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Do Nonopioid Medications Provide Effective Analgesia in Adult Patients With Acute Renal Colic?
SYSTEMATIC REVIEW SNAPSHOT
TAKE-HOME MESSAGE Nonsteroidal anti-inflammatory drugs are effective in the treatment of acute renal colic and may be more effective than other nonopioid medication. Do Nonopioid Medications Provide Effective Analgesia in Adult Patients With Acute Renal Colic?
METHODS
EBEM Commentators
DATA SOURCES The authors searched the Cochrane Renal Group’s Specialized Register for articles. This register contains studies from the following sources: CENTRAL, MEDLINE, EMBASE, and clinical trial registries. They also hand searched journals. STUDY SELECTION The authors included only randomized and quasi-randomized clinical trials of adults receiving nonopioid analgesia for acute pain caused by renal colic. Primary outcome measures included patientrated pain using a visual analog scale, time to relief, recurrence of pain, and need for rescue medications. The secondary outcome measure was adverse effects. DATA EXTRACTION AND SYNTHESIS Two authors independently reviewed all abstracts. Continuous variables were analyzed with mean difference, and dichotomous variables were reported as relative risks; 95% confidence intervals were included. Heterogeneity was assessed with I2. Data were pooled with the random-effects model, and risk of bias was assessed with a bias assessment tool.1 Subgroup analysis compared nonsteroidal antiinflammatory drugs with non–nonsteroidal anti-inflammatory drugs, placebo, antispasmodics, and combination therapy.
Volume
-,
no.
-
:
-
2015
Taneisha Wilson, MD Elizabeth M. Goldberg, MD Department of Emergency Medicine Brown University Providence, RI
Results Summary of reported outcomes for patient-reported pain, pain reduction, and the need for rescue medication. Outcome Measures Pain reduction NSAIDs vs placebo NSAIDsþantispasmodics vs NSAIDs alone Rescue medication NSAIDs vs placebo NSAIDs vs antispasmodics NSAIDsþantispasmodics vs NSAIDs alone
Number of Studies (Participants)
MD or RR (95% CI)
I2
3 (197) 9 (906)
2.3 (1.5–3.5) 1.0 (0.9–1.1)
15 59
4 (180) 4 (299) 4 (517)
0.4 (0.2–0.6) 0.3 (0.1–0.8) 1.0 (0.6–1.6)
24 65 10
MD, Mean difference; RR, relative risk; CI, confidence interval; NSAID, nonsteroidal anti-inflammatory drug.
Fifty studies (n¼5,734) were included in the systematic review, with 37 of these (n¼4,483) contributing to the meta-analysis. For patient-reported pain, nonsteroidal anti-inflammatory drugs were significantly superior to placebo. There was no added benefit in pain reduction between nonsteroidal anti-inflammatory drugs alone and nonsteroidal antiinflammatory drugs combined with an antispasmodic. In terms of the need for rescue medication, nonsteroidal antiinflammatory drugs were superior to placebo and superior to antispasmodics. There was no added benefit of combined treatment with nonsteroidal anti-inflammatory
drugs and antispasmodics compared with nonsteroidal antiinflammatory drugs alone. Gastrointestinal adverse effects such as nausea and vomiting and minor central nervous system adverse effects such as dizziness occurred more often with nonsteroidal anti-inflammatory drugs than non–nonsteroidal anti-inflammatory drugs, but no study reported major adverse events such as bleeding or renal failure. Adverse effects were not consistently reported and so could not be pooled.
