Pericardiocentesis with cisplatin for malignant pericardial effusion and tamponade

Abstract

AIM: To evaluate the role and outcome of pericardiocentesis with intrapericardial cisplatin instillation for malignant pericardial effusion resulting from esophageal cancer.

METHODS: We retrospectively studied 7 patients who underwent pericardiocentesis with intrapericardial cisplatin instillation for malignant pericardial effusion resulting from esophageal cancer. After pericardiocentesis, we performed catheterization of the pericardial space under ultrasonogram guidance. Malignant etiology of the pericardial fluid was confirmed by cytological examination. Subsequently, cisplatin (10 mg in 20 mL normal saline) was instilled into the pericardial space.

RESULTS: The mean total volume of the aspirated effusion fluid was 782 ± 264 mL (range, 400-1200 mL). The drainage catheter was successfully removed in all patients, and the mean duration of pericardial drainage was 7.7 ± 2.7 d (range, 5-13 d). No fluid reaccumulation was observed. Mean survival time was 120 ± 71 d (range, 68-268 d).

CONCLUSION: Pericardiocentesis along with catheter drainage appears to be a safe and effective for pericardial malignant effusion and tamponade, and cisplatin instillation prevents recurrence.

Key Words: Malignant pericardial effusion; Cardiac tamponade; Esophageal cancer; Pericardiocentesis; Cisplatin

INTRODUCTION

The most frequent causes of spontaneous pericardial tamponade are neoplastic invasion, idiopathic or infectious pericarditis, and uremia. Pericardial effusion is a known complication of many advanced malignancies, and has a strong impact on both the quality of life and prognosis. Malignant pericardial effusion and tamponade is a rare medical-surgical emergency that impairs cardiac function and causes death. To facilitate the diagnosis, it is necessary to identify the clinical features of this condition, and design adequate management strategies. Esophagectomy with reconstruction of the esophagus is associated with many fatal complications such as infection, anastomotic leakage, and respiratory and hemodynamic instability. The clinical syndrome of pericardial tamponade after esophagectomy has been relatively well reported. Acute distension of the stomach[1], herniation of the omentum[2], mediastinal bleeding[3] and even volvulus of the interposed colon[4] have been implicated as the clinical syndromes of pericardial tamponade. Moreover, the development of cardiac tamponade due to intra-pericardial fluid accumulation after esophagectomy has also been reported[5,6].

Here, we report the outcome of intrapericardial instillation of cisplatin (CDDP) for the treatment of malignant pericardial effusion and tamponade resulting from esophageal carcinoma.

MATERIALS AND METHODS

Patients

We retrospectively studied 7 male patients who underwent pericardiocentesis with intrapericardial instillation of CDDP for the treatment of esophageal cancer at the Department of Surgery, Social Insurance Yokohama Central Hospital, Yokohama, Japan, between March 1997 and April 2009. Their mean age was 67 ± 3.4 years (range, 61-71 years). Of the 7 patients, 5 underwent subtotal esophagectomy via a standard right thoracoabdominal approach along with three-field lymphadenectomy and reconstruction was performed using gastric pull-up with cervical anastomosis via the poststernal route, and the remaining 2 patients had undergone chemoradiotherapy previously.

Diagnosis and definition of severity of pericardial effusion and tamponade

Echocardiography was used for the diagnosis of pericardial effusion and tamponade. When the diastolic echo-free space between the left ventricular posterior wall and the pericardium was < 10 mm, the condition was classified as mild; when the space was 10-20 mm, the condition was classified as moderate; and when the space was > 20 mm, the condition was classified as severe pericardial effusion[7]. Cardiac tamponade was defined according to the clinical and echocardiographic criteria[8]. The presence of the classic tamponade symptoms such as tachycardia, dyspnea, or tachypnea with clear lungs, or signs of increased systemic venous pressure, hypotension, or pulsus paradoxus, or accompanied by echocardiographic findings was accepted as cardiac tamponade[7]. We performed pericardiocentesis on the patients with cardiac tamponade and moderate to severe pericardial effusion.

