Acute dyspnea due to right phrenic palsy during infusional chemotherapy

M. Mandala*,1, C. Ciano2, M. Ghilardi1, M. Cremonesi1, M. Cazzaniga1 and S. Barni1

1 Division of Medical Oncology, Treviglio Hospital, Treviglio, Italy; 2 National Neurologic Institute-C. Besta, Milan, Italy

*E-mail: mariomandala@tin.it

Central venous catheters (CVCs) are widely used in cancer patients, particularly for continuous infusional chemotherapy. CVCs have many complications, but with the exception of catheter-related bloodstream infections and thrombosis, most are rare. We describe a clinical case of acute dyspnea due to unexpected right phrenic nerve injury during 5-fluorouracil (5-FU) continuous infusion plus cisplatin and epirubicin chemotherapy (ECF schedule).

A 50-year-old woman had developed a locally advanced breast carcinoma (cT4dN2M0). A port, attached to an open-ended catheter tubing, was implanted on the right side in order to safely administer primary chemotherapy according to ECF schedule (5-FU 200 mg/m2 administered as continuous infusion and epirubicin 50 mg/m2 and cisplatin 50 mg/m2 every 3 weeks). The procedure appeared without acute complication such as haematoma or haemorrhage. A subsequent chest X-ray confirmed the correct positioning of the catheter and diaphragm. From July to August 2002 two cycles were administered. During the third cycle the patient presented with acute dyspnea and right shoulder pain. A chest radiography documented a raised right hemidiaphragm; a chest CT scan was negative for mediastinal involvement and thrombosis of the superior vena cava. The echocardiography evaluation and the radionuclide lung scanning was negative for pulmonary embolism. The electroneurography of the phrenic and peripheral nerves, bilaterally, showed clear right phrenic nerve injury concordant with axonal damage. Electroneurography of the peripheral nerve showed a normal sensory-motor conduction, a finding that does not support the hypothesis of a peripheral neurotoxicity. The chemotherapy was stopped and the patient underwent a radical mastectomy followed by adjuvant chemotherapy. The patient is still alive and is receiving palliative chemotherapy with trastuzumab and vinorelbine. There have been no respiratory complications during follow-up despite the hemidiaphragm remaining paralysed 12 months after removal of the catheter.

To our knowledge, this is the first report of such a phenomenon in patients with breast cancer during ECF chemotherapy. A previous large trial with ECF schedule did not report such a phenomenon [1].

Our clinical case differs from other similar clinical conditions reported in the literature. Reeves et al. described a permanent paralysis of the right phrenic nerve associated with thrombosis of the superior vena cava [2]. Munzone et al. hypothesized that vinorelbine [3], as previously reported in vitro [4], could have damaged the permeability of the endothelial barrier near the catheter tip, favouring the occurrence of the right phrenic nerve injury due to a chemical vasa nervorum vasculitis.

Nevertheless, phrenic nerve damage is a rare complication of central venous catheterization and the aetiology is not entirely understood. This type of complication can occur during or shortly after the insertion procedure and is generally due to direct trauma, local haematoma or the use of local anaesthesia, as the phrenic nerve travels in close proximity to the veins usually used for catheterization. When the ‘acute’ nerve damage is due to local haematoma or anaesthesia it may be transient and even resolve in a few hours or days [5]. On the contrary, delayed damage may be irreversible. According to Mir et al. this type of complication has been reported not only in patients undergoing chemotherapy but also in patients with long-term subclavian catheter used only for haemodialysis [6]. In addition, in delayed nerve damage it has been suggested that a catheter-related inflammatory reaction may be the cause of the phrenic damage, independent of the chemotherapy infusion.

In our clinical case, the diaphragmatic paralysis appears to be permanent, showing no improvement 12 months after catheter removal. The electroneurography of the bilateral phrenic and peripheral nerves is not able to exclude that the phrenic nerve damage may be due to a catheter-related inflammatory reaction, even if the onset during continuous infusional chemotherapy suggests that chemotherapy could play a role.

Since the use of an implanted catheter for infusional chemotherapy has increased dramatically in the past decade in cancer patients, and because of the different clinical features of the reported clinical cases, we strongly recommend careful monitoring of any shoulder pain occurring in patients during continuous infusion of chemotherapy, irrespective of the type of chemotherapy and thrombosis formation.

REFERENCES

1. Jones AL, Smith IE, O’Brien ME et al. Phase II study of continuous infusion 5-fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen. J Clin Oncol 1994; 12: 1259–1265.[Abstract]

2. Reeves JE Jr, Anderson WF. Permanent paralysis of the right phrenic nerve. Ann Intern Med 2002; 137: 551–552.[Free Full Text]

3. Munzone E, Nolé F, Orlando L et al. Unexpected right phrenic nerve injury during 5-fluorouracil continuous infusion plus cisplatin and vinorelbine in breast cancer patients. J Natl Cancer Inst 2000; 92: 755.[Free Full Text]

4. Mouchard-Delmas C, Devie-Hubert I, Dufer J. Effects of the anticancer agent vinorelbine on endothelial cell permeability and tissue-factor production in man. J Pharm Pharmacol 1996; 48: 951–954.[ISI][Medline]

5. Akata T, Noda Y, Nagata T et al. Hemidiaphragmatic paralysis following subclavian vein catheterization. Acta Anaesthesiol Scand 1997; 41: 1223–1225.[ISI][Medline]

6. Mir S, Serdaroglu E. An elevated hemidiaphragm 3 months after internal jugular vein hemodialysis catheter placement. Semin Dial 2003; 16: 281–283.[CrossRef][ISI][Medline]





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