Commentary Approximately 10% to 15% of patients in the United States will Annals of Emergency Medicine 1
Systematic Review Snapshot
have nephrolithiasis during their lifetime, which classically presents with acute colicky pain.2 Traditionally, narcotics have been used for severe renal colic pain, but heightened concern over opioids overuse and addiction has increased interest in non-narcotic medications.3 A previous metaanalysis revealed that single-bolus dosing of nonsteroidal antiinflammatory drugs and opioids was effective in the treatment of acute renal colic, but there was a higher risk of vomiting with the opioid evaluated, meperidine.4 Overall, nonsteroidal anti-inflammatory drugs were significantly more effective than placebo in treating renal colic, and antispasmodics were not superior to nonsteroidal anti-inflammatory drugs alone. Nonsteroidal anti-inflammatory drugs plus antispasmodic was more effective than nonsteroidal anti-inflammatory drugs alone for pain control but not for 50% pain reduction at 1 hour or for recurrent pain. In comparisons of nonsteroidal anti-inflammatory drugs, indomethacin appears less effective than the other nonsteroidal anti-inflammatory drugs except for lysine acetylsalicylate (intravenous aspirin). Other nonsteroidal anti-inflammatory drugs, including diclofenac and ketorolac, parecoxib, and ketoprofen, are comparable. This meta-analysis had several limitations. There was significant
2 Annals of Emergency Medicine
heterogeneity among the included studies for certain comparisons, including both randomized and quasi-randomized studies, and there were insufficient data to evaluate the efficacy of many specific agents. The nonopioids most commonly reported include metamizole (dipyrone), diclofenac, and indomethacin. Other limitations include the presence of bias among the studies identified, including but not limited to selection, attrition, and industry bias. There was also substantial variability in the methods used to establish the diagnosis (radiologic versus clinical), route of administration (oral versus intravenous versus intramuscular), and postintervention assessment. To be most relevant to the emergency department (ED) setting, future research should evaluate pain relief after the administration of commonly used intravenous nonopioids in patients with a clinical diagnosis of renal colic. No major adverse effects were reported with nonsteroidal antiinflammatory drugs or the comparators in this review. However, outcomes were assessed in the same visit and an underestimation of longer-term adverse events may have occurred. Hypersensitivity to nonsteroidal anti-inflammatory drugs was an exclusion criterion in this review, but anaphylaxis is a known adverse effect of this
drug class and may limit its use in patients with a known allergy. Emergency physicians may prefer to use opioids or non–nonsteroidal anti-inflammatory drugs for patients with preexisting renal compromise or advanced age and those receiving anticoagulation. However, nonsteroidal antiinflammatory drugs present an effective and safe option for acute renal colic pain in ED patients without contraindications to their use. Editor’s Note: This is a clinical synopsis, a regular feature of the Annals’ Systematic Review Snapshot (SRS) series. The source for this systematic review snapshot is: Afshar K, Jafari S, Marks AJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev. 2015;(6): CD006027. 1. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. 2. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350:684-693. 3. Kilaru AS, Gadsden SM, Perrone J, et al. How do physicians adopt and apply opioid prescription guidelines in the emergency department? a qualitative study. Ann Emerg Med. 2014;64:482-489.e1. 4. Holdgate A, Pollock T. Nonsteroidal antiinflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev. 2005;(2):CD004137.
Michael Brown, MD, MSc, Alan Jones, MD, and David Newman, MD, serve as editors of the SRS series.
Volume
-,
no.
-
:
-
2015
TAKE-HOME MESSAGE Nonsteroidal anti-inflammatory drugs are effective in the treatment of acute renal colic and may be more effective than other nonopioid medication. Do Nonopioid Medications Provide Effective Analgesia in Adult Patients With Acute Renal Colic?
METHODS
EBEM Commentators
DATA SOURCES The authors searched the Cochrane Renal Group’s Specialized Register for articles. This register contains studies from the following sources: CENTRAL, MEDLINE, EMBASE, and clinical trial registries. They also hand searched journals. STUDY SELECTION The authors included only randomized and quasi-randomized clinical trials of adults receiving nonopioid analgesia for acute pain caused by renal colic. Primary outcome measures included patientrated pain using a visual analog scale, time to relief, recurrence of pain, and need for rescue medications. The secondary outcome measure was adverse effects. DATA EXTRACTION AND SYNTHESIS Two authors independently reviewed all abstracts. Continuous variables were analyzed with mean difference, and dichotomous variables were reported as relative risks; 95% confidence intervals were included. Heterogeneity was assessed with I2. Data were pooled with the random-effects model, and risk of bias was assessed with a bias assessment tool.1 Subgroup analysis compared nonsteroidal antiinflammatory drugs with non–nonsteroidal anti-inflammatory drugs, placebo, antispasmodics, and combination therapy.
Volume
-,
no.
-
:
-
2015
Taneisha Wilson, MD Elizabeth M. Goldberg, MD Department of Emergency Medicine Brown University Providence, RI
Results Summary of reported outcomes for patient-reported pain, pain reduction, and the need for rescue medication. Outcome Measures Pain reduction NSAIDs vs placebo NSAIDsþantispasmodics vs NSAIDs alone Rescue medication NSAIDs vs placebo NSAIDs vs antispasmodics NSAIDsþantispasmodics vs NSAIDs alone
Number of Studies (Participants)
MD or RR (95% CI)
I2
3 (197) 9 (906)
2.3 (1.5–3.5) 1.0 (0.9–1.1)
15 59
4 (180) 4 (299) 4 (517)
0.4 (0.2–0.6) 0.3 (0.1–0.8) 1.0 (0.6–1.6)
24 65 10
MD, Mean difference; RR, relative risk; CI, confidence interval; NSAID, nonsteroidal anti-inflammatory drug.
