size 4 cuff on the left forelimb, was slightly high (150 to 210 mm Hg). Heart rate (HR) and rectal temperature were within reference ranges. Results of a neurologic examination were unremarkable. Mild thrombocytosis (platelet count, 44.3 × 104 platelets/μL; reference range, 14.3 × 104 platelets/μL to 40.0 × 104 platelets/μL) was the only abnormal finding on a CBC. A serum biochemical analysis was also performed and revealed a slightly high alkaline phosphatase activity (129 U/L; reference range, 8 to 100 U/L), a slightly low BUN concentration (7.2 mg/dL; [reference range, 8 to 30 mg/dL]), and mild hypocalcemia (8.3 mg/dL; [reference range, 9.0 to 11.8 mg/dL]). Thyroid hormone and ionized calcium concentrations were within reference ranges. Therefore, a functional thyroid tumor was ruled out. Urinalysis indicated a urine specific gravity of 1.029, a pH of 8, and trace proteinuria.
The patient underwent ultrasonographic examination of the ventral cervical region. An additional mandibular mass located dorsomedial to the right mandibular salivary gland was also identified. Because of the deep location of this mass, it was not palpable or otherwise evident on physical examination. Both masses had similar ultrasonographic appearances: well-demarcated and heterogenous echogenicity with moderate to severe blood flow signal. In addition, the right retropharyngeal and mandibular lymph nodes had decreased echogenicity, compared with the left retropharyngeal lymph node. Because surgery was planned, CT was performed to aid surgical planning. The mass in the region of the right thyroid gland was 3 × 2.5 × 4 cm and oval and showed strong contrast enhancement. The mandibular mass was 3 × 3 × 3 cm and was located medial to the right mandibular salivary gland adjacent the bifurcation of the right common carotid artery, with strong and irregular contrast enhancement. The right carotid artery, which was located ventral to the mass, was slightly compressed. There was no evidence of in-filtration or metastasis on CT (Figure 1). On the basis of the history and results of physical examination and diagnostic imaging, the presumptive diagnoses were a nonfunctional thyroid tumor (right thyroid mass) and an ectopic thyroid tumor (right submandibular mass). The owners elected to proceed with surgical treatment.
Transverse CT images (A and B) and a 3-D reconstructed CT image (C) of the cervical region of a 12-year-old male Beagle examined for a cervical mass and hoarseness. Notice the cervical mass (A, asterisk) at the level of the right thyroid gland, with medial compression of the trachea. A separate submandibular mass (B, dagger) is also evident, located between the right mandibular salivary gland (arrowheads) and the larynx. The larynx is displaced left of midline by the mass. Strong contrast enhancement of both masses is present. On 3-D reconstruction (C), the anatomic relationships between the right carotid artery (arrows), cervical mass (asterisk), and submandibular mass (dagger) are clear.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Transverse CT images (A and B) and a 3-D reconstructed CT image (C) of the cervical region of a 12-year-old male Beagle examined for a cervical mass and hoarseness. Notice the cervical mass (A, asterisk) at the level of the right thyroid gland, with medial compression of the trachea. A separate submandibular mass (B, dagger) is also evident, located between the right mandibular salivary gland (arrowheads) and the larynx. The larynx is displaced left of midline by the mass. Strong contrast enhancement of both masses is present. On 3-D reconstruction (C), the anatomic relationships between the right carotid artery (arrows), cervical mass (asterisk), and submandibular mass (dagger) are clear.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Transverse CT images (A and B) and a 3-D reconstructed CT image (C) of the cervical region of a 12-year-old male Beagle examined for a cervical mass and hoarseness. Notice the cervical mass (A, asterisk) at the level of the right thyroid gland, with medial compression of the trachea. A separate submandibular mass (B, dagger) is also evident, located between the right mandibular salivary gland (arrowheads) and the larynx. The larynx is displaced left of midline by the mass. Strong contrast enhancement of both masses is present. On 3-D reconstruction (C), the anatomic relationships between the right carotid artery (arrows), cervical mass (asterisk), and submandibular mass (dagger) are clear.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
