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Crit Care Med 2003 ; 31 : A123 . 252 Wheeler A , Steingrub J , Linde - Zwirble W , et al. Prompt administra- tion of drotrecogin alfa (activated) is associated with improved sur- vival . Crit Care Med 2003 ; 31 : A120 . 596 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 42 Anaphylactic Shock in Pregnancy Raymond O. Powrie Department of Medicine, Obstetrics and Gynecology, Warren Alpert School of Medicine at Brown University, RI, USA Introduction Anaphylaxis is a serious potentially life - threatening allergic reac- tion that is rapid in onset and requires prompt treatment. The pathophysiology, precipitants, and management of anaphylaxis are similar in pregnant and non - pregnant patients so this chapter will largely focus on the general management of this condition but will highlight pregnancy specifi c concerns when appropriate. Defi nitions “ Anaphylaxis ” is a term that is often imprecisely used. It was coined in 1902 from the Greek words ana (meaning backwards) and phylax (meaning guard) to describe the phenomenon where an agent that was administered for its protective effect had instead the opposite effect and instead caused harm. Strictly speaking, anaphylaxis refers to IgE - mediated immediate ( “ type 1 ” ) hyper- sensitivity reactions to proteins (see Table 42.1 ) [1 – 3] . However, in clinical practice, such reactions are often diffi cult to distinguish from other types of severe allergic reactions that are not mediated by IgE. Such non - IgE - mediated reactions are correctly termed “ anaphylactoid reactions ” . Although true anaphylaxis is more likely to cause hypotension and cardiac arrest than anaphylactoid reactions, the initial management of the two conditions is identi- cal and the two terms will therefore be used interchangeably in this chapter. Epidemiology Anaphylactoid reactions are responsible for 1% of emergency room visits and perhaps 1000 deaths per year in the US. Between 0.05 and 2% of individuals will have an anaphylactoid reaction over the course of their lifetime. Anaphylactoid reactions are more likely to occur in hospitalized patients, with estimates of the frequency of anaphylaxis in hospital varying from 1 in 2700 to 1 in 5100 admissions [4,5] . The incidence of anaphylaxis in preg- nant women is not known but there is no reason to believe that the incidence should be lower in this population, given both (i) the frequent need for both hospitalization and medications in this population and (ii) our present understanding of the immuno- logic changes in pregnancy. Precipitants Table 42.2 reviews the most commonly identifi ed precipitants of anphylactoid reactions in adults. Despite this extensive list, in up to 60% of cases, the precipitating agent cannot be identifi ed [6,7] . Some anaphylactic responses are only seen if the exposure is followed by physical exertion or exercise. Such a response is called “ food - dependent, exercise - induced anaphylaxis ” (FDEIAn). There are over 50 case reports that detail anaphylaxis occurring in obstetric patients in relation to their antenatal/intrapartum care and some of these causes are also listed in Table 42.2 . Risk f actors for a naphylaxis/anaphylactoid r eactions The following are some of the known risk factors for anaphylac- toid reactions. G e n d e r Women are more likely to have anaphylactoid responses in general and particularly to NSAIDs, latex and neuromuscular blockers. It is theorized that this relates to gender differences in antigen exposures, with women being more likely to have had prior exposures to antigens in cosmetics and skin - care products. Anaphylactic Shock in Pregnancy 597 Table 42.1 Gell and Coombs classifi cation of allergic reactions [30] . Type Clinical manifestations Mechanism I. Anaphylactic, immediate - type hypersensitivity True anaphylaxis as described in this chapter Exposure to antigen causes release of histamine, leukotrienes and prostaglandins from mast cells or basophils. Usually an IgE - dependent reaction II. Antibody - dependent cytotoxicity Hemolytic anemia, Interstitial nephritis Antigens or haptens that are closely associated with a cell bind to an antibody, which leads to cell death or tissue injury III. Immune complex disease Serum sickness Formation or deposition of antigen - antibody complexes causes damage to vessels and tissue IV. Cell - mediated or delayed hypersensitivity Contact dermatitis Tissue injury mediated by T cells which have been sensitized to antigens V. Idiopathic Maculopapular rash, Stevens – Johnson syndrome Not known Type of e xposure Parenteral exposure to antigens is much more likely to cause anaphylactoid reactions than is oral ingestion. Parenteral expo- sures may be less likely to present with hives and fl ushing and therefore anaphylaxis may be mistaken for other causes of hypo- tension [8] . Inhalational exposures can rarely lead to anaphylaxis and when this does occur, peanuts or latex are the most likely precipitants. Exposures to larger volumes of antigen are also more like to put a patient at risk than are smaller ones. Lastly, concomi- tant exposures to other antigens to which the patient may have an allergy also seem to put patients at increased risk. History of p rior e xposures Consistent exposure is less likely to cause anaphylactoid responses than intermittent ones. History of p revious a naphylactoid r esponse Anaphylactoid responses are more likely to occur in patients who have had anaphylaxis in the past. However, anaphylaxis does not predictably recur in every patient upon repeat exposure [9] . If it has been years since previous exposure to the precipitating antigen, IgE levels may have declined over time and the immune response may have become muted. History of a topy Patients with atopy are at increased likelihood of anaphylactoid reactions to most agents except for medications. Atopic and asth- matic individuals are also more likely to die when they do have anaphylaxis [10] . Pathophysiology True anaphylaxis is caused by the release of infl ammatory media- tors from the degranulation of mast cells and basophiles. This degranulation occurs in response