"Anafylaksi - fokus påp videre utredning" Anne Berit Guttormsen Department of Anaesthesia and Intensive Care, Haukeland University Hospital and Section for Anaesthesiology and Intensive Care, Department of Surgical Sciences, Medical Faculty, University of Bergen
Anaphylaxis in the OR is rare What caused the reaction? The next procedure? Follow-up, documentation and communication Information should be put in the journal
Incidence 70 80 reactions per year in Norway reported to the Norwegian network ~ 40% of the patients have a full follow-up Acute blood samples Allergological follow-up Early diagnosis and correct treatment is mandatory to achieve an optimal result for the patient, i.e survival
Aetiology Allergy is common, but progression of an allergic reaction to a severe life-threatening condition is rare. Most common causes of the life-threatening reactions are drugs, stinging insects and food. European Resuscitation council Guidelines for Resuscitation 2005
Early signs Urticaria Rhinitis Conjunctivitis Abdominal pain Vomiting and diarrhoea Flushing or pallor European Resuscitation council Guidelines for Resuscitation 2005
Due to Diagnosis is difficult Lack of consistent clinical information A wide range of presentations Always exclude anaphylaxis as the cause of the reaction. Misinterpretation might be fatal!
Anaphylaxis An acute general hypersensitivity reaction That takes place seconds/minutes after exposure with the drug/specimen in question The reaction involves one or more organ systems The symptoms vary Often dramatic, potentially lifethreatening Several mechanisms IgE/Non IgE Non allergic Classification Grade 1: Symptoms from the skin, only Grade 2: Systemic, not lifethreatening Grade 3: Systemic, lifethreatening Grade 4: Asystoli/or respiratory arrest Grade 5: Death Ring J, Messmer K. Lancet 1977
Patients
Patient 1 Male born 1972 (2006) He developed an itchy head, dizziness, facial oedema and hypotension 10-20 minutes after taking cough-syrup containing ethyl morphine. His wife suspected anaphylaxis and took him to hospital. On admission; BP was 84/58 mmhg, declining to 68/40 mmhg, and he still had the facial oedema. He was treated with adrenaline, i.v. fluids, steroids and antihistamines. He stabilized. Observed at the hospital for one night.
Patient 2 Male born 1935 (2005) (2005) Spinal anaesthesia, Bupivacaine with fentanyl. After 50 minutes; Urticaria, face, thorax lower part of abdomen and groins, itching sensation on his palms. A small decrease in blood pressure. Treatment Ephedrine 10 mg, antihistamine and steroids
(2001) Had Corsodyl mouth rinse after surgery in the mouth performed by the dentist. Five minutes after exposure his body felt itchy and strange He left the dentist office, went to his car, turned the switch, and 30 minutes later he woke up in the Emergency Department, at the local hospital He lost his drivers licence for 3 months because doctors thought he had a heart problem. Although the patient was convinced that the reaction was due to the mouth rinse.
Patient 3 Pregnant female born 1962 (2006) 1987 Forceps delivery performed without general anaesthesia. She was stable during the procedure Cervical laceration suture in general anaesthesia Induction of general anaesthesia Fentanyl, Thiopenthone, Suxamethonium
After induction she became cyanotic and hypotensive Treatment: Rapid infusion of dextran, iv ephedrine. Still low BP Reasons: Embolus to the lungs, amniotic fluid embolus, sepsis or allergy.
1990 Planned caesarean in general anaesthesia. She believes that she will die during the procedure! Induction: Fentanyl, Thiopentone and suxamethonium. Reaction: BP dropped to 48 mm/hg systolic. Vasoconstriction, bronchospasm, cyanosis, oedema in the face and the tongue. Treatment: Adrenaline 0,1 mg/ml in increments, Ephedrine in increments and steroids No follow-up no warning card!
Patient 4 Female born 1942 Breast cancer surgery (2005) Daycare surgery Premedication; paracetamol and a NSAID Induction; remifentanil and propofol, circulation stable. Subcutaneous injection of Patent Blue (sentinal node) 20 minutes after induction; BP cannot be measured, Sinus rhythm on ECG Read skin, but no urticaria, No bronchospasm Saturation 68-78% on FiO2 1.0. 10 minutes with BP < 65 mmhg systolic
The Emergency team was alarmed Treatment Chest compressions Intubation Extra iv lines Arterial line Ephedrine and phenylephrine Increments i.v with adrenaline, total 4 mg, Adrenaline infusion 0,1 µg/kg/min - 0,02 µg/kg/min Fluids
Follow-up Patient 1 Patient drinking cough syrup He refused re-challenge - but the most probable cause to the reaction was ethyl-morphine no other exposure He had antibodies towards morphine and pholcodine in serum Incremental challenge up to 5 mg showed tolerance to morphine. Patient 2 Patient with mouth rinse and spinal anaesthesia IgE mediated reaction towards Chlorhexidine specific IgE and positive skin test. Chlorhexidine in the mouth rinse and in the disinfectant used to wash the operation field
Patient 3 Pregnant female Suxamethonuim identified 19 years after the first reaction her GP referred her Patient 4 Patient with breast cancer Patent blue
Urticaria in a patient with a suspected reaction on patent blue
Challenges
Early diagnosis Early and adequate treatment Adrenaline and fluids are the cornerstones in treatment
Identify risk patients Key to success Patients who have suffered severe anaphylaxis A standardized follow-up to identify the cause of anaphylaxis in risk patients
There was a complete match between the suspected cause and the result of follow-up in only 7% of the cases
Follow-up Blood sampling stryptase Total IgE Specific IgEs Three samples from each patient Secondary follow-up
Anaphylaxis kit
Reporting Reaksjonsbilde Laveste målte BT Tid hypotensiv - SAP<80 mmhg Hjertefrekvens Endring av rytme / mmhg minutter /min Ventrikkeltachycardi Ventrikkelflimmer Asystoli Annet... Ingen endring Ventilasjon Høyeste målte luftveistrykk Laveste målte Hud Bronkospasme Luftveisødem Ingen reaksjon Rubor Urticaria Angioødem Ingen reaksjon % cmh2o GI CNS Brekning Annet... Ingen reaksjon Kramper Annet... Ingen reaksjon Andre manifestasjoner AnnetTekstReaksjonsbilde Design Torkel Harboe
The problem is That most drugs given during induction and maintenance of anaesthesia have cardiodepressive effects. Hypotension and tachycardia are rather common Overtriage!
N O O O H HO NCH 3 O H HO Pholcodine NCH 3 HO Morphine O + (H 3 C) 3 N O O + N (CH 3 ) 3 O Suxamethonium
stryptase -ImmunoCap Measures continously released inactive proformes (monomers) and active forms of α- and β-tryptase. Cannot differentiate between tryptase released from the mastcell or the basophil Mastcell 10-35 pg tryptase/cell Basophil ~ 0,04 pg tryptase/cell The proforms mirrors the number of mastcells Represents the basal level Elevated in mastocytosis
stryptase - ImmunoCap Mature β-tryptase, a serin-protease (tetramer) Stored in granulas of the resting mastcell Released to the circulation during activation of the mast cell Increased levels after iv stimuli and IgE mediated reactions A peak after 15-120 min, half-life 2 h After 24-28 h basal level is reached
stryptase Tryptase is a protease liberated from mastcells to blood by direct or indirect stimulation (anaphylaxis) Tryptase (U/L) 60 50 40 30 20 10 0 Ke=0.27/h, t 1/2 =2.5 t 0 6 12 18 Time (h) 24
S-tryptase (MCT) Sensitivity ~95%. Specificity ~70% (Fisher, Baldo, BJA 1998) 33 of 158 patients with elevated MCT did not have specific IgE 7 of 143 patients with specific IgE did not have elevated s-tryptase Elevation of MCT favours a IgE-mediated cause.
Allergy 2007, Guttormsen et al
Conclusions In anaphylaxis induced by NMBA in NMBA-IgEsensitized individuals there is a small decrease of serum IgE antibodies to suxamethonium. None of the patients became sero negative. There is no reason to doubt that these findings do not apply to other drugs. Serum IgE antibody levels in many patients seem to decrease over time
New blood sampling at allergy work-up. Still to be elucidated If the prick test is reliable in the immediate time frame after an adverse drug reaction as antibody detection is only available for a limited number of drugs Thus, a serum sample for analyses of IgE antibodies to QAI can be drawn right after the anaphylactic reaction
The Norwegian Network (1999) NARA Collaboration with the Norwegian Medicines Agency Primary registration Anaesthesiologists all over Norway identify patients and submit blood samples Common Database Bergen Communication Follow-up Follow-up Bergen Follow-up Oslo Follow-up Trondheim Follow-up Tromsø
Skin-prick test 1. 2.
Skin-prick test 3. 4.
D d (D+d)/2 >3mm Positive skin prick test = immunological reaction
Intracutaneous Initial wheel 5 mm test 2. 1. Positive: 10 mm wheel and rubor 3.
Prick-test : undiluted drugs Intradermal test: 1/10000-1/100 dilution
Anafylaksi under anestesi Kommunikasjon av kritisk informasjon internt i sykehus og mellom sykehus Anne Berit Guttormsen,, KSK, Haukeland Universitetssykehus Nils Oddvar Skaga, Ullevål l Universitetssykehus
Pasienteksempel Kvinne 38 år. Innlegges med en penetrerende skade i buken. Agitasjon og motorisk uro - umulig å undersøke Tåler du narkose nei jeg tåler ikke narkose jeg blir kvalm Rapid Sequence Induction gjennomføres med Ketalar 200 mg, Stesolid 5 mg, Fentanyl 0,1 mg og Curacit 100mg, intuberes Alvorlig anafylaktisk sjokk med bronkospasme, hypotensjon og cyanose. Rask diagnose, korrekt behandling.
Dokumentert i kritisk informasjon To alvorlige anafylaktiske sjokk Utredning har vist allergi mot Curacit, Norcuron, Esmeron Toleranse for Nimbex (ikke original dokumentasjon) Opplysningene ble ikke kommunisert til anestesilege
Tiltak: Traumeteamet blir varslet dersom koordinator ser at "kritisk info" foreligger i journalen når den åpnes.
Reaksjon 2006 (juli) 2006 (september) 2007 (august) Sykehus 1 2 3 Utredet Induksjon Forbehandling Reaksjon Fentanyl, Pentothal, Curacit, Norcuron Hypotensjon, bronkospasme rubor Propofol, Esmeron Deksklorfeniramin, Solucortef Hypotensjon, bronkospasme Ketalar, Stesolid, Curacit Hypotensjon, bronkospasme 2006 (oktober) IgE sux 3,2 Ku/l 3,1Ku/l 6,1 Ku/l Tryptase 125 µg/l 70,8 µg/l 106 µg/l
How do we become better? To train Patients Relatives Paramedics Nurses Doctors Anaphylaxis drill among hospital employees Focus on How to recognize anaphylaxis? How to treat appropriate doses and correct administration of adrenaline How to prevent new anaphylactic episodes to perform follow-up
Hos høyrisikopasientenh
http://www.ssai.info Vurder premedikasjon med antihistaminer og steroider Vurder anestesi i lateksfritt miljø Vurder å bruke lokal/regional anestesi gitt at pasienten ikke har hatt reaksjon ved bruk av slik teknikk Bruk inhalasjonsanestesi Bruk så få medikamenter som mulig Unngå neuromuskulære blokkere hvis mulig Vurder å unngå bruk av klorheksidin Vær forberedt på at pasienten kan få en ny anafylaktisk reaksjon
Be Alert Be Aggressive in your approach To give Adrenaline and Fluids Perform Follow-up