I think it is pretty safe to assume that most of us have a specific patient population that makes us squirm just a bit when we hear it mentioned over the radio. For many of us, it stems from a deficit in initial education surrounding all the intricacies and considerations that accompany each of these special populations. When I hear tones for an obstetric patient, I re-think my life choices for a couple of seconds. Obstetric education in nursing and EMS especially, spends a surplus of time with the management of patients during active labor but very little in the management of high risk critically ill patients. Clinicians should be just as well versed in the management of pregnancy induced hypertension, preeclampsia and eclampsia.
I’m pretty new in my role as a flight provider and as I was getting ready for the CFRN, I realized just how intimidating high risk OB patients can be. Even with experience in the ED, patients over 20 weeks pregnant would bypass us and head straight for the antepartum unit. As luck would have it, my very first call on the flight line was for an inter-facility transfer (though it turned out to be more akin to a hostage rescue) from a critical access ED. This 32 year old woman was dropped off by an unknown companion. He shared no other information apart from her being pregnant. Prior to our arrival she had suffered from several seizures requiring intubation. When we arrived her BP was 210/120 with a HR of 140 and she was over breathing the vent by at least twice the set rate. We took over care and started setting our priorities, the first being sedation. After getting her sedated appropriately, her pressure was 160/110 and the staff had a urine showing 3+ protein confirming the diagnosis of eclampsia. As a refresher, Preeclampsia = Hypertension + Proteinuria; Eclampsia = Preeclampsia + Seizures. We followed the standard treatments focused on blood pressure control and seizure prophylaxis and I was thankful the remainder of the transport was unremarkable. Following the flight, my preceptors and I took a minute to debrief a bit and we all came to the same general consensus... Thank God for protocols because we could not have managed her as smoothly as we did without them. In fact, all three of us agreed that we had next to no real idea what preeclampsia was at a pathophysiologic level and we imagined we weren’t alone.
Very little is known about the pathogenesis of preeclampsia. I for one, feel the most proactive with patient management if I can truly have a comprehensive understanding of the disease process affecting them. While preeclampsia is a complex disease process, it is better understood if we can relate the information to concepts we already know and understand. While we may not know all that much about the pathogenesis of preeclampsia, we sure do know quite a bit about the pathogenesises of hypertension.
What little we do know is preeclampsia is a congenital disorder of the placenta, hence the development later in pregnancy. Placental ischemia results via two specific mechanisms. The first is through an overproduction of a protein, tyrosine kinase 1, which acts as an antiangiogenic. This essentially limits the growth of new arterioles as the placenta forms, leading to an increased vascular resistance. The second mechanism is through an inhibition of endothelial nitric oxide synthase (e-NOS) leading to vasoconstriction of the placental bed (El-Sayed, 2017).
While at the surface this is just complex medical jargon, the important takeaway is a resulting increase in placental vascular resistance that eventually turns systemic using the same pathways. Now that isn’t so scary! Increased vascular resistance is a concept that we as clinicians understand and see all the time in our chronically ill patients. Think of your typical geriatric dialysis patient... their uncontrolled hypertension of 20+ years has obliterated their organ systems over time. Imagine taking 20 years of uncontrolled hypertension and confine it to 28 year old woman, carrying a 20 week fetus inside her. The symptomatology isn’t all that different at the end of the day!
Principle #1: Preeclampsia is a multi-organ disease
One of the most missed concepts in the management of preeclamptic patients is the fundamental understanding that inhibited e-NOS leads to systemic vasoconstriction, not just in the placenta. Profound vasoconstriction leads to increased blood pressure and subsequent endothelial destruction. The usual victims: the kidneys, liver, brain and lungs.
Increased pressure to kidneys increases permeability of the proximal tubules leading to proteinuria, a pre-requisite in the diagnosis of preeclampsia. What seems like a relatively insignificant finding has profound effects on a patient’s hemodynamics when we recall that albumin, a protein, is heavily responsible for maintaining oncotic pressure in the blood vessels. The loss of albumin met with an increased capillary permeability from damaged endothelium are the two items in the recipe of interstitial edema, a classic finding in preeclamptic patients.
