Prostate cancer can be managed by a variety of strategies, including extirpative and ablative surgery, radiation therapy, or even conservative methods that include active surveillance in selected low-risk patients. Given the relative lack of definite data to suggest cancer-specific outcome differences in certain groups of patients with localized prostate cancer treated by any of the above-mentioned methods, patients and their physicians are left with a variety of secondary factors to consider when making a choice between the available treatment options for their prostate cancer6. For patients, one of the most important factors in weighing prostatectomy against other treatment strategies is the potential postoperative pain and convalescence associated with surgery3.
Within the broad category of extirpative surgery, there are a variety of approaches to radical prostatectomy, including open prostatectomy, which can be performed via a retropubic or perineal approach, laparoscopic prostatectomy, or RARP. RARP has become popular because of its advantages such as three-dimensional visualization of the surgical field and shortening of the learning curve7. In addition, the incision length in RARP is rather short and postoperative pain is assumed to be minimal. While proponents of RARP suggest a variety of advantages to using a robot for pelvic surgery, including reduced blood loss, reduced transfusion requirements, improved dexterity of instruments, one of the main advantages appears to be decreased convalescence and reduced postoperative pain8-10.
One of the proposed benefits of adoptation of the da Vinci Surgical System for RARP is decreased postoperative pain compared with open radical prostatectomy, but there is limited prospective data on what a patient undergoing RARP might reasonably expect in terms of pain or analgesic requirements immediately after surgery and in the first week after recovering from the operation11. However, RARP has been reported to cause postoperative pain comparable to that of open prostatectomy in the immediate postoperative period1,12. Appropriate analgesia is needed after RARP to manage acute postoperative pain and minimize complications associated with narcotics use. However, the current literature only includes the use of opioids to treat pain in the perioperative setting of RARP2; only a small trial used oral acetaminophen as a measure for analgesia in RARP13.
Pain control during the perioperative period has focused on nonopioid analgesics instead of opioids, whose use is associated with many side effects such as ileus, respiratory compromise, delirium, hyperalgesia, urinary retention, and addiction potential14-16. Various perioperative multimodal anesthesia have emerged in the light of the nationwide focus on reducing opioid use to combat the opioid epidemic13,17. Multimodal analgesic strategies are effective in reducing these complications and accelerating patient recovery and discharge18. It is well known that postoperative stress and pain can cause hypoxia, fluid overload, immobilization, gastrointestinal paralysis, and fatigue19. These factors are interdependent and can be significantly influenced by postoperative management.
IV acetaminophen, which inhibits prostaglandin synthesis, has been approved by the US FDA for management of mild to moderate pain, management of moderate to severe pain with opioid analgesics, and reduction of fever in adults and children over 2 years of age20. Opioids such as fentanyl, hydrocodone, morphine, and oxycodone have been used perioperatively to reduce postoperative pain and discomfort21,22. Receiving nonopioid therapy would be effective not only in the perioperative period but also in the long term after surgery. Therefore, it not only avoids the side effects of opioids, but also reduces the overall cost of patient care by shortening the recovery time and length of stay in hospital21. IV acetaminophen is a fast and effective drug that can support the effects of opioids and has fewer side effects caused by NSAIDs such as gastrointestinal bleeding and renal dysfunction. Recently, several benefits of using IV acetaminophen in the perioperative setting have been shown to reduce overall opiate consumption in patients, improve analgesia, and reduce postoperative nausea and vomiting14,23-25. IV acetaminophen has been shown in several studies to be more advantageous than the oral form in the perioperative setting26,27. As a result, it is considered to be very versatile and safe for the elderly, with adequate postoperative analgesia having been achieved in patients undergoing a wide variety of surgical procedures and in many hospital settings.
Although IV acetaminophen has been studied in urologic surgery23,28, its use in prostatectomies has not been a focus and few studies on it are available. RARP is one of the most common procedures performed in men, and the results of the current study show the use of perioperative IV acetaminophen to be an ideal pain management for the patients after RARP.
Our hypothesis is that ATC administration of IV acetaminophen improves postoperative pain scores and reduce the number of on-demand analgesic drugs. We examined the effect of IV acetaminophen on ATC administration; in particular, we investigated pain scores and the number of rescue analgesics after RARP. The results suggest that ATC administration of IV acetaminophen was more effective than PRN administration in reducing pain intensity and frequency of rescue analgesics in the first two days following RARP. In addition, we encountered poor pain control when using conventional PRN dosing of analgesics and problems of unexpected and additional usage of postoperative analgesics. Given the predictable properties of postoperative pain after RARP, ATC administration of analgesics should be considered during the early postoperative period, while PRN administration should be considered once the patient's pain intensity and analgesic requirements decrease.
Urinary catheter insertion may cause various degrees of catheter-related bladder discomfort (CRBD) during the postoperative period in patients who have underwent surgical procedures, especially urinary intervention. CRBD symptoms associated with indwelling urinary catheters are similar to those of overactive bladder, including suprapubic discomfort, urinary urgency, pollakiuria, and a burning sensation29,30. This study evaluated the efficacy of ATC administration of IV acetaminophen in patients who underwent RARP and urinary catheterization for CRBD intensity. We found that intraoperative ATC administration of IV acetaminophen significantly decreased the severity of CRBD more than PRN administration did only at postoperative day 0.
We feel this information is valuable in counseling patients about their treatment options after diagnosis of localized prostate cancer, because the anxiety of potential pain associated with surgery is certainly a factor that weighs into a patient’s decision-making process. We think this study will give physicians an objective tool in counseling patients who are considering undergoing RARP but have reasonable concerns about what they may expect during their periods of convalescence. This information should be useful in counseling patients on the merits of RARP relative to other less invasive therapies for prostate cancer3.
There were some limitations in our study. First, this is a single center study of only the Japanese population, so it may not be applicable to other populations. We recommend more large-scale, well-designed RCTs on patients following RARP to improve confidence in our conclusions. Second, we investigated postoperative frequency of rescue analgesia for the evaluation of ATC administration. The rescue analgesics were different in our protocol, so we should improve the study protocol for a more accurate evaluation. Third, we did not evaluate side effects such as liver disfunction. Many drugs including analgesics were used during the perioperative period, and it was unclear whether any of the side effects were particular to acetaminophen. Therefore, we did not investigate complications in this study population.
In summary, the results of this study suggest the effectiveness of ATC dosing of acetaminophen during early postoperative recovery of patients following RARP, particularly in the first 2 days. Further research may be needed to determine if ATC administration benefits other populations following urologic surgery.