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Journal of Clinical and Translational... Mar 2018Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and... (Review)
Review
Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries, in this article we have attempted to reclassify CA based on portal and non-portal etiologies. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of >200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Some studies have also supported the use of agents such as orlistat, somatostatin, octreotide and etilefrine. Paracentesis and surgical interventions in the form of transjugular intrahepatic portosystemic shunt (commonly known as TIPS), peritoneal shunt, angiography with embolization of a leaking vessel, and laparotomy remain as treatment options for cases refractory to medical management.
PubMed: 29577037
DOI: 10.14218/JCTH.2017.00035 -
Hematology. American Society of... Dec 2022Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the... (Review)
Review
Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.
Topics: Adult; Male; Humans; Priapism; Anemia, Sickle Cell; Sildenafil Citrate; Etilefrine; Hemolysis; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 36485155
DOI: 10.1182/hematology.2022000380 -
The Journal of Sexual Medicine Jan 2012Priapism is a familiar problem to hematologists, well known for its association with sickle-cell disease (SCD). It also occurs in a variety of other hematological... (Review)
Review
INTRODUCTION
Priapism is a familiar problem to hematologists, well known for its association with sickle-cell disease (SCD). It also occurs in a variety of other hematological illnesses, nearly all forms of congenital hemolytic anemia, including other hemoglobinopathies and red blood cell membranopathies and enzymopathies.
AIM
Provide urologists with a comprehensive review of priapism in SCD, with an emphasis on the perspective of a practicing hematologist.
METHODS
Medline searches through July 2010 were conducted using the terms priapism, erectile dysfunction, and sickle cell.
MAIN OUTCOME MEASURES
Expert opinion was based on review of the medical literature related to this subject matter.
RESULTS
In men with SCD, large epidemiological studies have linked the risk of priapism to clinical markers of the severity of intravascular hemolysis. Extracellular hemoglobin and arginase released during hemolysis has been implicated in reducing nitric oxide bioavailability, although the relevance of hemolysis to vascular dysfunction has been challenged by some scientists. Consistent with the role of impairment of the nitric oxide axis, mice genetically deficient in nitric oxide production have also been shown to develop priapic activity. Provocative new data indicate that hemolysis-linked dysregulation of adenosine signaling in the penis contributes to priapism in sickle cell mice. Serious questions have arisen regarding the efficacy of mainstays of textbook dogma for treatment of acute severe priapism, including intravenous fluids, alkalinization, and exchange transfusion, and there is increasing acceptance for early aspiration and irrigation of the corpus cavernosum.
CONCLUSION
For patients with sickle cell with recurrent priapism, there is very limited evidence for a medical prophylaxis role for hydroxyurea, etilefrine, pseudoephedrine, leuprolide, sildenafil, and other agents. Recent publications have highlighted nitric oxide and adenosine signal transduction pathways as worthy of additional research. Research and clinical management of sickle-cell priapism is strengthened by multidisciplinary collaboration between hematologists and urologists.
Topics: Anemia, Sickle Cell; Hemoglobin, Sickle; Hemolysis; Humans; Male; Nitric Oxide; Priapism; Risk Factors
PubMed: 21554552
DOI: 10.1111/j.1743-6109.2011.02287.x -
Therapeutic Advances in... 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.
OBJECTIVES
Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.
DESIGN
We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.
DATA SOURCES AND METHODS
PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.
RESULTS
We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.
CONCLUSION
Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.
REGISTRATION
PROSPERO (Registration No. CRD42020191530).
PubMed: 35633931
DOI: 10.1177/20451253221092931 -
European Review For Medical and... Sep 2022The renin-angiotensin-aldosterone system (RAAS) activation is the milestone in ascites formation. Hypertonic saline solution (HSS) has attracted considerable interest...
OBJECTIVE
The renin-angiotensin-aldosterone system (RAAS) activation is the milestone in ascites formation. Hypertonic saline solution (HSS) has attracted considerable interest over the last years in ascites control. Other therapeutic models and concepts have been introduced to overcome diuretic resistance and control ascites. We aimed to evaluate the effects of adding HSS infusion and/or etilefrine to oral diuretics therapy on inflammatory and metabolic pathways, renal and systemic hemodynamics, and clinical outcomes by estimating the changes in selected biochemical and biological markers in cirrhotic patients with ascites.
