Continuing Education Activity

Multimodal pain control is an important modality to control pain in the post-operative period in all patients undergoing surgery or various other procedures. This is especially important in orthopedic surgeries, which often require extensive dissection and fixation of complex periarticular fractures and joint replacement procedures. Multimodal pain control is the use of multiple analgesic medications, opioids, and non-opioid and non-pharmacologic interventions to decrease pain at varying locations in the pain pathway. This allows the patient to benefit from several different medications that may potentiate one another, mitigate side effects of certain drug classes, and decrease the amount of use of opiates post-operatively.

Objectives:

• Summarize multimodal pain control and its benefits

• Review different drug classes utilized for managing pain with multimodal pain control, specifically in the orthopedic post-operative patient.

• Explain recommendations determined by evidence-based support of post-operative pain control after orthopedic surgery.

• Outline the benefits and effectiveness of multimodal pain control for the interprofessional team to make an informed decision about incorporating this into their practices.

Introduction

Multimodal Analgesia (MMA), also referred to as “balanced analgesia,” uses multiple analgesic medications, physical modalities, and cognitive strategies to affect peripheral and central nerve loci for the treatment of pain.[1] In light of the adverse side effects of opioid medication, the MMA model of pain management allows physicians an array of medicine and other modalities to help decrease the morbidity associated with opioid analgesics often used as monotherapy. The number of drug overdoses continues to rise every year, with opioids accounting for nearly two-thirds of the cases and being the leading cause of accidental death in the United States.[2][3] Orthopedic surgeons are attributed to writing 7.7% of all opioid prescriptions while only accounting for 2.5% of all prescribing physicians.[4] 

Orthopedic surgeons are challenged with the task of pain management while mitigating the risk associated with opioids. MMA allows orthopedic surgeons and other medical professionals a more modern and evidence-based approach in treating acute pain in their patients. The use of NSAIDs, acetaminophen, gabapentinoids, immediate-release opioids, cognitive therapy, peri-articular injections, and physical modalities, such as cryotherapy, will be reviewed in this article to assist the modern orthopedic surgeon in controlling pain in their patients in the postoperative period. In addition, this article will review the various drug classes, adverse effects, and contraindications and provide insight into special consideration to certain patients who are opioid-tolerant or suffer from comorbid conditions.

Function

NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) are common over-the-counter medications used daily for pain and inflammation. The mechanism of NSAIDs has been traditionally described by their peripheral efficacy on decreasing the pro-inflammatory mediators, prostaglandins. More recently, NSAIDs have been attributed to having a central role that augments its known peripheral action, by which it promotes the production of endogenous opioid peptides.[5] 

Due to fracture healing and fusion concerns, there are conflicting arguments in the orthopedic literature on the use of NSAIDs for pain control. Basic science studies have shown increased time to fusion in animal models using NSAIDs, though fracture healing has demonstrated mixed results. Hsu et al. recommend using NSAIDs in the MMA model due to a lack of high-quality evidence supporting decreased fracture healing in the clinical setting.[6] NSAIDs are proven to be effective for musculoskeletal pain, with head-to-head clinical studies noting equivalent pain control with NSAIDs compared with opioids with a reduced risk profile.[7][8] 

NSAIDs are used to target the associated inflammation. Recent studies have looked at the efficacy of pre-operative administration of NSAIDs and its result on postoperative pain scores. Pre-operative loading of meloxicam has been shown to decrease VAS pain scores in patients undergoing total knee arthroplasty for primary arthritis as compared to post-operative administration alone.[9] A resulting decrease in the amount of patient-controlled analgesia (PCA) was also seen. Contraindications with NSAIDs include peptic ulcer disease, chronic or end-stage renal disease, bronchial asthma, and breastfeeding women.[10]

Acetaminophen/Paracetamol

Acetaminophen is a commonly used over-the-counter analgesic, as well as antipyretic. It is the most common alternative for patients who cannot use NSAIDs due to contraindications stated previously. Its mechanism of action is complex as it acts on both the peripheral and central COX pathways, affecting the serotonergic, cannabinoid, and nitric oxide pathways [10]. Thus, they are used to target the pain cascade. Contraindications to the use of acetaminophen include liver disease or active alcohol intake, which can cause acute liver injury.

