1. Abdominal CT: Necessity, Nephropathy, and Allergy Myths Joe Lex, MD, FACEP, FAAEM Temple University School of Medicine Philadelphia, PA Joseph.Lex@TUHS.Temple.edu

2. Disclosure

3. Cape Town, SA

4. July 19 – 22 nd San Diego, California Four Speakers Only: Amal Mattu Ghazala Sharieff Joe Lex Greg Henry

5. Mediterranean Emergency Medicine Congress V 14-17 September 2009 Valencia, Spain Mediterranean Emergency Medicine Congress V 14-17 September 2009 Valencia, Spain

6. III Inter-American Conference on Emergency Medicine – Buenos Aires May 2010

10. Objectives Assess the necessity of oral and intravenous contrast materialAssess the necessity of oral and intravenous contrast material Discuss strategies to avoid adverse outcomes from intravenous contrastDiscuss strategies to avoid adverse outcomes from intravenous contrast

11. Question #1 How does oral contrast affect the accuracy of an abdominal CT scan?

12. Oral Contrast

13. History of Contrast “Step and Scan” replaced by helical technology“Step and Scan” replaced by helical technology Single-beam replaced by multiple beamSingle-beam replaced by multiple beam Rapid scans eliminate artifact from movement, respirations, peristalsisRapid scans eliminate artifact from movement, respirations, peristalsis

14. Importance of Contrast Many studies show no contrast required in most situationsMany studies show no contrast required in most situations Confounding variables:Confounding variables: –Scanner: dynamic vs. helical vs. multi-detector –Contrast: oral vs. IV vs. rectal –Interpreter reliability

15. Oral Contrast = Longer Stay High volume urban ED: 107,000 visits / yearHigh volume urban ED: 107,000 visits / year N = 183 patientsN = 183 patients Excluded trauma, pediatrics, pregnantExcluded trauma, pediatrics, pregnant Huynh LN, et al. Emerg Radiol. 2004 Jul; 10(6):310-3.

16. Oral Contrast = Longer Stay Huynh LN, et al. Emerg Radiol. 2004 Jul; 10(6):310-3. Time from Order to Scan Average Total ED Stay 102 scans: no oral contrast 104 minutes 358 minutes 81 scans with oral contrast 172 minutes 599 minutes

17. Oral Contrast: Accuracy 118 patients scanned before and after oral contrast118 patients scanned before and after oral contrast Blinded interpretation by different radiologistsBlinded interpretation by different radiologists Lee SY, et al. Emerg Radiol. 2006 May; 12(4):150-7.

18. Oral Contrast: Accuracy 11 had normal non-contrast but abnormal contrast11 had normal non-contrast but abnormal contrast 6 had abnormal non-contrast but normal contrast scans6 had abnormal non-contrast but normal contrast scans 4 had both scans abnormal, but disagreement over abnormality4 had both scans abnormal, but disagreement over abnormality Lee SY, et al. Emerg Radiol. 2006 May; 12(4):150-7.

19. Oral Contrast: Accuracy Post-hoc analysis: one true discordant resultPost-hoc analysis: one true discordant result Unblinded review: disagreement due to inter-observer variabilityUnblinded review: disagreement due to inter-observer variability Other studies: discrepancy rates up to 38%Other studies: discrepancy rates up to 38% Lee SY, et al. Emerg Radiol. 2006 May; 12(4):150-7.

20. Oral Contrast: Appendicitis Meta-analysis: 23 studies of CT for appendicitisMeta-analysis: 23 studies of CT for appendicitis CT without contrast similar to or better than CT with contrastCT without contrast similar to or better than CT with contrast Anderson BA, et al. Am J Surg. 2005 Sep; 190(3):474-8.

21. Oral Contrast: Appendicitis Without contrast With contrast Sensitivity95%92% NPV96%96% Specificity97%94% PPV97%89% Accuracy96%92% Anderson BA, et al. Am J Surg. 2005 Sep; 190(3):474-8.

