How likely is an allergic reaction to propofol in patients with egg or soy allergies?

Comment by InpharmD Researcher

The prescribing information for propofol states a contraindication for use in patients with allergies to egg and soy. Though there are case reports of young children with existing egg allergies experiencing allergic reactions suspected to be due to propofol, the vast majority of data available through numerous retrospective analyses demonstrate that the use of propofol is generally safe in patients with non-anaphylactic egg or soy allergies.

Background

A 2021 review concluded data from clinical trials suggest that propofol is safe for patients with nonanaphylactic food allergies. The authors recommend patients experiencing allergic reactions following administration of propofol should undergo further testing to definitively identify the specific trigger and prevent future unnecessary avoidance of preferred medication regimens.[1]

An article by the Childhood Allergy Committee of the Spanish Society of Allergy and Clinical Immunology noted that opinions among experts seem to vary regarding patients with egg allergies. Some experts recommend against using propofol in those with egg allergies while others would only restrict propofol use in those allergic to egg-white proteins (as lecithin is a product of the egg yolk). Other experts would only restrict use of propofol if a previous anaphylactic reaction was documented. The use of propofol in patients with eosinophilic esophagitis and food allergies have not observed a correlation between rates of adverse events between patients with and without food allergies. It is possible for patients to receive test doses of propofol to determine tolerance in those with a history of anaphylaxis. Therefore, the authors’ recommendations are that there are no contraindications for administering propofol to patients with non-anaphylactic egg allergy. For those with a history of anaphylaxis due to eggs, either an alternative agent or a trial dose may be administered. [2]

A 2016 editorial described the association between food allergies and possible propofol allergies. The author stated that thus far, there is enough evidence to prove the safety of propofol use in adult patients who are allergic to peanuts, soy, and/or egg. For children, it was stated that there had been documented cases of allergic reaction to propofol in patients who had previously experienced anaphylaxis to egg. For mild to moderate egg allergies, the author mentioned enough evidence for propofol use to be considered safe. However, for children who have experienced anaphylaxis to eggs, propofol use should be avoided. Overall, the author believed that there is no convincing evidence that propofol administration is unsafe in children who are allergic to peanuts or soy.[3]

References:

[1] Johnson JL, Hawthorne A, Bounds M, Weldon DJ. New perspectives on propofol allergy. American Journal of Health-System Pharmacy. Published online July 26, 2021:zxab298. doi:10.1093/ajhp/zxab298
[2] Martínez S, Lasa EM, Joral A, et al. Recommendations for the Use of Propofol in Egg-Allergic Patients. J Investig Allergol Clin Immunol. 2019;29(1):72-74. doi:10.18176/jiaci.0337
[3] Harper, N. J. N. (2016). Propofol and food allergy. British Journal of Anaesthesia, 116(1), 11–13. doi:10.1093/bja/aev401
Relevant Prescribing Information

In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL); and disodium edetate (0.005%); with sodium hydroxide to adjust pH. DIPRIVAN is isotonic and has a pH of 7 to 8.5.

DIPRIVAN is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products. [1]

References:

Diprivan (propofol injection, emulsion) [prescribing information]. Lake Zurich, IL: Fresenius Kabi USA, LLC; 2021.
Literature Review

A search of the published medical literature revealed 7 studies investigating the researchable question:

How likely is an allergic reaction to propofol in patients with egg or soy allergies?

Please see Tables 1-7 for your response.

