Cross-sensitization within antibiotics

The most reliable data exists for penicillin-based (β-lactam group) antibiotics and local antibiotic guidelines should detail antibiotics that are considered safe in patients with documented penicillin allergy. The risk of cross-reactivity or sensitization within the β-lactam group varies. A positive skin test reaction to penicillin infers a 2% risk of reacting on challenge to a cephalosporin and approximately 1% risk to a carbapenem. The safest approach in confirmed penicillin allergy is to avoid all β-lactam antibiotics, as reactions, although infrequent, can include anaphylaxis.

If patients are selectively allergic to the amoxicillin or ampicillin (aminopenicillins) side chain, rather than the β-lactam ring structure, then cephalosporins with an identical side chain should be avoided, but other β-lactam antibiotics do not need to be avoided. The estimated risk of cross-reactivity between aminopenicillins and cephalosporins with an identical side chain is around 24%, but this is based on limited data from a single country. The safest approach in aminopenicillin allergy is to avoid all β-lactam antibiotics unless assessed in an allergy clinic specifically for cross-reactivity.

Reliable data are not available on cross-reactivity for other antibiotic groups and therefore the safest advice is to avoid all structurally similar antibiotics.

Reactions to neuromuscular blocking drugs

Anaphylaxis to neuromuscular blocking drugs may be allergic or non-allergic: the clinical features may be indistinguishable. Mivacurium and atracurium commonly cause degranulation of mast cells. Mast-cell degranulation in the skin produces the familiar cutaneous flush, but more widespread degranulation of mast cells and basophils may result in life-threatening bronchospasm, hypotension and angioedema. Cisatracurium, rocuronium and vecuronium are not characterized by non-allergic anaphylaxis. Suxamethonium is the anaesthetic drug most likely to cause an allergic anaphylactic reaction. When a patient reports a previous adverse reaction to suxamethonium, it is often unclear whether the mechanism was anaphylaxis, a plasma cholinesterase deficiency causing ‘suxamethonium apnoea’, or even malignant hyperthermia (MH). In addition to obtaining copies of the relevant documentation, it is a relatively easy matter to exclude plasma cholinesterase deficiency with the appropriate blood test. The majority of MH-susceptible families, in the UK, are known to the MH Unit at St James’ Hospital, Leeds. If any uncertainty persists, the avoidance of trigger agents is straightforward, and rocuronium should be used in preference to suxamethonium to facilitate tracheal intubation. Sugammadex should be available in all obstetric units as a rescue drug in a ‘can’t intubate can’t ventilate (CICV) situation’.

Cross-sensitivity between neuromuscular blocking agents (NMBA) is present in a high proportion of patients who are diagnosed with NMBA-induced anaphylaxis. Contrary to common belief, cross-sensitivity is not confined within classes of NMBA: for example, a patient who has experienced allergic anaphylaxis to atracurium may be co-allergic to rocuronium or suxamethonium. Consequently, a patient with known or suspected allergy to a specific muscle-relaxant drug must not be exposed to any NMBA unless skin testing has confirmed a suitable alternative to which the patient is unlikely to be allergic. In practice this necessitates skin prick testing (SPT) followed, if negative, by intradermal testing (IDT). The sensitivity of IDT for NMBA is high. SPT is performed initially because, although the sensitivity of the test may be less than IDT, SPT is less likely to induce a significant reaction if the patient is allergic to the drug. There are no reliable blood tests for NMBA allergy. The sensitivity of the blood test for specific antibodies to suxamethonium is relatively poor and this test should not be used to exclude allergy because the consequences of a false-negative result could be catastrophic. It must be emphasized that skin testing must be performed only in expert centres with considerable experience of interpreting the results. Pregnancy is not an absolute contraindication to skin testing, but the decision should be left to the expert centre. The decision whether to perform skin testing will depend on the suspected allergen, the prior probability of allergy, the sensitivity and specificity of the test, and the likelihood of a serious reaction occurring if the patient becomes exposed to the allergen. Intubation of the trachea without muscle relaxants has not been investigated in the pregnant patient, but avoiding NMBA is associated with a 52% higher likelihood of difficult intubation in the non-parturient.

Reactions to analgesics

Reported allergy to opioid analgesia is common, which raises the question about management of pain in labour. A careful, unhurried history of events is important. Nausea and vomiting alone is highly unlikely to represent allergy. A localized itchy rash after the administration of IV morphine is characteristic of harmless non-specific histamine release and is not suggestive of allergy. A sensation of being acutely unwell after taking codeine is likely to be the consequence of ultra-fast metabolism to morphine as a result of CYP2D6 gene duplication, seen in 1%–7% of the population. Allergy to fentanyl, alfentanil and remifentanil is vanishingly uncommon. There are recent reports of serious adverse reactions to remifentanil during labour, but these are highly unlikely to be the result of allergy. Skin tests are not useful for investigating suspected allergy to morphine, diamorphine, pethidine or codeine because these drugs cause non-specific degranulation of mast cells in the skin. In contrast, fentanyl, alfentanil and remifentanil are not associated with false-positive skin tests. A blood test for specific-IgE to morphine is marketed, but its reliability is uncertain and it is not widely available in UK immunology laboratories.