The next organ on the hit-list is the liver. A resultant decrease in perfusion to the liver exists by the same antiangiogenic mechanisms discussed above however in the most severe cases, HELLP syndrome may occur. HELLP is one of the few things I personally remember from my obstetric education. However, extent of that recollection ends at the acronym Hemolysis Elevated Liver Low Platelets. Although only occurring in 0.2-0.8% of pregnancies, 80% of the cases exist with preeclampsia (Abildgaard & Heimdal, 2013). For the sake of brevity, I think HELLP is best left there as it could be an entirely separate blog in and of itself. The classic high yield bit of info that most of us probably remember is that preeclampsia + seizures = eclampsia. While correct, I’m sure few (except Sam) can recite the mechanism for this change. Essentially if uncorrected, the combination of systemic and cerebral vasoconstriction met with profound edema produces seizures. I went all through my obstetric education thinking that seizures were almost a guarantee for patents undergoing treatment for pre-eclampsia. It was portrayed to me as an inevitable complication when in reality, the occurrence is as low as 1.6 in 10,000 pregnancies (0.016%) in developed countries (Fishel Bartal & Sibai, 2020). Despite the low incidence, prevention of seizure activity should remain of high concern as the hypoxia that follows can be fatal to both mom and baby. Prevention and management of seizures is discussed more below under Principle #3. The last victim of the eclamptic assassin is seldom considered. The lungs are involved in the highest incidence of complication for preeclamptic patients though almost none of us even know to look!
Principle #2: Pulmonary edema is the most common severe complication
Pulmonary edema is considered to be the most common severe complication of these patients occurring in as many as 7% of all cases (Kubota-Sjogren & Nelson-Piercy, 2015). The trouble with preeclamptic pulmonary edema is that it often exists with perfectly clear lung sounds on auscultation, leading even some of the more experienced clinicians to miss it altogether. Capillary bed destruction and hypoalbuminemia is the recipe for edema, as previously discussed. However as this isn’t a chronic destruction, the capillary beds may not degrade enough to allow for fluid to build up all the way into the lungs. This leads to an interstitial edema taking place between the pulmonary capillary beds and the alveolus. This covert edema can be almost undetectable until it interferes with gas exchange enough to alter oxygen saturations. It takes astute prehospital clinicians to recognize preeclamptic non-caridogenic pulmonary edema as a severe complication. This is one particular area that I believe, if recognition improves, we can and make a difference.
Management of preeclamptic non-cardiogenic pulmonary edema shouldn’t be foreign to us. This disease process is one of altered oxygenation of which we are heavily trained to combat. Increasing FiO2 (the fraction of inspired oxygen) for a preeclamptic patient by means of supplementation is done as if she were any other medical patient. The pause should come when we discuss the use of PEEP (positive end expiration pressure) through CPAP or BiPAP. While PEEP is a powerful tool in the oxygenation battle, we should take into account the increase in abdominal pressure pushing up against the diaphragm and lungs. Given that we aren’t initially attempting to move fluid from the lungs back into the bloodstream (as is often the case in cariogenic pulmonary edema) lower PEEP pressures (2-4cm/H2O) may be beneficial as all we are attempting to do is leverage Fick’s Law by thinning out the thickness of the alveolar membrane. Admittedly this is more of a thought experiment as the evidence for CPAP in preeclampsia is focussed entirely on the treatment of sleep apnea rather than pulmonary edema.
Principle #3: Magnesium is a life-saving intervention
While the only definitive treatment for preeclampsia is delivery of the baby, medical management focuses on blood pressure control and seizure prophylaxis. Magnesium remains the drug of choice for initial and ongoing management, but why and what does it actually do? One of magnesium’s most potent functions is as a smooth muscle dilator. This derives its applications in the treatment of bronchospasm, cardiac dysrhythmias and yes... preeclampsia. As discussed above, preeclampsia is a disease of placental ischemia and insufficiency sparking systemic vasoconstriction and endothelial injury. Magnesium acts to promote cerebral vasodilation and minimize the risk of seizures by more than 50% for women with severe preeclampsia (Duley, Gulmezoglu, Henderson-Smart & Chou, 2010). That is far too successful to ignore in my opinion.
