Intravenous Dyes Class (3 per) PDF

12/15/23 INTRAVENOUS CONTRAST MEDIA & DYES Kelly Elmore, DNP, APRN-CR...

12/15/23 INTRAVENOUS CONTRAST MEDIA & DYES Kelly Elmore, DNP, APRN-CRNA Mary Baldwin University NAP Advanced Pharmacology for Anesthesiology Practice I Spring Semester 1 Iodinated Contrast Media ◦ Introduced in 1950s ◦ Among most commonly prescribed drugs ◦ Enhance radiologic imaging ◦ Good safety record ◦ Adverse effects often mild, self-limited ◦ Severe, life-threatening reactions possible 2 STRUCTURE ◦ Classified based on modification of 2,4,6-tri- iodinated benzene ring ◦ Physical characteristics ◦ Chemical characteristics ◦ Osmolality ◦ Iodine content ◦ Ionization in solution 3 1  12/15/23 Osmolality ◦ Related to chemical structure ◦ High-osmolality ICM ◦ Higher risk of adverse events ◦ ______________________________________________________ more common ◦ Examples: Renografin, Hypaque, Conray 4 Osmolality ◦ Low-osmolality ICM ◦ Non-ionic monomers (Omnipaque, Isovue, Optiray, Ultravist) are agents of choice ◦ Less adverse events, less chemotoxicity ◦ Less tissue damage with extravasation ◦ More costly 5 Osmotic Effects ◦ Transient decreases in renal blood flow ◦ Transient decrease in GFR ◦ Osmotically-induced ________________________________________ (dehydrating effect) 6 2  12/15/23 ICM Reactions ◦ Pathogenesis ◦ Direct cellular toxicity ◦ Enzyme induction ◦ Activation of complement, fibrinolytic, kinin, other systems ◦ Classification ◦ Idiosyncratic ◦ Nonidiosyncratic ◦ Contrast-induced nephropathy (CIN) 7 Idiosyncratic Reactions ◦ ◦ Within 20 min of injection ◦ Independent of dose administered ◦ ____________________________________________________________________ reaction ◦ NOT true hypersensitivity – no IgE antibodies involved ◦ Common in previous ICM reaction, asthma, food/drug/environmental allergies ◦ Do not necessarily recur 8 Idiosyncratic Reactions ◦ Symptoms ◦ Hives, pruritus ◦ Nausea, vomiting ◦ Diaphoresis ◦ Facial, __________________________________________________, bronchospasm, pulmonary edema ◦ HTN or HOTN (severe), tachycardia or bradycardia, arrhythmias ◦ Syncope ◦ Seizures ◦ Death 9 3  12/15/23 Nonidiosyncratic reactions ◦ Variety of possible reactions ◦ May be delayed ◦ 30 min to up to 7 days after ICM ◦ Resemble flu-like symptoms ◦ Caution in pregnancy ◦ Crosses placenta ◦ May be mutagenic to human cells ◦ Nonionic agents preferred if administered 10 Nonidiosyncratic Cardiovascular Reactions ◦ Direct ___________________________________________________________ effect on myocardium ◦ Vasovagal reactions ◦ May precipitate angina ◦ Risk for syncope ◦ Peripheral vasodilation, HOTN ◦ Lowered threshold for ventricular arrhythmias ◦ Risk for cardiac arrest ◦ Hyperosmolar IV fluids with ICM may cause HTN, pulmonary edema 11 Other Nonidiosyncratic Reactions ◦ Neuropathy, polyarthropathy ◦ Syncope ◦ Extravasation ◦ __________________________________ ◦ Tissue damage ◦ Depression ◦ Compartment syndrome ◦ Exacerbation of ◦ Metallic taste in mouth ◦ Cardiac disease, arrhythmias ◦ N/V ◦ Pheochromocytoma ◦ Constipation ◦ Sickle cell anemia ◦ Pruritus ◦ Hyperthyroidism ◦ Myasthenia gravis 12 4  12/15/23 Contrast-Induced Nephropathy ◦ Pathogenesis (?) ◦ Hemodynamic changes ◦ _______________________________________________________________________ ◦ Renal medullary ischemia ◦ Decreased nitric oxide, increased endothelin ◦ Cellular toxicity ◦ Increased O2 free radicals ◦ Osmotic load ◦ Increased blood viscosity ◦ Increased O2 consumption 13 Contrast-Induced Nephropathy ◦ Elevated creatinine (> 50% of baseline) ◦ Up to 25% have sustained renal