 

Food Allergy History and Reaction to Propofol Administration in a Large Pediatric Population

Design

Retrospective chart review

N= 177,360 administered propofol

N= 2,651 not administered propofol

Objective

To evaluate the rate of allergic reactions experienced during propofol-containing anesthesia in patients listed allergic to egg, soy, or peanut and compare that to non–food-allergic patients who received propofol-containing anesthesia; to evaluate the relationship between food allergy history and corroborating allergy testing data in the Electronic Medical Record (EMR)

Inclusion Criteria

Received anesthesia (with and without propofol); patients with or without listed food allergies to egg, soy, and/or peanut

Exclusion Criteria

N/A

Methods

Electronic medical records were reviewed to find pediatric patients with documented allergies who also received propofol. These patients were then reviewed for documentation indicative of intraoperative allergic reactions. Patients who did not receive propofol but were documented with allergies to egg, soy, and/or peanuts were also assessed for evidence of intraoperative allergic reactions. Signs and symptoms of allergic reactions included rash, hives, wheezing, bronchospasm, hypotension, tachycardia, and bradycardia. Patients with allergic reactions were also evaluated for the possible occurrence of anaphylaxis. The incidence of reactions in patients with documented allergies when undergoing anesthesia with propofol was compared to the incidence of reactions in patients without documented allergies who also received propofol. 

Duration

May 30, 2012, to October 1, 2018

Outcome Measures

 Reaction to propofol

Baseline Characteristics

  

All propofol patients (N= 177,360)

Age category

< 1 year

< 3 years

3-6 years

6-13 years

13-18 years

> 18 years

 

10,896 (6%)

22,242 (13%)

29,972 (17%)

48,524 (27%)

42,273 (24%)

23,432 (13%)  

Gender

Male

Female

Unknown

 

96,764 (55%)

80,417 (45%)

179 (0.1%)

Listed as allergic in EMR

Egg (n= 3,435)

 Peanut (n= 5,862) Soy (n= 2,011)  

Listed anaphylactic reaction to index food

 128 (4%) 568 (10%) 37 (2%)  

Allergy tested

 1,726 (50%) 2,522 (43%) 907 (45%)  

Tested positive

 976 (28%) 1,659 (28%) 322 (16%)  

Tested negative

 750 (22%) 863 (15%) 585 (29%)  

Results

Patients with allergic reactions to propofol

1

 2

3

4

5

6

7

Age, years

 4 10 14 16  9 19 21

Listed food allergy

 None None None Peanuts, tree nuts None None None

food allergy testing

 N/A N/A N/A No No N/A N/A

Tryptase

 + - + + - - -

Rash

 + + + - + - -

Hemodynamic instability

 + + + + + + +

Wheeze

 + + + - - + -

Bronchospasm

 - + + + + + -

Received epinephrine

 - + + + + + +

Advanced care

 + - + - - + +

Propofol allergy test result

 N/A + + N/A + + -

Positive for other allergens

 N/A Yes Yes N/A Yes Yes Yes

Reaction severity

 II II III III III IV III

The occurrence of proven propofol anaphylaxis during anesthesia in patients with no listed allergy to index foods was 0.06/10,000; occurrence in egg- and soy-allergic patients was 0/5,446.

Of the 2,651 administrations of a non-propofol anesthetics to patients who had a listed allergy to at least one index food, 0 had allergic reaction.

Study Author Conclusions

This study presents the largest cohort of pediatric patients evaluated for association between food allergy and propofol allergy, and found no association between food allergy history and propofol reaction. Furthermore, only a small proportion of patients listed allergic to index foods had supporting allergy testing, while a large proportion were negative or had no testing documented. We suggest the multiply allergic and atopic patients may have a similar likelihood to react to propofol as with other medications. Our findings, specifically, the lack of association between food allergy history and propofol reaction, will support providers in their decisions to include propofol in their anesthetic plan when caring for food-allergic patients.

InpharmD Researcher Critique

There were discrepancies between the number of patients who reported an allergy or did not report an allergy compared to the number of patients that were actually tested to confirm the claim or lack thereof. Possible bias may have been introduced depending on if providers altered or decreased the dose of propofol when administered to patients reporting egg or soy allergies; this study did not account for this possibility. 



