A case of maternal preeclampsia presenting as severe hyponatremia is reviewed. The hyponatremia proved refractory to oral fluid restriction and intravenous therapy. Only the delivery of the baby resulted in resolution over 24 hours. The sole cause of the hyponatremia appears to be placental dysfunction, and the mechanisms are discussed. Such cases are rarely reported in the literature and can have severe maternal and neonatal consequences. This case report was reviewed with the patient, and written consent was provided for this publication.
A 37-year-old primiparous woman presented to the labor ward at 40 + 6 weeks in early labor. She had an uncomplicated antenatal history, had no significant medical history, and was not on any medications. The only abnormality seen on the admission blood tests was the serum sodium of 127 mmol/L. Liver function tests, serum proteins, random blood glucose level, free T4, and platelet count were normal. A urinalysis on admission showed “one plus” of protein. Twenty-one hours later, an artificial rupture of membranes was performed. Concurrently, preeclampsia was diagnosed based on 3 diastolic blood pressure measurements over a 5-hour period, all exceeding 90 mm·Hg. A repeat urinalysis was not taken at this time, and spot urinary protein/creatinine ratios are not performed in the institution’s laboratory. At 28 hours, a lumbar epidural was placed for pain management. The anesthesiologist, while checking the platelet count (which was normal), observed that the serum sodium was 122 mmol/L on blood taken 7 hours earlier. The patient was placed on restricted oral fluids and a 0.9% Normal Saline intravenous infusion commenced at 120 mL/h. Enquiries excluded polydipsia, but there had been 2 emetic episodes. There was no diarrhea. No intravenous fluids had been given until the epidural was placed. The patient appeared euvolemic clinically, with minimal cardiovascular changes induced by the epidural. There was no evidence of cardiac failure or liver disease. An oxytocin infusion was not used to augment labor. The anesthesiologist repeated the serum sodium after the epidural, the result then being 120 mmol/L. At this alarming level of hyponatremia, the patient was made nil by mouth and the saline infusion increased to 150 mL/h. Discussions with the obstetrician about the timing of delivery, considering the risk of maternal seizures, then took place. The described management failed to reverse the hyponatremia with the serum sodium remaining at 121 mmol/L at 36 hours postadmission. The serum albumin was 30 g/L at that time. At this point, the patient was taken to theater for an emergency lower segment cesarean delivery for failure to progress, performed under epidural anesthesia. A healthy child was delivered, scoring American Pediatric Gross Assessment Record (APGAR) of 8, 8, and 9 at 1, 5, and 10 minutes, respectively. Ten units of intravenous oxytocin were required to increase uterine tone. The mother was taken to the intensive care unit postoperatively given the use of oxytocin in an already hyponatremic patient. She was allowed no oral intake overnight hence was on a 1.2L oral fluid restriction per day. Twenty units of oxytocin were infused in the first 4 hours of the intensive care admission to maintain uterine tone. Two hours postoperatively, her serum sodium remained at 122 mmol/L, serum osmolality was 252 mmol/kg, urinary osmolality was 405 mmol/kg, and urinary sodium level reported as <20 mmol/L. Liver function tests were normal, and the serum albumin had fallen to 21 g/L. The serum sodium returned to 133 mmol/L 32 hours after delivery. The Table shows the serum electrolyte, urea, creatinine, and glucose levels over this time. Throughout the admission, she remained alert and neurologically stable. At 14 hours postoperatively, the growth hormone was measured at 39.3 mIU/L, adrenocorticotropic hormone at 21 ng/L, and aldosterone (upright) at 750 μmol/L, which were all within the normal range. No sequelae were observed in the infant, although a serum sodium taken 12 hours postdelivery was 127 mmol/L, increasing to 133 mmol/L at 36 hours.
