Postoperative Pain Management After Intraoperative Remifentanil

Remifentanil hydrochloride, an esterase metabolized opioid with rapid onset and offset of action (1,2), complements the anesthetic armamentarium of other rapidly titratable drugs (e.g., propofol and volatile anesthetics). Unlike other opioids, at the cessation of remifentanil administration at the end of surgery or in the recovery room, its pharmacodynamic effects rapidly dissipate as a result of its metabolism by nonspecific esterases (1,3). As a consequence, the residual respiratory depressant and analgesic effects normally seen with other opioids are minimized (4,5). The absence of any residual analgesic effects after remifentanil-based anesthesia means that measures must be taken to prevent pain before the remifentanil infusion is discontinued; otherwise, patients may experience unacceptable pain in the postoperative period. 1 This is particularly important because postoperative pain is often difficult to control once it becomes established. The focus of this article is on strategies for postoperative pain management after remifentanil has been administered for intraoperative analgesia. Remifentanil does not accumulate in the body (1,2,6). Approximately 5–10 min after cessation of an infusion, any analgesic effect attributed to remifentanil is insignificant. Witkowski et al. (4) demonstrated that within 10 min of discontinuing a remifentanil/O2/N2O anesthetic or alfentanil/O2/N2O anesthetic in which no prophylactic analgesics for postoperative pain management were administered, significantly more patients complained of moderate to severe postoperative pain in the remifentanil group (43%) compared with the alfentanil group (11%). Dershwitz et al. (7) found that 92% of patients reported pain after discontinuation of a remifentanil/O2/N2O anesthetic at a median time of 21 min. Thus, there may be a critical transition period of ≤30 min after surgery during which analgesia may be lacking after a remifentanil anesthetic if the appropriate procedures have not been initiated. Four different approaches to postoperative pain management are discussed in this article: start of postoperative pain management before the end of surgery; start of postoperative pain management immediately after surgery; continuing the remifentanil infusion; and decreasing the remifentanil infusion and substitution with a longer-acting opioid. The choice of a particular postoperative pain therapy depends on the anticipated postoperative pain intensity, the type of surgery performed (in- or outpatient cases, major or minor surgery) and the capacity for postoperative monitoring and supervision. Management of Anticipated Mild or Moderate Pain After Remifentanil- Based Anesthesia The transition to postoperative analgesia for patients with mild or moderate pain is straightforward (Table 1). However, the traditional strategy of administering an analgesic after postoperative pain starts is often problematic. Table 1: Postoperative Pain Management: Anticipated Mild to Moderate PainPhilip et al. (8) studied patients with remifentanil-based anesthesia for short outpatient procedures in which postoperative pain management was not initiated before the onset of pain. They found that immediate postoperative pain treatment was required by more patients and that time to first analgesic requirement was significantly shorter for remifentanil patients compared with those receiving alfentanil intraoperatively (P< 0.05). Patients undergoing outpatient laparoscopic surgery with either remifentanil or alfentanil received no additional longer-acting intraoperative analgesics for postoperative pain management. The time to first analgesic use was significantly shorter for remifentanil patients compared with alfentanil patients. Overall postoperative analgesia with fentanyl in 12.5-μg increments was required by more remifentanil patients (87%) compared with alfentanil patients (65%) (P< 0.001) while in the hospital (8). In the 24-h period after discharge from the ambulatory center, the incidence of analgesic use for pain was similar between the two groups: 82% of the remifentanil patients and 77% of the alfentanil patients. Similar results were found by Guy et al. (9) for inpatient surgery. After craniotomy for supratentorial space-occupying lesions, 64% of patients who received remifentanil and 50% of those who received fentanyl intraoperatively required analgesics for headache within 8 h postoperatively (P= 0.22). However, the median time to first analgesic administration occurred significantly earlier in patients in the remifentanil group (34 vs 136 min;P= 0.04). It is clear from this and other studies (4,8,10,11) that postoperative pain may occur earlier after remifentanil-based anesthesia than after other opioids. The traditional approach to postoperative pain management (administration of