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Critical Care (London, England) Jun 2023To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
BACKGROUND
Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
METHODS
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
RESULTS
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
CONCLUSION
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.
Topics: Humans; Propranolol; Clonidine; Pilot Projects; Treatment Outcome; Brain Injuries, Traumatic; Adrenergic Agents
PubMed: 37296432
DOI: 10.1186/s13054-023-04479-6 -
International Journal of Molecular... Sep 2022Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension,... (Review)
Review
Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder.
Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension, coronary artery disease, and tachyarrhythmias. However, due to its ability to cross the blood-brain barrier and affinity towards multiple macromolecules, not only adrenoreceptors, it has also found application in other fields. For example, it is one of the very few medications successfully applied in the treatment of stage fright. This review focuses on the application of propranolol in the treatment of various types of anxiety and stress, with particular reference to stage fright and post-traumatic stress disorder (PTSD). Both mechanisms of action as well as comparison with other therapies are presented. As those indications for propranolol are, in most countries, considered off-label, this review aims to gather information that can be useful while making a decision about the choice of propranolol as a drug in the treatment of those mental conditions.
Topics: Anxiety; Anxiety Disorders; Humans; Propranolol; Stress Disorders, Post-Traumatic
PubMed: 36077489
DOI: 10.3390/ijms231710099 -
Ugeskrift For Laeger Mar 2019
Topics: Adrenergic beta-Antagonists; Anxiety Disorders; Humans; Propranolol
PubMed: 30931879
DOI: No ID Found -
World Journal of Emergency Surgery :... 2017The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant outcomes in severely burned patients (TBSA >20%).
METHODS
Relevant articles from randomized controlled trials were identified by a literature search in MEDLINE, EMBASE, and CENTRAL. We included trials involving patients with a severe burn (>20% of total body surface area affected). Trials were eligible if they evaluated propranolol and compared to usual care or placebo. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We conducted a meta-analysis using a random-effects model.
RESULTS
We included ten studies in our systematic review. These studies randomized a total of 1236 participants. There were no significant differences between propranolol and placebo with respect to mortality (RD -0.02 [95% CI -0.06 to 0.02]), sepsis (RD -0.03 [95% CI -0.09 to 0.04]), and the overall hospital stay (MD -0.37 [-4.52 to 3.78]). Propranolol-treated adults had a decrease in requirements of blood transfusions (MD -185.64 [95% CI -331.06 to -40.43]) and a decreased heart rate (MD -26.85 [95% CI -39.95 to -13.75]).
CONCLUSIONS
Our analysis indicates that there were no differences in mortality or sepsis in severely burned patients treated with propranolol compared with those who had usual care or placebo. However, the use of propranolol in these patients resulted in lower requirements of blood transfusion and lower values of heart rate. The evidence synthesized in this systematic review is limited to conclude that propranolol reduces the length of hospital stay among severely burned patients. Future trials should assess the impact of propranolol on clinically relevant outcomes such as mortality and adverse events.
Topics: Adrenergic beta-Antagonists; Burns; Humans; Patient Safety; Propranolol
PubMed: 28265298
DOI: 10.1186/s13017-017-0124-7 -
International Journal of Clinical... 2022This study aims to evaluate the effects of bevacizumab and propranolol from the point of view of a possible antiangiogenic effect in a model of primary nasal polyp (NP)...
OBJECTIVE
This study aims to evaluate the effects of bevacizumab and propranolol from the point of view of a possible antiangiogenic effect in a model of primary nasal polyp (NP) tissue culture.
METHODS
NP samples of 21 patients and normal healthy nasal mucosa samples of 7 patients were cultured. Samples were divided into four groups as follows (healthy nasal mucosa, NP without any treatment, NP treated with propranolol, NP treated with bevacizumab). Cultured tissues were formalin fixed and paraffin embedded. Tissue sections and immunohistochemical VEGF-A, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) expressions were evaluated. ELISA was also performed for each one of them.
RESULTS
Both propranolol and bevacizumab significantly decreased the expressions of VEGF-A and Ang-1, and they significantly increased the expression of Ang-2 in comparison to the control NP group. In the healthy nasal mucosa group, no significant expression of VEGF-A was seen, a slight (+) Ang-1 expression, and a high (+++) Ang-2 expression were observed.
CONCLUSION
Bevacizumab and propranolol exert an antiangiogenic effect on NP tissues, mainly by decreasing VEGF-A and Ang-1 expression, increasing Ang-2 expression.
