Transcript laryngeal edema

ANGIOEDEMA, LARYNGEAL EDEMA
DIAGNOSIS AND MANAGEMENT
Henriette Farkas
Semmelweis University
3 rd Department of Internal Medicine
Budapest, Hungary
[email protected]
UPPER AIRWAY OBSTRUCTION (UAO)
AETIOLOGY
FUNCTIONAL CAUSES
MECHANICAL
CAUSES
LARYNGEAL EDEMA
CNS depression
Foreign body aspiration
is a life-threatening condition characterized by acute or gradual onset with
Peripheral nervous system
Infections
swelling of the laryngeal mucosa
and neuromuscular abnormalities
Laryngeal edema
Haemorrhage and haematoma
Trauma
Burns
Neoplasm
Congenital
Miscellaneous
PATIENT’S COMPLAINTS, SIGNS
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Dysphagia
Sensation of a lump in the throat
Feeling of tightness
Voice changes
Hoarseness
Roughness
Resonant barky cough
Stridor
Dyspnea
Fear of asphyxation
Aphonia
Patient is unable to breathe, speak, or cough and may hold the throat
between the thumb and index finger (the universal choking sign)
Patient is anxious and agitated
PHYSICIAN EXAMINATION
1. Medical history (patient or relatives)
2. Physical examination
• Voice changes
• Hoarseness
• Roughness
• Resonant barky cough
• Stridor
• Dyspnea
• Aphonia
• Patient is anxious and agitated
• Vigorous attempts at respiration with intercostal and supraclavicular
retraction
• Patient becomes rapidly cyanosed
• Respiratory efforts diminish
• Loss of consciousness
• Heart rate and blood pressure raised, bradycardia
• Hypotension, cardiac arrest
• Death is inevitable if the obstruction is not relieved within 2-5 minutes
of the onset
EXAMINATION IN THE HOSPITAL
flexible fibreoptic laryngoscopy
Indirect laryngoscopy
Radiographic imaging
AP and lateral plain neck radiographs, CT, MRI
direct laryngoscopy
Congenital stenosis
Recurrent paralysis
Foreign body
Normal larynx
Infection
Laryngeal oedema
Tumor
THE EFFECT OF EDEMA ON THE CROSS SECTIONAL AREA OF THE
SUBGLOTTIC LARYNX
Physical
status
Neonate
Child
Adult
Normal
Subglottic
area (mm2)
Effect of 1
mm edema
12
48
147
3
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108
Reduction of
airway area
%
75
44
27
MANAGEMENT
Treatment consists of
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immediately ensuring an adequate airway
administration of oxygen
intravenous fluids
epinephrine, antihistamines and steroids
C1-INH concentrate, bradykinin receptor B2
antagonist, kallikrein inhibitor or FFP
PRINCIPLES OF AIRWAY MANAGEMENT TECHNIQUES
1. Try simple manoeuvres to open airway
• Jaw thrust is used when other methods have failed.
• Oro- or nasopharyngeal airway is useful in the
unconscious patient.
• If the patient is not immediately intubated the coma
position should be used.
PRINCIPLES OF AIRWAY MANAGEMENT TECHNIQUES
2. Endotracheal intubation
Method of choice for the unconscious apnoeic patient
PRINCIPLES OF AIRWAY MANAGEMENT TECHNIQUES
3. Surgical airway
• cricothyroidotomy
• percutanous tracheotomy
• emergency tracheostomy
CRICOTHYROIDOTOMY
Cricothyroidotomy is an emergency procedure when
intubation or tracheotomy are impossible. Relatively easy
way of providing an emergency airway. (cricothyroid
membrane is near the skin surface)
PERCUTANOUS TRACHEOSTOMY
PCT is cost-effective, safe, fast, and easy to perform
TRACHEOTOMY
Emergency tracheotomy rarely required.
Formal surgical tracheotomy under local anaesthesia
may be a prudent approach under some controlled conditions.
