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The Cochrane Database of Systematic... Nov 2017Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.
OBJECTIVES
To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS
We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings.
SELECTION CRITERIA
We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS
We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence).
AUTHORS' CONCLUSIONS
The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.
Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Chloral Hydrate; Dexmedetomidine; Diagnostic Techniques, Neurological; Electroencephalography; Humans; Hydroxyzine; Hypnotics and Sedatives; Infant; Melatonin; Midazolam; Music Therapy; Neuroimaging; Pentobarbital; Promethazine; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 29099542
DOI: 10.1002/14651858.CD011786.pub2 -
European Clinical Respiratory Journal 2023Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without...
BACKGROUND
Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome.
METHODS
Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma.
RESULTS
In our registry of 56,523 patients with COPD, 5,661 collected promethazine ( = 3,723) or melatonin ( = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine ( = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, <0.0001).
CONCLUSIONS
Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.
PubMed: 37680536
DOI: 10.1080/20018525.2023.2250604 -
Biomolecules Jun 2022Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential...
Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke, in which the temperature is decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C + P), plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C + P, DHC, C + P + DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor), and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expression of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 was measured with Western blotting. PH with a combination of C + P and DHC induced faster, longer, and deeper hypothermia, as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C + P and DHC.
Topics: Adenosine Triphosphate; Animals; Chlorpromazine; Gluconeogenesis; Glucose; Hypothermia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Lactates; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stroke
PubMed: 35740974
DOI: 10.3390/biom12060851 -
Cell Death & Disease Aug 2022Sepsis is a life-threatening syndrome with disturbed host responses to severe infections, accounting for the majority of death in hospitalized patients. However,...
Sepsis is a life-threatening syndrome with disturbed host responses to severe infections, accounting for the majority of death in hospitalized patients. However, effective medicines are currently scant in clinics due to the poor understanding of the exact underlying mechanism. We previously found that blocking caspase-11 pathway (human orthologs caspase-4/5) is effective to rescue coagulation-induced organ dysfunction and lethality in sepsis models. Herein, we screened our existing chemical pools established in our lab using bacterial outer membrane vesicle (OMV)-challenged macrophages, and found 7-(diethylamino)-1-hydroxy-phenothiazin-3-ylidene-diethylazanium chloride (PHZ-OH), a novel phenothiazinium-based derivative, was capable of robustly dampening caspase-11-dependent pyroptosis. The in-vitro study both in physics and physiology showed that PHZ-OH targeted AP2-associated protein kinase 1 (AAK1) and thus prevented AAK1-mediated LPS internalization for caspase-11 activation. By using a series of gene-modified mice, our in-vivo study further demonstrated that administration of PHZ-OH significantly protected mice against sepsis-associated coagulation, multiple organ dysfunction, and death. Besides, PHZ-OH showed additional protection on Nlrp3 and Casp1 mice but not on Casp11, Casp1/11, Msr1, and AAK1 inhibitor-treated mice. These results suggest the critical role of AAK1 on caspase-11 signaling and may provide a new avenue that targeting AAK1-mediated LPS internalization would be a promising therapeutic strategy for sepsis. In particular, PHZ-OH may serve as a favorable molecule and an attractive scaffold in future medicine development for efficient treatment of bacterial sepsis.
Topics: Animals; Caspase 1; Caspases; Humans; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Promethazine; Protein Kinases; Protein Serine-Threonine Kinases; Pyroptosis; Sepsis
PubMed: 35982051
DOI: 10.1038/s41419-022-05151-7 -
International Journal of Analytical... 2019This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its...
This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on an Agilent Technologies 1290 LC and a 6410 triple quadrupole mass spectrometer. The following parameters, the lower limit of quantification (LLOQ), calibration curve, accuracy, precision, stability, matrix effect, and recovery, were validated. The linear range of the developed method for PMZ, its metabolite promethazine sulfoxide (PMZSO), and schisandrin in rat plasma was 0.5-200 ng/mL ( > 0.995), with an LLOQ of 0.5 ng/mL, which completely met the determination requirements of biosamples. The intra- and interday precision (RSD, %) was below 13.31% (below 16.67% for the LLOQ) in various plasma, whose accuracy (bias, %) was from -8.52% to 11.40%, which were both within an acceptable range. This method was successfully applied to a pharmacokinetic herb-drug interaction study after oral administration of PMZ with or without water extract. The results demonstrated that coadministration with the water extract might affect the pharmacokinetic behaviors of PMZ. In turn, when taken together with PMZ, the pharmacokinetic parameters of schisandrin, the main active component of , were also affected. The method established in the current study was selective, simple, sensitive, and widely available with good linearity, high accuracy and precision, and a stable sample preparation process. Moreover, this analytical method provides a significant approach for the investigation of herb-drug interaction between and PMZ. The potential pharmacokinetic herb-drug interaction of PMZ- and schisandrin-containing preparations should be noted.