Gastrointestinal intolerance to NSAIDs is extremely common. They may also be responsible in some individuals for non-IgE-mediated swelling, rash or bronchospasm. Skin testing is not useful in making the diagnosis, but avoidance is not problematical. A graded challenge test may be the only way to confirm the diagnosis, but should be delayed until after delivery.

Local anaesthetic (LA) allergy

Allergy to LA is a real entity, but is extremely uncommon. The issue of supposed LA allergy usually arises because a patient has experienced unpleasant symptoms during dental treatment. Because LA drugs are the mainstay of obstetric anaesthesia and analgesia, it is important to investigate these suspected reactions to reassure the parturient. Exclusion of allergy on history alone is usually possible; the sensation of palpitations, headache and a feeling of impending catastrophe is characteristic of the systemic effects of vasoconstrictor agents used in dental surgery. Delayed swelling after dental treatment often results from tissue oedema, but occasionally represents stress-induced angioedema. The differential diagnosis includes latex allergy (see below). If allergy to LA cannot be excluded by taking a careful history, the parturient should be referred to a specialist centre for skin testing. The investigation pathway comprises SPT, IDT and sub-cutaneous challenge. Delayed hypersensitivity to prilocaine is sometimes seen after local anaesthetic cream is used to reduce the discomfort of venepuncture. This is not life-threatening and does not preclude the use of spinal or epidural analgesia with bupivacaine.

Allergy to chlorhexidine

Anaphylaxis to chlorhexidine appears to be increasing. Features of anaphylaxis may be immediate or delayed for up to 30 minutes following exposure. Individuals become sensitized by exposure to chlorhexidine in daily life and subsequent exposure in a healthcare setting may cause a life-threatening anaphylactic reaction. Severe anaphylaxis appears to be more likely when chlorhexidine gains access to the circulation during interventional procedures, such as central venous cannulation, cardiac catheterization, dental surgery and urethral catheterization. The MHRA issued a Medical Devices Alert (MDA) in July 2012 relating to chlorhexidine-coated central venous lines and haemodialysis catheters, and a second MDA in October 2012 relating to all medical devices and medicinal products containing chlorhexidine.

Some patients previously experience symptoms suggestive of chlorhexidine allergy that goes unrecognized. Increased awareness among healthcare professionals of chlorhexidine allergy might highlight this possibility and allow the patient to be referred for allergy testing before the occurrence of life-threatening allergy. Avoidance of chlorhexidine is a considerable undertaking, especially if an obstetric patient is admitted as an emergency, and therefore efforts to diagnose chlorhexidine allergy should be made as early as possible in pregnancy so that a management plan can be documented. The currently available blood test for IgE antibodies specific to chlorhexidine has a relatively high sensitivity and this should be the first step in the diagnostic pathway in the pregnant patient. If the specific IgE test is negative, despite a strong clinical history, the patient should be referred to a specialist allergy clinic so that the relative merits of skin testing can be discussed.

Latex allergy

All healthcare environments should have a documented protocol for managing patients who are allergic to natural rubber latex (NRL). Allergy to latex is discussed in detail in the AAGBI guidelines, Suspected Anaphylactic Reactions Associated with Anaesthesia, 2009. Anaphylaxis to latex is decreasing, probably because non-latex gloves and other equipment are increasingly used in healthcare. Type 1 latex allergy can usually be identified or excluded on history alone. If a patient can blow-up a party balloon without experiencing itch or swelling, it is highly unlikely that they are allergic to latex. If the history is suspicious of latex allergy, a blood test for latex-specific IgE should be performed, but the sensitivity is less than 85%. If the blood test is positive the prevailing latex-avoidance protocol should be invoked and the parturient should be offered referral to a specialist allergy centre for further investigation post partum. If the history is strongly suggestive of latex allergy and the blood test is negative, the parturient should still be offered referral to a specialist allergy centre to discuss skin testing. Preparation of the delivery room and operating theatre for a patient who is allergic to latex does not need to be an onerous undertaking if common sense is applied. All obstetric units should have a list of equipment that contains latex. It is necessary to remove all latex gloves and other latex-containing equipment from the room and a notice should be posted on the door. It is not necessary to remove items of equipment that do not contain latex. Because modern hospital rooms and operating theatres are equipped with forced ventilation, it is unnecessary to prepare the room earlier than a couple of hours before admitting a latex-allergic patient. Allergy to latex is not transmitted from mother to fetus, but the neonatal paediatric team should avoid using equipment that contains latex if they are present in the same room as the mother.

Allergy to intravenous colloids

Intravenous gelatins are a significant cause of anaphylaxis, although often overlooked. Onset is usually within minutes of starting an infusion. The reaction is usually IgE-mediated, but the sensitivity of the blood test for gelatin-specific IgE is very poor; diagnosis requires skin prick testing or intradermal testing. Intravenous starch solutions are no longer available in the UK.