Percutaneous pericardiocentesis and cytology

Echocardiography with fluoroscopy-guided subxiphoid pericardiocentesis using an 8-French pigtail drainage catheter with multiple side holes (Aspiration Seldinger Kit/Nippon Sherwood Medical Industries LTD) was performed under local anesthesia with mild sedation. After the catheter was placed into the pericardial space, we aspirated the fluid. Cytological examination was performed using the aspirate culture.

Instillation of CDDP

After the cytological examination-based confirmation of the malignant etiology of the pericardial fluid and the complete drainage of the fluid, we administered 10 mg of CDDP into the pericardial space during each pericardiocentesis via the catheter; subsequently, the catheter was clamped. The catheter was declamped the following day, and the fluid was re-aspirated. When the volume of the re-aspirated fluid was more than 30 mL, 10 mg CDDP was re-administered. When the volume of the re-aspirated fluid was less than 30 mL, the catheter was removed.

RESULTS

Echocardiography with fluoroscopy-guided pericardiocentesis using extended catheter drainage was performed in 7 patients with malignant cardiac tamponade resulting from esophageal cancer. Table 1 shows the patients’ characteristics. Staging of esophageal cancer was performed according to guidelines of the International Union Against Cancer Classification of Malignant Tumors (UICC), and the distribution of the various stages among the patients was as follows: IIB, 1/7 (14.3%); III, 3/7 (42.8%); and IVA, 3/7 (42.8%). The following clinical symptoms were observed in the patients; dyspnea was observed in all the patients (100%), and tachycardia was observed in 5 patients (71.4%).

Table 1 Characteristics of the patients.

Patient No.	Age	Sex	Stage of esophageal cancer	Former treatment	Symptoms
1	68	M	T2, N1, M0: Stage IIB	Esophagectomy + chemotherapy	Dyspnea, tachycardia
2	69	M	T3, N1, M0: Stage III	Esophagectomy + chemotherapy	Dyspnea, tachycardia
3	64	M	T2, N1, M0: Stage III	Esophagectomy + chemotherapy	Dyspnea
4	70	M	T3, N1, M1a: Stage IVA	Esophagectomy + chemotherapy	Dyspnea, tachycardia
5	71	M	T2, N1, M1a: Stage IVA	Chemoradiotherapy	Dyspnea, tachycardia
6	65	M	T2, N1, M0: Stage IIB	Esophagectomy + chemotherapy	Dyspnea, tachycardia
7	62	M	T2, N1, M1a: Stage IVA	Chemoradiotherapy	Dyspnea

Table 2 lists the outcomes of the patients who underwent pericardiocentesis with CDDP instillation. Total volume of the aspirated effusion fluid ranged from 400 to 1200 mL (median, 782 ± 264 mL). Pericardiocentesis with CDDP instillation was required twice in 2 patients (28.6%), 3 times in 4 patients (57.1%), and 5 times was in 1 patient (14.3%), (median, 3 times). The drainage catheter was successfully removed in all the patients. The duration of pericardial drainage ranged from 5 to 13 d (median, 7.7 ± 2.7 d). None of the patients showed fluid accumulation. Nausea, as a side effect of pericardiocentesis with CDDP instillation, was observed in 2 patients (28.6%); however, hematologic and renal toxicity did not develop in any of the patients. After pericardiocentesis with CDDP instillation, we performed systemic chemotherapy [5-fluorouracil (5-FU) + CDDP] in 3 patients (43%). The overall median survival time for these 7 patients was 120 ± 71 d (range, 68-268 d) (Table 3).

Table 2 Outcomes of intrapericardial instillation of cisplatin.

Patient No.	Amount of fluid (mL)	CDDP instillation (mg) × times	Duration of drainage (d)	Side effect	Reaccumulation of fluid
1	580	10 × 2	5	-	-
2	400	10 × 2	5	-	-
3	760	10 × 3	8	-	-
4	980	10 × 3	8	Nausea	-
5	1200	10 × 5	13	Nausea	-
6	685	10 × 3	8	-	-
7	870	10 × 3	8	-	-

CDDP: Cisplatin.