An IV catheter was placed in a cephalic vein with standard aseptic technique. The patient then received a single dose of cefazolinb (22 mg/kg [10 mg/lb], IV), followed by diazepamc (0.1 mg/kg [0.05 mg/lb], IV, once), and initiation of a constant rate infusion (CRI) of remifentanild (6 μg/kg/h [2.72 μg/lb/h], IV). After administration of remifentanil and diazepam, the dog became recumbent with an HR of 65 beats/min, which was considered indicative of profound sedation. After SC injection of 1 mL of 2% lidocaine, a 24-gauge, 3-cm-long, IV catheter was placed in the dorsal pedal artery for direct blood pressure monitoring. With the patient positioned in left lateral recumbency, the surgical site was prepared in standard fashion. Although the right submandibular mass was not palpable, compression and manipulation of the area during clipping and preparation of the skin for aseptic surgery resulted in a sudden increase in systolic arterial blood pressure to > 200 mm Hg (Figure 2). The systolic arterial pressure subsequently decreased when manipulation ceased, but increased again when manipulation of the affected area resumed.
Graph of systolic arterial blood pressure (solid line, mmHg) and heart rate (HR, dotted line; beats/min) versus time, as obtained from the anesthesia record of the patient in Figure 1. Specific times during which the patient underwent preoperative manipulation of the right submandibular mass during aseptic skin preparation (A), endotracheal intubation (B), thyroidectomy (C), submandibular mass resection (D), constant rate infusion (E) of sodium nitroprusside (0.05 to 0.2 μg/kg [0.02 to 0.09 μg/lb], IV) and esmolol (0.05 mg/kg, IV, 5 times), and extubation (F) are indicated. Although vital signs were recorded every 5 minutes, the patient developed acute hypertension with repeated large fluctuations in blood pressure occurring over periods of < 5 minutes during surgical manipulation of the submandibular mass. Therefore, peak values for systolic arterial blood pressure do not reflect the maximum blood pressure values; times when the systolic arterial pressure = 328 mm Hg (the highest value recorded by the monitoring equipment)e,f are indicated with asterisks. Blood pressure stabilized after the mass was resected.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Graph of systolic arterial blood pressure (solid line, mmHg) and heart rate (HR, dotted line; beats/min) versus time, as obtained from the anesthesia record of the patient in Figure 1. Specific times during which the patient underwent preoperative manipulation of the right submandibular mass during aseptic skin preparation (A), endotracheal intubation (B), thyroidectomy (C), submandibular mass resection (D), constant rate infusion (E) of sodium nitroprusside (0.05 to 0.2 μg/kg [0.02 to 0.09 μg/lb], IV) and esmolol (0.05 mg/kg, IV, 5 times), and extubation (F) are indicated. Although vital signs were recorded every 5 minutes, the patient developed acute hypertension with repeated large fluctuations in blood pressure occurring over periods of < 5 minutes during surgical manipulation of the submandibular mass. Therefore, peak values for systolic arterial blood pressure do not reflect the maximum blood pressure values; times when the systolic arterial pressure = 328 mm Hg (the highest value recorded by the monitoring equipment)e,f are indicated with asterisks. Blood pressure stabilized after the mass was resected.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Graph of systolic arterial blood pressure (solid line, mmHg) and heart rate (HR, dotted line; beats/min) versus time, as obtained from the anesthesia record of the patient in Figure 1. Specific times during which the patient underwent preoperative manipulation of the right submandibular mass during aseptic skin preparation (A), endotracheal intubation (B), thyroidectomy (C), submandibular mass resection (D), constant rate infusion (E) of sodium nitroprusside (0.05 to 0.2 μg/kg [0.02 to 0.09 μg/lb], IV) and esmolol (0.05 mg/kg, IV, 5 times), and extubation (F) are indicated. Although vital signs were recorded every 5 minutes, the patient developed acute hypertension with repeated large fluctuations in blood pressure occurring over periods of < 5 minutes during surgical manipulation of the submandibular mass. Therefore, peak values for systolic arterial blood pressure do not reflect the maximum blood pressure values; times when the systolic arterial pressure = 328 mm Hg (the highest value recorded by the monitoring equipment)e,f are indicated with asterisks. Blood pressure stabilized after the mass was resected.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Ketamineg (5 mg/kg [2.27 mg/lb], IV, once) was administered for laryngeal examination. Left displacement of the larynx by the submandibular mass was observed and considered to be the cause of hoarseness; there were no other abnormal findings. The patient then received alphaxalone,h titrated to effect (total dose, 2 mg/kg [0.9 mg/lb], IV), to achieve a sufficient depth of anesthesia for endotracheal intubation (8.0-mm-internal-diameter reinforced endotracheal tube). General anesthesia was maintained with 2% isofluranei in 2 L of oxygen/min delivered through a circle rebreathing system.j Hartmann solutionk (2.5 to 10 mL/kg/h [1.1 to 4.5 mL/lb/h]) was administered IV during the procedure.
