Cancer-related pain afflicts approximately 9 million people worldwide.
The prevalence of moderate to severe pain is 51%, ranging from 43% in stomach
cancer to 80% in gynecologic cancers. In rating their pain, the majority
of patients (69%) say that the worst pain is that which causes impairment
of their ability to function. The worldwide incidence of cancer continues
to increase, while the overall cure rate remains at approximately 50% in
developed countries and less than 30% in underdeveloped countries. Therefore,
cancer pain is a major health-care problem and has been defined a "world
medical emergency" by the World Health Organization (WHO).
Despite published guidelines for pain management, many cancer patients
experience considerable pain, and approximately half of them receive inadequate
The current recommended approach to the management of cancer pain consists
of the regular administration of opioids using the oral or parenteral route
and intermittent extra doses of opioids for occasional excess pain.[6,8,9]
The rationale for recommending regular opioid administration is twofold:
(1) to prevent the pain from returning by giving opioids at an interval
that maintains a stable blood level; and (2) to prevent patients from having
to wait for long periods between their request for analgesics and drug
administration by the nursing staff. This sequence of events is shown in
In some hospitals, the waiting period can be as long as 45 minutes.
Since the effects of the majority of opioid analgesics last no more than
4 hours, the repetition of 45-minute waiting cycles repeated six times
a day results in a minimum of 4 hours of pain per day. Although regular
administration of opioids is the recommended treatment strategy for cancer
pain, its effectiveness has not been conclusively demonstrated in randomized
Patient-controlled analgesia (PCA) is a relatively new technique that
permits patients to relieve pain by directly activating doses of parenteral
opioid analgesics. This technique offers an alternative to traditional
regimens and was developed in response to the undertreatment of pain in
hospitalized patients.[10,12] Patient-controlled analgesia has been employed
mainly for the management of pain associated with surgery and labor.[13-19]
Postoperative PCA has been found to be safe and effective even in children
from 5 to 15 years old.
A number of uncontrolled and controlled trials have confirmed the safety
and efficacy of PCA for postoperative pain.[21,22] Controlled trials have
found that, compared with patients receiving traditional opiate regimens,
patients on PCA report a similar or better level of pain control[23,24]
with a similar or lower total dose of opiates.[25,26] In one study, although
the total pain intensity and morphine dose did not differ between patients
treated with PCA and those who received regular opiate administration,
the final blinded choice of patients favored PCA.
Patient-controlled analgesia has also been successfully used in adults
and children with vaso-occlusive pain crisis of sickle cell disease.[28-30]
Grundy et al found that children over 6 years of age can manage PCA.
However, patients as young as 4 years of age have used this method effectively.
Patient-controlled analgesia is a very specific way of prescribing "as-needed"
analgesics because all parameters, such as route, drug concentration, total
dose, dosing frequency, and maximum daily or hourly doses are actually
prescribed by the physician. Patients decide whether or not they should
take a dose.
The important distinction between PCA and traditional as-needed dosing
emerges when PCA is mechanized. Figure 1
shows the usual cycle that is set in motion when a patient requests pain
medication. When the patient is using a PCA regimen, the observer (usually
a nurse) is eliminated. This means that when the patient perceives a need
for additional analgesia, the decision is not subject to judgment and administration
is not delayed by a third-party intervention.
A large variety of pumps are available for PCA. Most of them consist
of a drug reservoir and an injection or infusion system, which is operated
either manually or electronically.
Patient-controlled analgesia devices permit the patient to choose an
intermittent (demand) bolus, continuous infusion, or both intermittent
and continuous modes of administration. These devices can be used to deliver
the drug into a running intravenous infusion, the epidural space, or subcutaneously.
Bolus Demand Dose Systems--Whenever the patient feels that pain
relief is necessary, he or she can activate the system by pressing a button.
The unit dispenses an amount of analgesic that has been programmed by the
physician. In some devices, unauthorized alteration of dose parameters
is prevented by a number of safety factors. For example, devices may feature
a lock-out time that prevents overdosage. Some devices even require the
user to key in a secret code in order to change the system's programming.
Other simpler, less expensive devices contain no lock-out system.
