Patients may be mildly allergic to many substances, and this may become better or worse during pregnancy. Severe reactions, however, are rare on the labour ward, with anaphylaxis thought to complicate up to 3.4 in 100,000 deliveries. Although these reactions are divided into anaphylactic (release of histamine and other inflammatory mediators from mast cells via cross-linkage of IgE molecules on the cell surface by the antigen, after prior exposure), anaphylactoid (direct release of mediators from mast cells via interaction of molecules - e.g. drugs - with the cell surface) and others (e.g. direct complement activation), the distinction is largely academic since the clinical presentation is identical.
Most severe reactions on the labour ward are caused by drugs, especially antibiotics, intravenous anaesthetic drugs (particularly suxamethonium) and oxytocin; in the recent 6th National Audit Project (NAP6), all cases of severe obstetric anaphylaxis occurred in the operating theatre.
Traditionally, up to 10% of individuals with true penicillin allergy have been thought to be allergic to cephalosporins; more recent estimations put this figure at 1% for crossreactivity with first-generation cephalosporins, and a negligible risk with third- and fourthgeneration cephalosporins. Allergy to amide local anaesthetic drugs is rare but has been reported, as has allergy to preservatives used in local anaesthetic and other drug preparations. Symptoms related to local anaesthetic injection are more often due to a vasovagal episode, accidental intravascular injection or toxicity.
Non-steroidal anti-inflammatory drugs and paracetamol often cause rashes, but these are usually mild following brief oral or rectal courses, although severe reactions have been reported following intravenous administration. Reactions may also follow administration of gelatine intravenous fluids and blood. Latex allergy is more common in subjects with multiple exposures to latex such as medical or nursing staff, cleaners, those with neurological disease requiring repeated bladder catheterisation (e.g. spina bifida), and those with allergy to certain foodstuffs including avocados, bananas, kiwi fruit and chestnuts. Finally, other conditions not primarily allergic may also present in a similar way, for example amniotic fluid embolism.
Patients may have a history of previous allergic reactions to drugs or other substances, although many patients who give only a vague history are not truly allergic.
Problems and special considerations
Features range from mild skin rashes to severe urticaria, hypotension, bronchospasm, mouth/laryngeal swelling, abdominal pain, diarrhoea, a ‘feeling of impending doom’ and cardiovascular collapse. Initial hypotension is largely related to profound vasodilatation, which is followed by leakage of intravascular fluid into the interstitium. Cardiac depression (thought to be caused by circulating inflammatory mediators) may also contribute to hypotension. The cardiovascular effects are exacerbated by aortocaval compression. Maternal anaphylaxis can lead to compromised uterine blood flow and maternal hypoxia, and subsequent fetal compromise.
Features usually occur within a few seconds or minutes of exposure to the allergen. During caesarean section in latex-allergic subjects, anaphylaxis typically occurs 10-15 minutes after induction of anaesthesia and once surgery has started, since the most provocative stimulus is exposure via mucous membranes.
In NAP6, diagnosis and specific treatment of anaphylaxis were more likely to be delayed in obstetric than in non-obstetric cases. Since clinical features may develop at a time of great physiological change, e.g. during caesarean section or during/after delivery, it may be difficult to assess the situation and determine what has happened. Differential diagnoses include pulmonary embolism, amniotic fluid embolus, cardiac disease, complications of anaesthesia (including high neuraxial block and local anaesthetic toxicity), sepsis and haemorrhage. Administration of many different drugs together or within a short time is common, and this may further hinder the diagnosis (and is suspected of increasing the risk of a reaction).
