1 dr. zohair al aseri frcpc emergency medicine frcpc critical care medicine assistant professor...

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Dr. Zohair Al aseri

FRCPC Emergency Medicine

FRCPC Critical Care Medicine

Assistant Professor &

Chairman Dept. of Emergency Medicine

College of Medicine

King Saud University Hospitals

AnaphylaxisAnaphylaxis

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52 y o m pt presented to er c/o

Vomiting blood 2 times @ home

NO other complaints

PMH : PUD 10 y ago, HTN

Med : ACEI & metoprolol

V/S : tachy

CNS, CHEST& HEART exam were normal

Hg 50 ,

blood transfusion started

CASE 1

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52 y o m pt presented to ER c/o vomiting blood

GI consulted @ 1.00 am , came & decided to do endoscope in ER

Procedure started by sedation propafol iv & lidocain spray

Pt became hypotensive , itching all over ,a/w swelling

GI staff decided to leave & come back again If the pt became more stable.

CASE 1

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• What is your 1st line treatment ?

• What is your diagnosis?

• What are the indications of intubation in this pt?

• What are your choice of medication for induction & paralysis ?

• What about post intubation sedation & pain control ?

• What is your plan if your pt remain hypotesive after resuscitation?

52 y o m pt presented to ER c/o vomiting blood

CASE 1

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Definition

Anaphylaxis is derived from the Greek word ana meaning backward or against and phylaxis meaning protection

There is no universally accepted clinical definition of anaphylaxis

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Data regarding the incidence and prevalence of

anaphylaxis and the number of deaths

caused by it are limited.

Epidemiology in SA

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Foods Medications (eg, antibiotics)   Aspirin NSAID Venoms Latex Allergen vaccines Animal or human proteins Polysaccharids Exercise

Anaphylactic (IgE dependent)

EtiologyEtiology

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Anaphylactoid (IgE independent)

 Multimediator complement activation-

  Radiocontrast media

  ACEI

  Ethylene oxide gas on dialysis tubing???

  Protamine

AnaphylaxisAnaphylaxis

EtiologyEtiology

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Cytotoxic

Transfusion reactions to cellular elements (IgG,Igm)

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EtiologyEtiology

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Etiology

Idiopathic anaphylaxis is one of the most common causes, accounting for approximately one third of cases in retrospective studies

Its a diagnosis of exclusion.

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Pathophysiology

Some authors reserve the term anaphylaxis only for IgE-dependent events and the

term anaphylactoid to describe IgE-independent reactions that otherwise are

clinically indistinguishable.

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PathophysiologyPathophysiology

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o Histamineo Tryptaseo Platelet-activating

factoro Heparin

o PGDo Leukotriene o Histamine-releasing

factor o Chymase

Pathophysiology

Biochemical mediatorsBiochemical mediators

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• Postmortem serum tryptase might be useful in establishing anaphylaxis as the cause of death in subjects experiencing sudden death.

Increased postmortem tryptase levels have been

reported • 12% of healthy adults with sudden death• 40% of victims of (SIDS)

Pathophysiology

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•Recent findings: Anti-IgA is not responsible for most reactions.

•Anti-haptoglobin antibodies are responsible for more reactions than anti-IgA in Japan.

•The cause of most reactions is still not known.

•The incidence of reactions to platelets is the highest compared with fresh frozen plasma and red blood cells.

Anaphylactic transfusion reactions

Anaphylactic transfusion reactions. Current Opinion in Hematology. 10(6):419-423, November 2003.Gilstad, Colleen W.

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1–4:100

1–4:100

1:1,000

1:5,000

1:12,000

1:100,000

1:150,000

Febrile (FNHTR)

Allergic

Delayed hemolytic

TRALI

Acute hemolytic

Fatal hemolytic

Anaphylactic

Risks of Transfusion Complications

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•The most frequent potentially severe outcomes for red cell transfusion were hemolytic reactions and volume overload

•for platelet transfusion were major allergic reactions and bacterial contamination

Risks associated with transfusion of cellular blood components in Canada

Comprehensive review of risks associated with allogeneic red blood cell and platelet transfusions in Canada.

A 9-year retrospective review

"severe allergic" reactions occurred in 1:53,612 blood components•1:9630 platelets •1:28,831 FFP•1:57,869 RBC transfusions

Domen RE, Hoeltge GA: Allergic transfusion reactions. Arch Pathol Lab Med 2003, 127:316-

320. Nine-year retrospective review of all transfusion reactions reported to the Cleveland

Clinic transfusion service

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Generalized urticaria and angioedema are the most common manifestations .

Cutaneous manifestations might be delayed or absent in rapidly progressive anaphylaxis.

Manifestations

SKIN

Increased skin temperature (redistribution of blood)

Urticaria (hives) Flushing

Periorbital edema Perioral edema Diaphoresis Itching Burning

Manifestations

SKIN

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The next most common manifestations are The respiratory

symptoms

Manifestations

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Manifestations

SIGNS Increased RR Stridor (laryngeal edema) Wheezing (bronchospasm) Decreased pulmonary

compliance Pulmonary edema Respiratory failure

SYMPTOMS Dyspnea Chest discomfort Coughing Sneezing

Respiratory

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Manifestations

Hypotension Increased HR Decreased svr Dysrhythmias

• Retrosternal pain• MI• Cardiac arrest • ECG Changes

CVS

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Manifestations

CNS

Non-specific Disorientation LOC Dizziness Light-headedness Malaise

GI

Non-specific

Vomiting Diarrhea Nausea Abdominal pain

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Dyspnoea 61 (43) Wheeze 50 (35.2) Vomiting 27 (19.0) B.spasm 26 (18.3) Syncope &

dizziness 21 (14.8) R. rate ≥25 19 (13.4)

• Laryngeal edema 15 (10.6) • Hoarseness 14 (9.9) • SBP <90 mmHg 13 (9.2)• GCS <15 4(2.8) • Loc 3 (2.1) • Stridor 2 (1.4)• Cyanosis 2 (1.4)

ED AED Anaphylaxisnaphylaxis

A review of 142 patients in a single year

Anthony F. T. Brown MB Brisbane, Australia (J Allergy Clin Immunol 2001

133 (94%) of the 142 patients had cutaneous features.

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Fever

Hypotension

Generalised oozing from wounds or puncture sites

Haemoglobinaemia

Haemoglobinuria

Transfusion Reaction

Signs

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Feeling of apprehension or something wrong

Agitation

Flushing

Pain at venepuncture site

Pain (abdomen , flank or chest )

Transfusion Reaction

Symptoms

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TREATMENT Stop Administration of Antigen (blood)

Establish and maintain a/w

100% oxygen administration,

intravascular volume expansion.

Epinephrine

Systemic glucocorticosteroid

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AIR WAY

Low Threshold

Tube Size?

Induction Agent?

paralytic agent?

TREATMENTTREATMENT

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Bronchospasm

For bronchospasm resistant to epinephrine

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Give Nebulized (albuterol, salbutamol)

repeated doses

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Persistent Bronchospasm

Aminophylline, a phosphodiesterase inhibitor, weak bronchodilator that also increases R&L ventricular contractility and decreases pulmonary VR.

An IV loading dose of 5 to 6 mg/kg of aminophylline given over 20 m. should be followed by an infusion of 0.5 to 0.9 mg/kg /h

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To achieve rapid intravenous induction with minimal hemodynamic effect and little respiratory depression, etomidate

(Amidate) is the agent of choice.

IV Induction agent

Etomidate

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SEDATIVES

IV DOSE (mg/kg)

ONSET(min)

Effect on BP

Effect on ICP

Midazolam 0.2 – 0.4 1 – 2 Minimal Minimal

Etomidate 0.2 – 0.4 < 1 Minimal/

Thiopental 2 – 5 < 1

Ketamine 1 – 2 1 Minimal/

Propofol 2 – 3 < 1

AnaphylaxisAnaphylaxis & IVIA & IVIA

IV Induction agent

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Volume Expansion

Volume expansion is important

Initially, 1 to 3 L of RL ,NS

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Catecholamines

Life-saving

First-line catecholamines include epinephrine

Dopamine????

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EPINEPHRINE

α1 -adrenergic : Vasoconstriction

β1 -adrenergic Vasoconstriction Increased peripheral vascular resistance Increases myocardial contractility Decreased mucosal edema)

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EPINEPHRINE

β2 -adrenergic effects are of primary importance

Bronchodilation

Release of histamine, tryptase, and other chemical

mediators of inflammation from mast cells and

basophils by cAMP production)

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EPINEPHRINE

There are no absolute contraindications to epinephrine administration in

anaphylaxis

Contraindication

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HOW DO YOU GIVE IT?

The UK consensus panel on emergency guidelines states that the subcutaneous route of administration

for epinephrine has “no role” in anaphylaxis

EPINEPHRINEEPINEPHRINE

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Epinephrine absorption in adults

IM versus SQ injection

Prospective, randomized, blinded placebo- controlled 6-way crossover study in healthy allergic men age 18 to 35 y

CONCLUSION IM injection of epinephrine into the thigh

is the preferred method of administration in the initial treatment of anaphylaxis

F. Estelle R. Simons MD (Journal of Allergy and Clinical Immunology 2001)

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Epinephrine absorption in children

Prospective, randomized, blinded, study in 17 children with a history of anaphylaxis

SQ V/S IM from autoinjector.