References:

Bagley L, Kordun A, Sinnott S, Lobo K, Cravero J. Food allergy history and reaction to propofol administration in a large pediatric population. Paediatr Anaesth. 2021;31(5):570-577. doi:10.1111/pan.14147

 

Propofol use in pediatric patients with food allergy and eosinophilic esophagitis

Design

Retrospective chart review

N= 1,279

Objective

 To determine the rate of propofol use and associated complications in children undergoing esophagogastroduodenoscopy (EGD) with a clinical history of egg or soy allergy or eosinophilic esophagitis (EoE).

Study Groups

Egg or soy allergy (No EoE) (n= 73)

No egg or soy allergy (no EoE) (n= 1036)

EoE only (no egg or soy allergy) (n= 165)

EoE and egg or soy allergy (n= 91)

Inclusion Criteria

 Children age 0 to 18 years, underwent general anesthesia for EGD

Exclusion Criteria

 Procedures other than pH impedance was simultaneously performed with the EGD

Methods

Patient data that fulfilled the inclusion/exclusion criteria were analyzed to determine a pattern of EoE and other allergic-related outcomes in pediatrics with egg/soy allergy. Allergies were collected based on the patient's problem list along with anesthetic histories.

Duration

 Recruitment period: January 1, 2013 to June 30, 2014

Outcome Measures

  

Baseline Characteristics

  

Egg or soy allergy (No EoE) (n= 73)

No egg or soy allergy (no EoE) (n= 1036)

EoE only (no egg or soy allergy) (n= 165)

 EoE and egg or soy allergy (n= 91)

Age, years

 6.9 9.7 9.7 6.8
Female 42% 54% 32%

31%

Number of patients

 68 1005 130 76

Number of procedures

 73 1036 165 91

Number of procedures using propofol

 38 (52%) 747 (72%) 114 (69%) 27 (30%)

Results

Endpoint

No propofol

Propofol given

p-Value

  

Procedural complications in egg/soy allergic patients

Nausea and vomiting

Respiratory difficulties

Unanticipated admission

Anaphylaxis

n= 98

2

1

0

0

n= 64

1

1

0

0

 

1.00

1.00

-

-

  

Procedural complications in EoE patients

Nausea and vomiting

Respiratory difficulties

Unanticipated admission

Anaphylaxis

n= 115

8

0

0

0

n= 141

6

0

0

0

 

0.34

0

0

0

  

Procedural complications in non-allergic, non-EoE patietns

Nausea and vomiting

Respiratory difficulties

Unanticipated admission

Anaphylaxis

n= 323

14

4

0

0

n= 783

33

11

0

0

 

0.93

0.83

0

0

  

All patients received general anesthesia with 15 procedures being performed on 12 patients with history of egg allergyanaphylaxis. Six of those patients still received propofol.

Study Author Conclusions

 There was no difference in complication rates relative to propofol use. Propofol was used safely in pediatric patients with EoE and food allergy in this limited single-center review.

InpharmD Researcher Critique

 As mentioned by the author, the applicability of the results are limited as the true risk of food allergy (i.e. IgE or non-IgE-mediated food allergy) is uncertain due to the retrospective nature of the study. Positive allergy tests can be masked as sensitization rather than a true allergy. While the results are supportive of propofol's use in children with egg allergy, they are theoretical at best. There may also be mild reactions undocumented within the reports that would still be worth investigating.



References:

Mehta P, Sundaram SS, Furuta GT, Pan Z, Atkins D, Markowitz S. Propofol Use in Pediatric Patients With Food Allergy and Eosinophilic Esophagitis [published correction appears in J Pediatr Gastroenterol Nutr. 2018 Apr;66(4):709]. J Pediatr Gastroenterol Nutr. 2017;64(4):546-549. doi:10.1097/MPG.0000000000001291

 

No Evidence for Contraindications to the Use of Propofol in Adults Allergic to Egg, Soy, or Peanut

Design

Retrospective studies 

N= 273 (Study A); N= 520 (Study B)

Objective

To examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol

Study Groups

Study A (N= 273)

Study B (N= 520)

Inclusion Criteria

Study A: suspected perioperative allergic reaction and one of the following criteria apply to the suspected reaction: intravenous exposure ​<1h before the onset of reaction or other exposures (oral, subcutaneous, local, epidural, spinal, etc.) <2h before the onset of reaction. 

Study B: ≥16 yr of age tested for specific IgE to egg, soy or peanut as part of investigations for suspected food allergy in the Allergy Clinic.

Exclusion Criteria

Not explicitly stated.

Methods

Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut. 

Duration

Study A: Between 2004 and 2011

Study B: Between 2004 and 2012

Outcome Measures

Diagnosis of propofol allergy or signs of allergic reactions towards propofol

Baseline Characteristics

  

A

B

    

Overall patient demographic information was not provided for both Study A and B.

Results

Clinical details of patients testing positive to propofol in study A

Patient 1

Patient 2

Patient 3

Patient 4

Basic data

Gender

Age, yr

Known egg, soy, or peanut allergy

 

Female

25

No 

 

Female

20

No

 

Female 

37

No

 

Male

64

No

Information about reaction

Grade of reaction*

Symptoms† 

Treatment‡

Tryptase at time of reaction, μg litre−1

 

2

R, H

E, F

2.11

 

1

R

AH, S

NT

 

2

H, F

AH, S, E, F

3.37

 

D

H, T, B

E, P, F

82.5 

Investigation results

Baseline tryptase, μg litre−1

IgE: egg, soy

Phadiatop, kU litre−1

SPT, 10 mg ml-1

IDT, 10 mg ml-1

Provocation (maximum dose 10 mg i.v.)

 

3.25

Negative

<0.35

Negative

Negative

Positive

 

4.61

Negative

<0.35

Negative

Negative

Positive

 

4.24

Negative

<0.35

Negative

Negative

Positive

 

4.88

Negative

<0.35

Positive

Positive

Positive

NT, not tested.

*Reaction class: 1, mild reactions with generalized cutaneous signs, self-limiting; 2, moderate, multiorgan involvement may be self-limiting; 3, severe, life-threatening, usually multiorgan involvement, requires specific treatment; 4, cardiac arrest.23

† H, hypotension; T, tachycardia; R, rash; F, flushing; B, bronchospasm

‡ AH, antihistamine; S, steroid; E, ephedrine; F, fluids; P, phenylephrine

Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum.

In study B, there were no signs of allergic reactions towards propofol in 171 retrieved anesthetic charts from 99 patients with specific IgE to egg, soy or peanut.

Adverse Events

N/A

Study Author Conclusions

No connection between allergy to propofol and allergy to egg, soy, or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence-based and should be reconsidered.

InpharmD Researcher Critique

Retrospective chart reviews rely on the accuracy of previously reported data, and there is potential for selection bias. The sample size is based on a convenience sample, with no power calculation. Study B specifically excluded children <16 years of age, thus conclusions cannot be drawn with regard to children and propofol. 



References:

Asserhøj LL, Mosbech H, Krøigaard M, et al. No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†. Br J Anaesth. 2016;116(1):77-82. doi: 10.1093/bja/aev360
Possible anaphylaxis after propofol in a child with food allergy

Design

 Case report

Case Presentation

A 14 month old male (weight 10 kg) was undergoing treatment for acute respiratory decompensation. The patient's past medical history was significant for atopic disease, including reactive airway disease and eczema, as well as six previous hospitalizations (none requiring intubation). Patient's home medications included albuterol, acetaminophen, topical benzacaine, and budesonide (not administered in previous two months). Patient had documented allergies to eggs, peanut oil, and mold, confirmed via skin test at age seven months. Patient presented to hospital with difficulty breathing, worsening cough, and congestion. Patient had been diagnosed with an upper respiratory tract infection and conjunctivitis two days earlier. Patient had reported with temperature of 36.8 °C and O2 saturation of 75% on room air. Upon admission to hospital, patient received albuterol and ipratropium nebulization, methylprednisolone 2 mg/kg, and O2 via nasal cannula. 

