Pain management

1. Pain management

1.3. PICO table

For full details see the review protocol in appendix A.

Table 1

PICO characteristics of review question.

1.4. Clinical evidence

1.4.1. Included studies

Thirty-eight studies were included in the review;^{3, 4, 6, 9, 11, 15, 22, 27, 28, 32, 43, 49, 53, 54, 56, 62, 70, 71, 74, 77, 80, 82, 90, 93, 99, 100, 103, 114, 116, 120, 122, 123, 126, 129, 130, 133, 136, 144} these are summarised in Table 2 below. Twenty-two studies compared NSAIDS to opioids^{4, 6, 9, 25, 27, 28, 49, 53, 54, 56, 70, 71, 80, 90, 100, 103, 114, 116, 120, 123, 133, 144}, 3 studies compared NSAIDs to antispasmodics^{3, 32, 126}, 5 studies compared NSAIDs to paracetamol^{6, 22, 62, 93, 103}, 6 studies compared opioids to paracetamol ^{6, 11, 15, 82, 103, 122}, 4 studies compared NSAIDs to placebo ^{3, 74, 77, 136}, 2 studies compared opioid to antispasmodics ^{99, 130}, 1 study compared opioid to placebo ¹⁵, 1 study compared paracetamol to placebo ¹⁵, 1 study compared antispasmodics to placebo ³ and 4 studies compared combinations of pain relief medications. ^{54, 93, 126, 129} Evidence from these studies is summarised in the clinical evidence summaries below in Table 3 to Table 11.

See also the study selection flow chart in appendix C, study evidence tables in appendix D, forest plots in appendix E and GRADE tables in appendix H.

Two Cochrane systematic reviews were identified, however both were excluded. Both were excluded due to deviation from the review protocol to include drugs that are excluded in this review.

1.4.2. Excluded studies

See the excluded studies list in appendix I.

1.4.3. Heterogeneity

For the comparison of NSAID versus opioid/opiate, there was substantial heterogeneity between the studies when they were meta-analysed for the outcomes of pain intensity, partial pain relief, complete pain relief, need for rescue medication, reduction in pain by 50% and minor adverse events including vomiting, nausea and dizziness. For the comparison of NSAID versus paracetamol there was substantial heterogeneity between the studies when they were meta-analysed for the outcome pain intensity. For the comparison of NSAID versus antispasmodic, there was substantial heterogeneity between the studies when they were meta-analysed for the outcome of need for rescue medication. For the comparison of NSAID versus placebo, there was substantial heterogeneity between the studies when they were meta-analysed for the outcomes of pain intensity and complete pain relief. For the comparison of opioid/opiate versus paracetamol, there was substantial heterogeneity between the studies when they were meta-analysed for the outcome of pain intensity. Where pre-specified subgroup analyses (see Appendix A:) were either unable to be performed, or did not explain the heterogeneity, a random effects meta-analysis was applied to these outcomes, and the evidence was downgraded for inconsistency in GRADE.

1.4.4. Summary of clinical studies included in the evidence review

Table 2

Summary of studies included in the evidence review.

See appendix D for full evidence tables

1.4.5. Quality assessment of clinical studies included in the evidence review

1.4.5.1. NSAID versus opioid/opiate

Table 3

Clinical evidence summary: NSAID versus opioid/opiate.

1.4.5.2. NSAID versus paracetamol

Table 4

Clinical evidence summary: NSAID versus paracetamol.

1.4.5.3. NSAID versus antispasmodic

Table 5

Clinical evidence summary: NSAID versus antispasmodic.

1.4.5.4. NSAID versus placebo

Table 6

Clinical evidence summary: NSAID versus placebo.

1.4.5.5. Opioid/opiate versus paracetamol

Table 7

Clinical evidence summary: Opioid/opiate versus paracetamol.

1.4.5.6. Opioid/opiate versus antispasmodic

Table 8

Clinical evidence summary: Opioid/opiate versus antispasmodic.

1.4.5.7. Opioid/opiate versus placebo

Table 9

Clinical evidence table: Opioid/opiate versus placebo.

1.4.5.8. Paracetamol versus placebo

Table 10

Clinical evidence summary: Paracetamol versus placebo.

1.4.5.9. Antispasmodic versus placebo

Table 11

Clinical evidence summary: Antispasmodic versus placebo.

1.4.5.10. Combinations

Table 12

Clinical evidence summary: NSAID + antispasmodic versus NSAID.

Table 13

Clinical evidence summary: NSAID + antispasmodic versus antispasmodic.

Table 14

Clinical evidence summary: NSAID + opioid + antispasmodic versus NSAID + opioid.

Table 15

Clinical evidence summary: NSAID + opioid versus NSAID.

Table 16

Clinical evidence summary: NSAID + opioid versus opioid.

Table 17

Clinical evidence summary: NSAID + paracetamol versus NSAID.

Table 18

Clinical evidence summary: NSAID + paracetamol versus paracetamol.

See appendix F for full GRADE tables.

1.5. Economic evidence

1.5.1. Included studies

No relevant health economic studies were identified.

1.5.2. Excluded studies

No health economic studies that were relevant to this question were excluded due to assessment of limited applicability or methodological limitations.

See also the health economic study selection flow chart in appendix G.

1.5.3. Unit costs

Table 19

UK costs of pain drugs (not including method of administration).

Table 20

Other resource use.

1.8. The committee’s discussion of the evidence

1.8.1. Interpreting the evidence

1.8.1.1. The outcomes that matter most

The committee agreed that quality of life, pain, major adverse events and minor adverse events were the outcomes that were critical for decision making. Length of stay in hospital and use of healthcare services were also considered as important outcomes.

Evidence was reported for pain, major adverse events, minor adverse events, and length of stay. There was no evidence for the critical outcome of quality of life, or for the important outcome of use of healthcare services.

1.8.1.2. The quality of the evidence

For the majority of evidence in this review, the quality ranged from a GRADE rating of moderate to very low. This was due to a lack of blinding, presence of selection bias in terms of a lack of adequate randomisation and allocation concealment, and risk of measurement bias, resulting in a high or very high risk of bias rating. Evidence was further downgraded due to the presence of imprecision for many outcomes, and heterogeneity for some outcomes.

Six outcomes were given a high quality rating. This included pain in terms of reduction in pain by 50% and reduction in pain numerical rating scale (NRS) by >3, and came from a single large study of 1097 participants, in the opioid versus paracetamol comparison. In the NSAID versus paracetamol comparison, 2 outcomes (need for rescue medication and reduction in NRS pain score by >3) from the same study had a high quality rating, and in the NSAID versus opioid comparison the same study had high quality evidence for the persistent pain, and reduction in pain NRS score >3 outcomes.

1.8.1.3. Benefits and harms

Evidence for adults and children and young people was searched for, however none was identified for children and young people. The committee agreed that it would be appropriate for the recommendations to apply to both adults and children and young people based on consensus and current practice.

NSAID

The committee considered the evidence for NSAIDs and noted that the majority of the evidence was from studies that used an intravenous or intramuscular route of administration, whereas only one study used an oral preparation, and 4 used rectal preparations. It was noted that this differs from current practice, where oral or rectal are currently more common, and therefore the results may not reflect practice in the UK.

When compared to placebo, the committee noted that all pain outcomes apart from partial pain relief showed a clinically important benefit of NSAID.

When compared to paracetamol, the committee noted that there was no difference between the interventions in terms of pain intensity, but there were benefits of NSAIDs in terms of need for rescue medication and the number of people with persistent pain. The committee noted that the majority of the studies used an intravenous route for paracetamol. Only one study used an oral route and this was a very small study of low quality. The committee discussed that the evidence for pain intensity did not reflect experience from clinical practice, and considered that this may be due to the use of an intravenous route of administration for paracetamol. The committee noted that intravenous paracetamol is very different to other routes of administration in terms of speed of action and potency, and that intravenous paracetamol is not part of usual practice. Because of this, the committee agreed that this evidence cannot be extrapolated other routes of administration.

The committee considered the evidence for NSAIDs compared to opioids and noted that in terms of pain, the majority of evidence suggested either a clinical benefit of NSAIDs or no difference between the 2 interventions. The committee agreed that overall the evidence for adverse events demonstrated a clinical benefit of NSAIDs. The committee concluded that the evidence demonstrates that NSAIDs are more effective in terms of reducing the need for additional rescue medication, reducing both pain intensity and length of pain episodes, and have fewer adverse events. The committee also discussed the difficulties of administering opioids in clinical practice, and therefore the potential benefits of using NSAIDs, such as potentially shorter hospital stays and quicker pain relief for patients. The committee also considered the implications of prolonged opioid use and potential misuse, and agreed based on clinical experience and expertise that NSAIDs are therefore a safer option.

The comparison of NSAID and antispasmodics showed a benefit of NSAIDs for most pain and adverse events outcomes reported. There was no difference between the two interventions in terms of pain intensity, although the committee noted that this was a single study of low quality, and did show a trend towards a benefit of NSAIDs. The committee therefore agreed that overall, the evidence supported the use of NSAIDs over antispasmodics. Overall, the committee noted that the evidence demonstrated that NSAIDs were more clinically effective that placebo, opioids, paracetamol and antispasmodics, and therefore NSAIDs should be recommended as a first line pain relief. The committee noted from clinical experience that NSAIDs carry risks such as acute kidney injury (AKI), and therefore all patients receiving NSAIDs should be monitored for this risk, as well as all other associated side effects and contraindications. The committee discussed specifying a particular route of administration for NSAIDs, but agreed that the evidence was too varied in terms of the administration route used in the studies. They agreed unlike paracetamol, the difference between the routes in terms of potency and speed of action is not as significant for NSAIDs and that experience from clinical practice suggests that they are all equally effective, They noted that head to head comparisons of route of administration was not part of the protocol and so this was not specifically looked for in the evidence. Overall, the committee agreed to specify in the recommendation that any route of administration could be used. This also allows the recommendation to be applicable to a community setting, where oral or rectal NSAID can be used, as recurrent stone formers in particular tend to manage their pain at home. The committee considered that many of the studies were over 15 years old, and may be reflective of standard practice at that time, when intravenous NSAIDs were often used. However, the committee agreed that standard practice for NSAIDs administration has changed and now an oral or rectal route of administration is used. This is not based on evidence, but due to other factors such as changes in availability and ease of use. They therefore agreed that a research recommendation in this area would inform future practice.

Paracetamol

When compared to placebo, the committee noted that there was a benefit of paracetamol for both pain outcomes, and no difference or benefit of placebo in terms of adverse events. The committee noted that all evidence from this comparison came from a single study of 97 participants.

The committee also considered the evidence for NSAID versus paracetamol and opioid versus paracetamol. Overall, the committee agreed that the evidence suggested a benefit of paracetamol over placebo and opioids, but not when compared to NSAIDs. The committee therefore agreed that paracetamol should be recommended as a second line treatment where NSAIDs can’t be used or have not been effective.

The committee noted that all evidence for paracetamol was from studies that used an intravenous route of administration, apart from one small study that used an oral route. They agreed that this data could not be used to extrapolate to other routes of administration. Therefore, the committee agreed to specify that if paracetamol is used, it should be given intravenously.

Opioid

The committee noted that when compared to placebo, there was a clinical benefit of opioids in terms of need for rescue medication, but no clinical difference in terms of pain intensity, and some adverse events. The committee agreed that this suggests that there is no benefit of opioids over placebo, but noted that all evidence from this comparison came from a single study of 100 people and was all of low or very low quality.

When compared to intravenous paracetamol, the committee noted that the evidence suggested a clinical benefit of paracetamol in terms of reduction in pain by 50%, persistent pain and some adverse events, and no clinical difference in pain intensity, need for rescue medication and major adverse events outcomes. The committee agreed that this suggests there is no benefit of opioids over paracetamol, and that intravenous paracetamol should be offered before considering the use of opioids.

When compared to antispasmodics, the committee noted that there was no clinical difference between interventions for four of the six pain outcomes. The outcomes of complete pain relief and pain relief within 5 minutes outcomes showed a benefit of opioids in one study. The committee considered this evidence and agreed that there no clinical difference for many outcomes, and that overall the evidence also demonstrated there was no benefit of antispasmodics over opioids.

The GC also discussed the harms associated with increased risk of opioid misuse, and noted opioids are often used as the last management option when the maximum dose of other analgesics have been prescribed.

Overall, the committee agreed that the evidence showed a benefit of opioid over placebo, but no benefit when compared to paracetamol or NSAIDs, and little benefit when compared to antispasmodics. The committee therefore agreed that opioids be considered, but only when other treatment has not given sufficient pain relief or is contraindicated. At this point a suspected diagnosis of renal colic might be reconsidered if NSAID and paracetamol pain relief is not effective.

Antispasmodic

The committee considered the evidence for antispasmodics compared to placebo and noted that there was a clinical benefit of antispasmodics in terms of pain relief, and a clinical benefit of placebo in terms of unspecified minor adverse events. The committee noted that although this appears to show a benefit of antispasmodics in terms of pain, their use are not part of current practice, and further, all evidence came from a single study of 200 participants, and was of low and very low quality.

The committee also considered evidence from the comparisons of NSAID versus antispasmodics and opioid versus antispasmodics and agreed that overall, there was no benefit of antispasmodics over opioids or NSAIDs. The committee also considered the difficulties in giving antispasmodics in clinical practice, such as hypotension and tachycardia, and that all evidence in the review used an intravenous method of administration, whereas in clinical practice antispasmodics are more likely to be given orally. The committee noted that as the intravenous route is expected to be the most effective route of administration, it is likely that other routes of administration, such as oral, would be even less effective. Based on this, the committee agreed that antispasmodics should not be recommended.

Combinations

Four studies were included that compared combinations of pain relief drugs. One study compared NSAID + opioid + antispasmodic to NSAID + opioid. The evidence demonstrated a clinical benefit of the 3 intervention combination in terms of the need for rescue medication, but no clinical difference between the groups in terms of pain intensity, or any adverse events. The committee considered this evidence and agreed that because the evidence came from a single, small study, was of very low and low quality for all but one outcome, and showed no clinical difference for all but one outcome, there was not enough convincing evidence to recommend this combination. It was further noted that the study used an intravenous route of administration for the antispasmodic, which is not part of usual practice, and is associated with serious adverse cardiovascular events.

One study compared a combination of NSAID + antispasmodic with NSAID alone, and with antispasmodic alone. When compared with NSAID alone the committee noted that there were fewer people needing rescue medication in the NSAID alone group, and no difference for any other outcomes. Compared to antispasmodic alone there were also fewer people needing rescue medication and fewer people experiencing dizziness. The committee agreed that this was not convincing evidence to recommend this combination, compared to either drug alone.

One study compared a combination of NSAID + opioid with NSAID alone, and with opioid alone. When compared with NSAID alone, the committee noted that there were fewer people needing rescue medication, and no difference between groups in terms of adverse events. There was no difference between any of the outcomes when the combination was compared to opioid alone. The committee considered that this evidence was based on a small number of participants and was very low quality. They agreed that there was no convincing evidence that there was any additional benefit of combined treatment with NSAIDs and opioid, compared to either drug alone.

