Search

Background: Patients with ascites, hepatorenal syndrome, or both who have reduced plasma renin activity can benefit from midodrine, which is an a1-adrenergic agonist, by increasing the effective arterial blood volume by splanchnic vasoconstriction and decreasing nitrite as well as nitrate activity. This study aimed to assess the efficacy of midodrine in management of refractory ascites due to liver cirrhosis. Methods: The present case-control study included 100 patients who had refractory ascites due to liver cirrhosis. They were divided into 2 groups (50 each): The control group who received standard medical treatment (SMT), and the midodrine group who received SMT in addition to midodrine. Ascitic fluid study for calculation of SAAG and exclusion of spontaneous bacterial peritonitis was done for all participants. Patients were followed up one month of treatment. Results: After 1-month, mean values of body weight, paracentesis frequency, furosemide and spironolactone doses, S.creatinine were decreased significantly, mean arterial blood pressure and eGFR was significantly increased, among midodrine group (P<0.001). At cutoff value equal to 15 mg/day, midodrine played a role in protection against hepatorenal syndrome. After 1 week a statistically significant positive correlation was revealed between midodrine dose and mean arterial blood pressure (p<0.001), After 1 month, statistically significant negative correlations were revealed between midodrine dose and body weight, paracentesis frequency and diuretic doses (p<0.001). Also, a statistically significant positive correlation was found between midodrine dose and mean arterial blood pressure (p<0.05). Conclusions: The addition of midodrine to standard medical treatment (salt restriction and diuretics) has an important role in managing the refractory ascites with protection against hepatorenal syndrome at dose 15mg/day. So, it is considered safe adjuvant treatment for patients who had refractory ascites due to liver cirrhosis with little side effects. [ABSTRACT FROM AUTHOR]

Background An uncommon cause of reflex syncope is carotid sinus syndrome (CSS). In rare cases, this can be caused by compression of the carotid sinus by a progressive or invasive tumour. Case summary A 57-year-old female was presented at the emergency department with recurrent syncope in the morning. After initial observation, no heart rhythm abnormalities or syncope were observed. The day after discharge, she was presented again with a syncope. Hypotension and bradycardia were observed this time. Furthermore, a mass in the neck area was found near the carotid artery. She was admitted to the cardiology department with suspected carotid sinus syndrome for telemetric observation. Diagnostics by biopsy and PET-CT showed a metastasized squamous cell carcinoma of the tongue. Initial treatment of dexamethasone was started after which the recurrence of the syncope decreased. However, during admission, an in-hospital cardiac arrest occurred due to persistent vagal stimulation. As a result, the patient was started on neoadjuvant chemotherapy and midodrine, after which she experienced multiple complications and died. Discussion To the best of our knowledge, this is the first case report that shows an IHCA due to severe hypotension related to a carotid sinus syndrome. [ABSTRACT FROM AUTHOR]

Background: Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. Methods: 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. Results: Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). Conclusion: Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites. [ABSTRACT FROM AUTHOR]

Background: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF. Methods: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities. Results: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality. Conclusion: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies. [ABSTRACT FROM AUTHOR]

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy—aimed at counteracting hypotension or bradycardia—depends on the given phenotype. Discontinuation of blood pressure–lowering drugs, elastic garments, and blood pressure–elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. Methods This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP 20% of the baseline reading). Results We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. Conclusion The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. Clinical trial registration This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic.clinicaltrials.gov/ct2/show/NCT05548985 .

Background: Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine’s safety in HFrEF through extensive matched analysis. Methods: Patients with HFrEF (LVEF <50%) without malignancy, non-dialysis dependence, or non-orthostatic hypotension, were enrolled between 28 August 2013, and 27 August 2023. Propensity score matching (PSM) created 1:1 matched groups. Outcomes included mortality, stage 4 and 5 chronic kidney disease (CKD), emergency room (ER) visits, intensive care unit (ICU) admissions, hospitalizations, and respiratory failure. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for each outcome, and Kaplan-Meier survival analysis was performed. Subgroup analyses were conducted based on gender, age (20-<65 vs. ≥65), medication refill frequency, and baseline LVEF. Results: After 1:1 PSM, 5813 cases were included in each group. The midodrine group had higher risks of respiratory failure (HR: 1.16, 95% CI: 1.08–1.25), ICU admissions (HR: 1.14, 95% CI: 1.06–1.23), hospitalizations (HR: 1.21, 95% CI: 1.12–1.31), and mortality (HR: 1.090, 95% CI: 1.01–1.17). Interestingly, midodrine use reduced ER visits (HR: 0.77, 95% CI: 0.71–0.83). Similar patterns of lower ER visit risk and higher risks for ICU admissions, respiratory failure, and overall hospitalizations were observed in most subgroups. Conclusion: In this large-scale study, midodrine use was associated with reduced ER visits but increased risks of respiratory failure, prolonged ICU stays, higher hospitalizations, and elevated mortality in HFrEF patients. Further research is needed to clarify midodrine’s role in hemodynamic support and strengthen existing evidence. [ABSTRACT FROM AUTHOR]

Background: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. Objectives: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. Methods: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. Results: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. Conclusion and Relevance: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. Methods: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). Results: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. Conclusion: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. Clinical trial registration: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic.clinicaltrials.gov/ct2/show/NCT05548985. [ABSTRACT FROM AUTHOR]

• Refractory hypotension is common in critically ill patients. • Intravenous vasoactive medications limit discharge from the intensive care unit. • Oral vasoactive medication could facilitate weaning of these medications. • Midodrine has limited supporting evidence for intravenous vasopressor liberation. • Droxidopa or atomoxetine may be options in critically ill patients with hypotension. To evaluate the effects of droxidopa or atomoxetine on intravenous (IV) vasoactive agent discontinuation in cardiothoracic intensive care unit (ICU) patients with hypotension refractory to midodrine. Single-center, retrospective cohort study. Tertiary- and quaternary-care university teaching hospital. Included patients who received at least 4 consecutive doses of droxidopa or atomoxetine and remained on concurrent midodrine. Patients were excluded if they received study medication before admission, had clinical deterioration after study medication initiation requiring additional vasoactives/escalation of IV vasoactive dosage for at least 12 hours, had a diagnosis of hepatorenal syndrome, were prisoners, or were pregnant. Droxidopa, atomoxetine, or both. The primary endpoint was time to discontinuation of IV vasoactive agents after initiation of study medication, analyzed using a Kaplan–Meier estimate with the Wilcoxon method, censoring death within 24 hours of the last dose of study medication. No adjustment for repetitive analyses was made, as the analysis was hypothesis-generating. Of the 72 charts reviewed, 45 patients met inclusion criteria (18 atomoxetine, 17 droxidopa, and 10 both). There were no differences in median time to discontinuation of IV vasoactive agents (21.9 days v 8.0 days v 13.9 days, respectively; p = 0.259) or ICU or hospital length of stay between groups. A higher percentage of patients who survived to hospital discharge received both study medications or droxidopa alone (90% v 76.5%) than atomoxetine alone (44.4%, p = 0.028). Droxidopa and atomoxetine are oral vasoactive agents with potential mechanisms to facilitate IV vasopressor weaning for patients in the ICU with hypotension refractory to midodrine, but further prospective research is needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Midodrine was the first medication approved by the Food and Drug Administration (FDA) for the treatment of orthostatic hypotension. Pharmacologically, midodrine is a peripheral selective alpha-1-adrenergic agonist that can improve standing, sitting, and supine systolic blood pressure. Common side effects include bradycardia, supine hypertension, and paresthesia. A novel side effect of midodrineinduced nightmares has been reported in our patient. To our knowledge, this is the first reported case of midodrine-induced nightmares. OBJECTIVE: To investigate and report a clinically significant and unique drug adverse event of midodrine in the treatment of orthostatic hypotension. CASE PRESENTATION: This report describes a case of persistent nightmares associated with midodrine use in an 83-year-old male who experienced frequent syncope episodes treated with midodrine for orthostatic hypotension (OH). After the initiation of midodrine, the patient complained of increased nightmares, which quickly led to his refusal of the medication, despite the initial improvements in his blood pressure. The timing of administration included an evening dose at 21:00. This novel adverse event of midodrine-induced nightmares will be highlighted and explored in this case report. CONCLUSION: This case demonstrated a unique adverse event of nightmares caused by midodrine. It is hypothesized that autonomic dysfunction plays a role and further investigations should be conducted to confirm this theory. We hope that our case report highlights the importance of careful consideration when prescribing midodrine in older people with orthostatic hypotension. [ABSTRACT FROM AUTHOR]

Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney injury (HRS-AKI) accounts for most hospitalizations, and liver transplantation (LT) remains the ultimate and long-term treatment in such patients. However, HRS-AKI, being a functional renal failure, has a fair chance of reversal, and as such, patients who achieve reversal of HRS-AKI have better outcomes post-LT. In this review, we discuss the pharmacokinetics, pharmacodynamics and evidence to support the use of terlipressin in HRS-AKI while we also address predictors of response and the associated adverse events. Further, we discuss the role of terlipressin in the context of LT. The recommended treatment for HRS-AKI reversal includes a vasoconstrictor in addition to volume expansion with albumin. The three vasoconstrictor regimens generally used to treat HRS-AKI include octreotide plus midodrine, noradrenaline, and terlipressin. Of these, terlipressin is a widely used drug and has been recently approved by US Food and Drug Administration (USFDA) for HRS-AKI. Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant. Furthermore, terlipressin responders have improved transplant-free and post-transplant survival. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 60-year-old man with chronic spinal cord injury experiencing severe headaches, highlighting the differential diagnosis process and the eventual diagnosis of pituitary apoplexy. Topics include differential diagnoses for headaches in spinal cord injury patients, the importance of considering secondary causes such as pituitary adenomas, and the management approach for pituitary apoplexy involving neurosurgical consultation and hormone replacement therapy.

Purpose: Hepatorenal syndrome (HRS) is renal dysfunction associated with the hemodynamic consequences of advanced liver disease and cirrhosis. HRS is associated with a high mortality, and there remain high failure rates with first-line therapy aimed at improving perfusion. We report the use of droxidopa, an oral norepinephrine precursor, to aid in the management of HRS-AKI refractory to first-line therapy. Summary: A 51-year-old Caucasian male with alcohol-related cirrhosis presented with 1-week history of pre-syncope and falls. He was found to have acute kidney injury meeting diagnostic criteria of HRS based on absence of identifiable contributing factors. After no response to volume expansion, medical management was initiated with midodrine and octreotide and eventually escalated to norepinephrine intravenous infusion. The patient's renal function and urine output improved initially on norepinephrine, but worsened when attempting to wean to a suitable outpatient regimen, becoming dependent upon norepinephrine. On day 13 of hospitalization, droxidopa was initiated at a dose of 100 mg three times daily and titrated to a dose of 400 mg three times daily. Norepinephrine infusion was weaned and discontinued on day 16 of hospitalization. The patient remained hemodynamically stable and was able to be discharged on droxidopa 400 mg three times daily, midodrine 20 mg three times day, and octreotide 200 mcg three times daily. Conclusion: Droxidopa, an oral norepinephrine precursor, presents a novel adjunctive agent for management of HRS refractory to first-line medical management. [ABSTRACT FROM AUTHOR]

Postural orthostatic tachycardia syndrome (POTS) is common in children, with an excessive increment in heart rate when moving from the supine to upright position. It has significant negative impacts on the daily life of pediatric patients. The pathogenesis of POTS includes peripheral vascular dysfunction, central hypovolemia, abnormal autonomic function, a high-adrenergic state, impaired skeletal-muscle pump function, the abnormal release of vasoactive factors, and autoimmune abnormalities. Therefore, the empirical use of pharmacological treatments has limited therapeutic efficacy due to the diversity of its mechanisms. A crucial aspect of managing POTS is the selection of appropriate treatment targeting the specific pathogenesis. This review summarizes the commonly used pharmacological interventions, with a focus on their predictive indicators for treatment response. Factors such as heart rate variability, plasma biomarkers, and cardiac-function parameters are discussed as potential predictors of therapeutic efficacy, enabling the implementation of individualized treatment to improve therapeutic effectiveness. This review consolidates the current knowledge on POTS, encompassing its clinical characteristics, epidemiological patterns, underlying pathogenic mechanisms, and predictive indicators for treatment response. Further research is warranted to enhance the understanding of POTS and facilitate the development of more effective therapeutic approaches for this challenging syndrome. [ABSTRACT FROM AUTHOR]