Topics: Humans; Nasal Polyps; Bevacizumab; Propranolol; Vascular Endothelial Growth Factor A; Enzyme-Linked Immunosorbent Assay
PubMed: 36304979
DOI: 10.1155/2022/6174664 -
Neurobiology of Learning and Memory Apr 2016Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain... (Review)
Review
Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.
Topics: Adrenergic beta-Antagonists; Animals; Behavior, Animal; Disease Models, Animal; Extinction, Psychological; Fear; Humans; Memory; Propranolol; Rats; Stress Disorders, Post-Traumatic
PubMed: 26808441
DOI: 10.1016/j.nlm.2016.01.009 -
Biomedical Journal Jun 2019In this issue of the Biomedical Journal we discover how alternative splicing might modulate the cell-type specificity and exact function of a ubiquitous purinergic...
In this issue of the Biomedical Journal we discover how alternative splicing might modulate the cell-type specificity and exact function of a ubiquitous purinergic receptor and how the beta blocker propanolol can contribute to breast cancer therapy. Moreover, we learn which culture conditions generate the best vascularisation of tissue engineered bone and which are the clinical features of acute necrotising encephalopathy in adults. Other studies reveal, how laser irradiation can fix fractured all-ceramic dental restorations in situ, and finally that nuclear magnetic resonance holds great potential for the rapid detection of pathogens.
Topics: Alternative Splicing; Animals; Humans; Propranolol; RNA, Messenger
PubMed: 31466707
DOI: 10.1016/j.bj.2019.06.001 -
Molecules (Basel, Switzerland) Jul 2017Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol,...
Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC = 6 μΜ) and antiproteolytic activity (IC = 0.425 μΜ). The conjugate of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC = 0.315 μΜ) and good LOX inhibitory activity (IC = 66 μΜ). Compounds and , derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The isomer of also presented an interesting multitarget biological profile in vitro Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.
Topics: Animals; Cell Line; Cinnamates; Lipoxygenase; Lipoxygenase Inhibitors; Mice; Propranolol; Protease Inhibitors; Soybean Proteins; Glycine max
PubMed: 28757554
DOI: 10.3390/molecules22081247 -
Skin Research and Technology : Official... Apr 2023The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that...
BACKGROUND/OBJECTIVES
The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that several studies have comprehensive therapy regimens, including the best time to start Treatment, dosage, visit frequency, and treatment duration, there is still controversy about the best time to start and stop propranolol medication.
METHODS
Between January 2016 and February 2019, dermatologists experienced hemangioma treatment and recommended propranolol treatment for 232 IHs. A total of 90 patients completed the treatment process after undergoing a color Doppler ultrasound test.
RESULTS
Propranolol uniquely affects each IH. Ninety patients were divided into two groups in this study: entire regression (n = 40) and partial regression (n = 50). The entire regression group's initial treatment period (4.3 ± 2.97 months) was substantially shorter than the partial regression group's (5.2 ± 4.57 months) (p < 0.05). Between the entire regression group (23.4 ± 12.8 months) and the partial regression group (24.5 ± 16.6 months), there was no significant difference in time to reduce propranolol. The partial regression group (32.9 ± 25.3month) had a lengthier treatment course than the entire regression group (23.4 ± 13.7 months) (p < 0.05). The partial regression group (22%), like the entire regression group, had a higher recurrence rate (5%). The overall proportion of hemangiomas on the face (particularly periocular hemangioma) in the regression group was greater than in the control group.
CONCLUSION
The entire regression group's initial treatment time was significantly shorter than the partial regression group's. As a result, as soon as a hemangioma is discovered, it should be treated. To determine the appropriate time to reduce propranolol, we must evaluate the patient's age and the percentage of tumor regression. Periocular hemangioma may have a better prognosis than other types. Given the small number of patients in our study, we will need to do more research in the future to confirm our findings.
Topics: Child; Humans; Infant; Propranolol; Treatment Outcome; Hemangioma; Administration, Oral; Skin Neoplasms
PubMed: 37113082
DOI: 10.1111/srt.13310 -
British Medical Journal May 1969
Topics: Anxiety Disorders; Hallucinations; Heart Diseases; Humans; Male; Middle Aged; Propranolol; Psychoses, Substance-Induced
PubMed: 5781495
DOI: 10.1136/bmj.2.5654.445