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Patient-Controlled Analgesia Patient-Controlled Analgesia Jeffrey A. Grass, MD, MMM Department of Anesthesiology, Western Pennsylvania Hospital and Allegheny General Hospital, Pittsburgh, Pennsylvania One of the most common methods for providing post- aspects of PCA and provides extensive guidelines for operative analgesia is via patient-controlled analgesia the practice of PCA-administered opioids. In addition, (PCA). Although the typical approach is to administer potential adverse effects and recommendations for opioids via a programmable infusion pump, other their monitoring and treatment are reviewed. drugs and other modes of administration are available. This article reviews the history and practice of many (Anesth Analg 2005;101:S44–S61) atient-controlled analgesia (PCA) is commonly An Historical Perspective assumed to imply on-demand, intermittent, IV Gross undertreatment of acute pain has been well P administration of opioids under patient control chronicled over the last quarter century and likely (with or without a continuous background infusion). continues today. The traditional approach of IM opi- This technique is based on the use of a sophisticated oids given pro re nata (prn) results in at least 50% of microprocessor-controlled infusion pump that deliv- patients experiencing inadequate pain relief after sur- ers a preprogrammed dose of opioid when the patient gery. Marks and Sachar’s landmark 1973 publication pushes a demand button. Although this article focuses (2) ignited a philosophical revolution in practitioners’ on IV-PCA, it is important to note that PCA is a perception of the adequacy of conventional analgesic conceptual framework for administration of analge- practices. Not only did this study document that a sics (1). The broader concept of PCA is not restricted to large proportion of hospitalized patients were under- a single class of analgesics or a single route or mode of treated, it also exposed that physicians and nurses are administration. Nor should PCA imply the mandatory misinformed and lack sophistication regarding the ef- presence of a sophisticated and expensive infusion fective use of opioid analgesics. This began the shift in device. Any analgesic given by any route of delivery intellectual milieu from the quest for the “perfect” (i.e., oral, subcutaneous, epidural, peripheral nerve analgesic (with an ever-expanding opioid pharmaco- catheter, or transdermal) can be considered PCA if poeia) towards optimizing the mode of administration administered on immediate patient demand in suffi- and delivery system for the (perfectly adequate) anal- cient quantities. In this context, first reviewed is the gesic drugs that already existed. “traditional” system, then IV-PCA, beginning with an Roe (3) was the first to demonstrate, in 1963, that historical perspective, followed by a discussion of the small IV doses of opioids provide more effective pain PCA paradigm. Then presented is a comprehensive relief than conventional IM injections. Subsequently, review of clinical management issues, patient charac- Sechzer (4)—the true pioneer of PCA—evaluated the teristics influencing effective use, safety consider- analgesic response to small IV doses of opioid given ations, benefits, and limitations. Subsequently, alter- on patient demand by a nurse in 1968 and then by native routes of PCA delivery and future directions in machine in 1971 (5). Obviously, frequent administra- PCA technology and management are presented. tion of IV doses of opioid by nurses to large numbers of patients is impractical and cost prohibitive. Thus, the late 1960s witnessed development of PCA technol- ogies. Prototypic devices were developed by Sechzer Financial support for preparation of this manuscript was pro- (5), Forrest et al. (“Demand Dropmaster”) (6), and vided by an unrestricted educational grant from Endo Pharmaceu- ticals, Chadds Ford, Pennsylvania. Keeri-Szanto (“Demanalg”) (7). In 1976, the first com- Accepted for publication June 22, 2005. mercially available PCA pump, the “Cardiff Palliator,” Address correspondence and reprint requests to Jeffrey A. Grass, was developed at the Welsh National School of Med- MD, Chairman, Department of Anesthesiology, Western Pennsyl- vania Hospital, 4800 Friendship Avenue, Pittsburgh, PA 15224. icine (8). Since then, PCA devices have evolved enor- Address electronic mail to [email protected]. mously in technological sophistication, ease of use, ©2005 by the International Anesthesia Research Society S44 Anesth Analg 2005;101:S44–S61 0003-2999/05 ANESTH ANALG REVIEW ARTICLE GRASS S45 2005;101:S44–S61 PATIENT-CONTROLLED ANALGESIA Table 1. Points of Concern in Evaluation of Patient- Controlled Analgesia Devices Machine-user interface Programmability Flexibility Standard terminology Ability