CLASSIFICATION OF ANGIOEDEMA
• ALLERGIC
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NSAID-induced
Idiopathic
Associated with idiopathic or autoimmune urticaria
Associated with urticaria vasculitis
Infections and infestations
Angioedema with eosinophilia
Associated with some physical urticarias and with cholinerg
urticaria
Associated with contact urticaria
Angiotensin- converting enzyme inhibitor-induced
C1-INH deficiency
Hereditary angioedema with normal C1-INH
Kaplan, Graeves 2005
PATHOMECHANISM
IGE MEDIATED, I TYPE HYPERSENSITIVITY
Roitt
COMMON ALLERGENS
• Foods such as peanut, milk, nuts, shellfish, fish, eggs, and other
foods.
• Medications including penicillin and related or unrelated antibiotics,
may produce allergic reactions.
• Insect sting venom
• Less common causes are latex rubber in surgical gloves and enema
devices
SYMPTOMS
May be localized or part of a systemic anaphylactic reaction
• in acute allergic laryngeal edema, angioedema of the lips
and supraglottis, glottis, and infraglottis results in airway
obstruction
• systemic reaction consists of a variable combination of
urticaria (79%), bronchospasm (70%), shock,
cardiovascular collapse and abdominal pain
DIAGNOSIS
Prick test
Specific IgE
Use specific monoclonal antibodies against allergens
MANAGEMENT
ACUTE TREATMENT CONSISTS OF
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immediately ensuring an adequate airway
and administration of oxygen,
intravenous fluids,
epinephrine:im, iv
antihistamines and steroids
NEXT STEP
hyposensibilisation (bee, wasp venom)
INFORMATION, EMERGENCY CARE KIT
• Wear a medic alert
bracelet at all times
• Get information from
patient’s doctor and the
pharmacist before taking
any medication
• Read all food labels
carefully
• Carry with the patient an
emergency care kit so that
it can be self-administered
epinephrine
CLASSIFICATION OF ANGIOEDEMA
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Allergic
NSAID-induced
Idiopathic
Associated with idiopathic or autoimmune urticaria
Associated with urticaria vasculitis
Infections and infestations
Angioedema with eosinophilia
Associated with some physical urticarias and with cholinerg
urticaria
Associated with contact urticaria
ANGIOTENSIN- CONVERTING ENZYME INHIBITORINDUCED
Acquired C1-INH deficiency
Hereditary angioedema
Kaplan, Graeves 2005
KININ SYSTEM
HW kininogen
Angiotensinogen
kallikrein
Vasodilatation
Increased vascular
permeabity
renin
Angiotensin I
bradykinin
ACE
BK metabolits
Angiotensin II
Vasoconstriction
Vascular hypertrophy
Aldosterone release
EFFECT OF ACE INHIBITORS
kininogen
angiotensinogen
kallikrein
Vasodilatation
Increased vascular
permeabity
renin
bradykinin
Angiotensin I
ACE
ACE inhibitor
Angiotensin II
BK metabolits
ATII Blocker
Vasoconstriction
Vascular hypertrophy
Aldosterone release
ACE INHIBITORS
35 - 40 million patients worldwide are treated with ACE
inhibitors, ACE inhibitors are generally well tolerated.
ADVERSE EFFECTS:
Significant adverse effects include hypotension, renal
impairment, cough, and angioedema
Prevalence of angioedema: 0.1-0.7%
Angiooedema can first manifest itself from a few hours to 10
years after an ACE inhibitor has been first taken.Therefore
physicians fail to recognize the association.
MANAGEMENT OF ACE INHIBITOR-INDUCED
ANGIOEDEMA
ACUT TREATMENT
Avoid ACE inhibitors
Conservative treatment antihistamines with or
without steroids
Tongue and upper airway are involved,
intramuscular adrenaline should be used,
some patients require an artificial airway
C1 inhibitor concentrate,FFP, SDP, kallikrein inhibitor or
bradykinin receptor antagonist
has been successfully
MANAGEMENT OF ACE INHIBITOR-INDUCED
ANGIOEDEMA
LONG-TERM
Should not be switched to another ACE inhibitor.
