RÉSUMÉ
BACKGROUND: Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC). AIM: The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC. METHODS: This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1â :â 1 into two groups. Group A received oral midodrine (5â mg/8â h) and rifaximin (550â mg/12â h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period. RESULTS: In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (Pâ <â 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (Pâ <â 0.05). Survival rates demonstrated a noteworthy improvement (Pâ =â 0.014), substantiated by evidence in both univariate and multivariate regression analyses. CONCLUSION: Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.
Sujet(s)
Cirrhose du foie , Midodrine , Qualité de vie , Rifamycine , Rifaximine , Humains , Rifaximine/usage thérapeutique , Femelle , Midodrine/usage thérapeutique , Midodrine/effets indésirables , Mâle , Cirrhose du foie/complications , Cirrhose du foie/mortalité , Cirrhose du foie/traitement médicamenteux , Adulte d'âge moyen , Rifamycine/usage thérapeutique , Rifamycine/effets indésirables , Résultat thérapeutique , Association de médicaments , Adulte , Ascites/étiologie , Ascites/traitement médicamenteux , Ascites/mortalité , Encéphalopathie hépatique/traitement médicamenteux , Encéphalopathie hépatique/étiologie , Sujet âgé , Enquêtes et questionnaires , Péritonite/mortalité , Facteurs tempsRÉSUMÉ
BACKGROUND: Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. METHODS: 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. RESULTS: Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). CONCLUSION: Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.
Sujet(s)
Ascites , Hémorragie gastro-intestinale , Cirrhose du foie , Midodrine , Propranolol , Humains , Propranolol/administration et posologie , Propranolol/usage thérapeutique , Femelle , Midodrine/administration et posologie , Midodrine/usage thérapeutique , Mâle , Cirrhose du foie/complications , Ascites/étiologie , Adulte d'âge moyen , Hémorragie gastro-intestinale/prévention et contrôle , Hémorragie gastro-intestinale/étiologie , Association de médicaments , Antagonistes bêta-adrénergiques/administration et posologie , Antagonistes bêta-adrénergiques/usage thérapeutique , Varices oesophagiennes et gastriques/étiologie , Résultat thérapeutique , Adulte , Sujet âgé , Agonistes des récepteurs alpha-1 adrénergiques/administration et posologie , Agonistes des récepteurs alpha-1 adrénergiques/usage thérapeutiqueRÉSUMÉ
BACKGROUND: Hepatorenal syndrome (HRS), a multiorgan condition of acute kidney injury, is seen in advanced liver disease. This study aims to evaluate the current treatment for HRS. METHODS: The authors searched PubMed, Scopus and Google Scholar literature. After quality assessment, 31 studies were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology and the population, intervention, comparison and outcome scheme were used. We included human-controlled trials that evaluate the current treatment for HRS. Two authors independently screened articles for inclusion, extracted data and assessed the quality of included studies. RESULTS: This study investigated the studies conducted on the effects of different treatments on follow-up of HRS patients. We gathered 440 articles, so 31 articles remained in our study. Of which 24 articles were conducted on terlipressin versus placebo or other treatments (midodrine/octreotide, norepinephrine, etc) that showed the higher rate of HRS reversal was detected for terlipressin in 17 studies (10 of them were significant), 2 studies achieved an insignificant lower rate of the model for end-stage liver disease score for terlipressin, 15 studies showed a decreased mortality rate in the terlipressin group (4 of them were significant). CONCLUSION: This review showed that terlipressin has a significantly higher reversal rate of HRS than the other treatments. Even the results showed that terlipressin is more efficient than midodrine/octreotide and norepinephrine as a previous medication, in reverse HRS, increasing patient survival.
Sujet(s)
Maladie du foie en phase terminale , Syndrome hépatorénal , Midodrine , Humains , Terlipressine/usage thérapeutique , Vasoconstricteurs/usage thérapeutique , Midodrine/usage thérapeutique , Syndrome hépatorénal/traitement médicamenteux , Octréotide/usage thérapeutique , Indice de gravité de la maladie , Norépinéphrine/usage thérapeutiqueRÉSUMÉ
OBJECTIVES: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). METHODS: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months. RESULTS: Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms. CONCLUSION: Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.