This case appears to be an example of preeclampsia associated with severe hyponatremia, first definitively reported in 1993.1 Camara-Lemarroy et al2 reported what they thought was the 15th case. With few other case reports in the literature, this case may mark the 22nd example.3–5a However, Razavi et al5 state that the syndrome is underreported, claiming that it occurs in 9.7% of preeclampsia cases and more commonly with severe preeclampsia, multiple gestation pregnancies, and advanced maternal age. Given a preeclampsia rate of 10%, the resultant incidence would be 0.97% of all confinements. However, hyponatremia was defined as a serum sodium <130 mmol/L, and the incidence of severe hyponatremia (serum sodium <120 mmol/L) was unreported.6
The pathophysiology of preeclampsia-induced hyponatremia remains unknown. A decrease in serum sodium of 4–5 mmol/L occurs in normal pregnancy. There is an increase in free water retention as the threshold for stimulating the osmoreceptors for antidiuretic hormone (ADH) release is “reset,” presumably as a consequence of increased β-human chorionic gonadotropin.7 A syndrome of inappropriate secretion of ADH can be caused by pain, nausea, stress, and fear alone.8 Other mechanisms, such as vasodilation and subsequent arterial underfilling, are postulated to also increase ADH secretion. But these normal processes of pregnancy do not explain the severity of the hyponatremia in this case. Proposed mechanisms for severe hyponatremia include increased vasopressin sensitivity, placental overproduction of vasopressin, or placental reduction in vasopressinases, all resulting in inappropriate levels of ADH. Unfortunately, although a dysfunctional placental unit is a pleasingly logical fit with preeclampsia for a proposed etiology of severe hyponatremia, the reality is we are uncertain as to why the maternal serum sodium can decline to such low levels. This is partly due to the complexity of the role of ADH in the maternal patient with a variable volume status. Some have proposed measuring urinary sodium levels as a way of detecting inappropriately high ADH levels. Unfortunately, even in hyponatremic patients, ADH levels may be maintained due to hypovolemia. Dilute urine may still occur in this scenario, confusing interpretation.9 Thus, few cases reported meet inappropriate secretion of ADH criteria.2 Only 1 case has demonstrated raised vasopressin levels.1
Having no diagnostic criteria, hyponatremia caused by preeclampsia remains a diagnosis of exclusion. Polydipsia causing severe hyponatremia is reported, often with frightening sequelae.10 However, there was no polydipsia evident with this case. There was no preexisting syndrome of inappropriate ADH secretion. The adrenopituitary axis appeared to be intact, with normal aldosterone, growth hormone, and adrenocorticotropic hormone levels taken 14 hours postpartum. There was no heart failure, liver cirrhosis, or nephrotic syndrome. Admittedly, the absence of quantitative urinary protein measurements does not fully exclude nephrotic syndrome. However, the absence of clinical signs, and a postdelivery serum albumin of 30 g/L at 36 hours, makes it unlikely.
Given the severity of hyponatremia that can occur, there are implications for clinical practice. The maternal effects of severe hyponatremia are significant and potentially fatal when serum sodium falls <120 mmol/L. It is unknown whether the combined effects of preeclampsia and hyponatremia additively increase the risk of seizures. However serious neurological complications, such as central pontine myelinosis have occurred, albeit from inappropriately rapid corrective therapies.11 Less commonly known is the impact on the neonate; a neonate’s serum sodium closely reflects maternal levels.12 The resultant neonatal hyponatremia can cause polyhydramnios, jaundice, and tachypnea.8 Feeding difficulties, cyanotic episodes, and seizures have also been reported. Walter et al13 reported 2 cases of severe hyponatremia in neonates born to hyponatremic mothers; both neonates experienced cerebral edema postnatally.
Despite the severe consequences of missing a diagnosis of preeclampsia-induced hyponatremia, awareness remains low. Published guidelines and reviews on preeclampsia do not address this issue.
Without a proven pathophysiology, it is difficult to recommend therapy. This case, and others like it, suggests that preeclampsia caused the hyponatremia. Logically, it follows that emergent delivery, often required to manage preeclampsia, may be required to manage the hyponatremia. Indeed, the severity of the hyponatremia, and its resistance to therapy, was the trigger for an emergency cesarean delivery in one other case.4 However, this evidence is anecdotal. Prudence suggests that clinicians follow the current guidelines for preeclampsia and treat the hyponatremia conventionally. If delivery needs to be delayed, then oral fluid restriction and isotonic intravenous fluids would seem reasonable. Of course, isotonic fluids may exacerbate hyponatremia in a fluid-overloaded patient; thus, hypertonic saline should always be considered. In this case, fluid overload was considered unlikely. It is important to emphasize that treatment options are based on the severity of symptoms, not absolute levels of serum sodium. Also, the likelihood of symptoms increases with the speed of onset of hyponatremia.14 So, the choice of serum sodium <120 mmol/L as a definition of severe hyponatremia is an arbitrary guide for the likelihood of problems. It is not a therapy guide. Indeed, Verbalis et al14 suggest that 125 mmol/L is a more appropriate cutoff for risk of symptoms in a consensus statement.
In summary, severe hyponatremia induced by preeclampsia is reported rarely. However, given its consequences for both mother and baby, it behooves clinicians to be aware of this condition. This case serves to alert clinicians to the possibility of severe hyponatremia in patients with preeclampsia. With few cases, and little knowledge of the cause, treatment remains empirical. However, the silence of guidelines on this subject is concerning.15 The authors recommend that future guidelines on preeclampsia address the issue of preeclampsia-induced hyponatremia.
Name: Wallace Grimmett, MBBS, FANZCA.
Contribution: This author helped rewrite the original manuscripts, perform the literature searches, and rewrite the resubmissions.
Name: Julie Lee, BPharm, MBBS, FANZCA.
Contribution: This author helped review the original literature search providing extra references, review all rewrites, and provide the expert advice regarding hyponatremia and preeclampsia.
Name: James Doherty, MBBS.
Contribution: This author helped initiate the case study report and provide the original manuscript.
Name: Benjamin Cheung, MBBS, FANZCA, FCICM, VMO.
Contribution: This author helped review all manuscripts, especially with respect to grammar, and provide the guidance regarding management of hyponatremia.
Name: Meher Chinthamuneedi, MBBS, MD, PDCC, FANZCA, FCICM.
Contribution: This author helped review all manuscripts and provide the guidance regarding management of severe hyponatremia in the intensive care setting.
This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.
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