A Review of Non-Opioid Pain Management Strategies

By Chealsea Mikolowsky, PGY4

Opioids are some of the most commonly used medications in the ED for acute pain management. The epidemic of opioid abuse, addiction, and death in recent years, as well as the side effects and potential for respiratory depression and hemodynamic instability in patient receiving opioids has created a need for ED physicians to seek other strategies for pain management. As a result, many medications, as well as minor procedures, have emerged as potential adjuncts or replacements for opioid pain control. As ED physicians, it is essential to maintain a varied arsenal of strategies to treat our diverse and increasingly medically complex patient population. This post will seek to review these alternative strategies.

Ketamine

Ketamine, an NMDA receptor antagonist, has been suggested to have analgesic properties for decades, however there was little data until recently, and many physicians were hesitant to use ketamine for this purpose for fear on inducing dissociation and emergence reactions. Recently however, increased research has suggested that ketamine is in fact a safe, comparable, and useful adjunct or replacement for opioids in the treatment of acute pain as it lacks the respiratory depression and relative risk of hypotension compared to opioids. 

ACEP recommends IV infusion of 0.1-0.3 mg/kg infusion in 100 mls NS over 15 minutes, but some literature suggests you may go up to 0.5 mg/kg with minimal dissociative/ cognitive effects in some patients.  Doses beyond this risk partial dissociation causing psychological stress and emergence reactions without full dissociation occurring until doses of 1-2 mg/kg are reached. Continuous infusion should begin at 0.15 mg/kg//hr and can be titrated to effect with maximum doses of 2.5-5 mg every 30 minutes. Most common side effects include nausea and dysphoria which are easily managed. 

Ketamine Brain Continuum

Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Miller et al. 2015

A single center randomized, double blinded prospective trial comparing 0.1 mg/kg dose IV morphine infused over 5 minutes with 0.3mg/kg dose IV ketamine over same time for control of acute pain in the ED. Involved 45 participants at military hospital and level 1 trauma center and compared maximum reduction in numeric pain scores over 2 hours. Found no superiority of ketamine in maximum pain reduction but did find quicker onset and prolonged effect. It did not find significant differences in adverse events, nurse or provider satisfaction, emergence reactions or agitation, or vital signs. It did find an increased need for repeat dosing in the ketamine group. First study involving direct comparison of ketamine to opioids; prior studies used ketamine alone or as an adjunct to opioids with no control arm. This study was limited by a small sample size, possibly by the military population, and by the exclusion of chronic pain which presents a problem in the ED often requiring the use of opioids. It also suffered from a lack of general knowledge regarding the ideal dosing of ketamine for pain control. Still even lacking superiority, this study shows that ketamine does provide significant pain control for acute pain, comparable to morphine, with potentially quicker onset and longer effect. 

Lidocaine

The use of intravenous lidocaine for analgesia began in the 1960s, and has been studied specifically in the acute setting for use in renal colic, back pain, and limb ischemia, Currently the use of IV lidocaine for this purpose is most supported as an adjunct to opioids or NSAIDS or after these modalities have failed. The literature is of poor quality to recommend its singular use; however, it has been encouraging regarding its potential. The most supportive evidence appears to recommend it use in the treatment of renal colic and limb ischemia; with poor evidence to suggest its use in migraines. The dose suggested is 1.5 mg/kg over 15 minutes in 100 ml NS or an infusion, which requires cardiac monitoring and screening EKG, of 2 mg/kg/hr. 

The most crucial consideration when using IV lidocaine is toxicity. Sodium channel blockade is responsible for causing both CNS and cardiovascular symptoms beginning with tongue numbness, metallic taste, and lightheadedness and progressing to tinnitus, unconsciousness, seizures, and conduction abnormalities/hemodynamic compromise. CNS effects will appear prior to onset of cardiovascular symptoms and it is critical to identify them. Toxic effects begin at 4mg/kg and the treatment for severe or worsening toxicity is 20% lipid emulsion therapy. Providers should be familiar with this process before administering iv lidocaine. 

Lipid Emulsion

Literature Review:

Safety and efficacy of intravenous lidocaine for pain management in the emergency department: a systematic review. Silva et al. 2018.

Evaluates 6 RCTs and 2 case series to review the current literature involving the use of IV lidocaine for the treatment of acute and chronic pain in the ED. Focused on outcomes involving pain reduction, adverse event, risk of bias, and certainty. Found that IV lidocaine had efficacy in the treatment of renal coli and limb ischemia, but not for migraine headache. However, with so few and often small studies the evidence was to small to offer strong recommendations and more testing is needed regarding its safety compared to controls. Due to weak evidence, small trials, methodologic errors, it did not appear that IV lidocaine could be suggested for routine use. 

Nitric Oxide

This inhaled anxiolytic is a useful adjunct to pain control, be it with opioids or otherwise for quick but painful procedures such as I&Ds. Onset is within minutes and duration is between 4-5 minutes, making this an attractive option due to easy on/off nature and low side effect profile including nausea, vomiting, and headache. Varying concentrations exist to provide a range from mild sedation and anxiolysis/analgesia, to moderate sedation requiring full sedation protocol. Mild sedation can be obtained using the 30-50% with concentrations between 50% and 70%  associated with moderate levels of sedation and requiring physician at bedside. 50% NO is normally used in the ED. 

