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Annals of Hepatology 2021Among the complications of cirrhosis, hepatorenal syndrome (HRS) is characterized by having the worst survival rate. HRS is a disorder that involves the deterioration of... (Review)
Review
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.
Topics: Hepatorenal Syndrome; Humans
PubMed: 32846202
DOI: 10.1016/j.aohep.2020.07.008 -
Continuum (Minneapolis, Minn.) Feb 2020This article reviews the management of orthostatic hypotension with emphasis on neurogenic orthostatic hypotension. (Review)
Review
PURPOSE OF REVIEW
This article reviews the management of orthostatic hypotension with emphasis on neurogenic orthostatic hypotension.
RECENT FINDINGS
Establishing whether the cause of orthostatic hypotension is a pathologic lesion in sympathetic neurons (ie, neurogenic orthostatic hypotension) or secondary to other medical causes (ie, non-neurogenic orthostatic hypotension) can be achieved by measuring blood pressure and heart rate at the bedside. Whereas fludrocortisone has been extensively used as first-line treatment in the past, it is associated with adverse events including renal and cardiac failure and increased risk of all-cause hospitalization. Distinguishing whether neurogenic orthostatic hypotension is caused by central or peripheral dysfunction has therapeutic implications. Patients with peripheral sympathetic denervation respond better to norepinephrine agonists/precursors such as droxidopa, whereas patients with central autonomic dysfunction respond better to norepinephrine reuptake inhibitors.
SUMMARY
Management of orthostatic hypotension is aimed at improving quality of life and reducing symptoms rather than at normalizing blood pressure. Nonpharmacologic measures are the key to success. Pharmacologic options include volume expansion with fludrocortisone and sympathetic enhancement with midodrine, droxidopa, and norepinephrine reuptake inhibitors. Neurogenic supine hypertension complicates management of orthostatic hypotension and is primarily ameliorated by avoiding the supine position and sleeping with the head of the bed elevated.
Topics: Aged; Diagnosis, Differential; Disease Management; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged
PubMed: 31996627
DOI: 10.1212/CON.0000000000000816 -
Autonomic Neuroscience : Basic &... Dec 2020Neurogenic orthostatic hypotension (OH) is a disabling disorder caused by impairment of the normal autonomic compensatory mechanisms that maintain upright blood... (Review)
Review
Neurogenic orthostatic hypotension (OH) is a disabling disorder caused by impairment of the normal autonomic compensatory mechanisms that maintain upright blood pressure. Nonpharmacologic treatment is always the first step in the management of this condition, but a considerable number of patients will require pharmacologic therapies. Denervation hypersensitivity and impairment of baroreflex buffering makes these patients sensitive to small doses of pressor agents. Understanding the underlying pathophysiology can help in selecting between treatment options. In general, patients with low "sympathetic reserve", i.e., those with peripheral noradrenergic degeneration (pure autonomic failure, Parkinson's disease) and low plasma norepinephrine, tend to respond better to "norepinephrine replacers" (midodrine and droxidopa). On the other hand, patients with relatively preserved "sympathetic reserve", i.e., those with impaired central autonomic pathways but spared peripheral noradrenergic fibers (multiple system atrophy) and normal or slightly reduced plasma norepinephrine, tend to respond better to "norepinephrine enhancers" (pyridostigmine, atomoxetine, and yohimbine). There is, however, a spectrum of responses within these extremes, and treatment should be individualized. Other nonspecific treatments include fludrocortisone and octreotide. The presence of associated clinical conditions, such as supine hypertension, heart failure, postprandial hypotension, PD, MSA, and diabetes need to be considered in the pharmacologic management of these patients.
Topics: Humans; Hypotension, Orthostatic; Multiple System Atrophy; Parkinson Disease; Pure Autonomic Failure
PubMed: 32979782
DOI: 10.1016/j.autneu.2020.102721 -
Clinics in Geriatric Medicine Feb 2020Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity... (Review)
Review
Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions. OH can be caused by volume depletion, blood loss, cardiac pump failure, large varicose veins, medications, or defective activation of sympathetic nerves and reduced norepinephrine release upon standing. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and it is commonly associated with supine hypertension. Several therapeutic options are available.
Topics: Aged; Humans; Hypotension, Orthostatic; Parkinson Disease; Patient Care Management
PubMed: 31733702
DOI: 10.1016/j.cger.2019.09.002 -
Hepatology (Baltimore, Md.) Aug 2015Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the... (Comparative Study)
Comparative Study Randomized Controlled Trial
UNLABELLED
Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival.
CONCLUSION
Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS.
Topics: Aged; Albumins; Analysis of Variance; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatorenal Syndrome; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Kidney Function Tests; Liver Function Tests; Lypressin; Male; Middle Aged; Midodrine; Octreotide; Predictive Value of Tests; Survival Analysis; Terlipressin; Treatment Outcome
PubMed: 25644760
DOI: 10.1002/hep.27709 -
Intensive Care Medicine Oct 2020ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
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-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 h. Subjects received oral midodrine (20 mg) or placebo every 8 h 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 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; 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.
Topics: Adult; Australia; Humans; Hypotension; Intensive Care Units; Midodrine; Vasoconstrictor Agents
PubMed: 32885276
DOI: 10.1007/s00134-020-06216-x -
American Family Physician Jan 2022Orthostatic 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...
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.
Topics: Accidental Falls; Adolescent; Adult; Aged; Blood Pressure; Chest Pain; Diabetes Mellitus; Diet; Dizziness; Droxidopa; Fludrocortisone; Heart Disease Risk Factors; Heart Rate; Humans; Hypotension, Orthostatic; Middle Aged; Midodrine; Quality of Life; Supine Position; Systole; Young Adult
PubMed: 35029940
DOI: No ID Found -
Arquivos Brasileiros de Cardiologia Apr 2021Dysautonomia covers a range of clinical conditions with different characteristics and prognoses. They are classified as Reflex Syndromes, Postural Orthostatic...
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 <20 years) or HR ≥120 bpm, in the first 10 minutes in an orthostatic position or during the tilt test, without classical orthostatic hypotension associated. A slight decrease in blood pressure may occur. Symptoms appear or get worse in an orthostatic position, with dizziness, weakness, pre-syncope, palpitations, and other systemic symptoms being common.
Topics: Aged; Autonomic Nervous System Diseases; Brazil; Droxidopa; Humans; Hypotension, Orthostatic; Tilt-Table Test
PubMed: 33886735
DOI: 10.36660/abc.20200420 -
Clinical Kidney Journal Dec 2020Intradialytic hypotension (IDH) is a frequent and serious complication of chronic haemodialysis, linked to adverse long-term outcomes including increased cardiovascular... (Review)
Review
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.
PubMed: 33391741
DOI: 10.1093/ckj/sfaa078 -
Cureus Aug 2021Orthostatic hypotension (OH) refers to a significant reduction in blood pressure (BP) that occurs on standing. It mainly results when autonomic reflexes are impaired or...
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.
PubMed: 34532186
DOI: 10.7759/cureus.17156