to the cross - linking of mast cells bound to IgE with a precipitating antigen. The mediators initially released include histamine, prostaglandins, leukotrienes, and platelet activating factor. Later, cytokines, interleukin 3 and 4 and tumor necrosis factor may be released. The anaphylactic response can also be associated with stimulation of complement C3a, C4a and C5a. Alternations in arachidonic acid metabolism may also contribute to the anaphylactic syndrome in some cases. These mediators induce pruritus, vasodilation and increased vascular permeability. They can also cause respiratory muscle contraction, autonomic nervous system stimulation, platelet aggregation, recruitment of infl ammatory cells and increased gas- trointestinal motility. All of these responses contribute to the variable clinical presentation of anaphylaxis. Clinical p resentation Symptoms generally develop within 5 – 60 minutes of exposure to the inciting antigen. Parenteral administration leads to a more rapid response. Oral ingestion will take longer. In rare circum- stances, onset may be delayed up to several hours [11] . The mani- festations of anaphylaxis vary widely and are reviewed in Table 42.3 . Fatalities from anaphylaxis generally occur due to cardio- vascular collapse, and asphyxia from upper airway obstruction from edema or intractable bronchospasm. Timing and l ength of r eaction Most cases of anaphylaxis have a single severe response that resolves with treatment over a few hours. Some patients have a protracted syndrome that lasts for 24 – 48 hours. Between 1 and 20% of cases of anaphylactoid responses will have an acute phase followed by a period of recovery and then a recurrence between 1 and 8 hours after the initial presentation. Reports of a second wave of symptoms occurring up to 72 hours after the initial exposure exist but are rare [12 – 14] . The pathophysiology underlying such biphasic responses remains unclear. Biphasic reactions appear to Chapter 42 598 Table 42.2 Some precipitants of anaphylactoid reactions in adults [27,31 – 39] . Class of agent Specifi c agents Comments Medications True anaphylaxis to drugs requires previous exposure, but anaphylactoid responses can occur the fi rst time a medication is administered Antibiotics, especially β - lactams (penicillins and less commonly cephalosporins) Aspirin and other NSAIDs, particularly in patients with nasal polyps/chronic sinusitis and asthma Neuromuscular blockers Narcotics Antineoplastic compounds Insulin [40] ACE inhibitors [41] 4 – 10% of people who have received penicillins have penicillin - specifi c Ig E antibodies although very few of these patients will manifest anaphylaxis. Anaphylaxis from penicillins is said to occur in 0.04 – 0.2% of exposures, with death from anaphylaxis occurring in only 0.001% of all exposures. Most of these patients will have had prior exposure to penicillins but no documented allergy to it. Concerningly, one - third of patients who die of penicillin anaphylaxis do have a documented history of prior reactions to penicillin [42] . Although 20% of patients with PCN allergies will have laboratory or skin testing evidence of a cross - reaction to cephalosporins, only 1% will actually have a clinical reaction to cephalosporins. For this reason, it is now recommended that cephalosporins be withheld from patients with PCN allergies only if their response to PCN included hypotension or respiratory diffi culty. Anaphylactoid responses to non - β - lactam antibiotics are uncommon. NSAIDs can produce anaphylactoid responses by a variety of mechanisms, some of which are specifi c to a single drug, while others can occur with several different NSAIDs [43,44] . Selective COX - 2 inhibitors are less likely to cause anaphylactoid reactions than NSAIDs Insect bites/stings Tiatoma (kissing bugs or assassin bugs) and members of the order Hymenoptera [45] (yellowjackets, wasps, imported fi re ants and harvester ants) Foods [23,46 – 48] Seafood, fi sh, peanuts, tree nuts, vegetables such as carrots and celery, wheat and grain Although most commonly seen in children, food allergies can begin at any age in life. Food allergies are more likely to have bad outcomes in patients with asthma. Anaphylactoid reactions to seafood are not related to iodine content but rather to tropomyosin proteins. Celery and carrot anaphylaxis is more common in patients with allergies to pollens. Wheat and grain are particularly likely to be associated with “ food dependent, exercise - induced anaphylaxis ” (FDEIAn) Sulfi ting agents Sulfi tes (or sulfi ting agents) are a group of simple chemicals that include sulfur dioxide and sulfi te salts. Some of these agents are approved by the US FDA for use as food preservatives and to prevent food discoloration. Sulfi tes are most commonly found now in the following foods: dried soup mixes, vegetable juices, baked goods, canned or dried fi sh, dried fruit, relishes, shredded coconut, shrimp, lobster, scallops, olives, pickles, sauerkraut, dried noodle meals, molasses, gravies, potatoes, lemon and lime juice, jams and jellies, grape juice, wine, beer, maraschino cherries, dehydrated vegetables and fruit In 1986 the US FDA prohibited the use of sulfi tes on fruits and vegetables meant to be eaten raw. They also required companies to list on product labels sulfi ting agents that occur at concentrations of 10 ppm or higher, and any sulfi ting agents that had a technical or functional effect in the food regardless of the amount present Immunotherapy injections Antigen exposures given by allergists to downregulate systemic response in patients with allergies . drotrecogin alfa (activated) is associated with improved sur- vival . Crit Care Med 2003 ; 31 : A120 . 596 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J surgical intensive care patients . Crit Care Med 1988 ; 16 : 1222 – 1224 . 215 Doglio GR , Pusajo JF , Egurrola MA , et al. Gastric mucosal pH as a prognostic index of mortality in critically ill. ; 21 : S25 – S31 . 128 Lindeborg DM , Pearl RG . Recent advances in critical care medicine: inotropic therapy in the critically ill patient . Int Anesthesiol Clin 1993 ; 31 : 49 – 71 .