Upon worsening condition, he was emergency transported to a tertiary care hospital, prior to which he was intubated using propofol and rocuronium. Doses were not documented. Typical pediatric doses are propofol 0.5–2 mg/kg and rocuronium 0.5–1 mg/kg intravenously. At intubation, vital signs were HR 146 beats/min, RR 32 breaths/min, and BP 108/69 mm Hg. Thirty minutes later, the patient was hypotensive (BP 83/34 mm Hg) and tachycardic (HR 165 beats/min). Anaphylactic reaction to propofol was suspected. Patient was given 20 mL/kg bolus of NaCl 0.9% and terbutaline with a 0.1 mg intravenous bolus followed by a continuous infusion at 0.8 μg/kg/min. He was given methylprednisolone 3 hours prior; no epinephrine was administered. While being airlifted for transport, the patient's tachycardia continued but BP improved before again dropping, requiring a second saline bolus, after which his vitals improved and remained stable during the flight. 

Upon arrival at tertiary care hospital, patient was continued on terbutaline infusion, methylprednisolone 2 mg/kg/day (divided every 6 hours), continuous albuterol nebulization, ipratropium bromide via nebulizer every 6 hours, and maintenance intravenous fluids. Additionally, he was sedated with ketamine 1-mg/kg/hour and midazolam 0.1–0.5-mg/kg/hour infusions. Antimicrobial therapy was initiated for possible pneumonia with intravenous ampicillin/sulbactam 200 mg/kg/day (divided every 6 hours) and azithromycin suspension 10 mg/kg on day 1, then 5 mg/kg/day. Finally, he was also administered 3 doses of magnesium sulfate 75 mg/kg.

Patient gradually improved on day 2, allowing for discontinuation of ketamine and terbutaline infusions, and initiation of morphine infusion at 50 μg/kg/hour. By hospital day 4, ipratropium bromide was discontinued and significant respiratory therapy was not needed; O2 was tapered, and albuterol nebulization was used as-needed. Budesonide 0.5 mg via nebulization at bedtime was initiated. On day 5, patient was discharged with budesonide 0.5 mg via nebulization and albuterol at bedtime and as needed.

Patient's medical record was documented to include a propofol allergy, however, no skin testing was conducted to confirm. 

Study Author's Conclusion

As demonstrated in this case, propofol has the potential to cause life-threatening hypersensitivity reactions in patients with allergies to egg and/or soybeans. Several other medications have a food component, and care must be taken to avoid administration of these agents to patients with an interacting food allergy. It is imperative for patient safety that clinicians consider the potential for adverse drug events in patients with select food allergies.
References:

Hofer KN, McCarthy MW, Buck ML, Hendrick AE. Possible anaphylaxis after propofol in a child with food allergy. Ann Pharmacother. 2003;37(3):398-401. doi:10.1345/aph.1C227

 

Propofol Administration is Safe in Adult Eosinophilic Esophagitis Patients Sensitized to Egg, Soy, or Peanut

Design

Retrospective observational study

Objective

To investigate the safety of propofol administration for procedural sedation in EoE patients sensitized/allergic to egg, soy, peanut.

Study Groups

N= 60 patients total; n= 25 allergic to egg

Inclusion Criteria

Adult EoE patients, defined by age older than 14 years, with dysphagia and/or food impaction and persistent esophageal eosinophilia, on high-dose proton pump inhibitor therapy, who underwent at least one upper gastrointestinal endoscopy under propofol sedation.

Exclusion Criteria

N/A

Methods

In patients undergoing propofol sedation supervised by an endoscopist, all upper gastrointestinal endoscopies were performed according to a standard protocol. Propofol was administered as the sole sedative agent under the supervision. An initial bolus of 20–40 mg of propofol (Generic product 10 mg/ml) was administered intravenously in all patients. An observation period from 2 to 5 min was set to promptly detect immediate allergic reactions. Afterward, additional boluses of 20–40 mg at the discretion of the endoscopist were administered intended to a deep sedation target along the procedure.

Standardized food allergy work-up, including food-specific IgE and skin prick tests, was performed in all patients from both centers. Atopy patch test (APT) is not standardized and was not performed in one center, so therefore it was not evaluated. A patient was considered to be sensitized to a food with at least a positive result in one test. Food-specific serum IgE was determined from peripheral blood by using the ImmunoCAP test. All values above 0.35 KU/l were considered as a positive food serum-specific IgE test.

Skin prick test was carried out against egg (white and yolk), chicken (crossreactivity with egg), soy, and the remaining legumes potentially cross-reactant with soy (peanut, lentils, chickpea, and beans). Skin prick test was performed on the forearm with disposable lancets by pricking through a drop of the extract, which was then absorbed. Every individual drop was separated at least 2 cm of the next. Reactions were recorded by measuring the largest diameter of the wheal in millimeters at 15 min. Histamine (10 mg/ml) was used as positive control and saline solution as negative one. The test result was considered positive if the largest diameter of the wheal was at least 3 mm.

Duration

January 2009 and March 2013 in Spain

Outcome Measures

 

Primary outcome: instance of allergic adverse event

Secondary outcomes: other safety parameters during the procedure.

Baseline Characteristics

  

N=60

Average age, years (range)

   28 (14–56)

Female (%)

  6 (10%)

History of Anaphylaxis

  2 (3%)

History of Egg Allergy

  2 (30%)

Of note, only 2 participants had a documented history of allergy to egg. Soy allergy history was not specified.

Results

Twenty-five patients (41%) demonstrated a food sensitization to egg via IgE and skin prick tests. Thirty-two (53%) demonstrated a food sensitization to soy via IgE and skin prick tests. 

A total of 404 upper endoscopies were performed under propofol sedation.

No allergic adverse events were reported, except a transient bronchospasm after orotracheal intubation in an asthmatic adolescent receiving multiple drugs for anesthesia, in whom no sensitization to either propofol or its lipid vehicle was confirmed.

Adverse Events

Common Adverse Events: (or those deemed frequent; if not listed in study, use N/A or “Not disclosed”)

Serious Adverse Events: (or those deemed high risk; if not listed in study, use N/A or “Not disclosed”)

Percentage that Discontinued due to Adverse Events: (if not listed in study, use N/A or “Not disclosed”)

Study Author Conclusions

Propofol can be safely administered for procedural sedation in adult eosinophilic esophagitis patients, regardless of documented sensitization to egg, soy, or peanut. The present study adds objective evidence to the train of thought that propofol can be safely administered in these patients, opening up the debate to reconsider labeling warnings regarding the use of propofol in this context.

InpharmD Researcher Critique

Only 2 participants had a previous history of egg allergy. Of all participants, only 25 patients had a tested egg allergy with little detail regarding the specific response and extent of the allergy was included. Despite this study, data remains limited for patients with severe egg allergies. 



References:

Molina-Infante J, Arias A, Vara-Brenes D, et al. Propofol administration is safe in adult eosinophilic esophagitis patients sensitized to egg, soy, or peanut. Allergy. 2014;69(3):388-394. doi:10.1111/all.12360

 

Propofol Use in Children with Allergies to Egg, Peanut, Soybean, or Other Legumes

Design

Retrospective study 

N= 1,196

Objective

To assess the safety of propofol in children with egg, peanut, soybean, or legume allergy, or sensitivity, in a larger cohort than previously examined and also to compare the rates of potential allergic reaction in food-allergic children with those in children without food allergies

Study Groups

Allergic group (n= 304)

Control group (n= 892)

Inclusion Criteria

Children with immunologically confirmed egg, peanut, soybean, or legume allergy and who underwent general anesthesia with propofol at Princess Margaret Hospital for Children in Australia. 

Exclusion Criteria

Not explicitly stated. 

Methods

The study extracted details regarding allergy diagnosis, each anesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from a prospective anesthesia research database and acted as a control group.

Duration

Between 2005 to 2015

Outcome Measures

Allergic reactions

Baseline Characteristics

  

Allergic group (n= 304)

Control group (n= 892)

          

Age, years 

median (IQR [range])

 

5.0 (2.7 – 8.8 [0.0 – 18.0])

 

6.0 (3.9 – 9.6 [0.0 – 17.0])

          

Weight, kg

median (IQR [range])

 

18.6 (13.6 – 28.3 [3.1 – 88.7])

 

22.5 (16.5 – 36.3 [2.3 – 121.0])

          

ASA physical status

1

2

3

4

 

183 (28.2%)

298 (46.0%)

163 (25.2%)

4 (0.6%)

 

524 (58.7%)

351 (39.3%)

16 (1.8%)

0

          

Total propofol dose, mg

median (IQR [range])

 

80 (40 – 140 [4 – 1442])

 

50 (30 – 140 [4 – 2250])

          

Total propofol/kg body weight, mg*kg-1

median (IQR [range])

 

4.0 (2.4 – 5.4 [0.4 – 40.0])

 

2.4 (1.3 – 4.3 [0.2 – 29.9])

          

Anesthesia duration, min

median (IQR [range])

 

39 (24 – 64 [8 – 322])

 

47 (33 – 68 [6 – 1424])

          

Recovery area duration, min

median (IQR [range])

 

35 (28 – 45 [11 – 166])

 

40 (31 – 52 [11 – 1408])

          

Results

Summary of diagnosed allergy, medical history, nature of suspected reaction and clinical impression in ten patients with possible reactions following propofol exposure

Case

 Allergy Other allergies, atopy Background medical information  ASA physical status  Reaction sign  Treatment  Possible cause 

1

Egg white

Egg yolk

 EMLA, dressing, hayfever GEFS+, SCN1 Mutation, PEG fed, rhinoconjunctivitis 3  Tachycardia - Sepsis

2

Egg white

Egg yolk

Peanut

 Tegaderm dressing Wiskott–Aldrich Syndrome 2  Stridor -  Stridor after every tracheal intubation
3

Egg white

Peanut

 Cefaclor, shellfish Asthma, rhinoconjunctivitis 2  Mild audible wheeze without oxygen desaturation -  Asthma, current upper respiratory infection, wheeze directly after tracheal extubation
4

Egg white

Egg yolk

 - Juvenile myelomonocytic leukemia 3 

Generalized skin rash, cough

 Promethazine 7.5 mg Platelet infusion reaction. Tolerated propofol without any adverse event in five following procedures
5 Peanut

Ceftazidime 

 CF, asthma, eczema, rhinoconjunctivitis, MBL deficiency 3 3x cough CPAP After CT scan + bronchoscopy
6

Egg white

Egg yolk 

 Mosquito bite OSA, asthma, syringomyelia, MBL deficiency 3  Cough 4 mg Dexamethasone 10 mg Loratadine postop After two tracheal intubation attempts
7

Egg white

Egg yolk

Peanut

 Fentanyl, oxycodone, tapes, cow’s milk, chicken, kiwi fruit VACTERL syndrome premature, single right dysplastic kidney, eczema 3  Localised skin rash on operation side -  Reaction to Betadine
8

Egg white

Egg yolk

 - OSA 2  Brief oxygen desaturation to 85% CPAP OSA

Possible reaction causes
9

Egg white

Egg yolk

 - Born at 28 weeks gestation, chronic lung disease, bronchomalacia, gastroschisis, short gut syndrome, PEG & TPN-fed 3 Facial swelling (peri-oral and peri-orbital) 60 mg Hydrocortisone 3 mg Promethazine Likely intralipid reaction given previous history of facial swelling with TPN 
10

Egg white

Egg yolk

Peanut

 Whitefish, grass Asthma, rhinoconjunctivitis, eczema 2  Oxygen desaturation to 90%, wheeze 2 x 2.5 mg Ventolin, CPAP Atelectasis and mild bronchospasm following extubation

EMLA: eutectic mixture of local anaesthetic; GEFS+: Genetic epilepsy with febrile seizures plus; CF: cystic fibrosis; MBL deficiency: Mannose-binding lectin deficiency; CPAP: Continuous Positive Airways Pressure; OSA: obstructive sleep apnoea; VACTERL: Vertebral anomalies, anal atresia, cardiac defect, tracheo-esophageal fistula, renal abnormalities, limb abnormalities; TPN: total parenteral nutrition.