One study compared a combination of NSAID + paracetamol to both NSAID alone and paracetamol alone. When compared with NSAID alone, the committee noted that there was a clinical benefit of the combination in terms of pain intensity, but no difference in terms of need for rescue medication or adverse events. When compared to paracetamol alone, there was a benefit of the combination for both pain related outcomes, and no difference for adverse events. The committee highlighted that the route of administration of paracetamol in this study was oral, and that there did seem to be some benefit of combined NSAID and oral paracetamol. The committee considered that an advantage of oral paracetamol is that it can be used to self-manage pain at home by recurrent stone formers, without the need to visit A&E. However, they noted that the route of administration for the NSAID in this study was intramuscular, which would probably require a hospital visit. They also noted that self-managing with paracetamol would have implications for the ability to give further analgesia with paracetamol, and that clinicians would need to assess previous paracetamol consumption and wait for enough time to elapse before intravenous paracetamol could be administered. Overall, the committee considered that this was the only study using an oral preparation, and that it was very small and very low quality. They therefore agreed that there wasn’t enough evidence to recommend this combination.

The committee also noted that in all combination studies, the drugs are given at the same time, whereas in a real world scenario, combinations would be given in a staggered manner.

1.8.2. Cost effectiveness and resource use

No economic evidence was identified for this question.

Pain medication tends to be low cost. Unit costs presented to the committee as costs per single dose administration showed that this ranges from 20 pence to around £1. All trials from the clinical review used a single dose of pain medication as generally that is what would be required for an acute pain episode. Patients may then either take oral pain medication for further pain episodes or present to an emergency department (or in some cases GP) where they may be given pain relief in another form (intramuscular (IM)/intravenous (IV)).

Other resource use associated with administering pain relief depends on the type of drug and the method by which it is administered. IV administration will usually require an admission (or at least the patient being on a trolley in the hospital) and IM administration could be given by a GP. Therefore compared to oral administration, for which a patient could take a prescription away with them, IV or IM administration would require either a hospital or GP attendance to administer the drug every time the pain is unmanageable. Compared to providing other drugs intravenously, opioids require a longer hospital stay because patients need to be observed for longer periods before they can be discharged; for example, with IV paracetamol patients can be discharged more quickly. Anti-emesis is also usually given with opioids to combat the common side effect of nausea. Opioid prescribing can still be a controversial area due to the controlled nature of the drug, and the trade off from providing alleviation for significant pain but people often having to tolerate significant adverse events as a result.

In terms of what we can infer about cost effectiveness from the clinical review: when comparing the drugs to placebo, there was a clinical benefit on the pain outcomes demonstrating that the drugs work. The GC recognised that there is usually a large placebo effect with pain relief, particularly when delivered by the intravenous route. For acute pain episodes the period of time that quality of life would apply is very small because the pain episodes are short, therefore any QALY improvement will be very small, creating large ICERs. However, in spite of this it would not be ethical to deny people pain relief.

For drugs compared to each other:

NSAIDs versus opioids showed a clinical benefit for NSAIDs as they were associated with fewer minor adverse events and had less need for rescue medication, therefore the use of NSAIDs is expected to be less costly than opioids. Alongside this, NSAIDs are less likely to require other resource use such as staff time, making NSAIDs a dominant intervention compared to opioids.

NSAIDs versus paracetamol (predominantly IV paracetamol) gave contradictory results, as this comparison showed that patients who used NSAIDs needed less rescue medication, whereas paracetamol was associated with fewer adverse events of abdominal pain.

Opioids compared to (IV) paracetamol showed either benefit of paracetamol for pain or no difference, and also a shorter length of stay for paracetamol, (as more monitoring is required with opioids). There was also a benefit for paracetamol in terms of fewer adverse events. If paracetamol is also cheaper because of less resource use such as length of stay or staff time, then paracetamol is a dominant intervention compared to opioids.

The committee consensus, based on the clinical evidence, was that the analgesic role of opioids in this area is perhaps more prominent than it deserves to be. In current practice NSAIDs are the first drug of choice, and then usually IV morphine if this has not been effective. Patients might then also be given prescription NSAIDs to take away with them. The clinical evidence however suggested that both NSAIDs and paracetamol were more effective than opioids. The committee agreed on recommendations for NSAID as the first line analgesic, paracetamol (IV) as second line, and opioids should only be considered when other treatment has been ineffective or contraindicated. At this point a suspected diagnosis of renal colic might be reconsidered if pain relief is not working.

Some evidence was identified for combination treatment, which would have a higher cost associated with it, particularly if different interventions are delivered using different routes of administration. However the committee did not feel confident making recommendations based on this evidence.

The committee discussed the different patient groups that might be affected by these recommendations. Recurrent stone formers who suspect that they have renal colic, if they are familiar with the symptoms, may present to their GP rather than the emergency department. A recommendation specifying a particular preparation to be used may result in this group of people being referred to hospital, whereas an oral or suppository preparation would be as effective, with advice that the patient could go to hospital if these did not relieve their pain. The GC therefore wanted to make a recommendation for NSAIDs, without specifying the form of administration, in order to provide clinicians with the flexibility to make a decision on the preparation that was appropriate for the clinical scenario. If someone has presented to their GP rather than to an emergency department, their pain may not be extreme. If pain relief is needed out of hours, then a preparation could be given in the patient’s home without them needing to go to the hospital (e.g. IM).

There was discussion about the recommendation for IV paracetamol, because if this replaces current practice of using opioids, then this implies that a hospital attendance or admission is needed in order to have this administered (each time this is needed). This may be a change in practice if an oral form of an opioid could have been given instead. This may apply to recurrent stone formers who are more likely to be well managed in the community/primary care.

However, if someone was finding their pain unmanageable, they may go to hospital anyway because non-oral forms of pain relief are faster acting - and so some hospital attendances are likely to be considered necessary.

With new stone formers, a diagnosis of suspected renal colic will need to be confirmed, in which case a hospital attendance or possibly admission will be necessary. Diagnosis might be made at their first attendance to the hospital or they will come back within a certain timeframe, and further pain relief could be administered.

The committee acknowledged there is an element of flexibility in the recommendations to account for the different patient groups, making the resource impact variable depending on factors such as where people present (GP or hospital).

1.8.3. Other factors the committee took into account

The committee discussed the route of administration across all comparisons. It was noted that some comparisons included an intravenous route compared to an intramuscular route, and the committee discussed whether this comparison was appropriate, due to differences in the speed of action associated with these different routes. However, it was noted that the only studies reporting time to pain relief used an intravenous route in both arms. Further, there was only one study comparing an active drug to placebo that used an intravenous route in the placebo arm but not the drug arm.

When considering the evidence for paracetamol, the committee noted that intravenous paracetamol differed from other routes of paracetamol administration in terms of potency and speed of action. All the evidence for paracetamol apart from one small study, came from studies using an intravenous method. Therefore the committee agreed that based on the evidence, only an intravenous route of administration could be recommended.

Table 21

Route of administration.

The committee considered the evidence for NSAIDs, and agreed that it was heterogeneous in terms of the type of NSAID used in the comparisons, and the route of administration used, making comparisons difficult to interpret. It was noted that when considering the NSAID evidence, the majority of studies used either an intravenous or intramuscular route of administration, whereas in current practice an oral or rectal route of administration is often used. Only one small study of 94 participants looked at an oral route of NSAID administration compared to intramuscular opioid, and the committee noted that this study demonstrated a clinical benefit of opioid for the outcomes of unspecified minor adverse events, but no difference in terms of the number of pain free participants. The committee noted that this study had a high risk of bias, very serious imprecision, and was over 15 years old and therefore unlikely to reflect current practice. Therefore, the committee agreed that there was not sufficient evidence to specify a particular route of administration within the recommendation, and that the appropriate route of administration to use would depend on the clinical situation.

When considering the evidence for opioids, the committee noted that pethidine is less commonly used for renal colic in current UK practice; however of the 24 studies comparing opioids, 10 of them used pethidine. The committee therefore considered that the evidence may not be representative of UK practice.