A lock-out system may be desirable in patients who are confused and/or
have a history of addiction. However, it is important to keep in mind that
oral prescriptions have no lock-out mechanisms, and accidental overdose
does not occur in the great majority of patients taking these medications.
With regard to PCA, there is no evidence to suggest that a lock-out mechanism
is advantageous, although it can make the PCA device more expensive and
Bolus Demand and Continuous Infusion Systems--Most portable pumps
allow for continuous infusion of opioids in addition to a bolus demand
dose. The continuous opioid infusion provides a stable background plasma
Bolus Demand and Variable Infusion Systems--These are more complex
systems that automatically change the background infusion rate based on
the number of bolus demands made by the patient.
Choosing a Device for Cancer Pain--Such factors as the cost of
purchase or lease of the pump; cost of bags, tubing, connections, and other
supplies; yearly patient usage; health professional education and availability;
pharmacy time; and patient and family education and safety are the main
considerations when choosing a device.
Very inexpensive, simple devices, such as the Edmonton Injector, allow
PCA to be used even in underdeveloped countries. However, very simple devices
lack many of the safety features and continuous infusion functions found
in the electronic pumps.
Most of the experience with PCA has taken place in patients with acute
pain that requires treatment for less than 96 hours. Some of the characteristics
of postoperative PCA would not be useful for the management of chronic
pain: For example, postoperative patients activate the PCA device frequently,
sometimes several times in 1 hour, and receive small doses of opioid with
each bolus. This setting allows for a stable level of opiate without excessive
peaks in the blood concentration. Such a mode of administration would be
very uncomfortable for long-term use by cancer patients. A useful technique
in cancer patients would permit patients to receive boluses capable of
maintaining analgesia for several hours.
Hill et al[34,35] developed an algorithm and a sophisticated computer-pump
system that allows patients to reach a predetermined plasma opioid concentration
rapidly and to regulate their own pain control and side effects by manipulating
the steady-state concentration of analgesic. This pharmacokinetically based
PCA (PKPCA) system delivers a constant plasma concentration of opioids
between patient demands and regulates increases or decreases in steady-state
opioid concentration rather than just the frequency of bolus doses. The
program considers the minimum effective analgesic concentration to be 16
mcg/L for morphine, 0.6 mcg/L for fentanyl, 460 mcg/L for meperidine, and
10 mcg/L for alfentanil (Alfenta).[34,35] The pharmacokinetic parameters
used in these programs are individualized for each patient.
Similar methods for controlling plasma opioid concentration intraoperatively,
using population pharmacokinetic values, have been reported by other authors.[36,37]
Harrison described a similar approach using vecuronium (Norcuron) for
1. Bonica JJ: Cancer Pain, in Bonica JJ (ed): The Management of Pain,
2nd ed, vol 1, pp 400-460. Philadelphia, Lea and Febiger, 1990.
2. Vainio A, Auvinen A, with Members of the Symptom Prevalence Group:
Prevalence of symptoms among patients with advanced cancer: An International
Collaborative Group. J Pain Symptom Management 12:3-10, 1996.
3. Larue F, Colleau SM, Brasseur L, et al: Multicentre study of cancer
pain and its treatment in France. Br Med J 310:1034-1037, 1995.
4. Cancer Pain Relief and Palliative Care. Report of a WHO Expert Committee,
World Health Organization, Technical Report Series 804. Geneva, Switzerland,
5. Swerdlow M, Stjernsward J: Cancer pain relief. World Health Forum
6. Cancer Pain Relief. World Health Organization, Geneva, Switzerland
7. Cleeland CS, Gonin R, Hatfield AK, et al: Pain and its treatment
in outpatients with metastatic cancer. N Engl J Med 330:592-596, 1994.
8. Foley K: The treatment of cancer pain. N Engl J Med 313:84-95, 1985.
9. Cancer Pain: A Monograph on the Management of Cancer Pain. Health
& Welfare Canada, Minister of Supply and Services Canada, Ottawa H42-2/5
10. Graves DA, Foster TS, Batenhorst RL, et al: Patient-controlled analgesia.
Ann Intern Med 99:360-366, 1983.
