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Three Part Question

In [adult patients presenting to ED with renal colic], do [intradermal sterile water injections] provide [effective analgesia]?

Clinical Scenario

A 32 year old patient presents with severe loin to groin pain. He is otherwise fit and well. CT KUB shows a 5 mm stone at the vesico-ureteric junction. You have read about intradermal sterile water injections being used in the context of labour pain and musculoskeletal injuries and wonder whether they may also provide benefit in renal colic.

Search Strategy

MEDLINE and EMBASE were searched using OVID on the 10th of September 2024 using the following keyword strategy with no date or language restrictions:

(Renal colic.mp. OR exp *Renal Colic/ OR exp *Ureteral Calculi/ OR ureteric colic.mp. OR kidney stone.mp. OR exp *Kidney Calculi/ OR exp *Nephrolithiasis/ OR exp *Urinary Calculi/ OR urethral stone.mp. OR exp *Ureterolithiasis/) AND (sterile water.mp. OR intradermal water.mp. OR water injection.mp. OR subcutaneous water.mp. OR intracutaneous injection.mp. OR exp *Water/ AND exp *Injections/).

A supplementary search was carried out using the Cochrane and Google Scholar databases. The reference lists of abstracts that were identified as relevant were also screened for studies.

Search Outcome

Our search identified 205 papers. 50 duplicates were excluded. Review of titles and abstracts excluded a further 134 as they were not relevant to our question. 21 papers progressed to full text review. Nine were excluded as they were letters to editors (n = 5), reviews (n = 2), conference abstracts (n = 1) or case reports (n = 1). Seven further papers were excluded as they did not address our three-part question fully.

Six randomised controlled trials (RCTs) and one prospective cohort study were included in the final analysis. All studies measured change in patient-reported pain score as a primary outcome.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Az et al. 2024 Turkey	ED patients with renal colic and radiologically proven (CTKUB) renal tract stones n = 320 Mean age: 45 (range 18-60) Male: 48% Four intervention groups (A-D): A = 0.5 ml x 4 ISWI (n = 80) B = 75 mg diclofenac IM (n = 80) C = 1 g paracetamol IV (n = 80) D = 100 mg tramadol IM (n = 80)	RCT Level 2	Subjective pain improvement, Visual Analogue Scale (VAS)	No difference at baseline. At 15 mins, significant difference (p < 0.001) in VAS score: 1.25 in ISWI group (A) compared to 3.45 (B) 5.03 (C) and 3.49 (D). No difference at one hour.	Excluded patients > 60 or with diabetes, renal impairment, pregnant, or moderate-severe hydronephrosis. Short period (60 minutes) of follow-up only: unclear if ISWI provides sustained pain relief comparable to comparison groups. Recruitment of patients after radiology limits applicability of findings to emergency care, where analgesia is typically prescribed earlier when renal colic is suspected.
			Use of rescue analgesia	No significant difference in use of rescue analgesia compared to (B) and (C)
			Adverse effects (not pre-defined)	No adverse effects in ISWI group
Aykanat et al. 2023 Turkey	ED patients with suspected severe renal colic (NRS > 6) n = 85. Mean age: 39 (range 18-65) Male: 91% Three intervention groups: (A-C): A = 0.5 ml ISWI x 4 + diclofenac 75 mg IM (n = 29) B = 75 mg diclofenac IM alone (n = 28) C = 75 mg diclofenac IM + 1 mcg/kg fentanyl IV (n = 28)	RCT Level 2	Subjective pain improvement, Numerical Rating Scale (NRS)	Significant (p < 0.001) reduction in pain intensity at 1,5,30,60 minutes for (A) vs (B) and (C). No difference at 120 mins.	Excluded patients > 65, patients with milder pain (NRS < 7). No consecutive recruitment, patients only recruited when researchers on shift. Limited information provided about treatment protocol: unclear which side injection given on. Women were under-represented (9%) in the trial sample, even considering higher incidence of renal colic in men.
			Use of rescue analgesia	No significant difference in use of rescue analgesia
			Adverse effects (not pre-defined)	Less patients reported adverse effects n= 2 than (B) n = 8 and (C) n = 9, but no statistical analysis
Moussa et al. 2021 Lebanon	ED patients with renal colic and radiologically proven (CTKUB) renal tract stones, n = 150 Mean age: 38 (range 18-55) Male: 78% Three intervention groups: (A-C): A = 0.5 ml ISWI (n = 50) B = 75 mg diclofenac IM (n = 50) C = 0.5 ml isotonic saline injection (n = 50)	RCT Level 2	Subjective pain improvement (VAS)	No difference in VAS at baseline. ISWI as effective in relieving pain at 30 mins as diclofenac and better than isotonic saline. 1.98 (A) vs 1.88 (B) vs 6.5 (C). Comparable effect to diclofenac at 45 and 60 mins.	Short follow up time (60 mins). Control group significantly younger than others. Limited information provided about treatment protocol: unclear how many ISWI injections were given.
			Use of rescue analgesia	ISWI had comparable use to diclofenac. Both ISWI and diclofenac had lower need for rescue analgesia than (C), p < 0.0001.
Mozafari et al. 2020 Iran	ED patients with renal colic and radiologically proven renal tract stones, n = 94 Mean age: 35 (range 18-55) Male: 93% Two intervention groups (A, B): A = 0.5 ml x 4 ISWI (n = 46) B = Morphine 0.1 mg/kg IV (n = 48)	RCT Level 2	Subjective pain improvement (VAS)	Lower starting VAS in (A) group. At 15 mins, VAS in (A) 4.85 vs 6.2 in (B), p=0.02. From 30 mins onwards, morphine group had significantly lower VAS scores.	Excluded age >55 and weight >100kg. Significantly lower baseline VAS in (B), p<0.001. Recruitment of patients after radiology limits applicability of findings to emergency care, where analgesia is typically prescribed earlier when renal colic is suspected. Women under-represented (7%) in trial sample even considering higher incidence of renal colic in men.
			Use of rescue analgesia	3 in (A), 1 in (B). No statistical analysis.
			Adverse effects (not pre-defined)	22% in (A), 10% in (B), p < 0.001
Aras et al. 2017 Turkey	ED patients with renal colic and radiologically proven (USS +/- XRKUB +/- CTKUB) renal tract stones, n = 31 Mean age: 37 Male: 58% One intervention: 0.1 ml x 4 ISWI	Prospective cohort study Level 4	Subjective pain improvement (VAS)	ISWI significantly reduced VAS from 9.25 to 0.75 (p < 0.001) in the first minute post injection. This analgesic effect remained for the full 120 mins of follow up	Some patients also received NSAIDs, no subgroup analysis. 20% received rescue analgesia, does not state which or whether these patients were excluded. Limited information about recruitment: unclear if patients were given treatment based on suspicion or radiological confirmation of stone. Lack of control group. No clarification of imaging modality used to confirm stone.
			Adverse effects (not pre-defined)	4 patients declined further ISWI due to the pain experienced during application.
Xue et al. 2013 China	Pregnant ED patients with renal colic and radiologically proven (USS) renal tract stones, n = 45 Mean age: 27 Male: 0% Two intervention groups (A, B): A = 0.5 ml ISWI x1 (n = 21) B = 1 g paracetamol PO (n = 24)	RCT Level 2	Subjective pain improvement (VAS)	No significant difference in baseline VAS. At 15 minutes, VAS 3.1 in (A) and 6.9 in (B), p<0.001. Significantly lower VAS in (A) across whole 60 mins.	Selection bias: patients required USS confirmation of stone to be included, may have excluded patients with smaller or more distal stones. No blinding. Small sample size (n=45). Only pregnant women studies limits generalisability. Short follow up (60 mins). No comparison to typical first-line analgesia for renal colic.
			Use of rescue analgesia	5% in (A), 33% in (B)
			Adverse effects (not pre-defined)	None in either group
Ahmadnia et al. 2004 Iran	ED patients with renal colic and radiologically proven (USS +/- IVP) renal tract stones, n = 100 Mean age: 35 (range 21-55) Male: 72% Two intervention groups (A, B): A = 0.5 ml ISWI x 1 (n = 50) B = 0.5 ml normal saline x 1 (n = 50)	RCT Level 2	Subjective pain improvement (VAS)	No significant difference in baseline VAS. At 30 mins, VAS in (A) 0.76, 6.7 in (B), p < 0.0001. VAS in (A) remained significantly lower at 90 mins.	Narrow range of ages. Patients treated after imaging confirmation and not on suspicion of stones. No comparison to typical first-line analgesia for renal colic.
			Use of rescue analgesia	6% in (A), 34% in (B), p < 0.0001
			Adverse effects (not pre-defined)	None in either group

Comment(s)

The RCTs included in this BET review investigated intradermal sterile water injections (ISWI) – typically 4 injections of 0.5 ml volume into the most painful flank. The results indicate that ISWI can provide effective pain relief in renal colic. Currently, the National Institute for health and Care Excellence (NICE) recommend offering patients with suspected renal colic an NSAID by any route (NICE, 2019). When this is contraindicated, IV paracetamol can be used; opioids can be considered third line if pain relief is insufficient. Three trials used diclofenac as a comparison group. In these trials, ISWI was as effective or more effective than diclofenac, especially up to 30 minutes. ISWI also had fewer adverse effects when compared to diclofenac. However, there are numerous limitations to the studies and methodological inconsistencies. All but one of the studies required radiological evidence of stones prior to treatment. Renal colic can cause severe pain. In the ED, best practice is to give patients analgesia based on suspicion of stones rather than wait for radiology. It is therefore difficult to draw conclusions on whether ISWI is effective when treating on suspicion of stones based on these studies. No studies included patients older than 60. Some excluded patients with diabetes, renal dysfunction or cardiovascular disease. This limits generalisability to a group that are more comorbid and would potentially have the most to gain from having an analgesic option with limited side effects. Furthermore, the ISWI protocol differed between studies, with some opting for 4 point injection whereas others utilised a single point injection, with volumes of either 0.1ml or 0.5ml per injection. The comparison groups varied significantly between studies, from the gold standard NSAID to treatments such as oral paracetamol or IV tramadol which are very rarely used for renal colic in the UK. While ISWI appears to be a promising analgesic option, the lack of long-term follow-up and the exclusion of crucial patient groups limit the generalisability of the findings to the patients most likely to benefit from ISWI. A pragmatic multi-centre trial which includes elderly and comorbid patients, compares ISWI to a meaningful control such as diclofenac and looks at longer term pain outcomes is needed to establish ISWI as a treatment for renal colic in the emergency department.

Clinical Bottom Line

ISWI appears to provide rapid and effective pain relief in renal colic, particularly in the first 15-30 minutes post injection. It has few adverse effects and may be a viable option in patients where other types of analgesia are contraindicated.

References

1. Az et al. Intradermal Sterile Water Injection: Safe and Effective Alternative for Relief of Acute Renal Colic in the Emergency Department J Emerg Med. 2024;66(2):83-90.
2. Aykanat et al. The efficacy of intradermal sterile water application in severe renal colic: a randomised clinical trial Urolithiasis. 2023;51(1):121.
3. Moussa et al. Intradermal sterile water injection versus diclofenac sodium in acute renal colic pain: A randomized controlled trial Am J Emerg Med. 2021;44:395-400.
4. Mozafari et al. Comparing Intradermal Sterile Water with Intravenous Morphine in Reducing Pain in Patients with Renal Colic: A Double-Blind Randomized Clinical Trial Rev Recent Clin Trials. 2020;15(1):76-82.
5. Aras et al. Investigation of the effect of intracutaneous sterile water injection: A rapid and effective approach in urolithiasis-related renal colic treatment New J Urol 2017; 12 (3): 35-39
6. Xue et al. Intracutaneous sterile water injection versus oral paracetamol for renal colic during pregnancy: a randomized controlled trial Int Urol Nephrol. 2013;45(2):321-325.
7. Ahmadnia et al. Treatment of Renal Colic Using Intracutaneous Injection of Sterile Water Urology Journal. 2004;94:97-94.
8. National Institute for Health and Care Excellence Renal and ureteric stones: assessment and management [NG118] 2019