Date written: January 2025 – Public comment
Authors: CARI Guidelines Kidney Stones Working Group
GUIDELINE RECOMMENDATIONS |
Practice points
|
Scope of the guidelines
These guidelines deal with the management of acute pain from kidney stones in adults. Other clinical practice guidelines should guide management of acute pain management of kidney stones in children.
Background
Acute pain is the most common clinical manifestation of kidney stones (1, 2). Acute kidney pain accounts for one-third of all abdominal pain presentations to the emergency department (3) and is very often graded moderate to severe. Acute kidney pain is also the most common cause of repeat pain-related presentations to the emergency department (3). Most patients will request and require pain relief to control the pain (2) and report substantial impairment to quality of life (4) from episodes of recurrent pain.
As a fundamental part of the CARI Guidelines development process, lived experience workshops were undertaken in Auckland and Whangarei, Aotearoa New Zealand, in May 2021. Across the 28 workshop participants, all of whom experienced recurrent kidney stones, experiences of pain during episodes of acute kidney stones were one of the most highly discussed and prioritised topics. Participants also shared frustrations around being dismissed, and difficulties accessing appropriate pain relief and medical care.
“When it comes to pain, I think it’s getting treatment for that pain. Because by the time you get somewhere, the pain might’ve subsided. Then, they send you home, and the pain hurts again. So, it’s listening to people when they say they get that pain, and it’s ongoing.”
As a result, there is a need for clear guidance on management of acute pain from kidney stones. CARI Guidelines have reviewed the available literature to evaluate the safety and efficacy of pain management and treatment in kidney stones. Please note that the guideline development methods are available in Appendix 1, and the search strategy is detailed in Appendix 2.
Implementation and audit
Healthcare workers implementing these pain management recommendations for kidney stone patients should include a focused educational component to ensure people with recurrent kidney stones are informed of the efficacy and safety of pain medication. All recommendations are unlikely to be relevant clinical quality indicators, due to limitations in the certainty of the evidence. Additionally, the preferences and values for pain medication identified from the CARI Guidelines kidney stones workshops vary, with some participants expressing a desire for medications that may be perceived as stronger.
Guideline recommendations
We recommend non-steroidal anti-inflammatory drugs (NSAIDs) as first-line therapy for short-term management of acute pain from kidney stones.
(Strong recommendation, moderate certainty of the evidence)
Rationale
Evaluation of the scientific evidence from the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (8) indicates that NSAIDs may be superior in reducing pain and the need for rescue medication (4-7). Three systematic reviews and 13 randomised controlled trials (RCTs) found there were no differences in adverse events compared to paracetamol or placebo with standard care, and a reduction in adverse events compared to opioids (4-7). NSAIDs are widely available in settings where acute kidney stone pain is managed, with clinical staff exhibiting the appropriate skills and expertise. Patients’ preferences for timely intervention to manage pain, as identified at our patient involvement workshops, clearly highlights the need for a strong recommendation, despite the limitations of the available evidence.
Benefits and harms
The evidence review identified three systematic reviews (4-6) and a network meta-analysis (7), which highlighted that NSAIDs were superior to opioids, paracetamol, and combination therapy in both efficacy and safety for pain management of kidney stones (7):
Opioids
Pain reduction
Compared to opioids, NSAIDs demonstrated greater initial pain reduction at 30 minutes (11 RCTs, n = 1985, MD = –5.58, 95% CI: –10.22, –0.95; I2 = 81%), noting that the prediction interval (MD = –18.49 to 9.07) indicates that future studies may find no difference or worse pain reduction.
Rescue treatments
NSAIDs, compared to opioids, decreased the need for rescue treatment analgesia (RR = 0.73, 95% CI: 0.57, 0.94; I2 = 52%) (4).
