Severe Bleeding During Orthognathic Surgery for a Noonan Syndrome Patient

Noonan syndrome (NS) is an autosomal dominant disorder leading to abnormal development that can impact several areas of the body. NS presentation is variable and may include distinctive facial features, short stature, chest deformities, congenital heart defects, bleeding disorders, intellectual disabilities, and skeletal malformations.^1,2 The prevalence of NS is estimated at 1:1000 to 1:2500.¹ Previous reports have demonstrated the potential for anesthetic problems including impaired cardiopulmonary function, intubation difficulties, and coagulopathies.^3,4 Although patients with NS often require orthognathic surgery due to the high prevalence of malocclusion (50%–67%) and micrognathia (33%–43%),^1,5 little has been reported on the anesthetic management of patients with NS undergoing orthognathic surgery. Here, we report the case of a patient with NS who experienced severe bleeding during general anesthesia for orthognathic surgery.

CASE PRESENTATION

A 31-year-old woman (height 148 cm; weight 52 kg; body mass index 23.7 kg/m²) with NS was scheduled to undergo a Le Fort I osteotomy and bilateral sagittal splitting ramus osteotomy under general anesthesia. Cephalometric radiographs revealed mandibular prognathism due to maxillary hypoplasia and mandibular hyperplasia. She had a short stature, hypertelorism, a short neck, hypertrophic cardiomyopathy, an atrial septal defect, iron-deficiency anemia, and recurrent episodes of lymphoedema caused by arteriovenous malformations in both lower extremities. Transthoracic echocardiography (TTE) revealed mild left ventricular hypertrophy (interventricular septum width 16 mm; normal 8–12 mm) and mild mitral valve regurgitation and confirmed the atrial septal defect. There was no evidence of left ventricular outflow tract (LVOT) obstruction, and her ejection fraction was 60%.

Preoperative hematologic testing revealed a slight prolongation of the activated partial thromboplastin time (39.2 seconds) and a normal international normalized ratio (1.03) and platelet count (19 × 10⁴/μL), although her platelet function was not assessed. Considering the potential risk of bleeding with NS and her medical history of anemia, 4 units of autologous blood were deposited preoperatively after she underwent anemia treatment with oral iron therapy and subcutaneous injections of epoetin β. Her preoperative hemoglobin and hematocrit were 12.1 g/dL and 35.5%, respectively (Table).

Perioperative Changes in Hemoglobin/Hematocrit, Blood Loss, and Infused Fluids

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Upon arrival to the operating room, standard anesthesia monitors were applied, and a 22-gauge peripheral intravenous (IV) catheter was placed into left dorsum of her hand. General anesthesia was induced with propofol 100 mg, remifentanil infusion 0.3 μg/kg/min, and rocuronium 30 mg. Although previous reports demonstrated the potential difficult airways in patients with NS due to craniofacial abnormalities,^3,4 nasotracheal intubation was performed without difficulty. Ampicillin 1 g was administered prior to the surgical procedure to prevent infectious endocarditis. Anesthesia was maintained with sevoflurane 1%–3%, O₂ 1 L/min, air 3 L/min, remifentanil infusion 0.2–0.5 μg/kg/min, and intermittent fentanyl boluses (2050 μg total). Despite the use of 1% lidocaine with 1:200,000 epinephrine (lidocaine 110 mg, epinephrine 55 μg) for local anesthesia prior to the Le Fort I osteotomy, hemostasis was difficult to achieve from the start of the surgery even though her blood pressure was not elevated (109–93/53–44 mm Hg). Therefore, mild hypotensive anesthesia was started to reduce blood loss using a nitroglycerin infusion 0.5–0.8 μg/kg/min for a targeted mean arterial blood pressure of 65 mm Hg. At the end of the Le Fort I osteotomy, blood loss reached 825 mL and hematological examination revealed anemia (hemoglobin 7.6 g/dL; hematocrit 21.4%), so the 4 units of predeposited autologous blood were transfused to compensate (Table). The bilateral sagittal split ramus osteotomy was then started, and tranexamic acid 1 g was intravenously administered to improve hemostasis. However, the anemia did not improve until the end of the surgery (hemoglobin 7.5 g/dL; hematocrit 23.5%) due to the sustained bleeding from the surgical sites although her mean blood pressure was maintained at 60–65 mm Hg throughout the surgery (Table). Blood loss and IV fluid totals were 1442 mL and 2470 mL (crystalloid 1820 mL; colloid 650 mL), respectively. After the surgery, the patient was transported to the intensive care unit where 2 additional units of packed red blood cells were transfused. Thereafter, her anemia improved (hemoglobin 8.9 g/dL; hematocrit 27.6%).

On postoperative day 1, her hemoglobin and hematocrit levels were maintained (hemoglobin 8.7 g/dL; hematocrit 26.9%; Table). After confirming stable hemodynamics and adequate respiratory efforts, the patient was extubated and transported to the ward. As normal per our institution, she remained in the hospital throughout her uneventful postoperative course and was discharged home on postoperative day 14.

