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Cureus Mar 2020Introduction The benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain....
Introduction The benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain. Pralidoxime is the most often used oxime worldwide. In vitro experiments have consistently shown that oximes are effective reactivators of human acetylcholinesterase enzyme, inhibited by OP compounds. However, the clinical benefit of pralidoxime is still unclear. A recent meta-analysis has found that pralidoxime provides no significant improvement in outcome and rather may cause harm while increasing the economic burden in low-income communities where its use is the most prevalent. Objectives This study aimed to provide an updated evaluation of the efficacy of pralidoxime in addition to atropine alone in the treatment of patients with acute OP poisoning in terms of mortality, need for ventilator support, and the incidence of intermediate syndrome. The intermediate syndrome is a clinical syndrome that occurs 24 to 96 hours after the ingestion of an OP compound and is characterized by prominent weakness of neck flexors, muscles of respiration, and proximal limb muscles. Materials and methods We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases until January 2019 for randomized controlled trials (RCTs) in the English language that evaluated the use of pralidoxime in individuals of any age, gender or nationality presenting with an alleged history of OP intake. The primary outcome was mortality. Secondary outcomes were the need for ventilator support and the incidence of intermediate syndrome. The risk of bias in included studies was assessed using the tool recommended by the Cochrane Handbook of Systematic Review of Interventions. Treatment/control differences in these outcomes across included studies were combined using risk ratios (RR). Results Six randomized controlled trials (n = 646) fulfilled the inclusion criteria, including one further trial missed from the most recent systematic review. The risk of bias varied across studies, with Eddleston 2009 being of the lowest risk and Cherian 2005 being of high risk. The risk of mortality (RR = 1.53, 95% confidence interval (CI) 0.97 to 2.41, P = 0.07) and the need for ventilator support (RR = 1.29, 95% CI 0.97 to 1.71, P = 0.08) were not significantly different between the pralidoxime and the control group. There was a significant increase in the incidence of intermediate syndrome in the pralidoxime group (RR = 1.63; 95% CI 1.01 to 2.62, P = 0.04). Conclusions Based on our meta-analysis of the available RCTs, pralidoxime was not shown to be beneficial in patients with acute OP poisoning. Our findings are consistent with the other literature.
PubMed: 32257715
DOI: 10.7759/cureus.7174 -
The Journal of Trauma and Acute Care... Oct 2019Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A...
Antimotility agents for the treatment of acute noninfectious diarrhea in critically ill patients: A practice management guideline from the Eastern Association for the Surgery of Trauma.
BACKGROUND
Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice.
METHODS
The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay.
RESULTS
The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found.
CONCLUSION
Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea.
LEVEL OF EVIDENCE
Systematic Review/Guidelines, level III.
Topics: Adult; Antidiarrheals; Critical Illness; Diarrhea; Diet Therapy; Diphenoxylate; Gastrointestinal Motility; Humans; Loperamide; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31574060
DOI: 10.1097/TA.0000000000002449 -
Chinese Medical Sciences Journal =... Jun 2020Objective Post-operative cognitive dysfunction (POCD) and post-operative delirium (POD) are two common post-operative cerebral complications. The current meta-analysis... (Meta-Analysis)
Meta-Analysis
Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis.
Objective Post-operative cognitive dysfunction (POCD) and post-operative delirium (POD) are two common post-operative cerebral complications. The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride (PHC) on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients. Primary outcomes of interest included the incidences of POCD and POD; the secondary outcomes of interest included peri-operative mini-mental state examination (MMSE) scores. Two authors independently extracted peri-operative data, including patients' baseline characteristics, surgical variables, and outcome data. For dichotomous data (POCD and POD occurrence), treatment effects were calculated as odds ratio () and 95% confidential interval (). Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. For continuous variables (MMSE scores), treatment effects were calculated as weighted mean difference (WMD) and 95% . Statistical significance was defined as <0.05.Results Our search yielded 33 studies including 4017 patients. Meta-analysis showed that, the incidence of POCD in PHC group was comparable to that in saline group (=0.97; 95% : 0.58-1.64; =0.92), scopolamine group (=0.78; 95% : 0.48-1.27; =0.32) and atropine group (=1.20; 95% : 0.86-1.67; =0.29). The incidence of POD in PHC group was comparable to that in saline group (=1.53; 95% : 0.81-2.90; =0.19) and scopolamine group (=0.53; 95% : 0.06-4.56; =0.56), but higher than that in atropine group (=4.49; 95% : 1.34-15.01; =0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.
