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Multimodal Pain Relief in Critically Ill Trauma Patients

19 Mar 2021 5:54 PM | Anonymous

By: Amanda Bernarde, PharmD; PGY1 Pharmacy Resident, University of Missouri Health Care

Uncontrolled pain in the trauma patient population can lead to a variety of long-term, debilitating effects.1,2 Most prominently, patients experience impaired healing due to additional production of inflammatory factors, increased risk of infection, and psychological disorders persisting well past the initial injury.3 Due to the subjectivity of pain assessments and confounding factors, including sedating medications that can mask uncontrolled pain, recent exposure to opioids, and chronic versus acute pain etiologies, pain management remains a challenge in all patient populations.

Opioids continue to be the mainstay in pain management for trauma patients. However, due to their adverse effect profile, potential for misuse and abuse, and the ever-evolving drug shortage issues facing health care institutions, additional approaches to medication management are necessary to adequately control patients’ pain.2 Multimodal analgesia (MMA) is the concomitant use of both opioid and non-opioid pain medications for synergistic mechanisms of action in an effort to minimize opioid-related adverse effects. This approach combats the two sides of pain patients experience: nociceptive and neuropathic.2,4 Nociceptive pain is caused by mechanical harm to the body, which is the traditional sense of trauma-related pain and commonly managed by opioids, while neuropathic pain is an effect of inappropriate stimuli to the sensory system and not well controlled by opioids.

In a quasi-experimental study completed by Hamrick et al., investigators demonstrated the positive effects of MMA on cumulative oral morphine equivalents (OME) in critically ill trauma patients.5 Patients with three or more mechanisms of medication pain management had an average OME of 116.3 mg, while patients without MMA had an average OME of 479 mg spanning the first five days after injury. Beyond the overall reduction of opioid requirements when using a multimodal pain approach, use of non-opioids in addition to traditional regimens have significantly reduced intubation time and intensive care unit length of stay with a reduction of 2.64 and 4.25 days, respectively.6 This impact on both short-term and long-term outcomes can drastically alter a patient’s disease course and management beyond the acute setting.

There are a number of specific medication classes that have been explored in conjunction with opioids, including traditional over-the-counter pain medications, gabapentinoids, α-adrenergic agonists, and ketamine. Trauma patients given scheduled oral acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) in addition to opioids had an average OME reduction 6.34 mg and 10.18 mg, respectively, in the 24-hour period post-MMA.4 Though reduction in opioid requirements may have been a natural disease progression, several studies have found similar results in non-trauma patients.2,7,8 Gabapentin and pregabalin mitigate neuropathic pain and help prevent chronic pain, while α-adrenergic agonists, like dexmedetomidine and clonidine, work both peripherally and centrally to provide analgesia, anxiolysis, and sedation.2 Both medication classes have demonstrated effective reduction of OME and coinciding pain scores in non-trauma surgical patients, yet no studies have been conducted in critically ill trauma patients to illustrate the effects in this patient population. Lastly, in a recent systematic review and meta-analysis, ketamine administration in the pre-hospital setting was not found to be less effective at managing pain compared to opioids.9 This non-opioid analgesic has proven efficacious in decreasing pain scores and OME for both intranasal administration and intravenous administration in a variety of trauma population subsets.10,11 Each MMA approach, though successfully protocolized at many institutions, should be individualized to the patient, including end organ function, comorbid conditions precluding use, and baseline use of these medications which may reduce their efficacy in treating the acute pain needs of the patient.

In addition to the non-opioid medication therapies, there are nonpharmacologic approaches that can facilitate to both the physical progress and emotional aspects for trauma patients. One such nonpharmacologic therapy is early initiation of physical therapy. From a physical standpoint, assisted movement restores range of motion, promotes healing of injured tissues, and decreases long-term activation of inflammatory responses.12 Early mobilization has demonstrated a reduction of pulmonary, vascular, and cardiovascular complications, including pneumonia, pulmonary embolism, acute respiratory distress syndrome, deep vein thromboses, myocardial infarctions, and cardiovascular shock.12,13 Additionally, a statistically significant decrease in hospital length of stay by 2.4 days was shown when comparing early mobility to the control group (p=0.02). Though ICU length of stay was reduced by 1.5 days, these findings were not statistically significant, attributing the decrease in total length of stay to fewer complications when patients reached the general care floors. The positive effect of early physical therapy have prompted additional research in nonpharmacologic approaches to pain management, including mobilization in the emergency department and use of virtual reality.

The limitations and risks associated with long-term, high-dose opioid use remain a concern in practitioners’ minds in treating critically ill trauma patients. Despite the limited data in this patient population, literature from other non-traumatic surgeries has been extrapolated to trauma patients due to their similar pain management needs. In the studies available and those extrapolated, MMA has shown to significantly decrease opioid and overall analgesic requirements, intubated days, and intensive care unit and hospital length of stay, in addition to minimizing misuse and abuse of opioids by setting the same precedent in the outpatient world.

References:

  1. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306.
  2. Wampole CR, Smith KE. Beyond opioids for pain management in adult critically ill patients. J Pharm Pract. 2019;32(3):256-270.
  3. Karamchandani K, Klick JC, Linseky Dougherty M, Bonavia A, Allen SR, Carr ZJ. Pain management in trauma patients affected by the opioid epidemic: a narrative review. J Trauma Acute Care Surg. 2019;87(2):430-439.
  4. Gross JL, Perate AR, Elkassabany NM. Pain management in trauma in the age of the opioid crisis. Anesthesiol Clin. 2019;37(1):79-91.
  5. Hamrick KL, Beyer CA, Lee JA, Cocanour CS, Duby JJ. Multimodal analgesia and opioid use in critically ill trauma patients. J Am Coll Surg. 2019;228(5):769-775.e1
  6. Zhao H, Yang S, Wang H, Zhang H, An Y. Non-opioid analgesics as adjuvants to opioid for pain management in adult patients in the ICU: A systematic review and meta-analysis. J Crit Care. 2019;54:136-144.
  7. Polomano RC, Fillman M, Giordano NA, Vallerand AH, Nicely KL, Jungquist CR. Multimodal analgesia for acute postoperative and trauma-related pain. Am J Nurs. 2017;117(3 Suppl 1):S12-S26.
  8. Jibril F, Sharaby S, Mohamed A, Wibly KJ. Intravenous versus oral acetaminophen for pain: systematic review of current evidence to support clinical decision-making. Can J Hosp Pharm. 2015;68(3):238-247.
  9. Yousefifard M, Askarian-Amiri S, Rafiei Alavi SN, et al. The efficacy of ketamine administration in prehospital pain management of trauma patients: a systematic review and meta-analysis. Arch Acad Emerg Med. 2020;8(1):e1.
  10. Carver, TW, Kugler NW, Juul J, et al. Ketamine infusion for pain control in adult patients with multiple rib fractures: results of a randomized control trial. J Trauma Acute Care Surg. 2019;86(2):181-188.
  11. Bouida W, Bel Haj Ali K, Ben Soltane H, et al. Effect on opioids requirement of early administration of intranasal ketamine for acute traumatic pain. Clin J Pain. 2020;36(6):458-462.
  12. Chimenti RL, Frey-Law LA, Sluka KA. A mechanism-based approach to physical therapist management of pain. Phys Ther. 2018;98(5):302-314.
  13. Clark DE, Lowman JD, Griffin RL, Matthews HM, Reiff DA. Effectiveness of an early mobilization protocol in a trauma and burns intensive care unit: a retrospective cohort study. Phys Ther. 2013:93(2):186-196.

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