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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.

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.

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.

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.

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.

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.

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.

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.

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...

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.

Orthostatic hypotension (OH) refers to a significant reduction in blood pressure (BP) that occurs on standing. It mainly results when autonomic reflexes are impaired or when the intravascular volume is depleted. Symptoms can range from syncope, dizziness, even angina or stroke. Major mechanisms causing OH are autonomic dysfunction affecting the baroreflex, severe volume depletion, and adverse medication effects. Case reports have described neurologic symptom association with coronavirus disease 2019 (COVID-19) including dysautonomia. Although most common symptoms of COVID have been primarily respiratory including fever, cough, shortness of breath, myriad other presentations including neurological, gastrointestinal, cardiac, and thromboembolic presentations have also been described. We describe a patient who was found to have OH and recurrent falls secondary to underlying COVID-19 infection and associated dysautonomia who was successfully treated with midodrine and fludrocortisone.

Background: Terlipressin is the first-line pharmacological treatment for hepatorenal syndrome. When terlipressin is unavailable, midodrine/octreotide or norepinephrine, with albumin, represent the alternative treatments. The comparative efficacy of these alternative regimens remains unclear.Objective: To compare the efficacy of midodrine/octreotide to that of norepinephrine for the treatment of patients with hepatorenal syndrome.Methods: In the intensive care setting, sixty patients with hepatorenal syndrome were randomized to initially receive either 0.5 mg/h of norepinephrine (maximum 3 mg/h) or 5 mg of oral midodrine three times/day (maximum 12.5 mg three times/day) plus octreotide (100 μg/6 h) as subcutaneous injection (maximum 200 μg/6 h), together with albumin (20–40 g/day). Treatment was allowed for a maximum of 10 days. Survival was analyzed for up to 30 days. The primary efficacy outcome was the proportion of patients who achieved full response, defined as the return of serum creatinine to a value within 0.3 mg/dl of the baseline at the end of treatment.Results: There was a significantly higher rate of full response in the norepinephrine group (15/26, 57.60%) than the midodrine/octreotide group (5/25, 20%) (p = 0.006). Eleven (42.30%) patients in the norepinephrine group and 6 (24%) in the midodrine/octreotide group survived (p = 0.166).Conclusion: Norepinephrine plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with hepatorenal syndrome.(ClinicalTrials.gov, identifier: NCT03455322).https://clinicaltrials.gov/ct2/show/NCT03455322?cond = Hepatorenal+Syndrome&cntry = EG&draw = 2&rank = 1.

The development of acute kidney injury (AKI) is one of the most frequent complications in patients with cirrhosis. AKI due to volume depletion is the most common etiology and hepatorenal syndrome (HRS) is the second most common cause of AKI in these patients. HRS is the extreme form of kidney injury in patients with cirrhosis, which is caused due to a reduction in renal blood flow unresponsive to volume expansion. The literature involving HRS is rapidly evolving and newer tests and updated definitions have been proposed which allows timely identification and treatment. Here, we will discuss the definition, pathophysiology, prevention, diagnosis, and treatment of HRS.

Background: Intradialytic hypotension (IDH) is the most common complication during hemodialysis procedure. Midodrine, an oral α-1 adrenergic agonist, is commonly used to prevent IDH. However, limited data is available to demonstrate midodrine effectiveness in prevention of IDH in high-risk hemodialysis patients. Objective: To describe the clinical outcomes of using midodrine in patients receiving hemodialysis concerning the incidence of IDH. Also, we aimed to explore the appropriate dose for midodrine use to prevent IDH. Methodology A retrospective cohort of adult with end-stage-renal failure. Exposure: Midodrine. Outcomes measure: IDH was defined as a decline in systolic blood pressure (SBP) by ≥20 mmHg or a decline in main arterial pressure (MAP) by ≥10 mmHg during hemodialysis session. Recurrent IDH was defined as three or more episodes of IDH throughout a year of starting midodrine. Analysis: A descriptive analysis of the frequency of IDH and recurrent IDH. We also, compared the risk of recurrent IDH across various doses of midodrine use. Result: From a total of 68-screened patients’ charts, 45 patients were included in the final analysis. 41.8% (n=28) of the study population had an IDH that required additional interventions to restore the SBP and MAP. IDH occurred in 68% (n=19, P=0.03) of patients with hypoalbuminemia. Recurrent IDH occurred in 36% (n=16) of the patients over their hemodialysis procedure. Incidence of treatment failure (57%, p= 0.02) and recurrent IDH (36%, p=0.04) were statistically significant in patients who received midodrine three time per week (57%) in comparison to those who received more than three days per week Conclusion: This exploratory study shows that a considerable proportion of patients receiving midodrine did not develop IDH or recurrent IDH. A long-term follow-up study with larger number of patients in comparison to the control group would be useful to evaluate the magnitude of efficacy of midodrine in hemodialysis patients with high risk for IDH. Moreover, a future prospective trial that focus on an important clinical outcomes such as cardiovascular events and mortality with midodrin is warranted.

Ropinirole is an overall well-tolerated antiparkinsonian medication that is also used to treat restless leg syndrome (RLS). The incidence of side effects is low, with orthostatic hypotension (OH) only anecdotally reported. Additionally, it is known that the elderly population is very susceptible to adverse drug effects and the prevalence of prescribing cascades that these can trigger is unknown. A 71-year-old male with history of atrial fibrillation, well-controlled diabetes on oral agents, hyperlipidemia, hypertension, ischemic heart failure status post (s/p) implantable cardioverter-defibrillator (ICD) placement with improved ejection fraction (EF), transient ischemic attack (TIA), rheumatoid arthritis, RLS, aortic stenosis s/p mechanical aortic valve replacement on anticoagulation, deep venous thrombosis (DVT), and right knee replacement, presented to the ED with generalized weakness, with difficulty standing from seated position, followed by a fall without head trauma. Over the eight months prior to this presentation, the patient had had similar symptoms that resulted in four falls, two hospital admissions, and new prescriptions of midodrine and compression stockings. On admission, vital signs were remarkable for positive orthostatics with blood pressure (BP) 110/74 mmHg, heart rate (HR) of 86 bpm in supine position and BP 87/51 mmHg, HR of 70 bpm while in standing position. Physical exam was unremarkable except for a known ejection murmur and dry oral mucous membranes. Labs included a creatinine 3.6 mg/dl, blood urea nitrogen (BUN) 66 mg/dl, international normalized ration (INR) of 4.1, B-natriuretic peptide (BNP) of 313 pg/mL, troponin

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.

Background and objectives Pulmonary hypertension is commonly seen in end stage kidney disease and is most commonly due to elevated left heart pressures. There is limited data about vasodilator use during the management of Group 1 pulmonary arterial hypertension in the context of those who also have or later developed end stage kidney disease. The objective of this study was to determine safety and efficacy of vasodilator therapy in precapillary pulmonary hypertension requiring renal replacement therapy. Design This was a single-center retrospective case series. Patients were identified from our Pulmonary Hypertension Clinic using a historical roster from 2012 to 2020. Patients were included if they >18 years of age, had Group 1 or Group 4 (precapillary) pulmonary hypertension on right heart catheterization, and also had end stage kidney disease requiring either intermittent hemodialysis or peritoneal dialysis. Results 18 patients were identified with invasively confirmed Group 1 or Group 4 pulmonary hypertension and end stage kidney disease on renal replacement therapy. Scleroderma was the most common etiology for renal failure. 17 patients were treated with vasodilator therapy. Fifteen patients had paired right heart catheterizations that showed a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Therapy was relatively well tolerated but hypotension was common and midodrine was often helpful. Two patients had successful renal transplantation after starting vasodilator therapy. Conclusion We found vasodilator therapy was reasonably well tolerated and associated with a drop in mean pressure and pulmonary vascular resistance in patients with end stage kidney disease on dialysis.

Pure autonomic failure is a neurodegenerative disorder affecting the autonomic nervous system which clinically presents with orthostatic hypotension. It is a diagnosis of exclusion after detailed clinical examinations and relevant investigations. Here, we discuss a case of 68 years old male who had complaints of multiple episodes of loss of consciousness on standing from a sitting position for the last 3 years. The diagnosis was considered by clinical examinations revealing autonomic dysfunctions with normal appropriate investigations. The patient was treated successfully with midodrine, fludrocortisone, and other non-pharmacological interventions. We focused on doing various autonomic dysfunction tests in the evaluation of a patient with recurrent orthostatic hypotension. We suspect that pure autonomic failure might not have been considered in the differential diagnosis of recurrent orthostatic hypotension and suggest that it is to be kept as a differential in such a scenario. Midodrine has an effective role in syncope due to sympathetic vasoconstrictor failure.

Since the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, over seventy million cases have been reported worldwide. Patients present with various symptoms, including extra-pulmonary manifestations. However, manifestations on adrenal glands have not been reported extensively. Here, we present a case of functional adrenal insufficiency in a COVID-19 patient. A 61-year-old male with a history of hyperlipidemia presented with fatigue, cough, and dyspnea, subsequently tested positive for COVID-19. His blood pressure (BP) on admission was 128/68 mmHg with 86% oxygen saturation on room air. Dexamethasone 6mg daily was started for ten days. Remdesivir was contra-indicated, considering the ALT of 246 and AST of 248. On day seven of hospitalization, he had progressively worsening respiratory symptoms and was transferred to the Intensive Care Unit with BP of 105/63 mmHg. Within 48 hours, he showed positive orthostatic vitals with BP of 85/54 mmHg. Despite intravenous hydration, his BP was consistently low on subsequent days with 88/53 mmHg and 99/66 mmHg. His serum total cortisol level was 9.2 μg/dL, and he showed a positive response to IV Hydrocortisone 50mg as well as oral prednisone 10 mg the following day. We did not obtain a cosyntropin stimulation test because of recent corticosteroid therapy. Midodrine 2.5mg three times daily (TID) was started, then increased to 10 mg to maintain BP and alleviate orthostatic symptoms. However, symptomatic positive orthostatic vitals were persistent. He was discharged on midodrine 7.5 mg TID and Fludrocortisone 0.1 mg daily for suspicion of functional adrenal insufficiency. Additionally, a HDL level of 22 mg/dL was recorded (vs 56 mg/dL six months ago). At three months follow-up, he was off fludrocortisone and midodrine with improved orthostatic symptoms. Hypotension and orthostatic symptoms in COVID-19 could be due to IL-1, IL-6, or tumor necrosis factor-mediated reduction in ACTH secretion. Acute illnesses, including COVID-19, may also increase cortisol demand, causing adrenal insufficiency. Decreased HDL noted in our patient could be another etiology. "Critical Illness-Related Corticosteroid Insufficiency" (CIRCI) is a functional adrenal insufficiency that is not strictly dependent on cortisol level for diagnosis but mostly on the inadequacy of cortisol for inflammation control or supplying the raised metabolic demand. Decreased cortisol complex cleavage, increased activity of an enzyme responsible for cortisol inactivation, and decreased numbers and affinity of cortisol receptors were postulated to play a role. Therefore, adrenal insufficiency as a cause of hypotension following COVID-19 infection should not be overlooked despite normal cortisol levels.

Among the complications of cirrhosis, hepatorenal syndrome (HRS) is characterized by having the worst survival rate. HRS is a disorder that involves the deterioration of kidney function caused primarily by a systemic circulatory dysfunction, but in recent years, systemic inflammation and cirrhotic cardiomyopathy have been discovered to also play an important role. The diagnosis of HRS requires to meet the new International Club of Ascites-Acute Kidney Injury (ICA-AKI) and Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) criteria after ruling out other causes of kidney injury. At the time of diagnosis, it is important to start the medical treatment as soon as possible where three types of vasoconstrictors have been recognized: vasopressin analogs (ornipressin and terlipressin), alpha-adrenergic agonists (norepinephrine and midodrine) and somatostatin analogues (octreotide); all should be combined with albumin infusion. Among them, terlipressin and albumin are the first lines of treatment in most cases, although terlipressin should be monitor closely due to its adverse events. The best treatment of choice is a liver transplant, because it is the only definitive treatment for this disease.

Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress—or lack thereof—in improving outcomes of type 1 HRS over time. We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4–43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2–51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94–1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96–1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95–1.20, p = 0.26) and 0.97 (95% CI 0.85–1.12, p = 0.70). Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.

Background Observational studies suggest that hepatorenal syndrome (HRS) patients who receive pharmacological therapy before orthotopic liver transplantation display a post-transplant outcome similar to those without HRS. The aim of this study was to comprehensively compare and rank the pharmacological therapies for HRS. Methods We reviewed PubMed, Elsevier, Medline, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies that were published between 1 January 1999 and 24 February 2018. The primary endpoint was reversal of HRS. The secondary endpoints were the changes in serum creatinine (Scr) and serum sodium. We evaluated the different therapeutic strategies using network meta-analysis on the basis of Bayesian methodology. Results The study included 24 articles with 1,419 participants evaluating seven different therapeutic strategies for HRS. The most effective treatments to induce reversal of HRS were terlipressin plus albumin, noradrenaline plus albumin, and terlipressin, which had a surface under the cumulative ranking curve (SUCRA) of 0.086, 0.151, and 0.451, respectively. The top two treatments for decreasing Scr were dopamine plus furosemide plus albumin (rank probability: 0.620) and terlipressin plus albumin (rank probability: 0.570). For increasing serum sodium, the optimal treatment was octreotide plus midodrine plus albumin (rank probability: 0.800), followed by terlipressin plus albumin (rank probability: 0.544). Conclusions Terlipressin plus albumin and dopamine plus furosemide plus albumin should be prioritized for decreasing Scr in HRS, and octreotide plus midodrine plus albumin was the most effective at increasing serum sodium. Terlipressin plus albumin showed a comprehensive effect in both decreasing Scr and increasing serum sodium.

Background For patients with end stage renal disease undergoing hemodialysis, erythrocytosis occurs rarely. Erythrocytosis increases the risk of thrombosis, which is a common complication in hemodialysis patients. The risk of thrombosis may also be increased by hypotension. The purpose of our report is to examine the relationship between intradialytic hypotension and erythrocytosis. Case presentation We present a series of five patients with end stage renal disease and erythrocytosis (peak hemoglobin range 15.2–18.5 g/dL). All were erythropoiesis-stimulating agent naïve and non-smokers. Prior to developing erythrocytosis, each patient developed recurring episodes of intradialytic hypotension over several months. A statistically significant inverse correlation was observed between nadir intradialytic systolic blood pressure and hemoglobin concentration. In the index case, midodrine treatment resulted in resolution of the hypotension and erythrocytosis. Most of the patients had multiple acquired renal cysts, which is a potential source of erythropoietin. Four of the five cases developed arteriovenous dialysis access or deep venous thrombosis. Conclusions An association between intradialytic hypotension and erythrocytosis was observed in five cases. We postulate that chronic intermittent hypotension and renal ischemia may lead to erythropoietin secretion, and this cascade could represent a newly recognized cause of secondary erythrocytosis.

