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Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 3  |  Page : 366-372  

Ultrasonographic changes in transorbital measurement of optic nerve sheath diameter in magnesium sulfate-treated severely preeclamptic patients: A prospective observational study


1 Department of Obstetrics and Gynaecology, Teerthankar Mahaveer Medical College, Moradabad, Uttar Pradesh, India
2 Department of Anaesthesia and Pain, Teerthankar Mahaveer Medical College, Moradabad, Uttar Pradesh, India
3 Department of Surgery, Teerthankar Mahaveer Medical College, Moradabad, Uttar Pradesh, India
4 Department of Obstetrics and Gynaecology, Venkateshwara Institute of Medical Sciences, Gajraula, Amroha, Uttar Pradesh, India
5 Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Karnataka, India

Date of Submission25-Jul-2022
Date of Decision03-Sep-2022
Date of Acceptance13-Sep-2022
Date of Web Publication09-Dec-2022

Correspondence Address:
Asst. Prof. Radhika S Bhogawar
Department of Obstetrics and Gynaecology, Venkateshwara Institute of Medical Sciences, Gajraula, Amroha, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.aer_117_22

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   Abstract 

Introduction: Severe preeclampsia can lead to various complications including increased intracranial pressure (ICP) which can be catastrophic but difficult to detect because of variable nonspecific symptoms. Ultrasonography has been used as noninvasive measure to monitor optic nerve sheath diameter (ONSD) as a marker of raised ICP. Effect of MgSO4 on ICP can modify the management approach, need for additional monitoring, targeting hemodynamic goals, timing of delivery, and choice of anesthesia. We evaluated the effect of MgSO4 on raised ICP in severely preeclamptic patients using ultrasound-guided ONSD as a surrogate marker of ICP. Methodology: This prospective observational study was conducted after ethical committee approval and written informed consent from patients. Ultrasound-guided ONSD was measured and compared in 47 severe preeclamptic patients before and at 1 h, 4 h, 12 h, and 24 h after starting MgSO4 therapy. The analysis of data was done by one-way analysis of variance using Statistical Package for the Social Science. Results: Mean ONSD was 5.56 ± 0.30 mm in our study group. ONSD above 5.8 mm was seen in 17 (36.17%) patients and was considered as marker of raised ICP. There was a significant decrease in ONSD after 4 h of administration of MgSO4. No significant correlation was observed between mean arterial pressure, serum magnesium level, and ONSD. Conclusion: Ultrasound-guided ONSD measurement can be used as a quick, noninvasive bedside tool in severe preeclamptic patient on MgSO4 treatment as marker of ICP which help us in determining clinical severity, therapeutic response, and to decide further course of management.

Keywords: Intracranial pressure, magnesium sulfate, optic nerve sheath, preeclampsia, ultrasound


How to cite this article:
Rani K, Jain P, Bhogawar SD, Bhogawar RS, Prasad MK, Choudhary AK. Ultrasonographic changes in transorbital measurement of optic nerve sheath diameter in magnesium sulfate-treated severely preeclamptic patients: A prospective observational study. Anesth Essays Res 2022;16:366-72

How to cite this URL:
Rani K, Jain P, Bhogawar SD, Bhogawar RS, Prasad MK, Choudhary AK. Ultrasonographic changes in transorbital measurement of optic nerve sheath diameter in magnesium sulfate-treated severely preeclamptic patients: A prospective observational study. Anesth Essays Res [serial online] 2022 [cited 2023 Feb 3];16:366-72. Available from: https://www.aeronline.org/text.asp?2022/16/3/366/363126


   Introduction Top


Preeclampsia and eclampsia constitute the most common causes of hypertensive disorders in pregnancy, leading to many perinatal and maternal deaths worldwide. Preeclampsia involves multiple organ systems and is characterized by the development of high blood pressure with proteinuria after 20 weeks of gestation. Data suggests that this condition affects 7%–10% of all pregnancies.[1],[2],[3] However, preeclampsia may be associated with various complications such as pulmonary edema, deranged liver function, thrombocytopenia, renal impairment, recent-onset visual disorder, cerebral disorder,[4] increased intracranial pressure (ICP), intracranial hemorrhage, acute renal failure, congestive heart failure, placental abruption, disseminated intravascular coagulation, hypertensive encephalopathy, and retinal detachment, leading to 12% of total maternal mortality.[5]

