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Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-ProcessOther Non-Indexed Citations, Scopus, and Web of Science from inception.Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI,87.7 to210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI,2.8 to177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI,5.1 to51]; moderate certainty).Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.

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.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 pressure90 mm Hg or80% 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.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.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.

Background and aim Yahom Navakot (YN), is a Thai traditional medicine, consisting of 54 plants, for treating fainting and dizziness. Thus, YN might relieve orthostatic hypotension (OH) symptoms, but its therapeutic action is unclear. Therefore, this study evaluated YN in OH rats, using a head-up tilt test (HUT). Experimental procedure Rats were anesthetized, and OH induced via a 90oHUT, before and after administering vehicle, a YN powder suspension (10, 100 mg/kg), a YN aqueous extract (100 mg/kg), and midodrine (5 mg/kg). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), pulse pressure (PP) and heart rate (HR) were determined via the carotid artery. Plasma noradrenaline (NA) was evaluated. YN-induced vasoconstriction of isolated rat aorta rings was determined using organ bath technique. Results and conclusion Baseline BP increased with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine, while HR decreased, compared with vehicle and control. 90oHUT rapidly reduced SBP, DPB and MAP, but increased HR, for control and vehicle-treated groups, but BP was steady with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine. The 90oHUT-increase in HR was most pronounced with the 100 mg/kg YN powder suspension (the traditional formulation). This accords with increased plasma NA. YN also induced vasoconstriction in rat aorta via α1-receptor activation. Thus, the anti-hypotensive action of YN involved a stimulating effect on the heart and blood vessels via sympathetic activation. The results support the traditional use of YN and demonstrated the effectiveness of YN for OH prevention.

Background Hypotension and bradycardia are common hemodynamic complications following carotid artery stenting in patients with carotid artery stenosis. Intravenous fluid resuscitation and inotropes such as dopamine are conventional treatments for post-carotid artery stenting hypotension. However, in case of resistant hypotension, there is no clear treatment method. In this report, while intravenous fluid and inotropes did not resolve the patient’s hypotension, oral midodrine treated post-carotid artery stenting hypotension. Case presentation In this report, we present an 82-year-old Caucasian man complaining of a single episode of unilateral visual loss. The patient had left internal carotid artery stenosis and underwent carotid artery stenting. After the procedure, he developed prolonged post-carotid artery stenting hypotension, which was resistant to intravenous fluids and inotropes but immediately showed a promising response to oral midodrine. Conclusion Oral midodrine can be considered in treatment of post-carotid artery stenting hemodynamic complications.

Prolonged use of intravenous (IV) vasopressors in patients with septic shock can lead to deleterious effects.This study assessed the impact of midodrine administration on weaning off IV vasopressors and its economic value.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.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.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.

Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully.A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient.Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Resumen El síncope, definido como una pérdida transitoria de la conciencia que cursa con recuperación espontánea y completa, es secundario a un amplio grupo etiológico, incluido el de origen vasovagal desencadenado por una descarga adrenérgica u ortostatismo. El tratamiento de esta entidad incluye medidas no farmacológicas y farmacológicas, como la administración de midodrina, un agonista de los receptores a de acción periférica, usada en el control de la hipotensión ortostática y cuyo empleo ha demostrado mejoría en los síntomas de esta alteración. Se presenta el caso de una mujer de 18 años, con antecedente de síncope vasovagal en tratamiento con medidas no farmacológicas y midodrina desde seis meses antes, quien consultó al servicio de urgencias de un centro de atención de nivel IV por cuadro clínico consistente en ingestión intencionada de una sobredosis de midodrina. En el ingreso se documentaron crisis hipertensiva, bradicardia extrema y compromiso hepático y renal. Se indicó tratamiento sintomático con resolución de las alteraciones clínicas y paraclínicas e intervención del equipo de salud mental. Abstract Syncope, defined as a transitory loss of consciousness characterised by its rapid onset, short duration, and spontaneous complete recovery, is secondary to a wide ethiological group, such as the vasovagal origin triggered by an adrenergic discharge or orthostatism. The management of this entity includes both non-pharmacological measures and pharmacological treatment such as the use of midodrine, a peripherally acting alpha receptor agonist, used in the management of orthostatic hypotension, whose use has shown improvement in the symptoms of this condition. We present a clinical case of an 18-year-old woman, with a history of vasovagal syncope under treatment with midodrine and non-pharmacological measures for 6 months, who was admitted to the emergency department of a level IV care center due to an intentional intake of midodrine overdose. Upon admission, a hypertensive crisis with extreme bradycardia, and liver and kidney involvement were documented. Symptom´s management was started with resolution of clinical and paraclinical alterations, and intervention by the mental health team.