Gabapentinoids

Gabapentin, originally used as an anticonvulsant drug, is a commonly used modulator of neuropathic pain. It acts to inhibit the trafficking of protein subunits to decrease the amount of voltage-gated calcium channels on the plasma membrane of dorsal root ganglion neurons.[11] It has often been used in the treatment of diabetic neuropathic pain but has also been shown to be effective in treating acute pain. A meta-analysis looking at post-operative spine surgery showed a decrease in pain scores at 12 and 24 hours. In this same study, it was also shown that the addition of gabapentin to the normal post-operative pain regimen showed a significant decrease in total morphine consumption, as well as decreasing vomiting, pruritus, and urinary retention, which are associated with morphine use.[12] 

Gabapentin is a scheduled drug that has been misused in opioid-addicted patients. It can act to potentiate methadone high and negate symptoms of opioid withdrawal.[13] The use of gabapentin is associated with confusion, fatigue, and somnolence, which can be mitigated somewhat by using the lowest dose possible. A strategy used by some surgeons is to use gabapentin preoperatively at bedtime a couple of days before surgery. If needed, it can be increased to two or three times daily post-operatively.  If patients are unable to use gabapentin, then pregabalin can be substituted. Gabapentin is contraindicated in patients with myasthenia gravis and myoclonus disorders.[14][15]

Transcutaneous Electrical Stimulation (TENS)

TENS is a method of pain control in which a small voltage electrical current is delivered to the skin over the desired site of analgesia. This is a modality that can be used in the post-operative period to stimulate large diameter peripheral nerves, which are believed to decrease pain by activating opioid receptors through an endogenous pathway.[1] There are mixed results on the use of TENS as an adjunct to normal post-op pain control, some attributing the variation in results to the amplitude and frequency used during treatment. A meta-analysis including twenty-one randomized controlled trials found that TENS around the surgical site decreased post-op analgesic consumption by 26.5 % and decreased opioid use post-operatively by 35.5 %.[16] Contraindications to the use of TENS include severe lymphedema, compromised skin at the desired location of application, or the presence of a pacemaker or defibrillator.

Cryotherapy

Cryotherapy is a part of the traditional physical aspect of decreasing pain in an extremity, whether it is post-operative or treating a closed injury such as an ankle sprain. It is the use of an external cold source in an attempt to decrease the temperature of the tissue in that area. Ice packs, cold water therapy, gaseous cryotherapy, and continuous flow cryotherapy are all modalities used in cryotherapy. The effects on tissue include: decreased edema, decreased inflammatory mediators, and decreased blood flow via vasoconstriction or local vasculature.[17][18][19]

Various studies have looked at the effect of cryotherapy after orthopedic surgeries. Studies show a decrease in pain score as compared to controls, as well as a decrease in opioid use postoperatively when cryotherapy is used in conjunction with traditional methods of pain control.[20][21][22][23][24][25] 

Complications with cryotherapy include nerve palsies, mostly involving superficial peripheral nerves. These injuries range from brief paresthesia to complete nerve injury without return of function. It is important to have appropriate insulation between the cold source and the targeted area. This is especially important in areas with less subcutaneous fat or patients with less fat content.[6]

Nerve Blocks

Nerve blocks include local and regional anesthesia to the targeted area. Nerve blocks are commonly used methods of analgesia in elective orthopedic surgery cases, including arthroscopy and arthroplasty. These can be utilized preoperatively, intraoperatively, or post-operatively. Hsu et al. recommend using a continuous catheter over a single shot when administering a nerve block. They report better pain control with a decreased chance of rebound pain often associated with lower extremity blocks. There are various nerve block methods, and they may differ based on surgeon preference depending on the type of patient and surgical site. Problems include rebound pain and an increased risk of falls.[6]

Opioids

As discussed previously, opioids are a common medication used for severe acute pain. They are commonly used by orthopedic surgeons in the post-operative period for pain control. There is significant risk associated with their use, including misuse, addiction, and overdose. Opioids act by binding the mu-opioid receptor and inhibiting neurotransmitter release in the central nervous system. In their clinical practice guidelines, Hsu et al. recommend that opioids be used in the smallest dose and for the shortest amount of time possible. Short-acting opioids are preferred and recommended, as compared to long-acting opioids, which provide less opioid absorption per unit time.[6] The oral administration of opioids is preferred to IV administration in postoperative patients that can tolerate the oral route. Pain scores are equivalent, with a lower amount of morphine equivalents ingested in the oral administration group.[26] 

Multiple sources strongly recommend that opioids not be prescribed in conjunction with benzodiazepines due to the risk of increased sedation, overdose, and abuse. Park et al. noted a 3.9-time increase in overdose due to respiratory depression when using opioids in conjunction with benzodiazepines.[27] Opioids have been noted to be very effective and act synergistically when used with NSAIDs, compared to opioids as monotherapy.[28] Wojahan et al. looked at the number of opioids consumed after knee arthroscopy and observed that 81 % of patients take fewer than twenty pills postoperatively.[29] 

This leads to the notion that when utilizing opioids in the postoperative patient, orthopedic surgeons are writing prescriptions too high in quantity. This results in a medication surplus that is then available for misuse. This misuse may also involve diversion to use by persons not under the physician’s care. Adverse effects of opioids include nausea, vomiting, dizziness, constipation, somnolence, and headache.

