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*Keski-Suomen Saivaanhoitopiiri, Anestesiologia ja tehohoito, Jyväskylä, Finland; and
Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Essen, Germany
Address correspondence and reprint requests to Dr. med. Matthias Eikermann, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, FRG. Address email to matthias.eikermann{at}uni-essen.de
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Abstract |
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IMPLICATIONS: We report a patient with severe visceral and neurogenic pain from metastatic carcinoma of the colon resistant to multimodal oral analgesic therapy. Although there were empirical contraindications, epidural analgesia was successful, allowing the patient’s end-of-life planning of an "aware" death surrounded by the family.
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Introduction |
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We report long-lasting epidural analgesia maintained despite meningeal infection in a cancer patient with unbearable pain.
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Case Report |
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To reestablish the vanishing analgesic effect of opioids (3), we stopped opioid administration and inserted a thoracic epidural catheter (T7-8) followed by infusion of bupivacaine (0.175%) and clonidine (1.5 mg/L) using a patient-controlled pump (basal infusion, 10 mL/h; bolus, 5 mL). This strategy abolished pain for 8 wk. Thereafter, catheter dislocation paralleled recurrence of severe pain and another thoracic epidural catheter (T9-10) was inserted. However, during epidural injection of a bupivacaine test dose, the patient described a very sharp pain in the back. Because subsequent neurological examination revealed neck stiffness, increased white blood cell count (22,000/µL), and fever (38°C), we performed an urgent MRI of the spine. This showed inhomogeneous leptomeningeal enhancement at T9-L1 consistent with meningeal infection without an abscess (Fig. 1). As the patient did not consent to lumbar puncture for cultures and cerebrospinal fluid analysis, ceftriaxon (3 x 2 g/d) IV treatment was started after catheter withdrawal. Unfortunately, "opioid holiday" (3) failed to reestablish sensitivity to opioids, and large-dose IV opioids along with oral amitriptyline (150 mg/daily) and gabapentin (1.8 g/d) did not relieve the pain. Therefore, despite leptomeningeal pathology, we inserted an epidural catheter in the lumbar region (L2-3), considered to be less affected by infection, and antibiotic therapy was administered until the patient’s death. An infusion (10 mL/h) of bupivacaine (0.5%) combined with clonidine (2.1 g/L) and morphine (1.6 g/L) was required to achieve pain control. This resulted in plasma concentrations markedly exceeding those recommended (clonidine, 12 ng/mL; bupivacaine, 5.4 mg/L), but no neurologic or cardiac side effects occurred. After 4 wk under supervision of our outpatient service, the patient died at home without pain and surrounded by her family.
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Discussion |
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Even large-dose opioid treatment may be ineffective with pain of neural origin (4), and tricyclic antidepressant and/or antiepileptic drugs are more effective (5). In our patient, cancer had spread over the whole pelvis including bones, viscera, and neural tissue. Therefore, both visceral and neurogenic pain was targeted with a combination of an opioid, a tricyclic antidepressant, and an antiepileptic drug, but without success. When managing pain refractory to large-dose opioid therapy changing the route of drug administration or switching to another opioid may be useful (6). In our patient, opioid rotation and "opioid holiday" (3) failed to mitigate pain or sedation, and pain relief was achieved with an epidural infusion of local anesthetics. Thus, we recommend that epidural infusions of local anesthetics should be considered at the end of life in pain states refractory to multimodal therapy with large-dose opioids, antidepressants, and antiepileptic drugs (1,3).
When adequate pain relief cannot be achieved, patients or their relatives may ask their physicians to hasten death. In practice, terminal sedation, i.e., placing the patient under anesthesia during the dying process, which is unlikely to be legally challenged, may be practiced instead (7). However, the life drive of most humans is intense, and the desire to die may more likely reflect the feeling that being dead would be preferable to "living this way" (8). Furthermore, powerlessness seems to be the condition patients fear most (9), and an "aware death" is often considered relevant for a "good death" in modern western culture (10). Thus, to avoid unnecessary loss of a patient’s control and dignity, a distinction between "difficult" and "refractory" pain states is required (7).
As our patient showed otherwise untreatable pain at the end of life, we decided to maintain epidural pain management during sustained antibiotic therapy despite signs of infection, even with the risk of an epidural abscess (2).
There are no data providing useful recommendations on duration of antibiotic therapy to treat meningitis during epidural analgesia. Although duration of ceftriaxon therapy of 10–14 days may be sufficient to treat a bacterial meningitis (11), much longer treatment periods (up to 6 weeks) have been reported in patients with central nervous system infections from bacteria resistant to antibiotics (12) and in patients with hydrocephalus and with shunt infection when a colonized ventricular-peritoneal shunt is not removed (13,14). As ceftriaxon therapy was well tolerated in our patient, we sustained antibiotic therapy during the remaining 4 weeks of palliative therapy. Of note, as epidural analgesia was maintained after hospital discharge, we ensured daily visits of the terminal care outpatient service to reduce the risk of serious complications from a recurrent epidural infection.
Reinsertion of the epidural catheter below the region considered to be most affected by infection may have reduced the risk of development of an epidural abscess. However, as the lumbar epidural catheter was less effective in mitigating pain, adequate analgesia could not be achieved by local anesthetics alone without giving opioids in addition. Clonidine has analgesic properties when administered by spinal or epidural routes and is considered as equally effective as bupivacaine for postoperative pain therapy when very large doses (10 mg/kg) are given (15). However, there are no reports on the toxicity of large-dose clonidine during long-term administration (16). In our patient, large doses of clonidine resulting in large plasma concentrations (12 ng/mL) may have mitigated the otherwise "toxic" effects of large bupivacaine concentrations (5.4 mg/mL) (17). Reduced systemic toxicity of IV bupivacaine during clonidine pretreatment may be explained by antidysrhythmogenic properties of the 
2-adrenergic agonist (17).
In summary, epidural analgesia, despite empirical contraindications provided long-term relief of unbearable cancer pain without impairment of consciousness, allowing the patient to die at home surrounded by her family. It may be useful to reconsider institutional pain management standards proposed for epidural analgesia when unbearable pain occurs in patients with limited life expectancy.
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This article has been cited by other articles:
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  G. T. Linklater and L. Macaulay Epidural Analgesia in Advanced Cancer Patients Anesth. Analg., February 1, 2005; 100(2): 600 - 600. [Full Text] [PDF]
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M. Eikermann and J. Peters Epidural Analgesia in Advanced Cancer Patients Anesth. Analg., February 1, 2005; 100(2): 600 - 601. [Full Text] [PDF]
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S. Mercadante, H. J. Exner, J. Peters, and M. Eikermann Epidural Treatment in Advanced Cancer Patients * Response Anesth. Analg., May 1, 2004; 98(5): 1503 - 1504. [Full Text] [PDF]
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