espanolEl sincope puede clasificarse en reflejo (neuromediado), por hipotension ortostatica o secundario a patologia cardiovascular. Dado que el sincope reflejo tiene buen pronostico, el tratamiento va dirigido basicamente a la prevencion de recidivas. Se debe explicar a todo paciente el diagnostico, tranquilizarlo y asesorarle sobre el riesgo de recurrencia y la forma de evitar las situaciones y los factores desencadenantes. Las maniobras isometricas de contrapresion de miembros superiores e inferiores pueden evitar el desarrollo de sincope una vez iniciados los sintomas y evitando caidas. Puede considerarse el entrenamiento con basculacion para instruir a los pacientes jovenes. En pacientes con episodios muy recurrentes de la forma ortostatica del sincope vasovagal, puede considerarse la administracion de fludrocortisona o midodrina. El sincope por hipotension ortostatica se suele presentar en pacientes de edad y con tratamiento hipotensor. Debemos, en primer lugar, ajustar el tratamiento hipotensor. La ingesta de 400-500 ml de agua entre 3-4 veces al dia puede ayudar en ambos sincopes reflejo y por hipotension ortostatica. El sincope cardiogenico se presenta en pacientes con cardiopatia de base o electrocardiograma anormal, suele tener peor pronostico y debe conocerse su mecanismo final para establecer el tratamiento. EnglishSyncope can be classified as reflex (neuromediated) syncope, syncope due to orthostatic hypertension, or syncope secondary to cardiovascular pathology. Given that reflex syncope has a good prognosis, treatment is essentially aimed at preventing recurrence. The diagnosis must be explained to all patients and they must be reassured and advised on the risk of recurrence and how to avoid triggering situations and factors. Isometric counterpressure movements in the upper and lower limbs can avoid onset of syncope once symptoms have begun as well as prevent falls. Tilt training can be considered for instructing young patients. In patients with very recurrent episodes of the orthostatic form of vasovagal syncope, administration of fludrocortisone or midodrine can be considered. Syncope due to orthostatic hypotension tends to occur in elderly patients and those with hypotensive treatment. We must first adjust hypotensive treatment. Intake of 400 - 500 ml of water three to four times per day can help in both reflex and orthostatic hypotension syncope. Cardiogenic syncope occurs in patients with underlying cardiopathy or an abnormal electrocardiogram. It tends to have a poor prognosis and its end mechanism must be understood in order to establish treatment.

Midodrine is an antihypotensive agent used primarily in the adult population for orthostatic hypotension and reflex syncope, postural orthostatic tachycardia syndrome (POTS), and hemodialysis-induced hypotension. Limited information about midodrine ingestion and overdose exists in children with only a single case series reported in the literature. Varying presentations of midodrine ingestion in children have not been shown to be acutely life-threatening in doses up to 50 mg. We present a case of a 12-year-old who intentionally ingested 100 mg of midodrine and presented with a hypertensive emergency and seizure activity. This is the largest reported dose ingested in a child. The patient was observed and treated with a nicardipine infusion in the pediatric intensive care unit (PICU). Prompt identification and treatment of symptoms contributed to a favorable outcome with no neurologic deficits and complete recovery from an intentional ingestion of midodrine. Mechanism, duration of action, and management of midodrine ingestion including treatment for a hypertensive emergency in children are discussed. Commonly used pharmacologic agents to treat hypertension are reviewed. This case report of a significant ingestion of midodrine reviews management of hypertensive emergencies and provides information and guidance to healthcare professionals unfamiliar with this medication and its potentially fatal effects.

Background Acute-on-chronic liver failure (ACLF) is a syndrome of acute portal hypertension with high short-term mortality. ACLF patients have low mean arterial pressure (MAP), systemic vascular resistance, and high cardiac output. This, in turn, leads to an increased incidence of ascites, acute kidney injury, and hyponatremia. We evaluated the role of the early addition of midodrine, which has not been analyzed to date. Methods ACLF patients who were started on midodrine (Gr. A) in addition to standard of care (SOC) for ascites control were included and compared with those who received only SOC (Gr. B). The aim was to assess the hemodynamics, ascites control, diuretic-related complications, and mortality at 1 month. Results Forty-five ACLF patients (Gr. A-21; Gr. B-24) were included in the pilot study. At inclusion, the baseline characteristics were similar among the groups. The dose of midodrine was 22.5 (7.5–22.5) mg/day for 22.29 ± 8.75 days in Gr. A. Midodrine significantly improved the MAP and urinary sodium excretion. Only 33.34% of patients required paracentesis in Gr. A compared with 62.5% in Gr. B (p = 0.05). Gr. A patients tolerated a higher dose of diuretics than Gr. B. Diuretic-related complications developed in 54.2% of patients in Gr. B compared with only 23.8% in Gr. A (p = 0.03). Fourteen percent in Gr. A developed side effects to midodrine and required dose modification. Mortality at day 30 was similar in both groups. Conclusion Addition of midodrine improves the hemodynamics, tolerability of diuretics, and ascites control in ACLF patients.

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ(2)= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies.In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic.Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

We thank Fernández–Fernández et al. for their interest in our manuscript and for raising the question about the potential use of midodrine in patients with decompensated and worsening chronic heart failure.

