Peak VAPS scores occurred at 24 and 42 h postoperatively in the RLDH and MHRT groups, respectively. The most postoperative requested and delivered PCEA doses occurred at 18 and 36 h, respectively, in the RLDH group and at 24 and 6 h, respectively, in the MHRT group.
Neither IV nor oral opioids were administered to any patient in the MHRT group during the postoperative study period. However, in the RLDH group, four patients received IV fentanyl with the total cumulative dose being only 150 μg or less for each of these patients within the first 48 h postoperatively. No oral opioids were administered to RLDH patients.
Living related liver donation provides for the expansion of the potential pool of allografts available for transplantation (2). It is important that the overall success of this procedure is determined by the outcome of both the donor and the recipient. Although RLDH is considered safe, with infrequent major intraoperative and postoperative complications, one should evaluate the medical, psychological, and financial impact of donation as well as the resulting donor quality of life (3). Significant postoperative pain after RLDH can cause physical and psychological distress in an otherwise healthy group of patients. Living liver donation, however, as shown by Trotter et al. (3), did not affect the donor’s relationship with the recipient, and all patients stated they would donate again if necessary. In addition, the authors observed that postoperative pain was more intense than expected in the donor group and more severe when compared with the recipient patient group.
In this study, we found that despite the use of thoracic PCEA infusion catheters, RLDH patients still experienced significant postoperative pain. By comparing postoperative pain in RLDH patients with patients who underwent MHRT, we conclude there may be additional factors (beyond the significantly longer duration of surgery observed) predisposing this patient population to increased postoperative pain perception. As elucidated by Trotter et al. (3), patients who underwent RLDH had no abdominal symptoms or discomfort preoperatively, thereby making postoperative pain more noticeable. In contrast, some patients undergoing MHRT may already have associated abdominal pain preoperatively. Therefore, postoperative pain, although present, may be an improvement compared with their preoperative presentation. However, in this study, we did not specifically investigate the presence of preoperative pain in the MHRT group.
In both patient groups, the methods for surgical exposure were similar. However, overall RLDH patient surgical time was significantly longer than that observed in MHRT patients. It is possible that longer durations of tissue retraction and surgical manipulation may result in modulation of the neuroendocrine system, thereby causing more postoperative pain. The central nervous system responds to surgical stimulation in dynamic fashion with noxious stimuli sensitizing central neural structures involved in pain perception. Neuroplasticity (altered central nervous system sensory processing) is responsible for changes in pain perception after nociceptive stimulation (4). A prolonged duration of surgical stimulation can produce central sensitization and increases patient sensitivity to noxious stimuli over an expanded receptive field (i.e., hyperalgesia). In addition, peripheral nerve sensitization may also influence postoperative pain perception. In this case, prolonged tissue retraction can sensitize nociceptors, resulting in hyperalgesia at the site of injury as well as in surrounding nontraumatized tissue. Chemical mediators from damaged tissue, such as leukotrienes, bradykinins, histamine, and arachidonic acid metabolites, and increased activity of the sympathetic nervous system are potential modulators for this phenomenon (5).
In this study, PCEA infusions were activated intraoperatively after surgical incision in all patients in both groups. In the RLDH group, all patients underwent acute normovolemic hemodilution after induction of general anesthesia. Once finished, the PCEA basal rate infusions were started. In the MHRT group, all PCEA infusions were begun once the major portion of the hepatic resection was completed. Further prospective study is needed to examine whether application of the somewhat controversial concept of preemptive analgesia through administration of local anesthetic with or without opioid into the epidural space before skin incision would indeed decrease the effects of neuromodulation and plasticity on postoperative pain (6,7) and improve postoperative pain control. As demonstrated by Katz et al. (6) preincisional administration of a local anesthetic with fentanyl into the epidural space decreased postoperative morphine PCA consumption as well as postoperative hyperalgesia. The effect on postoperative pain was evident with standardized movement pain scores with preemptive administration of epidural local anesthetic decreasing the pain score. However, the authors stressed that psychological and mental health factors may also play a significant role in postoperative pain perception. In contrast, only pain scores at rest were evaluated and analyzed in this retrospective study.
Despite similar surgical techniques between patient groups, the peak VAPS scores occurred at 24 and 42 hours postoperatively in the RLDH and MHRT groups, respectively. Wilder-Smith et al. (8) demonstrated a biphasic nature of postoperative neuroplasticity. In the first 24 hours postoperatively, the predominant neuroplastic response was inhibition, whereas in the later postoperative period an excitation response with a reduction in pain threshold was observed. Interestingly, the authors found a decreased pain threshold at sites not directly affected by surgery, suggesting supraspinal neuroplasticity. In the present study, RLDH group patients experienced peak VAPS scores earlier in the postoperative course, indicating a possible greater influence from supraspinal excitory neuroplastic modulation.
