Dr Michael RoseDirector, RNSH Anaesthetic Allergy Service

Chair, Australian and New Zealand Anaesthetic Allergy Group (ANZAAG)

Chair, ANZCA Anaesthetic Allergy Subcommittee

Member, Australasian Society of Clinical Immunology and Allergy (ASCIA)

rnsaac@gmail.com

Anaesthetic anaphylaxis

July 2013

Bad days don’t always come with a warning..

Once upon a time….Elective anaesthesia was dangerous…..

Death/ morbidity due to :

Older drugsLess emphasis on surgical anaesthetic audit / CPDLack of patient workup/informationPoorer monitoringAirway emergenciesAnaphylaxisMH

Now, otherwise healthy patients “expect” to make it through without problems

Anaesthetic emergencies

Now….Anaphylaxis one of the most prominent causes of unanticipated sudden catastrophe

Incidence of :MH: 1:50,000 -1:100,000CICO: 1:12,500 - 1:50,000Anaphylaxis under anaesthesia: 1: 4,500

-1:10,000

What is anaphylaxis ?

Anaphylactic vs. anaphylactoid now obsolete terminology

Clinical anaphylaxis - the presence of the following Skin or mucosal changes – rash (erythema/urticaria) ,

peau d’orange, angioedema

Plus one of…Cardiovascular instability (hypotension, variable HR

changes)Respiratory insufficiency – bronchospasm, low satsGIT issues – pain, vomiting, diarrhoea

Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF et al. Second symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy and Clin Immunol 2006 ;117(2): 391-397

Severity Grading1. Cutaneous Signs

2. Moderate multi-organ involvement Includes hypotension, severe tachycardia, bronchial hyper-reactivity

3. Severe multi-organ involvementIncludes severe bronchospasm, arrhythmias, cardiovascular collapse

4. Cardiac and or respiratory arrest

5. Death (bad, lots of paperwork)

What makes anaesthetic anaphylaxis different from food anaphylaxis ?

Often sudden onset and severeIV administration of antigen generally (except chlorhex/dyes/latex)

Often other things occurring that may mimic anaphylaxis Insufflation of peritoneum Cardiac ischaemia Haemorrhage Intubation (bronchospasm)

Skin reaction often not seen at time or at all

Gastrointestinal symptoms not prominent/noticed

As a result…

Delayed/missed diagnoses

Unnecessary investigations

Anaesthetists or Immunologists??

Differing experiences of anaphylaxis

Differing approaches

Collaboration useful

ANZAAG has the best of both worlds

www.anzaag.com

What do we do?History:

of event from notes/anaesthetist/patientResults of already conducted investigations

(e.g. MCT, sIgE)Skin testing

Intradermal (standard +/- stronger “validated” concentrations)

Skin PrickSerum tests

Baseline MCTSIgEs (“RASTs”)

Morphine/pholcodine for NMBAsChlorhexidineLatexAntibiotics

IV ChallengeThe 1st year registrar 2am test….

Red flags of difficult casesPoor information / documentation

Not referred directly from the anaesthetist involved

Vague descriptions of events (mild hypotension, possible rash)

No MCTS

High normal or completely normal MCTs with a good clinical picture

Severe atopy and dermatographism

Causes – RNSAAC 2007-20131. NMBAs

2. Antibiotics

3. Chlorhexidine

4. Colloid

5. Patent Blue

6. (Local Anaesthetics – often type 4 hypersensitivity)

Muscle relaxant Cross-reactivity

Probably around 60% have at least one other NMBD cross-reacting

Some have multiple

Not entirely predicable by class/structure

Do not substitute without testing results!!

www.anzaag.com

Other ANZAAG resources

Mast cell tryptases• Samples:

• First sample when situation under control (ideal 60 mins)

• 2nd sample 4 hours• 3rd sample 24 hours or later

• The ‘delta’ tryptase from peak to baseline often most informative

• Serum tube 5-10mls, labeled with time of sample

• Cooled to 4 degrees if delay / transport• Post mortem samples can be useful in

sudden unexplained death

What’s topical

Chlorhexidine

Pholcodine

Patent Blue

When to test??????