an analgesic after the onset of pain) is not very effective, especially when remifentanil is used intraoperatively; studies clearly demonstrate that pain management should be initiated before the onset of pain. In an open, randomized, comparative study of 18 female ASA physical status I or II inpatients, aged ≥18 yr, scheduled to undergo gynecological laparoscopies (12), the first patient was assigned to receive IV piritramide 2 postoperatively titrated to effect once she expressed moderate or severe pain, as no data were available at the time for the level of pain occurring after laparoscopy using a remifentanil-based technique. This first patient was given a total of 10.5 mg of piritramide, and the following 12 patients received a titrated average of 9 mg of piritramide at the first expression of pain. Shivering was seen in a few patients, regardless of whether they had received isoflurane, enflurane, or propofol, and this was successfully treated with meperidine. Therefore, the last five patients received a bolus of meperidine/pethidine immediately after tracheal extubation, before the expression of any pain. At that time, they were all fully awake and oriented to time, place, and person. None of these last five patients complained of pain or shivering, and they were discharged from the recovery room to the ward 30 min after tracheal extubation without requiring any further pain management. These results suggest that the immediate postoperative IV administration of a longer-acting opioid after remifentanil-based anesthesia for short, less painful procedures associated with mild postoperative pain provides successful pain management without compromising the rapid recovery and clear patient sensorium that characterizes remifentanil anesthesia. The administration of intraoperative nonsteroidal antiinflammatory drugs or nonopioid analgesics in such procedures also provides effective postoperative pain control in most cases without the additional use of a postoperative opioid. Anticipated Moderate to Severe Postoperative Pain Surgical procedures with moderate postoperative pain include some outpatient procedures (e.g., herniorrhaphies, laparoscopic cholecystectomies). Other more elaborate procedures, such as placement and/or removal of external fixators on the foot or hand, can also be performed on an outpatient basis. When using traditional opioids, such as fentanyl or alfentanil, intraoperatively for these procedures, postoperative pain is usually treated with a combination of local infiltration and NSAIDs/analgesics (13–17). Claxton et al. (18) compared IV morphine with IV fentanyl for “painful” outpatient procedures. The procedures in their study were classified as having moderate postoperative pain and included operative arthroscopic surgery, removal of hardware, and breast augmentation. Typically, procedures with anticipated severe postoperative pain are performed exclusively on an inpatient basis. Examples of inpatient surgery with moderate to severe postoperative pain include major abdominal, trauma, and orthopedic surgeries, which are traditionally treated with parenteral analgesics (e.g., morphine, meperidine/pethidine, or piritramide). Postoperative pain management in these patients can be complex, as cases can be more involved and associated with greater intraoperative stress. Longer-acting and more potent drugs are often used, making emergence more variable in terms of speed and quality. Ideally, the patient awakens fairly rapidly but has enough analgesia to block at least moderate to severe pain. The patient usually needs supplemental analgesics shortly thereafter in the postanesthesia care unit. Classification of postoperative pain is difficult and is usually defined by the amount of postoperative analgesia needed to control the pain. Two approaches can be used if moderate to severe postoperative pain is anticipated. In the first approach, awakening is separated from postoperative pain. This can be accomplished by performing major regional blocks using local anesthetics and/or opioids for postoperative analgesia (19–23). These techniques could provide a rapid, painless emergence from an anesthetic during which remifentanil was the primary analgesic. The postoperative regional analgesia would not prolong emergence. In the second approach, awakening is balanced with postoperative pain. This usually involves using parenteral opioids for postoperative analgesia, i.e., IV opioids such as morphine or piritramide before the end of anesthesia. In orthopedic and trauma surgery with high incidences of moderate to severe postoperative pain, the combination of intraoperative NSAIDs and a longer-acting opioid provides satisfactory transition analgesia. Management of Moderate or Severe Postoperative Pain After Remifentanil-Based Anesthesia In major surgery, which can be associated with moderate or severe