All donor patients were healthy individuals without previous exposure to major surgical procedures. The pain tolerance in a patient group such as this may be less than in those patients previously exposed to procedures, such as patients with hepatic tumors. In addition, the donors all underwent RLDH for altruistic reasons without any medical indications. After completion of surgery and on awakening, the altruistic motivation may be suppressed as a result of the common sequelae of having undergone an extensive surgical procedure. Thus, donors were not benefiting medically from RLDH, but were, on the contrary, being temporarily debilitated as a result of part of a healthy organ being removed. This may make these patients more vulnerable to pain exaggeration. Diaz et al. (9) reported postoperative pain as being more than anticipated in 44% of donor patients despite the universal use of epidural analgesia and PCA. The same authors also made the interesting observation that female donors with a surgical history had more postoperative pain complaints than did male donors with a surgical history (9). Psychosocial variables including extent of social support, mental health status, degree of optimism, coping style, and mood have all been shown to influence the pain experience (6) and may have influenced the results of this investigation. Thus, the conscious pain experience is the result of chain processing occurring in the central nervous system, making the initial nociceptive event one of many contributing elements in a multifactorial pain experience (8). Unfortunately, because of the retrospective nature of this study, we were not able to obtain this additional information in the preoperative period.
We were surprised to find that patient postoperative VAPS scores had only a weak correlation with either the number of PCEA doses requested or delivered in either group. We believe this observation can be at least partially explained as a result of inadequate preoperative patient education regarding the use of PCEA catheter infusions. In addition, patients in both groups received similar postoperative nursing care. This included similar nursing competencies in assessing postoperative pain in patients with PCEA infusion catheters, as well as similar nursing staff to patient ratios in the PACU, SICU, and on the ward for both patient study groups. Thus, a difference in postoperative nursing care is an unlikely reason for the differences in postoperative pain observed.
This study has several other limitations to consider when designing possible future investigations to explore this topic. Because of the retrospective nature of the data collection, several variables, such as the initiation, activation, and anesthetic solution to be administered via PCEA infusion, were not controlled for. Also, no protocol was used for rescue dosing of epidural catheters if inadequate pain control was encountered. In several instances, patients received intermittent “clinician doses” of epidural anesthetic solution in addition to the preprogrammed patient-activated boluses. However, only minor adjustments were made to either the PCEA infusion catheter demand doses or basal infusion rates in those patients. In addition, the possible under-use of supplemental IV opioids should also be addressed in any future study, as well as more frequent (less than every 6 hours) postoperative pain assessments that may prompt more expeditious therapeutic intervention. The use of epidural catheters in hepatic surgery is controversial. Yong et al. (10) found no significant differences in living donor satisfaction regarding postoperative pain control in those receiving either IV PCA opioids or epidural analgesia. Also, the authors cautioned that postoperative coagulopathy after partial hepatectomy may interfere with the safe removal of the epidural catheter. However, no complications were reported in this particular study. In contrast, in a the review of 22 donor left lateral hepatectomies by Choudhry et al. (11) the authors observed superior postoperative pain relief with thoracic epidural analgesia without any reported complications. Borromeo et al. (12) described the observed postoperative perturbation of serum coagulation tests in patients after right hepatectomy, including increases in both prothrombin and activated partial thromboplastin times, with a concomitant decrease in the serum platelet count. In our experience, the resultant abnormal coagulation profile related to RLDH or MHRT typically normalizes 2–3 days after surgery and has not affected the management of any PCEA infusion catheter. However, postoperative vigilance after major hepatic surgery is paramount with close neurologic monitoring warranted.
In this study, RLDH patients experienced significantly more postoperative pain as compared retrospectively with patients who underwent MHRT. As a result of the longer surgical duration for donor hepatectomy, neuroplasticity may play a role in exaggerated postoperative pain perception along with various psychological factors, although this is unknown at this time. In addition, further prospective studies are needed to determine if the application of preemptive analgesia in these patients may offer some advantage for postoperative pain control. Although advocates for the use of PCEA infusion catheters in these patients, we believe these individuals require more extensive preoperative teaching on the use of these devices. In addition, the concept of PCEA infusion catheter dosing should be continually reinforced by those directly caring for these patients. Despite several recognized limitations of this study, we believe that the observed increased pain after RLDH, as compared with that seen after MHRT, is a real and likely multifactorial phenomenon that requires further prospective investigation.
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© 2004 International Anesthesia Research Society
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