Patient-controlled analgesia: a method for the controlled self-administration of opioid pain medications.

Key Words: Analgesia, Analgesics, Pain, Pharmacology, Self administration.

The use of biological and chemical substances for medicinal and religious purposes was common in antiquity. Oral ingestion, inhalation, or the topical application of some of these substances could evoke powerful physiological or psychological responses. Some of these effects were pleasant or beneficial, whereas others were potentially harmful or of little value. The reduction or elimination of pain and the production of sleep were two effects that were considered worthwhile, from the point of view of both the patient and the prescribing individual. Among the compounds found to have pain-relieving value was opium, and its use dates back over 3,000 years.1 Morphine, the pharmacologically active component of opium, was isolated in the early part of the 19th century and has been the most commonly used analgesic compound for more than 100 years.

Drug Delivery Strategies

When used for pain control, opioid analgesics, including morphine, are usually given according to a predetermined schedule or on in as-needed basis. These drugs are typically administered orally, by intramuscular injection or intravenous infusion, or by direct placement in the epidural or subarachnoid space[2,3] With the intent of establishing plasma concentrations at or slightly above a level referred to as the minimum effective analgesic concentration (MEAC). Minimum effective analgesic concentration is a drug-specific term and is defined as the lowest plasma concentration required to produce an acceptable level of pain relief. The MEAC varies among analgesic drugs and individuals.[4,5]

Evidence has accumulated over the past 30 years suggesting that these drug delivery strategies may not result in the desired degree of pain control and that many patients continue to suffer despite the well-intentioned efforts of physicians and nurses to provide pain relief.[6-8] Scheduled delivery systems frequently fail because of differences among individuals in the rate and efficiency with which they absorb and metabolize drugs. Such differences in human physiology make it difficult to maintain stable and therapeutically effective plasma concentrations of particular drugs over time. Austin et al[4,5] and Lehman and co-workers[9] have demonstrated a twofold to fivefold variability in the doseplasma concentration among different patients receiving fixed amounts of a particular drug. In addition, these authors4,5,9 found that patients differ significantly in plasma concentrations needed to produce adequate pain relief Effects observed when the concentration of opiate drugs in the plasma fluctuates range from nausea, vomiting, confusion, sedation, and respiratory arrest when concentrations are too high to inadequate pain control when plasma concentrations fall to subtherapeutic levels.

Dosage-on-demand protocols present a different set of challenges to effective pain management. Some studies[10-12] have shown that despite the fact that appropriate drugs and drug doses had been ordered, patients nonetheless did not receive sufficient medication to relieve their pain. Among the factors cited as contributing to this situation was reluctance on the part of the nursing staff to administer narcotic pain medications based on fear of producing medication-related side effects or of causing drug dependence or addiction.[13] Patients themselves may contribute to the problem of under-medication. Some patients believe that if they take narcotic pain medications while in the hospital, they may become addicted, and they fear what might happen after they are discharged from the hospital. Rather than ask for pain medications when needed, these individuals may elect to suffer in silence. Both of these problems can be addressed through education. Physicians and nurses can be better educated regarding the use of opiate drugs for pain control, and patients can be better informed regarding the actual risks associated with the proper use of narcotic pain medications.

Failure to overcome difficulties associated with the drug delivery strategies described will result in inadequate pain control when plasma concentrations fall below the MEAC or the occurrence of drug-induced side effects when plasma concentrations rise significantly above the MEAC. The concept of a therapeutic window refers to a range of plasma concentrations, which, when achieved, result in adequate pain relief without drug-induced side effects. Pain management would be enhanced by a method that would maintain plasma concentrations within the therapeutic window for that drug. Positive steps toward the attainment of this goal were taken with the introduction of patient-controlled analgesia (PCA).

Patient-controlled analgesia refers to a relatively new approach to drug delivery in which patients are allowed to self-administer small doses of opioid analgesics as needed to achieve adequate levels of pain control. Patient-controlled analgesia offers several clear advantages over other protocols for administering opioid analgesics, Fluctuations in plasma concentrations and analgesic effectiveness typically associated with scheduled delivery protocols are greatly reduced because medications can be administered more frequently and at lower individual doses. Fears related to the development of side effects and addiction that may be associated with dosage-on-demand protocols are reduced because the PCA system is programmed to limit the amount of drugs a patient is able to self-administer. An added benefit of this technique is that when patients are able to self-administer predetermined quantities of pain medications, nursing staff can be freed for other patient care activities that might be more demanding in terms of time and professional expertise.

