Stuck between a Rock and a Hard Place: Navigating Renal Colic Treatment

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Renal colic is a common presenting symptom in the ED, with an estimated prevalence as high as 10-15% in the US. (1) It accounts for approximately 1% of all ED visits per year. (27)  Most patients will pass these calculi spontaneously and do not require surgical intervention, therefore focus on pain relief is of utmost importance in the emergency department. (1) NSAIDs have shown to be as effective, if not more effective than opioids, making them a reliable first line agent. (4,5) Opioids still provide a viable option in those with kidney disease or gastric ulcer disease, however they may be best utilized as combination agents to decrease the need for rescue analgesia. There is weak evidence to support the use of IV acetaminophen, with high cost burden, limiting its utility. Additional agents such as ketamine, lidocaine and magnesium carry with them limited evidence and inconsistencies in the literature, limiting their use, with further studies required. Alpha blockers seem to provide a shorter duration to expulsion, fewer pain episodes, and less hospital admissions with surgical intervention, specifically with larger stones (>5mm). 

For some additional reading and listening on controversies in the management of kidney stones, check out our previous post and podcast.

NSAIDS: At least as Effective, if Not More Effective, than Opioids with Less Vomiting and Need for Rescue Analgesia

Renal colic from nephrolithiasis occurs when a renal calculus obstructs urinary flow, causing increased wall tension in the urinary tract. (4) This tension stimulates the release of prostaglandins that dilate the afferent arteriole arteries, causing diuresis and increased pressure in the urinary tract. (4) This viscous cycle is what’s thought to precipitate the level of pain experienced by the patient.  Based on this mechanism, NSAIDs are often employed for pain relief based on their inhibition of COX-1 and COX-2, preventing prostaglandin synthesis and vasodilation. 

NSAIDs appear to have a slight benefit over opioids in pain relief at 30 mins with lower vomiting rates and requirement for rescue analgesia when compared to opioids. (5) This appears to be consistent in the literature showing NSAIDs are at least as effective as opioids in treating renal colic. (4) Despite these results, a fear of adverse reactions caused by NSAIDs, specifically GI bleeding or renal failure, persists among clinicians. (5) The literature shows a paucity of side effects with minimum to no reports of serious adverse events. (1,2,4,5) A Cochrane Review of 50 studies comparing NSAIDs to non-opioids, specifically anti-spasmodic agents, found that NSAIDs were an effective treatment for renal colic when compared to non-opioid agents. (1) Interestingly, this review found the addition of antispasmodics to NSAIDs did not result in better pain control. (1)   

Route of administration is thought to play an additional role in onset of pain relief, with IV achieving the fastest rate. (7) However, there is some evidence that intramuscular injections of NSAIDs (specifically diclofenac) can provide not only adequate pain relief, but superior pain relief when compared to morphine/paracetamol. (7) This can be an effective and readily available method of pain reduction in patients with difficult to obtain IV access. Many of these studies use supratherapeutic doses of NSAIDs, specifically 30mg of ketorolac despite evidence to suggest adequate analgesia using ketorolac at its ceiling dose of 10mg. (6) As NSAIDs continue to show adequate/superior analgesia when compared to various medications, clinicians should remain mindful of the ceiling dose of ketorolac.

Opioids: Remain a viable option, should be used sparingly or in combo with ketorolac to reduce doses and need for rescue analgesia given inconclusive evidence of effectiveness compared to NSAIDs

Along with NSAIDs, opioids continue to play a large role in the management of renal colic. There remain many advantages in using opioids for pain relief in this patient population as opioids are cheap, effective and titratable. (8) In the event that patients require immediate analgesia without IV access, IN fentanyl provides rapid and efficient pain relief in patients presenting with renal colic. (10) This can be kept in a clinician’s back pocket for specific patient populations. However, fear of side effects including respiratory depression and hypotension, as well as the potential for addiction in the ongoing opioid epidemic, make them less enticing of an option. (8)

Despite much of the earlier literature using comparison arms treated with meperidine, more recent studies compared morphine with NSAIDs and paracetamol found that morphine was less effective in reducing pain at 30 minutes compared to NSAIDs and paracetamol. (5)

The literature has largely pivoted from a focus on opioids effectiveness to exploring possible alternative therapies to opioids or combination therapy to reduce the dosage of opioid or the need for rescue analgesia. Studies suggest the combination of morphine and ketorolac provide superior pain relief and reduce the need for rescue analgesia. (8,9) The benefit of combination therapy may be the reduction in the need for rescue analgesia. This decreased need for rescue analgesia can have potential benefits that should be studied further including decreased need for hospitalization and possibly limiting side effects involved with giving additional morphine. 