22. Oral Contrast: Conclusion Many radiologists very comfortable interpreting studies without oral contrastMany radiologists very comfortable interpreting studies without oral contrast Although oral contrast takes 90 minutes to opacify bowel, it adds 3 hours to ED stayAlthough oral contrast takes 90 minutes to opacify bowel, it adds 3 hours to ED stay

23. Oral Contrast: Conclusion Oral contrast adds little to accuracyOral contrast adds little to accuracy Local radiologist may not be comfortable interpreting studies without oral contrastLocal radiologist may not be comfortable interpreting studies without oral contrast

24. Intravenous Contrast

25. Question #2 How does intravenous contrast affect the accuracy of an abdominal CT scan?

26. IV Contrast: Risks Associated risksAssociated risks –Allergic and anaphylactoid reactions –Contrast induced nephropathy New scanners adequate to diagnose common problems without IV contrast: appendicitis, diverticulitis, pancreatitisNew scanners adequate to diagnose common problems without IV contrast: appendicitis, diverticulitis, pancreatitis

27. IV Contrast: Accuracy 164 unenhanced CT of patients with abdominal pain164 unenhanced CT of patients with abdominal pain Diagnosis made in 71 (43%)Diagnosis made in 71 (43%) Non-diagnostic given IV contrastNon-diagnostic given IV contrast All reviewed by 2 radiologistsAll reviewed by 2 radiologists No significant difference with IV contrastNo significant difference with IV contrast Basak S, et al. Clin Imaging. 2002 Nov-Dec; 26(6):405-7.

28. IV Contrast: Necessity Suspected appendicitis: unenhanced CT  laparoscopySuspected appendicitis: unenhanced CT  laparoscopy Appendicitis diagnosed…Appendicitis diagnosed… …by CT in 83/103 (80.6%) …at laparoscopy in 87/103 (84.5%) CT sensitivity 95.4%, specificity 100%CT sensitivity 95.4%, specificity 100% in't Hof KH, et al. Br J Surg. 2004 Dec; 91(12):1641-5.

29. IV Contrast: Necessity Unenhanced CT in 109 patientsUnenhanced CT in 109 patients Final diagnosis by surgery or F/UFinal diagnosis by surgery or F/U 66 TN, 37 TP, 4 FN, 2 FP66 TN, 37 TP, 4 FN, 2 FP –Sensitivity: 90%, Specificity: 97% –PPV and NPV: 95% –Accuracy: 94% Alternate diagnosis on CT: 22%Alternate diagnosis on CT: 22% Lane MJ, et al. AJR Am J Roentgenol. 1997 Feb; 168(2):405-9.

30. Conclusions: IV contrast CT technology has evolved rapidlyCT technology has evolved rapidly IV contrast adds little to accuracyIV contrast adds little to accuracy Local radiologists may not be comfortable interpreting studies without IV contrastLocal radiologists may not be comfortable interpreting studies without IV contrast

31. Radiology Coat of Arms

32. Allergic Reactions

33. Adverse Reaction Occurrence 112,000 patients112,000 patients Total reactions: 5.65 %Total reactions: 5.65 %MildModerateSeverePercent3.77%1.77%0.02% Total4200198022 Shehadi WH. Am J Roentgenol Radium Ther Nucl Med. 1975 May;124(1):145-52

34. Question #3 What is the connection between iodine and seafood or shellfish allergy and intravenous contrast material?

35. “Iodine Allergy” Physiologic impossibilityPhysiologic impossibility Iodine essential to lifeIodine essential to life Found in thyroid hormones, amino acidsFound in thyroid hormones, amino acids Shellfish allergy to muscle protein tropomyosinShellfish allergy to muscle protein tropomyosin Huang SW. Allergy Asthma Proc. 2005 Nov- Dec;26(6):468-9.

36. Seafood Allergy Anaphylactoid, not IgE mediatedAnaphylactoid, not IgE mediated No response to skin testingNo response to skin testing Recurrence: <25% repeatRecurrence: <25% repeat Increased risk: foods, asthma, hay-fever, hives, drug allergiesIncreased risk: foods, asthma, hay-fever, hives, drug allergies No additional risk for seafoodNo additional risk for seafood Schlifke A, et al. Can J Emerg Med. 2003; 5(3):166-168.

37. Question #4 If a patient says “I’m allergic to contrast dye,” can’t I just give some diphenhydramine and steroids before they’re injected?

38. Preventing Adverse Reactions ACR recommendation if history of moderate or severe reactionACR recommendation if history of moderate or severe reaction 50 mg prednisone 13, 7 & 1 hour prior 50 mg diphenhydramine 1 hour prior 32 mg methylprednisolone 12 & 2 hours prior http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID= 24981&CID=2131&VID=2&DOC=File.PDF http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID= 24981&CID=2131&VID=2&DOC=File.PDF

39. Does Pretreatment Work? Meta-analysis: six studiesMeta-analysis: six studies Four used antihistaminesFour used antihistamines –Pooled RR: 0.4 (95% CI 0.18–0.9) Insufficient data for pooled statistic for corticosteroidsInsufficient data for pooled statistic for corticosteroids –Suggested reduction for methylprednisolone Delaney A, et al. BMC Med Imaging. 2006 Apr 27;6:2.

