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The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2 -
Scientific Reports May 2021The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We...
The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3 and CD4 lymphocytes, and CD68 and CD206 macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4 lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.
Topics: Animals; Autonomic Nervous System; Blood Pressure; Cholinesterase Inhibitors; Heart; Heart Rate; Hemodynamics; Male; Myocardial Infarction; Pyridostigmine Bromide; Rats; Rats, Inbred SHR; Spleen
PubMed: 33953291
DOI: 10.1038/s41598-021-89104-8 -
BMJ Case Reports Apr 2021We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia...
We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia gravis (MG) was supported with positive acetylcholine receptor antibodies and abnormal repetitive stimulation study. He responded well to pyridostigmine, intravenous immunoglobulin and oral prednisolone. In this report, we describe the timing and progression of MG in our patient, and review the literature pertaining to the relationship between trauma and MG. The search for definitive evidence of causation may be impractical, but should not delay the recognition and management of a treatable condition.
Topics: Blepharoptosis; Diplopia; Humans; Male; Middle Aged; Myasthenia Gravis; Prednisolone; Pyridostigmine Bromide; Wounds and Injuries
PubMed: 33811091
DOI: 10.1136/bcr-2020-238415 -
Journal of Cellular and Molecular... May 2021Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial...
Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear. The present study examined the effects and underpinning mechanisms of chronic treatment with the cholinesterase inhibitor, pyridostigmine (PYR), in pressure overload HF induced by transverse aortic constriction (TAC) in mice. TAC mice exhibited characteristic adverse structural (left ventricular hypertrophy) and functional remodelling (reduced ejection fraction, altered myocyte calcium (Ca) handling, increased arrhythmogenesis) with enhanced predisposition to arrhythmogenic aberrant sarcoplasmic reticulum (SR) Ca release, cardiac ryanodine receptor (RyR2) hyper-phosphorylation and up-regulated store-operated Ca entry (SOCE). PYR treatment resulted in improved cardiac contractile performance and rhythmic activity relative to untreated TAC mice. Chronic PYR treatment inhibited altered intracellular Ca handling by alleviating aberrant Ca release and diminishing pathologically enhanced SOCE in TAC myocytes. At the molecular level, these PYR-induced changes in Ca handling were associated with reductions of pathologically enhanced phosphorylation of RyR2 serine-2814 and STIM1 expression in HF myocytes. These results suggest that chronic cholinergic augmentation alleviates HF via normalization of both canonical RyR2-mediated SR Ca release and non-canonical hypertrophic Ca signaling via STIM1-dependent SOCE.
Topics: Animals; Arrhythmias, Cardiac; Calcium; Cholinesterase Inhibitors; Heart Failure; Male; Mice; Mice, Inbred C57BL; Pyridostigmine Bromide; Ryanodine Receptor Calcium Release Channel; Stromal Interaction Molecule 1
PubMed: 33755308
DOI: 10.1111/jcmm.16356 -
BMJ Case Reports Mar 2021A 67-year-old man presented with progressive diplopia. On evaluation, he was noted to have bilateral palsies of cranial nerves III, IV and VI as well as a unilateral...
A 67-year-old man presented with progressive diplopia. On evaluation, he was noted to have bilateral palsies of cranial nerves III, IV and VI as well as a unilateral right true vocal fold paralysis. CT and MRI studies demonstrated a T2-bright left ethmoid mass with no evidence of bony erosion. Direct visualisation demonstrated a polypoid appearing mass of the left sphenoethmoid recess. Operative biopsy was pursued with final pathology demonstrating benign seromucinous hamartoma. Subsequent blood work demonstrated high titres of anti-acetylcholine receptor antibodies consistent with myasthenia gravis. The patient was started on pyridostigmine with improvement in his ocular cranial neuropathies.
Topics: Aged; Cranial Nerve Diseases; Diplopia; Hamartoma; Humans; Male; Myasthenia Gravis; Pyridostigmine Bromide
PubMed: 33722916
DOI: 10.1136/bcr-2020-240460 -
The Pan African Medical Journal 2020Among non-iatrogenic neuromuscular disorders, myasthenia gravis remains the most prevalent. Diagnosing this disorder may become challenging in certain cases such as in...
Among non-iatrogenic neuromuscular disorders, myasthenia gravis remains the most prevalent. Diagnosing this disorder may become challenging in certain cases such as in patients with coexisting comorbid illnesses and non-specific clinical symptoms. This is a case of atypical myasthenia gravis in a middle-aged hypertensive male, who initially presented symptoms suggestive of an acute ischemic stroke. Upon later investigation, prompted by persistent symptoms, the patient was found to have AchR antibodies and had the rare finding of a fissured and atrophied tongue (reversible on treatment). It is a well-known fact that brainstem strokes can present with bulbar weakness resulting in aspiration pneumonitis, as was with the clinical presentation in the below mentioned report. Due to the initial misdiagnosis, he had received medical therapy aimed towards stroke management and prevention. Further investigation leading to a definitive diagnosis, was followed by medical therapy with neostigmine, pyridostigmine and oral prednisolone, leading to significant improvement in symptoms. Hence as a mandatory measure, while dealing with a case of a new onset of weakness, especially in cranial musculature, myasthenia gravis must not be excluded from the list of differential diagnosis. Myasthenia gravis (MG) is a potential "stroke mimic" especially in the elderly. However, due to recent change in trends of stroke statistics, this disease should be considered a possibility even in younger patients.