Question
What was the likely etiology of the acute hypertension observed during preparation for surgery in this patient? In view of this event, should the anesthesia care plan have been modified? If yes, what factors should have been considered to optimize the likelihood of a successful outcome?
Answer
Because acute hypertension was observed with manipulation in the region of the submandibular mass during preparation for surgery, we suspected a functional ectopic thyroid tumor (ie, thyroid storm) as the cause. As intraoperative manipulation of the area was expected, the anesthesia care plan was adjusted accordingly. Sodium nitroprussidel and esmololm were prepared and available for rapid administration in the event that severe hypertension, hypertensive crisis (an acute increase in blood pressure, with systolic blood pressure > 180 mm Hg and diastolic blood pressure > 120 mm Hg) or tachyarrhythmias developed during surgery.
The patient was moved to the operating room and positioned in dorsal recumbency. Right thyroidectomy was performed via a skin incision over the right cervical mass and separation of the brachiocephalicus and sternohyoideus muscles. Careful dissection with sterile cotton swabs and right-angled forceps exposed the mass, with care taken to protect associated structures including the right carotid artery. Thyroidectomy was completed (duration, approx 1 h), with the patient remaining hemodynamically stable throughout. At completion of the thyroidectomy, the HR was 85 beats/min, systolic and diastolic arterial blood pressures were 143 and 57 mm Hg (mean arterial blood pressure, 80 mm Hg), respiratory rate was 20 breaths/min, minimum alveolar concentration of isoflurane was 1.4%, and remifentanil was being administered via constant rate infusion (CRI) at a rate of 8 μg/kg/h (3.6 μg/lb/h).
The incision was extended cranially to approach the submandibular mass, which was located dorsal to the carotid bifurcation. A small branch of the right carotid artery apparently supplying the mass was observed and was ligated and transected, and the mass was isolated from the surrounding tissues. Rumel tourniquets were applied for temporary occlusion of carotid arterial blood flow and to help maintain a bloodless operative field (Figure 3). During the surgical approach to the mass, an abrupt increase in systolic arterial blood pressure to 328 mm Hg was noted, which resolved when the surgeons ceased manipulation and dissection. Similar acute fluctuations in blood pressure occurred repeatedly during tumor resection (Figure 2). Once it was realized that these fluctuations were apparently caused by manipulation of the submandibular mass, the surgery was resumed with continuous dialogue between the surgeons and attending anesthesiologists regarding the patient's status. A sodium nitroprusside (0.05 to 0.2 μg/kg/min [0.02 to 0.09 μg/lb/min], IV) CRI was administered in an effort to manage the hypertensive crisis; however, this was ineffective in preventing further episodes of acute hypertension (systolic arterial blood pressure, > 300 mm Hg) and repeated blood pressure fluctuations. As the surgery proceeded, the patient also became tachycardic (HR, > 200 beats/min), and arrhythmias were observed. Esmolol (0.05 mg/kg, IV) was repeatedly administered as required to treat the tachyarrhythmias. Despite antihypertensive treatment and apparently adequate anesthetic depth, the blood pressure was difficult to manage and maintain within the reference range, and was controlled only with short pauses in tissue manipulation. After resection of the submandibular mass (duration of surgery, approx 2.5 hours), the patient remained hemodynamically stable, and the sodium nitroprusside infusion was discontinued. At the completion of surgery and before the vaporizer was turned off, the patient had an HR of 134 beats/min, systolic and diastolic arterial blood pressures of 130 and 60 mm Hg (mean arterial blood pressure, 85 mm Hg), and a respiratory rate of 12 breaths/min. The patient recovered from anesthesia without apparent complications.
Intraoperative photograph (A) and a cross section of the excised submandibular mass (B) of the patient in Figure 1. The right carotid artery (arrowheads) was immediately lateral to the submandibular mass; a small branch entered the tumor and was ligated and subsequently transected. Rumel tourniquets (white arrows) were placed around the carotid artery during dissection. Upon gross inspection, the parenchyma of the submandibular mass was pinkish with hemorrhagic foci. The transected carotid arterial branch is evident (black arrows). Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Intraoperative photograph (A) and a cross section of the excised submandibular mass (B) of the patient in Figure 1. The right carotid artery (arrowheads) was immediately lateral to the submandibular mass; a small branch entered the tumor and was ligated and subsequently transected. Rumel tourniquets (white arrows) were placed around the carotid artery during dissection. Upon gross inspection, the parenchyma of the submandibular mass was pinkish with hemorrhagic foci. The transected carotid arterial branch is evident (black arrows). Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Intraoperative photograph (A) and a cross section of the excised submandibular mass (B) of the patient in Figure 1. The right carotid artery (arrowheads) was immediately lateral to the submandibular mass; a small branch entered the tumor and was ligated and subsequently transected. Rumel tourniquets (white arrows) were placed around the carotid artery during dissection. Upon gross inspection, the parenchyma of the submandibular mass was pinkish with hemorrhagic foci. The transected carotid arterial branch is evident (black arrows). Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
The resected masses were fixed in neutral-buffered 10% formalin and submitted for histologic examination. Immunohistochemical staining for calcitonin, thyroglobulin (thyroid mass), and synaptophysin (submandibular mass) were performed to assist in differentiating chemodectoma versus thyroid tumor. In sections of the thyroid mass, 80% of cells were labeled with calcitonin, whereas 20% of them were positive for thyroglobulin; the submandibular mass was strongly positive for synaptophysin (Figure 4). In view of these results and the hypertensive crisis during surgery, the final diagnoses were a mixed thyroid carcinoma and a functional carotid body tumor (chemodectoma).