DISCUSSION

NS involves deregulated RAS/MAPK signal transduction pathways arising from PTPN11, SOS1, KRAS, and RAF1 gene mutations in 60% to 70% of NS cases.^8–11 This genetic disorder can result in a variable multitude of congenital abnormalities, including short stature, hypertelorism, congenital heart defects, chest deformities, and issues with hemostasis.^5–7 Although the patient in this case had several features common to NS, there was no reported history of any bleeding disorders. However, the patient experienced significant bleeding intraoperatively, particularly during the maxillary (Le Fort I) osteotomy, that required autologous transfusions to compensate for the blood loss and the administration of tranexamic acid to potentiate hemostasis.

Reportedly, 58% of patients with NS possess hemorrhagic conditions and 3% have severe bleeding diatheses.^6,12 Putative factors of bleeding diatheses in patients with NS include coagulation-factor deficiencies, thrombocytopenia, platelet dysfunction, and von Willebrand disease.¹² Coagulation and platelet abnormalities were present in 87.5% of patients with NS without a reported bleeding diathesis, demonstrating a strong predisposition for excessive perioperative bleeding even in the absence of any abnormal bleeding episodes.^13,14

Lack of a correlation between abnormal coagulation test results and a history of easy bruising with patients with NS has also been reported.⁷ This patient's routine preoperative bleeding tests revealed that prothrombin time-international normalized ratio (PT-INR) and platelet count were within normal, although platelet dysfunction was not evaluated and activated partial thromboplastin time was slightly prolonged. Because most patients with NS have bleeding diatheses, and coagulation defects may not be detected by routine screening, it is recommended that additional testing, like platelet function studies, individual coagulation factor levels (factors VIII, IX, XI, XII), and von Willebrand disease tests, should be obtained preoperatively.¹² Furthermore, it is recommended that patients with NS be referred to a hematologist preoperatively for further assessment.^6,12,13

It is also important to prepare for perioperative bleeding.¹⁵ In the present case, 4 units of autologous blood were stored preoperatively for anticipated intraoperative bleeding. However, 4 units of autologous blood were not enough to compensate the blood loss due to excessive bleeding, and additional packed red blood cells were transfused. To anesthetize patients with NS for major surgery, availability of enough blood derivatives is crucial. In addition, the present case had recurrent episodes of lymphoedema, which is resulted from arteriovenous malformation. Therefore, vascular malformation and fragility of vessels might have contributed to the excessive intraoperative bleeding that occurred.

Previous reports have demonstrated a potential for difficult airway management in patients with NS.^3,4 Difficulty with tracheal intubation in patients with NS can arise from craniofacial abnormalities, which include high palatal arch, dental malocclusion, and webbing of the neck.³ Even though in the present case the patient did have some noted craniofacial abnormalities, tracheal intubation was easily accomplished likely because of her mandibular protrusion.

Cardiovascular disease is one of the principal features of NS and is observed as frequently as 82%–90%.^9,10 Congenital heart defects are the major cardiovascular abnormality, with pulmonary stenosis being the most common (25%–71%), followed by atrial septal defects (4%–57%), hypertrophic cardiomyopathy (10%–29%), ventricular septal defects (1%–14%), arterial aneurysms (<1%), and others.¹⁰ In the present case, hypertrophic cardiomyopathy and mitral valve regurgitation were identified by preoperative screening with TTE, but the planned surgery continued as the patient did not present with apparent LVOT obstruction and never experienced any serious cardiac signs or symptoms such as syncope. Strategies for the anesthetic management of patients with hypertrophic cardiomyopathy include the following: 1) maintaining preload and afterload, and 2) avoiding excessive sympathetic activity, which induces LVOT obstruction.¹⁶ We used sevoflurane to maintain general anesthesia in this case because it causes mild myocardial depression and a modest decrease in systemic vascular resistance and blood pressure compared with other volatile anesthetics like isoflurane or desflurane.¹⁷

In orthognathic surgery, hypotensive anesthesia is commonly used to reduce blood loss and improve visibility of the surgical sites.¹⁸ However, vasodilator-induced hypotension is potentially unsafe in patients with hypertrophic cardiomyopathy because it reduces preload, which can lead to a decrease in cardiac output. Therefore, at the beginning of the operation, we did not attempt to perform hypotensive anesthesia, and mean arterial blood pressure was kept at ∼70 mm Hg. However, due to unexpected excessive bleeding, controlled hypotension was requested by the oral surgeons before the maxillary down fracture. We induced mild hypotensive anesthesia throughout the surgical procedure using a nitroglycerine infusion while carefully monitoring arterial pulse pressure variation, which helps quantify the changes in arterial pulse pressure during mechanical ventilation and is one of the dynamic variables that can predict fluid responsiveness.¹⁹

CONCLUSION

To perform orthognathic surgery for patients with NS, appropriate preoperative evaluations of any existing cardiovascular comorbidities, possible hemostatic abnormalities, and craniofacial abnormalities, which potentially leads to difficult airway management are required. Even if routine preoperative coagulation tests are normal, a more extensive hematologic evaluation may be recommended. Furthermore, preparations for addressing unexpected significant bleeding are crucial for the safe perioperative management of the patients with NS.