Patient-Controlled Analgesia
Advantages
22. J.A., a 50-year-old, 5′4′′, 50-kg woman, is immediately postoperative from a total abdominal hysterectomy for a neoplasm. Her laboratory values are remarkable for a SrCr of 1.3 mg/dL (normal, 0.6–1.0 mg/dL). She is allergic to penicillin. She will be admitted to the postsurgical floor for a planned stay of 2 to 3 days. What mode of pain management should be chosen for J.A.?
PCA is a popular method of administering analgesics and offers several advantages over traditional IM or IV opioid dosing. Patients treated with intermittent IM or IV dosing of opioids “as needed” can experience severe pain because the serum opioid concentration is allowed to fall to less than the minimum effective analgesic concentration (the concentration that provides approximately 90% pain relief). In addition, high peak plasma opioid concentrations can be seen with this administration method, often resulting in excessive nausea, vomiting, or sedation, as well as respiratory depression. Small, frequent opioid doses, as seen in PCA, minimize the peaks and valleys in serum concentrations seen with relatively larger intermittent IM or IV doses. This is helpful in avoiding adverse effects associated with high peak serum concentrations and inadequate pain relief caused by subtherapeutic serum concentrations. Small, frequent, patient-controlled dosing of opioids is efficacious because opioids have a steep sigmoidal dose–response curve for analgesia, resulting in the ability of a small opioid dose to move the plasma concentration from being subtherapeutic to above the minimum effective plasma concentration that will provide effective pain relief.147,148 In terms of safety, analgesia occurs at lower opioid dosages than sedation, and sedation generally precedes respiratory depression.149 Therefore, if a patient becomes sedated, self-administration of additional patient-controlled bolus doses will stop, allowing the serum opioid concentration to fall to a safe level.
Therapy can be individualized by using small doses of opioids at preset intervals (e.g., 1 mg morphine every 8 minutes), with the patient in control of his or her analgesic administration. An infusion pump, with a programmed on-demand dose (the dose the patient can self-administer) and number of minutes between allowable doses (lock-out interval), is equipped with a button that the patient presses to receive a dose. IV bolus is the most common PCA route, with opioids being the drugs of choice to provide postoperative analgesia. The epidural route can also be used in select patients.
If the patient is educated to use PCA properly, it can be used to alleviate anticipated pain before movement or physical therapy in a pre-emptive fashion. J.A. has undergone a procedure for which moderate-to-severe pain is expected in the immediate postoperative period. J.A.'s pain requirement in the immediate postoperative period could be met with PCA opioid administration after first administering a bolus dose of opioid, which is titrated to achieve the appropriate level of analgesia. When her opioid requirements decline or when she can tolerate oral intake, she can then be switched to oral analgesics.
Patient Selection
23. J.A.'s surgeon decides to prescribe PCA for postoperative pain management. How should J.A. be evaluated for her ability to appropriately participate in her analgesic administration?
Patients receiving PCA therapy must be able to understand the concept behind PCA and to operate the drug administration button. J.A. must be alert and oriented before being put in control of her own pain management. She must be able to comprehend verbal and/or written instructions regarding the function and safety features of the infusion pump and how to titrate drug as needed for satisfactory analgesia. PCA has been used successfully in children, generally after ages 8 or 9 (adjusting doses appropriately) and in elderly patients. PCA is not indicated in patients who are expected to require parenteral opioids for analgesia for <24 hours because these patients will generally be able to tolerate oral analgesics shortly after surgery.
Patient Instructions
24. J.A. is nervous about giving herself an overdose while using PCA. What instructions should be provided to her?
Patients often worry about the safety of PCA, which can lead to reluctance to provide themselves with adequate pain relief. J.A. should be informed that if she administers too large of an amount of the prescribed opioid analgesic, she should fall asleep. Because she is asleep, she will not press the button. When this adverse effect of the opioid has worn off, she will wake up (plasma opioid level has fallen back into or below the therapeutic range). This is an important safety feature of PCA and is the reason family members must not push the button for the patient. However, J.A. should also know that she may have to press the button several times (after the lock-out interval has passed) before her pain is relieved. She must also be informed that she may require a larger PCA dose, so it is important for J.A. to assess her pain relief from the “usual” dose most patients are initially started on following surgery. Accurate pain assessment following her prescribed dose is critical for ensuring that her dose is sufficient to provide the desired level of analgesia. She should also understand the possible adverse effects of her PCA medication and what can be done to prevent and treat these effects, as well as the advantages of providing herself with adequate analgesia (e.g., early ambulation). Finally, she should be told of the negligible risk of “narcotic” addiction from short-term PCA use and be given ample opportunity to ask questions.