The committee noted that many people self-manage pain at home before going to hospital or to their GP. They therefore agreed that it is important for clinicians to ask people with suspected renal colic about any previous analgesia use at home, as there is a risk of overdose particularly for paracetamol.

The committee discussed current practice for the paediatric population. This includes NSAIDs, paracetamol and/or opioids. Therefore they concluded that the recommendations should apply to both adults and children. The committee noted however, that as with adults, children receiving NSAIDs should be closely monitored for AKI.

References

1.

Abbasi S, Bidi N, Mahshidfar B, Hafezimoghadam P, Rezai M, Mofidi M et al. Can low-dose of ketamine reduce the need for morphine in renal colic? A double-blind randomized clinical trial. American Journal of Emergency Medicine. 2018; 36(3):376–9 [PubMed: 28821365]

2.

Afshar K, Jafari S, Marks AJ, Eftekhari A, MacNeily AE. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD006027. DOI: 10.1002/14651858.CD006027.pub2. [PubMed: 26120804] [CrossRef]

3.

Aganovic D, Prcic A, Kulovac B, Hadziosmanovic O. Clinical decision making in renal pain management. Acta Informatica Medica. 2012; 20(1):18–20 [PMC free article: PMC3545323] [PubMed: 23322949]

4.

al-Sahlawi KS, Tawfik OM. Comparative study of the efficacy of lysine acetylsalicylate, indomethacin and pethidine in acute renal colic. European Journal of Emergency Medicine. 1996; 3(3):183–6 [PubMed: 9023498]

5.

Al-Waili NS, Saloom KY. Intramuscular piroxicam versus intramuscular diclofenac sodium in the treatment of acute renal colic: double-blind study. European Journal of Medical Research. 1999; 4(1):23–6 [PubMed: 9892571]

6.

Al B, Sunar MM, Zengin S, Sabak M, Bogan M, Can B et al. Comparison of intravenous dexketoprofen trometamol, fentanyl, and paracetamol in the treatment of patients admitted to the emergency department for renal colic: a randomized controlled trial. American Journal of Emergency Medicine. 2017; 36(4):571–6 [PubMed: 29029797]

7.

Anonymous. Renal colic in adults: NSAIDs and morphine are effective for pain relief. Prescrire International. 2009; 18(103):217–21 [PubMed: 19882796]

8.

Asgari SA, Asli MM, Madani AH, Maghsoudi PA, Ghanaei MM, Shakiba M et al. Treatment of loin pain suspected to be renal colic with papaverine hydrochloride: a prospective double-blind randomised study. BJU International. 2012; 110(3):449–52 [PubMed: 22348304]

9.

Ay MO, Sebe A, Kozaci N, Satar S, Acikalin A, Gulen M et al. Comparison of the analgesic efficacy of dexketoprofen trometamol and meperidine HCl in the relief of renal colic. American Journal of Therapeutics. 2014; 21(4):296–303 [PubMed: 23665883]

10.

Aydogdu O, Burgu B, Gucuk A, Suer E, Soygur T. Effectiveness of doxazosin in treatment of distal ureteral stones in children. Journal of Urology. 2009; 182(6):2880–4 [PubMed: 19846149]

11.

Azizkhani R, Pourafzali SM, Baloochestani E, Masoumi B. Comparing the analgesic effect of intravenous acetaminophen and morphine on patients with renal colic pain referring to the emergency department: a randomized controlled trial. Journal of Research in Medical Sciences. 2013; 18(9):772–6 [PMC free article: PMC3872585] [PubMed: 24381620]

12.

Bahn Zobbe V, Rygaard H, Rasmussen D, Strandberg C, Krause S, Hartvig Hartsen S et al. Glucagon in acute ureteral colic: a randomized trial. European Urology. 1986; 12(1):28–31 [PubMed: 3948897]

13.

Barry HC. Low-dose morphine less effective than diclofenac or acetaminophen for renal colic. American Family Physician. 2016; 94(8):665

14.

Basar I, Bircan K, Tasar C, Ergen A, Cakmak F, Remzi D. Diclofenac sodium and spasmolytic drugs in the treatment of ureteral colic: a comparative study. International Urology and Nephrology. 1991; 23(3):227–30 [PubMed: 1889968]

15.

Bektas F, Eken C, Karadeniz O, Goksu E, Cubuk M, Cete Y. Intravenous paracetamol or morphine for the treatment of renal colic: a randomized, placebo-controlled trial. Annals of Emergency Medicine. 2009; 54(4):568–74 [PubMed: 19647342]

16.

Benyajati C. Comparative study of Baralgan and hyoscine-N-methyl bromide in the treatment of intestinal and renal colicy pain. Journal of the Medical Association of Thailand. 1986; 69(10):569–73 [PubMed: 3819615]

17.

Bergus GR. Pain relief for renal colic. Journal of Family Practice. 1996; 43(5):438–40 [PubMed: 8917139]

18.

Boubaker H, Boukef R, Claessens YE, Bouida W, Grissa MH, Beltaief K et al. Phloroglucinol as an adjuvant analgesic to treat renal colic. American Journal of Emergency Medicine. 2010; 28(6):720–3 [PubMed: 20637390]

19.

Bultitude M, Rees J. Management of renal colic. BMJ. 2012; 345(e5499):1–8 [PubMed: 22932919]

20.

Burrows PK, Hollander JE, Wolfson AB, Kurz MC, Richards L, DiFiore S et al. Design and challenges of a randomized clinical trial of medical expulsive therapy (tamsulosin) for urolithiasis in the emergency department. Contemporary Clinical Trials. 2017; 52:91–4 [PMC free article: PMC5167651] [PubMed: 27890522]

21.

Caravati EM, Runge JW, Bossart PJ, Martinez JC, Hartsell SC, Williamson SG. Nifedipine for the relief of renal colic: a double-blind, placebo-controlled clinical trial. Annals of Emergency Medicine. 1989; 18(4):352–4 [PubMed: 2650588]

22.

Cenker E, Serinken M, Uyanik E. Intravenous paracetamol vs ibuprofen in renal colic: a randomised, double-blind, controlled clinical trial. Urolithiasis. 2017; Epublication [PubMed: 28681267]

23.

Chaudhary A, Gupta RL. Double blind, randomised, parallel, prospective, comparative, clinical evaluation of a combination of antispasmodic analgesic Diclofenac + Pitofenone + Fenpiverinium (Manyana vs Analgin + Pitofenone + Fenpiverinium (Baralgan) in biliary, ureteric and intestinal colic. Journal of the Indian Medical Association. 1999; 97(6):244–5 [PubMed: 10645700]

24.

Cohen E, Hafner R, Rotenberg Z, Fadilla M, Garty M. Comparison of ketorolac and diclofenac in the treatment of renal colic. European Journal of Clinical Pharmacology. 1998; 54(6):455–8 [PubMed: 9776434]

25.

Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. Collaborative Group of the Spanish Society of Clinical Pharmacology. European Journal of Clinical Pharmacology. 1991; 40(6):543–6 [PubMed: 1884733]

26.

Cordell WH, Larson TA, Lingeman JE, Nelson DR, Woods JR, Burns LB et al. Indomethacin suppositories versus intravenously titrated morphine for the treatment of ureteral colic. Annals of Emergency Medicine. 1994; 23(2):262–9 [PubMed: 8304606]

27.

Cordell WH, Wright SW, Wolfson AB, Timerding BL, Maneatis TJ, Lewis RH et al. Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. Annals of Emergency Medicine. 1996; 28(2):151–8 [PubMed: 8759578]

28.

Curry C, Kelly AM. Intravenous tenoxicam for the treatment of renal colic. New Zealand Medical Journal. 1995; 108(1001):229–30 [PubMed: 7603654]

29.

