Anesth Analg 2003;97:1740-1742
© 2003 International Anesthesia Research Society
PAIN MEDICINE
Epidural Analgesia at End of Life: Facing Empirical Contraindications
Hans Juha Exner, MD*,
Jürgen Peters, MD
, and
Matthias Eikermann, MD
*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
 |
Abstract
|
|---|
In a patient with unbearable cancer pain at the end of life, long-lasting analgesia without impairment of consciousness could only be achieved with an epidural infusion of local anesthetics combined with opioids and clonidine. Despite leptomeningeal infection during prolonged treatment, epidural analgesia at the lumbar level provided analgesia using very large doses of local anesthetics combined with clonidine and morphine. Thus, terminal sedation was avoided, allowing the patient’s end-of-life planning of an "aware" death surrounded by her family. It may be useful to reconsider institutional pain management standards when unbearable pain occurs in patients with limited life expectancy.
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.
|
Introduction
|
|---|
Neuraxial analgesia with local anesthetics may provide immediate success in otherwise "intractable" pain when relief cannot be achieved by orally and IV administered analgesics (1). During local infections, bacteremia, and systemic infection, however, spinal or epidural catheterization probably should not be used because of a likely increased risk for an epidural abscess (2).
We report long-lasting epidural analgesia maintained despite meningeal infection in a cancer patient with unbearable pain.
|
Case Report
|
|---|
A 42-yr-old female with metastatic carcinoma of the colon and ileum, and with ileo-colic fistula and a history of Crohn’s disease, had severe lower abdominal pain. Furthermore, she had lancinating pain in dermatomes related to the lumbosacral plexus bilaterally. Magnetic resonance imaging (MRI) showed a tumor infiltrating the bladder and urethra and metastases in bones (os pubis, os sacrum, os ischii) and close to the lumbosacral plexus. Combined oral therapy with amitriptyline (150 mg/d), gabapentin (1.8 g/d), morphine (2.5 g/d), and naproxen (3 g/d), as well as opioid rotation to hydromorphone (800 mg/d), resulted in somnolence but did not relieve the pain.
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.
View larger version (69K):
[in this window]
[in a new window]
|
Figure 1. Magnetic resonance imaging scan of the lumbar spine. Axial image T2 with contrast shows leptomeningeal enhancement predominantly in the thoracic region without signs of abscess.
|
|
|
Discussion
|
|---|
In a patient with unbearable cancer pain at the end of life, long-lasting analgesia without impairment of consciousness was achieved with an epidural infusion of local anesthetics combined with opioids and clonidine. Despite leptomeningeal infection during prolonged treatment, epidural analgesia at the lumbar level provided analgesia using very large doses of local anesthetics combined with clonidine and morphine.
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.
|
References
|
|---|
- Bleeker CP. Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain: a case report. Eur J Pain 2001; 5: 325–9.[ISI][Medline]
- Swarm R, Cousins J. Anaesthetic techniques for pain control. In: Doyle D, Hanks G, MacDonald N, eds. Palliative Medicine. 2nd ed. Oxford: Medical Publications, 1999: 390–414.
- Breitfeld C, Eikermann M, Kienbaum P, et al. Opioid "holiday" following antagonist supported detoxification during general anesthesia improves opioid agonist response in a cancer patient with opioid addiction. Anesthesiology 2003; 98: 571–3.[ISI][Medline]
- Arnér S, Arnér B. Differential effects of epidural morphine in the treatment of cancer-related pain. Acta Anaesthesiol Scand 1985; 29: 332–6.
- Sindrup S, Jensen T. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999; 83: 389–400.[ISI][Medline]
- McQuay H. Opioids in pain management. Lancet 1999; 353: 2229–32.[ISI][Medline]
- Cherny NI, Portenoy RK. Sedation in the management of refractory symptoms: guidelines for evaluation and treatment. J Palliat Care 1994; 10: 31–8.[Medline]
- Loewy EH. Terminal sedation, self-starvation, and orchestrating the end of life. Arch Int Med 2001; 161: 329–32.
- Back AL, Wallace JI, Starks HE. Physician-assisted suicide in Washington state: patients’ requests and physicians responses. JAMA 1996; 275: 919–23.[Abstract]
- Clark D. Between hope and acceptance: the medicalisation of dying. BMJ 2002; 324: 905–7.[Free Full Text]
- Schaad UB, Suter S, Gianella-Borradori A. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 1990; 322: 141–7.[Abstract]
- Garlando F, Bodmer T, Lee C, et al. Successful treatment of disseminated nocardiosis complicated by cerebral abscess with ceftriaxone and amikacin: case report. Clin Infect Dis 1992; 15: 1039–40.[ISI][Medline]
- Chang WN, Lu CH, Huang CR, et al. Mixed infection in adult bacterial meningitis. Infection 2000; 28: 8–12.[ISI][Medline]
- Arthur AS, Whitehead WE, Kestle JRW. Duration of antibiotic therapy for the treatment of shunt infection: a surgeon and patient survey. Ped Neurosurg 2002; 36: 256–9.
- de Kock M, Gautier P, Pavlopoulou A, et al. Epidural clonidine or bupivacaine as the sole analgesic agent during and after abdominal surgery. Anesthesiology 1999; 90: 1354–62.[ISI][Medline]
- Seger DL. Clonidine toxicity revisited. J Toxicol Clin Toxicol 2002; 40: 145–55.[ISI][Medline]
- de Kock M, le Polain B, Henin D, et al. Clonidine pretreatment reduces the systemic toxicity of intravenous bupivacaine in rats. Anesthesiology 1993; 79: 282–9.[ISI][Medline]
Accepted for publication June 25, 2003.
Top
Abstract
Introduction