Who should test (? all anaesthetists/intensivists)

Chlorhexidine Catheter lubricantCentral linesMouth washes and lozengesSkin prepsAlcohol/chlorhexidine wipes

Risk versus benefit of making them mandatory

AustraliaNo central database, but many reports of

increasing incidence

NZSome centres report their cases of allergy to a

central body, the Centre for Adverse Reactions Monitoring (CARM)

In the 43 years from 1965 until April 2008, CARM had 54 reports of chlorhexidine reactions.

Four years later, by April 2012, these numbers had almost doubled to 100 reports

The Problem

Latex allergy –Widespread in hospital products

Not just perioperative

Often delayed onset of reaction

Concern after reactions increased after widespread use of latex products occurred

Less of an issue now with labeling and alternatives

Sound Familiar?

Blood collectors

Radiology procedures

ICU

Emergency department

General ward staff

The solution requires…

A Chlorhexidine formulary listFrom St George Hospital Sydney

30

Widespread use of chlorhexidine as an antiseptic

Clearly an effective antisepticBroad spectrumPersistent effect in skin

“One size fits all” approach

Controversies

www.chlohexidinefacts.com

Texas Childrens Hospital

2004 – Chlorhexidine routinely used on CVC dressing changes

2005 – Chlorhexidine mouthwashes daily for AML patients

qacA/B gene emerged in 200610% of MRSA 200922% of MRSA 2011

Resistance

JapanIssued a prohibition of chlorhexidine use on

mucosal membranes in 1984

USAFDA issued a warning about increasing

incidence of allergy from impregnated CVCs and other products in 1998

Warnings

Moves by health departments toward recommending chlorhexidine for all procedures

Good evidence for effectiveness of chlorhexidine on long duration lines (CVCs)

No good evidence of benefit for short duration peripheral access

Chlorhexidine baths pre-op?

Chlorhexidine policy

Chlorhexidine anaphylaxis is increasingBe prepared to treat

chlorhexidine allergic patientsBe extra vigilant dealing with

known chlorhexidine allergy patients

Risk versus benefitStill remains the most

effective antisepticRethink use of chlorhexidine

for low infection riskDevelop a chlorhexidine – free

policy at your hospital

Case discussions• 24yr male• Anaphylaxis under anaesthesia

for fundoplication• Cardiac arrest, rash,

angioedema• Treated promptly with

adrenaline (bolus and infusion) and IV fluid

• MCT 126mcg/L

Case 1 continued• Skin tested -

Positive to RocuroniumCross reactive to

• Suxamethonium• Cisatracurium• Pancuronium

Negative to Vecuronium

Subsequent safe anaesthesia with same induction drugs and vecuronium

Case 2

25 year old maleMetastatic bowel cancer

Has hemicolectomy and chemotherapy to reduce peritoneal and hepatic disease

Port inserted for chemo

Case 2 continuedDuring chemo

Multiple episodes of minor anaphylaxis from swabbing over port site before accessing

One episode of anaphylaxis after an infusion line was swabbed before piggy-backing a chemo solution

……….Unrecognised

Then…GA for peritonectomy/liver resection

Massive anaphylaxis after a chlorhexidine coated CVC is inserted through chlorhexidine/alcohol prep

Cardiac arrestResuscitated

Subsequently tested positive to chlorhexidine on intradermal, skin prick and sIgE tests

Subsequently

Meeting involving theatres, radiology, ICU about how to manage this patient and his multiple investigations without exposure to chlorhexidine

Chlorhexidine - free protocol developed

Case 342 yr malePercutaneous lithotripsyAnaphylaxis post induction

–fentanyl/propofol/Keflin/clonidine/dexamethasoneHypotension to 60mmHg plus rashRequired 500mcg total IV dose of adrenalineSingle MCT done intraoperatively (? Time)

elevated (15.9 mcg/ml)Postop-course complicated by bleeding. Given cephalexin as

part of treatment – caused severe red itchy rash

Intradermal testing at normal/higher concentrations negative to all, including cephalothin

Case 3 cont.Represented for testing on a second

occasion.Still negative to all tested meds

ButWhat if Keflin (cephalothin) was actually

cephazolin??

Tested positive intradermally and SPT to cephazolin