Curtis L, Burns A. Unit costs of health and social care 2017. Canterbury. Personal Social Services Research Unit University of Kent, 2017. Available from: https://www​.pssru.ac​.uk/project-pages/unit-costs​/unit-costs-2017/

30.

Daljord OA, Barstad S, Norenberg P. [Ambulatory treatment of an acute attack in urinary calculi. A randomized study of the effects of Petidin, Fortralin, Temgesic and Confortid]. Tidsskrift for den Norske Laegeforening. 1983; 103(12):1006–8 [PubMed: 6192515]

31.

Dash A, Maiti R, Akantappa Bandakkanavar TK, Arora P. Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety. Pain Medicine. 2012; 13(3):466–71 [PubMed: 22295884]

32.

Dawood Al-Waili NS, Saloom KY. Intravenous tenoxicam to treat acute renal colic: comparison with Buscopan Compositum. Journal of the Pakistan Medical Association. 1998; 48(12):370–2 [PubMed: 10531771]

33.

Ebell MH. NSAIDs vs. opiates for pain in acute renal colic. American Family Physician. 2004; 70(9):1682 [PubMed: 15554485]

34.

el-Sherif AE, Foda R, Norlen LJ, Yahia H. Treatment of renal colic by prostaglandin synthetase inhibitors and avafortan (analgesic antispasmodic). British Journal of Urology. 1990; 66(6):602–5 [PubMed: 2265331]

35.

Elliott JP, Evans JW, Gordon JO, Platt LO. Butorphanol and meperidine compared in patients with acute ureteral colic. Journal of Urology. 1979; 122(4):455–7 [PubMed: 384024]

36.

Engeler DS, Ackermann DK, Osterwalder JJ, Keel A, Schmid HP. A double-blind, placebo controlled comparison of the morphine sparing effect of oral rofecoxib and diclofenac for acute renal colic. Journal of Urology. 2005; 174(3):933–6 [PubMed: 16093996]

37.

Erden IA, Artukoglu F, Gozacan A, Ozgen S. Comparison of propofol/fentanyl and ketamine anesthesia in children during extracorporeal shockwave lithotripsy. Saudi Medical Journal. 2007; 28(3):364–8 [PubMed: 17334460]

38.

Ergene U, Pekdemir M, Canda E, Kirkali Z, Fowler J, Coskun F. Ondansetron versus diclofenac sodium in the treatment of acute ureteral colic: a double blind controlled trial. International Urology and Nephrology. 2001; 33(2):315–9 [PubMed: 12092646]

39.

Faridaalaee G, Mohammadi N, Merghati SZ, Khajeh FK, Naghipour B, Pouraghaei M et al. Intravenous morphine vs intravenous ketofol for treating renal colic; a randomized controlled trial. Emergency. 2016; 4(4):202–6 [PMC free article: PMC5007912] [PubMed: 27800541]

40.

Firouzian A, Alipour A, Rashidian Dezfouli H, Zamani Kiasari A, Gholipour Baradari A, Emami Zeydi 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. American Journal of Emergency Medicine. 2016; 34(3):443–8 [PubMed: 26704774]

41.

Fraga A, De Almeida M, Moreira-Da-Silva V, Sousa-Marques M, Severo L, Matos-Ferreira A et al. Intramuscular etofenamate versus diclofenac in the relief of renal colic: a randomised, single-blind, comparative study. Clinical Drug Investigation. 2003; 23(11):701–6 [PubMed: 17536883]

42.

Galassi P, Vicentini C, Scapellato F, Laurenti C. [Use of indomethacin and metamizole administered intravenously in renal colic: Comparative study]. Minerva Urologica. 1983; 35(4):295–300 [PubMed: 6674754]

43.

Garcća-Alonso F, Collaborative Group of the Spanish Society of Clinical Pharmacology. Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. European Journal of Clinical Pharmacology. 1991; 40(6):543–6 [PubMed: 1884733]

44.

Glina S, Damiao R, Afif-Abdo J, Maria CFS, Novoa R, Cairoli CED et al. Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial. International Brazilian Journal of Urology. 2011; 37(6):697–705 [PubMed: 22234000]

45.

Gonzalez Ramallo VJ, Muino Miguez A, Rodriguez de Castro E, Lazaro Bermejo C. [Intramuscular buprenorphine in the symptomatic treatment of renal colic]. Revista Clinica Espanola. 1990; 186(8):414 [PubMed: 2236778]

46.

Grissa MH, Claessens YE, Bouida W, Boubaker H, Boudhib L, Kerkeni W et al. Paracetamol vs piroxicam to relieve pain in renal colic: results of a randomized controlled trial. American Journal of Emergency Medicine. 2011; 29(2):203–6 [PubMed: 20934829]

47.

Hatipoglu Z, Gulec E, Turktan M, Izol V, Aridogan A, Gunes Y et al. Comparative study of ultrasound-guided paravertebral block versus intravenous tramadol for postoperative pain control in percutaneous nephrolithotomy. BMC Anesthesiology. 2018; 18(24) [PMC free article: PMC5816552] [PubMed: 29454333]

48.

Hazhir S, Badr YA, Darabi JN. Comparison of intranasal desmopressin and intramuscular tramadol versus pethidine in patients with renal colic. Urology Journal. 2010; 7(3):148–51 [PubMed: 20845288]

49.

Hetherington JW, Philp NH. Diclofenac sodium versus pethidine in acute renal colic. BMJ. 1986; 292(6515):237–8 [PMC free article: PMC1339208] [PubMed: 3081085]

50.

Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDS) versus opioids for acute renal colic. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004137. DOI: 10.1002/14651858.CD004137.pub3. [PubMed: 14974058] [CrossRef]

51.

Holdgate A, Pollock T. Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. BMJ. 2004; 328(1401):1–8 [PMC free article: PMC421776] [PubMed: 15178585]

52.

Holmlund D, Sjodin JG. Treatment of ureteral colic with intravenous indomethacin. Journal of Urology. 1978; 120(6):676–7 [PubMed: 366182]

53.

Hosseini MM, Yousefi A, Ghahramani L, Rastegari M, Ebrahimi AR. Comparison of the therapeutic effects of rectal diclofenac sodium and intramuscular pethidine injection in the treatment of acute renal colic: a randomized clinical trial. Journal of Clinical Trials. 2015; 5:3

54.

Hosseininejad SM, Ahidashti HA, Bozorgi F, Khatir IG, Montazar SH, Jahanian F 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. Bulletin of Emergency and Trauma. 2017; 5(3):165–70 [PMC free article: PMC5547203] [PubMed: 28795060]

55.

Iguchi M, Katoh Y, Koike H, Hayashi T, Nakamura M. Randomized trial of trigger point injection for renal colic. International Journal of Urology. 2002; 9(9):475–9 [PubMed: 12410926]

56.

Indudhara R, Vaidyanathan S, Sankaranarayanan A. Oral diclofenac sodium in the treatment of acute renal colic. A prospective randomized study. Clinical Trials Journal. 1990; 27(5):295–300

57.

Ioannidis S, Kampantais S, Ioannidis A, Gkagkalidis K, Vakalopoulos I, Toutziaris C et al. Dermal scarification versus intramuscular diclofenac sodium injection for the treatment of renal colic: a prospective randomized clinical trial. Urolithiasis. 2014; 42(6):527–32 [PubMed: 25074713]

58.

Jones JB, Dula DJ. The efficacy of sublingual hyoscyamine sulfate and intravenous ketorolac tromethamine in the relief of ureteral colic. American Journal of Emergency Medicine. 1998; 16(6):557–9 [PubMed: 9786536]

59.

Jones JB, Giles BK, Brizendine EJ, Cordell WH. Sublingual hyoscyamine sulfate in combination with ketorolac tromethamine for ureteral colic: a randomized, double-blind, controlled trial. Annals of Emergency Medicine. 2001; 37(2):141–6 [PubMed: 11174230]

60.

