Introduction
Cancer-related pain afflicts approximately 9 million people worldwide.[1] The prevalence of moderate to severe pain is 51%, ranging from 43% in stomach cancer to 80% in gynecologic cancers.[2] In rating their pain, the majority of patients (69%) say that the worst pain is that which causes impairment of their ability to function.[3] 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[4] and has been defined a "world medical emergency" by the World Health Organization (WHO).[5]
Despite published guidelines for pain management,[6] many cancer patients experience considerable pain, and approximately half of them receive inadequate analgesia.[3,7]
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 Figure 1.[10]
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 clinical trials.[11]
Patient-Controlled Analgesia
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.[20]
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(Drug information on 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.[27]
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[31] 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.[32]
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.
Available Devices
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 complicated.
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 opioid concentration.
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.[33]
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.
Pharmacokinetically Based PCA
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(Drug information on fentanyl), 460 mcg/L for meperidine, and 10 mcg/L for alfentanil(Drug information on 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[38] described a similar approach using vecuronium (Norcuron) for neuromuscular blockage.
A 70-year-old man with a history of localized prostate cancer treated with whole-pelvis radiation therapy with a boost to the prostate, in conjunction with androgen deprivation therapy 7 years prior, presented with lower back pain. A bone scan revealed an area of activity in the sacrum. What is the most likely diagnosis?
