Background
Renal colic is a common and deeply unpleasant presentation to the emergency department (ED), I can vouch for this having experienced it some years ago. I would give that experience zero-stars for pain (you can read my tripadvisor review here). You’ve no doubt seen several patients clutching their flank, sweating with pain and generally looking awful. Once you’ve excluded a few other mimics (notably AAA) then you’ll appreciate just how severe this pain can be. It’s thought to arise from a combination of ureteric spasm, increased peristalsis and pressure in the renal pelvis, often with an inflammatory component.
My standard approach is NSAIDs first and then opioids, and fluids, but despite this I still see patient in pain. Many patients won’t get complete relief even with my initial analgesia regimen, and thus need further dosing. What if we could do something more to perhaps relieve ureteric spasm>? Salbutamol is a smooth muscle relaxant, so might it have a role here?
Physiologically, the rationale is there. Salbutamol reduces ureteric tone and peristalsis in animal models, and with a good proportion excreted renally, local action seems plausible. Its side effect profile is familiar and tolerable, especially compared to more potent opioids. This week we have a paper looking at just this from our friends across the Pennines. The abstract is below, but as always read the full paper yourself.
Abstract
Background The pain of renal colic, mediated in part by ureteral spasm and inflammation, is often severe and difficult to control. Salbutamol has been shown to cause ureteral relaxation, but its effects on the pain of renal colic have never been studied. The objective of this trial was to investigate whether the use of intravenous salbutamol in addition to standard analgesia was associated with greater pain reduction compared with standard analgesia alone in patients presenting to emergency departments (EDs) with renal colic.
Methods This single-centre, double-blind, phase II, randomised, placebo-controlled trial recruited adult (≥18 years) ED patients with clinically suspected renal colic. Participants were randomised in a 1:1 ratio to receive either 250 µg of intravenous salbutamol or a placebo (0.9% sodium chloride). The primary outcome was the difference in the change in pain scores (measured on a 100 mm Visual Analogue Scale) from baseline to 30 min following trial treatment administration in participants with subsequently confirmed renal colic. A modified intention-to-treat analysis was undertaken for the primary population of participants with confirmed renal colic.
Results Consent was obtained from 151 patients; 108 participants with confirmed renal colic were included in the primary outcome analysis. There was no statistical difference between groups in median change in pain score at 30 min (salbutamol group −18 mm (IQR −25 to −3), placebo group −13 mm (IQR −33 to −1), difference 5 mm (95% CI −16 to 6, p=0.575)). No significant differences were found in the secondary outcomes related to pain, patient satisfaction or opiate requirement.
More adverse events (AEs) were observed in the salbutamol group (65) compared with placebo (42, p=0.02); no unexpected AEs were identified.
Conclusions This trial has not identified a clinically or statistically significant benefit from the addition of intravenous salbutamol to standard care for patients presenting to an ED with pain caused by renal colic.
Trial registration numbers The trial was registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), reference 2018-004305-11. It was also registered with the ISRCTN Registry, reference 14552440.
What Kind of Study Is This?
This was a single-centre, double-blind, randomised, placebo-controlled phase II trial run out of the Royal Derby Hospital, UK. Patients presenting to the ED with suspected renal colic were randomised 1:1 to receive either 250 micrograms of intravenous salbutamol or placebo (0.9% sodium chloride), alongside standard analgesia.
As a phase II trial, the main aim was to detect a signal of benefit – enough to justify a larger, more definitive phase III study. The primary outcome focused on pain reduction 30 minutes after drug administration in patients with confirmed renal colic, measured using the familiar 100mm Visual Analogue Scale (VAS).
Secondary outcomes included pain at other time points, morphine requirements, side effects, and patient satisfaction.
Phase II trials are early-stage studies designed to explore whether a treatment shows enough promise to justify larger, more definitive research. They typically focus on efficacy signals — looking for meaningful trends rather than definitive proof — and often use surrogate outcomes or smaller sample sizes. Unlike phase III trials, which are powered to detect statistically significant differences and influence clinical guidelines, phase II studies are primarily about deciding whether it’s worth going further. In this context, the authors were seeking an indication that salbutamol might be clinically useful, but the trial did not provide sufficient grounds to pursue a phase III study. So it’s unlikely to be a game changer, but it may be of interest.
Tell Me About the Patients
Recruitment ran from September 2019 to September 2022 (with a pandemic-related pause). Of the 1175 patients screened, 458 were eligible and 151 were consented. After accounting for exclusions and dropouts, 148 were randomised (74 per arm). The analysis focused on 108 patients with confirmed renal colic. That’s quite a reduction from the original screening number, but to be expected in this kind of trial.
Demographics were balanced. The mean age was early-to-mid 40s, about 70% male, and average baseline pain scores were high (median 67mm on VAS). Most had stones in the distal ureter, and sizes were small (mean 4–5mm), consistent with typical ED presentations. Also, smaller stones are more likeley to pass (rule of thumb under 1cm) , so if effective at pain relief there might also be a benefit to stone passage???
What Were the Measured Outcomes in This Study?
The primary outcome was the change in VAS pain score from baseline to 30 minutes after drug administration, in those with confirmed renal colic.
Secondary outcomes included:
- Change in pain score at other time points (15 min to 24 hours).