Jonsson PE, Olsson AM, Petersson BA, Johansson K. Intravenous indomethacin and oxycone-papaverine in the treatment of acute renal colic. A double-blind study. British Journal of Urology. 1987; 59(5):396–400 [PubMed: 3297230]

61.

KandaSwamy GV, Dhanasekaran AK, Elangovan A, John B, Viswaroop B, Vedanayagam KS. Randomized double blinded placebo controlled trial comparing diclofenac and piroxicam in management of acute renal colic and its clinical implications. Urology Journal. 2015; 12(2):2069–73 [PubMed: 25923150]

62.

Kaynar M, Koyuncu F, Buldu, Tekinarslan E, Tepeler A, Karata T et al. Comparison of the efficacy of diclofenac, acupuncture, and acetaminophen in the treatment of renal colic. American Journal of Emergency Medicine. 2015; 33(6):749–53 [PubMed: 25827597]

63.

Kekec Z, Yilmaz U, Sozuer E. The effectiveness of tenoxicam vs isosorbide dinitrate plus tenoxicam in the treatment of acute renal colic. BJU International. 2000; 85(7):783–5 [PubMed: 10792152]

64.

Khalifa MS, Sharkawi MA. Treatment of pain owing to acute ureteral obstruction with prostaglandin-synthetase inhibitor: a prospective randomized study. Journal of Urology. 1986; 136(2):393–5 [PubMed: 3090274]

65.

Kheirollahi AR, Tehrani M, Bashashati M. A comparison of the effect of intranasal desmopressin and intramuscular hyoscine N-butyl bromide combination with intramuscular hyoscine N-butyl bromide alone in acute renal colic. Journal of Research in Medical Sciences. 2010; 15(4):214–8 [PMC free article: PMC3082813] [PubMed: 21526084]

66.

Kromann-Andersen B, Sommer P, Finnerup B, Lendorf A, Lyngdorf P, Mouritsen AL et al. Acute pain due to kidney/ureter stones treated with intramuscular Voltaren or Ketogan. Ugeskrift for Laeger. 1987; 149(49):3324–6 [PubMed: 2895521]

67.

Kumar S, Behera NC, Sarkar D, Prasad S, Mandal AK, Singh SK. A comparative assessment of the clinical efficacy of intranasal desmopressin spray and diclofenac in the treatment of renal colic. Urological Research. 2011; 39(5):397–400 [PubMed: 21234555]

68.

Laerum E, Ommundsen OE, Gronseth JE, Christiansen A, Fagertun HE. Intramuscular diclofenac versus intravenous indomethacin in the treatment of acute renal colic. European Urology. 1996; 30(3):358–62 [PubMed: 8931970]

69.

Laerum E, Ommundsen OE, Grønseth JE, Christiansen A, Fagertun HE. Oral diclofenac in the prophylactic treatment of recurrent renal colic. A double-blind comparison with placebo. European Urology. 1995; 28(2):108–11 [PubMed: 8529732]

70.

Larkin GL, Peacock WF, Pearl SM, Blair GA, D’Amico F. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. American Journal of Emergency Medicine. 1999; 17(1):6–10 [PubMed: 9928687]

71.

Lehtonen T, Kellokumpu I, Permi J, Sarsila O. Intravenous indomethacin in the treatment of ureteric colic. A clinical multicentre study with pethidine and metamizol as the control preparations. Annals of Clinical Research. 1983; 15(5–6):197–9 [PubMed: 6364951]

72.

Lloret J, Munoz J, Monmany J, Puig X, Bonastre M, Brau J et al. Treatment of renal colic with dipyrone. A double-blind comparison trial with hyoscine alone or combined with dipyrone. Current Therapeutic Research - Clinical and Experimental. 1987; 42(6):1119–28

73.

Lund PG, Jensen SK, Therkildsen MH, Olsen JH. Treatment of acute pain due to ureteral calculi with intravenous indomethacin or pethidine. Ugeskrift for Laeger. 1986; 148(26):1601–4 [PubMed: 3529546]

74.

Lundstam S, Wahlander L, Kral JG. Treatment of ureteral colic by prostaglandin synthetase inhibition with diclofenac sodium. Current Therapeutic Research - Clinical and Experimental. 1980; 28(3 I):355–8

75.

Lundstam SOA, Leissner KH, Wahlander LA, Kral JG. Prostaglandin-synthetase inhibition with diclofenac sodium in treatment of renal colic: comparison with use of a narcotic analgesic. Lancet. 1982; 1(8281):1096–7 [PubMed: 6122892]

76.

Lupi A, Fierro A, Daniele E. The treatment of ureteral colic with intramuscular injection of pirprofen: a double-blind comparison trial with indomethacin. Current Therapeutic Research - Clinical and Experimental. 1986; 40(5):908–11

77.

Magrini M, Pavesi G, Liverta C, Bruni G. Intravenous ketoprofen in renal colic: a placebo-controlled pilot study. Clinical Therapeutics. 1984; 6(4):483–7 [PubMed: 6432325]

78.

Maldonado-Avila M, Garduno-Arteaga LM, Vela-Mollinedo RA, Jaspersen-Gastelum J, Virgen-Gutierrez F, Del Rosario-Santiago M et al. Comparison of three analgesic drug regimens with twelfth subcostal nerve block for pain control during extracorporeal shock wave lithotripsy. International Urology and Nephrology. 2018; 50(1):49–53 [PubMed: 29151179]

79.

Mankongsrisuk T, Nualyong C, Tantiwong A, Taweemonkongsap T, Amornvesukit T, Chotikawanich E. Efficacy of nephrostomy tract infiltration with bupivacaine before and after tubeless percutaneous nephrolithotomy: a randomized control study. Journal of the Medical Association of Thailand. 2017; 100(3 Supplement 2):S138–43

80.

Marthak KV, Gokarn AM, Rao AV, Sane SP, Mahanta RK, Sheth RD et al. A multi-centre comparative study of diclofenac sodium and a dipyrone/spasmolytic combination, and a single-centre comparative study of diclofenac sodium and pethidine in renal colic patients in India. Current Medical Research and Opinion. 1991; 12(6):366–73 [PubMed: 2044396]

81.

Martin Carrasco C, Rodriguez Vazquez M, Palacios Garcia R. [A double-blind study of the analgesic efficacy in kidney colic of the combination of dipyrone and spasmolytic with ketorolac trometamol]. Archivos Españoles de Urología. 1993; 46(9):763–8 [PubMed: 8304789]

82.

Masoumi K, Forouzan A, Darian AA, Feli M, Barzegari H, Khavanin A. Comparison of clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic: a randomized, double-blind, controlled trial. Emergency Medicine International. 2014; 2014:571326 [PMC free article: PMC4147290] [PubMed: 25197573]

83.

Miano L, Galassi P, Goldoni S. Tyropramide versus butylscopolamine bromide administered intravenously in renal colic. A multicentre study. European Review for Medical and Pharmacological Sciences. 1986; 8(4):449–55

84.

Miralles R, Cami J, Gutierrez J, Torne J, Garces JM, Badenas JM. Diclofenac versus dipyrone in acute renal colic: a double-blind controlled trial. European Journal of Clinical Pharmacology. 1987; 33(5):527–8 [PubMed: 3322848]

85.

Montiel-Jarquín Á J, Rocha-Rocha VM, Solís-Mendoza HA, Romero-Figueroa MS, Etchegaray-Morales I, Alvarado-Ortega I. Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room. Revista Medica del Instituto Mexicano del Seguro Social. 2017; 55 (Suppl 1):S20–5 [PubMed: 28212471]

86.

Mora Durban MJ, Extramiana Cameno J, Arrizabalaga Moreno M, Paniagua Andres P, Camp Herrero J, Milla Santos J et al. [Flubiprofen vs dipyrone combined with hyoscine: the analgesic efficacy in renal colic]. Archivos Españoles de Urología. 1995; 48(9):867–73 [PubMed: 8554391]

87.