Sujet(s)
Atteinte rénale aigüe , Hyponatrémie , Transplantation hépatique , Midodrine , Adulte , Humains , Enfant , Adolescent , Midodrine/usage thérapeutique , Transplantation hépatique/effets indésirables , Ascites/traitement médicamenteux , Ascites/étiologie , Hyponatrémie/complications , Hyponatrémie/traitement médicamenteux , Résultat thérapeutique , Cirrhose du foie/complications , Cirrhose du foie/chirurgie , Atteinte rénale aigüe/étiologie , Atteinte rénale aigüe/prévention et contrôleRÉSUMÉ
BACKGROUND: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. METHODS: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). RESULTS: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. CONCLUSION: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. CLINICAL TRIAL REGISTRATION: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05548985 .
Sujet(s)
Rachianesthésie , Arthroplastie prothétique de hanche , Hypertension artérielle , Hypotension artérielle , Midodrine , Humains , Sujet âgé , Midodrine/usage thérapeutique , Éphédrine/usage thérapeutique , Rachianesthésie/effets indésirables , Rachianesthésie/méthodes , Bradycardie/épidémiologie , Bradycardie/prévention et contrôle , Bradycardie/complications , Arthroplastie prothétique de hanche/effets indésirables , Hypotension artérielle/épidémiologie , Vasoconstricteurs , Hypertension artérielle/complications , Méthode en double aveugleRÉSUMÉ
Although orthostatic hypotension (OH) has long been recognized as a manifestation of autonomic dysfunction, a growing body of literature has identified OH as a common comorbidity of hypertension. This connection is complex, related to pathophysiology in blood pressure regulation and the manner by which OH is derived as the difference between 2 blood pressure measurements. While traditional therapeutic approaches to OH among patients with neurodegenerative disorders focus on increasing upright blood pressure to prevent cerebral hypoperfusion, the management of OH among patients with hypertension is more nuanced; resting hypertension is itself associated with adverse outcomes among these patients. Although there is substantial evidence that intensive blood pressure treatment does not cause OH in the majority of patients with essential hypertension, some classes of antihypertensive agents may unmask OH in patients with an underlying autonomic impairment. Practical steps to manage OH among adults with hypertension start with (1) a thorough characterization of its patterns, triggers, and cause; (2) review and removal of aggravating factors (often pharmacological agents not related to hypertension treatment); (3) optimization of an antihypertensive regimen; and (4) adoption of a tailored treatment strategy that avoids exacerbating hypertension. These strategies include countermaneuvers and short-acting vasoactive agents (midodrine, droxidopa). Ultimately, further research is needed on the epidemiology of OH, the impact of hypertension treatment on OH, approaches to the screening and diagnosis of OH, and OH treatment among adults with hypertension to improve the care of these patients and their complex blood pressure pathophysiology.
Sujet(s)
Maladies du système nerveux autonome , Hypertension artérielle , Hypotension orthostatique , Midodrine , Adulte , Humains , Hypotension orthostatique/diagnostic , Hypotension orthostatique/épidémiologie , Hypotension orthostatique/étiologie , Association américaine du coeur , Hypertension artérielle/diagnostic , Hypertension artérielle/traitement médicamenteux , Hypertension artérielle/épidémiologie , Midodrine/usage thérapeutique , Midodrine/pharmacologie , Pression sanguine , Antihypertenseurs/pharmacologie , Maladies du système nerveux autonome/diagnostic , Maladies du système nerveux autonome/épidémiologie , Maladies du système nerveux autonome/étiologieRÉSUMÉ
BACKGROUND: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. OBJECTIVES: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. METHODS: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. RESULTS: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. CONCLUSION AND RELEVANCE: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.