to eliminate programmable drug concentrations Customizable rate and dosing limit variables Adequate, easy to access and interpretable reports Report download capability (paper, Personal Digital Assistant, Personal Computer) Tamper protection Ease of ambulation Machine operability Pump mechanism Operational modes Figure 1. A theoretical representation of the steepness of the FDA approved for epidural and intrathecal concentration/response curve for opioids is shown. The x-axis is plasma opioid concentration; the y-axis is pain rated from severe delivery (bottom) to none (top). Circles represent sequential measurements Fail-safe mechanisms of opioid concentration and the corresponding pain values during Alarms and indicators an interval when opioid concentration is increasing. With increasing Upstream and downstream occlusion sensors opioid concentrations, progressive increases in concentration ini- Free flow impedance protection tially produce no change in pain, then over a finite range of con- Memory centrations, pain is attenuated, then further increases in opioid Mounting concentration produce no additional effect. MCP or “maximum Disposables concentration pain” is the maximum concentration of opioid asso- Reservoir type and capacity ciated with severe pain. MEAC or “minimum effective analgesic concentration” is the smallest opioid concentration at which pain is Infusion tubing (distinction of IV versus relieved. Adapted from Austin et al. (9). epidural) Adapted from (1). FDA ϭ Food and Drug Administration. establishing that pharmacodynamic variability in re- sponse to opioids accounts for individual differences in dose requirements. Tamsen et al. (10) and Dahl- flexibility, and portability. Although a discussion of strom et al. (11) subsequently studied the contribution PCA device technology is beyond the scope of this of pharmacokinetic and pharmacodynamic factors on review, issues concerning evaluation of PCA devices analgesic requirements of other opioids. Pharmacoki- are presented in Table 1. netic variables (volume of distribution, rates of distri- bution and elimination) consistently failed to correlate with dose requirement; in contrast, an individual’s The PCA Paradigm hourly opioid dose and their plasma opioid concen- Austin et al. (9) deserve credit for elucidating the tration did correlate. Further work by Tamsen et al. pharmacologic principles that are the basis for IV- (12) suggested that the individual’s MEAC may be PCA. They administered small increments of meperi- determined by preoperative cerebrospinal fluid (CSF) dine, measured plasma concentrations, and assessed endogenous opioid content: patients with larger CSF pain scores in patients to demonstrate the steepness of endogenous opioid content required smaller MEACs the concentration-effect curve for opioid analgesics to establish and maintain analgesia. (Fig. 1). A minimal increase in meperidine concentra- Two prerequisites for effective opioid analgesia tion (as little as 3%–5%) more than the maximum con- were thus established: 1) individualize dosage and centration associated with severe pain dramatically de- titrate to pain relief response to achieve the MEAC and creased pain. The smallest concentration at which pain establish analgesia, and 2) maintain constant plasma was relieved was termed the “minimum effective anal- opioid concentrations and avoid peaks and troughs gesic concentration” (MEAC). Minimal analgesia is (13). These requirements cannot be achieved with prn achieved with titration of opioid until the MEAC is or around-the-clock IM injections. Figure 2 depicts the achieved, which marks the difference between severe PCA paradigm and its inherent pharmacologic supe- pain and analgesia. Furthermore, these investigators riority over IM injections. After titration to achieve the found a discrete concentration of opioid within an indi- MEAC and establish analgesia, patients use PCA to vidual to consistently provide effective analgesia, maintain plasma opioid concentrations at or just whereas the discrete concentration that provided an- above their individual MEAC (“optimal plasma con- algesia varied considerably among individuals, thus centration”). In contrast, patients receiving IM bolus S46 REVIEW ARTICLE GRASS ANESTH ANALG PATIENT-CONTROLLED ANALGESIA 2005;101:S44–S61 Figure 2. This graphic compares analgesia achieved with two different analgesic regimens: intermittent bolus administration (nurse- administered analgesia) or frequent small doses (patient-controlled analgesia, PCA). The shaded area represents the target analgesic concentration. With intermittent bolus administration, there are frequent periods with concentrations more than and less than the target range. In contrast, PCA results in the opioid concentration being in the target
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