Use of Combination Therapy in Acute Pain Management

Segment Description: Expert pain specialists discuss the role of combination therapy and their experience treating patients with acute pain with a multimodal approach.

Benjamin W. Friedman, MD, MS: We’ve been spending a fair amount of time talking about different types of combination therapies, and how for quite a few patients, just 1 type of medication, an NSAID [nonsteroidal anti-inflammatory drug] or Tylenol, often isn’t sufficient. Many times, we have to use a multimodal approach. That could be a combination of pharmacologic and nonpharmacologic therapy, or using different types of pharmacologic therapy. Jeff, maybe you could tackle this. Do you want to talk about the advantages of a multimodal approach? To some extent, we’ve been discussing it already. But why is that in vogue now for the way to approach pain management?

Jeff Gudin, MD: We’re at least a decade or two into this concept of using a multimodal approach in the perioperative setting. If you look worldwide, there are protocols called ERAS, enhanced recovery after surgery, protocols. I talked a little about the pathophysiology of pain, how it’s multifaceted and it starts in the periphery and goes toward the CNS [central nervous system]. There’s the perfect rationale for using a multimodal approach. Can we block the message in the periphery with NSAIDs or local anesthetics? Can we block the message centrally with opioid-based medications, antidepressants, gabapentin, or anticonvulsant-like medications?

The whole concept here is that offering lower doses of multiple classes of medications saves you the adverse effects of higher doses. Hopefully we get, if not additive, then perhaps synergistic analgesia, giving the patient the best chance of relief. This concept of multimodal analgesia isn’t new. We’ve been doing it in the anesthesia world. Twenty or 30 years ago, we thought that we could maybe prevent pain by giving all these different classes of analgesics before the surgeon even makes his incision. If there’s this nociceptive cascade, it’s easier to stop it before it happens than to try to stop it after the dam breaks. The same thing goes for acute pain. Giving patients multiple classes of therapeutic agents, and as my colleagues have said, both pharmacologic and nonpharmacologic therapies gives the best chance of relief.

Benjamin W. Friedman, MD, MS: Francesca, what about your experience with multimodal analgesia? Are there different combinations of medications you commonly use for patients with acute pain?

Francesca Beaudoin, MD, MS, PhD: When I’m seeing somebody with acute pain, I like to think about what the menu of options for this person are, and given the person and the setting, choosing the most appropriate options from that menu. In the emergency department, I maybe have a wider arsenal than somebody who’s in a primary care office. I can do regional anesthesia, nerve blocks. I have options like low-dose ketamine, nonsteroidals, Tylenol, and opioids. I think about the person, their specific comorbidities, other patient factors, and underlying conditions, and I choose from that menu of options. Jeff did a nice job summarizing the rationale for why we might choose a multimodal approach.

There are some potential limitations to a multimodal approach. It can be a bit more intensive for the person themselves if we’re asking people to follow a more complex medication regimen because we’re asking them to take multiple medications or we’re bringing in a nonpharmacologic strategy. Are we asking them to go to physical therapy sessions, doing behavioral therapy, mindfulness, or acupuncture? It can get complicated for people. Then there are cost factors. Does their insurance cover the various pieces of it? Are there different co-pays?

It isn’t totally straightforward, and we don’t quite know which bundle of therapies to apply to that person in that moment. We aren’t there yet in terms of precision medicine, and the evidence isn’t there. There are some conditions in which there’s a lot of evidence behind it. As Jeff mentioned, the perioperative environment is well researched, along with other things, such as migraine. But there are other places where we still need to do a better job and the research hasn’t progressed.

Benjamin W. Friedman, MD, MS: Paul, how about your experience with the multimodal approach to analgesia? I don’t know if you want to specifically tackle a combination of NSAIDs and opioids or multimodal analgesia in general.

Paul Arnstein, RN, PhD, FAAN: When you think about physiology 101 of pain as far as there being transduction, transmission, modulation, and perception of pain, are we hitting all those targets? We have those opportunities that we can either amplify the pain or dampen it. Is there a therapy we can use, pharmacologic or nonpharmacologic, to dampen those? A lot of the things we’ve talked about as far as therapeutic options have targeted some of those multiple approaches.

The National Institutes of Health combined with the US Department of Health & Human Services came out with a document in 2019 on best practices in pain management. It talks about medications and restorative therapies, such as physical therapy, behavioral therapies, and complementary and integrative therapies, and how we need to piece these together. It might be multiple medications, or multiple medications combined with the behavioral or restorative therapies, or interventional approaches. But access is an issue. Especially if we think about the patient with gout; sending them to a physical therapist or to cognitive behavioral therapy might be difficult.

Now there are technologies that will remotely deliver some of these therapies to patients. They’re gaining evidence of effectiveness, but I’m not sure that we’re quite there as far as how we best integrate for the individual access to these different types of therapies. But it’s been somewhat of a no-brainer to use some of these combinations and think about if it’s an inflammatory-driven pain, to get an anti-inflammatory on board. If they need something stronger, do we use an opioid-sparing adjuvant? Or do we use an opioid for the patient? Or is a local anesthetic intervention appropriate? These have been mentioned by my colleagues, but that’s the standard way that we’re thinking about pain treatment.