Mortelmans LJM, Desruelles D, Baert JA, Hente KR, Tailly GG. Use of tramadol drip in controlling renal colic pain. Journal of Endourology. 2006; 20(12):1010–5 [PubMed: 17206893]

88.

Morteza-Bagi HR, Amjadi M, Mirzaii-Sousefidi R. The comparison of apotel plus low dose of morphine and full dose of morphine in pain relief in patients with acute renal colic. Addiction & Health. 2015; 7(1–2):66–73 [PMC free article: PMC4530196] [PubMed: 26322213]

89.

Moustafa F, Liotier J, Mathevon T, Pic D, Perrier C, Schmidt J. Usefulness of nefopam in treating pain of severe uncomplicated renal colics in adults admitted to emergency units: a randomised double-blind controlled trial. The ‘INCoNU’ study. Emergency Medicine Journal. 2013; 30(2):143–8 [PubMed: 22427403]

90.

Mozafari J, Masoumi K, Forouzan A, Motamed H, Saki MA, Dezham M. Sublingual buprenorphine efficacy in renal colic pain relief: a randomized placebo-controlled clinical trial. Pain and Therapy. 2017; 6(2):227–34 [PMC free article: PMC5693813] [PubMed: 29052805]

91.

Muriel-Villoria C, Zungri-Telo E, Diaz-Curiel M, Fernandez-Guerrero M, Moreno J, Puerta J et al. Comparison of the onset and duration of the analgesic effect of dipyrone, 1 or 2 g, by the intramuscular or intravenous route, in acute renal colic. European Journal of Clinical Pharmacology. 1995; 48(2):103–7 [PubMed: 7589022]

92.

Muriel C, Ortiz P, Mella G, Arellano M, Pereiro M, Franco J et al. Efficacy of two different intramuscular doses of dipyrone in acute renal colic. Methods and Findings in Experimental and Clinical Pharmacology. 1993; 15(7):465–9 [PubMed: 8255126]

93.

Narci H, Ugur M, Uzun H, Yandi M. Combining 1000 mg oral acetaminophen with 75 mg intramuscular diclofenac of analgesic efficacy for acute renal colic treatment. Scientific Research and Essays. 2012; 7(22):2017–21

94.

National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. London. National Institute for Health and Care Excellence, 2014. Available from: http://www​.nice.org.uk​/article/PMG20/chapter​/1%20Introduction%20and%20overview [PubMed: 26677490]

95.

NHS Improvement. Reference costs 2016/17: highlights, analysis and introduction to the data. London. 2017. Available from: https://improvement​.nhs​.uk/resources/reference-costs/

96.

Nicolas Torralba JA, Rigabert Montiel M, Banon Perez V, Valdelvira Nadal P, Perez Albacete M. [Intramuscular ketorolac compared to subcutaneous tramadol in the initial emergency treatment of renal colic]. Archivos Españoles de Urología. 1999; 52(5):435–7 [PubMed: 10427881]

97.

O’Connor A, Schug SA, Cardwell H. A comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. Journal of Accident and Emergency Medicine. 2000; 17(4):261–4 [PMC free article: PMC1725431] [PubMed: 10921813]

98.

Oliveira JeSL, Scherber K, Cabrera D, Motov S, Erwin PJ, West CP et al. Safety and efficacy of intravenous lidocaine for pain management in the emergency department: a systematic review. Annals of Emergency Medicine. 2018; Epublication [PubMed: 29395284]

99.

Oosterlinck W, De Sy W. A double blind comparison between meptazinol (Wy 22811) and ‘Buscopan’ Compositum in renal colic. Current Medical Research and Opinion. 1976; 3(10):716–8

100.

Oosterlinck W, Philp NH, Charig C, Gillies G, Hetherington JW, Lloyd J. A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic. Journal of Clinical Pharmacology. 1990; 30(4):336–41 [PubMed: 2341581]

101.

Pathan SA, Mitra B, Cameron PA. Titrated doses are optimal for opioids in pain trials - Authors’ reply. Lancet. 2016; 388(10048):961–2 [PubMed: 27598676]

102.

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. European Urology. 2017; 73:583–95 [PubMed: 29174580]

103.

Pathan SA, Mitra B, Straney LD, Afzal MS, Anjum S, Shukla D 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 [PubMed: 26993881]

104.

Pavlik I, Suchy J, Pacik D, Bokr R, Sust M, Villoria J et al. Comparison of cizolirtine citrate and metamizol sodium in the treatment of adult acute renal colic: a randomized, double-blind, clinical pilot study. Clinical Therapeutics. 2004; 26(7):1061–72 [PubMed: 15336471]

105.

Payandemehr P, Jalili M, Mostafazadeh Davani B, Dehpour AR. Sublingual buprenorphine for acute renal colic pain management: a double-blind, randomized controlled trial. International Journal of Emergency Medicine. 2014; 7(1):1–5 [PMC free article: PMC3892119] [PubMed: 24386894]

106.

Pellegrino H, Di Girolamo G, Marti ML, De los Santos AR. Comparison of lysine clonixinate 200 mg versus diclofenac 75 mg in the treatment of renal colic pain. Prospective double-blind clinical trial in parallel groups. Prensa Medica Argentina. 1999; 86(10):1015–21

107.

Persson NH, Bergqvist D, Melander A, Zederfelt B. Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic. Acta Chirurgica Scandinavica. 1985; 151(2):105–108 [PubMed: 3890435]

108.

Phillips E, Hinck B, Pedro R, Makhlouf A, Kriedberg C, Hendlin K et al. Celecoxib in the management of acute renal colic: a randomized controlled clinical trial. Urology. 2009; 74(5):994–9 [PubMed: 19589565]

109.

Porena M, Guiggi P, Balestra A, Micheli C. Pain killers and antibacterial therapy for kidney colic and stones. Urologia Internationalis. 2004; 72:(Suppl 1):34–9 [PubMed: 15133331]

110.

Porwal A, Mahajan AD, Oswal DS, Erram SS, Sheth DN, Balamurugan S et al. Efficacy and tolerability of fixed-dose combination of dexketoprofen and dicyclomine injection in acute renal colic. Pain Research and Treatment. 2012; 2012:295926 [PMC free article: PMC3347880] [PubMed: 22577544]

111.

Quilez C, Perez-Mateo M, Hernandez P, Rubio I. [Usefulness of a non-steroid anti-inflammatory, sodium diclofenac, in the treatment of renal colic: Comparative study with a spasmolytic and an opiate analgesic]. Medicina Clínica. 1984; 82(17):754–5 [PubMed: 6738191]

112.

Roberts G, Leslie R, Robb S, Siemens DR, Beiko D. Intraureteral lidocaine for ureteral stent symptoms post-ureteroscopy: a randomized, phase 2, placebo-controlled trial. Canadian Urological Association Journal. 2017; 11(10):326–30 [PMC free article: PMC5963444] [PubMed: 29382444]

113.

Romics I, Molnár DL, Timberg G, Mrklic B, Jelakovic B, Köszegi G et al. The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU International. 2003; 92(1):92–6 [PubMed: 12823389]

114.

Safdar B, Degutis LC, Landry K, Vedere SR, Moscovitz HC, D’Onofrio G. Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. Annals of Emergency Medicine. 2006; 48(2):173–81, 181.e1 [PubMed: 16953530]

115.

Sakr A, Salem E, Kamel M, Desoky E, Ragab A, Omran M et al. Minimally invasive percutaneous nephrolithotomy vs standard PCNL for management of renal stones in the flank-free modified supine position: single-center experience. Urolithiasis. 2017; 45(6):585–9 [PubMed: 28229197]

116.