PATIENTS AND METHODS
Ninety cirrhotic patients with ascites were studied after administration of HSS infusion (n=25) or etilefrine tablets (n=25), or both (n=25) plus standard diuretics therapy (SDT), or SDT alone (n=15). Serum levels of interleukin-6 (IL-6), aldosterone, leptin, and C-reactive protein (CRP). Hepatic and renal functions were measured at baseline, after eight days, then after 38 days.
RESULTS
A significant reduction in serum IL-6, serum aldosterone, Child-Pugh score, MELD-Na score, and increase in serum leptin, and mean arterial pressure (p<0.05) were noted after 38 days in HSS and combination groups. A significant improvement in diuresis, in all groups, urinary sodium excretion, and creatinine clearance (p<0.05) were increased after 38 days in all groups except the SDT group.
CONCLUSIONS
The results suggest that HSS, etilefrine, and their combination plus SDT are superior to SDT alone for ascites control and can exert some benefits on clinical, systemic, inflammatory, renal, and metabolic pathways without renal or hepatic dysfunction.
Topics: Aldosterone; Ascites; Biomarkers; C-Reactive Protein; Creatinine; Diuretics; Etilefrine; Furosemide; Humans; Interleukin-6; Leptin; Liver Cirrhosis; Saline Solution, Hypertonic; Sodium
PubMed: 36196711
DOI: 10.26355/eurrev_202209_29761 -
Bioscience Trends Sep 2018Hypotension commonly accompanies combined epidural and general anesthesia, and intravenous bolus ephedrine and etilefrine are widely used to correct hypotension. We have... (Randomized Controlled Trial)
Randomized Controlled Trial
Bolus administration of ephedrine and etilefrine induces transient vasodilation just after injection in combined epidural and general anesthesia patients: A randomized clinical study.
Hypotension commonly accompanies combined epidural and general anesthesia, and intravenous bolus ephedrine and etilefrine are widely used to correct hypotension. We have noticed that systemic vascular resistance (SVR) transiently decreases just after intravenous bolus administration of these drugs. The goal of the present study was to investigate whether bolus administration of these drugs decrease SVR just after intravenous administration in combined epidural and general anesthesia patients. We investigated 40 patients who were scheduled for elective abdominal surgery. Patients were chosen as subjects if their systolic arterial pressure decreased by 20% or to <100 mmHg at 30 min after the induction of general anesthesia. Baseline hemodynamic values were recorded, and after ephedrine 10 mg injection or etilefrine 2 mg injection (equipotent), the parameters were recorded again at 0.5 min and once each min for the next 5 min thereafter. The 40 patients were enrolled into the ephedrine (n = 20) or etilefrine (n = 20) treatment groups. Patient characteristics were comparable in both groups. After ephedrine injection, SVR decreased significantly at the 1-min time point, whereas after etilefrine injection, SVR decreased significantly at the 0.5- to 2-min time points compared with baseline values. SVR at the 0.5- to 1-min time points was lower in the etilefrine versus the ephedrine group. Both drugs transiently decreased SVR after intravenous injection, but etilefrine decreased SVR much more than ephedrine, indicating that more vasodilation occurred after the injection of etilefrine than after ephedrine. It is thus important to recognize the different characteristics of these drugs.
Topics: Adult; Anesthesia, Epidural; Anesthesia, General; Blood Pressure; Ephedrine; Etilefrine; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Vasodilation
PubMed: 30101824
DOI: 10.5582/bst.2018.01074 -
The Cochrane Database of Systematic... Sep 2017Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion... (Review)
Review
BACKGROUND
Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals.
OBJECTIVES
To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 September 2017.Date of most recent search of trial registries and of Embase: 12 December 2016.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed the risk of bias of the trials.
MAIN RESULTS
Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence but all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome. No significant effect of any of the treatments was seen compared to placebo. Immediate side effects were not found to be significantly different from placebo in the two trials where this information was reported. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers.
AUTHORS' CONCLUSIONS
There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.
Topics: Anemia, Sickle Cell; Diethylstilbestrol; Estrogens, Non-Steroidal; Humans; Male; Priapism
PubMed: 28926088
DOI: 10.1002/14651858.CD004198.pub3 -
European Annals of Otorhinolaryngology,... Oct 2021Intraoperative injury of the thoracic duct is an uncommon complication of head and neck surgery, which is difficult to manage and associated with serious consequences....