IV Acetaminophen: May be more effective than opioids, however evidence is weak and cost burden is high limiting its utility 

Since the approval of IV acetaminophen in the US in 2010, it’s use as an alternative agent for pain relief has been analyzed extensively, renal colic being no exception. The mechanism by which IV acetaminophen exerts its benefit in renal colic is as a weak COX-1 inhibitor. The IV formulation has many advantages including a fast time of onset of 5-10 minutes, a peak analgesic effect at 1 hour, and a duration of action of 4-6 hours. (11) In patients with contraindications to NSAIDs and opioids, IV acetaminophen has the potential to be an effective alternate agent. Despite these pros, the literature is inconsistent regarding the application of IV acetaminophen for renal colic. There’s weak evidence to support its effectiveness when compared to NSAIDs, albeit at an extra cost burden. (11) Morphine has been compared to IV acetaminophen in multiple studies with variable results seen in Table 1. Given the inconsistency in the literature regarding IV acetaminophen’s role in renal colic, as well as the significant cost burden associated with IV acetaminophen, clinicians should weigh the benefits and risks on a case-by-case basis before considering IV acetaminophen for renal colic.

Table 1: Studies comparing IV acetaminophen/paracetamol to morphine 

Ketamine: May be effective when combined with opioids to lower opioid dose and incidence of rescue analgesia, though evidence is limited and will require further study 

Ketamine has become more widespread in the emergency department and can provide adequate analgesia at pain dose. The role of ketamine may be limited in patients with renal colic; however, it may have a place when used in combination with morphine. A RCT by Abbasi et al. looked at morphine use in combination with ketamine and found that patients experienced adequate pain relief with decreased use of rescue analgesia, though the initial dose of morphine (0.1 mg/kg) remained the same. (17) IN ketamine showed a modest response in patients with renal colic, with a possible larger role in the future given route of administration and speed of onset. (18) However, with the current availability limitations and a paucity of literature on the use of IN ketamine for renal colic, it will be quite some time before this could be considered a viable option. 

Lidocaine: Not currently recommended given weak evidence and inconsistencies to support its effectiveness and safety as an analgesic 

As with ketamine, lidocaine has been explored as a helpful adjuvant therapy to help reduce the reliance on narcotics. Unlike with ketamine, the literature on lidocaine for renal colic is much more controversial. A systematic review of 8 studies using lidocaine as an analgesic for various presentations in the ED concluded there is currently limited evidence to support its use for renal colic. (19) In addition to the limited evidence that exists, the safety of lidocaine in the ED as an analgesic has not been adequately studied, and would need to evaluate for adverse effects to support its use. (19) Where lidocaine may have a more prominent role is in combination with an existing therapy to help reduce side effects and rescue analgesia. (20,21) This may be limited to a combination with morphine, as a RCT showed improvement in time to pain relief and nausea when combined with morphine but no improvement in pain relief when combined with ketorolac. (20,21) The remainder of the literature is weak, with existing case series and retrospective analyses looking at lidocaine as a sole agent for treatment of renal colic. (22,23) The use of lidocaine cannot be recommended based on the current literature. 

Magnesium: May be effective as a second line agent in cases refractory to opioids/NSAIDs, though evidence is limited and will require further study  

A literature search for pain management of renal colic also includes a few studies involving magnesium and its potential analgesic effect on the urinary system. It’s postulated that magnesium’s action as a smooth muscle relaxer and antagonism of NDMA receptors may lead to blockage of neurotransmission of pain. (25) Magnesium’s role may be in rescue analgesia; there appears to be no benefit when given in combination with ketorolac but may be effective as a second line agent to renal colic refractory to NSAIDs or opioids. (24,25) Patients that had pain refractory to their initial dose of morphine or ketorolac experienced pain relief when provided with magnesium as a second agent. (24) It’s an intriguing possibility that magnesium can serve as a rescue analgesia, further decreasing our reliance on narcotics. 

Alpha Blockers: Decreases time to stone passage, episodes of pain, hospital admissions and surgical intervention, specifically with larger stones (> 5mm)  

Based on a 2018 Cochrane Review and 2016 systematic review/meta-analysis, there does seem to be some benefit to alpha blockers in patients with larger stones (>5mm). (2,26) Patients who were prescribed alpha blockers had a shorter time to stone passage of about 3.79 days, fewer episodes of pain, and lower risks of both surgical intervention and hospital admissions. (26) These findings were independent of stone location. (26) As with all medications, adverse effects were recorded, specifically dizziness and syncope, of which risks were minimal compared to benefits. (26) Given that most stones encountered in the emergency department (< 1cm) will not require surgical intervention, providers should discuss the risks and benefits of this therapy with patients with the greatest consideration for treatment with stones >5mm.

References

  1. Afshar, K., et al., Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev, 2015(6): p. CD006027.

  2. Campschroer T, Zhu X, Vernooij RWM, Lock MTWT. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2018;2018(4). doi:10.1002/14651858.CD008509.pub3

  3. Minhaj FS, Hoang-Nguyen M, Tenney A, et al. Evaluation of opioid requirements in the management of renal colic after guideline implementation in the emergency department. Am J Emerg Med. 2020;38(12):2564-2569. doi:10.1016/j.ajem.2019.12.042

  4. Holdgate, A. and T. Pollock, Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. BMJ, 2004. 328(7453): p. 1401.

  5. Pathan SA, Mitra B, Cameron PA. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic [Figure presented]. Eur Urol. 2018;73(4):583-595. doi:10.1016/j.eururo.2017.11.001

  6. Motov S, Yasavolian M, Likourezos A, Pushkar I, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug; 70 (2):177-184.