Photomicrographs of sections of the thyroid mass (A) and submandibular mass (B) surgically resected from the patient in Figure 1. A—Notice the cells of the thyroid mass often form variably sized areas of colloid (arrows). H&E stain; bar = 200 μm. Upper inset—Twenty percent of neoplastic cells of the thyroid mass were positive for thyroglobulin. Immunohistochemical stain for thyroglobulin; bar = 100 μm. Lower inset—Eighty percent of neoplastic cells of the thyroid mass were positive for calcitonin. Immunohistochemical stain for calcitonin; bar = 100 μm. B—Neuroendocrine cells with a moderate amount of eosinophilic vacuolated granular cytoplasm are arranged in nests and packets within a fine fibrovascular stroma. There is marked anisokaryosis, but a low mitotic rate. H&E stain; bar = 200 μm. Inset—Notice the strong immunohistochemical staining for synaptophysin. Immunohistochemical stain for synaptophysin; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Photomicrographs of sections of the thyroid mass (A) and submandibular mass (B) surgically resected from the patient in Figure 1. A—Notice the cells of the thyroid mass often form variably sized areas of colloid (arrows). H&E stain; bar = 200 μm. Upper inset—Twenty percent of neoplastic cells of the thyroid mass were positive for thyroglobulin. Immunohistochemical stain for thyroglobulin; bar = 100 μm. Lower inset—Eighty percent of neoplastic cells of the thyroid mass were positive for calcitonin. Immunohistochemical stain for calcitonin; bar = 100 μm. B—Neuroendocrine cells with a moderate amount of eosinophilic vacuolated granular cytoplasm are arranged in nests and packets within a fine fibrovascular stroma. There is marked anisokaryosis, but a low mitotic rate. H&E stain; bar = 200 μm. Inset—Notice the strong immunohistochemical staining for synaptophysin. Immunohistochemical stain for synaptophysin; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
Photomicrographs of sections of the thyroid mass (A) and submandibular mass (B) surgically resected from the patient in Figure 1. A—Notice the cells of the thyroid mass often form variably sized areas of colloid (arrows). H&E stain; bar = 200 μm. Upper inset—Twenty percent of neoplastic cells of the thyroid mass were positive for thyroglobulin. Immunohistochemical stain for thyroglobulin; bar = 100 μm. Lower inset—Eighty percent of neoplastic cells of the thyroid mass were positive for calcitonin. Immunohistochemical stain for calcitonin; bar = 100 μm. B—Neuroendocrine cells with a moderate amount of eosinophilic vacuolated granular cytoplasm are arranged in nests and packets within a fine fibrovascular stroma. There is marked anisokaryosis, but a low mitotic rate. H&E stain; bar = 200 μm. Inset—Notice the strong immunohistochemical staining for synaptophysin. Immunohistochemical stain for synaptophysin; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1379
The patient recovered from surgery without any notable complications and remained in the intensive care unit for 3 days. Analgesia was provided by means of a CRI of remifentanil (4 to 6 μg/kg/h [1.8 to 2.7 μg/lb/h]) for the first 8 hours, followed by application of a fentanyl patch.n Thyroid hormone and ionized calcium concentrations were rechecked 1 day after surgery. Thyroid-stimulating hormone concentration was slightly increased (0.453 ng/mL), with total T4 (0.680 μg/dL), free T4 (< 0.30 ng/dL), and ionized calcium concentrations (0.89 mmol/L) moderately decreased. The patient's blood pressure, which was monitored with Doppler sphygmomanometry, was stable during the postoperative hospitalization period. Furthermore, clinical or laboratory signs suggestive of target organ damage caused by the hypertensive crisis were not observed, and the patient was discharged 3 days after surgery. Total T4, free T4, and ionized calcium concentrations were within reference ranges 12 days after surgery, but thyroid-stimulating hormone concentration remained high 4 months after surgery. Follow-up physical examinations and repeated radiographic and ultrasonographic examinations showed no signs of recurrence or metastasis. At the most recent follow-up examination, 152 days after surgery, the patient was reported to be doing well. In addition, the owner reported that the patient's personality became more relaxed after surgery.
Discussion
In the patient described in the present report, intraoperative manipulation of a submandibular mass resulted in a hypertensive crisis characterized by a sudden increase in systolic arterial blood pressure to > 300 mm Hg. Two possible causes for the intraoperative hypertensive crisis were considered. First, because the patient had concurrent submandibular and thyroid masses, the submandibular lesion was initially suspected to be a functional ectopic thyroid tumor. Systemic hypertension has been associated with thyroid adenocarcinoma,1 and thyroid storm (excessive secretion of thyroid hormone from an overactive thyroid gland or leakage from a damaged thyroid gland) could have occurred during surgery.2 However, apart from hypertension, the patient described did not show any other clinical signs or clinicopathologic abnormalities associated with thyroid storm, such as fever, gastrointestinal and neurologic signs, or hepatic dysfunction.2 The patient was also considered to be euthyroid on the basis of a preoperative thyroid hormone panel. Therefore, rather than thyroid storm, excessive catecholamine secretion from a functional carotid body tumor was thought to be the primary cause of the hypertensive crisis observed in this dog.