In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a food-allergic child with a previous history of intralipid allergy

Adverse Events
See "Results"

Study Author Conclusions
We conclude that a genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

InpharmD Researcher Critique

Given the retrospective nature of the study, the study assumed an allergy for every positive reaction on skin prick testing or IgE testing, which may not always equate with a clinical allergy. Moreover, only 132 (43%) of 304 children in allergic group were exposed to propofol within one year after positive testing, and it is likely that some may have lost their clinical reactivity between testing and propofol exposure. 

For two possible reaction causes, patients were not further tested to determine whether the reaction was due to propofol sidechains or the food component.



References:

Sommerfield DL, Lucas M, Schilling A, et al. Propofol use in children with allergies to egg, peanut, soybean or other legumes. Anaesthesia. 2019;74(10):1252-1259. doi:10.1111/anae.14693

 

Allergic Reactions to Propofol in Egg-Allergic Children

Design

Retrospective chart review

N= 28

Objective

To determine whether children with an immunoglobulin (Ig)E-mediated egg and/or soy allergy had an allergic reaction after propofol use

Study Groups

Egg-allergic patients (N= 28)

Inclusion Criteria

Children with IgE-mediated egg and/or soy allergy who had propofol administered at the Children’s Hospital Westmead (CHW), Sydney.

Exclusion Criteria

Children tolerating whole egg (i.e., boiled or scrambled egg) or soy, or if the SPT/serum-specific IgE levels were not performed within 12 months of propofol administration.

Methods

A retrospective chart review of propofol administration to egg- and/or soy-allergic pediatric patients at the CHW for 1999 to 2010 was performed. 

Duration

Between 1999 to 2010

Outcome Measures

Allergic reactions.

Baseline Characteristics

  

Egg-allergic patients (N= 28)

Median age at the time of anesthesia, years

 2.4 (range, 1-15)

Age range

<5 years

5-10 years

>10 years

 

21 (75%)

5 (18%)

2 (7%)

Male

21 (75%) 

Atopic disease at the time of first propofol administration 

Eczema

Asthma

Peanut allergy

 

17 (61%)

9 (32%)

12 (43%)

Time period since last reaction to egg and first propofol administration

<12 months

12-24 months

>24 months

(n= 19)

7 (37%)

8 (42%)

4 (21%) 

Results

Twenty-eight egg-allergic patients with 43 propofol administrations were identified.

There was one nonanaphylactic immediate allergic reaction (n=1 of 43, 2%) that occurred 15 minutes after propofol administration in a 7-year-old boy with a history of egg anaphylaxis and multiple other IgE-mediated food allergies (cow’s milk, nut, and sesame). SPT to propofol was positive at 3 mm. No other egg-allergic child reacted to propofol.

Adverse Events

N/A

Study Author Conclusions

Despite current Australian labeling warnings, propofol was frequently administered to egg-allergic children. Propofol is likely to be safe in the majority of egg-allergic children who do not have a history of egg anaphylaxis. Until further evidence from a prospective study is available, propofol should not be administered to any child with a history of egg anaphylaxis.

InpharmD Researcher Critique

The study is subject to the limitations inherent to a retrospective analysis besides its small sample size. 



References:

Murphy A, Campbell DE, Baines D, et al. Allergic reactions to propofol in egg-allergic children. Anesth Analg. 2011;113(1):140-144. doi:10.1213/ANE.0b013e31821b450f