11. Portenoy RK, Coyle N: Controversies in the long-term management
of analgesic therapy in patients with advanced cancer. J Pain Symptom Management
12. Burns JW, Hodsman NBA, McLintock TTC, et al: The influence of patient
characteristics on the requirements for post-operative analgesia. Anaesthesia
13. Ferrante FM, Lu L, Jamison SB, et al: Patient-controlled epidural
analgesia: Demand dosing. Anesth Analg 73: 547-552; 1991.
14. Boulanger A, Choiniere M, Roy D, et al: Comparison between patient-controlled
analgesia and intramuscular meperidine after thoracotomy. Can J Anaesth
15. Bosek V, Miguel R: Comparison of morphine and ketorolac for intravenous
patient- controlled analgesia in postoperative cancer patients. Clin J
Pain 10:314-318, 1994.
16. Cohen S, Amar D, Pantuck CB, et al: Postcesarean delivery epidural
patient-controlled analgesia: Fentanyl or sufentanil? Anaesthesia 78:486-491,
17. Boudreault D, Brasseur L, Samii K, et al: Comparison of continuous
epidural bupivacaine infusion plus either continuous epidural infusion
or patient-controlled epidural injection of fentanyl for postoperative
analgesia. Anaesth Analg 73:132-137, 1991.
18. Curry PD, Pacsoo C, Heap DG: Patient-controlled epidural analgesia
in obstetric anaesthetic practice. Pain 57:125-128, 1994.
19. Woodhouse A, Hobbes AFT, Mather LE, et al: A comparison of morphine,
pethidine and fentanyl in the postsurgical patient-controlled analgesia
environment. Pain 64:1078-1076, 1996.
20. Lawrie SC, Forbes DW, Akhtar TM, et al: Patient-controlled analgesia
in children. Anaesthesia 45:1074-1076, 1990.
21. Owen H, Mather LE, Rowley K: The development and clinical use of
patient-controlled analgesia. Anaesth Intensive Care 16(4):437, 1988.
22. Hill HF, Adam MM, Coda BA: Patient-controlled analgesic infusion,
in Max M, Portenoy R, Lask E, (eds): Advances in Pain Research and Therapy,
vol 18, pp 507-523. New York, Raven Press, 1991.
23. Nayman J: Measurement and control of post-operative pain. Ann R
Coll Surg Engl 651:419, 1979.
24. Dahl JB, Daugaard JJ, Larsen HV, et al: Patient-controlled analgesia:
A controlled trial. Acta Anaesthiol Scand 41: 744, 1987.
25. McGrath D, Thurston N, Wright D, et al: Comparison of one technique
of patient- controlled postoperative analgesia with intramuscular meperidine.
Pain 37:265, 1989.
26. Bennet RL, Batenhorst RL, Bivins BA, et al: Drug use pattern in
patient-controlled analgesia. Anaesthesia 57:A210, 1982.
27. Bollish SJ, Collins CL, Hirking DM, et al: Efficacy of patient controlled
versus conventional analgesia for postoperative pain. Clin Pharmacokinet
28. Schechter NL, Berrien FB, Katz SM: The use of patient-controlled
analgesia in adolescents with sickle cell pain crisis: A preliminary report.
J Pain Symptom Management 3:109-113, 1988.
29. Gonzales ER, Bahal N, Hansen LA, et al: Intermittent injection vs
patient-controlled analgesia for sickle cell crisis pain: Comparison in
patients in the emergency department. Arch Intern Med 151:1373-1378, 1991.
30. Shapiro BS: The management of pain in sickle cell disease. Pediatr
Clin North Am 36:1029-1045, 1989.
31. Grundy R, Howard R, Evans J: Practical management of pain in sickling
disorders. Arch Dis Child 69:256-259, 1993.
32. Chapman CR, Hill HF: patient-controlled analgesia in a bone marrow
transplant setting. Psychological aspects, in Foley KM, et al (eds): Advances
in Pain Research and Therapy, vol 16, pp 231-247. New York, Raven Press,
33. Bruera E, Macmillan K, Hanson J, et al: The Edmonton injector: A
simple device for patient-controlled subcutaneous analgesia. Pain 44:167-169,
34. Hill HF, Jacobson RC, Coda BA, et al: A computer-based system for
controlling plasma opioid concentration according to patient need for analgesia.