Patient-controlled analgesia should be viewed as a technique for administering as opioid pain medications. Most PCA systems in use today are used to deliver drugs by the intravenous route; however, PCA has been used for subcutaneous, epidural, or subarachnoid infusion as well.[2,3,14] Patient-controlled analgesia using the intravenous route has been shown by several investigators[15-17] to provide better pain relief than intramuscular injection of opioid drugs. Bollish et al[15] have shown that patient satisfaction associated with PCA is substantially greater than with other delivery techniques, in part because plasma concentrations of analgesic drugs can be more effectively controlled and because patients report less discomfort when they are able to exert a degree of control over their own individual pain experience. The ability to control pain and discomfort reduces anxiety and fear, which in turn leads to reduced suffering and a decreased sensitivity to pain.[18-21]

General Indications and Contraindications

Patient-controlled analgesia is indicated when oral administration of an analgesic medication is not possible or when oral administration does not result in adequate pain relief. This method is not indicated in situations where oral administration is effective or with patients who are unable for one reason or another to operate the device properly. Patient-controued analgesia is also contraindicated if health care professionals lack the requisite knowledge and skill to use the technique safely and effectively.

Patient--Controlled Analgesia Device Characteristics

The PCA system consists of a programmable infuser, a delivery method that places the infused drug in a desired location, and a mechanism the patient can use to self-administer measured doses of a prescribed medication. Several types of PCA systems are commercially available, some designed for patients who are restricted to bed and others of a smaller, more portable design intended for patients who are free to move around. System components range in sophistication and complexity from simple syringe drivers to electronically controlled implantable systems. Patient-controlled analgesia devices differ mainly in the programmable parameters that determine the amount of drug that can be self-administered over a fixed period of time.

The two most common modes of PCA in use today are demand dosing and constant rate infusion with demand dosing. With demand dosing, patients are able to obtain a preset dose by activating the PCA system, usually by depressing a button. Pain medications are delivered only when the PCA system is activated. The PCA pump can be programmed to limit the amount of drug a patient can receive per demand as well as the number of demands that result in drug delivery. These restrictions reduce the possibility of overmedication and the occurrence of side effects.

Constant rate infusion with demand dosing differs in that the patient receives a continuous small dose of the analgesic drug in an attempt to maintain stable plasma levels of the analgesic drug. Should the pain worsen for some reason, activation of the PCA system would result in the administration of an additional small dose of the pain medication that will raise the plasma concentration slightly and re-establish pain relief.

The ability to maintain stable plasma concentrations of an analgesic drug over time is related in part to the degree to which variables associated with drug delivery can be regulated. Two key variables are demand dose and lockout interval. Demand dose refers to the amount of drug a patient will receive each time the PCA system is activated. The amount delivered per demand is determined by the prescribing physician, taking into account the pharmacological properties of the particular drug being used, its potential to interact with other drugs the patient may be receiving, and patient-specific factors such as allergies to particular compounds or previous experience with opiate analgesics. Demand dose may vary among patients but will generally fall within a therapeutic range specific for that drug. Demand dose is a programmable variable that can be changed during the course of treatment as the pain-producing condition changes naturally or as a result of therapeutic intervention. Keeri-Szanto[22] has shown that if the demand dose is changed during treatment with PCA, patients will typically adjust their demand rate accordingly to maintain a stable drug plasma concentration.

The lockout interval is the length of time following administration of single dose during which further demands will not result in additional drug administration. The lockout interval can be thought of as a fixed length of time during which pain medications will not be administered even though patients may attempt to activate the system. The length of the lockout interval is a function of the pharmacokinetic and pharmacodynamic properties of the drug being considered for use. It is determined in part by drug-specific factors such as how a particular drug is distributed, stored, and ultimately eliminated from the body. The purpose of the lockout interval is to prevent overmedication. Like demand dose, the lockout interval can be preset and readjusted during treatment. The possibility of overmedication exists if the lockout interval is too short. If the interval is too long, plasma concentrations may drop to subtherapeutic levels and pain may return.

Some PCA devices permit the user to preset or regulate other parameters of drug delivery. Among these adjustable variables are loading dose, background infusion rate, and dose rate. Loading dose refers to a specific amount of drug that the PCA system can be programmed to deliver as an initial, single dose in an effort to quickly elevate plasma concentration and relieve pain. Loading dose for a particular drug is that dose that can be administered to induce analgesia in a patient who is not currently receiving opiate pain medications, but who will continue to receive that drug using PCA.

