The Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study.

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.

Droxidopa or Atomoxetine for Refractory Hypotension in Critically Ill Cardiothoracic Surgery Patients.

OBJECTIVE: 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. DESIGN: Single-center, retrospective cohort study. SETTING: Tertiary- and quaternary-care university teaching hospital. PARTICIPANTS: 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. INTERVENTIONS: Droxidopa, atomoxetine, or both. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

The Impact of Midodrine on Guideline-Directed Medical Therapy in Patients Admitted With Systolic Heart Failure.

ABSTRACT: Midodrine is occasionally used off-label to treat hypotension associated with advanced heart failure (HF); however, its association with changes in prescription of guideline-directed medical therapy (GDMT) is unknown. We sought to evaluate the effect of midodrine on the GDMT prescription pattern and clinical outcomes of patients with decompensated systolic HF. We retrospectively identified 114 patients admitted to our hospital in 2020 with decompensated systolic HF who were prescribed midodrine on discharge and compared them with 358 patients with decompensated systolic HF who were not prescribed midodrine. At 6 months, the midodrine group had more initiation or up-titration of beta blockers, renin-angiotensin-aldosterone system inhibitors, and sodium-glucose cotransporter-2 inhibitors compared with the nonmidodrine group. Survival at 6 months was similar between the 2 groups, but the midodrine group had more frequent rehospitalization for HF. Our findings suggest that midodrine is associated with improved GDMT in patients with decompensated HF but may be associated with worse prognosis.

Midodrine-Induced Nightmares in the Treatment of Orthostatic Hypotension: A Case Report.

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 midodrine-induced 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.

Terlipressin vs Midodrine Plus Octreotide for Hepatorenal Syndrome-Acute Kidney Injury: A Propensity Score-Matched Comparison.

INTRODUCTION: Evidence on the comparison of treatments for hepatorenal syndrome-acute kidney injury (HRS-AKI) in a US population is limited. An indirect comparison of terlipressin plus albumin vs midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy. METHODS: Cohorts of patients treated for HRS-AKI characterized by inclusion of patients with serum creatinine (SCr) <5 mg/dL and baseline acute-on-chronic liver failure grades 0-2 and exclusion of patients listed for transplant if model for end-stage liver disease scores ≥35 were pooled from (i) the CONFIRM and REVERSE randomized controlled trials (N = 159 meeting eligibility criteria from N = 216 overall, treated with terlipressin) and (ii) a retrospective review of medical records from 10 US tertiary hospitals (2016-2019; N = 55 treated with MO meeting eligibility criteria from N = 200 overall). The primary end point comparing the 2 cohorts was HRS reversal defined as achieving SCr ≤1.5 mg/dL at least once during the treatment. Covariate balancing propensity scoring was used to adjust for differences in baseline characteristics. RESULTS: HRS-AKI reversal was achieved in 52.35% of terlipressin-treated patients compared with 20% of MO-treated patients (adjusted mean difference 32.35%, 95% confidence interval [CI] 17.40-47.30, P < 0.0001). Terlipressin-treated patients had increased overall survival (adjusted hazard ratio 0.57, 95% CI 0.35-0.93, P = 0.02) but similar transplant-free survival (adjusted hazard ratio 0.79, 95% CI 0.53-1.17, P = 0.24). Achievement of HRS-AKI reversal was associated with increased OS and TFS regardless of treatment ( P < 0.001). DISCUSSION: Consistent with prior reports, terlipressin plus albumin is more effective in improving kidney function and achieving HRS-AKI reversal than MO plus albumin based on indirect comparison in a US population.