Sujet(s)
Midodrine , Adulte , Humains , Midodrine/effets indésirables , Études rétrospectives , Maladie grave/thérapie , Vasoconstricteurs , Hospitalisation , Unités de soins intensifsRÉSUMÉ
Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients' responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer-Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 µmol/L vs. 332.7 ± 56 µmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974-0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 µmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer-Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit. Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children. What is Known: ⢠Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events. What is New: ⢠A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.
Sujet(s)
Midodrine , Syncope vagale , Humains , Enfant , Midodrine/usage thérapeutique , Acide urique , Projets pilotes , Syncope vagale/traitement médicamenteux , Courbe ROCRÉSUMÉ
OBJECTIVE: To evaluate the effects of droxidopa or atomoxetine on intravenous (IV) vasoactive agent discontinuation in cardiothoracic intensive care unit (ICU) patients with hypotension refractory to midodrine. DESIGN: Single-center, retrospective cohort study. SETTING: Tertiary- and quaternary-care university teaching hospital. PARTICIPANTS: Included patients who received at least 4 consecutive doses of droxidopa or atomoxetine and remained on concurrent midodrine. Patients were excluded if they received study medication before admission, had clinical deterioration after study medication initiation requiring additional vasoactives/escalation of IV vasoactive dosage for at least 12 hours, had a diagnosis of hepatorenal syndrome, were prisoners, or were pregnant. INTERVENTIONS: Droxidopa, atomoxetine, or both. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time to discontinuation of IV vasoactive agents after initiation of study medication, analyzed using a Kaplan-Meier estimate with the Wilcoxon method, censoring death within 24 hours of the last dose of study medication. No adjustment for repetitive analyses was made, as the analysis was hypothesis-generating. Of the 72 charts reviewed, 45 patients met inclusion criteria (18 atomoxetine, 17 droxidopa, and 10 both). There were no differences in median time to discontinuation of IV vasoactive agents (21.9 days v 8.0 days v 13.9 days, respectively; p = 0.259) or ICU or hospital length of stay between groups. A higher percentage of patients who survived to hospital discharge received both study medications or droxidopa alone (90% v 76.5%) than atomoxetine alone (44.4%, p = 0.028). CONCLUSIONS: Droxidopa and atomoxetine are oral vasoactive agents with potential mechanisms to facilitate IV vasopressor weaning for patients in the ICU with hypotension refractory to midodrine, but further prospective research is needed.
Sujet(s)
Droxidopa , Hypotension artérielle , Midodrine , Humains , Droxidopa/effets indésirables , Midodrine/effets indésirables , Chlorhydrate d'atomoxétine/usage thérapeutique , Maladie grave , Études rétrospectives , Hypotension artérielle/diagnostic , Hypotension artérielle/traitement médicamenteux , VasoconstricteursRÉSUMÉ
ABSTRACT: Midodrine is occasionally used off-label to treat hypotension associated with advanced heart failure (HF); however, its association with changes in prescription of guideline-directed medical therapy (GDMT) is unknown. We sought to evaluate the effect of midodrine on the GDMT prescription pattern and clinical outcomes of patients with decompensated systolic HF. We retrospectively identified 114 patients admitted to our hospital in 2020 with decompensated systolic HF who were prescribed midodrine on discharge and compared them with 358 patients with decompensated systolic HF who were not prescribed midodrine. At 6 months, the midodrine group had more initiation or up-titration of beta blockers, renin-angiotensin-aldosterone system inhibitors, and sodium-glucose cotransporter-2 inhibitors compared with the nonmidodrine group. Survival at 6 months was similar between the 2 groups, but the midodrine group had more frequent rehospitalization for HF. Our findings suggest that midodrine is associated with improved GDMT in patients with decompensated HF but may be associated with worse prognosis.
Sujet(s)
Défaillance cardiaque systolique , Défaillance cardiaque , Midodrine , Inhibiteurs du cotransporteur sodium-glucose de type 2 , Humains , Midodrine/effets indésirables , Défaillance cardiaque systolique/diagnostic , Défaillance cardiaque systolique/traitement médicamenteux , Études rétrospectives , Inhibiteurs du cotransporteur sodium-glucose de type 2/usage thérapeutique , Hospitalisation , Défaillance cardiaque/diagnostic , Défaillance cardiaque/traitement médicamenteux , Défaillance cardiaque/induit chimiquement , Antagonistes bêta-adrénergiques/effets indésirables , Débit systolique , Antagonistes des récepteurs aux angiotensines/usage thérapeutiqueRÉSUMÉ
Orthostatic hypotension is defined as a drop in systolic blood pressure of at least 20mmHg or a drop in diastolic blood pressure of at least 10mmHg within 3minutes of standing. It is a common disorder, especially in high-risk populations such as elderly subjects and patients with neurological diseases, and is associated with markedly increased morbidity and mortality. Its management can be challenging, particularly in cases where supine hypertension is associated with severe orthostatic hypotension. Education of the patient, non-pharmacological measures, and drug adaptation are the cornerstones of treatment. Pharmacological treatment should be individualized according to the severity, underlying cause, 24-hour blood pressure profile, and associated coexisting conditions. First-line therapies are midodrine and fludrocortisone, which may need to be combined for optimal care of severe cases.
Sujet(s)
Hypertension artérielle , Hypotension orthostatique , Midodrine , Maladies du système nerveux , Humains , Sujet âgé , Hypotension orthostatique/diagnostic , Hypotension orthostatique/épidémiologie , Hypotension orthostatique/étiologie , Midodrine/usage thérapeutique , Hypertension artérielle/complications , Hypertension artérielle/traitement médicamenteux , Pression sanguine , Maladies du système nerveux/complicationsRÉSUMÉ
Background Midodrine was the first medication approved by the Food and Drug Administration (FDA) for the treatment of orthostatic hypotension. Pharmacologically, midodrine is a peripheral selective alpha-1-adrenergic agonist that can improve standing, sitting, and supine systolic blood pressure. Common side effects include bradycardia, supine hypertension, and paresthesia. A novel side effect of midodrine-induced nightmares has been reported in our patient. To our knowledge, this is the first reported case of midodrine-induced nightmares. Objective To investigate and report a clinically significant and unique drug adverse event of midodrine in the treatment of orthostatic hypotension. Case Presentation This report describes a case of persistent nightmares associated with midodrine use in an 83-year-old male who experienced frequent syncope episodes treated with midodrine for orthostatic hypotension (OH). After the initiation of midodrine, the patient complained of increased nightmares, which quickly led to his refusal of the medication, despite the initial improvements in his blood pressure. The timing of administration included an evening dose at 21:00. This novel adverse event of midodrine-induced nightmares will be highlighted and explored in this case report. Conclusion This case demonstrated a unique adverse event of nightmares caused by midodrine. It is hypothesized that autonomic dysfunction plays a role and further investigations should be conducted to confirm this theory. We hope that our case report highlights the importance of careful consideration when prescribing midodrine in older people with orthostatic hypotension.
Sujet(s)
Hypotension orthostatique , Midodrine , Sujet âgé de 80 ans ou plus , Humains , Mâle , Agonistes alpha-adrénergiques/effets indésirables , Pression sanguine , Rêves , Hypotension orthostatique/induit chimiquement , Hypotension orthostatique/traitement médicamenteux , Midodrine/effets indésirables , États-UnisRÉSUMÉ
Primary Sjogren's syndrome (pSS) is an autoimmune connective tissue disorder with multisystem manifestations. We here report a previously healthy woman who presented with autonomic dysfunction in the form of severe dizziness without any apparent sensory neuropathy. Detailed history and examination revealed the signs and symptoms of Sjogren's syndrome such as constipation and dry eyes and mouth, following which anti-SSA and SSB antibodies were found to be positive. Finally, a diagnosis of pSS was established after ruling out all the other causes of autonomic dysfunction in addition to the clinical and laboratory evidence. The patient was treated with the maximum doses of midodrine and fludrocortisone, yet no progress was noticed. Hence, a trial of steroids was started and she showed a significant clinical improvement. Our patient presented with pure autonomic failure associated with Sjogren's syndrome, making it an extremely rare entity.