Calcium channel blockers and/or thiazides are appropriate
as alternative antihypertensives. Beta blockers are
contraindicated in the initial setting.
Alternative medications: are AT II receptor blockers
Several cases of angioedema associated with ATII receptor
although the overall incidence appears lower than that with
ACE inhibitors.
CLASSIFICATION OF ANGIOEDEMA
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Allergic
NSAID-induced
Idiopathic
Associated with idiopathic or autoimmune urticaria
Associated with urticaria vasculitis
Infections and infestations
Angioedema with eosinophilia
Associated with some physical urticarias and with cholinerg
urticaria
Associated with contact urticaria
Angiotensin- converting enzyme inhibitor-induced
ACQUIRED C1-INH DEFICIENCY
HEREDITARY ANGIOEDEMA
Kaplan, Graeves 2005
HEREDITARY ANGIOEDEMA (HAE)
Type I (Donaldson, 1963)
C1-inhibitor (C1-INH) deficiency
Type II (Rosen, 1965)
Type III
(Bork, Binkley, 2000, Martin 2001)
Normal C1-INH
HEREDITARY ANGIOEDEMA (HAE)
Type I. II
• autosomal dominant inheritance
• deficiency of C1 inhibitor
• onset of symptoms: in childhood
• prevalence: 1:10 000, 1:50 0000
• mortality: 20-30 %
HEREDITARY ANGIOEDEMA (HAE)
Type III
• Mainly in vomen
• Percipitating factors: oral contraceptive therapy,
hormone replacement treatment, pregnancy
• Symptoms: similar to HAE Type I and II
• Subgroup: missense mutation in factor XII gene
• Normal C1-INH function
• Not respond antihistamine treatment
• Tranexamic acid, C1-INH concentrate?
HEREDITARY ANGIOEDEMA (HAE) TYPE I & II
Autosomal dominant
inheritance
Deficiency of C1-inhibitor
(C1-INH)
Two phenotype HAE I and II
Prevalence: 1/50 000
Mortality: 20-30%
Osler Am J Med Sci 1888; Donaldson Am J Med 1963; Rosen J Clin Invest 1971
PATHOMECHANISM
C1-INH
FXII
FXIIa
Prekallikrein
C1
C42
HWK
Kallikrein
C1rs
Plasminogén
C2 kinin
Bradykinin
Plasmin
DIAGNOSIS OF HAE
 Family history
 Clinical symptoms
asymptomatic
 Measurement of complement
• pedigree analysis
in HAE
• genetic testing
Confirm the diagnosis
in uncertain cases
Prenatal diagnostics
Agostoni A Medicine 1992
SUBCUTANEOUS SYMPTOMS
Farkas H Acta Dermato-Venereol 2001
SUBCUTANEOUS SYMPTOMS
Bork K Am J Med 2006
SUBMUCOSAL SYMPTOMS
Upper airway mucosa
Pharyngeal edema
Laryngeal edema
Bork K Transfus Apher Sci 2003; Tsunoda Laryngoscope 2000
SUBMUCOSAL SYMPTOMS
Intestinal mucosa
intense, colicky abdominal pain
 nausea and vomiting
 postattack (watery) diarrhea
 can mimic an „acute abdomen”
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Unnecessary surgical
intervention
Bork K Am J Gastroenterol 2006
ABDOMINAL ULTRASOUND
Nonspecific but extremely sensitive method
ascites
edematous intestinal wall
In patients with known HAE
 Differential diagnosis
Recurrent abdominal complaints with ascites
 HAE should be considered if all other differential diagnostic options have
been ruled out.
Farkas H Eur J Gastroenterol Hepatol 2001; Acta Paediatr 2002
COMPLEMENT PROFILES
IN C1-INH DEFICIENCIES
Type
C1-INH C1-INH
C1q
antigen function
C4
AntiC1-INH
HAE-I
N
L
L
L
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HAE-II
N
N/H
L
L
-
AAE-I
L
L
L
L
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AAE-II
(autoimm.)
L
N/L
L
L
+++
Agostoni A J Allergy Clin Immunol. 2004
MANAGEMENT
COUNSELING &
EDUCATION
TREATMENT
FOLLOW-UP
Bowen J Allergy Clin Immunol 2004
COUNSELING & EDUCATION
Individualized information to patient and parents
Written information to school, pediatrician, & family practitioner
Multilanguage infocard, hne service, hospital for emergencies
Patient diary
Drug for emergency
Patient organizations, websites
Farkas H Transfus Apher Sci 2003
TREATMENT
stress
minor
trauma
infection
Elimination of precipitating factors
drugs
hormons
(estrogens)
Prophylaxis with drugs
Management of attack
Farkas H Lancet 2001; Bouillet L Dermatology 2003
PROPHYLAXIS WITH DRUGS
Long-term
antifibrinolytic agents (tranexamic acid)
• ≥1 attack per
month or
• history of lifethreatening
attacks
attenuated androgens
C1-INH concentrate
Short-term
Before surgery
and
instrumentation
on the
oropharynx,
head and neck
attenuated androgens
5 days before the intervention and for
2 days after
C1-INH concentrate, SDP, FFP
Cicardi M J Allergy Clin Immunol 1991; Farkas H J Oral Maxillofac Surg 1999
SIDE EFFECTS
ATTENUATED ANDROGENS
Danazol, stanozolol,
oxandrolone
-seborrhoea, acne, hirsutism, weight gain, hair
loss, deeping of the voice, menstrual
irregularities,decrease breast size, myalgia,
fatigue, headaches, SHBG ↓
-inzulin resistance↑, plasma glucagon↑,
LDL, cholesterol↑, a HDL-cholesterol↓,
Apo-AI and Apo-AII↓, TBG↓
-erythrocytosis, polycythaemia, thrombocytosis,
eosinophylia, leukopenia, Prot. C, S ↑,
antithrombin III ↑, haematuria
-transaminase↑, hepatocellular adenoma
and liver carcinoma
ANTIFIBRINOLYTIC AGENTS
Tranexamic acid
Epsilon-amino-caproic acid
thrombosis
postural hypotension
muscular pain and weekness
creatine kinase ↑
aldolase ↑
rhabdomyolysis
myositis
fatigue
Cicardi M J Allergy Clin Immunol. 1997; Széplaki G J Allergy Clin Immunol. 2005
FOLLOW-UP
SIDE EFFECTS
MINIMAL EFFECTIVE DOSE
blood cell count
liver & renal function,
lipid profile, CK
urinalysis
abdominal ultrasound
HIV, Hepatitis A,B,C, serology
vaccination to Hepatitis B
ALTERATION IN STATUS
ADJUSTMENT OF THERAPY
Gompels M Clin Exp Immunol 2005; Farkas H Lancet 1999
MANAGEMENT OF ATTACK
SEVERE
MILD
pharyngeal/laryngeal
face, lips edema
abdominal attack
severe edema of
extremities, trunk
neck & genitals
Edema of the
extremities,
Mild abdominal attack
C1-INH concentrate, FFP,SDF
tranexamic acid or danazol
for 2-3 days
Corticosteroids, antihistamines, and epinephrine are
INEFFECTIVE
Farkas H JACI 2007; Prematta M Ann Allergy Asthma Immunol 2007; Bork K Transfusion 2005
FUTURE TREATMENT OPTIONS
Trauma
Prekallikrein
XIIa Faktor
hC1-INH,
rhC1-INH
Kallikrein inhibitor, DX88
Kallikrein
Bradykinin
ACE
Des-Arg9-Bradykinin
HMW-Kininogen
edema
Bradykinin receptor
antagonist Icatibant
Bork K J Allergy Clin Immunol 2007; Van Doom M J Allergy Clin Immunol 2005; Levy J Expert Opin Investig Drugs 2006
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