Paraganglia are groups of neuroepithelial chief cells found in various anatomic locations throughout the body (including the aortic and carotid bodies, vagus nerve, and adrenal medulla).3,4 These chief cells originate from the neural crest and are capable of producing various biologically active amines.3 Previous reports4,5 indicate that all paraganglia store catecholamines, and substantial evidence suggests that both clinically evident and silent paragangliomas (ie, neuroendocrine tumors of paraganglial origin) produce catecholamines.5 Most catecholamine-secreting paragangliomas release norepinephrine, although a few have been reported to secrete epinephrine or dopamine.3 In human patients, a 4- to 5-fold increase in norepinephrine concentration is typically required to produce symptoms, such that affected individuals may have markedly increased catecholamine concentration without symptoms.5
The most common sites for the development of chemodectomas in dogs and cats are the aortic and carotid bodies.6,7 The carotid bodies, which function as chemoreceptors, are sensitive to changes in pH and partial pressures of oxygen and carbon dioxide.3,8 Carotid body tumors arise from the carotid bodies located at the bifurcation of the common carotid artery.7–9 Although such tumors are more commonly malignant versus aortic body tumors, carotid body tumors are generally slow-growing masses that rarely metastasize or invade regional structures.6,8–10 Therefore, affected patients may be examined for non-specific clinical signs resulting from a space-occupying mass, including dyspnea and voice changes. Signs of neurologic and circulatory disorders are often absent until advanced stages of disease.10,11 Although neuroendocrine cells may secrete catecholamines, dopamine, and serotonin, carotid body tumors have been reported to be nonfunctional in small animals.6 However, it has been reported12–15 that 1% to 3% of carotid body tumors are functionally active in human patients.
Although rare, functional tumors in dogs that secrete excessive catecholamines include pheochromocytomas16 or, in extremely rare cases, intracardiac chromaffin paragangliomas.17 To date, systolic blood pressure > 300 mm Hg has only been described in dogs with pheochromocytoma.18 The patient of the present report remained hemodynamically stable during thyroidectomy, but acute fluctuations in blood pressure were observed upon manipulation of the carotid body tumor. However, a limitation of this report is that the maximum blood pressure that the monitoring equipment (monitore and invasive blood pressure transducerf) could record was 328 mm Hg, a value that we repeatedly observed during tumor manipulation. Therefore, in reality, the patient's blood pressure may have been > 328 mm Hg during surgery. For the patient described, blood pressure stabilized after the tumor was removed and remained within the reference range during all postoperative follow-up evaluations. Furthermore, the owners suggested that the dog's personality changed from an excited and impatient state to a more relaxed and docile state after surgery. Considering these features, although we were unable to definitively confirm the diagnosis on the basis of pre- and postoperative measurement of serum or urine normetanephrine and metanephrine concentrations, we suspect that the carotid body tumor in the dog of this report was functional.
The patient of the present report had both a mixed thyroid tumor and a carotid body tumor. Such tumors may have similar characteristics in terms of location and clinical signs and should therefore be carefully differentiated.19 Several cases have been reported where carotid body tumors were mistakenly diagnosed as thyroid tumors and vice versa.19,20 Also, in patients with multiple tumors in the head and neck region, a tumor may be mistaken for a metastatic lymph node. Multiple endocrine neoplasms syndrome21 describes patients with tumors of at least 2 endocrine organs and is typically of genetic origin. Simultaneous development of thyroid and carotid body tumors has been reported in both dogs and humans,22–24 such that this may perhaps not be exceedingly rare, considering the rarity of these 2 types of tumors. Cells of the carotid body and C cells of the thyroid gland both originate from the neural crest during embryogenesis.21,23 Therefore, careful and thorough clinical and laboratory evaluation of patients with a presumptive diagnosis of a neuroendocrine tumor is advised to rule out concurrent neoplasia.
