Should we Systematically Measure Plasma Magnesium Levels in the Treatment of Severe Preeclampsia/Eclampsia?

Introduction

Magnesium sulfate administration is essential in the treatment of severe preeclampsia/eclampsia [1, 2, 3]. The treatment monitoring is essentially clinical, except in cases of renal failure [4, 5]. However, acute renal failure may be included in the clinical picture of severe preeclampsia/eclampsia. This purely clinical approach seems to underestimate actual frequency of magnesium overdose in the treatment of severe preeclampsia/eclampsia. Thus, through this reports of clinical series, we want to check the relevance of clinical examination in detecting magnesium overdose signs in severe preeclampsia/eclampsia with measuring magnesium plasma levels.

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Patients and Methods

This is a retrospective study of all patients that were hospitalized in surgical intensive care from 2008 to 2013 for severe preeclampsia/eclampsia and received magnesium sulfate treatment with a biological monitoring of magnesium levels. The approval of the ethics committee was required. For the inclusion of patients, we conducted a study of clinical records of obstetric patients. From this set, severe preeclamptic/eclamptic patients were identified. We then turned our attention to patients whose magnesium had been measured through treatment monitoring (Figure 1). The definitions of severe preeclampsia/eclampsia are those given by scholarly associations [4]. The magnesium sulfate was administered according to the protocol of the French Society of Anesthesia and Intensive Care [6]. The recommended therapeutic concentrations are between 2 and 4 mmol/l (4 and 8 mEq/l) [4]. The data is expressed in averages (first quartile-third quartile).

Results

Ten patients were admitted for severe preeclampsia/eclampsia. Six of them had received biological monitoring of magnesium sulfate treatment (Figure 1).

From these measurements, we point out that magnesium was above therapeutic concentrations in two patients, while it was below the therapeutic range for the other four patients (Table 1). Paradoxically, signs of overdose were present in only one patient, with magnesium levels at 1.8 mEq/l. additionally; the duration of treatment was practically identical in five of the patients that were treated for severe preeclampsia/eclampsia. For the sixth, the treatment duration was very brief (one hour) and the magnesium levels were low. In this patient, hereditary hypofibrinogenemia was ultimately diagnosed. Systolic blood pressure at admission was moderate (≥ 90 mmHg and < 110 mmHg) for three patients. Diastolic blood pressure was severe (> 110 mmHg) for one patient and moderate (≥ 90 mmHg < 110 mmHg) for another. Caesarean section performed under general anesthesia was the most frequent mode of delivery (5 cases). A history of fetal death and preeclampsia were present in two and three cases, respectively. The average lactate was 0.8mmol/l (0.7-2.0 mmol/l). Two patients were intubated and ventilated upon admission. Liver failure was present in three patients. The average rate of AST enzymes was 49 (21-763 IU/l) and the ALT, 21 (10-438 IU/l).

Creatinine was high for all patients, with an average of 145 (76-183 µmol/l) (Table 2). The average prothrombinemia rate was 76%, and thrombocytopenia was present in five patients, including one severe case. Despite these organ failures, no deaths were recorded. The median length of stay in the ICU was 4 days (1-8 days). The complications that arose during these stays were hemodynamic pulmonary edema (2 cases) and nosocomial bacterial pneumonia (1 case).

Discussion

The improvement of obstetric care has undoubtedly contributed to the reduced frequency of female admissions to the ICU. However, this study had the risk of being a small sample size. Over an observation period of six years, only six patients met the inclusion criteria set out in our work. Despite this, the information drawn from this study cannot be seen as any less important. First, therapeutic concentrations can be surpassed quickly with the administration protocol developed by scholarly associations [6, 7]. The role of initial renal failure can then be discussed. Dose reduction is suggested by urinary magnesium excretion reduction [8]. In addition, four patients had subtherapeutic plasma concentrations, and eclampsia was diagnosed in one of these patients. Underdosing may have played a role. Second, the absence of severe clinical presentations related to magnesium sulfate overdose as reported in numerous scientific works, and where the monitoring of treatment was limited to clinical examination alone, should under no circumstances discourage the biological examination. Indeed, there is no parallel between the clinical signs and the plasma concentration of magnesium.

The choice between the measurement of ionized or non-ionized magnesium remains under debate. For some authors, the ionized magnesium measurement seems essential because of pathophysiological changes induced by the disease; for others, however, the biological determination in one form or another was sufficient because of the correlation that exists between the two [4, 9, 10]. Third, early treatment of severe preeclampsia/eclampsia based on clinical presumption can turn out to be unjustified. Indeed, symptoms and clinical signs of the disease can be included in the clinical picture of many other conditions [8]. One of our patients had early treatment with magnesium sulfate based on the clinical presumption of severe preeclampsia. This fact highlights the need for a rigorous management approach, which must take into account different diagnoses. The observed complications, nosocomial bacterial pneumonia and hemodynamic pulmonary edema, would be the consequences of severe preeclampsia/eclampsia. Additionally, it may be accompanied by neurological issues of varying degrees, exposing the patient to the risk of pulmonary aspiration and secondary pneumonia. Moreover, increased systemic vascular resistance, an essential component of high blood pressure in preeclampsia/eclampsia, exposes the left ventricular to dysfunction. This is compounded by the reduction of edema and vascular filling often in hypovolemic patients [11, 12, 13, 14, 15, 16, 17]. If persistent hypertension (10.4%), generalized edema (7.1%) and severe thrombocytopenia (6.2%) were the major complications in the Kuwaiti study, in other studies they were represented by pulmonary edema, acute renal failure, aspiration pneumonia and cardiac arrest [11, 12, 18, 19]. Moreover, the demographic characteristics of our patients do not differ from those of other authors [16, 18]. Conclusion In light of the above, monitoring magnesium plasma concentration in the treatment of severe preeclampsia/eclampsia seems necessary as underdosing and overdosing remain possible. However, the weakness of our numbers prevents us from making a recommendation in this regard. Conducting a larger study will undoubtedly create a consensus concerning this aspect of therapeutic care. References

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