Background infusion rate refers to frequency of administration of set doses of an analgesic drug that is independent of patient demand. The intent of administering predetermined low doses of a drug in this manner is to reduce the disequilibrium between the central nervous system and blood plasma concentrations that results when only intermittent doses are delivered. When infusion rate and plasma concentration are held constant, there will be a direct relationship between plasma concentration and the degree of pain relief produced.

Dose rate refers to the amount of drug delivered per unit of time. Dose rate is closely related to both demand dose and lockout interval. The dose identified in the dose rate can be delivered in a single dose or in multiple incremental doses of a smaller amount until the prescribed dose has been administered. A comparison of the number of attempts made with the number of doses administered provides a useful measure of the effectiveness of PCA for that patient. For example, a much greater number of attempts than permitted administrations suggests poor pain control and possibly the need to increase the background infusion rate or to decrease the lockout interval.

Therapeutic Goals and Requisite Knowledge

The overall goal of pain management strategies using PCA is to produce adequate and sustained analgesia without side effects at a reasonable cost. Adequate analgesia using opioid compounds administered intravenously is achieved when plasma concentrations reach the level referred to as the MEAC. As mentioned earlier, the MEAC is the plasma concentration of a particular drug that produces effective analgesia without side effects. A major goal of pain control efforts using PCA technology is therefore to regulate drug delivery so that the MEAC is achieved and maintained for as long as may be necessary.

Knowledge of pharmacology is an essential prerequisite for the effective and appropriate use of PCA. Clinicians must be familiar not only with drug indications and contraindications, but also with pharmacodynamic and pharmacokinetic properties of particular opiate drugs. These latter considerations include the absorption, distribution, biotransformation, and elimination characteristics of various opioid analgesics. In addition, clinicians must be familiar with specific physiologic responses that may occur when drugs bind to specific receptor populations within as well as outside the brain. Knowledge of these issues and principles serves as the basis for selecting appropriate opiate drugs and for determining their proper use in a PCA system.

Patient-Controlled Analgesia in Selected Pain Conditions

Postoperative Pain

Surgical procedures are commonly associated with pain during the post-operative period. A somewhat unique aspect of postoperative pain is the fact that the immediate cause of pain is known and its intensity and duration when managed in conventional ways are generally well understood.[5,9,15] For these reasons, postoperative pain offers a useful model for studies comparing different analgesics and analgesia delivery systems. Changes in pain intensity or duration achieved by different drug delivery methods can be used as a measure of the effectiveness of these methods.

Opioids have been the drug of choice in the management of postoperative pain for more than 100 years, with morphine serving as the gold standard against which other drugs are measured. Typically, pain-relieving drugs are administered by nursing personnel using the intramuscular route. The effectiveness of postoperative pain control using conventional drug delivery methods has been questioned recently in reports by Marks and Sachar[6] and Donovan,[10] who have shown that despite adequate orders for pain medications, many of these patients continue to experience moderate to severe pain. In addition, many of these patients reported dissatisfaction with the pain control methods used.[10] Some investigators[23,24] have argued that this result is not related to the opioid medications themselves, but rather to inadequacies and deficiencies in drug delivery protocols. In comparative studies,[25-32] PCA has been shown to provide more complete and long-lasting postoperative analgesia than previously used methods and to increase patient satisfaction with pain management during the entire postoperative period. Patient-controlled analgesia has been used most extensively in the management of pain associated with the surgical procedures involving thoracic, abdominal, and pelvic structures. Pain associated with orthopedic surgery has also been managed effectively by means of PCA.

Cancer Pain

A majority of patients who develop cancer will experience pain associated with their disease. The pain may be localized or diffuse in nature and may wax and wane in severity over time. The fluctuating intensity of cancer pain makes PCA desirable in that patients themselves can deal with pain exacerbations when they occur. Patient-controlled analgesia is particularly helpful in patients with malignancies involving the gastrointestinal tract who may be unable to use oral medications. Studies[33-35] have demonstrated the value of PCA in the management of cancer-related pain. Ferrell and co-workers[36] recently reviewed the literature regarding the value of PCA in the management of cancer pain. These investigators noted that PCA may be of particular value when the oral route is unavailable, the total dose required to achieve effective pain control is excessive, or the need exists to control breakthrough pain. In addition, Ferrell et al describe circumstances under which it might be inappropriate to use PCA as a first-line approach to pain management. Patient-controlled analgesia is not indicated for patients who are confused, sedated, or otherwise unable to operate the device appropriately. It may not be appropriate when oral therapy has not been adequately tested or when medical personnel have not been adequately trained in its use.[36] Oral administration is preferred because of its relative ease and safety. Because of the risks associated with overmedication, only appropriately trained health care providers should institute PCA therapy.