Effect of midodrine on the prognosis of patients with septic shock: a systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the efficacy and safety of midodrine on treating patients with septic shock. MATERIALS AND METHODS: Literature search was conducted in PubMed, the Cochrane Library, and Embase. The Mantel-Haenszel method was used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). The mean differences (MD) or standardized mean difference (SMD) were calculated using the inverse variance for continuous variables. Data analysis was performed using Review Manager 5.3. RESULTS: A total of 6 studies were finally included in this meta-analysis. Adding midodrine to patients with septic shock was associated with a reduction in hospital mortality [risk ratio (RR) 0.76; 95% CI, 0.57-1.00; p=0.05] and intensive care unit (ICU) mortality (RR 0.59; 95% CI, 0.41-0.87; p=0.008). However, there were no significant differences in the duration of intravenous vasopressors [standardized mean difference (SMD) -0.18; 95% CI, -0.47-0.11; p=0.23], intravenous vasopressor reinstitution (RR 0.58; 95% CI, 0.19-1.80; p=0.35), the length of ICU stay [mean difference (MD) -0.53 days; 95% CI, -2.24-1.17; p=0.54], and the length of hospital stay (MD -2.40 days; 95% CI, -5.26-0.46; p=0.10) between midodrine group and intravenous vasopressor alone group. CONCLUSIONS: The additional use of midodrine might reduce hospital mortality and ICU mortality in patients with septic shock. More high-quality randomized controlled trials are needed to verify this conclusion.

Refractory bradycardia and hypotension in patients with autonomic dysfunction treated with pseudoephedrine.

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5-C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.

Oral midodrine does not expedite liberation from protracted vasopressor infusions: A case-control study.

Vasopressor dependence is a common problem affecting patients in the recovery phase of critical illness, often necessitating intensive care unit (ICU) admission and other interventions which carry associated risks. Midodrine is an orally administered vasopressor which is commonly used off-label to expedite weaning from vasopressor infusions and facilitate discharge from ICU. We performed a single-centre, case-control study to assess whether midodrine accelerated liberation from vasopressor infusions in patients who were vasopressor dependent. Cases were identified at the discretion of treating intensivists and received 20 mg oral midodrine every eight h from enrolment. Controls received placebo. Data on duration and dose of vasopressor infusion, haemodynamics and adverse events were collected. Between 2012 and 2019, 42 controls and 19 cases were recruited. Cases had received vasopressor infusions for a median of 94 h versus 29.3 h for controls, indicating prolonged vasopressor dependence amongst cases. Midodrine use in cases was not associated with faster weaning of intravenous (IV) vasopressors (26 h versus 24 h for controls, P = 0.51), ICU or hospital length of stay after adjustment for confounders. Midodrine did not affect mean heart rate but was associated with bradycardia. This case-control study demonstrates that midodrine has limited efficacy in expediting weaning from vasopressor infusions in patients who have already received relatively prolonged courses of these infusions.

Efficacy of Preoperative Oral Midodrine in Preventing Hypotension After Spinal Anesthesia in Young Adults: A Randomized Controlled Trial.

BACKGROUND: Midodrine was effectively used for prophylaxis against hypotensive syndromes such as postural hypotension and intradialytic hypotension, and during the recovery phase of septic shock. In our study, we aimed to assess the efficacy of prophylactic administration of midodrine tablets before spinal anesthesia in reducing the occurrence of hypotension. METHODS: This randomized placebo-controlled study embraced 67 patients aged 18 to 40 years undergoing elective knee surgery under spinal anesthesia. Patients were randomized to midodrine group (given 10-mg tablets of midodrine) or placebo group (given placebo tablets), and tablets were administered 1 hour before spinal anesthesia (intrathecal injection of 12.5-mg 0.5% hyperbaric bupivacaine and 15-µg fentanyl). The primary outcome was the occurrence of hypotension, defined as a systolic blood pressure <90 mm Hg or <80% of baseline. Secondary outcomes were hemodynamic characteristics (mean arterial pressure [MAP] and heart rate [HR]) after spinal anesthesia, ephedrine dose, and occurrence of complications including bradycardia, vasovagal attacks, reactive hypertension nausea, vomiting, and shivering. RESULTS: The number of patients who became hypotensive after spinal anesthesia was 5 (14.7%) in midodrine group versus 14 (42.4%) in the placebo group; relative risk (95% confidence interval) was 0.35 (0.14-0.85) ( P = .021). The median (interquartile range) total dose of ephedrine was significantly lower in midodrine group 0 (0-10) mg than in placebo group (0 (0-15) mg; the Hodges-Lehmann median difference (95% confidence interval) was 0 (0-5) mg ( P = .015). For MAP data, the group × time interaction was significant ( P = .038), and the MAP was significantly lower in the placebo group than in the midodrine group after intrathecal injection at 2 minutes ( P = .047), 10 minutes ( P = .045), 15 minutes ( P < .001), 20 minutes ( P = .007), 30 minutes ( P =.013), 45 minutes ( P = .029), 60 minutes ( P = .029), and at the end of surgery ( P < .001). For HR data, the group × time interaction was nonsignificant ( P = .807), and the difference in means (95% confidence interval) between groups collapsing over time was -1.4 (-3.1 to 0.2) beats/min ( P = .096). There was no significant difference between the 2 groups regarding the occurrence of complications. CONCLUSIONS: Prophylactic administration of 10-mg midodrine tablets before spinal anesthesia is an effective method in the prevention of hypotension in young adult patients undergoing elective orthopedic knee surgery.

LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial.

BACKGROUND: Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited. METHODS: The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions. DISCUSSION: LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021.

Putting midodrine on the MAP: An approach to liberation from intravenous vasopressors in vasodilatory shock.

PURPOSE: Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the intensive care unit (ICU) and hospital, translating to higher risk of infection, delirium, immobility, and cost. Acceleration of vasopressor liberation can aid in reducing these risks. Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy. This clinical review summarizes primary literature and proposes a clinical application for midodrine in the recovery phase of vasodilatory shock. SUMMARY: Five studies with a total of over 1,000 patients conducted between 2011 and 2021 were identified. In observational studies, midodrine administration was demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in patients recovering from vasodilatory shock. These findings were not replicated in a prospective, multicenter, randomized controlled trial. In this review, literature evaluating midodrine use for IV vasopressor liberation is summarized and study limitations are discussed. CONCLUSION: On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.

Midodrine improves clinical and economic outcomes in patients with septic shock: a randomized controlled clinical trial.

BACKGROUND: Prolonged use of intravenous (IV) vasopressors in patients with septic shock can lead to deleterious effects. AIMS: This study assessed the impact of midodrine administration on weaning off IV vasopressors and its economic value. METHODS: It is a prospective randomized controlled study of 60 resuscitated patients with septic shock who demonstrated clinical stability on low-dose IV vasopressors for at least 24 h. Participants were randomized into two groups: norepinephrine (IV norepinephrine) and midodrine (IV norepinephrine + oral midodrine 10 mg thrice a day). A cost comparison was applied based on the outcomes of both groups. RESULTS: The median duration of norepinephrine administration in the midodrine and norepinephrine groups was 4 and 6 days, respectively (p = 0.001). Norepinephrine weaning time was significantly less in the midodrine versus norepinephrine groups (26 and 78.5 h, respectively; p < 0.001). Mortality was 43.3% versus 73.3% in the midodrine and norepinephrine groups, respectively (p = 0.018). The mean length of stay was comparable in the two groups. The midodrine group showed cost-saving results versus the norepinephrine group. CONCLUSION: The use of midodrine in septic shock patients significantly reduced IV norepinephrine duration, weaning period during the septic shock recovery phase, and mortality. Thus, the use of midodrine is dominant with less cost, better outcome and a cost-saving option in terms of budget impact analysis. This study was registered at clinicaltrials.gov (NCT 03,911,817) on April 11, 2019.

Midodrine and albumin versus albumin alone for the secondary prophylaxis of acute kidney injury in a patient with cirrhosis and ascites.