Table 3 Outcomes of the patients.

Patient No.	Additional therapy (systemic)	Survival (d)	Cause of death
1	5-Fu + CDDP	126	Lung and pleural metastases
2	5-Fu + CDDP	268	Pleural metastases
3	5-Fu + CDDP	137	Lung and bone metastases
4	-	68	Lung and pleural metastases
5	-	61	Lung and bone metastases
6	-	104	Lung and pleural metastases
7	-	77	Pleural metastases

5-Fu: 5-fluorouracil.

DISCUSSION

Cardiac tamponade can occur in any type of pericarditis case, but it is more commonly observed in neoplastic, tuberculous, and purulent pericarditis cases than in viral or idiopathic pericarditis cases. Pericardial effusion is a known complication of many advanced malignancies, and it has a strong impact on both the quality of life and prognosis. To facilitate the diagnosis of patients with malignant disease, it is necessary to identify the clinical features of cardiac tamponade and design adequate management strategies. Cardiac tamponade, observed in up to 15% of patients with cancer, can develop because of the malignant involvement of the pericardium under metastatic disease conditions, contiguous extension, or primary involvement[9]. Pericardial effusion in patients with esophageal carcinoma is most commonly associated with radiation and/or chemotherapy, and rarely with esophago-pericardial fistula[10]. All our 7 patients had advanced esophageal cancer; of them, 5 patients underwent esophagectomy and chemotherapy and the remaining 2 had undergone chemoradiotherapy previously.

The following are the typical signs of acute cardiac tamponade; a decrease in the arterial blood pressure, increase in the central venous pressure, and a small, quiet heart. The diagnosis of pericardial effusion and cardiac tamponade was confirmed using echocardiography and according to the clinical and echocardiographic criteria[8]. Because all our patients showed symptoms of dyspnea with or without tachycardia, it was necessary to confirm the diagnosis using echocardiography.

Accumulation of fluid in the pericardial space in patients is often not evident until the development of cardiac tamponade. Pericardiocentesis is generally performed as an initial treatment for symptomatic pericardia effusion and cardiac tamponade; however, re-accumulation of the fluid after pericardiocentesis is often observed. Hence, alternative procedures to pericardiocentesis, including insertion of a pleuropericardial window[11], total or partial pericardiectomy[12], external radiotherapy[13], local instillation of a chemotherapeutic agent[14], local instillation of a sclerosing agents[15], and systemic chemotherapy[16], are often performed. A review article that summarized the results of previous studies showed that the overall success rate of pericardiocentesis was 44.4%; indwelling pericardial catheters, 76.3%; and intrapericardial administration of sclerosing or cytotoxic agents, 81.6%, and that intrapericardial instillation was an effective treatment strategy for malignant pericardial effusion[17].

The most serious complications of pericardiocentesis are laceration and perforation of the myocardium and the coronary vessels. Safe execution of pericardiocentesis was achieved by performing echocardiography under fluoroscopic guidance. Recent large echocardiographic series have shown that the incidence of major complications after echocardiography was 1.3%-1.6%. In fluoroscopy-guided percutaneous pericardiocentesis, cardiac perforations occurred in 0.9% cases, serious arrhythmias in 0.6%, arterial bleeding in 1.1%, pneumothorax in 0.6%, infection in 0.3%, and a major vagal reaction in 0.3%[8,18]. In our study, pericardiocentesis was performed echocardiographically under fluoroscopy guidance, and no complications developed. We believe that echocardiography with fluoroscopy-guided pericardiocentesis appears to be a safer alternative for pericardiocentesis.

The most appropriate type of pericardial drainage is subject to debate. In principle, less aggressive procedures are preferred, but at the same time, the procedures must be able to prevent recurrence of effusion accumulation. Simple needle pericardiocentesis can often resolve tamponade initially, but the probability of relapse is very high.

