Dr Ahmaed Nabil

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Case Presentation

• By
• Dr Ahmaed Nabil
• Assistant Lecturer Of Anesthesia
• Ain Shams University

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Case

• A 23-years-old man is scheduled to undergo an
  ORIF of a carpal scaphoid fracture, using a bone
  graft to be harvested from the iliac crest.
• Induction of general anesthesia and intubation
  were uneventful.
• When cefazolin 1 g is administered intravenously
  a rash appears over the face and chest. The heart
  rate is 135 beats per minute and the blood
  pressure drops to 70/40 mmHg

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Questions

• What is the mechanism of anaphylaxis? What is the
  difference between anaphylactic and anaphylactoid
  reactions?
• What treatment should be administered to this
  patient? What else should be checked on physical
  examination?
• What are the medications most often implicated in
  anaphylaxis? In anaphylactoid reactions?

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Questions

• What is the percentage of patients allergic to
  penicillin who will have a reaction when
  challenged with a cephalosporin?
• What antibiotic would you use for clean
  orthopedic surgery in a patient reporting a
  penicillin allergy or a reaction to
  cephalosporins?

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What is the mechanism of anaphylaxis?

• Anaphylaxis is an IgE-mediated allergic reaction.
  
• The most common mechanism for an anaphylactic
  reaction is the degranulation of mast cells and
  basophils with the subsequent release of
  inflammatory mediators, which are responsible for
  the symptoms and signs.

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What is the difference between anaphylactic and
anaphylactoid reactions?

• Anaphylactoid reactions are clinically
  indistinguishable from anaphylaxis. However, the
  mechanism of action differs in that IgE is not
  involved.
• Anaphylactoid reactions are a result of direct
  degranulation of mast cells and basophils with
  release of the same mediators as in anaphylactic
  reactions

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Anaphylactoid reaction

• In practice, it does not matter whether or not
  the reaction is IgE or non-IgE mediated.
• The immediate management of the patient is the
  same
• the patient will need to avoid the drug in the
  future, irrespective of the mechanism of the
  reaction

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What else should be checked on physical
examination?

• 1st we have to know that true anaphylaxis during
  anesthesia is very rare.
• Many anesthetists may never see such a reaction
  and few will see more than one during their
  working life.
• However, because the consequences of anaphylaxis
  can be serious and potentially life-threatening,
  it is important for anaesthetists to know what
  the clinical signs are and how to deal with them.

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Physical Examination

• The reported incidence of anaphylactic reactions
  during general anaesthesia varies considerably
  between 1 in 950 to 1 in 20,000 anaesthetic
  procedures.

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Physical Examination

• Clinically, a mild reaction is manifested as
• flushing
• urticaria
• redness
• localized edema.

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Physical Examination

• While a severe reaction is manifested by
• shock (severe hypotension)
• bronchospasm
• widespread edema
• massive intravascular fluid
• loss resulting in dramatically
• reduced filling of the heart
• and subsequent severe hypotension

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What treatment should be administered to this
patient?

• Causes need to be excluded first
• Exaggerated hypotensive response to the induction
  agent
• Bronchospasm resulting from the mechanical
  effects of endotracheal intubation in susceptible
  patients
• Vagal response causing severe bradycardia (e.g.
  During laparoscopy , ophthalmic procedures, etc)

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Other causes

• Covert hemorrhage.
• Unexpectedly extensive sympathetic blockade
  during epidural or intrathecal neuraxial
  anesthesia
• Acute exacerbation of pre-existent asthma
  independent of an aesthesia

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For treatment

• 1.Call for help and inform the surgical team
• 2.Stop administration of the drug(s) likely to
  have caused the reaction. It is recommended to
  stop all the drugs that are possible to stop, as
  at this time the causative agent can not be
  determined.
• 3.(ABC) , Maintain airway give 100 oxygen.
• 4.Lie patient flat with feet raised

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Epinephrine Is the drug of choice when
resuscitating patients during anaphylactic shock
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Epinephrine

• Epinephrine acts by two mechanisms
• It reverses vasodilatation by its a-agonist
  effects
• It blocks further degranulation of mast cells or
  basophiles through its ß-agonist effects.
• It may also improve cerebral perfusion
  independent of its effect on blood pressure by
  ß2-mediated vasodilatation, and it is very
  effective in the treatment of bronchospasm.

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For treatment (contd)

• 5.Give adrenaline (epinephrine)
• 50100 µg (0.51 mL of a 110,000 solution found
  in pre-filled syringes,
• or 0.050.1 mL of the more commonly used 11,000
  solution), or 0.01 mg/kg in children.
• Should be administered subcutaneously if the
  patient is merely hypotensive, and may be
  repeated as needed.
• Higher doses and the intravenous route should be
  used if the reaction is severe, or if cardiac
  arrest supervenes.

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For treatment (contd)

• The European guidelines say that
• Intravenous administration should be done
  instead of the subcutaneous route
• Titrated doses (10-20mic for moderate cases and
  100-200 mic for severe cases) are given
• To be repeated every one to two minutes until
  restoration of arterial blood pressure.