Increased ICP is one of the most feared consequences of preeclampsia,[6] and can progress to eclampsia a more serious complication in severely preeclamptic pregnant patients.[7] However, the clinical signs of increased ICP show delayed presentation and are nonspecific in nature such as headache, blurred vision, vomiting, lack of energy, and making them difficult to identify. In 10%–15% of preeclamptic patients who develop seizures, there are no systemic signs of brain pathology.[8] Progression to eclampsia increases the risk of cerebrovascular accident, long-term neurologic consequences, and neurocognitive dysfunction.[9] Moreover, presentations of preeclamptic features can be deceptive as explained previously when identifying increased ICP. The gold standard invasive procedure for determining ICP which has many complications is to insert an intraventricular catheter through a burr hole.[10] Ultrasound-guided ONSD measurement has been used in many studies as a reliable, quick, bedside, and noninvasive modality to assess raised ICP.[1],[11] ONSD has been used in pregnancy-induced hypertension (PIH) as an indirect measure of increased ICP as raised ICP exerts pressure on subarachnoid space around the optic nerve hence increasing the sheath diameter.[12],[13]

Because the optic nerve sheath is a direct extension of the meninges, the optic nerve sheath diameter (ONSD) could be utilized as an indirect marker for elevated ICP. A study conducted on neurotrauma patients showed that the sensitivity and specificity of bedside sonographic measurement were 93.2% and 91.1%, respectively, in comparison to CT scan. The ONSD had a positive and negative predictive value of 89.1% and 94.4%, respectively, in identifying elevated ICP, according to this study.[14]

The use of magnesium sulfate (MgSO4) to treat eclampsia dates back to 1925. Its use continues to this day and had decreased the risk of conversion from preeclampsia to eclampsia by more than 50%.[15],[16] MgSO4 prevents and decreases seizure recurrence in severe preeclamptic and eclamptic patients.[16]

However, understanding the effect of magnesium used for seizure prophylaxis on ICP could modify the line of management, including the requirement for supplemental monitoring, change in hemodynamic goals, and use of other measures to reduce ICP. It may also revise the delivery time and choice of anesthesia.[6]

A medical literature database search literature search did not reveal any study on ONSD and ICP changes following Mg administration in preeclamptic patients revealing that the effect of MgSO4 on ONSD in severely preeclamptic patients has not been studied in any study up to date.

The aim of this study was to assess the effect of MgSO4 on increased ICP in severely preeclamptic parturients using USG-guided ONSD as a measure of ICP. Considering ONSD as a surrogate marker of ICP, our null hypothesis is that, in severely preeclamptic parturients, MgSO4 will not lead to a decrease in the increased ICP.


   Methodology Top


The study was conducted through a joint coordinated effort between the department of obstetrics and gynecology and anesthesia after ethical committee approval. It was observational study prospective in nature. The Indian Clinical Trials Registry (ICMR-NIMS) ID of the study is CTRI/2019/08/020951. Our study falls into the prospect of the Strengthening the Reporting of Observational studies guidelines, in accordance with enhancing the quality and transparency of health research reporting guidelines.

Fifty parturient who gave written informed consent were recruited for the study. These antenatal patients were admitted after fulfilling the diagnostic criteria of severe preeclampsia, as per the guidelines provided by the American College of Obstetricians and Gynaecologists Task Force[4] on hypertension in pregnancy, and were scheduled to receive MgSO4 therapy before delivery. Patients diagnosed with severe preeclampsia were managed with antihypertensive, MgSO4, and termination of pregnancy. Pritchard's MgSO4 regimen of loading doses of intravenous 4 g and intramuscular dose of 10 g with maintenance dosing of 5 g intramuscular every 4 h in alternate buttocks was followed in all patients.[17] All patients with previous ocular surgeries or ocular trauma; patients who underwent cranial surgeries or with intracranial pathology; patients with chronic hypertension, hyperthyroidism, severe myopia, or glaucoma; patients with deranged renal function with oliguria; patients with preexisting cardiac or pulmonary pathology; patients with altered mental status; patients who were severely preeclamptic that had already started MgSO4 therapy; and patients who developed seizures were excluded from the study. Every effort was taken to ensure patient comfort and minimize pain. The procedure was done by a senior anesthesiologist who had performed more than 50 ONSD ultrasonography examinations and took around 2 min. The ONSD was compared in all severely preeclamptic patients before the administration of magnesium sulfate and serially thereafter at 1st, 4th, 12th, and 24th h. Patients were comfortably laid down in a supine position. High frequency (7–12 MHz) probe (linear array) (Micromaxx, Sonosite, USA) was kept horizontally over the closed eyeball on its superior aspect without any undue pressure. The wrist joint was rested lightly over the forehead for better stability. Using the B scanning mode (two-dimensional), the probe was positioned in a manner to appreciate the entry of the optic nerve into the eye globe. The ONSD width was calculated around 3 mm posterior to the optic disc; perpendicular to the vertical axis of the plane scanned. The final ONSD value used for calculation in our study was the average of three measured values from each eye.[7] Patients with ONSD above 5.8 mm were suspected to have increased ICP.[18],[19] The change in ultrasound-guided ONSD measurement before and after MgSO4 treatment in severely preeclamptic patients constituted the primary outcome. The secondary outcome was the changes in hemodynamic parameters and the correlation between ONSD and mean arterial pressure and levels of serum magnesium. Heart rate (HR), systolic, diastolic, and mean blood pressure (SBP, DBP, and MAP) were serially recorded. Any associated symptoms or complications were noted.