insufficiency, oliguria ◦ Elevated risk ◦ Preexisting renal insufficiency (5 – 10x) ◦ _____________________________________________________________** ◦ CHF class IV ◦ NSAID, aminoglycoside use ◦ Elderly ◦ Repeated, large doses of ICM 14 15 5  12/15/23 16 Management Considerations ◦ Adequate history and physical assessment preoperatively ◦ Advanced life support equipment, drugs readily available ◦ Treat nonidiosyncratic reactions as necessary 17 Management Considerations ◦ Moderate, severe idiosyncratic reactions ◦ VS monitored ◦ Cardiovascular support ◦ Airway, ventilatory support as needed ◦ Antihistamines (H1 blockers, diphenhydramine; H2 blockers, famotidine) may be administered after epinephrine for anaphylaxis ◦ IV fluid for HOTN – use iso-osmolar (NS, LR) 18 6  12/15/23 Management Considerations ◦ CIN ◦ IV fluids, supportive treatment to restore volume and electrolyte balance ◦ _____________________________________________________________________________ ◦ 600 mg twice daily with adequate hydration may be effective for prevention ◦ Antioxidant, enhances NO-induced vasodilation 19 Management Considerations ◦ CIN ◦ Theophylline ◦ Sodium bicarbonate ◦ Diuretic use ◦ Not recommended to hold routine diuretics or ACE-Inhibitors ◦ Mannitol, furosemide not recommended for prevention 20 Management Considerations ◦ Prevention ◦ Corticosteroids – standard of care in US, controversial in Europe ◦ Lower-level evidence supporting use ◦ Methylprednisolone, prednisolone multiple dose regimen prior to ICM (usually reserved for previous moderate-severe reaction) ◦ H2 blockers may have role in prevention ◦ Typical regimen ◦ H1 blocker _________________________________50 mg, 1 hr before ICM; optional H2 blocker added 21 7  12/15/23 EW REVI 22 Intraoperative IV Dye Use https://www.thelancet.com/journals/langas/article/PIIS2468-1253%2817%2930216-9/fulltext 23 Fluorescence-Guided Surgery ◦ Increasing use of minimally invasive surgery ◦ Assists in improving visibility of different types of tissue ◦ Applications ◦ Sentinel lymph node mapping ◦ Tumor detection ◦ Visualization of vital structures ◦ Angiography and tissue perfusion ◦ Near-infrared light spectrum fluorescent agent (“fluorophore”) ◦ Imaging system excites and detects fluorophore https://ironmanmattress.ca/blog/what-is-the-difference-between-red-light-infrared-and-near-infrared-light-therapy/ 24 8  12/15/23 https://www.frontiersin.org/articles/10.3389/fbioe.2022.1042546/full https://journals.sagepub.com/doi/abs/10.1177/17085381211032826?journalCode=vasb 25 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jso.25105 26 Indocyanine Green (ICG) ◦ Nonspecific contrast agent in the near-infrared region ◦ Absorption and emission: 800 - 850 nm ◦ 25 mg vial of sterile green powder ◦ Reconstitute with _______________________________________________________ provided ◦ Use within 6 hrs ◦ No changes is safety efficacy in pediatrics, geriatrics ◦ Fetal safety data not established ◦ Adverse reactions ◦ Hypersensitivity reactions (eg, hives) ◦ Antihistamines, corticosteroids, epinephrine ◦ Anaphylaxis (w/fatality reported) 27 9  12/15/23 Indocyanine Green ◦ Highly protein bound to albumin ◦ Hepatic & biliary uptake/clearance ◦ ½ time 2.5 - 3 min. ◦ Administration ◦ Preoperatively or intraoperatively ◦ Visualization time ranges 1 - 30 min. ◦ Dose ◦ Dependent on procedure ◦ Adults 5 mg ◦ Peds 2.5 mg ◦ Max 2 mg/kg 28 Indigo Carmine ◦ Nonspecific contrast agent in the near infrared region ◦ Absorption & excitation: max 615 nm ◦ Uses ◦ Cystoscopy for ureteral injury & flow ◦ Obstetrics for amniotic fluid leak assessment ◦ Administration ◦ IV or