Patient-controlled analgesia is also helpful in achieving rapid pain relief for pain exacerbations in patients taking oral pain medications. Once adequate analgesia is achieved by means of PCA, the effective parenteral dose can be used to determine an equivalent oral dose for continued long-term use (Table). The shift back to oral medications only can take just a few hours and can help eliminate the need for multiple readjustments over several days that might otherwise be needed to achieve adequate pain control.

Table. Equianalgesic Doses of Commonly
Used Opioid Analgesic Drugs(a)
                          Administration Route
                          mg)
                                     Intra-       Intravenous
Drug                      Oral      muscular
Morphine                   30         10            5
Meperidine                300         75           37.5
Hydromorphone               7.5        1.5          0.7

Labor and Delivery Pain

The physical and physiological events associated with labor and delivery are widely regarded as being painful.37 Women today have a variety of options available for reducing pain associated with labor and delivery, including peripheral nerve blocks, epidural anesthesia, acupuncture, transcutaneous electrical nerve stimulation, and a variety of systemic analgesics. Scott[38] reported in 1970 on the value of PCA via the intravenous route for pain associated with labor, Since that time, there has been only limited interest in the use of PCA in labor, in part because of the efficacy of epidural anesthesia, which is favored by many practitioners.[39] Pain levels change during labor, increasing to greatest intensity immediately before delivery. Patient-controlled analgesia can be useful in establishing plasma levels of analgesic medication needed to produce pain relief in the early stages of labor. Plasma concentration can then be easily and quickly increased by the woman herself as pain increases in later stages. Studies[40-42] have demonstrated effective analgesia by this method without ill effect on the fetus. More recently, patient-controlled epidural analgesia has been tried with good results.[43] Further studies, however, are needed to fully determine the safety and efficacy of this latter approach.

Patient-controlled analgesia has been effectively used in the management of postsurgical pain associated with caesarean delivery.[44,45] In studies that compared different routes of administration, investigators[11,12,44] found that although analgesic effectiveness was essentially the same for nurse-administered intramuscular drugs and PCA, patients preferred PCA. Perhaps the strongest argument favoring the use of PCA in delivery and in the management of postcaesarean incision pain is that the patient herself can exercise some degree of control over her pain.

Conclusion

Patient-controlled analgesia is a relatively new method for managing pain that provides the patient with limited control over the amount of pain medication received. Its use is well established in pain centers and other clinical settings where pain problems are common and where effective pain control is an important part of the overall treatment plan. Better pain control means that physical therapy programs that might be delayed or modified because of pain can be implemented as originally planned and functional improvement can be brought about sooner than might otherwise occur. Physical therapy is not contraindicated in patients using PCA.

Because some physical therapy procedures may produce discomfort, the question may arise as to whether PCA should be used during or before physical therapy intervention. There is no evidence to suggest that activation of the PCA system during treatment interferes with treatment in any way or produces a level of analgesia that might mask treatment-related discomfort. This question, however, deserves further study because of the potential benefit reduced pain might have on the overall outcome of therapy. The question of whether PCA should be used prior to physical therapy has not been formally addressed. Some patients may activate the PCA system prior to therapy in the hope of preventing or lessening pain that, by prior experience, they know will follow treatment. The extent, however, to which this practice actually occurs and the effect it may actually have on treatment outcome are unknown. The goal of making a patient comfortable and the use of certain physical modalities with pain-relieving properties (ie, heat and cold) before a potentially painful therapeutic procedure is not uncommon in clinical practice. It is reasonable to suggest on those grounds that pain relief by pharmacological means might permit patients to participate in certain therapeutic activities that they might otherwise avoid. A thorough investigation of issues related to the prophylactic use of PCA prior to physical therapy is warranted.

Patient-controlled analgesia is likely to be used with greater frequency and effectiveness in the future, largely as a consequence of new discoveries in clinical pharmacology and improvements in technology related to drug delivery systems. Physical therapists will need to be familiar with these advances if they are to take full advantage of the new opportunities for patient care that effective pain management will provide. Such opportunities include earlier intervention and the potential to progress more rapidly toward functional recovery.

References

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MF Nolan, PhD, PT, is Associate Professor, Departments of Neurology and Anatomy, College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, Address all correspondence to Dr Nolan at Department of Anatomy, College of Medicine, University of South Florida, MDC Box 6, 12901 Bruce B Downs Blvd, Tampa, FL 33612 (USA). M-CB Wilson, MD, is Assistant Professor, Department of Neurology, College of Medicine, University