A variety of drugs were administered as part of the anesthetic care plan for the patient of the present report. Considering the properties of the drugs administered, it is possible that ketamine may have contributed to the hypertension and tachycardia observed. Intravenous administration of ketamine, which increases systemic arterial blood pressure, HR, and cardiac output by direct stimulation of the CNS, results in increased concentrations of plasma catecholamines by inhibiting norepinephrine reuptake into postganglionic sympathetic nerve endings.25 However, ketamine was administered to the dog of this report after severe hypertension was first observed during preoperative manipulation and aseptic preparation for surgery. Also, a single dose of ketamine and diazepam administered IV has a short duration of action (approx 20 minutes),25 and the intraoperative hypertensive crisis developed approximately 2 hours after ketamine administration. Considering these factors, the effect of ketamine as a contributor to the hypertensive crisis was considered minimal.
Because chronic hypertension can result in target organ damage,26,27 prompt treatment for intraoperative acute hypertension or hypertensive crisis is essential to prevent organ damage and reduce overall morbidity and mortality rates.16,26 Because the biochemical activity of catecholamine-secreting paragangliomas is very similar to that of pheochromocytomas, a similar anesthesia care plan can be devised for these patients.4 In the dog of the present report, the intraoperative hypertensive crisis was treated with sodium nitroprusside, a potent vasodilator with a rapid onset and short duration of action, whereas the tachyarrhythmias were treated with esmolol, a short-acting β-adrenergic receptor blocker with a rapid onset of action.28 Esmolol was effective in managing the tachyarrhythmias; however, sodium nitroprusside was less effective in controlling blood pressure in this case. Sufficient decreases in blood pressure were observed only when surgical manipulation was ceased. Recently, Fishbein et al29 reported that risk factors for hemodynamic instability in human patients with paragangliomas included tumor size (tumors > 3 to 4 cm), uncontrolled hypertension, and high preoperative catecholamine concentrations. On the basis of the results of preoperative CT, the carotid body tumor in the dog of this report was approximately 3 cm in diameter. This, in addition to the fact that the patient's blood pressure was not effectively controlled preoperatively, may have increased the risk for intraoperative hemodynamic instability. Although it is difficult to determine why sodium nitroprusside was less therapeutically effective in this case than expected, we suspect that the uncontrolled preoperative hypertension and larger tumor size may have contributed. The anesthesiologist should ask the surgeon to discontinue surgical manipulation if hypertension is not responsive to pharmacologic treatment.3 Because circulating catecholamines have a short half-life (1 to 2 minutes), even short pauses in the surgery may be the most effective means of controlling blood pressure.3 In our patient, continuous dialogue between the surgeons and anesthesiologists regarding the patient's status during carotid body tumor manipulation was helpful in managing the hypertensive crisis.
Various other medications could be considered both pre- and intraoperatively to reduce morbidity and mortality in affected patients. The release of norepinephrine, which activates α-adrenergic receptors, results in vasoconstriction, hypertension, and decreased vascular volume.16 Therefore, phenoxybenzamine, which is a nonselective α-adrenergic receptor antagonist, can be administered for 1 to 4 weeks prior to anesthesia to allow for gradual vasodilation, reestablishment of vascular volume, cardiac recovery, and stabilization of blood pressure.3,16 Previous studies3,16 have reported that such pretreatment with phenoxybenzamine resulted in significantly lower mortality rates in both human patients and dogs. In the present case, a functional tumor had not been suspected prior to surgery; therefore, phenoxybenzamine treatment for preoperative α-adrenergic receptor blockade was not considered. An intraoperative hypertensive crisis requires immediate attention, and treatment should be started when systolic arterial pressure reaches 180 mm Hg.16 The administration of short-acting antihypertensive drugs with a rapid onset is currently the preferred method for maintaining intraoperative hemodynamic stability.16 Apart from sodium nitroprusside as for the patient of this report, magnesium sulfate may also be administered to treat hypertensive crises in human patients with a pheochromocytoma. Magnesium sulfate decreases blood pressure by various mechanisms, including inhibition of catecholamine release, direct inhibition of catecholamine receptors, and vasodilation.16 Also, unlike sodium nitroprusside, it does not usually result in profound hypotension.16 If phenoxybenzamine and magnesium sulfate had been administered pre- and intraoperatively in the patient of the present report, these may have been helpful in mitigating the hypertensive crisis observed.