Fifty studies (n¼5,734) were included in the systematic review, with 37 of these (n¼4,483) contributing to the meta-analysis. For patient-reported pain, nonsteroidal anti-inflammatory drugs were significantly superior to placebo. There was no added benefit in pain reduction between nonsteroidal anti-inflammatory drugs alone and nonsteroidal antiinflammatory drugs combined with an antispasmodic. In terms of the need for rescue medication, nonsteroidal antiinflammatory drugs were superior to placebo and superior to antispasmodics. There was no added benefit of combined treatment with nonsteroidal anti-inflammatory
drugs and antispasmodics compared with nonsteroidal antiinflammatory drugs alone. Gastrointestinal adverse effects such as nausea and vomiting and minor central nervous system adverse effects such as dizziness occurred more often with nonsteroidal anti-inflammatory drugs than non–nonsteroidal anti-inflammatory drugs, but no study reported major adverse events such as bleeding or renal failure. Adverse effects were not consistently reported and so could not be pooled.
Commentary Approximately 10% to 15% of patients in the United States will Annals of Emergency Medicine 1
Systematic Review Snapshot
have nephrolithiasis during their lifetime, which classically presents with acute colicky pain.2 Traditionally, narcotics have been used for severe renal colic pain, but heightened concern over opioids overuse and addiction has increased interest in non-narcotic medications.3 A previous metaanalysis revealed that single-bolus dosing of nonsteroidal antiinflammatory drugs and opioids was effective in the treatment of acute renal colic, but there was a higher risk of vomiting with the opioid evaluated, meperidine.4 Overall, nonsteroidal anti-inflammatory drugs were significantly more effective than placebo in treating renal colic, and antispasmodics were not superior to nonsteroidal anti-inflammatory drugs alone. Nonsteroidal anti-inflammatory drugs plus antispasmodic was more effective than nonsteroidal anti-inflammatory drugs alone for pain control but not for 50% pain reduction at 1 hour or for recurrent pain. In comparisons of nonsteroidal anti-inflammatory drugs, indomethacin appears less effective than the other nonsteroidal anti-inflammatory drugs except for lysine acetylsalicylate (intravenous aspirin). Other nonsteroidal anti-inflammatory drugs, including diclofenac and ketorolac, parecoxib, and ketoprofen, are comparable. This meta-analysis had several limitations. There was significant
2 Annals of Emergency Medicine
heterogeneity among the included studies for certain comparisons, including both randomized and quasi-randomized studies, and there were insufficient data to evaluate the efficacy of many specific agents. The nonopioids most commonly reported include metamizole (dipyrone), diclofenac, and indomethacin. Other limitations include the presence of bias among the studies identified, including but not limited to selection, attrition, and industry bias. There was also substantial variability in the methods used to establish the diagnosis (radiologic versus clinical), route of administration (oral versus intravenous versus intramuscular), and postintervention assessment. To be most relevant to the emergency department (ED) setting, future research should evaluate pain relief after the administration of commonly used intravenous nonopioids in patients with a clinical diagnosis of renal colic. No major adverse effects were reported with nonsteroidal antiinflammatory drugs or the comparators in this review. However, outcomes were assessed in the same visit and an underestimation of longer-term adverse events may have occurred. Hypersensitivity to nonsteroidal anti-inflammatory drugs was an exclusion criterion in this review, but anaphylaxis is a known adverse effect of this
drug class and may limit its use in patients with a known allergy. Emergency physicians may prefer to use opioids or non–nonsteroidal anti-inflammatory drugs for patients with preexisting renal compromise or advanced age and those receiving anticoagulation. However, nonsteroidal antiinflammatory drugs present an effective and safe option for acute renal colic pain in ED patients without contraindications to their use. Editor’s Note: This is a clinical synopsis, a regular feature of the Annals’ Systematic Review Snapshot (SRS) series. The source for this systematic review snapshot is: Afshar K, Jafari S, Marks AJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev. 2015;(6): CD006027. 1. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. 2. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350:684-693. 3. Kilaru AS, Gadsden SM, Perrone J, et al. How do physicians adopt and apply opioid prescription guidelines in the emergency department? a qualitative study. Ann Emerg Med. 2014;64:482-489.e1. 4. Holdgate A, Pollock T. Nonsteroidal antiinflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev. 2005;(2):CD004137.
Michael Brown, MD, MSc, Alan Jones, MD, and David Newman, MD, serve as editors of the SRS series.
Volume
-,
no.
-
:
-
2015