Heart Rhythm After Intravenous Methylprednisolone Administration

Study Overview
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Brief Summary
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High doses of intravenous (iv.) glucocorticoids (GCs) are commonly used as a treatment for many autoimmune and inflammatory disorders. According to the European Group on Graves' Orbitopathy (EUGOGO) guidelines, intravenous methylprednisolone (IVMP) is an accepted first-line agent for active, moderate-to-severe and very severe Graves' orbitopathy (GO). This treatment is proven to be more efficient and safer than oral GCs. However, some patients may experience adverse cardiovascular effects during the administration of iv. GCs, which in rare cases may even be fatal. There are limited data, mostly obtained from case reports, reporting the occurrence of cardiac arrhythmias, acute myocardial infarction or heart failure. Increased heart rhythm (HR) has drawn attention of researchers as a possible adverse effect correlated with IVMP. During this study, investigators performed 72-hours of Holter ECG and ambulatory blood pressure monitoring (ABPM) to evaluate the impact of IVMP on patients with moderate-to-severe GO, concerning HR and blood pressure (BP) changes. In order to elucidate possible mechanism of observed changes, researchers investigated the level of potassium in serum and urine and catecholamines (epinephrine, norepinephrine) in serum. All patients were treated routinely according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines active, moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).

Detailed Description
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The clinical status of patients was evaluated before each pulse, including blood pressure monitoring, glucose level monitoring and symptoms of infection. HR and BP was measured continuously for 3 consecutive days (the day before, the day of IVMP and the day after IVMP) during 1st, 6th and 12th IVMP pulse, using 24-hour Holter ECG and ABMP. Serum laboratory tests for potassium, epinephrine and norepinephrine were measured 3 times the day before and the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP. Additionally, urine samples for potassium were collected 5 times the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP.

Official Title
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Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy

Conditions
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Graves Disease, Graves Ophthalmopathy, Heart Rhythm Disorder, Hypertension, Blood Pressure, Heart Failure

Intervention / Treatment
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* Drug: Intravenous Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: active, moderate-to-severe GO according to EUGOGO classification euthyroidism completion of 12 IVMP pulses. Exclusion Criteria: cardiovascular morbidity (such as chronic heart failure and/or coronary heart disease) uncontrolled hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg) contraindications to IVMP therapy previous GCs treatment in the last 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| active, moderate-to-severe GO<br>Each participant received IVMP according to EUGOGO recommendations (cumulative dose of methylprednisolone 4.5 g, treatment duration 12 weeks in single weekly intravenous pulses, first 6 weeks 0.5g of IVMP, next 6 weeks 0.25g of IVMP). | Drug: Intravenous Methylprednisolone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour Holter ECG Monitoring - 1st pulse mean HR | Analysis of changes in mean HR between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP | 72 hours | 
| 24-hour Holter ECG Monitoring - 6th pulse mean HR | Analysis of changes in mean HR between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP | 72 hours | 
| 24-hour Holter ECG Monitoring - 12th mean HR | Analysis of changes in mean HR between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum potassium levels Day 0 - Day 1 | Change in value of potassium between day before and day of 1st pulse of IVMP | 48 hours | 
| Serum epinephrine levels Day 0 - Day 1 | Change in value of epinephrine between day before and day of 1st pulse of IVMP | 48 hours | 
| Serum norepinephrine levels Day 0 - Day 1 | Change in value of norepinephrine between day before and day of 1st pulse of IVMP | 48 hours | 
| Urine potassium levels Day 0 | Change in value of potassium during the day of 1st pulse of IVMP | 24 hours | 
| 72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP | Analysis of changes in mean BP between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP | 72 hours | 
| 72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP | Analysis of changes in mean BP between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP | 72 hours | 
| 72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP | Analysis of changes in mean BP between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP | 72 hours |