Adverse events
Compared to other treatments, NSAIDs had fewer adverse events (RR = 0.53, 95% CI: 0.40, 0.69) with lower incidence of vomiting compared with opioids (RR = 0.41, 95% CI: 0.24, 0.70; p < 0.009, I2 = 54%) (4). Another review found no difference in adverse events between NSAIDs and meperidine (6).
Paracetamol
Pain reduction
NSAIDs may make no difference to pain at 30 mins compared to paracetamol (4 RCTs, n = 1325, MD = –5.67, 95% CI: –17.52, 6.18; p = 0.35, I2 = 89%). However, one RCT (n = 1095) identified that at both 60 minutes (MD = 6.60, 95% CI: 4.37, 8.83) and 90 minutes (MD = 3.4, 95% CI: 2.01, 4.79) NSAIDs (Diclofenac) were superior to paracetamol for pain reduction. Additionally, RCTs (9, 10) found varying results, with NSAIDs demonstrating benefit compared to paracetamol in pain reduction using VAS scores.
Rescue treatments
NSAIDs, compared to paracetamol, probably decrease rescue treatments (2 RCTs, n = 1145, risk ratio = 0.56, 95% CI: 0.42, 0.74; p < 0.001, I2 = 0%). However, two RCTs (9, 10) probably found no difference in the need for rescue analgesia between the NSAID parecoxib and paracetamol (RR = 1.32, 95% CI: 0.87, 2.00).
Adverse events
Systematic reviews found there was probably no difference between treatment-related adverse events in people treated with NSAIDs and paracetamol (4 RCTs, n = 1325, RR = 1.10, 95% CI: 0.47, 2.58; p = 0.82, I2 = 0%) or vomiting rates (2 RCTs, n = 1195, RR = 0.54, 95% CI: 0.15, 2.00; p = 0.36, I2 = 0%) (4).
Placebo and standard care
Pain reduction
Compared to placebo with standard care, NSAIDs reduced pain by 50% within 60 minutes (3 studies, n = 197, RR = 2.28, 95% CI: 1.47, 3.51; I2 = 15%).
Rescue treatments
Compared to placebo with standard care, NSAIDs decreased the need for rescue analgesia treatment (4 studies, n = 80, RR = 0.35, 95% CI: 0.20, 0.60; I2 = 24%), with no difference between intravenous and intramuscular administration (4).
Antispasmodic medication
Pain reduction
The Afshar 2015 review (5) found that NSAIDs, compared to antispasmodic medication, may have a 50% greater effect on pain (7 studies, n = 359, RR = 1.89, 95% CI: 1.12, 3.19; I2 = 88%). When only compared to studies that used hyoscine, the effect was increased, and heterogeneity decreased (5 studies, n = 196, RR = 2.44, 95% CI: 1.61, 3.70; I2 = 28%). Additionally, the NSAIDs reduced VAS pain scores, compared to antispasmodics (5 studies, n = 303, MD = –12.97, 95% CI: –21.80, –4.14; I² = 74.49%). The combination of NSAIDs with antispasmodics, compared to NSAIDs alone, probably reduced mean VAS pain scores (2 studies, n = 310, MD = –1.99, 95% CI: –2.58, –1.40; I2 = 0%) but combination therapy probably had no effect on more objective measures of 50% reduction in pain (9 studies, n = 906, RR = 1.00, 95% CI: 0.89, 1.13; I2 = 59%).
Rescue treatments
NSAIDs, compared to antispasmodics, probably reduced the need for rescue analgesia (4 studies, n = 299, RR = 0.34, 95% CI: 0.14, 0.84; I² = 65%). The combination of NSAIDs with antispasmodics, compared to NSAIDs alone, probably reduced the need for rescue analgesia (7 studies, n = 589, RR = 0.99, 95% CI: 0.62, 1.57; I2 = 10%).