- Qualitative pain assessments via the McGill Pain Questionnaire.
- Morphine use over the following 24 hours.
- Occurrence of AKI.
- Side effect profiles and adverse events.
- Patient-reported satisfaction.
- Feasibility markers to inform future trials.
What Are the Main Results?
Primary outcome:
- Median pain reduction at 30 minutes in the salbutamol group: −18mm (IQR −25 to −3).
- Median pain reduction in placebo: −13mm (IQR −33 to −1).
- Difference: −5mm (95% CI −16 to 6, p=0.575).
This fell well short of the pre-specified minimum clinically important difference (MCID) of 13mm. It was neither statistically nor clinically significant. The confidence intervals just about pass the limit of clinical significance, but it seems unlikely that there will be any clinically meaningful effect here.
Secondary outcomes:
- Pain scores at all other time points were similar between groups.
- No difference in McGill Pain Questionnaire results.
- Morphine use, AKI rates, and satisfaction were all statistically comparable.
- However, the salbutamol group had more adverse events (65 vs 42, p=0.022), particularly tremor and palpitations.
Feasibility-wise, the study recruited to time and target, with good patient and clinician engagement.
Should we believe the results?
This is a solidly designed and pragmatically executed trial. It’s a credit to the authors that they pulled it off during the turbulence of COVID-19. That said, a few caveats deserve discussion.
Firstly, this is a pragmatic trial, meaning it reflects real-world ED practice rather than an idealised, tightly controlled lab setting. Generally that’s something that we prefer at St Emlyn’s (real world clinicians prefer real world trials). Patients were enrolled based on suspected renal colic, not confirmed diagnosis, though the primary analysis focused on the latter group.
Blinding at allocation was good, but it may have been easy to spot those who received salbutamol due to the associated side effects like tremor and tachycardia. We know this as almost half the salbutamol group correctly guessed their allocation, compared to just 20% in the placebo group. This may have biased subjective measures, though pain scores remained unimpressive even with this potential unblinding.
The delay between consent and administration (due to needing pharmacy-prepared, blinded medication) might also have diminished any benefit. Pain may have improved spontaneously or with initial standard analgesia in the interim, masking the effect of the trial drug.
The authors chose to do their primary analysis amongst those patients who had confirmed renal colic. That would not have been my preference as it’s almost always best to analyse on an intention to treat basis. On this occasion a sensitivity analysis looking at the date from an ITT perspective found the same none significant finding…… it would have been tricky if they had differed! I think this is OK in a phase II trial, but in a phase III I would go for an ITT at point of randomisation (though it looks very unlikely that we will see a phase III trial on this topic after this study).
Finally, the choice of intravenous administration is interesting. When I read the title I aimagined it was going to be by nebuliser as that’s what we do in conditions such as hyperkalaemia. I don’t think that would affect the results, just interesting to note.
Should We Change Practice Based on This Study?
In short: no.
The data simply don’t support the routine use of intravenous salbutamol as an adjunct in the acute management of renal colic. Pain reduction was marginal and below the threshold of clinical relevance. Side effects were more common, and there was no impact on other key outcomes like opiate use or satisfaction.
While this trial doesn’t entirely rule out a role for beta-agonists in renal colic, it does make it very unlikely that salbutamol – at least in this dose and form – offers anything useful in the ED setting. The authors are clear: there’s no justification for a phase III trial.
It sdid make me think about other drugs though. I’m found similar papers and findings on the use supplemental magnesium for renal colic. Itwould make similar a pathophysiological argument (and people seem to give magnesium for everything these days), but sadly there appears to be little benefit there either.
Perhaps the real takeaway is that renal colic still hurts – a lot – and we’re not as good at treating it as we’d like to think.
Summary
This well-conducted phase II trial explored whether intravenous salbutamol could offer additional pain relief for patients presenting to ED with renal colic. The physiological rationale was plausible, and the logistics feasible – but the results are clear: no clinically meaningful improvement in pain, and more side effects.
References
- Johnson GD, Tabner A, Fakis A, et al Salbutamol for analgesia in renal colic: a prospective, randomised, placebo-controlled phase II trial Emergency Medicine Journal 2025;42:378-386.
- Magnesium Sulfate Versus Lidocaine as an Adjunct for Renal Colic in the Emergency Department: A Randomized, Double-Blind Controlled TrialToumia, Marwa et al.Annals of Emergency Medicine, Volume 84, Issue 6, 670 – 677
- Simon Carley, “JC: Tamsulosin and Renal Colic. St Emlyn’s,” in St.Emlyn’s, July 12, 2018, https://www.stemlynsblog.org/jc-tamsulosin-and-renal-colic-st-emlyns/.
- Gregory Yates, “Intranasal ketorolac in renal colic,” in St.Emlyn’s, August 9, 2024, https://www.stemlynsblog.org/intranasal-ketorolac-renal-colic/.
- Simon Carley, “JC: Should USS be first investigation for renal colic? St.Emlyn’s,” in St.Emlyn’s, October 11, 2014, https://www.stemlynsblog.org/jc-uss-first-investigation-renal-colic-st-emlyns/.
- Rick Rolling. https://en.wikipedia.org/wiki/Rickrolling
