Wisconsin Medical Journal

Document Sample
Wisconsin Medical Journal Powered By Docstoc
					 Your Practice




                      Clinical Questions #2
Editor’s note:
This is the second
                       Initial treatment of biliary colic: Are NSAIDs
installment in a       better than opiates?
series of “Clinical
Questions.”            David Meyers, MD; David A. Feldstein, MD
Readers are pre-
sented with a case     Patient
and clinical ques-
                       A 45-year-old healthy male presents to urgent care clinic with acute right upper quadrant
tion. An evidence-
based answer is        (RUQ) abdominal pain without fevers. The patient’s exam confirms a tender RUQ with-
provided on a later    out rebound or guarding. He is found to have a white blood cell count of 15,000 with
page. The answer       normal liver function and biliary tests. He is clinically diagnosed with biliary colic and an
includes how the       abdominal ultrasound is ordered to evaluate for acute cholecystitis. The ultrasound con-
evidence was found
                       firms gallstones without evidence of biliary tree dilation or obstruction.
and evaluated.

                       Clinical Question
                       In a patient with acute biliary colic, does initial treatment with NSAIDS versus opiates
                       prevent the development of acute cholecystitis?

                       How and where could you locate evidence to answer this question?
                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       How would you treat this patient?

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________

                       ________________________________________________________________________________________




                       Turn to page 63 for one possible approach.



                               Wisconsin Medical Journal • 2005 • Volume 104, No. 4                               9
Suggested Approach for Clinical Question #2
Search Strategy for a Therapeutic Question                                       a. 93% of patients in the diclofenac group had improvement
1. Using Ovid Interface, search Cochrane Database of Systematic                     in pain
   Reviews (1st Quarter 2005):                                                   b. 62% of patients in the placebo group had improvement in
   a. “biliary colic” or “biliary tract disease” or “acute chole-                   pain
      cystitis” or “cholecystitis”                                               c. 50% relative increase in patients with improvement of pain
   b. “nonsteroidal” or “anti-inflammatory” or “NSAIDs”                             in the diclofenac group compared to the placebo group
   c. combine (a) and (b)                                                        d. 3 patients would have to be treated with diclofenac to
   d. No matches relevant to the case                                               cause pain improvement in 1 patient (95% CI, 2-10)
2. Search repeated in Database of Abstracts of Reviews of Effects           2.   Development of cholelithiasis-related complications (includ-
   (DARE), and ACP Journal Club (shown as “EBM Reviews                           ing acute cholecystitis, obstructive jaundice, cholangitis, or
   Full Text - Cochrane DSR, ACP Journal Club, and DARE”                         pancreatitis) comparing diclofenac vs. placebo
   using the Ovid Interface):                                                    a. 48% of patients in the diclofenac group developed chole-
   a. No matches relevant to the case                                               lithiasis-related complications
3. Search all years of Medline (1966 to March Week 2 2005)                       b. 81% of patients in the placebo group developed choleli-
   using Ovid interface:                                                            thiasis-related complications
   a. “exp biliary tract disease” (exploded MESH Heading)                        c. 41% relative decrease in complications in those patients
   b. “exp cholecystitis” (exploded MESH Heading)                                   treated with diclofenac compared with placebo
   c. “biliary colic” (keyword)                                                  d. 3 patients would have to be treated with diclofenac to
   d. combine (a) or (b) or (c) limited to English Language and                     prevent a cholelithiasis-related complication in 1 patient
      Human studies                                                                 (95% CI, 2-12)
   e. “Anti-inflammatory Agents, Non-Steroidal” (exploded
      MESH heading)                                                         Henderson et al
   f. combine (d) and (e)                                                   1. Pain response
   g. “random$” (keyword) Used to limit the results to ran-                    a. No statistically significant difference in pain control be-
      domized trials.                                                              tween the ketorolac and meperidine groups at any time
   h. combine (f) and (g)                                                          interval studied.
   i. 11 studies – two of which pertained to the question:                  2. Side Effects
      i. Akriviadis EA, et al, Treatment of biliary colic with                 a. Statistically significant higher incidence of nausea and diz-
          diclofenac: a randomized, double-blind, placebo-con-                     ziness in those treated with meperidine compared to ke-
          trolled study.                                                           torolac.
      ii. Henderson SO, et al, Comparison of intravenous ke-
          torolac and meperidine in the treatment of biliary colic.         Applying the Evidence to the Patient
                                                                            • The case patient is similar to those in the studies. Thus, the
Study Characteristics                                                         results should apply.
                                                                            • IM diclofenac is not available in the United States, but intra-
 Study (Authors)       Akriviadis et al         Henderson et al               venous ketorolac is readily available.
 Study Type            Prospective, double-     Prospective, double-
                       blind, randomized,       blind, randomized           Summary
                       placebo-controlled
                                                                            The well-done study by Akriviadis demonstrated that diclofenac
 Patients              53 patients with acute   324 patients with
                       biliary colic and        clinically diagnosed        dramatically decreased the risk of progressing to acute cholecys-
                       cholelithiasis demon-    acute biliary colic         titis compared to placebo. The study by Henderson had some
                       strated by ultrasound                                methodological flaws, but showed that ketorolac is at least as ef-
 Intervention          IM diclofenac vs         IV ketorolac vs             fective as meperidine at relieving the pain associated with biliary
                       placebo                  IV meperidine
                                                                            colic. Henderson also showed that patient’s had less side effects
 Primary End Points    Response to pain         Response to pain (No
                       and development of       assessment was per-         (nausea and dizziness) with ketorolac.
                       cholelithiasis-related   formed of cholelithiasis-       Unfortunately IM diclofenac is not available in the United
                       complications            related complications)      States. It is likely that the benefits seen with diclofenac are a drug
                                                                            class effect. Therefore, IV ketorolac should have a similar effect
Validity of Evidence (Akriviadis et al)                                     on decreasing progression to acute cholecystitis.
• Properly randomized trial.
• Follow-up was at least 72 hours for all 53 patients. This is long         Conclusion
  enough to witness the progression of biliary colic to cholecys-           Ketorolac may be safely used in the initial treatment of pain associ-
  titis.                                                                    ated with biliary colic. It is at least as effective as meperidine for
• Follow-up was also reasonably complete with only a 3.6%                   pain relief with fewer side effects. Given ketorolac’s potential role
  drop out rate.                                                            in the prevention of progression to acute cholecystitis, it should be
• Intention to treat analysis was used.                                     considered first line therapy.
• The study was “double-blinded,” though there likely was unin-
  tentional unblinding by the treatment nurses who delivered the            Bibliography
  yellow-discolored diclofenac medication.                                  1. Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J,
• The diclofenac and placebo groups were similar at the start of                Markantas A, Garyfallos A. Treatment of biliary colic with
  the study and were treated equally throughout the trial other                 diclofenac: a randomized, double-blind, placebo-controlled
  than the experimental intervention.                                           study. Gastroenterology. 1997;113(1):225-231.
• Overall this study is of high methodologic quality.                       2. Henderson SO, Swadron S, Newton E. Comparison of
                                                                                intravenous ketorolac and meperidine in the treatment of
Study Results                                                                   biliary colic. J Emerg Med. 2002;23(3):237-241.
Akriviadis et al
1. Pain response comparing diclofenac vs. placebo


                                          Wisconsin Medical Journal • 2005 • Volume 104, No. 4                                                 63
5