O slideshow foi denunciado.
Utilizamos seu perfil e dados de atividades no LinkedIn para personalizar e exibir anúncios mais relevantes. Altere suas preferências de anúncios quando desejar.

Perioperative anaphylaxis

Perioperative anaphylaxis

Presented by Natthiya Pholmoo, MD.

December 25, 2020

  • Seja o primeiro a comentar

  • Seja a primeira pessoa a gostar disto

Perioperative anaphylaxis

  1. 1. PERIOPERATIVE ANAPHYLAXIS N AT T H I YA P H O L M O O , M D
  2. 2. INCIDENCE • The incidence of anaphylactic reactions during procedures or surgery has shown wide variations from 1 in 1,250 to 1 in 20,000. • The mortality is higher than from other causes of anaphylaxis and ranges from 3% to 9%. GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  3. 3. PATHOPHYSIOLOGY • IgE : Approximately 60% of intraoperative anaphylaxis reactions are thought to be mediated by IgE. • Nonspecific complement activation • Mas-Related G-Protein-coupled Receptor X2 can activate mast cells independent of IgE with exposure to opioids and neuromuscular blockers.
  4. 4. DELAY IN DIAGNOSIS • Delay in diagnosis – Intubated – Sedated – Draped Early skin signs and typical symptoms (eg, pruritus, feeling faint, and dyspnea) are not easily delineated.
  5. 5. CLINICAL PATTERNS • Isolated hypotension or cardiovascular collapse without any skin symptoms may be the initial presentation of intraoperative anaphylaxis. • In the surgical setting, it is important to consider anaphylaxis when hypotension or bronchospasm does not respond to usual therapy or cardiovascular collapse occurs unexpectedly.
  6. 6. CLINICAL PATTERNS GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  7. 7. CLINICAL PATTERNS • Grade I : skin manifestations • Grade II - mild - multiple system involvement - reactions are not life-threatening - more commonly associated with non-IgE-mediated reactions • Grade III : life-threatening symptoms • Grade IV : cardiac and/or respiratory arrest reactions - more commonly associated with IgE-mediated reactions • Grade V : Death
  8. 8. DIFFERENTIAL DIAGNOSIS • Any condition predisposing to shock can lead to hypotension as the initial presentation. – Myocardial ischemia – Cardiac arrhythmias – Pulmonary embolism – Hemorrhage – Sepsis – Hypovolemia
  9. 9. DIFFERENTIAL DIAGNOSIS • Upper airway mimickers of anaphylaxis – Airway swelling as a result of a difficult intubation – Angiotensin converting enzyme inhibitor related angioedema – C1-esteraseedeficient hereditary and acquired angioedema – Airway manipulation in patients with underlying airway hyperreactivity, or with undiagnosed or insufficiently treated asthma, can also lead to bronchospasm – Bronchospasm can also present in patients with chronic obstructive pulmonary disease following intubation or due to light anesthesia. – Histamine release from medications, mucus plugs, mechanical obstruction, pulmonary aspiration, pulmonary edema, pulmonary embolism, and pneumothorax.
  10. 10. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  11. 11. MIMIC • The anesthetics can cause cardiovascular changes that can mimic early anaphylaxis and make early recognition difficult. • Inhaled anesthetics cause a decrease in systemic vascular resistance and consequently a drop in mean arterial pressure. • Inhaled anesthetics can cause an increase in heart rate.
  12. 12. MIMIC • Isoflurane and desflurane, are pungent and can irritate the airways when used at higher levels. – may be exacerbated in patients with reactive airway disease, leading to bronchospasm. • Propofol : causes a dose-dependent decrease in blood pressure that may be associated with a compensatory tachycardia.
  13. 13. ETIOLOGIES • Neuromuscular blocking agents (NMBAs) • Antibiotics • Latex • Disinfectants : chlorhexidine, povidone iodine, bacitracin • Dyes • Sugammadex • Hypnotics • Opioids • Colloids • Blood products • Oxytocin • Ethylene oxide
  14. 14. NEUROMUSCULAR BLOCKING AGENTS • Most common cause : 50% to 70% of perioperative anaphylaxis events • Both an IgE-mediated mechanism and a non-IgE-mediated mechanism via direct nonspecific mast cell activation. • The IgE recognition site for the neuromuscular blockers is their substituted ammonium ions and molecular environment. • Ammonium structures : materials containing tertiary and quaternary ammonium groups including ; over-the-counter drugs, cosmetics, disinfectants, and food products • In Norway : consumption of pholcodine, opioid antitussive GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  15. 15. NEUROMUSCULAR BLOCKING AGENTS • Cross-sensitivity is approximately 60% to 70% among the neuromuscular blockers. • Only 7% show sensitivity to all the neuromuscular blockers. • Often show cross-sensitivity – pancuronium and vecuronium – succinylcholine and gallamine – cis-atracurium and atracurium GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  16. 16. NEUROMUSCULAR BLOCKING AGENTS • Increased allergic risk - Succinylcholine - Rocuronium : most common in UK • less risk - Atracurium : most common in UK - Cis-atracurium - Pncuronium • Atracurium is associated with histamine release : which may lead to bronchospasm and hypotension GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019 Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  17. 17. Jamma Li, Oliver G. Best, Michael A. Rose, Sarah L. Green, Richard B. Fulton, Marc J. Capon, Benedict A. Krupowicz, Suran L. Fernando, Assessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis, British Journal of Anaesthesia, 2019