40. Does Pretreatment Work? Steroid pretreatment reduced…Steroid pretreatment reduced… …respiratory symptoms from 1.4% to 0.4% …respiratory and hemodynamic symptoms from 0.9% to 0.2% NNT to prevent one severe reaction: 100 – 150NNT to prevent one severe reaction: 100 – 150 Tramer MR, et al. BMJ. 2006 Sep 30; 333(7570):675.

41. Conclusions Pretreatment… …in unselected patients not useful …recommended in patients with prior anaphylaxis …may not prevent severe or life threatening reactions Life threatening reactions rare

42. Question #5 What about the patient with a history of asthma? Does that increase the risk of an allergic reaction?

43. Asthmatics and IV contrast Risk of serious reaction increased 5-fold in patients with asthma, multiple allergiesRisk of serious reaction increased 5-fold in patients with asthma, multiple allergies Rate of serious reactions still sufficiently low (0.1%) that pre- medication not advisedRate of serious reactions still sufficiently low (0.1%) that pre- medication not advised Morcos SK. Br J Radiol. 2005 Aug; 78(932):686-93.

44. Question #6 Should we do a serum creatinine on everyone before they get an intravenous contrast load?

45. Contrast Induced Nephropathy Definition of CINDefinition of CIN –Absolute  in Cr of 0.5mg/dL –Relative  of 25% in 48 hours Biggest risk: preexisting  CrBiggest risk: preexisting  Cr  exponentially with Cr  exponentially with Cr –Baseline Cr <1.5 mg/dL: 2% –Baseline Cr >2.5 mg/dL: 20% Moore RD, et al. Radiology. 1992 Mar; 182(3):649-55.

46. When to Check Creatinine Age > 70 yearsAge > 70 years CHFCHF CirrhosisCirrhosis DiabetesDiabetes Multiple myelomaMultiple myeloma AnemiaAnemia SepsisSepsis HypotensionHypotension HypertensionHypertension Nephrotoxic drug: NSAID, ACE inhibitor, furosemideNephrotoxic drug: NSAID, ACE inhibitor, furosemide

47. Question #7 Can I prevent contrast- induced nephropathy by giving the patient NAC or bicarb or something else?

48. What DOESN’T Work Diuresis: mannitol, furosemide “Flush” contrast through kidneys“Flush” contrast through kidneys Intuitively make sinceIntuitively make since Actually increase CIN rateActually increase CIN rate Solomon R, et al. N Engl J Med 1994 Nov 24; 331(21):1416-30

49. What DOESN’T Work Common vasodilators: dopamine, fenoldopam Increase renal flowIncrease renal flow Intuitively make sinceIntuitively make since Actually increase CIN rateActually increase CIN rate Stone GW et al. Rev Cardiovasc Med. 2001;2 Suppl 1:S31-6.

50. What DOESN’T Work Other vasodilators: atrial natriuretic peptide, calcium channel blockers, ACE- inhibitors, endothelin receptor antagonists Intuitively make sinceIntuitively make since Actually increase CIN rateActually increase CIN rate

51. What DOESN’T Work Aminophylline / theophylline Several studiesSeveral studies Results conflictingResults conflicting Pannu N et al. JAMA 2006 Jun 21; 295(23):2765-69

52. What DOESN’T Work Aminophylline / theophylline “Theophylline may reduce the incidence of CIN with an efficacy that is perhaps comparable to that reported in studies of N- acetylcysteine. However, findings are inconsistent across studies.” Bagshaw SM, et al. Arch Intern Med. 2005 May 23;165(10):1087-93.

53. Preventing CIN NSS better than D5½NS 1620 patients for angiography1620 patients for angiography D5½NS: 2.0% incidence CIND5½NS: 2.0% incidence CIN NSS: 0.7% incidence of CINNSS: 0.7% incidence of CIN Mueller C, et al. Arch Intern Med. 2002 Feb 11; 162(3):329-36.

54. Preventing CIN NaHCO3 better than NSS (??) Replace 150mL in 1 liter D 5 W with three amps of NaHCO 3Replace 150mL in 1 liter D 5 W with three amps of NaHCO 3 Infuse 3 mL/kg for 1 hour before and 1 mL/kg for 6 hours after contrast administrationInfuse 3 mL/kg for 1 hour before and 1 mL/kg for 6 hours after contrast administration CIN reduced from 13.6% to 1.7%CIN reduced from 13.6% to 1.7% Merten GJ, et al. JAMA. 2004 May 19; 291(19):2328-34.

