Swelling Concerns: Angioedema in the Pregnant Patient

Case Study

You and your partner are called to a rural residence for a 34-year-old female patient who is pregnant and experiencing a headache. When you arrive on the scene, you find the patient sitting at the kitchen table. You first notice the swelling around her lips; her tongue appears huge and protruding from her mouth. The second thing you notice is that she looks very pregnant. She is alert and oriented and tries to talk to you, but is having difficulty secondary to the tongue swelling. Her sister is there with her and is “translating.” You find out that the patient is approximately 32 weeks gestation with her first pregnancy, with no complications, but hasn’t had any prenatal care. Otherwise, she has no medical history, medications, or allergies. She started to experience a headache about an hour ago, and the tongue swelling began about 15 minutes ago when they called 911. You get the monitor on her, and her vital signs are as follows: HR 113, sinus, B/P 187/96, O2 sat 97% on room air, Resp 22, and glucose 103. You continue your assessment and find that her skin appears normal, warm, and dry, PERRL, lungs are clear, abdomen is gravid but otherwise unremarkable, upper extremities are normal, and lower extremities are edematous. What do you do?

Bradykinin-Mediated Angioedema

My friend Tyler wrote a blog about angioedema not too long ago. He discussed the difference between histamine-mediated and bradykinin-mediated presentation. You can read his blog here:

For this blog, I will stick to the bradykinin-mediated presentation of the patient's pathophysiology in the case study.

Bradykinin is a chain of nine amino acids that increases the inflammatory response. It works as a vasodilator, creating capillary leakage and swelling, mainly affecting the tongue, face, lips, and upper airway. It also frequently affects the GI tract, creating generalized abdominal pain, nausea, vomiting, and diarrhea.

Bradykinin-mediated angioedema usually presents slower, sometimes over hours, can continue for days if left untreated, and can be preceded by general flu-like symptoms. Unlike a typical histamine release or anaphylactic reaction, the patient usually won’t have red, itchy skin with other manifestations like hives or urticaria. In addition, it’s likely the remaining airway and lungs will be unaffected. Does that mean that it won’t happen? Nope; we all know patients don’t follow the rules.

Pregnancy-Induced Hereditary Angioedema

Hereditary angioedema is a genetic condition in which the body doesn’t make enough C1-esterase inhibitor proteins (Type I) or doesn't make enough of the protein but doesn’t utilize it properly (Type II). Most people who have hereditary angioedema have a family history of it. However, this condition can happen spontaneously, meaning a mutation could happen randomly without the person having a history in their family and not knowing they have the condition.

A pregnant patient experiencing angioedema is a rare disease pathology; however, it can be something you could encounter in your career. Take it from me because I have cared for the patient above. A pregnant patient with hereditary angioedema can manifest in many ways, including stress, changes in estrogen levels, increased plasma levels, and or preeclampsia/eclampsia.

During pregnancy, estrogen levels increase significantly. This estrogen level change can alter the bradykinin pathway by decreasing C1-esterase protein levels; however, how this happens isn’t completely understood. There are also inconsistencies in how this affects women with a history of hereditary angioedema. In one study I read, women who know they have hereditary angioedema have reported vast differences in whether they have had increased numbers of angioedema attacks when pregnant. 38% reported they have had increased instances of angioedema, and 30% reported no changes at all during pregnancy.

Airway Management

The airway is always the priority, and in the words of Ken Larson, oxygenation is king. If the patient can no longer maintain their airway and you need to intervene, your actions may depend on your scope of practice. For BLS providers, using NPA and OPA, with BVM and suctioning, is reasonable for continuing to ventilate and oxygenate the patient. Supraglottic airways may buy you time until you deliver the patient to definitive care or can intercept with an ALS or Critical Care team.

If you plan to RSI the patient, carefully consider the medications you choose for induction. Ketamine is not recommended for patients with angioedema. Although Ketamine has bronchodilatory properties, it may promote catecholamine release, which could theoretically worsen swelling in some cases of hereditary angioedema. The catecholamine surge can increase endothelial cell permeability, thus increasing fluid leaking into the tissues and resulting in increased swelling.

Succinylcholine is also not recommended. Succinylcholine triggers histamine release from mast cells, which can lead to vasodilation and increased vascular permeability. This can worsen angioedema for those who already have a high bradykinin level. Also, Succinylcholine mimics acetylcholine at some receptors, activating bradykinin downstream and increasing its production, increasing swelling.

Another thing I found interesting about Succinylcholine is the need to exercise caution with pregnant patients. During pregnancy, plasma levels increase by 40% to 50% by the third trimester. Because of this, pseudocholinesterase levels in the plasma decrease, leading to Succinylcholine spending more time in the bloodstream and not being metabolized. This means more is reaching the receptors, resulting in longer paralysis time.

In this case, the safest medications to facilitate intubation would be Etomidate, Fentanyl, and Rocuronium. Propofol and Vecuronium would also be safe and considered for continued sedation and paralysis.

Interventions & Treatments

Treatment for pregnancy-induced angioedema is the same as treatment for non-pregnant patients. It’s important to note that standard treatments for allergic reactions, such as epinephrine, antihistamines, and corticosteroids, are generally ineffective in HAE, as the condition is not mediated by mast cells. It’s worth a try, though, if you are uncertain if the reaction is truly HAE.

The preferred treatments for acute management of hereditary angioedema (HAE) are Berinert, a C1 esterase inhibitor concentrate, or Icatibant, a bradykinin B2 receptor antagonist. Unfortunately, these medications are often unavailable outside of tertiary care centers, and even in those settings, they may not be consistently stocked.

In situations where first-line agents are inaccessible, fresh frozen plasma (FFP) can be used as an alternative. FFP contains C1 esterase inhibitor and may help mitigate symptoms, but it typically provides only partial or delayed relief and, in some cases, may exacerbate symptoms due to additional bradykinin release. For adults, you can administer two units of type AB FFP. For patients weighing less than 50kg, it is recommended that you obtain type-specific FFP. This reduces the chance of adverse reactions during administration.

Another treatment option is the administration of Tranexamic Acid (TXA). TXA inhibits the activation of Plasminogen to Plasmin, reducing the amount of bradykinin produced. One gram can be administered slowly via IV push over 10 minutes. Thankfully, TXA is a medication that is usually readily available on an ALS truck or in the local emergency department.

In this specific case, the patient is also pre-eclamptic. To prevent seizure activity and provide neuroprotection to the fetus, a 4-gram loading dose of Magnesium followed by a 2-gram an hour infusion should be administered.

Blood pressure control can be addressed using a beta blocker or a calcium channel blocker. Nifedipine is a great option; however, it is typically not carried prehospital. The dose would be a 10mg tablet every 10 minutes x3. Nifedipine also works well concurrently with Magnesium, according to an OBGYN I recently discussed with, "They are besties".

An option that may be more readily available is Labetalol. The initial dose of Labetalol for treating severe hypertension in preeclampsia is 20 mg administered intravenously over two minutes. If the blood pressure remains elevated, systolic pressure of 160 mmHg or higher, or a diastolic pressure of 110 mmHg or higher, an additional 40 mg IV dose may be given after 10 minutes. If further control is needed, 80 mg IV can be administered every 10 minutes as necessary, with a maximum cumulative dose not exceeding 300 mg.

As always, you'll need to monitor the fetal heart rate, whether ultrasound or doppler, at least every 15 minutes. Fetal heart rate can vary based on gestational age and activity, but it should typically be between 120 and 160 bpm.

Anything higher or lower can be indicative of fetal distress and can be a good indicator of how well you are resuscitating the mom. Be aware that the patient could have perfect vital signs, and the fetus could still be poorly perfused and or oxygenated. If the fetus is showing signs of distress, consider additional oxygenation, fluids, and placing the mom in the left lateral position if able. In addition, regularly assess if there are any premature rupture of membranes, contractions, or vaginal bleeding.

Case Study Continued

This patient was transported to the local emergency department and received TXA along with FFP. Invasive airway management wasn't required. In addition, the patient’s hypertension/preeclampsia was addressed with Nifedipine and Magnesium. She was transferred by helicopter to a facility with Level I medical ICU services, along with OB services and adjacent Level IV NICU capabilities. Both the patient and the baby did well.

“The moral responsibility of the healer is to step inside the patients’ experiences and accompany them through the worst moments with empathy and expertise” -Dr. Paul Farmer

Resources

Agostoni, Angelo, et al. “Hereditary and Acquired Angioedema: Problems and Progress: Proceedings of the Third C1 Esterase Inhibitor Deficiency Workshop and Beyond.” Journal of Allergy and Clinical Immunology, vol. 114, no. 3, 1 Sept. 2004, pp. S51–S131, www.jacionline.org/article/S0091-6749(04)01757-9/fulltext#secd2250489e9961, https://doi.org/10.1016/j.jaci.2004.06.047. Accessed 7 Mar. 2021.

Hasara, Shannon, et al. “Tranexamic Acid for the Emergency Treatment of Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema.” Cureus, 20 Sept. 2021, https://doi.org/10.7759/cureus.18116.

Hébert, Jacques, et al. “Bradykinin-Induced Angioedema in the Emergency Department.” International Journal of Emergency Medicine, vol. 15, 26 Mar. 2022, p. 15, www.ncbi.nlm.nih.gov/pmc/articles/PMC8966254/#:~:text=Bradykinin%20binds%20the%20bradykinin%20B2, https://doi.org/10.1186/s12245-022-00408-6. Accessed 29 Mar. 2023

“Hereditary Angioedema (HAE) Symptoms, Causes & Treatment.” Cleveland Clinic, 31 Mar. 2025, my.clevelandclinic.org/health/diseases/hereditary-angioedema. Accessed 1 Apr. 2025.

Hick, John. Pregnancy Induced Hereditary Angioedema. 11 Mar. 2025.

Pirahanchi, Yasaman, and Sandeep Sharma. “Physiology, Bradykinin.” Nih.gov, StatPearls Publishing, 6 Jan. 2019, www.ncbi.nlm.nih.gov/books/NBK537187/.

Ward, R. M., & Varner, M. W. (2019). Principles of Pharmacokinetics in the Pregnant Woman and Fetus. Clinics in Perinatology, 46(2), 383–398. https://doi.org/10.1016/j.clp.2019.02.014