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13 Articles in Volume 18, Issue #3
Anger Expression & Chronic Pain
Ask the Expert: Should reliance on gabapentin/pregabalin be limited?
Chronic Pain in Children
Considering Comorbidities When Selecting Medications for Chronic Pain Management (Part 1)
Dousing the Physician Burnout Epidemic: An AMA Perspective
Harnessing the Power of Words
Inside ASRA with David Provenzano, MD
Management of Intrathecal Therapies by Interprofessional Teams
Nurse Burnout in Pediatric Pain Management: A Model and Pilot Intervention
Physician Burnout: An Oldtimer’s View
Reporting Metrics, Media Coverage...Letters from the Minds of Peers and Patients
The Case for Slow-Release Anesthetics
The Impact of Pain Practice

The Case for Slow-Release Anesthetics

With many cases of chronic pain stemming from surgery, perioperative analgesics that offer a longer duration of action may be the right move.

As pain practitioners and anesthesiologists well know, chronic pain does not just magically appear. It starts with acute pain. Many pain management experts, including this author, would say that a great deal of that acute pain is created during surgery, even under the best surgical hands. This is simply due to the fact that an injury has taken place, both organically to the actual peripheral tissue, and inorganically, due to central neuroplastic changes. Variability in perioperative care, in combination with these peripheral and neuroplastic changes, may exacerbate acute pain, thus increasing the chances of a patient developing chronic pain.

The Perioperative Factor in Today’s Medical Climate

It is estimated that there are almost 100 million surgical procedures performed yearly in America.1-3 Approximately 80% of patients undergoing surgery report pain intensity that is moderate, severe, or extreme during the first two weeks post-procedure.1-3 Perioperative care is complex and a multimodal approach, where interventions involving procedures, medications, and techniques, may be necessary to ensure a successful outcome. While this approach is not new, the implementation of multimodal care has taken decades and remains widely unused in a “best practices” manner. In fact, some practitioners and hospital systems continue to think that chronic pain is “not their problem” once a patient leaves their facility, and they often fail to invest in options that might reduce or prevent a patient’s progression toward chronic pain. An “ounce of prevention” is simply not in their lexicon.

The science supporting a sound perioperative protocol using regional anesthesia with local anesthetics has been available for a quarter-century, yet, changing behaviors and habits in medicine continues to be challenging. In some cases, logistics and finances prevent hospital systems and surgical centers from providing adequate regional anesthesia. In other cases, the anesthesiologists or licensed registered nurse anesthetists may not feel comfortable or may not be trained in regional anesthesia. Finally, surgeons may prevent regional anesthesia or may not be active advocates or participants in a multimodal perioperative pain program for their patients because they deem it slows their cases or creates more logistical hassles.

A well-oiled perioperative machine, however, is likely to result in better patient outcomes, including reduced post-operative pain and reduced central and peripheral sensitization, which may both lead to lower opioid utilization—and thus, fewer opioid side effects. Overall, lower levels of chronic pain are likely to be reported among post-surgical patients.

Steps toward Improved Regional Anesthesia Programs

There are a variety of techniques that may be used during the perioperative period to optimize post-operative outcomes. One technique is regional anesthesia, which may encompass a variety of potential procedures, such as:

  • epidural or spinal blockage in combination with local anesthetics during surgery
  • various nerve blocks with corresponding anesthetics during surgery (read about a newly approved expanded use of bupivacaine liposome injectable suspension)
  • local anesthetics infiltrated to the surgical site during surgery
  • indwelling catheters that infuse local anesthetics postoperatively.

Managing the Management

Even with the right approaches in place, physicians and staff must be well trained. To manage a successful regional anesthesia program, in the author’s experience, a hospital or surgery center needs to employ:

  • anesthesiologists who have been trained in the most current regional anesthesia techniques and surgeons who are supportive of these techniques
  • nurses and staff who understand how to manage the pumps/catheters during and after regional anesthesia (read more on managing intrathecal pumps)
  • pharmacists who are knowledgeable in pump drug delivery and the medications used
  • administrators who encourage investment in and budget for a regional anesthesia program.