Apart from ONSD, all observations were recorded by an observer who was not aware of the ONSD values. We used the software “G-Power” version 3.1.9.2 for determining the accurate sample size. The minimum sample size needed was 45, with a one-tailed significance level of 5% (alpha = 0.05) and the power of the study (1-beta) being 0.95. The total sample size was increased to 50 to account for any loss or dropout of patients from any reason during the study. Data were recorded in an Excel sheet and all calculations were performed using SPSS (Statistical Package for the Social Sciences; SPSS Inc., version 21). The data are expressed as average mean and standard deviations (SD). Quantitative data were reported as frequencies and in percentage values. We used a one-way analysis of variance test to compare numerical variables at different time intervals, and for analyzing variables between two different time intervals in the test group, a post hoc test (Tukey's test) was applied. For analysis purpose, P < 0.05 was considered statistically significant. The correlations between MAP, serum magnesium level, and ONSD were calculated by simple linear regression.


   Results Top


A total of 56 patients were included; however, six patients were excluded from the trial as some declined to participate and others did not match the inclusion requirements. One patient developed seizure so was excluded from the study. Two patients were in the second stage of labor at 24 h so ONSD measurement was not performed and they were excluded from the trial. Overall, 47 patients underwent analysis [Figure 1]. [Table 1] shows the demographic and clinical profile of the patient. [Table 2] shows the ONSD before and after MgSO4 treatment [Figure 2]a and [Figure 2]b at 1, 4, 12, and 24 h. ONSD decreased significantly after 4 h of administration of MgSO4 as compared to baseline (P < 0.01) [Table 2] and [Figure 2]b. [Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7] show the results of ONSD measurements, neurological symptoms, and serum magnesium levels before and after MgSO4 administration. Fifteen patients (31.91%) presented with neurological symptoms and 10 of them had increased ICP (ONSD >5.8 mm), which was significantly reduced to three (6.38%) at the end of 24 h of administration of MgSO4. [Figure 3] shows a significant decrease in neurological symptoms in patients after administration of MgSO4 (P < 0.05). After 1 h of MgSO4 treatment, hemodynamic measurements revealed a significant (P < 0.01) reduction in blood pressure [Table 8]. The correlation between MAP and ONSD was determined by simple linear regression at different time intervals. The regression equation was [F [1,45] = 0.967, P 0.331] before MgSO4 injection, with a nonsignificant R2 of 0.021. The regression equations at the 1st, 4th, 12th, and 24th h following injection of MgSO4 were (F [1,45] = 1.327, P = 0.255), with an R2 of 0.029; (F [1,45]) = 0.703, P = 0.406), with an R2 of 0.015; (F [1,45] = 3.577, P = 0.065), with an R2 of 0.074; and (F [1,45] = 1.456, P = 0.234), with an R2 of 0.031, respectively. At all-time intervals, the correlation between MAP and ONSD was not significant. The correlation between serum MgSO4 level and ONSD as shown in [Table 7] was also found to be insignificant at all time intervals. The regression equations before administration of MgSO4 and at 1st, 4th, 12th, and 24th h following administration were (F [1,45] = 0.072, P = 0.79), with an R2 of 10.002; (F [1,45] = 0.035, P = 0.853), with an R2 of 0.001; (F [1,45] = 0.420, P = 0.5201), with an R2 of 0.009, (F [1,45] = 3.767, P = 0.06), with an R2 of 0.021; and (F [1,45] = 0.072, P = 0.79), with an R2 of 0.002, respectively.
Figure 1: Consort Flow Diagram

