This is Dr. Joshua Rosenau, and I will be presenting this talk on non-opioid postoperative pain management strategies. These are my relevant disclosures for this talk. In decades past, physicians were often told that pain was not adequately being treated and that we were not aggressively using opioids to treat pain. We were told that patients were unnecessarily suffering because of our reluctance to use opioids. As we now know, over the last two decades, our increasingly aggressive use of opioids has created a significant crisis in this country. Now we are using too many opioids, and we need to find strategies to manage patients' pain with strategies that do not use opioids. Postoperative pain is a special case, both because of the injury that we inflict upon patients with surgery and because many patients in neurosurgery come to the operating room already having used chronic opioids. We divide pain into nociceptive and neuropathic categories, with nociceptive pain being pain typically due to tissue injury. This means that most postoperative pain tends to be nociceptive in nature. Theoretically, opioids are good treatments for nociceptive pain. However, we currently are not favoring significant amounts of postoperative opioids for several reasons. First, their lack of efficacy at treating pain long-term. Also, they can have significant side effects, such as confusion and other cognitive problems, urinary retention, nausea and vomiting, and opioid-induced constipation. Many patients feel that there is a social stigma involved with being on chronic opioids that makes them appear to be drug abusers, and there is the risk of dependence or psychological addiction with long-term use. In trying to reduce postoperative opioid requirements, a strategy involves preoperative, intraoperative, and postoperative components. This is the headline from an article in the New York Times from a few years ago written by an American expatriate who underwent a hysterectomy in Germany. She admittedly favored the American style of medicine and would bring medications over from the U.S. that they did not have readily available in Germany. When preparing for her surgery, she was initially shocked by her surgeon's insistence that she was not going to receive any postoperative pain medications and would instead manage her pain through entirely behavioral methods, period. The article depicts how she learned to listen to her surgeon's advice and actually did very well without any postoperative opioids. This is just an example of how we may manage pain that we previously thought was only treatable with opioids through, in this case, exclusively non-opioid methods. So preoperative pain management strategies work to modify pain transmission before it starts. For instance, the study from 2011 involving 29 patients who were undergoing a lumbar fusion were randomized to either preoperative oral methadone or intraoperative intravenous sufentanyl, period. The preoperative methadone group had a 50% lower postoperative opioid requirement and lower visual analog scale pain scores. The principle behind this is that the preoperative administration of methadone stopped transmission of pain by blocking opioid receptors at the time the injury was occurred in surgery and the pain cascade began. By blocking this initial pain cascade, there is a lower pain requirement to treat postoperatively. Oral gabapentin and pregabalin are both medications that were initially approved with anti-epileptics and both have some neuropathic pain indications right now. For both of these, most of their current American prescriptions are for the treatment of neuropathic pain. One review of randomized controlled trials of preoperative gabapentin showed that the mean reduction in visual analog scale was 10.7 millimeters, which is basically one unit out of a 10 centimeter scale, and the total reduction of opioid use was 7 milligrams at 24 hours. The question is, is this really significant or does it validate the lack of role in using oral gabapentin for nociceptive pain? Oral gabapentin in some centers is a significant part of the overall preoperative strategies to reduce pain and is part of some centers' ERAS or enhanced recovery after surgery protocols as well. In Anesthesia Analgesia in 2012, Clark and colleagues reviewed the trials of preoperative gabapentin and pregabalin for the prevention of chronic postoperative pain. They found three trials of pregabalin that fit their criteria. All of these showed a significant reduction in chronic postoperative pain. There were also eight trials of gabapentin, which met their criteria, four of which showed a significant reduction in chronic postoperative pain. Interestingly, this reduction was not dependent on the dose of the medications and the reduction was more significant for pregabalin. A randomized trial investigating gabapentin versus placebo in patients undergoing lumbar fusion used a 150 mg gabapentin dose preoperatively, followed by 150 mg daily. All the patients were given access to PCA pumps postoperatively. This study showed that while there were fewer complications in the gabapentin group, there was no significant change between the groups in the pain level, opioid usage in the hospital before discharge, length of stay, or performance on physical therapy. Another meta-analysis of randomized controlled trials of pregabalin for acute postoperative pain involved a total of 7,200 patients. Most of the studies were graded as rather low quality evidence, and overall the 24-hour morphine sparing effect was also rather low. A neurosurgical trial, which was a double-blind randomized controlled trial involving 88 patients who were given either pregabalin or placebo, showed that there was a reduced opioid consumption and NRS score among the patients who got pregabalin. However, only the NRS score at one month was considered significant. The NRS change at three months was not significant. So the question still arises, does pregabalin prevent long-term postoperative pain? The evidence seems to show that there is a mild reduction initially after surgery, but so far there is no good evidence that long-term it produces a sustained reduction in postoperative pain. Other strategies often include the very standard infusion of local anesthetic into the incision region before the scalpel hits the skin. There have been numerous trials in many disciplines that demonstrate a postoperative reduction in pregabalin scores and opioid use from this. Many of these trials are in the thoracic surgery literature period. Again, the principle behind this is preventing the afferent barrage of pain signals from bombarding the nervous system and thus setting up a cascade of pain for later. One study in neurosurgery from 2010 involving 25 patients undergoing posterior cervical fusion involved these patients having a subfascial catheter for intra-wound postoperative buprenorphine infusion implanted. These patients did use significantly less opioid when compared to historical control patients. Their NRS was lower and their length of stay was significantly lower. Similarly, looking at patients undergoing lumbar discectomy who were divided into two groups, everybody got wound and muscle local anesthetic, but group 2 received a small pledge of fat soaked in methylprednisolone that was placed over the decompressed root. This study showed that while the visual analog scale pain ratings were not significantly different, the group who received the fat soaked in steroid used significantly less postoperative Demerol. A randomized trial from 2010 looking at 104 patients divided into two groups undergoing lumbar surgery, patients received either placebo or 0.5 mg per kg infusion of ketamine intravenously at anesthesia induction, and then this was continued until wound closure. The results of this study showed that the patients receiving the ketamine had significantly lower morphine equivalents at 24 and 48 hours, as well as lower pain scores in the recovery room and out to six weeks. And more interestingly, when the patients were then further stratified by their preoperative morphine use, it was noted that the effect was not significant for patients who were on lower amounts of preoperative opioids and the effect was more significant for patients who were on larger amounts of postoperative opioids. Studies such as the one shown previously in this presentation involving the subcutaneous infusion of bupivacaine have led to the development of long-acting liposomal bupivacaine injections. These are injections into the wound that have a delayed release of the bupivacaine into the wound over anywhere up to 96 hours. Studies looking at spinal surgery and randomizing patients or using case control studies with liposomal versus standard bupivacaine showed that the liposomal bupivacaine patients, at least in this study from 2016, used about half the amount of morphine postoperatively period. However, this decrease did not actually reach statistical significance and there was also no significant difference in the length of stay or complications such as wound infection. There have been further other studies looking at the utility of liposomal bupivacaine. This study from 2016 involved 80 patients undergoing an open lumbar microdiscectomy, all of whom received skin infiltration with standard bupivacaine and 40 of the 80 patients received liposomal bupivacaine above the fascia and all patients had available other standard postoperative pain treatments. The liposomal bupivacaine cohort had a non-statistically significant decrease in their length of stay by one day, but there was no significant difference in the overall visual analog scale ratings of pain postoperatively for the two groups. There was no significant difference in the 30-day emergency department visits for pain from either group and the liposomal bupivacaine group did have a significantly decreased time using postoperative IV opioids, though. However, again, this result does call into question the overall utility of the medication. Intravenous acetaminophen is a relatively recent addition to our armamentarium that has garnered a significant amount of interest as a non-opioid intravenous pain treatment. This study from the Journal of Neurosurgery in 2018 was a blinded RCT involving 204 patients who either received 1,000 mg of IV acetaminophen every 8 hours for 48 hours versus placebo, and as you can see from this table from the paper, there was no significant difference in the narcotic requirements out to 48 hours. This was a study involving patients undergoing craniotomy rather than spine surgery. Interestingly, there was one time point, which was postoperatively at 24 hours, where the treatment group did have a statistically lower pain score, but that was the only time point in the 48 hours of the study period. Ketorlac is another intravenous medication, in this case a non-steroidal anti-inflammatory medication that has also been used frequently as a non-opioid postoperative pain strategy. There is always some concern with NSAIDs and the risk of hemorrhage. This study from the Journal of Neurosurgery Pediatrics in 2016 was a retrospective review from a single center looking at 1,451 pediatric patients whose mean age was just under 5 years old who've undergone a variety of pediatric procedures, and of these patients, almost 1,000 received intravenous Ketorlac. Out of the entire cohort, there were 7 clinically significant hemorrhage, which involved 4 patients who'd received Ketorlac and 3 who had not. The actual percentage of each cohort that had a significant hemorrhage was actually lower in the Ketorlac group than in the non-Ketorlac group. Importantly, there was no difference in the overall hemorrhage rate, including radiographic, not clinically significant hemorrhages, even though the Ketorlac group percentage was slightly higher than the non-Ketorlac group. Another review from 2013 looking retrospectively at over 4,000 patients undergoing craniotomy of which 1,500 received postoperative Ketorlac, there were a total of 43 intracerebral hemorrhages, but only 8 were in the cohort that had received Ketorlac, and the relative risk for an intracerebral hemorrhage postoperatively with Ketorlac was significantly lower for the Ketorlac group than the group that had not received the NSAID. The comprehensive discussion of ERS protocols is beyond the scope of this presentation, but just to briefly discuss the topic, ERS protocols vary by institution. Each center tends to develop their own customized version of this. They involve preoperative preparation, such as weight control, sleep apnea management, management of other comorbidities, such as diabetes and hypertension, and aggressive tobacco and alcohol cessation measures. On the day of surgery, patients are often given a carbohydrate load several hours preop, such as a sports drink, as discussed earlier in this presentation, pre-anesthesia medications that can be oral or intravenous are given, intraoperative strategies, such as maintaining proper body temperature, fluid management, and, at times, intravenous ketamine are conducted. This includes other measures, such as the liposomal bupivacaine infusions that were mentioned previously, and postoperatively, early removal of urinary catheters and mobilization, gum chewing to improve bowel function in those patients that have had intra-abdominal procedures, and the use of opioid alternatives, such as were described here, are all part of an overall strategy to enhance recovery from surgery and reduce complications on length of stay. Thank you for taking the time to log on and watch this presentation.

non-opioid postoperative pain management

aggressive use of opioids

nociceptive and neuropathic pain

limitations and side effects of opioids

alternative pain management strategies