Clin Pharmacokinet 20(4):319-330, 1991.
35. Hill KF, Mackie AM, Jacobson RC: Pharmacokinetic aspects of patient-controlled
analgesia, in Ferrante, et al (eds): Recent Advances in Patient-Controlled
Analgesia, pp 214-222. Oxford, Blackwell Scientific Publications, 1990.
36. Alvis MJ, Reves JG, Govier AV, et al: Computer-assisted continuous
infusion of fentanyl during cardiac anesthesia: Comparison to a manual
method. Anaesthesia 62:41-49, 1985.
37. Ausems ME, Stanski DR, Hug CC: An evaluation of the accuracy of
pharmacokinetic data for the computer-assisted infusion of alfentanil.
Br J Anaesth 57:1217-1225, 1985.
38. Harrison MJ: Prediction of infusion rates: Computer study. Br J
Anaesth 64:283-286, 1990.
39. Portenoy RK, Hagen NA: Breakthrough pain definition, prevalence
and characteristics. Pain 41:273, 1990.
40. Bruera E, Macmillan K, Kuehn N, et al: Circadian distribution of
extra doses of narcotic analgesics in patients with cancer pain: A preliminary
report. Pain 49:311-314, 1992.
41. Bruera E, Fainsinger R, Spachynski K, et al: Clinical efficacy and
safety of a novel controlled release morphine suppository and subcutaneous
morphine in cancer pain: A randomized evaluation. J Clin Oncol 13(6):1520-1527,
42. Citron ML, Croghan MK, Parris WCV, et al: Use of rescue analgesic
for breakthrough pain in chronic cancer patients (abstract). Proceedings
International Association Study of Pain World Pain Congress, p 21, 1996.
43. Kavaliers M, Hirst M: Daily rhythms of analgesics in mice: Effects
of age and photoperiod. Brain Res 279:387, 1983.
44. Jorgensen BC, Schmidt F, Hertel S, et al: Patient-controlled analgesic
therapy by sublingual buprenorphine. Clin J Pain 4(2):75, 1988.
45. Glare PA, Walsh TD, Pippenger CE: Letter: Normorphone, a neurotoxic
metabolite. Lancet 335:725-726, 1990.
46. Bruera E: Subcutaneous administration of opioids in the management
of cancer pain, in Foley K, Ventafridda V (eds): Advances in Pain Research
& Therapy, vol 16, pp 203-218. New York, Raven Press, 1990.
47. Portenoy RK, Foley KM, Stulman J, et al: Plasma morphine and morphine-6-glucuronide
during chronic morphine therapy for cancer pain: Plasma profiles, steady-state
concentrations and the consequences of renal failure. Pain 47:13, 1991.
48. Ripamonti C, Bruera E: Guidelines for the drug treatment of CNS
adverse effects of opioids. CNS Drugs, in press, 1997.
49. Rotter JB: Some problems and misconceptions related to the construct
of internal versus external locus of control. J Consult Clin Psychol 43:56-67,
50. Ferrante FM: Patient characteristics influencing effective use of
patient-controlled analgesia, in FM Ferrante, Ostheimer W, BG Covino (eds):
Patient Controlled Analgesia, pp 51-59. London, Blackwell, 1990.
51. Johnson LR, Magnani B, Chan V, et al: Modifiers of patient-controlled
analgesia efficacy. I. locus of control. Pain 39:17-22, 1989.
52. Johnson LR: Psychological modifiers of PCA efficacy. Anaesthesia
53. Zech DFJ, Lehmann KA: Transdermal fentanyl in combination with initial
intravenous dose titration by patient-controlled analgesia. Anticancer
Drugs 6(3):44-49, 1995.
54. Portenoy RK, Foley KM, Inturrisi CE: The nature of opioid responsiveness
and its implications for neuropathic pain: New hypotheses derived from
studies of opioid infusions. Pain 43:273, 1990.
55. Bruera E, Brenneis C, Michaud M, et al: Patient-controlled subcutaneous
hydromorphone vs continuous subcutaneous infusion for the treatment of
cancer pain. J Natl Cancer Inst 80(14):1152-1154, 1988.
56. Ferrell BR, Ferrant M, McCaffery M: Routes of opioid administration
for cancer pain: Controversial. American Pain Society's 10th Annual Scientific
Meeting, p 119, 1991.
57. Bruera E, Macmillan K, Hanson J, et al: The Edmonton staging system
for cancer pain: Preliminary report. Pain 37:203-209, 1989.
58. Bruera E, Miller L, McCallion J, et al: Cognitive failure in patients
with terminal cancer: A prospective study. J Pain Symptom Management 7(4):192-195,
59. Massie MJ, Holland J, Glass E: Delirium in terminally ill cancer
patients. Am J Psychiatry 140:1048-1050, 1983.
60. Kerr I, Sone M, DeAngelis C, et al: Continuous narcotic infusion
with patient-controlled analgesia for chronic cancer pain in outpatients.
Ann Intern Med 108:554, 1988.
61. Grochow L, Sheider V, Grossman S, et al: Does intravenous methadone
provide longer lasting analgesia than intravenous morphine? A randomized,
double-blind study. Pain 38:151, 1989.
62. Urquhart ML, Klapp K, White PF: Intravenous versus subcutaneous
hydromorphone for patient-controlled analgesia. Anaesthesia G7:A231, 1987.
63. Bruera E, Ripamonti C: Alternate routes of administration of opioids
for the management of cancer pain, in Patt R (ed): Cancer Pain, pp 161-84.
Philadelphia, JB Lippincott, 1993.
64. Hill HF, Chapman CR, Kornell J, et al: Self-administration of morphine
in bone marrow transplant patients reduces drug requirement. Pain 40:121-129,
65. Mache AU, Coda BC, Hill HF: Adolescents use patient-controlled analgesia
effectively for relief from prolonged oropharyngeal mucositis pain. Pain
66. Hill HF, Chapman CR: Patient-controlled analgesia versus continuous
infusion morphine in cancer patients: Lack of tolerance development. Pain
67. Hill HF, Mackie Am, Coda BA, et al: PCA administration: A comparison
of steady-state morphine infusions with bolus doses. Cancer 67:873, 1991.
68. Eimeral D, Magora F, Shir Y, et al: Patient-controlled analgesia
with epidural methadone by means of an external infusion pump. Schmertz-pai-Doleur
69. Harmer U: Route of administration for patient-controlled analgesia:
Intravenous, intramuscular or oral, in Harmer M, Rosen M, Vickers MD, (eds):
Patient-controlled Analgesia, pp 126-131. Oxford, Blackwell Scientific
70. Devulder J: PCA and cancer pain. Acta Anaesthesiol Belg 43:53-56,
71. Hardy PAJ, Wells JCD: Patient-controlled intrathecal morphine for
cancer pain: A methods used to assess morphine requirements and bolus doses.
Clin J Pain 6:57-59, 1990.
72. Shoulong L, Jianlong W, Rongzeng W, et al: Clinical application
of patient-controlled apparatus for ventricular administration of morphine
in intractable pain: Report of 28 cases. Neurosurgery 29:73-75, 1991.
73. Sawe J, Hansen J, Ginman C, et al: Patient-controlled dose regimen
of methadone for chronic cancer pain. Br Med J 282:771-773, 1981.
74. Mercadante S, Sapio M, Serretta R, et al: Patient-controlled analgesia
with oral methadone in cancer pain. Ann Oncol 7:613-617, 1996.
75. Bruera E, Fainsinger R, Moore M, et al: Clinical note: Local toxicity
with subcutaneous methadone. Experience of two centers. Pain 45:141-143,
76. Baumann TJ, Batenhorst RL, Graves DA, et al: Patient-controlled
analgesia in the terminally ill cancer patient. Drug Intell Clin Pharm
77. Bennet RL: Patient-controlled analgesia for the treatment of the
pain of terminal cancer: Description of an initial clinical experience,
in Harmer M, Rosen M, Vickers MD (eds): Patient-Controlled Analgesia, pp
160-169. Oxford, Blackwell Scientific Publications, 1985.
78. Citron ML, Johnston-Early A, Boyer M, et al: Patient-controlled
analgesia for severe cancer pain. Arch Intern Med 146:734-736, 1986.
