Download How to Minimize Radiographic Contrast Reactions

How to Minimize Radiographic
Contrast Reactions:
Anaphylactoid & Acute Renal
Injury
Charles E. Chambers, MD, FSCAI, FACC
VP, Society of Cardiovascular Angiography and Interventions
Professor of Medicine and Radiology
Pennsylvania State University College of Medicine
Radiographic Contrast Media (RCM)
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First introduced in 1923 (SrBr) to study the urinary tract,
with NaI introduced in 1924.
RCM makes fluid visible by increasing x-ray (60-125 photon
kVp) absorbance based on elemental atomic number and
density with iodine best.
Minimum iodine concentrations are 300 mg/ml (normal
range 320-400 mg/dl).
Classification is based upon an agents ability to dissociate
(ionic) or not dissociate (nonionic) into ionic particles when
introduced into blood.
Criteria for “Ideal” Radiographic
Contrast Media
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Must be liquid at room temperature with
viscosity similar to blood.
It must contain an element with sufficiently high
atomic number in a concentration adequate to
provide an x-ray absorbance that is 10 percent
greater than blood.
It’s components must be biocompatible, with
the lowest side effect profile, and easily
eliminated from the body.
Hirshfeld JW. Radiographic Contrast Agents. In Cardiac Imaging, ed Marcus, Schelbert, Skorton, Wolf, 1991
Radiographic Contrast Media
Classification is based upon the agent’s ability to dissociate (ionic) or not dissociate (nonionic) into ionic particles
Ionic Monomer
Nonionic Monomer
Ionic Dimer
Nonionic Dimer
Radiographic Contrast Media
Product
Type
I Concentration
Osmolality
(mgI/mL)
(mOsm/kg H2O)
---------------------------------------------------------------------------------------------------------
Monomers
iohexol (Omnipaque)
iopamidol (Isovue)
ioxilan (Oxilan)
iopromide (Ultravist)
ioversol (Optiray)
non-ionic
non-ionic
non-ionic
non-ionic
non-ionic
350
370
350
370
350
844
796
695
774
792
non-ionic
ionic
320
320
290
600
Dimers
iodixanol (Visipaque)
ioxaglate (Hexabrix)
__
Kozak M, Chambers, CE. Cardiac Catheterization Laboratory: In: Kaplan, JA, ed. Kaplan's Cardiac Anesthesia. 6th ed., 2011
“Allergic” Reactions to RCM
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Differentiate Chemotoxic from Anaphylactoid
Anaphylactoid not anaphylactic since non-IgE medicated , therefore no
skin tests are available or invitro tests to detect potential allergic
rxns
Allergy to “fish” is unrelated to RCM allergy since the presence of
iodine in fish and contrast media is not a common antigenic factor.
A trial administration of a small dose of contrast may well not
detect potential reactions to the therapeutic dose.
Incidence of Repeat Anaphylactoid Contrast Reactions
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Without prophylaxis- 44%
With steroid and diphenhydramine-5%
With steroids, diphenhydramine, and non-ionic contrast-0.5%
Reisman RE. Anaphylaxis, in Allergy and Immunology, AM Coll of Physicians, 1998
Anaphylactoid Reaction Prophylaxis
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Prednisone: 50 mg po 6pm, midnight, and 6 AM
prior to catheterization.
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Most important dose likely the one >12 hrs prior.
Diphenhydramine: 50mg, given IV on call
Non-ionic contrast used.
Limited role for H2 blockers and ephedrine.
Should not use H2 without H1.
 Ephedrine not proven beneficial in the cardiac pt.
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Emergent procedures, limited data:
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Hydrocortisone, 200 mg IV q 4 hrs, until procedure .
Goss JE, Chambers CE, Heupler. Systemic Anaphylactoid Rxns to RCM/ CCD 1995. 34: 88-104.