Background The American Society for Parenteral and Enteral Nutrition (ASPEN)/ Society of Critical Care Medicine and the European Society for Clinical Nutrition and Metabolism guidelines recognize that critically ill patients receiving stable, low doses of vasopressors have experienced the advantages of early initiation of enteral nutrition (EN). However, clinical questions remained unanswered including vasopressor combinations associated with complications, the advent of other therapies during hypotensive states, as well as the volume and content of EN that might contribute to the development of a nonocclusive mesenteric ischemia (NOMI). Presentation A 68-year old male with a history of hypertension, hyperlipidemia, atrial fibrillation, coronary artery disease with two-vessel bypass grafting, and peripheral vascular disease underwent subtotal excision of an infected right axillofemoral-femoral bypass graft. Postoperatively, EN was held because of hemodynamic instability and postsurgical complications. A fiber-free, high-protein, and low-residue formula was started at 10 ml/h while the patient was receiving stable doses of midodrine, norepinephrine, and vasopressin. Despite advancement of tube-feed rates to goal, nasogastric output never exceeded 300 ml. Computerized tomography of the abdomen showed diffuse bowel distention with pneumatosis, concerning for bowel ischemia. No surgical interventions were pursued, and the patient died. Conclusions Our patient developed NOMI postoperatively while receiving EN. Further studies addressing EN route, trophic vs full EN, recommended formula, the safety of vasoactive agents, the addition of fiber to EN, and continuous venovenous hemodiafiltration in relation to NOMI are needed, as there continues to be clinical controversy regarding these topics.

Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS). We evaluate the real-life effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine in a nonintensive care unit (non-ICU) setting in the United States, where terlipressin is not available. The diagnosis of HRS and definitions of response to therapy were based on 2015 guidelines from the International Club of Ascites. In adult patients with HRS without partial or full response to oral midodrine and subcutaneous octreotide, norepinephrine was administered at a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline. We assessed predictors of response and treatment outcomes. A total of 61 patients were administered midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD-Na (Model for End-Stage Liver Disease-sodium) score was 30 (interquartile range [IQR] 24-35). Responders were more likely to have alcohol-related liver disease and lower Acute-on-Chronic Liver Failure (ACLF) grade. Of the nonresponders, 20 were then administered norepinephrine, of whom 45% achieved full or partial response. Achieving an MAP increase of ≥10 mm Hg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant-free survival at 90 days (88% versus 27%; P = 0.02); 5 of 20 patients experienced norepinephrine treatment-related adverse events, namely arrhythmias. Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide. Based on these data, we propose a practical stepwise algorithm for vasoconstrictor therapy to manage HRS in situations where terlipressin is not an option.

Enantiomeric resolution of the drug and complete separation from its degradation products was successfully achieved on a PAK IG-3 (150 × 4.6 mm i.d., 3 µm particle size) column, using UV detector at a wavelength of 290 nm, with mobile phase consisting of acetonitrile, 20 mM ammonium bicarbonate at the ratio of 95:05 (v/v), and a flow rate of 0.7 mL/min. In order to subjected to stress conditions, the drug has been exposed to alkaline, acidic, neutral, oxidative, and photolytic conditions. The products of degradation were well resolved from the main peak and proved the method's stability-indicating method. The method linear ranged between 10-110 μg/mL and 5-100 μg/mL for (+) and (-) midodrine enantiomers and regression analysis showed a correlation coefficient value (

Background Stress urinary incontinence is a common and widespread problem among women that can significantly reduce the quality of life of those affected and potentially result in limitations to the lives and activities of their friends and family members. We aimed to observe the effect of floating needle therapy combined with acupuncture point embedding in the treatment of female stress urinary incontinence after childbirth. Methods A total of 64 postpartum female stress urinary incontinence patients who were treated and hospitalized in the Urology Clinic of the Ningbo Traditional Chinese Medicine Hospital of the Zhejiang Province from September 2020 to August 2021 were randomly allocated to the experimental group and the control group, each with 32 cases. The control group was treated with the drug midodrine combined with Kegel training, and the experimental group was treated with floating needle therapy combined with acupoint embedding. After 8 weeks of continuous treatment, the pelvic floor muscle strength, urinary incontinence score, and the improvement of urine leakage in the 1 h pad test were observed. We then evaluated the clinical efficacy of the 2 groups and the state of urinary incontinence at 3 months and 6 months as assessed by telephone follow-up. Results After treatment, the pelvic floor muscle strength of the 2 groups had significantly increased, and both the urinary incontinence score and the urine leakage volume of the 1 h pad test were significantly reduced. The pelvic floor muscle strength of the experimental group was significantly higher than that of the control group after treatment, the urinary incontinence score and the amount of urine leakage of the 1 h pad test were significantly lower than those of the control group. The total effective rate of the experimental group was 90.63% (27/32), which was higher than that of the control group (71.88%, 23/32). Conclusions With the benefits of being both convenient and efficient, floating needle therapy combined with press-needle acupoint embedding is effective in treating female stress urinary incontinence after childbirth. Trial registration Chinese Clinical Trial Registry ChiCTR2100047558.