79. Citron ML, Kalra J, Seltzer VL, et al: Patient-controlled analgesia
for cancer pain: A long- term study of inpatient and outpatient use. Cancer
Invest 10(5):335-341, 1992.
80. Swanson G, Smith J, Bulich R, et al: Patient-controlled analgesia
for chronic cancer pain in the ambulatory setting: A report of 177 patients.
J Clin Oncol 7:1903-1908, 1989.
81. Bruera E: Continuous sc infusion of narcotics using a portable disposable
device in patients with advanced cancer. Yearbook of Cancer 24:416-417,
82. Bruera E, Macmillan K, Selmser P, et al: Decreased local toxicity
with subcutaneous diamorphine (heroin): A preliminary report. Pain 43:91-94,
83. Vanier MC, Labrecque G, Lepage-Savary D, et al: Comparison of hydromorphone
continuous subcutaneous infusion and basal rate subcutaneous infusion plus
PCA in cancer pain: A pilot study. Pain 53:27-32, 1993.
84. Meuret G, Jocham H: Patient-controlled analgesia (PCA) in the domiciliary
care of tumor patients. Cancer Treat Rev 22(suppl A):137-140, 1996.
85. Gourlay GK, Plummer JK, Cherry DA, et al: Comparison of intermittent
bolus with continuous infusion of epidural morphine in the treatment of
severe cancer pain. Pain 47:135-140, 1991.
86. Chrubasik J, Chrubasik S, Martin E: Patient-controlled spinal opiate
analgesia in terminal cancer: Has its time really arrived? Drugs 43(6):799-804,
87. Arner S, Arner B: Differential effects of epidural morphine in the
treatment of cancer- related pain. Acta Anaesthesiol Scand 39:32-36, 1985.
88. Brunk SF, Delle M: Morphine metabolism in man. Clin Pharmacol Ther
89. Hanks GW, Aherne GW, Hoskin PJ, et al: Explanation for potency of
repeated doses of oral morphine? Lancet 2:732-735, 1987.
90. Ventafridda V, Ripamonti C, Sbanotto A, et al: Mouth care, in Doyle
D, Hanks GWC, MacDonald N (eds): Oxford Textbook of Palliative Medicine,
pp 434-447. Oxford, Oxford University Press, 1993.
91. Chapko MK, Syrjala KL, Schilter, et al: Chemoradiotherapy toxicity
during bone marrow transplantation: Time course and variation in pain and
nausea. Bone Marrow Transplant 4:181-186, 1989.
92. Hill HF, Mackie A, Coda BA, et al: Evaluation of the accuracy of
a pharmacokinetically- based patient-controlled analgesia system. Eur J
Clin Pharmacol 43:67-75, 1992.
93. Hill HF, Coda BA, Mackie AM, et al: Patient-controlled analgesic
infusions: Alfentanil versus morphine. Pain 49:301-310, 1992.
94. Chandler SW, Trissel LA, Weinstein SM: Combined administration of
opioids with selected drugs to manage pain and other cancer symptoms: Initial
safety screening for compatibility. J Pain Symptom Manage 12:168-171, 1996.
95. White P: Mishaps with patient-controlled analgesia. Anaesthesia
96. Notcutt W: Overdose of opioid from patient-controlled analgesia
pumps. Br J Anaesth 68:450, 1992.
97. Thomas DW, Owen H: Patient-controlled analgesia: The need for caution.
Anaesthesia 43:770-772, 1988.
98. Grey TC, Sweeney ES: Patient-controlled analgesia. JAMA 259:2240,
99. Daschner F: Cost-effectiveness in hospital infection control-lessons
for the 1990s. J Hospital Infect 13:325-336, 1989.
100. Geroulanos S, Attinger B: Nosocomial infections, risks and consequences.
Schweizerische Rundschau fur Medizin Praxis 80:291-296, 1991.
101. Rosen M, Williams B: The valued-Y-Cardiff connector (VYCCON). Anaesthesia
102. Kluger MT, Owen H: Patients' expectations of patient-controlled
analgesia. Anaesthesia 45:1072-1074, 1990.