Our results indicate that pre-emptive administration of oral pregabalin does not reduce postoperative opioid consumption, PONV, PACU time or LOS in patients undergoing RALP. Considering the possible side effects related to use of pregabalin14, our results do not encourage to use pregabalin in patients undergoing RALP. Instead we were able to demonstrate the feasibility of a new multimodal analgesic protocol that has not been earlier introduced for patients undergoing RALP. Patients receiving this regimen needed only small amount of opioids for postoperative pain and can be discharged soon after the procedure.
The groundwork of multimodal analgesic regimen is formed by paracetamol in combination with a non-steroidal anti-inflammatory drug (NSAID) or a cyclooxygenase 2 (COX2) inhibitors, when no contraindications are encountered, and local anesthesia– a combination proposed by the guidelines from the American Society of Anesthesiologists task force on acute pain management20 Ketamine, a traditional anesthetic, has been shown to be an effective adjunct for postoperative analgesia at low doses.21 Systemic corticosteroids, like dexamethasone are often used for the prevention of PONV, but have also been shown to reduce postoperative pain in many types of surgery.22
Trabulsi et al (2010) demonstrated in their retrospective study a positive effect of multimodal analgesia on postoperative opioid consumption after RALP.7 In addition to paracetamol and celecoxib (COX2-inhibitor), their regimen included 150 mg single-dose of pregabalin as premedication. Compared to conventional analgesic regimen use of above-mentioned premedication decreased postoperative opioid consumption. In more recent meta-analyses pregabalin as a component of postoperative acute pain management protocol has been generally questioned. While pregabalin may have a minimal opioid-sparing effect, the risk of serious adverse effects seems to be increased and a routine use of pregabalin for postoperative pain treatment cannot be recommended.14,23
Our multimodal analgesia regimen included esketamine, betamethasone and metamizole-pitofenone. Pre-emptive use of esketamine for postoperative pain has been studied in several patient groups and there is strong evidence suggesting its use intraoperatively.24 Use of glucocorticoids as an adjunct to general anesthesia has been shown to decrease postoperative pain, but glucocorticoids have previously studied mainly in orthopedic patients.25 There is also evidence that intraoperative use of betamethasone decreases PONV after general anesthesia.26 Single dose metamizole has been shown to have good analgesic effects on postoperative pain27 and it is often administered together with a spasmolytic compound pitofenone. The above mentioned intraoperative multimodal analgesia has been used in Turku University Hospital for RALP patients over eight years.
Multimodal analgesia often includes also utilization of local anesthetic-based regional analgesic techniques. In our multimodal analgesia protocol patients received local anesthetic infiltration to the troacar openings. Transversus abdominis plane block (TAP) has been recently introduced as part of multimodal anesthesia and analgesia of RALP28. TAP has been shown to reduce pain and opioid consumption after RALP29 and may be done by the surgeon under visual control or by anesthesiologist under ultrasound guidance. However, to reach a high success rate, this procedure requires training.30
Due to its minimally invasive nature, the RALP is associated with decreased pain levels compared to open prostatectomy.3 Immediately after RALP, the main source of pain/discomfort is abdominal, followed by catheter related, penile and bladder-spasm-related discomfort. With current analgesic regimens, abdominal pain after RALP is mild to moderate – on average rated 3 to 4 of 10 on a pain scale.4 A recent systematic review on the optimal perioperative pain regimen for radical prostatectomy concluded that there is a lack of evidence to develop an optimal pain management protocol in this patient population and specific studies comparing pain and analgesic requirements for open and minimally invasive surgical procedures are warranted.8 In the face of current opioid crisis, an attempt to minimize the use of opioids perioperatively should become a part of standard care for all surgical patients.18,19
The majority of patients undergoing RALP at high-volume centers are discharged on the first postoperative day.31 In our study the median of LOS was 31 hours, which is in line with earlier findings. Postoperative pain was well controlled and major part of patients did require opioids on first postoperative day. The main reasons for discharge later than on the first postoperative day were logistical i.e. patient living in the rural areas needing a special means of transportation or suspicion of acute postoperative complication such as bleeding or infection.
Perioperative dosing of pregabalin has been recently surveyed in various laparoscopic surgery patient populations. In a very recent randomized controlled trial patients undergoing laparoscopic colorectal surgery and receiving two doses of oral pregabalin had lower postoperative opioid consumption but similar pain scores compared to control group.32 A prospective study with patients undergoing laparoscopic living donor nephrectomy receiving two doses of oral pregabalin had lower postoperative opioid consumption but similar pain scores compared to the control group.33 Contrary to these, a recent randomized controlled trial with similar setting to our study concluded that pregabalin together with celecoxib offered no analgesic superiority over standard opioid care in postoperative pain therapy following laparoscopic cholecystectomy. Recent large systematic review including 39 trials on endoscopic abdominal surgery found no clinically significant analgesic effect for perioperative used gabapentinoids. Use of perioperative pregabalin was associated with greater risk of adverse events.34 Our findings together with this systematic review suggest that routine use of pregabalin for patients undergoing laparoscopic surgery cannot be recommended.
Our retrospective study has some limitations. First, while patients after RALP experience mild to modest pain and the amounts of opioids are modest as well, it is difficult to demonstrate meaningful difference. Furthermore, owing to the lack of data, we were not able to reliably assess the postoperative pain scores, or the amount of opioid use after discharge. For the same reason, we were not able to assess the incidence of chronic pain and hyperesthesia in the long term. The retrospective design of the study could have also affected the results, even when only consecutive patients were included to avoid any selection bias. On the other hand all patients in our study received a standardized multimodal anesthesia and only few experienced surgeons were involved in the procedure. Moreover, we were able to demonstrate an effective multimodal anesthesia protocol associated with few side effects and a short LOS.
To strengthen the findings of our study, the effect of pregabalin on postoperative opioid consumption and pain of patients undergoing RALP could be studied in a prospective manner. Another medication worth giving an opportunity as a part of multimodal analgesic regimen would be alpha-2-agonist clonidine, which has been shown to reduce postoperative opioid consumption35,36, but has not been studied in patients undergoing RALP. While deep Trendelenburg position during RALP often comes with a rise in mean arterial blood pressure37, clonidine’s ability to provide perioperative hemodynamic stability could be of use.
According to our findings, patients undergoing RALP that receive paracetamol and etoricoxib as premedication, esketamine, betamethasone, metamizole-pitofenone, fentanyl and local infiltration anesthesia intraoperatively, and paracetamol for postoperative pain need only small amounts of opioids postoperatively. While our findings demonstrated that routine use of pre-emptive pregabalin does not decrease postoperative opioid consumption in patients undergoing RALP, perioperative use of pregabalin may still have potential benefits in patients with a history of neuropathic or chronic pain.