Current Status of Patient-Controlled Analgesia in Cancer Patients
Current Status of Patient-Controlled Analgesia in Cancer Patients
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