Cognitive Strategies

Cognitive strategies are great tools to implement for all patients before and after surgery. Providing patients with an appropriate estimate or overestimate of the pain level to expect postoperatively is a good strategy to help prepare patients for their surgery. In patients with co-morbid psychological issues including anxiety, low appreciation of self-worth, and major depression have been noted to experience more pain per nociception.[30] 

There is significant variation in the pain perceived among patients due to varying psychosocial issues. Patients who suffer from comorbid anxiety, major depression, opioid tolerance, and low self-worth may benefit from psychiatry consultation while admitted to the hospital. Of utmost importance is the honest, direct dialogue between the surgeon and the patient regarding pain relief expectations. Enlisting the support of acute pain services and addiction medicine services is recommended in the clinical guidelines by Hsu et al.[6]

Issues of Concern

Opioid Safety

Opioids can be associated with significant morbidity if not handled appropriately. On the other hand, they can be a great tool to control postoperative pain when used correctly in the appropriate patient. In the in-patient and out-patient setting, it is important to constantly reassess patient pain and make changes to the pain regimen accordingly. It is particularly important in the in-patient setting that a sedation status be performed before and after administration of each opioid medication or other medications with sedating effects, for that matter. This is recommended in the clinical practice guidelines by Hsu et al.[6] 

Pasero designed an opioid sedation scale to help monitor patients and guide medication regimen changes in the in-patient setting.[31] Since sedation is an impending sign of respiratory distress, this direct monitoring of the patient before and after receiving medication is vital. Hsu et al. also recommend co-prescribing naloxone for patients who are at increased risk for respiratory depression. No studies demonstrate that this directly decreases prescription overdoses. Still, it has been seen to decrease overdoses on a community scale when naloxone has been made available to illicit drug users. Patients who would benefit from this include previous drug abusers and patients with anxiety who may be prescribed benzodiazepines from other providers. It is also recommended that all physicians register and monitor the Prescription Drug Monitoring Drug program (PDMP) before prescribing pain medication.

Clinical Significance

Multimodal analgesia is the future for the alleviation of pain in many fields of medicine. The field of orthopedic surgery has been at the forefront of this new tool's clinical use and innovation for postoperative pain relief. This model shows benefit in many ways in the clinical setting. Orthopedic surgery can often be associated with significant pain in the early postoperative period. Balancing the need for pain control while mitigating risk for adverse effects such as opioid dependence and adverse effects of medication with comorbid conditions can be difficult. MMA provides a broad array of medications and strategies that can be combined to work synergistically with one another to help orthopedic surgeons treat their patients in the most efficacious and safe way possible. Recent studies corroborate the idea that this model helps decrease post-operative pain beyond the standard monotherapy opioid regimen. This leads to less opioid use and, therefore, less risk to the patient.[32] 

Individual surgeons often create their own regimens with respect to how they approach MMA. Hsu et al. have broken their pain regimens into classes based on the severity of the injury and the associated surgery. The classes include major musculoskeletal surgery, minor musculoskeletal surgery, and non-operative or closed treatment. These recommended regimens include opioid management as well as alternative or adjuvant non-opioid medications (NSAIDs, gabapentin, acetaminophen).[6] This can be a good starting point for the young physician or physician that has not yet adopted an MMA approach in their practice.

Enhancing Healthcare Team Outcomes

Just as successful multi-modal pain management requires different classes of medications, enhancing team outcomes requires many different types of team members.  Some coordination may be required by a pain management doctor, anesthesiologist, pharmacists, PACU nurses, recovery nurses, and pre-operative nurses.  Successful multi-modal pain management requires a streamlined strategy from pre-op to intra-op and post-op, including regional anesthesia, patient counseling, and multiple medications, but this has been shown to reduce narcotic usage and lead to successful postoperative pain management.[33]  [Level 4]