BACKGROUND: Acute kidney injury (AKI) in a patient with cirrhosis has high short-term mortality. Midodrine has shown promising results in the treatment of AKI-hepatorenal syndrome (HRS-AKI). AIMS: To compare midodrine and albumin versus albumin alone for the secondary prophylaxis of HRS-AKI. PATIENTS AND METHOD: Open labeled, nonrandomized, pilot study. Patients with a diagnosis of HRS-AKI were recruited after complete recovery. Patients were given midodrine daily (15 mg) and injection albumin infusion 20 g weekly in group-A (Gp-A) and injection albumin 20 g weekly with no midodrine in group-B (Gp-B). The primary endpoint was the recurrence of AKI-HRS, and the secondary endpoint was ascites tap in 2-month period. RESULTS: A total of 42 patients were enrolled in Gp-A, n = 22, and Gp-B, n = 20. There was no significant difference between the groups (Gp-A vs. Gp-B) in terms of age, model stage liver disease, Child-Turcotte-Pugh score and serum creatinine at inclusion (1.27 ± 0.1 vs. 1.22 ± 0.2 mg/dL). During follow up ten patients (50%) in Gp-B and four patients (18%) in Gp-A develop HRS-AKI (P = 0.04). The mean number of ascites tap was significantly higher in Gp-B compared to Gp-A (2.6 ± 0.5 vs. 1.9 ± 0.5) in 2 months. There was a significant increase in mean arterial pressure in Gp-A compared to Gp-B on days 7, 15, 30, 45 and 60. There was a significant difference in mean arterial pressure at day 7 in patients who developed HRS-AKI versus those who did not develop HRS-AKI [(n = 14, 65.5 ± 5.5) vs. (n = 28,74.6 ± 9.2 mm Hg), P = 0.02]. CONCLUSIONS: Midodrine along with albumin infusion, is helpful in the secondary prophylaxis of HRS-AKI and reduces the number of ascites tap. However, a large randomized study is required for further validation.

Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate.

BACKGROUND: Hepatorenal syndrome (HRS) remains a serious complication of cirrhosis with a high mortality rate. There is little information on the effect of standardizing albumin, midodrine and octreotide combination on treatment response in patients with HRS. OBJECTIVE: The aim of the study was to determine the impact of a standardized HRS treatment regimen on renal function recovery. The primary outcome was full response rate. Secondary outcomes included partial and no response rates, 30-day all-cause mortality, ICU length of stay (LOS), hospital LOS, liver transplantation and total dose of albumin. METHODS: This retrospective study evaluated the impact of using a standardized approach with albumin, midodrine and octreotide on treatment response rates compared to a historical group. RESULTS: Of the patients with HRS, 28 received a standardized approach with albumin, midodrine and octreotide while 60 received a nonstandardized approach. Ten percent of patients achieved full response in the prestandardization group compared with 25% in the poststandardization group (P = 0.07). Renal replacement therapy was significantly more prevalent in the prestandardization group vs. poststandardization group (45% vs. 21.4%, P = 0.03). Liver transplantation was performed significantly more often in the prestandardization group compared the poststandardization group (23% vs. 3.6%, P = 0.02). Amount of albumin used was statistically lower in the poststandardization group (425 vs. 332 g, P = 0.05). No significant differences in days of HRS treatment, mortality rate, hospital and ICU LOS were observed. CONCLUSION: A trend towards improved treatment response rate was observed after standardizing the HRS treatment regimen. Standardized therapy led to significantly lower rates of renal replacement therapy and liver transplantation, suggesting patients in poststandardization were effectively managed medically without requiring further intervention.

Case report: severe myoclonus associated with oral midodrine treatment for hypotension.

RATIONALE: Midodrine is widely used in the treatment of hypotensive states, there have been no reports of myoclonus associated with midodrine use in hypotension with chronic kidney disease. PATIENT CONCERNS: We report a 58-year-old female patient with chronic kidney disease (CKD) presenting with involuntary tremor 2 h after taking midodrine, which became more frequent after 6 h. Brain CT and neurological examination did not yield findings of note. Blood chemistry showed serum albumin of 3.1 g/L, ALT of 19 U/L, AST of 22 U/L, SCr of 273.9 µmol/L, K of 2.94 mmol/L, Ca of 1.63 mmol/L, and Mg of 0.46 mmol/L. Her BP was maintained at 83-110/56-75 mmHg. Her urine volume was 600-1000 mL/d, and her heart rate was within a range of 90-100 beats/min. DIAGNOSIS: Chronic kidney disease (CKD), hypotension, metabolic acidosis, hypocalcemia, hypokalemia, and hypomagnesemia. INTERVENTIONS: Midodrine treatment was stopped and the patient was treated with intravascular rehydration and furosemide. Myoclonus ceased one day after midodrine withdrawal. LESSONS: Oral midodrine is widely used in the treatment of orthostatic hypotension, recurrent reflex syncope and dialysis-associated hypotension and the adverse effects are mostly mild. However, clinicians should be alert for midodrine-induced myoclonus, especially in patients with CKD.