Sujet(s)
Maladies du système nerveux autonome , Midodrine , Syndrome de Gougerot-Sjögren , Femelle , Humains , Syndrome de Gougerot-Sjögren/complications , Syndrome de Gougerot-Sjögren/diagnostic , Syndrome de Gougerot-Sjögren/traitement médicamenteux , Maladies du système nerveux autonome/diagnostic , Maladies du système nerveux autonome/traitement médicamenteux , Maladies du système nerveux autonome/étiologie , Fludrocortisone/usage thérapeutique , Midodrine/usage thérapeutiqueRÉSUMÉ
INTRODUCTION: Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney injury (HRS-AKI) accounts for most hospitalizations, and liver transplantation (LT) remains the ultimate and long-term treatment in such patients. However, HRS-AKI, being a functional renal failure, has a fair chance of reversal, and as such, patients who achieve reversal of HRS-AKI have better outcomes post-LT. AREAS COVERED: In this review, we discuss the pharmacokinetics, pharmacodynamics and evidence to support the use of terlipressin in HRS-AKI while we also address predictors of response and the associated adverse events. Further, we discuss the role of terlipressin in the context of LT. EXPERT OPINION: The recommended treatment for HRS-AKI reversal includes a vasoconstrictor in addition to volume expansion with albumin. The three vasoconstrictor regimens generally used to treat HRS-AKI include octreotide plus midodrine, noradrenaline, and terlipressin. Of these, terlipressin is a widely used drug and has been recently approved by US Food and Drug Administration (USFDA) for HRS-AKI. Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant. Furthermore, terlipressin responders have improved transplant-free and post-transplant survival.
Sujet(s)
Atteinte rénale aigüe , Syndrome hépatorénal , Midodrine , Humains , Adulte , Terlipressine/effets indésirables , Syndrome hépatorénal/traitement médicamenteux , Syndrome hépatorénal/étiologie , Vasoconstricteurs/effets indésirables , Midodrine/usage thérapeutique , Atteinte rénale aigüe/traitement médicamenteuxRÉSUMÉ
BACKGROUND: Hepatorenal syndrome (HRS) is characterized by severely reduced renal perfusion that precipitates rapid morbidity and mortality. Terlipressin is the only US Food and Drug Administration-approved treatment to improve kidney function for adults with HRS with a rapid reduction in kidney function. Prior to the approval of terlipressin, unapproved vasoconstrictive agents used in HRS treatment were octreotide/midodrine and norepinephrine with albumin. METHODS: A cohort decision-tree model representing a US hospital perspective assessed the clinical outcomes and direct medical costs (based primarily on hospital charges) of treating HRS with terlipressin + albumin (ALB) versus midodrine/octreotide (MID/OCT)+ALB, or norepinephrine (NorEp)+ALB. Treatment efficacy was defined by clinical response (complete/HRS reversal, partial, or no response) based on change of serum creatinine derived from published clinical trial reports. The proportions of patients with complete response were: terlipressin + ALB (36.2%), NorEp + ALB (19.1%), and MID/OCT + ALB (3.1%). Model outcomes included utilization of HRS-related healthcare resources (hospital and intensive care, outpatient and emergency department, dialysis, and transplantations), adverse events, and HRS-related mortality. Outcomes were assessed for the initial hospitalization in the base case and at 30, 60, and 90 days post-discharge. RESULTS: Total costs incurred over the initial hospitalization with terlipressin + ALB were lower vs NorEp + ALB, primarily due to higher ICU costs with NorEp + ALB ($7,433 vs $61,897). TER + ALB was associated with higher total costs vs MID/OCT + ALB due to higher pharmacy costs with terlipressin + ALB. The cost per complete response achieved of terlipressin + ALB ($451,605) was half that of NorEp + ALB ($930,571) and one-tenth that of MID/OCT + ALB ($4,942,123). CONCLUSIONS: HRS patients treated with terlipressin experienced better clinical outcomes and a lower cost per treatment response vs other unapproved treatments. ICU days and pharmacy costs were key cost drivers distinguishing the treatment groups. These outcomes suggest that terlipressin is cost-effective on the basis of total cost per response achieved.