PubMed: 31885590
DOI: 10.1155/2019/3497045 -
Cureus Jun 2022[This corrects the article DOI: 10.7759/cureus.25467.].
Correction: Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.
[This corrects the article DOI: 10.7759/cureus.25467.].
PubMed: 38348429
DOI: 10.7759/cureus.c66 -
BioMed Research International 2013Promethazine hydrochloride is a first-generation H1 receptor antagonist, antihistamine, and antiemetic medication that can also have strong sedative effects. The... (Review)
Review
Promethazine hydrochloride is a first-generation H1 receptor antagonist, antihistamine, and antiemetic medication that can also have strong sedative effects. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r was translated into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function.
Topics: Epidermis; Histamine H1 Antagonists; Humans; Inflammation; Promethazine; Skin Diseases
PubMed: 24350243
DOI: 10.1155/2013/151509 -
Frontiers in Medicine 2016Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients...
A Prospective, Randomized, Double-Blinded, Double-Dummy Pilot Study to Assess the Preemptive Effect of Triple Therapy with Aprepitant, Dexamethasone, and Promethazine versus Ondansetron, Dexamethasone and Promethazine on Reducing the Incidence of Postoperative Nausea and Vomiting Experienced by...
INTRODUCTION
Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy.
MATERIALS AND METHODS
This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days.
RESULTS
The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found.
CONCLUSION
This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients undergoing craniotomy under general anesthesia. Future trials testing new PONV prophylaxis regimens in this surgical population should be performed to gain a better understanding of how to best provide prophylactic treatment.
PubMed: 27458584
DOI: 10.3389/fmed.2016.00029 -
European Journal of Translational... Sep 2022Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine...
Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine hydrochloride in reducing children's agitation during the ocular examination for trauma. In this interventional-clinical trial study, a total of 62 children referred to Al-Zahra Ophthalmology Hospital in Zahedan, Iran, were evaluated in two matched groups (case (n = 31) and control (n = 31)) for an initial examination of ocular trauma. Finally, the intervention was performed (giving placebo or promethazine hydrochloride cough syrup 20 minutes before the initial ocular examination at 0.5 mg/kg), and the demographic information form and researcher-made questionnaire modeled on the Cohen-Mansfield Agitation Inventory (CMAI) were completed. The obtained results revealed that the mean scores of physical/aggressive behaviors (p ˂ 0.001), physical/nonaggressive behaviors (p = 0.013), verbal/aggressive behaviors (p ˂ 0.001), and hiding behaviors (p ˂ 0.001) were significantly lower in the promethazine hydrochloride-receiving group than the placebo group. These findings demonstrated that promethazine hydrochloride cough syrup facilitated the examination among the pediatric patients who suffered from traumatic ocular injuries. However, further studies in this field need to be carried out through randomized controlled trials.
PubMed: 36073862
DOI: 10.4081/ejtm.2022.10808 -
Frontiers in Medicine 2016Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence...
The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study.
INTRODUCTION
Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia.
METHODS
The research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review.
RESULTS
The overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6), 15.1 (±25.8), and 21.1 (±25.4) hours, respectively. The overall incidence of nausea and vomiting after 24-120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval ≥500 ms before and/or after surgery.
CONCLUSION
Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the treatment of PONV in patients undergoing neurological surgery under general anesthesia. More studies with a control group should be performed to demonstrate the efficacy of this regimen and that palonosetron is a low risk for QTc prolongation.
CLINICALTRIALSGOV IDENTIFIER
NCT02635828 (https://clinicaltrials.gov/show/NCT02635828).
PubMed: 26870733
DOI: 10.3389/fmed.2016.00001