Background The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. Methods In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. Conclusion The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Background A single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion. Methods and Results Spontaneously hypertensive rats on a low‐salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α‐adrenergic agonist midodrine (4 mg/kg per day), or a high‐salt diet (all groups n=6–7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA‐mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA‐treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA‐treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin. Conclusions Intact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure–lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alphaChanges in intraurethral pressure (IUP) induced by midodrine (alphaBoth silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction.Alpha

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with suspected acute kidney injury in patients with cirrhosis.This article provides practical advice for the management of patients with cirrhosis and acute kidney injury based on the best available published evidence. This best practice document is not based on a formal systematic review. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Clinical GastroenterologyHepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Acute kidney injury (AKI) should be diagnosed when the serum creatinine increases by ≥0.3 mg/dL within 48 hours or is ≥50% from baseline or when the urine output is reduced below 0.5 mL/kg/h for6 hours. BEST PRACTICE ADVICE 2: Preventive measures against the development of AKI in cirrhosis include (1) avoidance of potentially nephrotoxic medications like nonsteroidal anti-inflammatory drugs (NSAIDs), (2) avoidance of excessive or unmonitored diuretics or nonselective beta-blockade, (3) avoidance of large-volume paracentesis without albumin replacement, and (4) counseling patients to avoid alcohol use. BEST PRACTICE ADVICE 3: (A) Investigation is directed to determining the cause of AKI, which can be due to hypovolemic causes (volume responsive, and the most common cause of AKI in patients with cirrhosis); acute tubular necrosis; hepatorenal syndrome with AKI (HRS-AKI) (a functional renal failure that persists despite volume repletion); HRS with acute kidney disease, a type of functional renal failure of3 months- duration in which criteria for HRS-AKI are not met; or postrenal, which occurs only rarely. (B) The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry (Na+ and urea) and selected urinary biomarkers, and renal ultrasound. BEST PRACTICE ADVICE 4: A rigorous search for infection is required in all patients with AKI. A diagnostic paracentesis should be carried out to evaluate for spontaneous bacterial peritonitis; blood and urine cultures and chest radiograph are also required. There is no role for routine prophylactic antibiotics in patients with AKI, but broad-spectrum antibiotics should be started whenever infection is strongly suspected. BEST PRACTICE ADVICE 5: When AKI is diagnosed, diuretics and nonselective beta-blockers should be held, NSAIDs discontinued, the precipitating cause of AKI treated, and fluid losses replaced, administering albumin 1 g/kg/d for 2 days if the serum creatinine shows doubling from baseline. Urine output, vital signs, and when indicated, echocardiography or CVP (if there is a pre-existing central line) should be used to monitor fluid status. BEST PRACTICE ADVICE 6: When the serum creatinine remains higher than twice the baseline value despite these measures, treatment of HRS-AKI should be initiated with albumin at a dose of 1 g/kg intravenously on day 1 followed by 20-40 g daily along with vasoactive agents (terlipressin; if terlipressin is not available, either a combination of octreotide and midodrine; or norepinephrine, depending on institutional preferences) and continued either until 24 hours following the return of the serum creatinine level to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a total of 14 days of therapy. BEST PRACTICE ADVICE 7: Terlipressin should be initiated as a bolus dose of 1 mg every 4-6 hours (total 4-6 mg/d). The dose should be increased to a maximum of 2 mg every 4-6 hours (total 8-12 mg/d) if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value. Alternatively, clinicians can administer terlipressin by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d, or reversal of HRS. As per Food and Drug Administration restrictions, terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of90%. BEST PRACTICE ADVICE 8: Oral midodrine when used should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily with octreotide (starting with 100 μg and titrating upward to 200 μg subcutaneously 3 times daily). BEST PRACTICE ADVICE 9: Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to50 mL/h for at least 4 hours. BEST PRACTICE ADVICE 10: The risks of ischemic side effects of terlipressin and norepinephrine include angina and ischemia of fingers, skin, and intestine. These side effects may be lowered by starting at the lowest dose and gradually titrating upward. BEST PRACTICE ADVICE 11: Fluid status should be closely monitored because of the risk of pulmonary edema with excessive use of albumin. BEST PRACTICE ADVICE 12: Renal replacement therapy (RRT) may be used in the management of (A) AKI secondary to acute tubular necrosis; (B) HRS-AKI in potential candidates for liver transplantation (that is, RRT should not be used in patients with HRS-AKI who are not candidates for liver transplantation); and (C) AKI of uncertain etiology in which the need for RRT may be considered on an individual basis. BEST PRACTICE ADVICE 13: Transjugular intrahepatic portosystemic shunts should not be used as a specific treatment of HRS-AKI. BEST PRACTICE ADVICE 14: Liver transplantation is the most effective treatment for HRS-AKI. Pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes. Selected patients with HRS-AKI may require simultaneous liver kidney transplantation based on updated Organ Procurement and Transplantation Network listing criteria.