Certainty of the evidence
The overall certainty of the evidence was graded as moderate. The systematic reviews of RCTs varied, but all had limitations in the available evidence for critical outcomes, such as >50% reduction in pain and the need for rescue analgesia. Reviews comparing NSAIDs to opioids had study limitations, inconsistencies, and study imprecision evident. Reviews comparing NSAIDs and paracetamol exhibited concerns about imprecision due to the small number of events and inconsistencies between the other RCTs identified in the review. Reviews comparing NSAIDs to placebo with standard care demonstrated concerns about imprecision, with few events for critical outcomes of pain reduction and the need for rescue analgesia. Finally, reviews comparing NSAIDs to antispasmodics included studies with methodological limitations. However, the network meta-analysis was well conducted and dealt with many of the issues of imprecision evident in the existing pairwise systematic reviews; hence, the evidence certainty was rated as moderate due to study limitations.
Preferences and values
The CARI Guidelines lived experience workshops conducted in Auckland and Whangarei Aotearoa New Zealand in May 2021 identified appropriate and effective pain management as one of the key concerns for individuals who experienced kidney stones. Often, people with kidney stones described difficult and ineffective management of their pain during an episode of kidney stones, mainly when presenting at hospital emergency departments.
“If you go to the A and E [Accident and Emergency], that’s what usually happens. They start you off on probably taking some paracetamol… and slowly building up to the better drugs, I suppose. But most of the stuff they start you off with doesn’t touch it.”
The negative encounters and frustrations towards the healthcare system and clinicians were exacerbated by the experiences of often excruciating pain, reported by most workshop participants.
“[when asked to rate pain levels]… on a scale of one to 10… 11/10… [another participant] You only got to 11? I got to 22…”
“Everything was uncomfortable. Standing, lying, sitting… You’re crawling up the walls…”
“Well, I actually fainted from one stage from the pain… I was in the hospital, and they wouldn’t believe me…”
In addition, participants shared a preference for the “strong stuff” – namely, opioid therapy – due to the perception that it was the only effective treatment option for acute kidney stone pain. However, participants expressed concerns about the risk of addiction, with some sharing their addiction experiences, particularly due to the higher doses required to maintain pain relief efficacy.
“I was chewing over half a card of Tramadol a day and I was having about four or five Sevredol tablets and two codeine [tablets] on top of that. I just couldn’t live without it, and it got worse and worse and worse…”
Further, participants shared that, despite opioids being an effective temporary pain management option, the consequences of regular consumption may be severe, particularly the impacts on their ability to participate in daily life, and on their capacity to work and meet the demands of their occupations.
“There’s no point in having like Tramadol and Sevredol, and be like, “Yeah, I’m going to function.” You might as well just fall on your face. You’re not there… it just wipes you completely off of the earth”.
Improved communication between providers and patients is required, particularly regarding the benefits and harms of pain medication in managing acute pain from kidney stones.
Equity
From an equity perspective, the management of pain from kidney stones was identified as a challenge by the participants in the CARI Guidelines consumer workshops. Patient characteristics influence prescribing rates of pain medication (11); it is well documented that disparities in pain management occur, with those most marginalised across ethnicity, gender and age receiving inadequate pain medication across multiple settings (12). Workshop participants shared their negative experiences of bias from healthcare professionals when presenting at ED for acute pain episodes due to their ethnicity or because of their ongoing pain relief requests.
“I wanted the pain relief, saying “give me pain relief”…. And then I was Māori, requesting pain relief, wanting more pain relief… still asking for more pain relief. And so, then I wasn’t getting much care at all, because I was just totally judged.”
[re: waiting in ED] “… And you’re crawling up the walls and then they have to check to make sure you’re not a druggie, and not just trying to get a fix…”
“I get treated as if you’re some sort of addict going in… but you know why you’re there… they don’t look at your history properly…”
While the specific disparities and the impacts on prescribing rates for pain management of kidney stones for disadvantaged groups is not well understood, these guidelines aim to reduce inequity by recommending prescribing pain management therapy based on up-to-date evidence.
Resources and other considerations
To the knowledge of the CARI Guidelines Kidney Stones Working Group, there is no available cost-effectiveness analysis examining pain medication for kidney stones, particularly in emergency department settings where medication is administered. NSAIDs are commonly available in all emergency departments, with clinical staff having the required expertise for administration.
We recommend paracetamol or opioids are used as second-line therapy for short-term management of acute pain from kidney stones.
(Strong recommendation, low certainty of the evidence)
Rationale
While NSAIDs are superior to other analgesia, their duration is short; complete and 50% pain relief is measured at 30 minutes in most RCTs (4), while other RCTs examine pain relief up to 90 mins (6). Regular use of NSAIDs is cautioned in patients with kidney disease and cardiac disease; as an alternative, paracetamol or opioids are still effective in pain reduction when compared to placebo. Their use should be considered in patients with an intolerance to NSAIDs, pain refractory to NSAIDs, or as additional therapy to assist in pain control. The CARI Guidelines Working Group recognises that a clear stepwise approach to acute pain management for kidney stone patients may help alleviate the disparity in access to medication for marginalised people, such as those of non-white ethnicity and women (11, 12). Despite the limitations of the available evidence, the strong emphasis for a clear stepwise approach to acute pain management for kidney stones, as expressed by people with lived experience of disease, as well as the potential to improve equity, led to the rating of the recommendation as strong. The Working Group recognise that most people in this situation would prefer the recommended second-line course of pain management.
Benefits and harms
Paracetamol is effective in reducing acute pain associated with kidney stone episodes (6). Paracetamol is as effective as NSAIDs in pain relief at 30 mins for acute kidney stones pain (4 RCTs, n = 1325, MD = –5.67, 95% CI: –17.52, 6.18; p = 0.35; I2 = 89%) (4); however, another RCT (n = 1095) found that NSAIDs (diclofenac) were superior to paracetamol for pain reduction at 60 mins (MD = 6.60, 95% CI: 4.37, 8.83), and 90 minutes (MD = 3.40 95% CI: 2.01, 4.79) (6). NSAIDs, compared to paracetamol, also decrease the need for rescue therapy (2 RCTs, n = 1145, RR = 0.56, 95% CI: 0.42, 0.74; p < 0.001, I2 = 0%) (4). The reviews also found no difference between treatment-related adverse events (4 RCTs, n = 1325, RR = 1.10, 95% CI: 0.47, 2.58; p = 0.82, I2 = 0%) or vomiting rates (2 RCTs, n = 1195, RR = 0.54, 95% CI; 0.15, 2.00; p = 0.36, I2 = 0%). Compared to opioids (morphine), paracetamol had no effect on pain at 15 minutes, but decreased pain at 30 mins (VAS; 3 RCTs, MD = –3.92, 95% CI: –6.41, –1.43) (6). However, the systematic review reported no difference in adverse events between morphine and paracetamol in people treated for acute pain from kidney stones (RD = –0.11, 95% CI: –0.27, 0.05) (6).
Certainty of the evidence
The certainty of the evidence was low. The outcomes identified in the systematic reviews were limited. The few RCTs had a small number of participants comparing paracetamol with other pain relief medications. As a result, the certainty of the evidence has been downgraded due to imprecision and methodological limitations of the included RCTs.
Preferences and values
Participants at the 2021 CARI Guidelines Kidney Stones Consumer Workshops expressed frustration at the stepwise approach to pain medication during episodes of kidney stones. There was a perception that opioids were the most effective medication but a reluctance towards their use due to concerns of addiction, with participants describing instances of discrimination and feeling judged as people with a substance use disorder looking for drugs. Additionally, an Irish study conducted with 33 participants with kidney stones disease in urology outpatient clinics described the impact of the acute pain on their mental health, leading to a fear of recurrence. Pharmacological management was seen as the only means to manage acute pain from kidney stones, with morphine mentioned as the only medication that worked for one participant (13).