BACKGROUND
Intraoperative injury of the thoracic duct is an uncommon complication of head and neck surgery, which is difficult to manage and associated with serious consequences. We report a case of lymphorrhoea of the neck refractory to all the usual treatments that resolved in response to a treatment strategy described in thoracic and visceral surgery: use of a sympathomimetic drug, etilefrine. To our knowledge and after review of the literature, this is the first reported case of lymphorrhoea of the neck treated by etilefrine.
CASE REPORT
Our patient presented massive lymphatic fluid leakage following left neck dissection as part of the management of oropharyngeal cancer with lymph node metastases. The treatments usually proposed, such as intraoperative repair and appropriate dietary and drug management, were not effective, resulting in multiple, severe complications. After evaluation of the benefit-risk balance, treatment with etilefrine was introduced at the dosages proposed in the literature for the management of chylothorax. This treatment allowed complete resolution of the lymphatic fluid leak after one week.
DISCUSSION
Etilefrine can therefore be added to the treatment options for the management of lymphatic fluid leaks refractory to the usual treatments.
Topics: Chylothorax; Etilefrine; Humans; Neck; Neck Dissection; Thoracic Duct
PubMed: 33608232
DOI: 10.1016/j.anorl.2021.02.006 -
Saudi Pharmaceutical Journal : SPJ :... Oct 2022Etilefrine hydrochloride (ET) is a water-soluble drug that is used to treat hypotension, but it has a bitter taste and low bioavailability due to undergoing the...
Etilefrine hydrochloride (ET) is a water-soluble drug that is used to treat hypotension, but it has a bitter taste and low bioavailability due to undergoing the first-pass effect. Thus, this study aimed to develop and evaluate oral medicated jelly (OMJ) containing ET that could offer an easily taken palatable dosage form with higher bioavailability. OMJ is a novel palatable drug delivery system that can easily be taken by pediatric and geriatric patients, as well as those with dysphagia. Moreover, OMJs offer rapid disintegration in saliva and rapid drug absorption through the buccal mucosa, avoiding the first-pass effect and increasing the drug bioavailability. Natural polymers such as pectin, guar gum, xanthan gum, tragacanth gum, and sodium alginate were used as jellifying agents, with the addition of calcium chloride as a crosslinking agent, to prepare OMJs using the heat and congealing method. The prepared OMJs were investigated by testing their viscosity, release, and texture analysis of firmness, consistency, stickiness, cohesiveness, springiness, gumminess, and chewiness using a texture analyzer. A full factorial design (2 × 5) was utilized to select the optimized OMJ. The optimized OMJ (J2), containing 4 % pectin, had a 7563 ± 55 cps viscosity, 8.32 ± 0.21 N firmness, 5.72 ± 0.18 µJ consistency, 1.30 ± 0.04 mJ stickiness, and 96.02 ± 3.74 % ET dissolved after 10 min. ET release was significantly increased (greater than4-fold) from the optimized OMJ compared with the market tablet. Moreover, the obtained results clarified the stability and the acceptable palatability of the optimized OMJ. The clinical investigation on healthy human volunteers revealed that the optimized OMJ (J2) had significantly higher C (1.7 folds) when compared with the market tablet with a relative bioavailability of 154.55 %. Therefore, OMJs can be considered as promising, palatable, and easily swallowed dosage form that could enhance the bioavailability of drugs undergoing the first-pass effect.
PubMed: 36387345
DOI: 10.1016/j.jsps.2022.07.004 -
Biomedicine Hub 2020Etilefrine, a sympathomimetic agent, is reportedly effective against postoperative chylothorax. However, its effectiveness in treating congenital chylothorax was...
Etilefrine, a sympathomimetic agent, is reportedly effective against postoperative chylothorax. However, its effectiveness in treating congenital chylothorax was unknown. We report herein a case of refractory congenital chylothorax treated with etilefrine in a late preterm neonate with massive fetal chylous pleural effusion. The chylothorax was unresponsive to previous treatments, including dietary and pharmacological treatment and thoracic duct ligation. The pleural effusion decreased after intravenous etilefrine was begun on day of life (DOL) 84 and resolved after the addition of chemical pleurodesis with OK-432 on DOL 90. This combination therapy may be a viable treatment option for cases of congenital chylothorax that are unresponsive to other treatments.
PubMed: 33564667
DOI: 10.1159/000509903