Therapy for Anaphylactoid Reactions
Minor-Uticaria, with or without
Skin Itching
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Bronchosapsm
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No therapy
Diphenhydramine, 25-50mg IV
Epinephrine 0.3 cc of 1:1,000 solution subQ q 15 min up to 1 cc
Cimetadine 300 mg or ranitadine 50 mg in
20 cc NS IV over 15 mins
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Facial/Laryngeal Edema
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Call anesthesia
Assess airway
 O2 mask, Intubation, Tracheostomy
tray
Mild-Epinephrine sq
Moderate/Severe: Epi-IV 0.3 cc of 1:1,000
solution sub-Q q 15 min, 1 cc
Diphenhydramine 50 mg IV
Hydrocortisone 200-400 mg IV
Optional: H2 blocker
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Oxygen
Mild- albuterol inhaler, 2 puffs
Moderate-Epinephrine 0.3 cc of 1:1,000 sub-Q
up to 1 cc
Severe-Epinephrine IV as bolus 10
micrograms/min then infusion 1 to 4
micrograms/min
Diphenhydramine 50 mg IV
Hydrocortisone 200-400mg IV
Consider H2 blocker
Hypotension/Shock
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Epinephrine IV boluses
Large volumes 0.9% NS (1-3 l)
CVP, PA catheter
Airway, intubation as needed
Diphenhydramine 50 mg IV
Hydrocortisone 400mg IV
If unresponsive…
 H2 blocker
 Dopamine/nor epinephrine
2011 PCI Guidelines
3.3 Anaphylactoid Reactions
Recommendations
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Class I
1. Patients with prior evidence of an anaphylactoid reaction to contrast
media should receive appropriate steroid and antihistamine prophylaxis
prior to repeat contrast administration . (Level of Evidence B)
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Class III: No Benefit
1. In patients with prior history of allergic reactions to shellfish or
seafood, anaphylactoid prophylaxis for contrast reaction is not
beneficial. (Level of Evidence: C)
Delayed Contrast Reaction
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Uncommon
Exclude
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Clopidogrel
Other drugs
Consider
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Steroids
Other Dx.
Contrast Induced Nephropathy (CIN)
Contrast Induced Acute Kidney Injury
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Definition: an increase in serum Cr from baseline
of >25%, or absolute >0.25 or 0.5 mg/dl.
Baseline renal disease increases risk as assessed by
eGFR or CrCl; age, sex , and obesity factors in
estimating eGFR/CrCl.
Renal dysfunction is identifiable by 48 hrs and
most often returns to baseline by 7-10 days.
Pre-procedural Clinical Risk Factors
for Contrast Induced Nephropathy
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Modifiable Risk Factors
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Contrast volume
Hydration status
Concomitant nephrotoxic
agents
Recent contrast
administrations
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Non-modifiable Risk
Factors
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Diabetes/Chronic kidney
disease
Shock/hypotension
Advanced age (> 75 yrs)
Advanced congestive heart
failure
Klein LW, Sheldon MA, Brinker J, Mixon TA, Skeldiong K, Strunk AO, Tommaso CL, Weiner B, Bailey SR, Uretsky B, Kern M, Laskey W
. The use of radiographic contrast media during PCI: A focused review. Cathet Cardiovasc Int 2009; 74: 728-46
Multi-factorial Predictors of CIN
Variable
Score
 Hypotension 5
 IABP use
5
 CHF
5
 SCR>1.5
4
 Age.75
4
 Anemia
3
 DM
3
 Contrast Volume 1/100
Odds Ratio
2.537
2.438
2.250
2.053
1.847
1.601
1.508
1.290
Mehran R J. Am Coll Cardiolo. 2004;44:1393-99.
P Value
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
Multi-factorial Predictors of CIN
Cardiac Complication in Patients with
CIN Post PCI
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Mayo Clinic Registry of 7,586 pts post PCI
Patients with CIN had increased rates of:
CABG
 Q-MI
 CK Rise
 Low BP
 Shock
 Cardiac Arrest
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p=0.004
p< 0.001
p<0.001
p<0.001
p<0.001
p<0.001
Rihal CS. Circ. 2002; 105:2259-64.
Mortality with CIN
Non- RCM Related Procedural
Complications Resulting In Renal Injury
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Cholesterol Emboli
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Renal Insufficiency
identified week(s) later
Livedo reticularis
Necrotic toes
Eosinophilia
Crystals on bx
Cholesterol
Emboli
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Pre-Procedure
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Reducing CIN Risk
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Not Prevention
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Identify Risk
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Optimize hydration status.
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High risk: eGFR <60 ml/1.73 m2
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Contrast to CrCl ratio
Contrast
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NSAID stop if possible
N-acetylcysteine, mixed
reviews, no clear benefit
Procedure
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Schedule outpatient for early arrival
and/or delay procedure time to allow
time to accomplish the hydration.
Normal Saline preferred over
D5 ½ normal
Sodium Bicarbonate, mixed
reviews
Medications
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Low risk: eGFR > 60 ml/1.73 m2
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Hydration
Volume, repeat studies
Type-non-ionic/isoosmolar
Post Procedure
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Hydration: Normal Saline & PO
2011 PCI Guidelines
3.2 Contrast-Induced Acute Kidney
Injury Recommendations
Class I
1. Patients should be assessed for risk of contrast-induced AKI before PCI. (Level of
Evidence: C)
2. Patients undergoing cardiac catheterization with contrast media should receive
adequate preparatory hydration . (Level of Evidence: B)
3. In patients with chronic kidney disease (creatinine clearance <60cc/min), the volume
of contrast media should be minimized . (Level of Evidence: B)
Class III: No Benefit
1. Administration of N-acetyl-L-cysteine is not useful for the prevention of contrastinduced AKI . (Level of Evidence: A )
Contrast Dose
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Maximal Allowable Contrast Dose (MACD)
5 cc contrast x body wgt (kg)/ baseline Cr
 Brown et al, Circ Interv, 2010.
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Volume to Creatinine Clearance Ratio
Contrast volume/ CrCl
 Laskey, JACC 2007, unselected population, 3.7 ratio
 Gurm et al, JACC, 2011, <2 safe; >3 concern
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Contrast Type
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Low osmolar or Iso-osmolar better than high
osmolar contrast
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Iso-osmolar may be better than certain low osmolar
contrast (iohexol) but has not consistently been proven
for all low osmolar agents.
Keys
Low-osmolar or iso-osmolar
 Limit dose
 Repeat studies>72 hrs, if clinically possible
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Gadolinium
Gadolinium chelates used extensively in MR
imaging.
 Once Considered a potential “substitute” for
iodonated RCM in pts with renal insufficiency
and anaphylactoid reactions.
 Advantages have not been documented and
visualization is an issue compared with
iodonated RCM.
 Nephrotic Systemic Fibrosis (NSF) or
Nephrotic Fibrosing Dermopathy (NFD)
identified in patients with baseline renal
dysfunction following gadolinium.
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N-acetylcysteine: a Meta-analysis
of 20 Randomized Trials
20 Random Trials, N=2195, CI 95%; Nallamothu BK et al. Am J Med. 2004; 117:938-47
Other Considerations
Carbon Dioxide
 Alternative Contrast Agent
 Used in conjunction with
small dose of iodinated
contrast
 Potential Neurotoxicity
 Recommended only below
diagram
Volume: Hydration
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Diuretics not of benefit
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mannitol may be detrimental
Sodium Bicarbonate: inconsistent
data, unclear benefit
0.9 NS better than 0.5 NS
IV better than oral
Pre and post hydration preferred,
CHF patient dependent.
Rudnick. Prevention of Contrast-induced Nephropathy, 2013
Other Considerations
Hemofiltration and
Hemodialysis
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Neither can be
recommended routinely
In Stage 5 CKD, more
information is needed
Drugs
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Atrial natriuretic peptide
Statins
Ascorbic Acid
Trimetazidine
Renal Guard System
Fluid management device that guides fluid
replacement.
More information required before routinely
recommended.
Recommendations for Decreasing Risk of
Contrast Induced Acute Renal Injury/CIN
Manage Medications
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Withhold, if clinically appropriate, potentially nephrotoxic drugs including
aminoglycoside antibiotics, anti-rejection medications and nonsteroidal antiinflammatory drugs (NSAID).
Manage Intravascular Volume (Avoid Dehydration)
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Administer a total of at least 1L of isotonic (normal) saline beginning at least 3
hrs before and continuing at least 6-8 hrs after the procedure.
i. initial infusion rate 100 to 150 ml/hr adjusted post
procedure as clinically indicated
Radiographic Contrast Media
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Minimize volume
Low- or iso-osmolar contrast agents
Post-Procedure: Discharge/Follow-Up
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Obtain follow-up SCr 48 hrs post procedure
Consider holding appropriate medications until renal function returns to normal,
i.e. metformin, NSAID
Final Thoughts and Questions