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For treatment (contd)

• I.V infusion at a dose of 0.05 to 0.1 mic /kg
  might be used instead of repeated bolus
  administration of epinephrine.
• If I.V route is not immediately availbale, the
  I.M route can be used(0.3-0.5 mg) with injection
  to be repeated every 5-10 minutes depending on
  the patient hemodynamic status.
• In the same situation, the intra tracheal route
  can be used if the trachea is intubated knowing
  that one third of the dose will enter the
  circulation

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For treatment (contd)

• High doses of epinephrine are more efficacious
  but cases of myocardial ischemia or even
  infarction after epinephrine administration have
  been reported.

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Other measures include

• Start rapid i.v volume expansion with crystalloid
  or colloid.
• Increased vascular permeability can transfer 50
  of intravascular fluid into the extravascular
  space within 10 minutes.
• The amount of fluid administered should be based
  on hemodynamic parameter

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Other measures include

• Intravenous steroids
• (e.g., methylprednisolone 12 mg/kg intravenously
  or hydro cortisone 100-500mg (I.V) repeat q46
  hourly as needed).
• Steroids may have no effect for 46 hours, but
  may prevent persistent or biphasic anaphylaxis.

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Other measures include

• Anti-H1 medications (e.g., diphenhydramine 25
  100 mg IV).
• Anti-H2 medications (e.g., ranitidine 1 mg/kg
  IV).
• Glucagon (15 mg IV)
• in severe reactions. Glucagon directly activates
  adenyl cyclase and bypasses the ß-adrenergic
  receptor. It may reverse refractory hypotension
  and bronchospasm. Glucagon or atropine should be
  used in ß-blocked patients to increase an
  inappropriately slow heart rate.

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Other measures include

• In case of refractory hypotension, military
  antishock trousers (MAST) may significantly
  improve hemodynamics.

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Other measures include

• Save any blood samples that have been collected
  prior to or during the procedure. These may be
  required for testing.

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Other measures include

• If cardiac arrest supervenes, advanced cardiac
  life support (ACLS) protocols should be followed,
  including epinephrine, atropine, etc.
• Prolonged resuscitative efforts are encouraged,
  since recovery is more likely to be successful in
  anaphylaxis, in which the subject is often a
  young individual with a healthy cardiovascular
  system

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Further management

• The chest should be auscultated since
  bronchospasm is often triggered by anaphylactic
  or anaphylactoid reactions.
• If bronchospasm does not respond to the treatment
  administered for anaphylaxis, inhaled ß2-agonists
  and possibly aminophylline should be added to the
  regimen.
• Volatile anesthetics can also be used (if that
  is not already the case, and if the blood
  pressure allows) for their bronchodilating
  properties.

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Note

• If pregnant
• start with ephedrine(10 mg to be repeated every
  1-2 minutes)because of the risk of hypoperfusion
  of the placenta caused by epinephrine and the
  patient should be placed in the left lateral
  decubitus.
• In case of ineffectiveness, switch to epinephrine

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To summarize

• Immediate measures
• a. Assess airway, breathing, circulation
• b. Administer epinephrine SQ 50100 µg or 0.01
  mg/kg in children repeat as needed(or iv/im)
• General measures
• a. Expedite surgery position the patient supine
  elevate lower extremities
• b. Administer 100 oxygen
• c. Administer normal saline or colloids if there
  is severe hypotension

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To summarize

• Specific measures
• a. Glucocorticoids methylprednisolone 12 mg/kg
  IV repeat q 46 hourly as needed
• b. H1 antagonists diphenhydramine 25100 mg IV
• c. H2 antagonists ranitidine 1 mg/kg IV
• d. Glucagon 15 mg IV
• e. Nebulized ß2-agonists
• f. Aminophylline 5 mg/kg IV over 30 min, then
  0.9 mg/kg/hr IV follow serum levels (therapeutic
  range 815 µg/mL)
• g. Military antishock trousers (MAST)

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To summarize

• Supervening cardiac arrest, in addition to ACLS
  protocol
• a. Rapid volume expansion
• b. Prolonged resuscitative efforts

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What are the medications most often implicated in
anaphylaxis? In anaphylactoid reactions?