The Pursuit of Longer Duration of Action

The most commonly used regional anesthetics include spinal blockade, epidural blockade, nerve blockade, and infiltration of local anesthetic to the surgical site. All of these options provide temporary analgesia and may reduce peripheral and central sensitization to the surgical injury.

Unfortunately, the duration of action of these techniques is typically limited from a few hours to less than one day. This short duration of action created the need for infusion pumps and elastomeric bag technology through indwelling catheters, which have been around in some format since the last millennium. These devices enable clinicians to administer local analgesic directly into the wound for several days. However, additional safety and competency concerns, such as training, attention to detail, dosing, infection, catheter disconnection, and more, may arise with the use of such devices.

To overcome these challenges, anesthetics that have a longer half-life or technologies that allow for a longer duration of action are needed. Encapsulating technologies have emerged as a leading option.

Encapsulation & Liposomal Preparations

Encapsulation of the local anesthetic enables prolonged release and extended duration of action. In addition, encapsulated analgesics present with a lower side effect profile due to the lower peak plasma concentration, lower systemic exposure, and lower risk of overdose.4

In October 2011, the US Food and Drug Administration approved, for example, liposomal bupivacaine (bupivacaine liposome injectable suspension) for single-dose infiltration into the surgical site to produce post-surgical analgesia.5 The medication is slowly released from the multivesicular liposomes after infiltration into the surgical area. This results in prolonged analgesia for 72 hours with a corresponding reduction in post-operative pain and less use of opioids. When used, there is no need for additional tubing, catheters, device programming, or extensive nursing and staff training.

Liposomal preparations may be used as a way of delivering controlled-release medications. These nano-sized particles, or bubbles, release their contents as they dissolve. In terms of limitations, liposomal local anesthetics have a short shelf life and may be expensive. As a result, researchers continue to focus on the development of alternative products and technologies. Some slow-release local anesthetics in the R&D pipeline include:

  • implantable anesthetics, which may contain a slow release, high-dose formulation of a local anesthetic
  • polymer-based formulations, which may be molded to solid or paste-like formulations according to the required type of application and dose
  • polymicrospheres, which are currently used in commercial vaccine development.6 These biodegradable, mechanically stable polymers, synthesized from a polylactide acid polymer (PLA) or a copolymer of polylactide-coglycolide acid (PLGA), are advantageous due to retention for prolonged periods at the action site, where the encapsulated drug may be released slowly.
  • injectable pastes and solid polymers, which are made from compounds found naturally in the body (eg, ricinoleic acid and lactic acid). These local anesthetics may be advantageous due to their ease and consistent preparation.
  • proliposomal products, which have a longer shelf life, may be stored at room temperature, and are easier to produce. They may even provide longer analgesia. Liposomes appear and begin releasing their ropivacaine contents only when the oil comes into contact with aqueous (water-containing) solutions, such as blood plasma.

The Push Forward

The future of longer-duration or slow-release local analgesics in the perioperative setting has exciting potential. As this article went to press, one biotech company announced Phase 3 success with a nonopioid, long-acting local anesthetic that demonstrated both a statistically significant reduction in pain intensity for 72 hours post-surgery, and an increase in the number of patients that remained opioid-free for 72 hours.7

Overall, the global economics for slow-release anesthetics make sense, as a small upfront investment may yield an exponential savings down the road. Pain practitioners may have to wait and see if perioperative pain management evolves to universally apply a multimodal approach to minimizing acute pain and thus, prevent potential transitions to chronic pain.

In the short term, as institutions develop and implement policies, procedures, training, and administrative guidelines around the use of opioids to ensure their safe and appropriate utilization, the use of liposomal bupivacaine as an encapsulated slow-release anesthetic may offer an integral component of managing post-surgical multimodal pain.

Last updated on: April 12, 2019
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