Plasma epinephrine concentrations, HR, BP, and adverse effects were monitored.

F. Estelle R. Simons MD Winnipeg, Manitoba, Canada Allergy and Clinical Immunology 

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The IM route of injection is preferable.

Epinephrine SQ 0.27 ± 0.04

Epinephrine IM 0.3

Epinephrine absorption in childrenEpinephrine absorption in children

IM EpinephrineIM Epinephrine

The IM route has several benefits:

• There is a greater margin of safety.

• It does not require intravenous access.

• The IM route is easier to learn.

The best site for IM injection is the anterolateral aspect of the middle third of the thigh.

Adrenaline IM dose – adults0.5 mg IM (= 500 micrograms = 0.5 mL of 1:1000) adrenaline

Adrenaline IM dose – children> 12 years: 500 micrograms IM (0.5 mL) i.e. same as adult300 micrograms (0.3 mL) if child is small or prepubertal

> 6 – 12 years: 300 micrograms IM (0.3 mL)> 6 months – 6 years: 150 micrograms IM (0.15 mL)< 6 months: 150 micrograms IM (0.15 mL)

IM EpinephrineIM Epinephrine

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IV EPINEPHRIN

IV Epiniphrine

Indications

1) Shock

2) Coma & hypotension

3) Stridor + a/w edema

4) No response to I/M epiniphrine

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IV IV EPINEPHRINEPINEPHRIN

0.1 mg (0.1 ml) of 1:1,000 with 10 ml of n/s.

This is equivalent to a 100 mcg bolus given at 10 mcg/min.

Once therapy has begun, a continuous infusion could be delivered with 0.5 to 5 mcg/min titrated to clinical response.

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Epinephrine infusions

Useful in patients with persistent hypotension or bronchospasm after initial resuscitation

Infusions should be started at 5 to 10 μg/min (approximately 0.05–0.1 μg/kg per minute) and titrated to correct hypotension.

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Catecholamine Infusions

Norepinephrine infusions may be required

5 to 10 μg/min (0.05–0.1 μg/kg per mi) and titrated to correct hypotension.

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Inject hydrocortisone slowly intravenously or intramuscularly,

The dose of hydrocortisone for adults and children depends on age:>12 years and adults: 200 mg IM or IV slowly>6 – 12 years: 100 mg IM or IV slowly>6 months – 6 years: 50 mg IM or IV slowly<6 months: 25 mg IM or IV slowly

AnaphylaxisAnaphylaxis

Steroid

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Antihistamine

Ranitidine50 mg in adults (1 mg/kg) in children,

diluted in 5% dextrose to a total volume of 20 mL and injected IV over 5 minutes.

Cimetidine (4 mg/kg) may be administered to adults,

but no pediatric dosage in anaphylaxis has been established.

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Improve outcomes???

a randomized, double-blind, 91 adult patients with acute allergic syndromes were treated with

1. 50 mg of diphenhydramine and Placepo

2. 50 mg of diphenhydramine and 50 mg of ranitidine

Lin RYAnn Emerg Med. November 2000

HH11 and H and H22 antagonists antagonists

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Ranitidine Placebo(n=48) (n=43)

Methylprednisolone 28 27

Additional H2 blocker

2 0Epinephrine 17 9Additional antihistamine

2 10Albuterol nebulization

6 7

Treatment

HH11 and H and H22 antagonists antagonists

Lin RYAnn Emerg Med. November 2000

Antihistamine

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Antihistamine

Conclusion: These findings favour the recommendation for

using combined H1 and H2 antihistamines in acute allergic syndromes.

Lin RYAnn Emerg Med. November 2000

AnaphylaxisAnaphylaxis

Unlikely to be lifesaving in a true anaphylaxis Inject chlorphenamine slowly IV or IM The dose of chlorphenamine depends on age:

>12 years and adults: 10 mg IM or IV slowly >6 – 12 years: 5 mg IM or IV slowly >6 months – 6 years: 2.5 mg IM or IV slowly <6 months: 250 micrograms/kg IM or IV slowly

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Antihistamine

AnaphylaxisAnaphylaxis

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Biphasic Anaphylaxis

Rare. Rates between 5% to 20%. Recurrence Ranging from mild to sever life-

threats

TTT

Prolonged observation is required.