Hepatorenal syndrome (HRS) is a rare and sudden life-threatening complication of the liver. Patients with HRS should receive immediate treatment with a drug that narrows blood vessels known as a vasoconstrictor. Terlipressin is the most common vasoconstrictor used for patients with HRS. Other common vasoconstrictors are midodrine with octreotide and norepinephrine. This study aimed to compare the cost of terlipressin with those of midodrine with octreotide and norepinephrine while also considering how well each of them worked to reverse HRS. This was done using an economic model. This economic model assessed the costs of the vasoconstrictor drugs and the costs of treating HRS, including costs attributable to drug acquisition, adverse events, organ transplantation, dialysis, and institutional encounters (i.e. hospitalization, ICU, emergency department, and outpatient visits). The magnitude of these costs depends on how well each drug reversed HRS. Based on inputs derived from their respective clinical trials, 36% of patients who were given terlipressin had a complete response (HRS was reversed), 19% of patients who were given norepinephrine had a complete response, and 3% of patients who were given midodrine with octreotide had a complete response. The total cost per patient was approximately $163,481 for terlipressin, $177,298 for norepinephrine, and $155,030 for midodrine with octreotide. When the costs were evaluated against how well the drugs worked to reverse HRS, the lowest cost per HRS reversal was $451,605 when treated with terlipressin. The cost per reversal for norepinephrine was $930,571 and for midodrine with octreotide was $4,942,123. These results show that terlipressin works well and is more cost-effective for US hospitals compared with the other unapproved treatment options for HRS with rapid reduction in kidney function.
Sujet(s)
Syndrome hépatorénal , Midodrine , Adulte , Humains , États-Unis , Terlipressine/usage thérapeutique , Vasoconstricteurs/usage thérapeutique , Midodrine/usage thérapeutique , Syndrome hépatorénal/traitement médicamenteux , Analyse coût-bénéfice , Octréotide/usage thérapeutique , Post-cure , Sortie du patient , Norépinéphrine/usage thérapeutique , Résultat thérapeutique , Albumines/usage thérapeutique , HôpitauxRÉSUMÉ
INTRODUCTION: Evidence on the comparison of treatments for hepatorenal syndrome-acute kidney injury (HRS-AKI) in a US population is limited. An indirect comparison of terlipressin plus albumin vs midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy. METHODS: Cohorts of patients treated for HRS-AKI characterized by inclusion of patients with serum creatinine (SCr) <5 mg/dL and baseline acute-on-chronic liver failure grades 0-2 and exclusion of patients listed for transplant if model for end-stage liver disease scores ≥35 were pooled from (i) the CONFIRM and REVERSE randomized controlled trials (N = 159 meeting eligibility criteria from N = 216 overall, treated with terlipressin) and (ii) a retrospective review of medical records from 10 US tertiary hospitals (2016-2019; N = 55 treated with MO meeting eligibility criteria from N = 200 overall). The primary end point comparing the 2 cohorts was HRS reversal defined as achieving SCr ≤1.5 mg/dL at least once during the treatment. Covariate balancing propensity scoring was used to adjust for differences in baseline characteristics. RESULTS: HRS-AKI reversal was achieved in 52.35% of terlipressin-treated patients compared with 20% of MO-treated patients (adjusted mean difference 32.35%, 95% confidence interval [CI] 17.40-47.30, P < 0.0001). Terlipressin-treated patients had increased overall survival (adjusted hazard ratio 0.57, 95% CI 0.35-0.93, P = 0.02) but similar transplant-free survival (adjusted hazard ratio 0.79, 95% CI 0.53-1.17, P = 0.24). Achievement of HRS-AKI reversal was associated with increased OS and TFS regardless of treatment ( P < 0.001). DISCUSSION: Consistent with prior reports, terlipressin plus albumin is more effective in improving kidney function and achieving HRS-AKI reversal than MO plus albumin based on indirect comparison in a US population.