Transcript edited for clarity

Segment Description: Expert pain specialists discuss the role of combination therapy and their experience treating patients with acute pain with a multimodal approach.

Benjamin W. Friedman, MD, MS: We’ve been spending a fair amount of time talking about different types of combination therapies, and how for quite a few patients, just 1 type of medication, an NSAID [nonsteroidal anti-inflammatory drug] or Tylenol, often isn’t sufficient. Many times, we have to use a multimodal approach. That could be a combination of pharmacologic and nonpharmacologic therapy, or using different types of pharmacologic therapy. Jeff, maybe you could tackle this. Do you want to talk about the advantages of a multimodal approach? To some extent, we’ve been discussing it already. But why is that in vogue now for the way to approach pain management?

Jeff Gudin, MD: We’re at least a decade or two into this concept of using a multimodal approach in the perioperative setting. If you look worldwide, there are protocols called ERAS, enhanced recovery after surgery, protocols. I talked a little about the pathophysiology of pain, how it’s multifaceted and it starts in the periphery and goes toward the CNS [central nervous system]. There’s the perfect rationale for using a multimodal approach. Can we block the message in the periphery with NSAIDs or local anesthetics? Can we block the message centrally with opioid-based medications, antidepressants, gabapentin, or anticonvulsant-like medications?

The whole concept here is that offering lower doses of multiple classes of medications saves you the adverse effects of higher doses. Hopefully we get, if not additive, then perhaps synergistic analgesia, giving the patient the best chance of relief. This concept of multimodal analgesia isn’t new. We’ve been doing it in the anesthesia world. Twenty or 30 years ago, we thought that we could maybe prevent pain by giving all these different classes of analgesics before the surgeon even makes his incision. If there’s this nociceptive cascade, it’s easier to stop it before it happens than to try to stop it after the dam breaks. The same thing goes for acute pain. Giving patients multiple classes of therapeutic agents, and as my colleagues have said, both pharmacologic and nonpharmacologic therapies gives the best chance of relief.

Benjamin W. Friedman, MD, MS: Francesca, what about your experience with multimodal analgesia? Are there different combinations of medications you commonly use for patients with acute pain?

Francesca Beaudoin, MD, MS, PhD: When I’m seeing somebody with acute pain, I like to think about what the menu of options for this person are, and given the person and the setting, choosing the most appropriate options from that menu. In the emergency department, I maybe have a wider arsenal than somebody who’s in a primary care office. I can do regional anesthesia, nerve blocks. I have options like low-dose ketamine, nonsteroidals, Tylenol, and opioids. I think about the person, their specific comorbidities, other patient factors, and underlying conditions, and I choose from that menu of options. Jeff did a nice job summarizing the rationale for why we might choose a multimodal approach.

There are some potential limitations to a multimodal approach. It can be a bit more intensive for the person themselves if we’re asking people to follow a more complex medication regimen because we’re asking them to take multiple medications or we’re bringing in a nonpharmacologic strategy. Are we asking them to go to physical therapy sessions, doing behavioral therapy, mindfulness, or acupuncture? It can get complicated for people. Then there are cost factors. Does their insurance cover the various pieces of it? Are there different co-pays?

It isn’t totally straightforward, and we don’t quite know which bundle of therapies to apply to that person in that moment. We aren’t there yet in terms of precision medicine, and the evidence isn’t there. There are some conditions in which there’s a lot of evidence behind it. As Jeff mentioned, the perioperative environment is well researched, along with other things, such as migraine. But there are other places where we still need to do a better job and the research hasn’t progressed.

Benjamin W. Friedman, MD, MS: Paul, how about your experience with the multimodal approach to analgesia? I don’t know if you want to specifically tackle a combination of NSAIDs and opioids or multimodal analgesia in general.

Paul Arnstein, RN, PhD, FAAN: When you think about physiology 101 of pain as far as there being transduction, transmission, modulation, and perception of pain, are we hitting all those targets? We have those opportunities that we can either amplify the pain or dampen it. Is there a therapy we can use, pharmacologic or nonpharmacologic, to dampen those? A lot of the things we’ve talked about as far as therapeutic options have targeted some of those multiple approaches.

The National Institutes of Health combined with the US Department of Health & Human Services came out with a document in 2019 on best practices in pain management. It talks about medications and restorative therapies, such as physical therapy, behavioral therapies, and complementary and integrative therapies, and how we need to piece these together. It might be multiple medications, or multiple medications combined with the behavioral or restorative therapies, or interventional approaches. But access is an issue. Especially if we think about the patient with gout; sending them to a physical therapist or to cognitive behavioral therapy might be difficult.

Now there are technologies that will remotely deliver some of these therapies to patients. They’re gaining evidence of effectiveness, but I’m not sure that we’re quite there as far as how we best integrate for the individual access to these different types of therapies. But it’s been somewhat of a no-brainer to use some of these combinations and think about if it’s an inflammatory-driven pain, to get an anti-inflammatory on board. If they need something stronger, do we use an opioid-sparing adjuvant? Or do we use an opioid for the patient? Or is a local anesthetic intervention appropriate? These have been mentioned by my colleagues, but that’s the standard way that we’re thinking about pain treatment.

Transcript edited for clarity