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Risk Of Biphasic Anaphylaxis

Joyce M. Lee MD Children's Hospital, Harvard Medical School

Biphasic Anaphylactic Reactions in Paediatrics

Iincidence :6%

Delayed epinephrine injection

Steroids do not prevent biphasic reactions

The time from the onset of symptoms to the reaction

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Anaphylaxis in Pregnancy The management of anaphylaxis in pregnancy

consists of

Maternal Resuscitation

Close monitoring of the fetal status

Iimmediate delivery of the fetus if compromised.

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Treatment depends on the severity of the reaction and consists of

Fluid resuscitation Oxygen Epinephrine H1 and H2 blockers Corticosteroids.

Anaphylaxis in Pregnancy

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What are the bad prognostic signs of anaphylaxis?

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β-Adrenergic blockade

Paradoxical bradycardia

Profound hypotension

Severe bronchospasm.

These agents might impede treatment effectiveness with epinephrine.

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β-Adrenergic blockade

• Glucagon, 1-5 mg (20-30 μg/kg [maximum, 1 mg] in children), IV over 5 minutes,

followed by an infusion of 5-15 μg/min.

(Aspiration precautions should be observed because glucagon may cause n & v.)

TTT:

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release of epinephrine

from the adrenal cortex

Hypotension

release of ACE leading to the production of angiotensin 2, a

potent vasocontrictor

Vasocontriction &

Decreased

Vascular Permeability

Site of action of

ACE inhibitors &

angiotensin 2 antagonist

Site of action of

ACE inhibitors &

angiotensin 2 antagonist

Persons taking ACEI and/or angiotensin II antagonists

will have a diminished compensatory response

Persons taking ACEI and/or angiotensin II antagonists

will have a diminished compensatory response

ANAPHYLAXIS

and ACE

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The heart in anaphylaxis

High-dose epinephrine administered iv (ie, rapid progression to high dose).

1-3 mg (1:10,000 dilution) slowly administered iv over 3 minutes

3-5 mg administered iv over 3 minutes

4-10 μg/min infusion.

1

2

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OUTCOME

a)RESPIRATORY b)LOC c)CVS

What is the NO. 1 cause of death in anaphylaxis?

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Causes of Death In Anaphylaxis

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PROGNOSIS

Bad prognostic signs

A/W B.Asthma Rapid manifestations after exposure Late epi inj. epi requirement CAD B.B ACEI

be aware & prepared

Questions

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Ranitidine 50 mg in adults (1 mg/kg) in children, diluted in

5% dextrose to a total volume of 20 mL and injected IV over 5 minutes

IV Epinephrine***

Diphenhydramine 50 mg of IV/IM

Anaphylaxis Algorithm (Hypotension due to Antigen )

Check ABCs in Monitored bed

Methylprednisolone (Solu-Medrol) 125 mg IV

•100% oxygen administration, establish and maintain a/w

0.3 mL Epinephrine 1:1,000 IM* in lateral aspect of the thigh Repeated dose if still hypotensive in 3-4 minutes

Reassess ABCs

Hypotension YesNO

High Risk Patient**

NO

Observe for 6 hours

• •Airway compromise •Requirement of high doses of epinephrine•History of Cornary Artery Disease •History of B.Asthma•Patient on B.Blockers or ACEI

IV N/S 500—1000ccBolus

For bronchospasm resistant to epinephrine give nebulized (salbutamol)

Stop Administration of Antigen (i.e. blood)

***IV Epinephrine0.1 mg (0.1 ml) of 1:1,000 with 10 ml of n/s .

this is equivalent to a 100 mcg bolus given at 10 mcg/min .a continuous infusion of 0.5 to 5 mcg/min titrated to clinical response .

Epinephrine should not be administered IV to patients with normal BP

Start Glucagon, 1-5 mg (20-30 μg/kg ( maximum, 1 mg in children,)

iv bolus over 5 minutes followed by infusion of 5—15 μg/min.

Still Hypotension

Reassess ABCs

Is the patient on B. Blockers?

ICU Admission

D/C Home with prednisone 50 mg once per day for 5 days

,diphenhydramine 25 – 50 mg po Q 6—8 h for 2 days and consider 0.3 mg epi pen prescription in food allergy induced anaphylaxis

Stable

Unstable

Yes

Low threshold for Intubaion if any one of the following present*

Persistent airway and/or sever tongue swelling Respiratory FailureRespiratory Distress Hypoxia

Reassess ABCs

Prepared by Dr Zohair Alaseri Feb 2006

*Prepare for difficult air way and call anaesthesia for back up

NO

Yes

Yes

NO

**High Risk Patient