Choice of Agent
25. Meperidine is ordered for J.A.'s PCA. Is this a reasonable drug choice for her?
Ideally, opioids for PCA administration have a rapid onset and intermediate duration of action (30-60 minutes), with no accumulation, ceiling effect, or adverse effects. The physicians, nurses, and pharmacists involved with the care of the patient should be familiar with the drug selected for PCA. Morphine is by far the most common choice for PCA, although other opioids such as fentanyl and hydromorphone can be used. Drug choice is based on past patient experiences, allergies, adverse effects, and special considerations, such as renal function. Meperidine has a metabolite, normeperidine, which is renally excreted; has a long half-life; and can cause cerebral irritation and excitation. Symptoms of CNS toxicity from normeperidine include agitation, shaky feelings, delirium, twitching, tremors, and myoclonus/tonic-clonic seizures. These symptoms can be seen when meperidine is administered in higher doses and/or for a prolonged period.150,151 The presence of renal insufficiency increases the risk of accumulation of normeperidine.150 Meperidine also inhibits serotonin reuptake and has a fairly high serotonergic potential. The risk of a patient developing the serotonin syndrome is greater when meperidine is coadministered with another drug that has moderate or high serotonergic potential (e.g., fluoxetine, fluvoxamine, paroxetine, venlafaxine).152 For these reasons, meperidine is a poor choice for analgesia, particularly for J.A. who has diminished renal function. Morphine is conjugated with glucuronide in hepatic and extrahepatic sites (particularly the kidney) to its two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide; both metabolites are excreted primarily in the urine. Morphine-6-glucuronide is an active metabolite that can accumulate in patients with renal failure, resulting in prolonged analgesia, sedation, and respiratory depression.153 Because of J.A.'s diminished renal function, morphine should probably be avoided because other options exist. Hydromorphone is not metabolized to an active 6-glucuronide metabolite, and fentanyl is metabolized to inactive metabolites. Either hydromorphone or fentanyl is an appropriate analgesic choice for J.A. Hydromorphone is chosen. Table 9-16 lists common doses and lock-out intervals for drugs administered by PCA.154,155,156
Dosing
26. J.A. was not receiving an opioid prior to surgery (e.g., she is opioid naive). What dose of hydromorphone and what lock-out interval should be used for her initial PCA pump settings?
If J.A. is experiencing pain before PCA has been initiated, she should receive a loading dose of IV hydromorphone titrated to achieve baseline pain relief (usually up to 1 mg). Once adequate analgesia is achieved, demand doses of 0.2 mg with a lock-out interval of 8 minutes would be a good choice to maintain analgesia for this opioid-naive patient. If J.A.'s pain is not relieved after two to three demand doses within 1 hour, the demand dose can be increased to 0.3 mg.
| Table 9-16 Adult Analgesic Dosing Recommendations for Intravenous Patient-Controlled Analgesiaa | ||||||||||||||||||||||||||||||||
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Use of a Basal Infusion
Many PCA infusion pumps offer a continuous infusion setting for a basal infusion during intermittent dosing. Use of a basal (continuous) infusion has not been shown to improve analgesia and likely increases the risk of adverse effects (due to the potential of an opioid overdose in some patients). Therefore, routine basal (continuous) infusion of opioids cannot be recommended for acute pain management. In an opioid-naïve patient such as J.A., however, continuing to increase the demand dose increases the risk of excessive sedation and respiratory depression (due to high peak levels). Also, J.A. describes her pain as moderate to severe in intensity and fairly constant in nature when she does not regularly push the demand button. For J.A., a continuous infusion would be beneficial. As a rule of thumb, an opioid-naïve patient experiencing acute pain (that can change quickly) should only receive about one-third of her average hourly usage as a continuous infusion or 1 mg/hour of morphine (or its equivalent, which would be 0.2 mg/hour for hydromorphone). For J.A., begin a continuous infusion of 0.2 mg/hour hydromorphone in addition to her demand dose of 0.3 mg every 8 minutes. Because the onset of action of hydromorphone is about 5 minutes, shortening the lock-out interval is not a good idea because J.A. could access the next dose of hydromorphone before the effects of the initial dose can be appreciated. That could lead to significant adverse effects, such as excessive sedation and respiratory depression.
Adverse Effects
28. The next day, J.A. requested only a few demand doses and reports adequate pain relief with her PCA, but now complains of feeling slightly groggy and nauseated. Bowel sounds are noted on physical examination, and J.A. plans to try to take clear liquids later that morning. What are the adverse effects of PCA opioids, and how can J.A.'s complaints be addressed?
Opioids given by PCA can produce adverse effects similar to those given by other parenteral routes. Sedation, confusion, euphoria, nausea and vomiting, constipation, urinary retention, and pruritus can be experienced, and these can be managed by dose adjustments or pharmacologic intervention. Respiratory depression is very rare with PCA opioid administration.155 However, elderly patients, patients with severe underlying systemic disease or pre-existing respiratory compromise, and those who are receiving other sedative-hypnotics concomitantly are predisposed to respiratory depression.148 Technical problems must also be ruled out. The PCA pump should be checked to ensure that it is delivering the correct drug and dose, programming should be checked for accuracy (e.g., drug concentration, dosing interval), and the opioid reversal agent naloxone must be readily available. Monitoring for efficacy and adverse effects of PCA therapy should include pain intensity and quality, response to treatment, number of on-demand requests, analgesic consumption, BP, heart rate, respiratory rate, and level of sedation, as well as the presence of other adverse effects of opioids such as nausea and itching.
J.A.'s PCA hydromorphone dose could be reduced to manage her sedation and nausea. However, her pain control must be carefully reassessed to ensure efficacy of the newly lowered dose. An order for an antiemetic could also be provided. NSAIDs (ketorolac IM/IV or other NSAID orally) are not sedating; thus, they could be added to the analgesic regimen to provide analgesia and allow a reduction in her opioid dose. However, because of J.A.'s compromised renal function, NSAIDs should be administered with caution and in lower doses (e.g., 15 mg IM/IV ketorolac). Before administering ketorolac, J.A.'s hydration status should be evaluated to ensure that she is not hypovolemic.157 If J.A. is able to take fluids orally, PCA should be discontinued and oral analgesics administered as needed. As healing occurs, her pain intensity should lessen, and oral opioid/acetaminophen products should manage her pain adequately.
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