postoperative pain, four studies have reported the use of remifentanil in the immediate postoperative period for the control of postoperative pain before transitioning patients to longer-acting analgesics (10,11,24,25). The postoperative pain regimen and the results related to this type of management are summarized in APPENDIX 1. Using remifentanil in the tracheally extubated patient in the immediate postoperative period requires close monitoring and supervision to ensure individual titration of analgesic versus respiratory depressant effects, which occurs in 14%–42% of treated patients (10,11,24,25). The authors of all four studies conclude that, although an infusion of remifentanil for postoperative analgesia is effective, this form of pain management may only be appropriate in certain highly monitored settings. Bolus doses of remifentanil for postoperative analgesia are associated with an increased risk of respiratory depression and apnea and are generally not recommended (10,25). By nature of its pharmacokinetic properties, remifentanil can be used as an infusion at analgesic doses. Morphine, or any other moderate- to long-acting traditional opioid, can be given via boluses or a combination of infusion and boluses (i.e., patient-controlled analgesia). In one study (24), patients received either 0.15 mg/kg morphine (M group) or a placebo bolus (R group) 20 min before the end of major general surgery. From the end of surgery to 35 min postextubation, the R group received an infusion of 0.1 μg · kg−1 · min−1 remifentanil, and the M group received a placebo infusion. Patients also received either remifentanil infusion rate increases of 0.025 μg · kg−1 · min−1 and a placebo bolus (R group) or 2-mg morphine bolus doses and a placebo infusion rate increase (M group) as required for pain management during the first 25 min postoperatively. Successful analgesia, defined as no or mild pain with adequate respiration (>8 breaths/min; SpO2 > 90%) was achieved in a greater proportion of the remifentanil patients compared with the morphine patients (58% and 33%, respectively) 25 min after extubation (P< 0.05). The median remifentanil rate for successful analgesia was 0.125 μg · kg−1 · min−1 (range 0.05–0.23 μg · kg−1 · min−1), and the median number of 2-mg morphine doses was two (range zero to five). In conclusion, remifentanil (≤ 0.23 μg · kg−1 · min−1) was more effective for immediate postoperative analgesia than preemptive treatment with morphine (0.15 mg/kg) followed by morphine boluses (up to five 2-mg boluses). Results of this and other studies (11,26) suggest that a larger initial dose of morphine may be more effective and that once pain is established it is more difficult to treat. However, using a remifentanil infusion delayed, but did not eliminate, the need for alternative analgesia. Once the remifentanil infusion was discontinued, its effects dissipated rapidly, and pain could not adequately be managed by the two divided doses of morphine. Similar results were found in a previous multicenter investigation (11). From discontinuation of the postoperative remifentanil infusion until 30 min thereafter, 32% of the treated patient population had no or mild pain. In 157 patients undergoing abdominal, spine, joint replacement, or thoracic surgery, the remifentanil infusion was continued for at least 45 min into the postoperative period (10). During the first 30 min, remifentanil was titrated to ensure that patients had no or mild pain. At the end of the 30-min period, 78% of infusion rates were in the range of 0.05 to 0.15 μg · kg−1 · min−1, 5% were <0.05 μg · kg−1 · min−1, and 17% were >0.15 μg · kg−1 · min−1. Of the patients, 64% had no or mild pain at the end of the 30-min titration period. This approach can also be modified by combining the traditional opioid with a remifentanil infusion. In this technique, the opioid is titrated together with the remifentanil infusion. As more opioid is given, the remifentanil infusion is decreased to a small (i.e., analgesic) dose rate. This can be accomplished during dressing application in the operating room or as the patient is admitted to the PACU. A moderate dose of traditional opioid is started 30 min before the end of surgery, and the remifentanil infusion is continued (at the same or slightly smaller dose) into the PACU. The remifentanil is titrated down, and more of the other opioid is given as necessary. A simple and effective transition for the immediate management of postoperative pain in patients undergoing major abdominal surgery could be the administration of a longer-acting opioid 20–30 min before the end of surgery (Table 2). While remifentanil is dosed at the therapeutic optimum until the end of surgery and provides a maximal blockade of painful stimuli intraoperatively, a bolus of morphine 15 mg or piritramide 15 mg prevents the establishment of