It has been reported that laryngeal paralysis and Horner syndrome were the most common postoperative complications after surgical excision of carotid body tumors in dogs.8 Furthermore, potential complications of thyroidectomy include hemorrhage, hypothyroidism, megaesophagus, and laryngeal paralysis secondary to iatrogenic recurrent laryngeal nerve injury.30 The dog described in the present report remained in the intensive care unit for 3 days after surgery to monitor for complications. There was no evidence of postoperative hemorrhage, Horner syndrome, or laryngeal paralysis. Because the carotid bodies detect changes in pH and partial pressures of oxygen and carbon dioxide, dysregulation of carotid body chemoreceptors can result in hyperpnea and dyspnea.9 Although our patient was occasionally tachypneic after surgery, there was no evidence of dyspnea or hyperpnea.
In the patient described in the present report, arterial catheterization for direct blood pressure monitoring was performed prior to induction of anesthesia. This allowed for recognition of severe hypertension during surgical preparation and external manipulation around the submandibular mass, which in turn allowed for modification of the anesthesia care plan (preparation of sodium nitroprusside and esmolol for intraoperative use). Because catecholamine-secreting tumors, (eg, pheochromocytomas and intracardiac chromaffin paragangliomas) are seldom able to be palpated externally because of their anatomic location, the diagnosis of a functional tumor is generally dependent on results of laboratory tests. However, the clinical course and outcome described for the patient of this report suggests that response to preoperative tumor manipulation may indicate a functional tumor. In cases in which such manipulation results in severe hypertension, a catecholamine-secreting tumor should be suspected and the possibility of an intraoperative hypertensive crisis should be considered. Vigilant monitoring and the immediate availability of appropriate drugs to assist in maintaining hemodynamic instability are required.
Acknowledgments
Supported by the Basic Science Research Promotion program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2011-0007777) and the BK21 PLUS program and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University.
Footnotes
811-B Doppler flow detector, Parks Medical Electronics Inc, Aloha, Ore.
Chong Kun Dang Pharmaceutical Corp, Seoul, Republic of Korea.
Samjin, Seoul, Republic of Korea.
Ultiva, GlaxoSmithKline Korea, Seoul, Republic of Korea.
FI/Carescape Monitor B650, GE Healthcare, Helsinki, Finland.
Transpac IV monitoring kit, ICU Medical Inc, San Clemente, Calif.
Ketalar, Yuhan, Seoul, Republic of Korea.
Alfaxan, JUROX Pty Ltd, Rutherford, NSW, Australia.
Ifrane, Hana Pharm Co Ltd, Hwaseong, Republic of Korea.
FO-20S ACOMA anesthesia machine, ACOMA Medical Industry Co Ltd, Tokyo, Japan.
Daihan Pharmaceutical Co Ltd, Seoul, Republic of Korea.
Nitropress, Hospira Korea Co Ltd, Seoul, Republic of Korea.
Brevibloc, Jeil Pharmaceutical Co Ltd, Seoul, Republic of Korea.
Durogesic Dtrans transdermal patch, Janssen Korea Ltd, Hwaseong, Republic of Korea.
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