  18. 18. ANTIBIOTICS • The most common antibiotics : Cefazolin • The reactions to the antibiotics occurred - within 5 minutes : 74% - between 6 and 10 minutes : 18% - between 11 and 15 minutes : 5% GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  19. 19. LATEX • Reactions to latex tend to occur later in the surgery, typically after significant mucosal exposure. • Latex sensitization has decreased. • The incidence of cases of latex anaphylaxis has decreased as a result of - identification of at-risk patients - the use of preventive measures : latex-free equipment (primary prevention) : powder-free gloves
  20. 20. DISINFECTANTS : CHLORHEXIDINE • Clean the skin before insertion of epidural catheters, arterial lines, and central venous lines. • It is also used on the skin of the abdomen, chest, or other body part prepared for surgery. • Urinary catheters are passed using chlorhexidine gel. • Urologic procedures were most common • Male predominance
  21. 21. DISINFECTANTS : CHLORHEXIDINE • Absorption through mucosal surfaces : urethra and bladder • Skin : incision and epidural especially if the chlorhexidine is not dry before the procedure • Chlorhexidine skin testing has been shown to be predictive of allergic sensitivity and to correlate with in vitro chlorhexidine specific IgE testing. • Sensitization to chlorhexidine can occur from home products such as mouthwash, toothpaste, dressings, ointments, and over the-counter disinfectant solutions for cuts and wounds.
  22. 22. DISINFECTANTS : CHLORHEXIDINE • Often unrecognized and lack of clear labeling • Reaction onset in the perioperative setting varies (rapid or delayed) • Patients with anaphylaxis have a history of mild localized reaction to earlier exposure • Lack of standardized testing • A skin test may have to be read 20–30 mins after SPT and IDT • Several centres recommend routine testing with Chlorhexidine. • May be coincident with other drug allergies Chiewchalermsri, C., Sompornrattanaphan, M., Wongsa, C., & Thongngarm, T. (2020). Chlorhexidine Allergy: Current Challenges and Future Prospects. Journal of asthma and allergy, 13, 127–133. https://doi.org/10.2147/JAA.S207980 Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  23. 23. Chiewchalermsri, C., Sompornrattanaphan, M., Wongsa, C., & Thongngarm, T. (2020). Chlorhexidine Allergy: Current Challenges and Future Prospects. Journal of asthma and allergy, 13, 127–133. https://doi.org/10.2147/JAA.S207980 https://www.mims.com/thailand/ drug/info/chlorsep
  24. 24. DISINFECTANTS : POVIDONE-IODINE • Few case reports of reaction to povidone-iodine. • These are usually associated with the application of the povidone- iodine to the mucosa or skin. • These reactions can occur at variable times during surgery. • Povidone iodine can be safely used in patients with shellfish allergy, because the allergenic component of shellfish is tropomyosin.
  25. 25. DYES • Blue dyes are used to identify sentinel lymph nodes in melanoma and breast cancer. • The 2 most commonly used dyes are patent blue V and isosulfan blue. : They are structurally very similar and cross-reactive. • Methylene blue, however, is structurally different. : Cross-reactivity would not be expected between methylene blue and patent blue V, it has been reported. • Reactions to the blue dyes can be delayed compared with the intravenously administered medications. This may be due to slow absorption from the lymphatics and subcutaneous tissue.
  26. 26. SUGAMMADEX • A reversal agent for neuromuscular blockers • The incidence : 1 in 2500 at a single Japanese hospital • Reactions to sugammadex occur late in the surgery because they are given to reverse neuromuscular blockade. • The sensitizing trigger to sugammadex is not definitively known. Cyclodextrin, is found in food additives and cosmetics and this potentially could be sensitizing. • There are reports of patients reacting to a sugammadex-rocuronium complex. Testing to rocuronium and sugammadex individually may be negative, but when combined result in a positive test result.
  27. 27. HYPNOTIC AGENTS The hypnotic induction • Propofol : most common • Ketamine • Midazolam • Etomidate * Reactions to midazolam, etomidate, ketamine, local anesthetics and inhalational agents appear to be extremely rare.
  28. 28. PROPOFOL • Allergic reactions to propofol are uncommon and account for less than 2% of all reactions to general anesthetics. • Propofol (2-6-diisopropyl-phenol) is currently formulated in a lipid vehicle containing 10% soybean oil, 1.2% egg lecithin, 2.25% glycerol. • Recent studies show that propofol is safe to use in children and adults with egg, soy, or peanut allergy. • True allergic reactions to propofol are likely to be secondary to the 2 isopropyl groups. • Many patients who develop anaphylaxis after first exposure may do so because of sensitivity to the di-isopropyl radical that is found in many dermatological products and lipid formulations. • History of prior use of parenteral nutrition with intralipids and sensitivity to dermatological products is important. • Skin tests with 10% intralipid Koul, A., Jain, R., & Sood, J. (2011). A critical incident report: Propofol triggered anaphylaxis. Indian journal of anaesthesia, 55(5), 530–533. https://doi.org/10.4103/0019-5049.89898
  29. 29. OPIOIDS • Incidence of allergic reactions to opioids is 1 in every 100,000 to 200,000 anesthetics. • IgE‐mediated hypersensitivity to opiates and semisynthetic opioids is very rare. • Many opioids (eg, morphine and meperidine) cause the direct release of histamine, causing dermatologic manifestations including urticaria, itching, and vasodilation. • Large doses of morphine used during cardiac anesthesia did not show any bronchospasm or angioedema.
  30. 30. OPIOIDS ▪ There is little or no evidence of cross‐reactivity between the different opioid subclasses – Phenylpiperidines : alfentanil, fentanyl, remifentanil, sufentanil, meperidine – Diphenylheptanes : methadone and propoxyphene – Phenanthrenes : morphine, codeine ▪ Cross‐ reactivity between morphine and codeine is reported.
  31. 31. COLLOIDS Colloids commonly used in the operating room • Albumin • Dextran • Hetastarch • Gelatin
  32. 32. COLLOIDS • Gelatin is the colloid most likely to lead to an allergic reaction. • Gelatins and dextrans are more likely than albumin or hetastarch to cause an allergic reaction. • Albumin is the colloid least likely to lead to an allergic reaction. • Colloids that belong to the same group such as Hemaccel and Gelofusin (which are both gelatins) have been proven to have cross- reactivity.
  33. 33. BLOOD PRODUCTS • Urticarial reactions are seen in 0.5% of all transfusions with frozen plasma. • Allergic reactions to red blood cells and platelets may occur as well. • The reaction may present as itching, swelling, or a rash. These symptoms can be avoided with diphenhydramine pretreatment in patients who previously had severe urticarial reactions. • True anaphylactic reactions to blood products are infrequent (0.6 per 1000 transfusions)
  34. 34. OXYTOCIN • Oxytocin and analogues are used widely, but only few cases of perioperative anaphylaxis are reported. • As rapid injection and high doses can induce hypotension, tachycardia, flushing and chest discomfort, a relative over‐dose can be misdiagnosed as anaphylaxis. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  35. 35. • Ethylene oxide (EO) is a gas used to sterilize most medical devices. • Reactions are rare in the perioperative setting in general. • There seems to be increased risk of sensitization in myelomeningocele patients and patients with ventriculoperitoneal shunts. • It is rarely possible to completely avoid EO, but an EO minimized procedure is advised • Pretreatment with omalizumab has been tried successfully. ETHYLENE OXIDE Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  36. 36. SIGNS AND SYMPTOMS • When hypotension occurs unexpectedly, with or without tachycardia, or is unresponsive to vasopressors, perioperative anaphylaxis should be considered. • Bradycardia or unchanged heart rate may be seen, especially in patients on β‐blockers. • Paradoxical bradycardia occurring during extreme hypovolaemia has been reported in patients with perioperative anaphylaxis. • Bronchospasm is usually a feature in patients with underlying airway hyperreactivity. • Cutaneous signs, such as urticaria and generalized erythema, are often present in anaphylaxis, but can be absent during severe hypotension and may reappear after restoration of adequate circulation. • Signs from the gastrointestinal tract are absent during general anaesthesia, but may be present during regional anaesthesia.
  37. 37. INVESTIGATION The aims of perioperative anaphylaxis investigation • Identify a culprit drug • Identify safe alternatives • ensure safe future anaesthesia ▪ Reactions grade 2‐4 should always be referred for investigation. ▪ Transient self‐limiting flushing or localized erythema is unlikely to represent significant hypersensitivity and does not need investigation.
  38. 38. INVESTIGATION Documentation should include • anaesthetic record • all drug charts (preoperative, theatre and recovery) • anaesthetist's notes • details of any surgical • other perioperative exposures (disinfectants, local anaesthetic sprays/gels, dyes, cements) • details of all procedures (arterial, venous and urinary catheters, stents).