Many people, particularly elderly, experience dizziness upon standing. It is important to always measure the blood pressure and heart rate in the supine and standing position in these patients. In case of orthostatic hypotension with an insufficient increase in heart rate, one has to consider autonomic dysfunction. Alpha-synucleopathies are frequent causes of autonomic dysfunction, including Parkinson's disease, Pure Autonomic Failure and Multiple System Atrophy. The quality of life can significantly be improved in patients with autonomic dysfunction due to life-style measures (increased salt and water intake, compressive stockings, head-up sleeping) and medication to increase blood pressure (fludrocortisone, midodrine). There is often a considerable delay in the diagnosis of autonomic dysfunction, which prevents adequate treatment. The main message of this paper is that we should all search for orthostatic hypotension in patients with dizziness and, in case of insufficient heart rate increase, refer these patients for autonomic function testing.

Vasovagal syncope (VVS) can occur in every third of human population. Clinical symptoms of VVS areas a result of arterial hypotension with critical global cerebral hypoperfusion due to vasodilatation and bradicardia. Bradicardia is manifested as sinus node dysfunction and atrioventricular conduction disturbances due to activation of nervus vagus. Asystole can take place in some cases. Lack of efficacy of permanent pacemaker founds in patients to prevent of VVS. The results of double blind placebo controlled studies, European and American expert's opinions, probable causes of lack of efficacy of pacemakers in such category of patients and way of solution of this problem are discussed in the review. Syncope recurrences in spite of pacemaker implantation, risk of surgery complications and good life prognosis are arguments for therapeutic approach, now suitable for the most of patients with VVS. Case report (VVS with asystole but without of pacemaker implantation) with successful follow-up is analyzed in the article.

Dysautonomia covers a range of clinical conditions with different characteristics and prognoses. They are classified as Reflex Syndromes, Postural Orthostatic Tachycardia Syndrome (POTS), Chronic Fatigue Syndrome, Neurogenic Orthostatic Hypotension (nOH) and Carotid Sinus Hypersensitivity Syndrome. Reflex (vasovagal) syndromes will not be discussed in this article. Reflex (vasovagal) syndromes are mostly benign and usually occur in patients without an intrinsic autonomic nervous system (ANS) or heart disease. Therefore, they are usually studied separately. Cardiovascular Autonomic Neuropathy (CAN) is the term most currently used to define dysautonomia with impairment of the sympathetic and/or parasympathetic cardiovascular autonomic nervous system. It can be idiopathic, such as multisystemic atrophy or pure autonomic failure, or secondary to systemic pathologies such as diabetes mellitus, neurodegenerative diseases, Parkinson's disease, dementia syndromes, chronic renal failure, amyloidosis and it may also occur in the elderly. The presence of Cardiovascular Autonomic Neuropathy (CAN) implies greater severity and worse prognosis in various clinical situations. Detection of Orthostatic Hypotension (OH) is a late sign and means greater severity in the context of dysautonomia, defined as Neurogenic Orthostatic Hypotension (nOH). It must be differentiated from hypotension due to hypovolemia or medications, called non-neurogenic orthostatic hypotension (nnOH). OH can result from benign causes, such as acute, chronic hypovolemia or use of various drugs. However, these drugs may only reveal subclinical pictures of Dysautonomia. All drugs of patients with dysautonomic conditions should be reevaluated. Precise diagnosis of CAN and the investigation of the involvement of other organs or systems is extremely important in the clinical suspicion of pandysautonomia. In diabetics, in addition to age and time of disease, other factors are associated with a higher incidence of CAN, such poor glycemic control, hypertension, dyslipidemia and obesity. Among diabetic patients, 38-44% can develop Dysautonomia, with prognostic implications and higher cardiovascular mortality. In the initial stages of DM, autonomic dysfunction involves the parasympathetic system, then the sympathetic system and, later on, it presents as orthostatic hypotension. Valsalva, Respiratory and Orthostatic tests (30:15) are the gold standard methods for the diagnosis of CAN. They can be associated with RR Variability tests in the time domain, and mainly in the frequency domain, to increase the sensitivity (protocol of the 7 tests). These tests can detect initial or subclinical abnormalities and assess severity and prognosis. The Tilt Test should not be the test of choice for investigating CAN at an early stage, as it detects cases at more advanced stages. Tilt response with a dysautonomic pattern (gradual drop in blood pressure without increasing heart rate) may suggest CAN. Treatment of patients at moderate to advanced stages of dysautonomia is quite complex and often refractory, requiring specialized and multidisciplinary evaluation. There is no cure for most types of Dysautonomia at a late stage. NOH patients can progress with supine hypertension in more than 50% of the cases, representing a major therapeutic challenge. The immediate risk and consequences of OH should take precedence over the later risks of supine hypertension and values greater than 160/90 mmHg are tolerable. Sleeping with the head elevated (20-30 cm), not getting up at night, taking short-acting antihypertensive drugs for more severe cases, such as losartan, captopril, clonidine or nitrate patches, may be necessary and effective in some cases. Preventive measures such as postural care; good hydration; higher salt intake; use of compression stockings and abdominal straps; portioned meals; supervised physical activity, mainly sitting, lying down or exercising in the water are important treatment steps. Various drugs can be used for symptomatic nOH, especially fludrocortisone, midodrine and droxidopa, the latter not available in Brazil. The risk of exacerbation or triggering supine hypertension should be considered. Chronic Fatigue Syndrome represents a form of Dysautonomia and has been renamed as a systemic disease of exercise intolerance, with new diagnostic criteria: 1 - Unexplained fatigue, leading to occupational disability for more than 6 months; 2 - Feeling ill after exercising; 3 - Non-restorative sleep; 4 - One of the following findings: cognitive impairment or orthostatic intolerance. Several pathologies today have evolved with chronic fatigue, being called chronic diseases associated with chronic fatigue. Postural orthostatic tachycardia syndrome (POTS), another form of presentation of dysautonomic syndromes, is characterized by sustained elevation of heart rate (HR) ≥30 bpm (≥40 bpm if