Well, great that it is so effective, but how much are we supposed to be giving? Most magnesium protocols focus on a high dose bolus (typically 4grams over 20min) followed by an infusion of 2-4g/hour. I don’t know about you, but these numbers have always made me squirm. For those of us who have given magnesium in the past for the treatment of bronchoconstriction or cardiac dysrhythmias, you have likely noticed what happens when given too quickly. Not only does the administration burn, but patients can get hypotensive and drowsy. I have seen that toxicity happen at doses as low as 1g/hour for patients who already had therapeutic levels prior to administration. If we recall, normal therapeutic magnesium levels are around 1.5-2.2mg/dL and in a healthy patient with adequate renal function, toxicity is rare as it is readily excreted. That is all fine and sensible, but what if we are now giving upwards of 6 grams in that first hour? Can that really be safe? YES! In fact, for every 1g of magnesium a serum change of 0.18mg/dL can be expected (Hansen & Bruserud, 2018). Given that therapeutic levels for preeclamptic patients hovers around 7.0mg/dL, we shouldn’t fear administering high doses when clinically indicated.
I have the cure for what Magnesium?ales you Knowing the normal therapeutic levels are helpful, but in the prehospital environment, we typically don’t have any means of measuring electrolyte levels. Luckily we can evaluate for therapeutic levels through clinical assessment. Deep tendon reflexes (DTRs) are a highly sensitive indicator used to evaluate for toxicity. In fact, loss of DTRs is the first clinical sign of magnesium toxicity (Nanduri, Saleem & Khalaf, 2020). In the event your patient does become toxic, chances are you already carry the cure! Intravenous calcium as either calcium chloride or calcium gluconate can be used to offset the intracellular load of magnesium and reverse severe signs and symptoms. In an effort to maintain electrical neutrality both cations will displace one another depending on the intravascular availability.
Preeclampsia is a severe condition that threatens the lives of both mother and baby if unrecognized and untreated. EMS responders are often the first on the scene of severely ill pregnant women and should be well versed in their understanding and management of this disease. In surveying several peers, I learned that many LEMSA protocols allow for the administration of magnesium only after an eclamptic seizure has taken place. There seems to be room to start conversations with your medical directors about policy and procedure that focuses on the early recognition and management of preeclampsia in the field. Prevention of seizures is best done with aggressive administration of magnesium though in conversations with many prehospital providers, they are far more comfortable with treating via benzodiazepines like midazolam. While it is certainly easier to administer when compared to a magnesium infusion, it doesn’t address the root of the issue... impaired cerebral blood flow. At the end of the day, the last thing any of us want is for a 30 week pregnant patient to seize on our watch. So... reach for the mag!
Peer Review: Nicholas Leyva FPC & Tabitha Kovac RN
Abildgaard, U., & Heimdal, K. (2013). Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): A Review. European Journal of Obstetrics & Gynecology and Reproductive Biology, 166(2), 117-123. https://doi.org/10.1016/ j.ejogrb.2012.09.026
Duley, L., Gulmezoglu, A. M., Henderson-Smart, D. J., & Chou, D. (2010). Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database of Systematic Reviews. https://doi.org10.1002/14651858.cd000025.pub2
El-Sayed, A. A. F. (2017). Preeclampsia: A review of the pathogenesis and possible management strategies based on its pathophysiological derangements. Taiwanese Journal of Obstetrics and Gynecology, 56(5), 593-598. https://doi.org/10.1016/j.tjog.2017.08.004 Fishel Bartal, M., & Sibai, B. M. (2020). Eclampsia in the 21st Century. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2020.09.037
Kubota-Sjogren, Y., & Nelson-Piercy, C. (2015). Fulminant antenatal pulmonary oedema in a woman with hypertension and superimposed preeclampsia. BMJ Case Reports. https://doi.org/ 10.1136/bcr-2015-212751
Hansen, B. A., & Bruserud, O. (2018). Hypomagnesemia in critically ill patients. Journal of intensive care, 6, 21. https://doi.org/10.1186/s40560-018-0291-y
Nanduri, A., Saleem, S., & Khalaf, M. (2020). Severe hypermagnesemia. Chest, 158(4). https:// doi.org/10.1016/j.chest.2020.08.946