Management options
Immediate management of severe reactions consists of intravenous adrenaline 50 μg boluses (or 0.5 mg intramuscularly if not experienced at giving intravenous vasopressors) with prompt assessment and management of the airway and administration of 100% oxygen. Intravenous fluid resuscitation is required to correct the deficit caused by decreased systemic vascular resistance and extravasation secondary to increased vessel permeability; the patient should always be monitored for signs of volume overload that may be precipitated by the physiological changes that ensue after delivery. An adrenaline infusion may be required if several boluses are required. Aortocaval compression must be avoided at all times, and fetal monitoring should be instituted. Adrenaline may cause uteroplacental vasoconstriction and uterine hypotony, which may contribute to fetal hypoxia and postpartum haemorrhage respectively; however it remains first-line treatment and should not be withheld when indicated. Intravenous chlorpheniramine 10 mg and hydrocortisone 200 mg may be given to reduce the effects of subsequent inflammatory mediator release. Urgent caesarean delivery may be considered in cases of fetal compromise or to reduce maternal hypotension secondary to aortocaval compression, but this may be challenging in the presence of maternal hypoxia and cardiovascular instability. For less severe reactions (e.g. urticaria only), chlorpheniramine alone may suffice.
In an acute reaction, blood should be taken for tryptase levels as soon as possible and at 1-2 and 24 hours. The enzyme is normally present in mast cells and in minuscule amounts in the plasma; an increase in plasma concentration therefore represents mast cell degranulation (but does not distinguish between anaphylactic and anaphylactoid reactions). Immunoglobulin and complement levels may be suggestive, but not diagnostic, of an allergic response. If a severe reaction is suspected, the anaesthetist involved should refer the patient for testing; a suggested referral form and a list of allergy centres can be found on the Association of Anaesthetists of Great Britain and Ireland (AAGBI) website. Normally investigation will involve skin tests (prick testing ± intradermal testing). Further tests may be performed on plasma (e.g. radioallergoabsorbent test (RAST) looking for concentrations of a specific antibody, e.g. to latex) or occasionally basophils or other cellular components, if skin testing is not diagnostic. The patient should be advised to obtain a ‘MedicAlert’ bracelet and given written details of all the drugs tested and the results, in case she should require a subsequent anaesthetic. A copy of the letter should also be sent to her general practitioner.
It is important that mothers with a previous history of severe allergic reactions are identified antenatally and on arrival to the labour ward. Wherever possible, the previous anaesthetic record should be obtained and a plan for the woman’s care documented. Management of the known allergic case includes a general state of readiness (emergency preparedness) and awareness as well as the obvious avoidance of any known allergens. Latex-allergic patients may be identified from the history in most cases by asking about food allergies and skin reactions after exposure to rubber gloves, condoms, etc. If patients have had a previous severe reaction where the allergen is unknown, pre-treatment with H1- and H2-antagonists ± steroids should be considered, although whether this should be routinely done if the allergen is known and can be avoided is controversial. Routine screening of all women by using skin or blood testing is generally not indicated, since precautions should be taken on the basis of a strong history even if testing produces negative results.
Key points
• In severe allergic reactions, immediate management is with oxygen, adrenaline and intravenous fluids.
• Hydrocortisone and chlorpheniramine are second-line drugs.
• Blood should be taken for mast cell tryptase levels as early as possible and at 1-2 and 24 hours.
• Subsequent testing should include skin testing.
Further reading
Adriaensens I, Vercauteren M, Soetens F, et al. Allergic reactions during labour analgesia and caesarean section anaesthesia. Int J Obstet Anesth 2013; 22: 231-42.
Association of Anaesthetists of Great Britain and Ireland. Management of a patient with suspected anaphylaxis during anaesthesia. London: AAGBI, 2009. www.aagbi.org/sites/default/files/ana_we b_laminate_final.pdf (accessed December 2018).
Cook TM, Harper N. Anaesthesia, Surgery and Life-Threatening Allergic Reactions. Report and Findings of the Royal College of Anaesthetists’ 6th National Audit Project: Perioperative Anaphylaxis. London: RCoA, 2018. www.nationalauditprojects.org.uk/NAP6Report (accessed December 2018).
Hepner DL, Castells M, Mouton-Faivre C, Dewachter P. Anaphylaxis in the clinical setting of obstetric anesthesia: a literature review. Anesth Analg 2013; 117: 1357-67.
Soar J, Perkins GD, Abbas G, et al. European Resuscitation Council Guidelines for Resuscitation 2010, Section 8. Cardiac arrest in special circumstances: electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation 2010; 81: 1400-33.