Efficacy of atomoxetine versus midodrine for neurogenic orthostatic hypotension.

OBJECTIVE: The efficacy and safety of 1-month atomoxetine and midodrine therapies were compared. Three-month atomoxetine and combination therapies were investigated for additional benefits. METHODS: This prospective open-label randomized trial included 50 patients with symptomatic neurogenic orthostatic hypotension (nOH). The patients received either atomoxetine 18 mg daily or midodrine 5 mg twice daily and were evaluated 1 and 3 months later. Those who still met the criteria for nOH at 1 month received both midodrine and atomoxetine for an additional 2 months, and if not, they continued their initial medication. The primary outcome was an improvement in orthostatic blood pressure (BP) drop (maximum BP change from supine to 3 min after standing) at 1 month. The secondary endpoints were symptom scores, percentage of patients with nOH at 1 and 3 months. RESULTS: Patients with midodrine or atomoxetine treatment showed comparative improvement in the orthostatic BP drop, and overall only 26.2% of the patients had nOH at 1 month, which was similar between the treatment groups. Only atomoxetine resulted in significant symptomatic improvements at 1 month. For those without nOH at 1 month, there was additional symptomatic improvement at 3 months with their initial medication. For those with nOH at 1 month, the combination treatment resulted in no additional improvement. Mild-to-moderate adverse events were reported by 11.6% of the patients. INTERPRETATION: One-month atomoxetine treatment was effective and safe in nOH patients. Atomoxetine improved orthostatic BP changes as much as midodrine and was better in terms of ameliorating nOH symptoms.

Effect of alpha agonists on the prevention of postparacentesis circulatory dysfunction in patients with refractory or recurrent ascites: a meta-analysis.

Postparacentesis circulatory dysfunction (PCD) is one of the commonest complications encountered in patients with refractory or recurrent ascites. Alpha agonists like clonidine and midodrine have been studied in various clinical trials for the prevention of PCD with varied results. This meta-analysis was done to evaluate the effect of alpha agonists on prevention of PCD in patients of refractory or recurrent ascites. A standard meta-analysis protocol was developed and registered in the International Prospective register of Ongoing Systematic Reviews. After performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from five relevant articles. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed in selection, analysis, and reporting of findings. Random effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. The random effect model analysis revealed a mean reduction of 2.63 ng/ml/h (95% CI: -4.46 to -0.8; P = 0.005) in plasma renin activity (PRA), mean reduction of 255.37 pg/ml (95% CI: -441.23 to -69.5; P = 0.007) in plasma aldosterone levels, and a mean increase of 0.14 mg/dl (95% CI: -0.13 to 0.41; P = 0.32) in serum creatinine levels favouring add-on alpha agonist group. In meta-regression, change in PRA (P = 0.79) and plasma aldosterone (P = 0.93) did not show a significant difference due to variation in follow-up duration across various studies. Add-on alpha agonists bring about a significant reduction in PRA and plasma aldosterone compared to standard medical treatment and thus prevents the occurrence of PCD in patients with refractory or recurrent ascites.

Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study.

BACKGROUND AND AIMS: Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment. Less costly treatment alternatives such as vasoconstrictors have been investigated, but the results are controversial. Midodrine, an oral α1-adrenergic agonist, increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure. Our aim is to assess whether or not morbidity in terms of renal dysfunction, hyponatremia, systemic, or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine. PATIENTS AND METHODS: Seventy-five patients with cirrhosis and refractory ascites were randomized to receive albumin infusion, oral midodrine for 2 days, or oral midodrine for 30 days after therapeutic large volume paracentesis (LVP). The primary endpoints were development of renal impairment or hyponatremia, change in systemic and portal hemodynamics, cost, and mortality in the short-term and long-term follow-up. RESULTS: No significant difference was found between groups in the development of renal impairment, hyponatremia, or mortality 6 and 30 days after LVP. A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group. Renal perfusion improved significantly with the midodrine intake for 30 days only. The cost of midodrine therapy was significantly lower than albumin. CONCLUSION: Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost. Long-duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion.