#313 Individualized Multimodal Analgesia

“Opioid-sparing” sounds like an automatic win until you look closely at what replaces the opioids. We take on one of the toughest questions in modern anesthesiology: how do we reduce opioid-related harm without trading it for medication interactions, kidney injury, bleeding risk, rebound pain, or poorly controlled postoperative pain?

We break down what individualized multimodal analgesia really means in day-to-day anesthesia practice. That starts before the first dose is ordered, with a preoperative assessment that weighs comorbidities, baseline renal function, hydration status, and potential drug-drug interactions. We also dig into the medication safety side of multimodal protocols, including why CYP2D6 matters for common oral opioids like hydrocodone, oxycodone, and tramadol, and how CYP2D6 inhibitors such as certain antidepressants can change opioid effectiveness and even extend opioid use after discharge.

Regional anesthesia remains a cornerstone, but we stay honest about the pitfalls: incomplete coverage, visceral pain that sneaks through, and the timing mismatch that can trigger rebound pain 12 to 24 hours after a single-shot block, sometimes when the patient is already home. We also discuss when continuous peripheral nerve blocks may better match the duration of perioperative stress and inflammation, plus the practical barriers that determine whether advanced regional techniques are feasible.

If you care about opioid-sparing anesthesia, patient safety, and better postoperative recovery, listen and share this with a colleague. Subscribe to the podcast, leave a review, and tell us: what’s one change you’ll make to your multimodal analgesia plan after hearing this?

For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/313-individualized-multimodal-analgesia/

© 2026, The Anesthesia Patient Safety Foundation

Transcript

The Future Of Pain Control

SPEAKER_00 0:00

As we look forward to the future of anesthesia care, I envision a continued shift towards truly individualized multimodal analgesia, where the focus is not on eliminating a specific medication class, but on selecting the right combination of therapies for each patient.

Alli 0:15

Our show today focuses on two of the APSF patient safety priorities: opioid-related harm and medication safety. When it comes to opioid-sparing anesthesia, this practice can help to mitigate opioid-related harm, which is important to help keep patients safe during anesthesia care. But we need to consider that if we remove opioids from our toolbox, this may introduce different patient risks, including medication interactions, poorly controlled pain, and even acute kidney injury. Hello

Why Opioid Decisions Affect Safety

Alli 0:49

and welcome back to the Anesthesia Patient Safety Podcast. I'm your host, Allie Bechtel. Today we are challenging you to evaluate your anesthesia practice when it comes to opioid administration, multimodal analgesia, and patient safety. The big takeaways are number one, it starts with the preoperative assessment and evaluation of coexisting diseases, baseline renal function, hydration status, and potential drug-drug interactions to make a plan for analgesic selection and reduce the risk of acute kidney injury and bleeding. Number two, multimodal analgesia with regional techniques, non-opioid medications, and low-dose opioids when needed has been shown to improve pain control and functional recovery while minimizing opioid-related adverse events. And number three, frequent patient reassessment is important to evaluate pain scores, sedation level, respiratory status, ambulation, pulmonary hygiene, appropriate monitoring, adverse drug effects, and functional recovery, with changes made to the analgesic plan as needed, depending on the patient's condition. Before

Sponsor Thanks And Safety Mission

Alli 2:00

we dive further into the episode today, we'd like to recognize GE Healthcare, a major corporate supporter of APSF. GE Healthcare has generously provided unrestricted support to further our vision that no one shall be harmed by anesthesia care. Thank you, GE Healthcare. We wouldn't be able to do all that we do without you. Our

Featured Article And Author Voices

Alli 2:24

featured article is Reconsidering Opioid Sparing Anesthesia: The Case for Individualized Multimodal Anogesic Care by Shirley Burns and Dunworth. This is an APSF newsletter article that was published online May 14th, 2026. To follow along with us, head over to apSF.org and click on the newsletter heading. The first one down is newsletter articles. Then you can scroll down until you get to our featured article, and I will include a link in the show notes as well. We have exclusive content today from two of the article authors. First up, we are going to hear from Lori Shirley, and I asked her what got her interested in this topic.

SPEAKER_01 3:04

Hi, my name is Lori Shirley, and I'm a CRNA and NIH-funded pain and opioid researcher at Vanderbilt Health in Nashville, Tennessee. I got interested in the topic of patient safety considerations with multimodal analgesia while writing a grant on the role of cytochrome P450, CYP2D6 gene, on opioid effectiveness. Not only does a person's genotype affect opioid metabolism and therefore analgesia and side effect severity, but also so did the interactions with other drugs they are taking that may inhibit CYP2D6 activity. Strong CYP2D6 inhibitors include many of the antidepressants our patients are taking as they come into surgery, such as fluoxetine and peroxetine. Other inhibitors may be introduced as part of our multimodal protocols, such as silicoxib and duloxetine. And this is just one gene. As the number of medications one is taking increases, the risk of drug gene interaction increases exponentially. This is the multimodal paradox. And as new medications are being introduced into our multimodal toolbox, we need to be mindful of these concerns.

Alli 4:14

Thank you, Lori, for helping to introduce this topic and help kick off the show today. Now it's time to get into the article. Over the past 10 years, we have seen a shift towards reduced opioid administration due to the opioid epidemic, enhanced recovery pathways, and concern for opioid-related adverse events. This has led to the practice of opioid-sparing anesthesia with a focus on multimodal analgesia, which includes regional anesthesia techniques, non-opioid systemic analgesics, and adjunctive modalities to eliminate interoperative and postoperative opioid use. Following a strict protocol may introduce different patient safety risks, including inadequate analgesia, increased physiological stress, renal injury, bleeding, or unsupervised opioid escalation after discharge from the hospital.

When Opioid Sparing Backfires

Alli 5:08

Let's take a look at some of these unintended consequences now. First up, we have the risk of inadequate pain management, which may lead to increased risk for postoperative delirium, delayed recovery, and chronic pain. What does the literature tell us about non-opioid analgesia and analgesic efficacy? The Initiative on Methods, Measurement and Pain Assessment in Clinical Trials, or Impact Group, evaluated 73 randomized controlled trials on opioids-bearing analgesic approaches. They found that only 18% included pain as a primary outcome. Remember, our goal here is adequate pain relief following surgery, not just decreased opioid administration. We need studies that evaluate pain measures, perhaps at multiple prior endpoints like opioid use and pain, or using a single composite endpoint of opioid use and pain, or even using a non-inferiority study design for non-opioid analgesics on pain outcomes following surgery. I will include the citation to this article in the show notes. If you're thinking about doing any research on opioid-sparing analgesia, we hope that you will use this research for considerations and recommendations for research design and conduct, analysis, and interpretation of clinical trials.

CYP2D6 Interactions And Prolonged Use

Alli 6:29

Next up, we have considerations for increased risk of drug-drug interactions. This is where we get into the medication safety. When we talk about multimodal analgesia, we are often talking about three or more medications that act at different receptors. When patients take five or more medications, there is an 80% risk of potential cytochrome P450-mediated interactions. The CYP2D6 enzyme is something that we need to pay attention to since it metabolizes most oral opioids, including oxycodone, hydrocodone, and tramidol. Strong CYP2D6 inhibitors include fluoxetine, buproprion, peroxetine, and moderate inhibitors include duloxetine and salicoxib. When there is concurrent consumption of another medication metabolized by CIP2D6, there may be competitive inhibition by stronger affinity CYP2D6 substrates and non-competitive inhibition interactions by CIP2D6 inhibitors. Let's look at the 2024 article by WIT and colleagues: Prolonged Postoperative Hydrocodone Usage Due to Psychotropic Drug Interaction. This study involved 224 patients hospitalized with lower and limited upper extremity injuries who were prescribed hydrocodone as well as a psychotropic medication. There were two patient subsets, including 178 patients on a psychotropic medication that was a CYP2D6 inhibitor, and 46 patients on a medication that did not inhibit this enzyme. For the results, patients on a psychotropic medication with inhibitor activity had a longer duration of opioid use after discharge with a median of 33 days compared to only four days in the non-inhibitor group. There were no significant differences in in-hospital pain outcomes. Thus, patients are at risk for increased duration of postoperative opioid use when taking a CIP2D6 inhibitor. And these findings were replicated in a study following joint replacement surgery as well. Another surgery revealed that for geriatric patients, after controlling for age, comorbidities, and kidney function, each additional CYP2D6 inhibitor medication decreased the enzyme activity by half. This is an important drug-drug interaction that we need to be aware of when designing multimodal analgesia plans, especially for patients taking medications with CIP2D6 inhibitor activity.

Non-Opioid Risks: Kidneys Breathing Bleeding

Alli 9:08

Our next consideration involves risks from non-opioid analgesics, and yes, there may be adverse effects from common non-opioid medications used as part of a multimodal analgesia strategy. Gabapentin administration is associated with respiratory and central nervous system depression, cognitive dysfunction, and gabapentin misuse. Due to some of these concerns, gabapentin has been removed from many enhanced recovery protocols. There are concerns about kidney injury following administration of non-steroidal antiinflammatory drugs and cyclooxygenase 2 selective inhibitors in older patients and patients undergoing cardiac, urological, or robotic surgeries. Another concern is bleeding risk, especially with non-selective NSAIDs, especially in patients taking other antiplatelet medications and undergoing high bleeding risk procedures. Keep in mind that overall, these medications are likely safe and have an important role in multimodal analgesia. Have you ordered tramadol recently? This is a weaker mu agonist that may be used as a rescue opioid, but tramadol use is associated with increased risk of dementia and prolonged postoperative opioid use compared to other opioids.

Nerve Blocks And Rebound Pain

Alli 10:29

We are moving along nicely and have made it to considerations for peripheral nerve blocks. Regional anesthesia has a very important role in multimodal analgesia protocols, but we need to remain vigilant for adequate pain control and options for rescue. Here are some concerns: inappropriate block selection and incomplete analgesia. For example, when a somatic block is used for an abdominal, pelvic, or thoracic procedure, an epidural analgesia would have provided improved pain control. Poorly controlled visceral pain leading to sympathetic activation, increased myocardial oxygen demand, impaired respiratory mechanics, and delayed recovery. Potential for false sense of analgesic adequacy following technically successful block. Incomplete or time-limited analgesia that may result in delay in administration of rescue pain medications, timing mismatch following single-shot blocks, leading to significant rebound pain 12 to 24 hours after the block, which may be at home after discharge. And rebound pain, leading to increased opioid consumption, unplanned healthcare utilization, and patient distress. The use of continuous peripheral nerve blocks offers a longer duration for analgesia and a better match for the duration of perioperative stress response and inflammation. This may help to decrease rebound pain and unsupervised rescue opioid use. The availability of advanced analgesic strategies like continuous peripheral nerve blocks, as well as other advanced regional anesthesia approaches and adjunctive technologies, including hot and cold compression devices and perioperative cryoneurolysis, varies depending on the institution and care setting. Limitations may include having a pathway for follow-up, appropriate training and competency, cost, insurance coverage, and other institutional resources. In addition, this is an example of an emerging technology, and long-term safety data and standardized guidelines are still being studied and created. Okay,

Building An Individualized Analgesia Plan

Alli 12:42

now we need to bring it all together to our new goal for opioid-sparing, patient-centered analgesia that is safe, effective, and individualized. This approach uses judicious opioid use when appropriate, combined with multimodal analgesia, including regional techniques, non-opioid medications, and low-dose opioids when needed to improve pain control and functional recovery with minimal opioid-related adverse effects. This is how we accomplish our goal. Careful preoperative assessment and planning with evaluation of comorbidities, baseline renal function, hydration status, and potential drug-drug interactions. Incorporation of the preoperative assessment into the perioperative workflow guided by patient-specific risk profiles. Frequent reassessment with pain scores, as well as evaluation for sedation, respiratory status, ability to ambulate, participation in pulmonary hygiene or physical therapy, adverse drug effects, and overall functional recovery. And dynamic adjustment of the analgesic plan to avoid poorly controlled pain and averse events. The author summarized the goal for aligning analgesic plans with patient physiology, surgical factors, and postoperative care capacity to achieve the broader mission of peroperative safety rather than prioritizing opioid avoidance targets. There is a call to action for anesthesia professionals to incorporate a flexible, patient-centered, opioid-sparing, multimodal approach that supports perioperative safety and recovery while addressing the complexities of surgical pain management. Before

Future Vision And Practical Challenge

Alli 14:25

we wrap up for today, let's go behind the scenes again to hear from another one of the authors.

SPEAKER_00 14:30

Hello, my name is Michael Burns. I am a nurse anesthesist and assistant program director of the Nurse Anesthesia Program at Vanderbilt University School of Nurse Anesthesia.

Alli 14:39

I asked Michael what he envisions for the future in this area. This is what he had to say.

SPEAKER_00 14:46

As we look forward to the future of anesthesia care, I envisioned a continued shift towards truly individualized multimodal analgesia, where the focus is not on eliminating a specific medication class, but on selecting the right combination of therapies for each patient. Regional anesthesia will, of course, remain a cornerstone of this approach because of its ability to improve patient pain control, reduce opioid requirements, and support enhanced recovery. So moving forward, our challenge is to ensure that regional anesthesia techniques and multimodal pain strategies remain patient-centered and thoughtfully applied to minimize unwanted side effects to optimize recovery. As this pendulum continues to swing towards reduced opioid use, we must be cautious not to overlook the risk associated with alternative opioid experience strategies.

Alli 15:33

Thank you so much to Lori and Michael for contributing to the show today. We hope that this has given you something to think about when planning your next anesthetic. Perhaps you will make individualized multimodal analgesia part of your practice.

Questions Resources And Subscribing

Alli 15:48

If you have any questions or comments from today's show, please email us at podcast at apf.org. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit apSF.org for detailed information and check out the show notes for links to all the topics we discussed today. We are so glad that you joined us on the show today. Just a reminder that the APSF newsletter is evolving and new articles are being published online every couple weeks. This way, we can bring you important safety information that is timely, relevant, and reflective of the dynamic nature of modern anesthesiology practice. We hope that you will subscribe to the APSF newsletter to ensure that all of the latest updates arrive in your inbox. Check out the show notes for more information. And while you're at it, make sure that you are subscribed to this podcast because we will be featuring the new articles here on the show. Until next time, stay vigilant and stay informed so that no one shall be harmed by anesthesia care.