Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: A randomised study

Background and aimsNewer studies suggest that carvedilol, a beta-blocker with a moderate anti-alpha-1 activity, is superior to propranolol in reducing the portal pressure and risk of variceal bleeding. The effect on arterial blood pressure is a matter of concern especially in decompensated patients.Aimsto assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic, humoral, and respiratory characteristics in cirrhosis.MethodsPatients with cirrhosis and portal hypertension were randomised to receive carvedilol (n = 16) or propranolol (n = 13). Cardiac, systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months.ResultsArterial blood pressure, heart rate, and cardiac output decreased equally, central circulation time and systemic vascular resistance increased significantly but similarly. Central blood volume, plasma volume and arterial compliance were unaltered. The QT_c interval and renin levels decreased in the carvedilol group, however not significantly different from the propranolol group. Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups. Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups (−17% and −20%, non significant).ConclusionsSystemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could not demonstrate any significant difference between the two treatments.     

Gray colored glasses: Is major depression partially a sensory perceptual disorder?

Background

Major depression is a neuropsychiatric disorder that can involve profound dysregulation of mood. While depression is associated with additional abnormalities besides reduced mood, such as cognitive dysfunction, it is not well established that sensory perception is also altered in this disorder (aside from in psychotic depression). Recent studies have shown that visual processing, in as early a stage as the retina, is impaired in depression. This paper examines the hypothesis that major depression can involve alterations in sensory perception.

Methods

A Pubmed literature search investigated several lines of evidence: innervation of sensory cortex by serotonin and norepinephrine; antidepressant drugs and depression itself affecting processing of facial expressions of emotion; electroencephalography (EEG) studies of depressed persons and antidepressant drugs; involvement of the serotonergic 5HT2A receptor in both depression and hallucinogenic drug action; psychotic depression involving sensory distortions; dopamine possibly playing a role in depression; and the antidepressant effect of blocking the NMDA receptor with ketamine.

Results

Data from each of these lines of evidence support the hypothesis that major depression can involve sensory perceptual alterations.

Conclusions

Loss of interest in one's daily activities and inability to experience pleasure, also known as anhedonia, in major depression may in part be mediated by sensory abnormalities, whereby normal sensory perceptions are no longer present to activate reward circuitry.

Limitations

The data supporting the hypothesis tend to be associative, so further confirmation of the hypothesis awaits additional controlled experiments.     

Propranolol for infantile hepatic hemangioendothelioma: Clinical evaluation of drug efficacy and safety using a single-center patient cohort

Introduction and objectivesInfantile hepatic hemangioendothelioma (IHHE) is a benign liver tumor, associated with hypothyroidism and vascular malformations along the skin, brain, digestive tract and other organs. Here, we determined a single-center patient cohort by evaluating the effectiveness and safety of propranolol and sirolimus for the treatment of IHHE.Patients and methodsWe performed a monocentric and observational study, based on clinical data obtained from 20 cases of IHHE treated with oral propranolol and sirolimus at the Shanghai Children's Medical Center (SCMC), between December 2017 and April 2019. All cases were confirmed by abdominal enhanced CT examination (18/20, 90%) and sustained decrease of alpha fetoprotein (AFP) (2/20, 10%).Propranolol treatment was standardized as once a day at 1.0 mg/kg for patients younger than 2 months, and twice a day at 1.0 mg/kg (per dose) for patients older than 2 months. Sirolimus was used to treat refractory IHHE patients after 6 months of propranolol treatment, and initial dosing was at 0.8 mg/m² body surface per dose, administered every 12 h. Upon treatment, abdominal ultrasound scanning was regularly performed to evaluate any therapeutic effects. All children were followed up for 6–22 months (mean value of 12.75 months). The clinical manifestations and therapeutic effects, including complications during drug management, were reviewed after periodic follow-up.ResultsThe effective rate of propranolol for the treatment of children with IHHE was 85% (17/20). In most cases, the AFP levels gradually decreased into the normal range. A complete response (CR) was achieved in 3 cases, partial response (PR) for 14 cases, progressive disease (PD) for 2 cases and stable disease (SD) was only detected once. Lesions decreased in two PD patients after administration of oral sirolimus. No serious adverse reactions were observed.ConclusionThis study indicates that both propranolol and sirolimus were effective drugs for the treatment of children with IHHE at SCMC.     

两种药物治疗婴幼儿表浅型血管瘤的疗效及安全性分析

目的研究外用马来酸噻吗洛尔和口服普萘洛尔治疗婴幼儿表浅型血管瘤的疗效及安全性。方法将我院2017年10月~2018年4月收治的200例表浅型血管瘤婴幼儿患者分为外用组与内服组,各100例。外用组采用外用的马来酸噻吗洛尔溶液治疗,内服组采用口服普萘洛尔治疗,用药时间为12个月,每月定期进行复查,比较两组患儿治疗前后的疗效、血管瘤血流峰值(PSV)和阻力系数(RI),并监测副反应的情况。结果治疗后,外用组显效率为70%,内服组显效率为67%,治疗效果无显著性差异(P>0.05);治疗后,两组的PSV、RI均得到改善,无显著性差异(P>0.05);治疗后,外用组不良反应显著低于内服组(P<0.05),且两组均未出现严重不良反应。结论采用外用马来酸噻吗洛尔治疗婴幼儿表浅型血管瘤安全性比口服普萘洛尔安全性好,效果显著,不良反应少,值得推广使用。     

Effect of propranolol vs prednisolone vs propranolol with prednisolone in the management of infantile hemangioma: A randomized controlled study

Aims and Objectives

The purpose of this study was to compare the efficacy of orally administered propranolol versus prednisolone versus both in the treatment of potentially disfiguring or functionally threatening infantile hemangiomas.

Material and Methods

A prospective study of 30 patients aged 1 week–8 months was randomized into three equal groups. These were as follows: A, propranolol (2–3 mg/kg/d); B, prednisolone (1–4 mg/kg/d); and C, receiving both for a minimum duration of 3 months. Dimensions, color, consistency, ultrasonography, photographic documentation based on Visual Analogue Scale (VAS) were recorded before and periodically after starting treatment. A minimum 75% improvement was considered as success with no regrowth up to 1 month of stopping treatment.

Results

Mean initial response time (days) in A (4.1 ± 3.3 SD) and C (4.7 ± 3.4SD) was significantly lower than B (9.78 ± 7.8SD) (p < 0.047). Significant change in consistency was noted very early in A (24 hours) compared to B and C (8 days). VAS results are as follows: (a) color fading—significant reduction in A within 48 hours compared to B and C (p = 0.025), (b) flattening—more significant and earlier in A and C than B (p < 0.05), and (c) mean reduction in size: significant in A and C at 3 months (p = 0.005, p = 0.005), 6 months (p = 0.005, p = 0.008), 12 months (p = 0.005, p = 0.008), and 18 months (p = 0.02, p = 0.04), whereas in B, it was seen only at 6 months (p = 0.008).

Conclusions

Propranolol had a consistent, rapid therapeutic effect compared to prednisolone. A combination of the two had a comparable but not higher efficacy than propranolol alone. Prednisolone was associated with a higher number of complications, thereby decreasing patient compliance.     

Beta-blockers for the treatment of problematic hemangiomas

OBJECTIVE:

To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas.

METHODS:

A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy.

RESULTS:

Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%).

CONCLUSIONS:

Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment.