Eur J Cardiothorac Surg 2003;24:580-587
© 2003 Elsevier Science NL
Successful management of acute pulmonary embolism after surgery for lung cancer
Toru Sakuragi*,
Yukinori Sakao,
Kojiro Furukawa,
Kazuhisa Rikitake,
Satoshi Ohtsubo,
Yukio Okazaki,
Masafumi Natsuaki,
Tsuyoshi Itoh
Department of Thoracic and Cardiovascular Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
Received 28 March 2003;
received in revised form 4 June 2003;
accepted 12 June 2003.
* Corresponding author. Tel.: +81-952-34-2345; fax: +81-952-34-2061
e-mail: sakurat{at}post.saga-med.ac.jp
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Abstract
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Objective: Although many case reports of acute pulmonary embolism (APE) have been published, the literature dealing with the management of APE after resection of lung cancer is limited. This report describes seven cases of successful management of APE after surgery for lung cancer and discusses how to manage this problematic complication. Methods: The medical charts of seven patients with APE after lobectomy and complete mediastinal lymphnode dissection were retrospectively reviewed. Results: Six patients collapsed during their first attempt at walking after surgery in conjunction with a dramatic respiratory change. All these patients promptly underwent enhanced spiral computed tomography (CT) scanning. Bilateral clots were detected in all patients and one patient with a deep venous thrombus (DVT) in the femoral vein had a temporary inferior vena cava filter implanted. Non-surgical therapy was used for six patients: thrombolysis (systemic urokinase) and anticoagulant (heparin or argatroban) for four patients and only anticoagulant therapy started on the day after the operation using argatroban for two. There were no bleeding problems with these thrombolysis and/or anticoagulant therapies except in one case of hemorrhage induced by heparin usage on the day after the operation. None of the cases required allotransfusion in connection with these therapies. Thromboembolectomy was performed for one patient who was hemodynamically unstable due to massive embolism and primary atrial fibrillation. All patients were discharged from our hospital without major complications. Conclusions: Patients with pulmonary embolism after surgery for lung cancer can be treated aggressively with anticoagulants with/without fibrinolitics or even with pulmonary embolectomy on cardiopulmonary bypass, without excessive risk of bleeding complications. Enhanced spiral CT scanning was very helpful for making a simultaneous diagnosis of APE and DVT. The use of argatroban in conjunction with activated clotting time monitoring should be effective without causing bleeding problems during the early stages after pulmonary resection for lung cancer.
Key Words: Acute pulmonary embolism • Deep venous thrombus • Lobectomy • Mediastinal lymph node dissection • Lung cancer • Argatroban
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1. Introduction
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Pulmonary thromboembolism is a well-recognized fatal complication following lung resection [1,2] occurring in up to 5% of cases [3]. In Japan, acute pulmonary embolism (APE) has been relatively uncommon [4] but is being increasingly recognized as a factor responsible for in-hospital deaths [5]. Clinical experience has shown that there are ethnic differences between Japanese and Caucasians in response to anticoagulation therapy [5]. Preoperative thromboembolic prophylaxis with heparin has not been in common use in Japan. Because the incidence of diagnosed APE has been increasing in Japan due to changes in lifestyle, aging of the population, clinicians' enhanced awareness of APE, and advances in diagnostic modalities [5,6], many institutes have begun to accept the perioperative administration of heparin in spite of the fact that there is no evidence provided by Japanese studies of the efficiency of the use of perioperative anticoagulant as seen in Western studies [7].
To reduce hospital morbidity and mortality, it is extremely important that APE is identified and treated early [8], because the prognosis for patients with reduced lung parenchyma and pulmonary artery diameters is poor [1,9]. We successfully managed seven patients who developed APE after lobectomy with systematic mediastinal lymph node dissection for lung cancer. These favorable clinical outcomes would be the result of our close supervision of the patients during their first attempt at walking after the resection and aggressive diagnosis with enhanced spiral computed tomography (CT) scanning and choice of adequate treatment options.
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2. Patients and methods
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Between 1995 and 2002, 372 patients underwent pulmonary resection for lung cancer in our institute without specific pharmacologic prophylaxis for deep venous thrombosis (DVT), but with aggressive diagnostic strategies including spiral CT (electron-beam CT scanner C-150XP; Imatron, San Francisco, CA, USA or multi-detector row CT Light Speed QX/i; GE Medical System, Milwaukee, WI, USA) enhanced with contrast media with 3-mm thick contiguous section. CT scans were obtained for the patients with potential APE who complained of dyspnea with the dramatic change of clinical signs (respiratory rate, O2 saturation, consciousness level and cardiac arrest) in the postoperative period. Seven out of 372 patients (1.9%) were confirmed to be with APE by CT.
The treatment for all patients was initiated immediately based on the results of CT scanning. Our basic treatment strategy was that the hemodynamically stable patient would be indicated to non-surgical treatments and unstable patient would be indicated to thromboembolectomy on cardiopulmonary bypass (CPB). In the non-surgical treatments, anticoagulant was continuously administered into the vein to maintain the activated clotting time (ACT) in a range of 150–200 s. The patients who had shown several days of recovery after pulmonary resection underwent thrombolysis (intravenous infusion of urokinase) with simultaneous anticoagulant administration. The patients who would be treated on the day after pulmonary resection underwent anticoagulant therapy alone because of the danger of bleeding in the thoracic space. In patients with DVT, a temporary inferior vena cava (IVC) filter would be implanted just after CT scanning.
The patients' medical charts were reviewed for patient profiles (age, sex, height, weight, operative procedures for lung cancer, operation time, amount of intraoperative bleeding, intraoperative transfusion, and pathological diagnosis of tumor), onset of APE (day of onset after pulmonary resection, trigger, respiratory rate before and after onset, oxygen saturation measured by pulse oxymeter, blood pressure, consciousness level and appearance of thrombus on enhanced spiral CT scanning), treatment (treatment type, days between pulmonary resection and treatment initiation, treatment regimen and bleeding problems), and outcomes.
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3. Results
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3.1. Patients characteristics
(Table 1) Median operation time was 325 min. The amount of intraoperative bleeding was less than 500 ml in all cases (median: 409 ml) except in one case of combined chest wall resection. No secondary atrial fibrillation after pulmonary resection was detected with electrocardiogram monitoring.
3.2. Onset of pulmonary embolism
(Table 2) Six of the seven patients collapsed with dyspnea, which was accompanied by rapid and short breathing and low arterial saturation as measured by pulse oxymeter, despite sufficient oxygen supply. The other patient (patient 2) suffered circulatory arrest and was intubated immediately. Six of the patients showed their symptoms during their first attempt at walking. Four patients, including the one with circulatory arrest, showed loss of consciousness (syncope) at the onset.
Three patients (2, 5, and 6) had early onset of APE on the day after the resection. Patient 2 suddenly developed dyspnea followed by syncope and circulatory arrest during the first walk. Cardiac output was restored by immediate resuscitation and we had suspected the arrest was due to arrhythmia rather than pulmonary embolism. The patient recovered gradually with antiarrythmia but collapsed again with dyspnea and tachypnea during the walk on the seventh postoperative day. Signs of circulatory instability (low blood pressure, tachycardia, and cold sweat) were observed, leading us to make diagnosis of low cardiac output syndrome.
The four patients showed relatively late onset (patients 1, 3, 4 and 7) of APE. The three had been subject to prolonged immobilization after the surgery. Patients 1 and 3 because of complaints of pain and patient 4 because of mandatory postoperative intubation for 3 days due to laryngeal edema resulting from simultaneous resection of a laryngeal cyst. Patient 7 had moved well since the day after surgery but he fell into collapse on fourth postoperative day.
The CTs reviewed bilateral embolism in all seven patients. The scans clearly showed clots not only in the central pulmonary artery (Fig. 1
) but also in the second to fourth division pulmonary arteries (Fig. 2A
). Simultaneous scanning of regions below the abdomen was performed for six of the APE patients and DVT was reviewed in the left femoral vein of one patient (Fig. 3
).
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Fig. 1. Enhanced spiral computed tomography shows clots in pulmonary trunk to bilateral main pulmonary artery (patient 7).
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Fig. 2. (A) Thrombi in the right middle pulmonary artery (large arrow) and in the left subsegmental arteries (small arrows). Even in the second to fourth division pulmonary arteries, thrombi can be clearly detected with enhanced spiral CT (patient 5). (B) The thrombi have been reduced by administration of only anticoagulant therapy, heparin and argatroban (patient 5).
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Fig. 3. Thrombus in the left femoral vein detected by CT (arrow). Triangle: right femoral artery and vein.
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3.3. Treatment and outcomes
(Table 3) Six patients underwent non-surgical therapy because of their stable circulatory condition. In a patient with DVT (patient 7), a temporary IVC filter was implanted just after CT scanning and had been placed during the thrombolysis.
Four who had shown several days of recovery after pulmonary resection (patients 1, 3, 4 and 7) underwent thrombolysis (intravenous infusion of urokinase) with simultaneous anticoagulant administration (heparin or argatroban). None of these patients had a chest tube implanted at the start of the therapy. They were examined for intrathoracic hematomas by chest X-ray.
The other two patients (5 and 6) underwent anticoagulant therapy alone because of the danger of bleeding resulting from the start of the treatment on the day after pulmonary resection. In patient 5, the bolus and continuous infusion of heparin alone for 24 h caused blood loss down the chest drains, which increased the anemia and made it progressive. Argatroban, a unique synthetic direct thrombin inhibitor, was used instead of heparin, and made it possible to maintain adequate ACT while preventing intrathoracic bleeding. Chest drains were removed on the fifth postoperative day, and the patient was discharged on day 21. The CT scan after the anticoagulant therapy showed there was no thrombus in the pulmonary arteries (Fig. 2B). Patient 6 underwent anticoagulant therapy with continuous argatroban infusion alone, and had a successful outcome without any bleeding episodes despite having undergone combined resection of the chest wall and neck lymph node dissection.
One patient (patient 2) underwent thromboembolectomy because of deterioration of the circulatory condition that would have progressed, if the high afterload on the right ventricle had not been immediately relieved.
Sodium warfarin was administered to all patients for 3–6 months.
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4. Discussion
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An issue of vital importance in the management of unexpected APE is the early detection of it followed by adequate treatments. Our seven cases, as well as the cases reported in both the English and Japanese literature (Table 4), show that sudden respiratory distress together with dramatic changes in clinical signs (hypotension, tachycardia, wheeze, etc.) occurred in most cases. An important finding is that in 12 of the 27 cases listed in Table 4, the first clinical sign of APE was syncope or cardiac arrest. And pulmonary emboli may be difficult to differentiate from other forms of respiratory failure after pulmonary operations, such as pulmonary edema, cardiac failure, infection and bronchospasm [8]. Actually, several cases in some series were initially diagnosed as one of these secondary pathologies [8,10,11]. When syncope, circulatory arrest or sudden respiratory distress accompanied by changes in clinical signs are observed after pulmonary resection, APE should be strongly suspected.
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Table 4. Cases of acute pulmonary embolism after surgery for lung cancer reported in the English or Japanese literature
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Our experience shows that special attention should be paid to patients during their first attempt at walking after the operation. Early occurrence of postoperative APE is demonstrated in the literatures (Table 4) by the fact that about half of the patients had the onset on postoperative days 1 or 2. This also proves that walking in the early postoperative period should be very carefully supervised.
We wish to emphasize that spiral CT scanning enhanced by contrast media is exceedingly useful for the quick and safe detection of not only PE but also of DVT and for ruling out other pathologies such as pneumonia, pneumonitis and pulmonary edema in the thorax. In all our seven patients, the thrombi in the pulmonary arteries were almost immediately detected by CT scanning—something which cannot be accomplished with a perfusion lung scintigram. In addition, CT scanning is also less invasive than pulmonary angiography, which cannot simultaneously check for DVT. It may actually move the thrombus up to the pulmonary artery and/or create a new pulmonary thrombus because of the catheter technique employed. Chen et al. [12] reported a case of APE after pneumonectomy diagnosed by CT pulmonary angiogram, in which a thrombus was produced in the right atrium and IVC.
We decided on non-surgical treatment for cases in a stable circulatory condition and surgical treatment for cases that were hemodynamically unstable. Some investigators have commented that postoperative PE should be considered an indication for embolectomy because of the risk of hemorrhage associated with thrombolysis [13,14]. However, the mortality associated with pulmonary embolectomy remains high (with an overall mortality rate of 44% quoted by Schmid et al. [15]) despite modern operative techniques using CPB [13,15], moreover, the appropriate surgical facilities may not always be readily available [16]. Girard et al. [17] and Sayeed and Nashef [16] reported successful use of thrombolysis combined with intra-arterial urokinase or recombinant tissue plasminogen activator (rTPA) after lung resection. We also successfully used systemic thrombolysis for four patients who had been in stable circulatory condition for several days after pulmonary surgery.
Nevertheless, bleeding remains a major problem associated with thrombolysis and anticoagulant therapy in the early post-surgical period [16,17]. We found that argatroban was very useful for controlling APE after surgery for lung carcinoma. To complete a radical resection of lung cancer, not only dissection of the mediastinal and hilar lymph nodes but also a combined resection of adjacent organs and tissues may have to be performed (such as the ribs in our patient 6), which increases the risk of post-surgical bleeding associated with anticoagulant therapy and/or thrombolysis. Argatroban ([2R, 4R]-4-methyl-L-[N-(3-methyl-1,2,3,4 tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine carboxylic acid) is a low-molecular-weight arginine derivative that binds thrombin competitively [18]. Tamao et al. [19] reported that argatroban inhibited fibrin formation via its potent thrombin inhibitory effect and concluded that argatroban would be effective for thrombotic disease even when this was the only drug used. Ohteki et al. [20] have reported on their clinical experience of argatroban. They found that it showed a clearly anticoagulant effect without adversely affecting fibrinolytic activity or platelet functions. Although argatroban was used only for the last three patients and so it seems premature to recommend it as standard treatment without further clinical studies to determine the validity of this drug, we expect to use argatroban alone first for cases with hemodynamic stability and at risk of bleeding complications. Even if on the second or third postoperative day, it would be allowed to use fibrinolytics with the monitoring of the drainage tube if the clinical conditions would be deteriorating by only argatroban usage.
In conclusion, we successfully detected seven APE cases after lobectomy aggressively using spiral CT enhanced by contrast media. All of them were successfully treated by surgery for one patient and anticoagulant therapy and/or thrombolytic therapy for the others. Early reliable diagnosis using CT could save the patients of APE even after pulmonary surgery.
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Abstract
1. Introduction