Nitric Oxide is overall quite safe and associated with few adverse events, but for the safety of all involved, good mask seal must be obtained to prevent any effect to staff. Nitric oxide is not safe in pregnancy or if administering staff are pregnant. 

At Einstein, we have a sentry sedate nitric oxide dispensing system. This holds 2 nitric oxide cylinders and 2 oxygen cylinders. To use nitric oxide for mild sedation/ anxiolysis, begin by administering 100% O2 and gradually increasing the nitric oxide concentration to 30-50%, down-titrating the O2. In 2-4 minutes patient should feel “floaty” or report a tingling sensation; now you may start the procedure, remembering appropriate analgesia as well. 100% O2 should be administered for 2-3 minutes after discontinuation of nitric oxide to prevent diffusion hypoxia where nitrogen diffusing out of the blood dilutes the oxygen concentration in the alveolus. Again, always ensure good mask seal. 

IV Acetaminophen

IV acetaminophen is an interesting talking point in the discussion of non-opioid pain modalities as Tylenol has the advantages of being non-opioid, non-NSAID for the various populations that cannot tolerate these and have few to no side effects. However, previously it has been very expensive, making an unattractive option in the ED, used most often in the post-surgical setting. This year multiple manufacturers will start producing the drug, so this may change soon. Evidence however, does not appear to show superiority to its oral form, which will likely continue to limits its use in the ED but further research is needed as it may certainly be of more use in specific populations. Dosing is the same and side effects are limited as with oral administration. 

Literature Review

Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomized controlled trial Furyk et al. Emerg Med J. 2018;35(3):179-84.

A single center prospective double blind randomized controlled trial comparing 1 gram IV paracetamol to 1 gram oral paracetamol in ED patients with acute moderate to severe pain who had already received opioid pain control.  Assessed pain levels using visual analog scale and each arm received a placebo in the corresponding form be it IV or oral. Primary outcome was VAS pain score reduction at 30 minutes. Secondary outcomes included need for rescue analgesia, side effects, adverse events, and patient satisfaction with overall pain care after data collection was completed. This study did not show superiority of iv paracetamol to oral for the primary or secondary outcomes.  Did show nonsignificant increase in patient satisfaction towards the IV form. 

This study was well designed and answered an important question. The use of a double dummy is very important to eliminate bias. However, it was limited by its size and the fact that it is single center. It is also important to note that all participants had already received opioid medication, therefore the effect of acetaminophen here is masked. Lastly, as are many studies of acute pain in the ed, this was a convenience sampling. Interestingly there was a non-significant increase in patient satisfaction in the IV group. (Possibly suggesting some supra-tentorial effect!) These findings do appear to be in keeping with other literature on the subject that suggest that iv acetaminophen is not superior to its oral form for acute pain. While this makes it use imprudent as it is currently much more expensive, as the price is lowered it may become useful in patients who cannot tolerate PO and/or cannot tolerate NSAID pain control. 

Nerve Blocks

Regional anesthesia with intradermal lidocaine is a useful adjunct or even primary treatment for pain control during laceration repair, abscess drainage, and the management if upper and lower extremity fractures. Ultrasound guidance should be used as often as possible and increases the safety of the procedure. We are very familiar with this procedure in the ED for digital nerve blocks, and more recently for femoral nerve blocks, but there are many nerves which can be easily utilized for analgesia using landmarks and ultrasound. Below is a chart of nerve plexus which can be utilized, doses of various anesthetics, and a reminder of the dosage of lipid emulsion in LAST (toxicity) from the Annals of Emergency Medicine and EMDocs.

Nerve Blocks

https://www.annemergmed.com/article/S0196-0644(18)30262-2/fulltext

With an increasing rate of opioid abuse, and a not insignificant side effect profile, it’s time to start reconsidering our knee jerk reaction to reach for the morphine. There are multiple other modalities which may aid us in our overall goal of pain management and reduce our need for opioids, even if they do not eliminate them. As a responsible ED doc, it’s important to be aware of them and next time ask yourself, “How can I better this patient’s pain?” 

REFERENCES

Miller JP, Schauer SG, Ganem VJ, et al. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015;33(3):402-408.

E Silva LOJ, Scherber K, Cabrera D, et al. Safety and efficacy of intravenous lidocaine for pain management in the emergency department: a systematic review. Ann Emerg Med. 2018;72(2):135-144.e3.

Sin, B., et al, The Use of Intravenous Acetaminophen for Acute Pain in the Emergency Department  Acad Emerg Med 23(5):543, May 2016

Furyk et al. Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomized controlled trial Emerg Med J. 2018;35(3):179-84.

Cisewski, David, MD. Pain Profiles: Intravenous vs. Oral Paracetamol, EMDocs.net, 2018

Cisewski, David, MD. Pain Profiles: Feeling Blocked?, EMDocs.net, 2018

Milne, Ken, MD. Is Intravenous Lidocaine for Pain Safe and Effective in the ED?. ACEPNow. 2018. 

Greenfield, Lisa, MD. Nitrous Oxide For Pediatric Sedation. EMResident. 2015. 

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