postoperative pain once remifentanil has been discontinued. This strategy offers the advantage of initiating postoperative pain management intraoperatively with the preferred analgesic used in the recovery room and in the general ward. After the initial intraoperative bolus, patients may receive a second reduced bolus in the recovery room (RR) or may be immediately transferred to a patient-controlled analgesia device delivering the same opioid. Table 2: Postoperative Pain Management: Anticipated Moderate to Severe PainConclusion Clinical experience with remifentanil has shown that it is indeed a short-acting opioid with an evanescent action. The clinical effects of the initial pharmacokinetic and pharmacodynamic data with remifentanil have now been consistently shown across a range of different surgery and patient types. Remifentanil may enable profound intraoperative analgesia that can be titrated to individual patient requirements without compromising recovery, which is both rapid and predictable. With the intraoperative use of traditional opioids, the analgesic management of a surgical patient can be divided into two distinct stages: intraoperative and postoperative. The prolonged effects of the traditional opioids used for intraoperative analgesia, e.g., fentanyl, can be used to reduce or delay postoperative pain until treated with routine postoperative pain medication in the RR or PACU. With remifentanil-based anesthesia, the rapid offset of remifentanil means that active postoperative pain management must be considered before arrival in the RR or PACU. Postoperative pain management therefore may be integrated into one analgesic concept starting with premedication or induction, giving remifentanil before any nociceptive stimulus and continued intraoperatively. Postoperative pain therapy is started before the antinociceptive effect of remifentanil ceases and is continued in the RR and ward. Clinical results offer a number of strategies to achieve this, depending on the anticipated level of postoperative pain, the concurrent anesthetics to be used, the duration of surgery, and whether an inpatient or outpatient procedure is being performed. In outpatient surgery, it is advantageous to have the patient wake up quickly for early discharge. Short-acting drugs such as propofol, desflurane/sevoflurane, and remifentanil seem to be appropriate for this purpose. Whatever is used intraoperatively, a supplemental analgesic will be needed for the immediate postoperative period (e.g., local infiltration, NSAIDs). For inpatient surgery, rapid emergence is not as essential, and the short-acting drugs are less compulsory. However, when postoperative pain is classified as mild, these short-acting drugs can be advantageous. There are many cases in which a short-acting opioid such as remifentanil can be effective in providing intraoperative hemodynamic stability for the patient without the risk of the drug accumulating and prolonging postoperative recovery. For inpatient cases in which mild postoperative pain is anticipated, the lack of residual analgesia when remifentanil is discontinued presents fewer problems and is easily managed (Table 1). In cases in which moderate to severe postoperative pain is anticipated, an early postoperative pain management plan should be followed to provide immediate postoperative pain control and to transition patients to ward analgesia. This can be achieved by continuing the remifentanil infusion at markedly reduced (i.e., analgesic) doses into the immediate postoperative setting, ensuring appropriate supervision to enable dose titration with maintenance of adequate respiration, before transferring patients to ward analgesia (10,11,24). However, this approach may be unsatisfactory, as it can be associated with a higher incidence of respiratory depression and muscle rigidity compared with other pain managements. Moreover, after discontinuing the remifentanil infusion for discharge to the general ward, another pain treatment must be initialized to ensure adequate pain relief. Another, probably more efficient, approach to the management of moderate to severe postoperative pain may be achieved by administering a longer-acting IV opioid as a bolus 20–30 min before the end of surgery (24,26). The kinetics and dynamics of remifentanil are such that if another potent opioid is given at that time, it will not interfere with the rapid recovery profile of remifentanil, which means that postoperative analgesia can be provided without the concern of residual opioid side effects, such as respiratory depression, after the remifentanil infusion is discontinued. NSAIDs such as ketorolac, nonopioid analgesics, local infiltration, epidural, patient-controlled analgesia, or longer-acting opioids are also suitable options depending on the degree of postoperative pain, the surgical procedure, and the patient.