Background:Vasovagal syncope is the most common cause of syncope in childhood and its treatment is not at a satisfactory level yet. We aimed to investigate patients who were diagnosed with vasovagal syncope, did not benefit from conventional treatment, received midodrine treatment, and to evaluate their response to midodrine treatment.Methods:Files of 24 patients who were diagnosed with recurrent vasovagal syncope, did not benefit from non-pharmacological treatments, and received midodrine treatment during June 2017–October 2019 were retrospectively analysed.Results:In total, 24 patients received a treatment dose of midodrine at 5 mg/day (2.5 mg BID) included in the study. The mean number of syncope was 5.75 ± 2.67 prior to treatment. Following treatment, the mean number of syncope was 0.42 ± 0.89. It was observed that syncope episodes did not recur in 17 patients, but it recurred in 4 out of 7 patients in the first 3 months of the treatment and did not recur in the following months. The episodes improved in two patients with an increase in the treatment dose, but the syncope episodes continued in only one patient.Conclusion:It was concluded that midodrine treatment was effective and safe in adolescents with recurrent vasovagal syncope.

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.

Aims Syncope can lead to injuries. We determined the frequency, severity, and predictors of injuries due to syncope in cohorts of syncope patients. Methods and results Participants were enrolled in the POST2 (fludrocortisone) and POST4 (midodrine) vasovagal syncope (VVS) randomized trials, and POST3 enrolled patients with bifascicular block and syncope. Injury was defined as minor (bruising, abrasions), moderate (lacerations), and severe (fractures, burns, joint pain), and recorded up to 1 year after enrolment. A total of 459 patients (median 39 years) were analysed. There were 710 faints occurred in 186 patients during a 1-year follow-up. Fully 56/186 (30%) of patients were injured with syncope (12% of overall group). There were 102 injuries associated with the 710 faints (14%), of which 19% were moderate or severe injuries. Neither patient age, sex, nor the presence of prodromal symptoms associated with injury-free survival. Patients with bifascicular block were more prone to injury (relative risk 1.98, P = 0.018). Patients with ≥4 faints in the prior year had more injuries than those with fewer faints (relative risk 2.97, P Conclusion Injuries are frequent in syncope patients, but only 4% of injuries were severe. None of age, sex, and prodromal symptoms associate with injury.

PURPOSE: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α(1)-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement. METHODS: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥24 hours. Subjects received oral midodrine (20 mg) or placebo every 8 hours in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates. RESULTS: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10.0–54.0] vs 22.5 [10.4–40.0] hours; difference, 1.0 hour; 95% CI, −10.4 to 12.3 hours; p=0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p=0.02). CONCLUSION: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients. TRIAL REGISTRATION: NCT01531959, registered on February 13, 2012

Intradialytic hypotension (IDH) is a frequent and serious complication of chronic haemodialysis, linked to adverse long-term outcomes including increased cardiovascular and all-cause mortality. IDH is the end result of the interaction between ultrafiltration rate (UFR), cardiac output and arteriolar tone. Thus excessive ultrafiltration may decrease the cardiac output, especially when compensatory mechanisms (heart rate, myocardial contractility, vascular tone and splanchnic flow shifts) fail to be optimally recruited. The repeated disruption of end-organ perfusion in IDH may lead to various adverse clinical outcomes affecting the heart, central nervous system, kidney and gastrointestinal system. Potential interventions to decrease the incidence or severity of IDH include optimization of the dialysis prescription (cool dialysate, UFR, sodium profiling and high-flux haemofiltration), interventions during the dialysis session (midodrine, mannitol, food intake, intradialytic exercise and intermittent pneumatic compression of the lower limbs) and interventions in the interdialysis period (lower interdialytic weight gain and blood pressure–lowering drugs). However, the evidence base for many of these interventions is thin and optimal prevention and management of IDH awaits further clinical investigation. Developing a consensus definition of IDH will facilitate clinical research. We review the most recent findings on risk factors, pathophysiology and management of IDH and, based on this, we call for a new consensus definition of IDH based on clinical outcomes and define a roadmap for IDH research.