Equity
The most marginalised people with acute pain due to kidney stones are known to receive inadequate pain medication within multiple settings (11, 12). Following a stepwise approach, as our guidelines recommend, will ensure consistent pain management for people with acute pain due to kidney stones and may help to combat the inequities currently seen in management.
Resources and other considerations
Paracetamol and opioids are widely available in both Australia and New Zealand at little cost. Clinical staff across emergency departments and paramedics have the required skills for their use in the management of acute pain associated with kidney stones. To our knowledge, no cost-effectiveness evaluation on paracetamol use has been undertaken.
Practice points
Regular NSAIDs should be used with caution in people with reduced kidney function and cardiac comorbidities.
In pregnancy non-pharmacological options for pain management for kidney stones should be considered before analgesia due to potential adverse foetal outcomes associated with commonly used pain medication.
Rationale
There is limited data to support pain medication in the management of acute kidney stones in pregnancy. Many of the commonly used therapies in adults, NSAIDs, paracetamol and opioids, are associated with adverse foetal and childhood development outcomes (8).
All recommended pain medication is short-acting (30-90 mins), and rescue pain relief should be anticipated and planned for before the effects of analgesia wear off.
Rationale
The systematic reviews identified primarily reported pain reduction to 30 minutes. However, trials did note up to 90 minutes (4-6). Analgesia is short-acting, and rescue relief should be planned and anticipated to minimise patient discomfort.
Analgesia and pain control is only one aspect of acute pain management of kidney stones. The definitive treatment should be aimed at early removal of the stone to relieve obstruction.
Rationale
The ultimate management for acute kidney stones is for the extraction of the stone to relieve the pain and possible obstruction. Pain relief is vital to alleviate discomfort but is not the sole management target. We advise that an early plan for stone extraction (by conservative, medical, or surgical therapies) be addressed and implemented as needed.
Suggestions for future research
- No trial examined the efficacy of analgesia administered orally. Most patients will require a substantial wait until they arrive in the emergency department and are assessed prior to analgesia administration. We recommend clinical trials in outpatient settings with oral administered pain relief medication to guide the optimal management of acute pain in people with kidney stones.
- Further clinical trials comparing antispasmodics combined with NSAIDs compared to NSAIDs alone for acute pain management in kidney stones are required.
- Tailored education programs on acute pain during kidney stone episodes could be evaluated as an implementation of these guidelines to support self-management of acute pain during stone episodes in people with recurrent kidney stones.
CARI Guidelines Kidney Stones Working Group
David J Tunnicliffe1, 2
Lyn Lloyd3
Adam Mullan4
Andrew Mallett5,6,7,8
Ieuan Wickham9
Alex Currie9
Nadya York
Brydee Cashmore1, 2
Matthew Jose10*
Hicham Hassan 11, 12*
*Authors have contributed equally as Co-Convenors of the Guideline Working Group.
Affiliations
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, NSW, Australia
- Nutrition and Dietetics, Te Toka Tumai, Auckland, Health New Zealand
- Northland Renal Services, Te Tai Tokerau, Northland, New Zealand
- Department of Renal Medicine, Townsville University Hospital, Douglas, QLD, Australia
- College of Medicine and Dentistry, James Cook University, Douglas, QLD, Australia
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Queensland, QLD, Australia
- Consumer Partner
- School of Medicine, University of Tasmania, Hobart, TAS, Australia
- Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
- School of Medicine, Lebanese American University School of Medicine, Beirut, Lebanon
Conflict of interest
The CARI Kidney Stones Working Group have no relevant conflicts of interests to report.
Funding
CARI Guidelines receives funding from the Australian and New Zealand Society of Nephrology, the Australian Living Evidence Collaboration, and the National Health and Medical Research Council Emerging Leadership 1 Investigator grant (APP1197337).
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