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Figure 2: (a) ONSD before MgSO4 administration. (b) ONSD after 4 h of MgSO4 administration. ONSD = Optic nerve sheath diameter

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Figure 3: Patients with neurological signs and symptoms before and after MgSO4 administration

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Table 1: Demographic profile and clinical characteristics of patients

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Table 2: Optic nerve sheath diameter at various time intervals in comparison to baseline

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Table 3: Optic nerve sheath diameter at various time intervals in comparison to 1 h

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Table 4: Optic nerve sheath diameter at 12 h and 24 h in comparison to 4 h

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Table 5: Optic nerve sheath diameter at 12 h in comparison to 24 h

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Table 6: Neurological symptoms before and after magnesium sulfate administration

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Table 7: Serum magnesium levels before and after magnesium sulfate administration

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Table 8: Hemodynamic variables of the patients

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   Discussion Top


Preeclampsia is the world's second leading cause of maternal death, with acute cerebral complications accounting for the vast majority of cases. Raised 1CP can be disastrous and its symptoms often develop quite late and are unreliable in severely preeclamptic patients. ICP measurement using invasive techniques remains the gold standard for the diagnosis of raised ICP; however, its use is associated with various complications and its application in pr-eclamptic and eclamptic patients is cumbersome.[12] Ferro et al. concluded that patients suffering from severe preeclampsia had significantly higher ONSD compared to healthy pregnant controls. Ferro et al. also found that ultrasonographic measurement of the ONSD can be used to assess elevated ICP and risk stratify patients with severe preeclampsia.[7] ONSD has been employed as a surrogate measure of elevated ICP in both pregnant and critically ill patients in intensive care units in a number of studies.[11],[18],[20] Patients with elevated ICP had a mean ONSD of 5.80 ± 0.45 mm, which was significantly higher than patients with normal ICP (5.30 ± 0.61 mm). ONSD's optimal cutoff point for detecting elevated ICP was 5.6 mm, with a sensitivity of 93.75% and a specificity of 86.67%.[21]

Due to the anatomical continuity of the intracranial and intraorbital spaces, cerebrospinal fluid (CSF) can move freely between them. Thus, increase in ICP can be reflected as increase in ONSD. The feasibility of using ultrasonographic measurement of ONSD to identify ICP is increasingly being reported. Jeon et al. found that ONSD measured with bedside ultrasound and directly measured ICP with an external ventricular drain catheter had a strong correlation (r = 0.77, P < 0.01). A variety of regimens are being used for MgSO4 for prophylactic as well as therapeutic use for seizure control in severe preeclampsia.[22] The mechanism of action of MgSO4 in preeclampsia is uncertain. Euser and Cipolla suggested various possible mechanisms, such as vasodilation through calcium antagonism, which decreases myosin contractility and promotes tunica media relaxation, or the production of nitrous oxide. Another possibility is that it may inhibit endothelial platelet aggregation through prostaglandin. This reduction in cerebral vasospasm may prevent eclampsia and cerebral ischemia. The authors also suggested that MgSO4 may directly reduce cerebral edema.[23]

In their study, Wang et al. measured ultrasonographically guided ONSD and obtained opening CSF pressure through a lumbar puncture, and then these values were compared after treatment for raised ICP at follow-up, concluding that reduction in ICP was associated with decrease in the ONSDs. They came to the conclusion that ultrasonographic ONSD readings could be a useful, noninvasive method for dynamically measuring ICP.[24] There have been studies comparing ONSD in preeclamptic and healthy pregnant women, and previous researches found a significant difference between them. The past literature has documented ONSD measurement as a noninvasive approach for assessing the incidence of preeclamptic patients with elevated ICP.[12],[19],[25]

In the current study before MgSO4 treatment, the average diameter of the optic nerve sheath in severely preeclamptic patients was 5.56 ± 0.30 mm. In their study, Singh and Bhatia found ONSD to be 5.6 ± 0.37 and 4.7 ± 0.46 mm in severely preeclamptic and normal term pregnant women, respectively. The mean ONSD decreased significantly at 4, 12, and 24 h after the administration of magnesium sulfate. Omran et al. result showed a significant decrease in ONSD measurement between baseline and after magnesium injection at 1st, 6th, and 24th h in his study.[26] However, there was no significant difference in ONSD after 1h of magnesium administration in our study which probably was because of different magnesium dosing regimens used in the two studies.