Shock is common in the intensive care unit, affecting up to one third of patients. Treatment of shock is centered upon managing hypotension and ensuring adequate perfusion via administration of fluids and catecholamine vasopressors. Due to the risks associated with catecholamine vasopressors, interest has grown in using catecholamine-sparing agents such as midodrine and methylene blue. Midodrine is an orally administered alpha-1 adrenergic agonist while methylene blue is an intravenously administered blue dye used to restore vascular tone and increase blood pressure. Separate MEDLINE, Scopus, and Embase database searches were conducted to assess literature revolving around these agents. Examples of search terms included "midodrine", "methylene blue", "critically ill", "shock", and "catecholamine-sparing." Several studies have evaluated their use in patients with shock and found potential benefits in terms of causing significant elevations in blood pressure and hastening catecholamine vasopressor discontinuation with few adverse effects; however, robust evidence is lacking for these off-label indications. Because of the variety of dosing strategies used and the incongruences between patient populations, it is also challenging to define finite recommendations. This review aims to summarize current evidence for the use of midodrine and methylene blue as catecholamine-sparing agents in critically ill patients with resolving or refractory shock.

Neurogenic orthostatic hypotension (nOH), a drop in blood pressure upon standing resulting from autonomic malfunction, may cause debilitating symptoms that can affect independence in daily activities and quality-of-life. nOH may also be associated with cardiovascular comorbidities (e.g., supine hypertension, heart failure, diabetes, and arrhythmias), making treatment decisions complicated and requiring management that should be based on a patient's cardiovascular profile. Additionally, drugs used to treat the cardiovascular disorders (e.g., vasodilators, β-blockers) can exacerbate nOH and concomitant symptoms. When orthostatic symptoms are severe and not effectively managed with nonpharmacologic strategies (e.g., water ingestion, abdominal compression), droxidopa or midodrine may be effective. Droxidopa may be less likely than midodrine to exacerbate supine hypertension, based on conclusions of a limited meta-analysis. In conclusion, treating nOH in patients with cardiovascular conditions requires a balance between symptom relief and minimizing adverse outcomes.

DOI：10.3969/j.issn.1672⁃6731.2020.05.016

Introduction: Autonomic dysfunction is an integral part of Parkinson disease (PD) complex and can be seen both in early and advanced stages. There is a paucity of medicines available to manage autonomic dysfunction in PD and this adds to the considerable morbidity associated with the illness.Areas covered: The pathophysiology and the available therapeutic options of autonomic dysfunction seen in PD are discussed in detail. The potential targets for novel regimens are reviewed and the available literature on the drugs emerging in management of autonomic dysfunction in PD is highlighted.Expert opinion: In the current scenario, there are several drugs that can be tried for constipation viz stool laxatives, prucalopride, prokinetic agents and a high fiber diet. Bladder dysfunction has been treated with β-agonists and with mirabegron, a selective β-3 agonist, the anticholinergic side effects are minimized, and the drug has been found to be effective. Orthostatic hypotension is managed with midodrine while droxidopa is a new drug with promising efficacy. Botulinum toxin works best for management of sialorrhea, but repeated injections are needed.

Orthostatic hypotension is defined as a decrease in blood pressure of 20 mm Hg or more systolic or 10 mm Hg or more diastolic within three minutes of standing from the supine position or on assuming a head-up position of at least 60 degrees during tilt table testing. Symptoms are due to inadequate physiologic compensation and organ hypoperfusion and include headache, lightheadedness, shoulder and neck pain (coat hanger syndrome), visual disturbances, dyspnea, and chest pain. Prevalence of orthostatic hypotension in the community setting is 20% in older adults and 5% in middle-aged adults. Risk factors such as diabetes mellitus increase the prevalence of orthostatic hypotension in all age groups. Orthostatic hypotension is associated with a significant increase in cardiovascular risk and falls, and up to a 50% increase in relative risk of all-cause mortality. Diagnosis is confirmed by performing a bedside simplified Schellong test, which consists of blood pressure and heart rate measurements after five minutes in the supine position and three minutes after moving to a standing position. If the patient is unable to stand safely or the clinical suspicion for orthostatic hypotension is high despite normal findings on the bedside test, head-up tilt table testing is recommended. Orthostatic hypotension is classified as neurogenic or nonneurogenic, depending on etiology and heart rate response. Treatment goals for orthostatic hypotension are reducing symptoms and improving quality of life. Initial treatment focuses on the underlying cause and adjusting potentially causative medications. Nonpharmacologic strategies include dietary modifications, compression garments, physical maneuvers, and avoiding environments that exacerbate symptoms. First-line medications include midodrine and droxidopa. Although fludrocortisone improves symptoms, it has concerning long-term effects.