  39. 39. INVESTIGATION • All IV exposures given within 1 hour of reaction onset • All other exposures (intramuscular, subcutaneous, spinal, epidural, other local exposures) given within 2 hours of reaction onset are investigated. • A study on fatal anaphylaxis reported that median times to cardiac arrest varied with route of administration being - 5 minutes after IV injection -15 minutes after SC injection - 30 minutes after oral intake. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  40. 40. INVESTIGATION In patients with a past history of perioperative anaphylaxis , but where details of drug exposures are not available, it may be necessary to test with • Latex • Chlorhexidine • Ethylene oxide • Simple battery of drugs : propofol, fentanyl, remifentanil and a NMBA to ensure safe future anaesthesia. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  41. 41. INVESTIGATION • Drugs that have been continued or re‐administered in the same anaesthetic after recovery of the reaction should still be considered for testing due to the risk of a possible refractory phase or antiallergic therapy masking symptoms. • Drugs that have been continued for several days after the antiallergic therapy has been stopped, for example local anaesthetic infusion in an epidural, or continuous infusion of propofol for several days in intensive care, are less likely causes.
  42. 42. INVESTIGATION • The ideal timing of investigations is not known. • It is recommended that testing takes place 1‐4 months postevent and at least 4‐6 weeks postevent to avoid false‐negative results. • British guidelines have suggested that investigations can take place immediately after the event. • Negative skin test results before 4 weeks postevent may not exclude allergy and later re‐testing may be needed. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  43. 43. INVESTIGATION • Children with perioperative anaphylaxis are investigated using the same approach as for adults. • There are no specific data about test sensitivity and specificity in this age group. • In small children, IDT may be omitted or carried out after pretreatment with topical lidocaine, if lidocaine is not a suspected culprit. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  44. 44. SKIN TESTING Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  45. 45. SKIN TESTING Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  46. 46. SKIN TESTING GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  47. 47. IN VITRO TESTING • Serum Tryptase • Plasma histamine • Specific IgE testing (sIgE) • Basophil activation test (BAT) • Histamine release (HR)
  48. 48. SERUM TRYPTASE • Tryptase, a mast cell protease, is a preformed enzyme that is also released during mast cell activation. • Tryptase serum levels peak approximately 15 minutes to 120 minutes after the anaphylactic reaction onset, and declines under first-order kinetics with a half-life of approximately 2 hours. GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  49. 49. SERUM TRYPTASE • It is recommended to measure tryptase within 1‐3 hours after a suspected perioperative anaphylaxis. • An acute serum tryptase level greater than [1.2 x serum baseline tryptase] + 2 mcg/L has been recommended to confirm acute mast cell degranulation. • Measuring baseline tryptase has an additional purpose, as elevated baseline levels might be indicative of underlying clonal mast cell disorders. • The baseline sample should be taken a minimum of 24 hours after the reaction. GeraldW.Volcheck, David L. Hepner, Identification and Management of Perioperative Anaphylaxis, The Journal of Allergy and Clinical Immunology: In Practice, 2019
  50. 50. SPECIFIC IGE TESTING • β‐lactam antibiotics • NMBAs • Latex • Chlorhexidine • Ethylene oxide • Morphine • Gelatin • Sensitivity and specificity are high for Latex and Chlorhexidine (near 100%) assays. • sIgE can be measured on the sample taken at the time of reaction, but if negative, it needs to be repeated 4‐6 weeks later.
  51. 51. BASOPHIL ACTIVATION TEST • BAT can be performed for all drugs. • BAT can be used to identify both culprit drugs and potential safe alternatives.
  52. 52. DRUG PROVOCATION TESTING • Full‐dose DPT represents the “Gold Standard” when investigating immediate hypersensitivity to drugs. • It has had limited use in perioperative anaphylaxis due to the strong pharmacologic effects of perioperative drugs, for example respiratory depression, paralysis and anaesthesia. • Consensus on the use of DPT in this setting is lacking. • DPT can be performed when skin tests are equivocal/negative with the aim to exclude sensitization to the culprit drug or to test a safe alternative.
  53. 53. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, Laguna JJ, Chiriac AM, Terreehorst I, Voltolini S, Scherer K. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy. 2019 Oct;74(10):1872-1884. doi: 10.1111/all.13820. Epub 2019 Jun 18. PMID: 30964555.
  54. 54. ขอบคุณ!

×