56. Patient Oriented Outcomes

58. Preventing CIN N-acetylcysteine (NAC) Suggest NAC does nothing to prevent CINSuggest NAC does nothing to prevent CIN Rather it interferes with proper measurement of serum CrRather it interferes with proper measurement of serum Cr DOE rather than POEM??DOE rather than POEM?? Hoffman U et al. J Am Soc Nephrol. 2004 Feb; 15(2):407-410.

59. Preventing CIN N-acetylcysteine (NAC) 87 adults with renal insufficiency87 adults with renal insufficiency Half received 900-mg injection of NAC one hour before and another immediately after contrast medium injectedHalf received 900-mg injection of NAC one hour before and another immediately after contrast medium injected Other half: hydration onlyOther half: hydration only Poletti PA, et al. AJR Am J Roentgenol. 2007 Sep;189(3):687-92.

60. Preventing CIN N-acetylcysteine (NAC) Serum creatinine and cystatin C measured at admission and on days 2 and 4 after CTSerum creatinine and cystatin C measured at admission and on days 2 and 4 after CT 25% or greater increase in SCr in 9/43 (21%) in control group and in 2/44 (5%) in NAC group25% or greater increase in SCr in 9/43 (21%) in control group and in 2/44 (5%) in NAC group Poletti PA, et al. AJR Am J Roentgenol. 2007 Sep;189(3):687-92.

61. Preventing CIN N-acetylcysteine (NAC) 25% or greater increase in cystatin C concentration in 9/40 (22%) in control group and in 7/41 (17%) in NAC group25% or greater increase in cystatin C concentration in 9/40 (22%) in control group and in 7/41 (17%) in NAC group Poletti PA, et al. AJR Am J Roentgenol. 2007 Sep;189(3):687-92.

62. CIN: Conclusions Virtually all studies require pretreatment 12 hours or more in advance of procedureVirtually all studies require pretreatment 12 hours or more in advance of procedure Hydration helps: no controversyHydration helps: no controversy NAC impractical for EM practice, MAY helpNAC impractical for EM practice, MAY help Bicarbonate: no protectionBicarbonate: no protection Vitamin C: no protectionVitamin C: no protection

63. Question #7 What if my patient takes metformin?

64. Metformin and IV Contrast Metformin-associated lactic acidosis (MALA): complicationMetformin-associated lactic acidosis (MALA): complication Recommendation #1: withhold metformin 48h before IV contrastRecommendation #1: withhold metformin 48h before IV contrast Recommendation, modified: withhold metformin for 48h after IV contrastRecommendation, modified: withhold metformin for 48h after IV contrast

65. Metformin Contraindications HypersensitivityHypersensitivity DKADKA Diabetic comaDiabetic coma Chronic liver diseaseChronic liver disease CHFCHF Vitamin B-12 deficiencyVitamin B-12 deficiency Recent MIRecent MI ShockShock Severe systemic diseaseSevere systemic disease Pulmonary insufficiencyPulmonary insufficiency

66. MALA Comprehensive review: 18 cases Literature reviewLiterature review Data reported to manufacturersData reported to manufacturers Reports to FDAReports to FDA McCartney MM, et al. Clin Radiol. 1999 Jan; 54(1):29-33.

67. MALA Most were taking metformin despite contraindicationsMost were taking metformin despite contraindications Exactly one case of MALA reported in patient with normal renal functionExactly one case of MALA reported in patient with normal renal function McCartney MM, et al. Clin Radiol. 1999 Jan; 54(1):29-33.

68. MALA: Conclusion Although evidence is scanty, it is prudent to withhold metformin for 48 hours following contrast studyAlthough evidence is scanty, it is prudent to withhold metformin for 48 hours following contrast study

69. Some Final Thoughts Much has changed from early days of CT scanningMuch has changed from early days of CT scanning What was accepted ten years ago is no longer trueWhat was accepted ten years ago is no longer true Talk with your radiologists about their comfort levelsTalk with your radiologists about their comfort levels

70. Some Final Thoughts There is probably no way to prevent allergic reactionsThere is probably no way to prevent allergic reactions There may be no way to prevent CIN in ED patientsThere may be no way to prevent CIN in ED patients