Suppurative pleural effusion caused by intrathoracic infection is the main manifestation of acute empyema (1). Severe empyema can be complicated by acute respiratory distress syndrome (ARDS) or, in severe cases, by respiratory and circulatory failure which can lead to death. Conventional treatments for acute empyema and ARDS include thoracic drainage and mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT) may be necessary to provide effective respiratory and circulatory support and correct water and electrolyte imbalances (2). Additionally, a surgical procedure should be considered and may be critical to remove the focus of the infection completely, especially when conservative treatment has not been effective despite the extreme risk. Herein, we describe the case presentation of a 51-year-old man with acute empyema secondary to an acute lung abscess rupture complicated by a sudden cardiac arrest caused by rapidly progressing severe hypoxemia who was successfully treated with ECMO combined with CRRT and thoracoscopic minimally invasive surgery for persistent alveolar fistula.

A 51-year-old man was admitted to emergency intensive care unit (EICU) of the Second Affiliated Hospital of Jiaxing University (Jiaxing, China) in July, 2020, due to a cough accompanied by left chest pain and high fever. On the afternoon of admission, he experienced sudden shortness of breath and a cough with yellow purulent foul-smelling sputum accompanied by systemic profuse sweating. Chest computed tomography (CT) was performed immediately (Fig. 1) and showed a left upper lung abscess and left empyema, considered indicative of infection. A cardiac color ultrasound showed blunt and paradoxical apex movement and mild aortic valve, mitral valve, and tricuspid regurgitation. His blood tests showed metabolic acidosis and hypoxemia and white blood cell (WBC) count of 65.5x10⁹/l. The patient had a history of ankylosing spondylitis, a kind of autoimmune disease, and had been taking immunosuppressive drugs, including salazosulfadimidine and adrenocortical hormone. However, his family medical history was unremarkable.

After admission, bedside left thoracic closed drainage was performed immediately. After placement of a 24F thoracic drainage tube, a large amount of yellow pus and foul-smelling pleural effusion were drained. Simultaneously, meropenem (1.0 g Q6h) and Vancomycin (0.5 g Q12H) was administered empirically as anti-infection measures. According to the bacteriological results of the pleural effusion after thoracic closed drainage, both gram-positive cocci and gram-negative bacilli were found in the pleural fluid smear, and the bacterial culture results indicated Streptococcus constellations. The blood culture was negative at that time. His chest distress improved, but his oxygenation levels remained unstable. A dynamic blood gas reanalysis revealed continuous deterioration of hypoxia and acidosis. He was ventilated with an endotracheal intubation ventilator 32 h after admission, and a second chest CT (Fig. 2) was performed immediately; it showed multiple infections in both lungs and a large consolidation in the left lung. A mega dose of methylprednisolone (500 mg) was administered to reduce inflammation. Compared with previous examinations, these conditions progressed significantly and rapidly, and he continued to present with low oxygenation under pure oxygen ventilation with endotracheal intubation. Thirty-four hours after admission, he experienced ventricular fibrillation and sudden cardiac arrest three times in the following two hours. Aggressive treatment, including cardiac compression, electrical defibrillation, and drug treatment, was immediately initiated. ECMO using veno-arterial catheterization (VA-ECMO) (flow rate, 2.8 l/min) was performed immediately after cardioversion. One hour after ECMO placement, arterial blood gas analysis showed a partial pressure of oxygen of 131 mmHg, suggesting a substantial improvement in his hypoxia and acidosis.

Four hours after ECMO implantation, the patient had continuous anuria and a urea nitrogen level of 8.9 mmol/l, and his creatinine levels rose to 150.7 µmol/l. Bedside CRRT was performed immediately. The treatment mode was set to continuous venovenous hemofiltration (flow rate, 2,000 ml/h). The patient's condition gradually improved after this. On the 8th day after admission, both ECMO and CRRT were withdrawn after six days of treatment. On the 11th day, chest CT showed that the pulmonary infection had improved significantly. Tracheal extubation was then performed. After the patient was transferred to the thoracic surgery ward for subsequent treatment, he continued to have air bubble overflow in the left chest tube (1-2 degrees of air leakage) while coughing. On the 20th day after admission, he developed a low-grade fever and leukopenia. Routine blood tests showed a WBC count of 1.8x10⁹/l, neutrophil count of 0.2x10⁹/l (11.3%), and hemoglobin level of 67 g/l. Drug-induced myelosuppression was considered after discussion with a multidisciplinary team (MDT). All drugs, including antibiotics, were discontinued, and a subcutaneous injection of granulocytes was subsequently administered. Three days later, his body temperature was back to normal.

