1. Assistant Lecturer Of Anesthesia
Case Presentation By
Dr Ahmaed Nabil
Assistant Lecturer Of Anesthesia
Ain Shams University

2. 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

3. 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?

4. 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?

5. 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.

7. 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

8. 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

9. 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.

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

11. Physical Examination Clinically, a mild reaction is manifested as:
flushing
urticaria
redness
localized edema.

12. 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

13. 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);

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

15. 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

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

17. Epinephrine Epinephrine acts by two mechanisms:
It reverses vasodilatation by its α-agonist effects
It blocks further degranulation of mast cells or basophiles through its β-agonist effects.
It may also improve cerebral perfusion independent of its effect on blood pressure by β2-mediated vasodilatation, and it is very effective in the treatment of bronchospasm.

18. For treatment (cont’d);
5.Give adrenaline (epinephrine):
50–100 μg (0.5–1 mL of a 1:10,000 solution found in pre-filled syringes,
or 0.05–0.1 mL of the more commonly used 1:1,000 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.

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

20. For treatment (cont’d);
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( 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

21. For treatment (cont’d);
High doses of epinephrine are more efficacious but cases of myocardial ischemia or even infarction after epinephrine administration have been reported.

22. 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

23. Other measures include
Intravenous steroids
(e.g., methylprednisolone 1–2 mg/kg intravenously or hydro cortisone mg (I.V); repeat q4–6 hourly as needed).
Steroids may have no effect for 4–6 hours, but may prevent persistent or biphasic anaphylaxis.

24. Other measures include
Anti-H1 medications (e.g., diphenhydramine 25– 100 mg IV).
Anti-H2 medications (e.g., ranitidine 1 mg/kg IV).
Glucagon (1–5 mg IV)
in severe reactions. Glucagon directly activates adenyl cyclase and bypasses the β-adrenergic receptor. It may reverse refractory hypotension and bronchospasm. Glucagon or atropine should be used in β-blocked patients to increase an inappropriately slow heart rate.

25. Other measures include
In case of refractory hypotension, military antishock trousers (MAST) may significantly improve hemodynamics.

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

27. 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

28. 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 β2-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.

29. 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

30. To summarize: Immediate measures General measures
a. Assess airway, breathing, circulation
b. Administer epinephrine SQ 50–100 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

31. To summarize: Specific measures
a. Glucocorticoids: methylprednisolone 1–2 mg/kg IV; repeat q 4–6 hourly as needed
b. H1 antagonists: diphenhydramine 25–100 mg IV
c. H2 antagonists: ranitidine 1 mg/kg IV
d. Glucagon: 1–5 mg IV
e. Nebulized β2-agonists
f. Aminophylline: 5 mg/kg IV over 30 min, then 0.9 mg/kg/hr IV; follow serum levels (therapeutic range 8–15 μg/mL)
g. Military antishock trousers (MAST)

32. To summarize: Supervening cardiac arrest, in addition to ACLS protocol
a. Rapid volume expansion
b. Prolonged resuscitative efforts

33. The commonly used drugs during anaphylaxis are:
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

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

35. 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

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

37. 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 3–7% rate of allergic reaction to cephalosporin is expected, versus 1–2% in patients with no history of penicillin allergy. History is the most important element here.

38. 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 2–10 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.

39. 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 30–60 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.

40. Case (cont’d)
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?

41. 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.

42. Postoperative Recommendations
This patient should be told that the administration of any β-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

43. 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

44. 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.

45. 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

46. 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.

47. 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

48. 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

49. 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.