• The commonly used drugs during anaphylaxis are
• Antibiotics
• Aprotinin
• IV anaesthetics, e.g. thiopental, propofol,
  midazolam
• Latex rubber
• Local anaesthetics
• Neuromuscular blocking agents (NMBAs)
• Non-opioid analgesics, e.g. NSAIDs
• Opioid analgesics, e.g. morphine, alfentanyl,
  fentany

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Others

• Plasma volume expanders, e.g. gelatins, starches
• Pre-medication drugs
• Preservatives
• Protamine
• Radiocontrast media
• Skin antiseptics, e.g. chlorhexidine, iodine

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Others

• The rate of anaphylactic reactions with iodinated
  contrast has significantly decreased because
  sensitive individuals are being pretreated with
  steroids and antihistamines, and non-ionic
  contrast with less potential to cause allergic
  reactions is being used.
• Latex has emerged as a cause of anaphylactic
  reaction , probably because of the increasing use
  of latex gloves and barriers. Patients who have
  undergone multiple surgeries, and healthcare
  workers are especially at risk

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Others

• Anaphylactoid reactions are commonly caused by
  morphine, d-tubocurarine, certain antibiotics
  (e.g., vancomycin, ciprofloxacin), aspirin
  (possibly through inhibition of cyclooxygenase),
  and succinylcholine

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What is the percentage of patients allergic to
penicillin who will have a reaction when
challenged with a cephalosporin?

• In patients with true allergy to penicillin, a
  37 rate of allergic reaction to cephalosporin
  is expected, versus 12 in patients with no
  history of penicillin allergy. History is the
  most important element here.

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What is the percentage of patients allergic to
penicillin who will have a reaction when
challenged with a cephalosporin?

• A morbilliform rash (i.e., resembling measles),
  consisting of macular lesions that are red and
  are usually 210 mm in diameter but may be
  confluent in places, is a benign reaction that
  does not qualify as allergic. In a patient who
  had a morbilliform rash, cephalosporins can be
  given safely.

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What antibiotic would you use for clean
orthopedic surgery in a patient reporting a
penicillin allergy or a reaction to
cephalosporins?

• If true allergy to penicillin or cephalosporins
  is reported, it is prudent to use clindamycin 600
  mg intravenously. Vancomycin 1,000 mg
  intravenously administered over 3060 minutes can
  be used as well. Rapid vancomycin administration
  may cause the red man syndrome secondary to a
  non-immune-mediated release of histamine, i.e.an
  anaphylactoid reaction.

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Case (contd)

• Once blood pressure and heart rate returned to
  normal, the rash was subsiding and the chest
  auscultation was clear. Should surgery be allowed
  to proceed or should the case be cancelled? What
  will you tell the patient postoperatively?

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Answer

• The case can probably be allowed to proceed after
  rapid resolution of the event.
• Upper airway edema should be excluded prior to
  extubation.
• The presence of a leak around the endotracheal
  tube should be determined by deflating the
  endotracheal tube cuff and occluding the tube
  manually.

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Postoperative Recommendations

• This patient should be told that the
  administration of any ß-lactam antibiotic might
  be fatal.
• He should be given a letter detailing the
  reaction and specifically naming the medication
  involved, and he should be instructed to wear a
  bracelet indicating his allergy.
• Allergy specialists sometimes perform skin tests
  to identify the causative drug

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Who are at risk for anaphylaxis during anesthesia?

• Patients who are allergic to one of the drugs or
  products likely to be administered or used during
  anaesthesia and for which the diagnosis had been
  established by a previous allergy
  investigation(e.g Deprivan and eggs).
• Patients who have shown clinical signs suggesting
  an allergic reaction during a previous
  anaesthesia.
• Patients who have experienced clinical
  manifestations of allergy when exposed to latex

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Other patients

• Children who have had multiple operations,
  especially those with spina bifida, because of
  the high rate of sensitization to latex
• Patients who have experienced clinical
  manifestations of allergy to kiwi, banana,
  chestnut,buckwheat, etc., because of the high
  rate of cross-reactivity with latex.

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Others

• Patients who are atopic (for example, those with
  allergic asthma or hay fever) or those who are
  allergic to a drug or other product that is not
  likely to be used during the course of the
  anesthesia are not to be considered at risk for
  anaphylaxis during anesthesia

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Note

• For those patients who are at risk as defined
  above , an allergy investigation looking for
  specific sensitization should be proposed before
  any anesthetic procedure.
• Nevertheless, no matter which tests are used,
  they do not guarantee an absolutely correct
  diagnosis.

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1ry prevention

• Total avoidance of contact with latex from the
  first surgical procedure and in the medical
  environment of infants with spina bifida prevents
  the acquisition of latex sensitivity .
• There is actually no way to prevent primary
  sensitization to muscle relaxants. Anaphylactic
  reactions to these agents can occur in the
  absence of their prior administration

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2ry prevention

• The only effective secondary preventive measure
  is to IDENTIFY THE RESPONSIBLE ALLERGEN and then
  completely avoid it.
• For patients sensitized to latex, a latexfree
  environment is effective for the prevention of an
  anaphylactic reaction.
• The latex-free environment must include the
  operating rooms, the postoperative recovery room
  and some other sectors of the hospital

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Note

• The intravenous administration of antibiotics for
  preoperative prophylaxis should be started in the
  operating room with the patient awake and being
  monitored, 5 to 10 minutes before anesthesia
  induction.
• Because there is no evidence of crossreactivity
  between propofol and muscle relaxants, the use of
  propofol in patients allergic to a muscle
  relaxant is not contraindicated.

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