In our study, 36.17% of patients had a diameter above 5.8 mm, which was assumed to be a value where 95% of patients were at risk of raised ICP [Table 6].[27] A study by Arzpeyma et al. found that 34.2% of preeclamptic parturients had diameters equal to or greater than 5.8 mm, which is very similar to our findings.[25] Dubost et al. found that (5/26) 19% of all preeclamptic patients evaluated had an ONSD of greater than 5.8 mm, which was lower than our findings. However, Brzan Simenc et al., 13 (43%) parturients with severe preeclampsia had an ONSD over 5.8 mm before delivery, which is only slightly higher than that of our study. They attributed this difference to the presence of neurological symptoms such as headache and visual disturbances, which were more common in their study (53%, compared to 31% in the Dubost et al.'s study).[19],[28] In another study, Omran et al. found that ONSD readings were over the cutoff mark of 5.8 mm in 100% of their patients, owing to the fact that 70% of their patients had neurological manifestations.[26] Fifteen (31.91%) out of 47 patients in our study developed neurological symptoms in our study, of which only 10 patients had an ONSD >5.8 mm as compared to 100% in Omran et al.'s study. This probably suggests the occurrence of comparatively lower neurological symptoms in our study. In the current study, one (2.12%) patient had neurological symptoms at the end of 24 h. Ten (58.82%) patients with ONSD >5.8 mm presented with neurological symptoms, as compared with only five (16.67%) patients where ONSD <5.8 mm, showing greater severity in patients where ONSD is above this threshold [Table 6]. In one (5.88%) patient in our study, ONSD was above 5.8 mm after 24 h.

There was a reduction in blood pressure (SBP/DBP/MAP) post-MgSO4 in our study which was significantly decreased at 4th, 12th, and 24th h. It may be hypothesized that this decrease in blood pressure may be a contributing factor for the decrease in ICP. Patients with severe preeclampsia were simultaneously given antihypertensive treatment, which may be a cause of decreased blood pressure and hence ICP, but it would not have been ethical to prevent patients with severe preeclampsia from receiving antihypertensive treatment. However, linear regression between MAP and ONSD could not establish any significant correlation between them in our study. This finding was also supported by a pilot study from Omran.[26]

In our study, symptoms and signs signifying raised intracranial tension were present. Headache (25.53%) and visual disturbance (6.38%) were noted, but no significant correlation could be established between ONSD and neurological symptoms. Previous studies by Dubost et al. and Brzan Simenc et al. also could not establish any correlation between these factors.[19],[28] In our study, 8.5% of patients had epigastric pain, while Dubost et al. found that the percentages of patients who suffered from headache and epigastric pain were 53.84% and 30.77%, respectively. Dubost et al. did not document the incidence of nausea and vomiting; however, two patients in our study experienced these symptoms, which may be attributed to the large sample size.[19] The possible reason for the discrepancy between Dobost et al. and our study is large sample size (47) in our study as compared to only 13 patients in Dobost et al.'s study. Moreover, headache and visual disturbances are nonspecific symptoms of raised ICP and may not be present in all preclamptics and that possibly explains why we could not establish any fixed correlation between them and ONSD.

In our study, the main limitation was that the confounding factor of antihypertensive use in decreasing the ICP cannot be ruled out. Anesthetic effect on cerebral physiology also needs further clarification and evaluation. Although the sample size of our study was statistically calculated, a larger study population size could have emphasized and strengthened our findings. This study could also have been extended by including cases of moderate preeclampsia.


   Conclusion Top


We concluded that ultrasound-guided ONSD measurement is a quick noninvasive bedside tool that can be used in severe PIH patients to assess and classify as per clinical severity, determine the therapeutic response of MgSO4, and decide the course of management. MgSO4 therapy in severe preeclampsia plays a significant role in decreasing ONSD and hence can be used as acceptable surrogate marker for decrease in ICP.

Acknowledgments

We sincerely acknowledge Dr. Aditi Khare, UmmeAfifa for helping in collection of patient data and completion of statistical calculation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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