Background Midodrine hydrochloride is an alpha-1 agonist that has been used in the management of syncope in patients with orthostatic hypotension, vasovagal syncope and vasodepressor carotid sinus syndrome when non-pharmacological means have failed. However, there are very limited information about its use, tolerability and side effects among the elderly population. Objectives We aim to document effectiveness of Midodrine in patients who have been diagnosed with neurocardiogenic syncope assessed and managed at a specialist falls and syncope outpatient unit. We monitored for changes in patients' symptoms, adverse reactions reported and optimum drug dosages that have shown benefit in this cohort of patients. Methods A prospective observational study of 33 subjects aged between 68 and 94 (mean age 79) who have been started on Midodrine therapy following positive tilt table test or confirmed diagnosis of symptomatic orthostatic hypotension despite conservative managements. They have been followed up for a mean of 2.9 years. Results 81% of patients( n=27) reported significant improvement in their symptoms. Although 7 patients reported adverse reactions to Midodrine, the majority of the patients tolerated the therapy well and continued on the treatment except for one patient who experienced gastrointestinal discomfort and withdrew completely. Commonest side effects are pruritus and piloerection, but they are not amenable to treatment due to underlying mechanism of action of Midodrine on hair follicles. The dosage varies from 2.5mg to 10mg, taken at 8am, 12pm and 5pm due to risk of nocturnal supine hypertension. Higher dose did not correlate with higher possibility of experiencing side effects. Conclusion Midodrine appears to be effective, safe and well tolerated among the elderly population. It should be considered in the management of patients with neurocardiogenic syncope when non-pharmacological means have failed, irrespective of age. This observational study requires further confirmation by randomised control studies with larger sample size.

Arteriovenous fistula (AVF) dysfunction is one of the common obstacles in performing hemodialysis treatment. Acute and chronic thrombosis of the fistula, stenosis, and hematomas are the major causes of the dysfunction. Here, we present an unexpected complication of midodrine use which caused in AVF dysfunction in a female patient who was suffering from hemodialysis-related hypotension.

Background Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. Ascites formation in patients with Kristeen E. cirrhosis, portal hypertension, or both usually results from hyperdynamic circulatory Zaki dysfunction. Aim of the Work to investigate the effect and prognostic value of treatment of hepatorenal syndrome in patients with liver cirrhosis and massive ascites by LVP, somatostatin analogue and midodrine intake and its effect on renal resistive index. Patients and Methods This study was carried on 40 patients divided into 4 groups where 10 patients (G1) received midodrine therapy and albumin infusion, 10 patients (G2) had tapping of ascites with albumin infusion, 10 patients (G3) received octreotide therapy and albumin infusion and the last 10 patients (G4) received octreotide, midodrine and albumin infusion. All patients were subjected to careful history taking and thorough clinical examination. Before and after intervention, patients had laboratory investigation including complete blood picture, liver function tests, renal function test and ascitic fluid analysis in addition to renal artery Doppler imaging. Results The study revealed considerable decline in RI in G1 (midodrine group), the change fell short of statistical significance. However, our study showed significant effect of midodrine administration on renal functions as expressed by serum creatinine, blood urea and creatinine clearance. In G3 (octreotide group), the effect of treatment on renal artery RI was minimal. The other group that perceived significant decline in renal artery resistive index was G4 (midodrine and octreotide group). Conclusions LVP and midodrine combination administration resulted in significant decrease in creatinine clearance. Renal artery resistive index has significant correlation with creatinine clearance in studied group and can be used as non-invasive tool.

Midodrine is a prodrug metabolized to the peripheral acting alpha agonist desglymidodrine and is used to treat orthostatic hypotension. Reports of overdose are rare, consequently there is little gu...

IntroductionIntensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock.Methods and analysisWe will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay.Ethics and disseminationEthics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials.PROSPERO registration numberCRD42021260375.

Background: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.Methods: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.Results: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.Conclusion: The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Purpose To assess the feasibility and physiological efficacy of adjunctive midodrine in patients with vasopressor-dependent hypotension. Materials and methods This was a pilot, open label, randomised controlled trial. Patients were enrolled from two tertiary intensive care units on low dose intravenous vasopressor therapy for more than 24 h. We randomly assigned patients to receive either adjunctive midodrine (10 mg every 8 h) or usual care. The primary efficacy outcome was time to cessation of intravenous vasopressor therapy. Secondary outcomes included protocol compliance, ICU and hospital length of stay. Results We screened 381 patients over 22-months and enrolled 62 (32 in midodrine group, 30 in usual care group). Median time to cessation of vasopressor infusion was 16.5 h for midodrine vs 19 h for usual care (p = 0.22). Time in ICU (50 [25.50, 74.00] hours for midodrine v 59 [38.50, 93.25] hours for usual care, p = 0.14) and hospital length of stay (9 days vs. 7.5 days, p = 0.92) were similar. Protocol compliance was 96.9%. One patient ceased midodrine early due to symptomatic bradycardia. Conclusions Adjunctive midodrine therapy was feasible with acceptable compliance, duration of therapy, and safety profile. However, at the chosen dose, there was no evidence of physiological or clinical efficacy.

Background Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. Objective To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. Design Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481). Setting 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. Patients Patients with recurrent vasovagal syncope and no serious comorbid conditions. Intervention Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. Measurements The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. Results The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. Limitation Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. Conclusion Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. Primary funding source The Canadian Institutes of Health Research.