Topics: Diagnosis, Differential; Diagnostic Errors; Drug Therapy, Combination; Humans; Ischemic Stroke; Male; Middle Aged; Myasthenia Gravis; Neostigmine; Prednisolone; Pyridostigmine Bromide
PubMed: 33654524
DOI: 10.11604/pamj.2020.37.305.27032 -
International Journal of Medical... 2021: Sugammadex has been shown to be associated with prolongation of prothrombin time and activated partial thromboplastin time. However, it is not known whether it could... (Randomized Controlled Trial)
Randomized Controlled Trial
: Sugammadex has been shown to be associated with prolongation of prothrombin time and activated partial thromboplastin time. However, it is not known whether it could be associated with enhancing postoperative hypocoagulation. The objective of this study was to analyze the effect of 4 mg/kg of sugammadex on thromboelastography (TEG) parameters in surgical patients. After Institutional Review Board approval, a prospective double-blinded randomized controlled study was conducted between September 2016 and April 2017. Sixty adult patients scheduled for laparoscopic abdominal surgery were randomly allocated to receive either sugammadex 4 mg/kg (sugammadex group) or pyridostigmine 0.15 mg/kg in combination with glycopyrrolate 0.4 mg (control group) to reverse rocuronium-induced neuromuscular blockade at the completion of surgery. Blood samples were collected three time points; After the final suture of surgery (baseline) (T1), and at 10 min (T2) and 1 h (T3) after administration of the study drug. Whole blood was analyzed by TEG using TEG 5000 (Hemonetics Corp, Braintree, MA, USA). The primary endpoints were comparison of coagulation time (K, time to 20 mm clot amplitude), R (reaction time), alpha angle, and maximal amplitude (MA) between two groups. Coagulation time was significantly prolonged in sugammadex group after 10 min of the study drug administration compared to control group (mean value 1.3 ± 0.4 vs. 1.5 ± 0.4, P = 0.03). However, R, alpha angle and MA value were not different between two groups. Sugammadex 4 mg/kg showed an increase in coagulation time in surgical patients. Physician should aware the potential enhancement of hypocoagulation by sugammadex in the setting of high risk of postoperative bleeding.
Topics: Adult; Blood Coagulation; Dose-Response Relationship, Drug; Female; Glycopyrrolate; Humans; Laparoscopy; Male; Middle Aged; Neuromuscular Blockade; Partial Thromboplastin Time; Postoperative Hemorrhage; Prospective Studies; Prothrombin Time; Pyridostigmine Bromide; Rocuronium; Sugammadex; Thrombelastography; Young Adult
PubMed: 33628086
DOI: 10.7150/ijms.42563 -
Hypertension (Dallas, Tex. : 1979) Apr 2021[Figure: see text].
Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome: Effects of Pyridostigmine and Digoxin.
[Figure: see text].
Topics: Adult; Baroreflex; Blood Pressure; Cardiotonic Agents; Cholinesterase Inhibitors; Digoxin; Dizziness; Female; Heart Rate; Humans; Hypovolemia; Outcome Assessment, Health Care; Patient Positioning; Postural Orthostatic Tachycardia Syndrome; Pyridostigmine Bromide; Sympathetic Nervous System
PubMed: 33423527
DOI: 10.1161/HYPERTENSIONAHA.120.16113 -
Frontiers in Immunology 2020We present a case of a 37-year-old man with HIV infection who had been on antiretroviral therapy for one year. He was admitted to our hospital with red and swollen eyes,...
We present a case of a 37-year-old man with HIV infection who had been on antiretroviral therapy for one year. He was admitted to our hospital with red and swollen eyes, acute onset progressive exophthalmos, and intermittent diplopia endured for 7 days. His symptoms, exam, and imaging led to a diagnosis of immune reconstitution inflammatory syndrome associated orbital myositis. His symptoms improved considerably after glucocorticoid therapy. Following a reduction in the oral prednisone dose, he re-presented with left ptosis, which rapidly progressed to bilateral ptosis. Diagnostic testing led to the diagnosis of immune mediated myasthenia gravis. Treatment with pyridostigmine bromide, prednisone, and tacrolimus was initiated. One month later, the patient's symptoms improved significantly. There was a probable association between his symptoms and autoimmune immune reconstitution inflammatory syndrome. This report highlights the importance of recognizing autoimmune disorders in human immunodeficiency virus-infected patients undergoing antiretroviral therapy. Orbital myositis and myasthenia gravis in human immunodeficiency virus-infected patients correlate closely with immunity status following a marked increase in CD4 T cell counts.
Topics: Adult; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Myasthenia Gravis; Orbital Myositis; Prednisolone; Pyridostigmine Bromide; Tacrolimus
PubMed: 33381117
DOI: 10.3389/fimmu.2020.595068 -
BMJ Case Reports Dec 2020
Topics: Blepharoptosis; Child; Cholinesterase Inhibitors; Eye Movements; Female; Humans; India; Muscle Weakness; Pyridostigmine Bromide; Treatment Outcome
PubMed: 33372023
DOI: 10.1136/bcr-2020-239211