Neurogenic orthostatic hypotension (nOH) is a sustained reduction in blood pressure (BP) upon standing that is caused by autonomic dysfunction and is common among patients with a variety of neurodegenerative disorders (eg, Parkinson's disease, multiple system atrophy, pure autonomic failure). A systolic BP drop of ≥20 mmHg (or ≥10 mmHg diastolic) upon standing with little or no compensatory increase in heart rate is consistent with nOH. Symptoms of nOH include light-headedness, dizziness, presyncope, and syncope; these symptoms can severely impact patients' activities of daily living and increase the likelihood of potentially dangerous falls. Because of their patient contact, nurses and nurse practitioners can play a key role in identifying and evaluating patients at risk for nOH. It is advisable to screen for nOH in patients presenting with one or more of the following characteristics: those who have disorders associated with autonomic failure, those with episodes of falls or syncope, those with symptoms upon standing, those who are elderly or frail, or those taking multiple medications. Initial evaluations should include questions about postural symptoms and measurement of orthostatic BP and heart rate. A review of medications for potential agents that can have hypotensive effects should be performed before initiating treatment. Treatment for nOH may include non-pharmacologic measures and pharmacologic therapy. Droxidopa and midodrine are approved by the US Food and Drug Administration for the treatment of symptomatic nOH and symptomatic OH, respectively. nOH is associated with the coexistence of supine hypertension, and the two disorders must be carefully managed. In conclusion, timely screening and diagnosis of patients with nOH can streamline the path to disease management and treatment, potentially improving patient outcomes.

Purpose: To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock. Materials and Methods: PubMed, Scopus, Clinicaltrials.gov, and published abstracts were searched from inception to November 2018 for studies comparing outcomes in shock after midodrine initiation versus no midodrine. Results: Three studies with 2533 patients were included. Patients in whom midodrine was added to intravenous vasopressor therapy compared to intravenous vasopressor therapy alone experienced similar intensive care unit (ICU; mean difference [MD]: 1.38 days, 95% confidence interval [CI]: −3.48 to 6.23, I2 = 93%) and hospital lengths of stay (MD: 4.37 days, 95% CI: −3.45 to 12.19, I2 = 93%) and intravenous vasopressor duration after midodrine initiation (MD: 7.28 days, 95% CI: −0.86 to 15.41, I2 = 97%). Mortality was similar between groups (odds ratio: 0.74, 95% CI: 0.44-1.27, I2 = 65%). Qualitative assessment of reporting biases revealed minimal location bias, moderate selective outcome reporting bias, no selective analysis reporting bias, and no conflict of interest bias. Conclusions: Midodrine had no effect on ICU or hospital length of stay. These results were highly susceptible to the study heterogeneity and availability. Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management.

Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless, considering its high short-term mortality rate and the shortage of liver grafts, a pharmacological treatment is of utmost importance, serving as a bridge to liver transplant. The clinical management of hepatorenal syndrome is currently based on the use of a vasoconstrictor in association with albumin. Terlipressin, noradrenaline and the combination of midodrine and octreotide could be used to treat hepatorenal syndrome. Among these options, terlipressin seems to gather the strongest body of evidence regarding efficacy and should be considered the first line of treatment whenever available and in the absence of contraindications. Treatment with a vasoconstrictor and albumin should be promptly initiated after the diagnosis of hepatorenal syndrome in order for patients to have higher chances of recovery.

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.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.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.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.

Background Syncope is a symptom associated with a wide range of pathological conditions, ranging from benign to life threatening. The most frequent is the reflex syncope that may be challenging to treat because of the complex and partially unknown pathophysiological mechanism that has to be addressed by the chosen therapy. Areas of uncertainty Head-up tilt testing is so far the only clinical test able to reproduce reflex syncope, but its diagnostic yield has been recently redefined. A new mechanism such as adenosine-sensitive syncope and idiopathic atrioventricular block have been recently described, and the appropriate therapy is not yet established. There is uncertainty on the efficacy of theophylline and on the use of cardiac pacing in these patients. Data sources Clinical trial published data and position paper from the main expert groups on fludrocortisone, midodrine, etilefrine, beta-blockers, and cardiac pacing as useful therapies for patients affected by reflex syncope. Therapeutic advances Theophylline proved in observational trials to be efficient in preventing reflex syncope recurrences in patients with documented spontaneous paroxysmal conduction disorders comparable to cardiac pacing in a subgroup of patients. Reboxetine and sibutramine may elicit a significant pressor and tachycardic effect able to delay the onset of symptoms during head-up tilt testing. Droxidopa has short-term effects on improving the symptoms because of orthostatic hypotension. Cardiac pacing is effective in preventing reflex syncope recurrences with best results when the indication for pacemaker implantation was based on the documentation of bradycardia or asystole during the spontaneous event by a cardiac monitor. External compression using elastic bandage or compressive stockings is able to prevent the decrease in blood pressure in patients with orthostatic hypotension. Conclusions The optimal management of the complex diagnostic and therapeutic options can be achieved following a standardized and evidence-based approach to the patient with syncope.

Background: Hepatorenal Syndrome (HRS) is a unique form of acute kidney injury seen in patients with acute liver failure or chronic liver disease in absence of any other iden-tifiable cause of renal failure. Hepatorenal syndrome is asso-ciated with significant morbidity and mortality.Aim of Study: The aim of this study was to assess the safety and efficacy of Erdosteine versus N-acetyl cysteine with octreotide and albumin in the treatment of hepatorenal syndrome in cirrhotic patients.Patients and Methods: The study enrolled 60 liver cirrhosis patients diagnosed to have hepatorenal syndrome who were randomized to receive Erdosteine 300mg or N-acety-lcysteine 600mg three times daily with octreotide (100μgsc three times a day) midodrine (12.5mg orally three times a day) and albumin (1g/kg body weight up to a maximum of 100g) or receive octreotide, midodrine and albumin as a control for two weeks. Renal function was assessed before and after treatment. Side effects and improvement of liver function were recorded.Results: In NAC group; creatinine level was significantly lower after the second week of therapy than baseline level (p=0.006), also there was significantly higher GFR after the first and the second weeks of therapy than baseline level (p= 0.038, 0.001 respectively) and significant higher GFR after the second week than after the first week of therapy (p= 0.015). Meanwhile, no significant difference of creatinine or GFR was detected in Erdosteine group or when the three groups were compared.In NAC group, Child-Pugh score significantly improved compared to control group after 2 weeks of therapy (p=0.004). In the first and second weeks of therapy, the grade of enceph-alopathy was significantly lower in Erdosteine group (p=0.032, 0.040) and in NAC group (p=0.009, 0.004) compared to control group.The side effects were few with no significant difference between their occurrences in the three groups. Conclusion: This study was a pilot study that investigated the effects of Erdosteine versus NAC on human patients with HRS. No significant difference of creatinine or GFR was detected when Erdosteine, NAC and control groups were compared. Improvement of Child-Pugh score in NAC group and hepatic encephalopathy in Erdosteine group were second-ary outcomes of our study.As these drugs had a high safety profile, we recommend further studies using higher doses of the drugs for longer periods and enrollment of larger number of patients to optimize treatment of HRS.

Shock syndromes are associated with unacceptably high rates of mortality in critically ill patients despite advances in therapeutic options. Vasodilatory shock is the most common type encountered in the intensive care unit. It is manifested by cardiovascular failure, peripheral vasodilatation, and arterial hypotension leading to tissue hypoperfusion and organ failure. Hemodynamic support is typically initiated with fluid resuscitation strategies and administration of adrenergic vasopressor agents in nonresponsive patients to restore arterial pressure with subsequent adequate organ reperfusion. Unfortunately, high catecholamine dosing requirements may be necessary to achieve targeted hemodynamic goals that may increase the risk of vasopressor-induced adverse events. The purpose of this article is to review the clinical efficacy and safety data and potential role in therapy for catecholamine-sparing agents in vasodilatory shock. Adjunctive therapeutic options to reduce vasoactive support requirements without compromising arterial pressure include arginine vasopressin and analogs, corticosteroids, midodrine, methylene blue, and angiotensin II. Although concomitant vasopressin and corticosteroids have a more defined role in evidence-based guidelines for managing shock, clinicians may consider other potential catecholamine-sparing agents.