A chest CT on the 35th day after admission (Fig. 3) demonstrated that the exudation in both lungs was absorbed, but a left upper lung abscess with bronchopleural fistula was considered as a possible diagnosis. After MDT discussions, minimally invasive surgery-having only a single-hole (Fig. 4A)-was performed the next day, including wedge resection of the left upper lung lesion and empyema removal. Intraoperative exploration revealed a peripheral abscess with an alveolar fistula in the left upper lung lesion. The total operation time was ~70 min. During intraoperative exploration, lesions were observed in the visceral pleura. The surrounding lung tissues showed inflammatory changes and demonstrated a brittle texture. After the lesion was removed using Endo-GIA staplers (Ethicon, Somerville, NJ, USA), 4-0 prolene thread (Ethicon) was used for continuous suture reinforcement of the wound surfaces to reduce postoperative air leakage.

Chest radiography performed the day after surgery revealed no significant hydropneumothorax in the left thoracic cavity (Fig. 4B). There was no air leakage in the left thoracic duct one week postoperatively. The chest tube was removed two weeks postoperatively and chest radiography at three weeks (Fig. 4C) showed that the left lung had recovered well. Postoperative pathology (Fig. 4D) revealed fibrous hyperplasia with massive neutrophil and plasma cell infiltration, and massive foam cell accumulation in the alveolar space in the left upper lung. His vital signs were stable, and he was discharged uneventfully. The timeline of the treatment process is shown in Fig. 5. The critical information that reflects the severity of the disease included partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio (P/F ratio) and endogenous creatinine clearance rate (Ccr) are shown in Fig. 6. After one year of postoperative follow-up, his cardiopulmonary function continued to be stable, with no recurrence of infection.

ARDS caused by acute intrathoracic infection usually progress rapidly because of systemic inflammatory storm, especially in patients with a history of autoimmune disease. With accumulating evidence (3,4), ECMO has demonstrated strong potential for a good prognosis and good application prospects in the treatment of adult ARDS. For example, venovenous ECMO (VV-ECMO) plays a definitive role in improving hypoxia, correcting carbon dioxide retention, and protecting lung tissue (2). However, controversies still remain regarding the selection of VV-ECMO or VA-ECMO (5). After an MDT discussion, the patient finally underwent VA-ECMO. The reasons were: first, echocardiography on admission revealed paradoxical movement of the ventricular wall, significantly elevated creatine kinase myocardial band (142 ng/ml, ref 0-5), myoglobin (>3,000 ng/ml, ref 20-80), and high-sensitivity troponin levels (1,592 ng/l, ref 0-0.04), suggesting pre-existing infectious myocarditis and myocardial damage. Second, he had experienced three episodes of ventricular fibrillation and sudden cardiac arrest due to hypoxia, so the myocardial damage was substantially aggravated. Third, he experienced hemodynamic instability after cardiopulmonary resuscitation. Although VA-ECMO can increase the risk of stroke, bleeding, renal failure, and cobra syndrome (i.e., selective upper body hypoxia) compared to that with VV-ECMO (6-8), this patient experienced no associated adverse events.

Protection of renal function and hemofiltration are especially important in the presence of multiple organ failure. The main purpose of CRRT is to remove excessive water and metabolic waste, correct water and electrolyte imbalances. CRRT is mostly used for treating acute and chronic kidney diseases. Since CRRT can also remove various cytokines and inflammatory mediators, it has likewise been successfully applied to the treatment of severe liver, lung, heart, pancreas, and other organ damage as well as sepsis (9). For this patient, we conducted bedside CRRT to protect the patient's renal function in the early stages of renal impairment, and thus avoided additional deterioration of renal function, adjusted the stability of his internal environment, and provided the proper preconditions for drug efficacy. It should be also noted that CRRT can remove small molecules, promoting the recovery of cardiac function (his left ventricular ejection fraction increased from 39 to 58%). Moreover, CRRT can also help patients with severe ARDS with hemodynamic instability by accurately implementing fluid management strategies (10,11). A previous retrospective study showed better fluid management with than without CRRT among surviving patients treated with ECMO, and that fluid overload during ECMO was an important factor associated with a poor prognosis (12).

After the patient was transferred to the general ward at our hospital, chest CT showed a left upper lung abscess (~1.5 cm in diameter) with an alveolar fistula accompanied by two clinical problems: persistent air leakage in the left chest tube and intermittent low-grade fever. A prior study confirmed that surgical treatment should be selected for patients with small lung abscesses, localized empyema, symptoms lasting >12 weeks, and little hope for the efficacy of conservative treatment (13). Additional surgical indications include massive hemoptysis, persistent septic fever, bronchopleural fistula, and empyema caused by abscess rupture (14). Recommended surgical methods include lobectomy, segmentectomy, and pulmonary wedge resection, which are selected according to the lesion size and location (14). The prognosis for surgery depends on the patient's systemic status and immune function. Although postoperative mortality as high as 11-28% was reported, as of 2005 the mortality rate has decreased with the recent popularization of effective and minimally invasive techniques (15).

In summary, acute empyema may rapidly develop into ARDS and lead to fatal consequences especially in immunocompromised patients, thus this critical situation warrants vigilance from clinicians. Also, timely and effective use of ECMO can increase the success rate of rescue, and the choice of ECMO mode depends on comprehensively evaluating the patient's condition. Moreover, minimally invasive surgery, even for high-risk patients, should still be considered when conservative treatment fails.