Recurrence, which is observed in 40%-70% of patients with large malignant pericardial effusion, may be prevented by intrapericardial instillation of sclerotic or cytotoxic agents, immunomodulators, systemic antitumor treatment, radiation therapy, percutaneous balloon pericardiotomy, or surgical methods[19,20]. Surgical drainage (or pericardiectomy, its major equivalent) is excessively required for many patients. The best option is to perform pericardiocentesis using the Seldinger technique, i.e. inserting a pigtail drainage catheter that can be retained in the pericardium until the drainage is complete[17]. If effusion recurs after the removal of the pigtail catheter, a sclerosing agent (tetracycline or bleomycin) can be instilled into the pericardial sac, or subxiphoid balloon pericardiotomy can be performed[17].

With regard to the cytotoxic agents that can be used for intrapericardial instillation, Maisch et al[20] studied the effectiveness of tetracycline, 5-FU, and CDDP in 20 patients with recurrent malignant pericardial effusion, and observed favorable outcomes (no fluid re-accumulation) only after CDDP instillation.

With regard to the side effects and complications of CDDP instillation, Maisch et al[19] reported that myocardial ischemia occurred in 1 of 42 patients studied, and there were no other complications. Fiorentino et al[21] reported that mild nausea occurred in all patients, but hematologic and renal toxicity and local or infectious complications did not occur in any patients in their study. In our study, 2 patients (28.6%) developed nausea. However, no significant side-effects were observed in the study of Tondini et al[22] CDDP instillation did not cause hypotension and retrosternal pain, as is observed after the instillation of some other agents[19]; hence, it is thought to be a reasonable cytotoxic agent for intrapericardial administration. After the intrapericardial instillation of CDDP, 3 of the 7 patients in our study underwent systemic chemotherapy (5-FU + CDDP). The overall mean survival time after intrapericardial instillation of CDDP was reported to be 2.8 ± 1.3 mo by Maisch et al[19] and it was 120 ± 71 d (range, 68-268 d) in our study. Maisch et al[19] performed intrapericardial instillation of CDDP for patients with neoplastic pericardial effusion without esophageal cancer, but our patients had esophageal cancer. Moreover, the overall mean survival time in our study was longer than that of the study by Maisch et al[19].

We conclude that pericardiocentesis with intrapericardial instillation of CDDP is effective for the treatment of malignant pericardial effusion resulting from esophageal cancer. In our study, the number of patients with pericardial constriction was very small for conducting statistical evaluation, but it is thought that pericardiocentesis with intrapericardial instillation of CDDP is a safe and feasible treatment in cases of medical-surgical emergency. Moreover, additional systemic chemotherapy after pericardiocentesis with intrapericardial instillation of CDDP may prolong the survival time of patient.

COMMENTS

Background

Pericardial effusion in patients with esophageal carcinoma is most commonly associated with radiation and/or chemotherapy, and rarely with esophago-pericardial fistula. Here, the authors report the outcome of intrapericardial instillation of cisplatin (CDDP) for the treatment of malignant pericardial effusion and tamponade resulting from esophageal carcinoma.

Research frontiers

After the intrapericardial instillation of CDDP, 3 of the 7 patients in this study underwent systemic chemotherapy (5-fluorouracil + CDDP). The overall mean survival time after intrapericardial instillation of CDDP was 120 ± 71 d (range, 68-268 d) in this study. And the overall mean survival time in this study was longer.

Innovations and breakthroughs

The authors conclude that pericardiocentesis with intrapericardial instillation of CDDP is effective for the treatment of malignant pericardial effusion resulting from esophageal cancer.

Applications

In this study, the number of patients with pericardial constriction was too small to conduct statistical evaluation, but it is thought that pericardiocentesis with intrapericardial instillation of CDDP is a safe and feasible treatment in cases of medical-surgical emergency. Moreover, additional systemic chemotherapy after pericardiocentesis with intrapericardial instillation of CDDP may prolong the survival time of patient.

Peer review

This is a well written manuscript describing a series of well organized experiments. It is about malignant pericardial effusion and tamponade resulting from esophageal carcinoma. Not many cases of this disease have been reported and this is an original case series.