IM ◦ ½ life 4 - 5 min. ◦ Dose: 5 mL injection ◦ Safety data not established in pregnancy ◦ May cause _____________________________-adrenergic stimulation 29 Methylene Blue (MB) ◦ Nonspecific contrast agent in near infrared region ◦ Absorption and excitation peaks at 700 nm ◦ Lower capacity to penetrate tissues (vs. ICG) ◦ Ampules and prefilled syringes common ◦ Incompatible with normal saline ◦ Can dilute in 50 ml D5W and administer immediately ◦ Pregnancy category ____________ ◦ Black box warning for fetal harm ◦ Avoid in G6PD deficiency, hepatic/renal impairment, most antidepressant drugs 30 10  12/15/23 Methylene Blue & Methemoglobinemia ◦ Reduced to leucomethylene blue by NADPH ◦ Reduces ferric ion (Fe3+) of MetHb to ferrous state (Fe2+) of Hb ◦ Also combines with cyanide to form cyanmethemoglobin ◦ In high concentrations, ferrous iron of reduced Hb converted back to ferric iron → ___________________________________ https://toxandhound.com/toxhound/refractory-methemoglobinemia/ 31 Methylene Blue & Vasoconstriction ◦ Inhibition of nitric oxide synthase (required for production of nitric oxide) ◦ Inhibition of guanyl cyclase reducing the formation of ______________________ ◦ Vasopressor uses ◦ Vasoplegia syndrome (cardiac surgery following bypass) ◦ Septic shock, refractory HOTN ◦ Anaphylaxis ◦ Liver transplantation https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/15971/Intraoperative_vasoplegia___methylene_blue_to_the_rescue.pdf?sequence=1 32 Methylene Blue ◦ Highly bound to albumin ◦ Dose ◦ 0.25 - 2 mg/kg IV (depending on indication) ◦ Can be administered as an infusion up to 3 mg/kg/hr ◦ Administer slowly over 5 - 30 min. 33 11  12/15/23 Methylene Blue ◦ Adverse effects ◦ MB is a potent ______________________________________________________________ ◦ Fatal serotonin toxicity risk in pts on antidepressants ◦ Hemolysis ◦ Hypersensitivity reactions ◦ HTN, angina ◦ Reduced mesenteric, cutaneous perfusion 34 Oximetry ◦ IV dyes interfere with the infrared or red wavelengths detected by optical technology-based monitors ◦ Pulse oximeter ◦ Cerebral oximeter ◦ Oxyhemoglobin absorbs more infrared (emits 940 nm) ◦ Deoxyhemoglobin absorbs more red (emits 660 nm) ◦ IV dyes with lower absorption peaks decrease the absorption ratio of red & infrared wavelengths detected by oximeters ◦ → Falsely _____________________________ oxygen saturation readings ◦ Reports of reduced bispectral index readings with methylene blue (??) 35 END! 36 12  12/15/23 References ◦ https://emedicine.medscape.com/article/422855-overview ◦ Flood, P., Rathmell, J. P., & Shafer, S. (2015). Stoelting's pharmacology and physiology in anesthetic practice (5th ed.). Philadelphia: Wolters Kluwer Health. ◦ Sendeski, M. M. (2011). Pathophysiology of renal tissue damage by iodinated contrast media. Clinical and Experimental Pharmacology and Physiology, 38(5), 292-299. doi:10.1111/j.1440-1681.2011.05503.x ◦ https://reference.medscape.com/drug/omnipaque-oraltag-iohexol-343760 ◦ https://www.frontiersin.org/articles/10.3389/fbioe.2022.1042546/full ◦ https://www.drugs.com/pro/indocyanine-green.html ◦ https://journals.sagepub.com/doi/abs/10.1177/17085381211032826?journalCode=vasb ◦ https://toxandhound.com/toxhound/refractory-methemoglobinemia/ ◦ https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/15971/Intraoperative_vasoplegia___methylene_blue_to_the_rescue.pdf?sequence=1 ◦ https://www.rxlist.com/indigo-carmine-drug.htm ◦ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384414/ ◦ https://pubs.asahq.org/anesthesiology/article/105/1/228/9333/Methylene-Blue-Treatment-for-Methemoglobinemia-and 37 13