Salameh S, Hiller N, Antopolsky M, Ghanem F, Abramovitz Y, Stalnikowics R. Diclofenac versus tramadol in the treatment of renal colic: a prospective, randomized trial. Open Emergency Medicine Journal. 2011; 4:9–13

117.

Sanahuja J, Corbera G, Garau J, Pla R, Carre MC. Intramuscular diclofenac sodium versus intravenous Baralgin in the treatment of renal colic. Annals of Pharmacotherapy. 1990; 24(4):361–4 [PubMed: 2183488]

118.

Sanchez-Carpena J, Dominguez-Hervella F, Garcia I, Gene E, Bugarin R, Martin A et al. Comparison of intravenous dexketoprofen and dipyrone in acute renal colic. European Journal of Clinical Pharmacology. 2007; 63(8):751–60 [PubMed: 17571256]

119.

Sanchez-Carpena J, Sesma-Sanchez J, Sanchez-Juan C, Tomas-Vecina S, Garcia-Alonso D, Rico-Salvado J et al. Comparison of dexketoprofen trometamol and dipyrone in the treatment of renal colic. Clinical Drug Investigation. 2003; 23(3):139–52 [PubMed: 23340921]

120.

Sandhu DPS, Iacovou JW, Fletcher MS, Kaisary AV, Philip NH, Arkell DG. A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic. British Journal of Urology. 1994; 74(6):690–3 [PubMed: 7827834]

121.

Sen H, Erturhan S, Sadioglu E, Bayrak O, Seckiner I. A comparison of efficacy of doxazosin 4 and 8 mg in medical expulsive therapy of distal ureteral stones: a prospective randomized clinical trial. Urolithiasis. 2017; 45(5):461–4 [PubMed: 27717996]

122.

Serinken M, Eken C, Turkcuer I, Elicabuk H, Uyanik E, Schultz CH. Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial. Emergency Medicine Journal. 2012; 29(11):902–5 [PubMed: 22186009]

123.

Shirazi M, Salehipour M, Afrasiabi MA, Aminsharifi A. Analgesic effects and safety of desmopressin, tramadol and indomethacin in patients with acute renal colic: a randomized clinical trial. Bulletin of Emergency and Trauma. 2015; 3(2):41–5 [PMC free article: PMC4771265] [PubMed: 27162901]

124.

Sjodin JG. Clinical experience of indomethacin in pain from ureteral stone. Scandinavian Journal of Urology and Nephrology. 1983; 75(Suppl):35–6 [PubMed: 6367024]

125.

Slade N. Clinical blind trial of three drugs in the control of renal colic. British Journal of Urology. 1967; 39(1):22–5 [PubMed: 5336761]

126.

Snir N, Moskovitz B, Nativ O, Margel D, Sandovski U, Sulkes J et al. Papaverine hydrochloride for the treatment of renal colic: an old drug revisited. A prospective, randomized study. Journal of Urology. 2008; 179(4):1411–4 [PubMed: 18289563]

127.

Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urology. 2012; 12:13 [PMC free article: PMC3508963] [PubMed: 22559856]

128.

Sommer P, Kromann-Andersen B, Lendorf A, Lyngdorf P, Moller P. Analgesic effect and tolerance of Voltaren and Ketogan in acute renal or ureteric colic. British Journal of Urology. 1989; 63(1):4–6 [PubMed: 2645969]

129.

Song SW, Kim K, Rhee JE, Lee JH, Seo GJ, Park HM. Butylscopolammonium bromide does not provide additional analgesia when combined with morphine and ketorolac for acute renal colic. Emergency Medicine Australasia. 2012; 24(2):144–50 [PubMed: 22487663]

130.

Stankov G, Schmieder G, Zerle G, Schinzel S, Brune K. Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain. World Journal of Urology. 1994; 12(3):155–61 [PubMed: 7951343]

131.

Stein A, Ben Dov D, Finkel B, Mecz Y, Kitzes R, Lurie A. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic. American Journal of Emergency Medicine. 1996; 14(4):385–7 [PubMed: 8768161]

132.

Supervia A, Peuro-Botet J, Nogues X, Echarte JL, Mingukz S, Iglesias ML et al. Piroxicam fast-dissolving dosage form vs diclofenac sodium in the treatment of acute renal colic: a double-blind controlled trial. British Journal of Urology. 1998; 81(1):27–30 [PubMed: 9467472]

133.

Thompson JF, Pike JM, Chumas PD, Rundle JS. Rectal diclofenac compared with pethidine injection in acute renal colic. BMJ. 1989; 299(6708):1140–1 [PMC free article: PMC1838035] [PubMed: 2513026]

134.

Torchi B, Villani U, Bruni G, Lavezzari M, Mandelli V. Intravenous indoprofen in the management of renal colic. International Journal of Clinical Pharmacology Research. 1983; 3(3):167–73 [PubMed: 6384073]

135.

Udén P, Rentzhog L, Berger T. A comparative study on the analgesic effects of indomethacin and hydromorphinechloride-atropine in acute, ureteral-stone pain. Acta Chirurgica Scandinavica. 1983; 149(5):497–9 [PubMed: 6637313]

136.

Vignoni A, Fierro A, Moreschini G, Cau M, Agostino A, Daniele E et al. Diclofenac sodium in ureteral colic: a double-blind comparison trial with placebo. Journal of International Medical Research. 1983; 11(5):303–7 [PubMed: 6357890]

137.

Walden M, Lahtinen J, Elvander E. Analgesic effect and tolerance of ketoprofen and diclofenac in acute ureteral colic. Scandinavian Journal of Urology and Nephrology. 1993; 27(3):323–5 [PubMed: 8290910]

138.

Warren MM, Boyce WH, Evans JW, Peters PC. A double-blind comparison of dezocine and morphine in patients with acute renal and ureteral colic. Journal of Urology. 1985; 134(3):457–9 [PubMed: 2863392]

139.

Wolfson AB, Yealy DM. Oral indomethacin for acute renal colic. American Journal of Emergency Medicine. 1991; 9(1):16–19 [PubMed: 1985642]

140.

Wood VM, Christenson JM, Innes GD, Lesperance M, McKnight D. The NARC (nonsteroidal anti-inflammatory in renal colic) trial. Single-dose intravenous ketorolac versus titrated intravenous meperidine in acute renal colic: a randomized clinical trial. Canadian Journal of Emergency Medical Care. 2000; 2(2):83–9 [PubMed: 17637129]

141.

Xue P, Tu C, Wang K, Wang X, Fang Y. Intracutaneous sterile water injection versus oral paracetamol for renal colic during pregnancy: a randomized controlled trial. International Urology and Nephrology. 2013; 45(2):321–5 [PubMed: 23443875]

142.

Yakoot M, Salem A, Yousef S, Helmy S. Clinical efficacy of Spasmofen suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial. Drug Design, Development and Therapy. 2014; 8:405–10 [PMC free article: PMC4018316] [PubMed: 24851039]

143.

Yencilek F, Aktas C, Goktas C, Yilmaz C, Yilmaz U, Sarica K. Role of papaverine hydrochloride administration in patients with intractable renal colic: randomized prospective trial. Urology. 2008; 72(5):987–90 [PubMed: 18789511]

144.

Zamanian F, Jalili M, Moradi-Lakeh M, Kia M, Aghili R, Aghili SM. Morphine suppository versus indomethacin suppository in the management of renal colic: randomized clinical trial. Pain Research and Treatment. 2016; 2016:4981585 [PMC free article: PMC4814695] [PubMed: 27073696]

145.

Ziapor B, Motamed H, Verki MM, Norani H. Comparison of effect of morphine-chlorpheniramine combined versus morphine alone in alleviating acute renal colic pain: a randomized clinical trail. Jundishapur Journal of Natural Pharmaceutical Products. 2017; 12 (3):e15585

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