  7. Pathan SA, Mitra B, Straney LD, et al. Delivering safe and effective analgesia for management of renal colic in the emergency department: A double-blind, multigroup, randomised controlled trial. Lancet. 2016;387(10032):1999-2007. doi:10.1016/S0140-6736(16)00652-8

  8. Safdar, B., et al., Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. Ann Emerg Med, 2006. 48(2): p. 173-81, 181 e1.

  9. Hosseininejad, S.M., et al., Efficacy and Safety of Combination Therapy with Ketorolac and Morphine in Patient with Acute Renal Colic; A Triple-Blind Randomized Controlled Clinical Trial. Bull Emerg Trauma, 2017. 5(3): p. 165-170.

  10. Belkouch, A., et al., Does intranasal fentanyl provide efficient analgesia for renal colic in adults? Pan Afr Med J, 2015. 20: p. 407.

  11. Sin B, Koop K, Liu M, Yeh JY, Thandi P. Intravenous Acetaminophen for Renal Colic in the Emergency Department: Where Do We Stand? Am J Ther. 2017;24(1):e12-e19. doi:10.1097/MJT.0000000000000526

  12. Zhili X, Linglong C, Shuang J, Baohua Y. Comparing the analgesic effect of intravenous paracetamol with morphine on patients with renal colic pain: A meta-analysis of randomized controlled studies. Am J Emerg Med. 2020;38(7):1470-1474. doi:10.1016/j.ajem.2020.03.061

  13. Masoumi, K., et al., Comparison of clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic: a randomized, double-blind, controlled trial. Emerg Med Int, 2014. 2014: p. 571326.

  14. Serinken, M., et al., Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial. Emerg Med J, 2012. 29(11): p. 902-5.

  15. Bektas, F., et al., Intravenous paracetamol or morphine for the treatment of renal colic: a randomized, placebo-controlled trial. Ann Emerg Med, 2009. 54(4): p. 568-74.

  16. Azizkhani, R., et al., Comparing the analgesic effect of intravenous acetaminophen and morphine on patients with renal colic pain referring to the emergency department: A randomized controlled trial. J Res Med Sci, 2013. 18(9): p. 772-6.

  17. Abbasi, S., et al., Can low-dose of ketamine reduce the need for morphine in renal colic? A double-blind randomized clinical trial. Am J Emerg Med, 2018. 36(3): p. 376-379.

  18. Farnia, M.R., et al., Comparison of intranasal ketamine versus IV morphine in reducing pain in patients with renal colic. Am J Emerg Med, 2017. 35(3): p. 434-437.

  19. LOJ, E.S., et al., Safety and Efficacy of Intravenous Lidocaine for Pain Management in the Emergency Department: A Systematic Review. Ann Emerg Med, 2018. 72(2): p. 135-144 e3.

  20. Firouzian, A., et al., Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med, 2016. 34(3): p. 443-8.

  21. Motov S, Fassassi C, Drapkin J, et al. Comparison of intravenous lidocaine/ketorolac combination to either analgesic alone for suspected renal colic pain in the ED. Am J Emerg Med. 2020;38(2):165-172. doi:10.1016/j.ajem.2019.01.048

  22. Soleimanpour, H., et al., Parenteral lidocaine for treatment of intractable renal colic: a case series. J Med Case Rep, 2011. 5: p. 256.

  23. Soleimanpour, H., et al., Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol, 2012. 12: p. 13.

  24. Chen LF, Yang CH, Lin TY, et al. Effect of magnesium sulfate on renal colic pain: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2020;99(46):e23279. doi:10.1097/MD.0000000000023279

  25. Maleki Verki M, Porozan S, Motamed H, Fahimi MA, Aryan A. Comparison the analgesic effect of magnesium sulphate and Ketorolac in the treatment of renal colic patients: Double-blind clinical trial study. Am J Emerg Med. 2019;37(6):1033-1036. doi:10.1016/j.ajem.2018.08.040

  26. Hollingsworth, J.M., et al., Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ, 2016. 355: p. i6112.

  27. Motov S, Drapkin J, Butt M, Monfort R, Likourezos A, Marshall J. Pain management of renal colic in the emergency department with intravenous lidocaine. Am J Emerg Med. 2018;36(10):1862-1864. doi:10.1016/j.ajem.2018.07.021

Authorship

Written by: Anthony Martella, MD

Peer Review: Hannah Hughes, MD MBA

Editing/Posting/Graphics: Jeffery Hill, MD MEd