Abstract

Background: This study aims to evaluate our approaches and outcomes in patients who developed hemoptysis following pulmonary endarterectomy.

Methods: Pulmonary endarterectomy was performed in 460 patients at Kartal Koşuyolu Training and Research Hospital between March 2011 and September 2017. Clinical characteristics, perioperative management and postoperative outcomes of 10 patients (2.1%) (4 males, 6 females; mean age 48.3±16.5 years; range 21 to 76 years) with massive pulmonary hemorrhage following pulmonary endarterectomy were evaluated.

Results: Mean period of diagnosis for chronic thromboembolic pulmonary hypertension was 17±13.6 months. All patients were New York Heart Association functional class II (n=2), III (n=5) or IV (n=3). For the treatment of massive pulmonary hemorrhage, intraoperative extracorporeal membrane oxygenation was used in six patients (60%), while conservative treatments were used in four patients (40%). In-hospital mortality rate was 50% (n=5); the causes for mortality were septic shock in two patients, multiple organ failure in two patients and intracranial hemorrhage in one patient. Survival was achieved in two patients on extracorporeal membrane oxygenation and three patients receiving conservative treatment. Functional and hemodynamic improvement was observed in all surviving patients.

Conclusion: Despite the relatively low incidence of massive pulmonary hemorrhage after pulmonary endarterectomy, it is a potentially fatal complication. Our approach focuses on early diagnosis with a multidisciplinary team and management with bronchoscopy, bronchial blockers and use of extracorporeal membrane oxygenation. The choice of treatment depends on the site and origin of the hemorrhage, the availability of equipment and expertise, and the potential short- and long-term advantages and disadvantages.

Pulmonary endarterectomy (PEA) is the only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The success of PEA depends upon complete endarterectomy of the intima, chronic organized thromboembolic material, and part of the media of the affected pulmonary arteries (PAs).[1] Despite the technically challenging nature and the increasing frequency of this surgery, pulmonary hemorrhage remains a rare occurrence after PEA, with a reported incidence of 0.5 to 2%.[2,3] While the exact mechanism of pulmonary hemorrhage after PEA is often unknown, surgical trauma resulting in the disruption of the arterial adventitia and/or increased capillary permeability following restored perfusion as a form of severe acute lung injury are both plausible mechanisms.[4] Initial management focuses on the maintenance of hemodynamics and gas exchange. Since the beginning of the implementation of PEA in our center,[5] patient referrals have increased substantially over the years, and we have become more experienced in the procedure and its complications. We have previously published two case reports about the management of pulmonary hemorrhage following PEA.[6,7] In this study, we a imed to evaluate our approaches and outcomes in patients who developed hemoptysis following PEA.

Methods

A total of 460 consecutive patients underwent PEA at Kartal Koşuyolu Training and Research Hospital between March 2011 and September 2017. The medical records of 10 patients (2.1%) (4 males, 6 females; mean age 48.3±16.5 years; range 21 to 76 years) with massive pulmonary hemorrhage following surgery were reviewed to evaluate the clinical characteristics, perioperative management and the postoperative outcomes. All data were collected prospectively and entered into a database. Demographic features such as age, gender, age of onset, duration of disease and pulmonary function tests, complications, in-hospital mortality, and length of hospital stay were recorded. The diagnosis of CTEPH was established by sixminute walking test, while the presence of mismatched perfusion defects on the ventilation perfusion scan was associated with evidence of pulmonary hypertension on transthoracic echocardiogram, despite adequate anticoagulation for at least three months. Diagnosis and cardiopulmonary hemodynamic characteristics were determined by computed tomography pulmonary angiography (CTPA) and right heart catheterization (RHC). Our indications for PEA were as follows: New York Heart Association functional class greater than II and absence of significant comorbidities and CTPA or scintigraphic evidence of obstruction of the pulmonary arterial tree. Our technique of PEA was previously described.[5] S hortly, t he o peration was performed on deep hypothermia (20°C) for both lungs under complete circulatory arrest. A true endarterectomy was accomplished and, when it was completed on both sides, circulation with warming was restarted (Figure 1). Weaning from cardiopulmonary bypass (CPB) was performed with care. Any hemorrhage that was noted in the endotracheal tube upon separation from CPB was defined as massive pulmonary hemorrhage. Our algorithm for treatment of hemoptysis is presented in Figure 2. Initial fiberoptic bronchoscopy (FOB) was performed to identify the color and location of the hemorrhage. Frothy and bright red hemorrhage suggested reperfusion lung injury or pulmonary edema and conservative treatment with phenylephrine 10 mg and vasopressin 20 U diluted to 10 mL with normal saline via the endotracheal tube and hyperventilation (volume control mode, respiratory rate 15 breaths/minute, tidal volume 500 mL, fraction of inspired oxygen 100%, and positive end-expiratory pressure [PEEP] 15 centimeters of water [cmH2O]) was performed. Heparin was reversed with intravenous protamine (350 mg) and coagulopathies were corrected with fresh frozen plasma and platelets. On the other hand, if color of the hemorrhage was dark red, suggestive of tear in PA, the bronchus in which the hemorrhage was observed was occluded with a bronchial blocker and extracorporeal membrane oxygenation (ECMO) was instituted because of hypoxia and hemodynamic instability. The bronchial blocker was deflated and removed 24 or 48 hours after the surgery if there was no evidence of ongoing hemorrhage. When no active hemorrhage was confirmed and oxygenation/ ventilation had improved on two-lung ventilation, ECMO was weaned.

Figure 1: Surgical specimens of all cases except case 1, 3 and 5.[6,7,9]

Figure 2: A general algorithm for treatment of hemoptysis.
PA: Pulmonary artery; CPB: Cardiopulmonary bypass; ECMO: Extracorporeal membrane oxygenation.

In order to detect any hemorrhage point intraoperatively, we adopted the technique described by Morsolini et al.[8] A fter e ndarterectomy w as completed in one lung, the main PA was filled with saline. At this time, gentle positive pressure was delivered to the airway through the anesthetic circuit, and bubbling was checked in the PA lumen. The area was then flooded with saline solution and rechecked with hand ventilation. If bubbling was visualized, under circulatory arrest, that particular branch of the PA was closed with an 6/0 pronene suture (PROLENE® Polypropylene Suture, Ethicon, CA, USA). Operative mortality was defined as death in hospital or within 30 days of surgery. Length of in-hospital and intensive care unit (ICU) stay were noted. The study protocol was approved by the Kartal Koşuyolu Training and Research Hospital Ethics Committee. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical analysis
All data were collected, tabulated and statistically analyzed. Numerical variables were presented as mean and standard deviation. Continuous random variables were presented as median and range (maximum-minimum values). Statistical analyses were carried out using SPSS for Windows version 13.0 software (SPSS Inc., Chicago, IL, USA).

Results

The pre- and intraoperative characteristics of patients are presented in Table 1. Eight patients presented with a history of pulmonary embolism, while two patients had a history of deep venous thromboembolism. Exerciseinduced dyspnea was the presenting symptom in seven patients. One patient had Behçet’s disease,[9] one had hydatid cyst and one had systemic lupus erythematosus (SLE). No coagulation disorders were defined.

Table 1: Demographic and clinical characteristics of patients

Conservative treatment was used in four cases and ECMO in six cases (60%). All patients required the technique intraoperatively, either venoarterial (VA) or venovenous (VV), because of hypoxia and hemodynamic instability.

The in-hospital mortality rate was 50% (n=5). Two patients on ECMO and three patients on conservative treatment survived.

Case 1- The detailed history of the case was previously reported.[7] Following PEA, hemorrhage from right lower lobe bronchi was observed in a 38-year-old female patient with a diagnosis of SLE. The bronchus was occluded with a Fogarty balloon catheter. A right femoral peripheral VA-ECMO was instituted. She was successfully weaned from ECMO on the fourth postoperative day (POD). On POD seven, she was weaned from ventilation and discharged on the 19^th POD.

Case 2- A 54-year-old female patient with RHC had mean pulmonary artery pressure (mPAP) of 36 mmHg and calculated pulmonary vascular resistance (PVR) of 380 dynes/s/cm-5. Following PEA, pinky bright massive pulmonary hemorrhage (800 mL) was observed. Positive End Expiratory Pressure 15 cm H2O was applied; phenylephrine 10 mg and vasopressin 20 U diluted to 10 mL with normal saline were administered via the endotracheal tube. The hemorrhage subsided, but soon copious amounts of pink frothy sputum suggestive of pulmonary edema appeared in the endotracheal tube. The patient was brought to the ICU requiring significant inotropic support and was ventilator dependent with reperfusion lung injury for two days. She was discharged on the 14^th POD.

Case 3- A 21-year-old female patient with Behçet’s disease and RHC had mPAP of 45 mmHg and PVR of 977 dynes/s/cm-5. After endarterectomy was completed in the right lung, we used the technique explained above.[8] She was weaned from CPB without any problem. She was discharged on the eighth POD.

Case 4- A 61-year-old male patient with chronic obstructive pulmonary disease and RHC had mPAP of 56 mmHg and PVR of 977 dynes/s/cm-5. Although the operative course was uneventful, massive pulmonary hemorrhage occurred. Fiberoptic bronchoscopy showed hemorrhage from left main bronchi, which was occluded with blocker. Although a right femoral and jugular peripheral VV-ECMO was instituted, the patient died on the 10th POD due to sepsis.

Case 5- The detailed history of the case was previously reported.[6] A 32-year-old male patient with a history of hydatid cysts presented with PEA. Conservative treatment and physiological lung exclusion were performed. We stapled the right main PA and the right main bronchus leaving the pulmonary veins intact. On POD three, ECMO was used due to hypoxia and hypercarbia. The patient was successfully weaned from ECMO on POD seven. Unfortunately, the patient died on POD 12 due to septic shock.

Case 6- A 49-year-old female patient with RHC had mPAP of 36 mmHg and PVR of 800 dynes/s/cm-5. Following PEA, massive pulmonary hemorrhage was observed in right main bronchi, which was occluded and central VA-ECMO was instituted. However, the patient died on the eighth POD due to multiple organ failure.

Case 7- A 5 6-year-old f emale p atient w ith R HC had mPAP of 32 mmHg and PVR of 960 dynes/s/cm-5. Hemorrhage was observed in right main bronchi after PEA, which was occluded and central VA-ECMO was instituted. Unfortunately, the patient experienced multiple organ system failure and residual pulmonary hypertension refractory to pulmonary vasodilator therapy. She died on 19^th POD.

Case 8- A 61-year-old m ale patient with RHC h ad mPAP of 48 mmHg and PVR of 896 dynes/s/cm-5. Hemorrhage was observed in right main bronchi following PEA, which was occluded and central VA-ECMO was instituted. However, the patient died on the third POD due to intracranial hemorrhage.

Case 9- A 35-year-old male patient with RHC had mPAP of 60 mmHg and PVR of 960 dynes/s/cm-5. Hemorrhage in right main bronchi was blocked and central VA-ECMO was instituted. He was successfully weaned from ECMO on the fourth POD. On POD six, he was weaned from ventilation and discharged on the 18^th POD.

Case 10-<7b> A 7 6-year-old f emale p atient w ith R HC had mPAP of 65 mmHg and PVR of 1760 dynes/s/cm-5. The operative course was uneventful, but massive pulmonary hemorrhage (1000 mL) was observed at separation from CPB. Conservative treatment was used. She was ventilator-dependent with reperfusion lung injury for four days. She was discharged at POD 21.