Topics: Cognitive Dysfunction; Delirium; Humans; Incidence; Postoperative Complications; Quinuclidines
PubMed: 32684232
DOI: 10.24920/003630 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2020Organophosphorus (OP) insecticide self-poisoning is a global problem, killing tens of thousands of people every year. Oxidative stress has been proposed to play a...
Organophosphorus (OP) insecticide self-poisoning is a global problem, killing tens of thousands of people every year. Oxidative stress has been proposed to play a pathological role in OP poisoning, but whether it plays a direct toxic role is currently unclear. To determine whether there is consistent evidence of oxidative stress in patients with acute OP insecticide self-poisoning, and whether there are animal or human trial data that indicate that treatment of oxidative stress provides clinical benefit, which would suggest a direct toxic effect of oxidative stress. We conducted a systematic review using the PubMed, EMBASE and MEDLINE databases, and the Cochrane Database of Systematic reviews, based upon the following search terms and keywords: "organophosphate poisoning", "oxidative stress" and "antioxidant". All articles relevant to the aims of the study were included. Articles related to chronic OP poisoning, to use of medicines without antioxidant benefits, or to subjects other than oxidative stress were excluded. The search returned 256 results of which 17 studies were considered relevant and grouped under the following categories: observational human studies ( = 11) and intervention studies in animals ( = 4) and humans ( = 2). Oxidative damage to lipids and proteins was reported in all eleven human studies. Eight of nine studies reported variable increases in a weak marker of lipid peroxidation, malondialdehyde. In two case-control studies, erythrocyte membrane malondialdehyde concentrations were 380% and 160% higher in cases than controls, while plasma malondialdehyde concentrations were ∼63% higher in cases than controls in three case-control studies. In a prospective study, plasma malondialdehyde did not increase significantly from baseline in moderate or severely poisoned patients. Five case-control studies measured thiol residues as markers of protein oxidative damage and found variable changes after poisoning. No evidence of oxidative DNA damage was found in the one study that investigated it. After treatment with an antioxidant, all four studies showed an improvement in either markers of oxidative damage or antioxidant activity. One mouse study with a relatively low risk of bias showed that administration of acetylcysteine 200 mg/kg reduced malondialdehyde by 35% and increased survival by more than 60%. We found two small randomised controlled trials reporting the use of acetylcysteine as an adjunct to standard treatment in acute OP poisoning. The trials found that acetylcysteine reduced atropine requirements by 77% and 55%, but did not affect clinically relevant outcomes. Several studies showed evidence of OP insecticide-induced oxidative damage and antioxidant activity, suggesting that endogenous antioxidant defences are triggered in acute OP poisoning. However, the markers of lipid peroxidation used were weak, there was high inter-individual variability between studies in results and quality, and marked variation between the OP insecticides involved. Animal data provide some evidence that antioxidants alleviate adverse effects of acute poisoning, suggesting that oxidative stress may directly cause clinical harm. Acetylcysteine appeared beneficial in animal studies, but this could be mediated increased synthesis of the endogenous detoxifying agent, glutathione, rather than through a direct antioxidant effect. The two human clinical studies were too small to provide any clear evidence to support the use of acetylcysteine in OP poisoning. Further research into the mechanisms of oxidative stress in acute OP poisoning, combined with large unambiguous clinical trials of antioxidants, are required before they can be used routinely in treatment.
Topics: Acute Disease; Animals; Antioxidants; Humans; Insecticides; Organophosphate Poisoning; Organophosphorus Compounds; Oxidative Stress
PubMed: 31810386
DOI: 10.1080/15563650.2019.1693589 -
Environmental Science and Pollution... Oct 2019Glucagon-like peptide-1 (GLP-1) is involved in postprandial glucose homeostasis. Secretion of which involves a cholinergic pathway. Anticholinergic agent like atropine...
Glucagon-like peptide-1 (GLP-1) is involved in postprandial glucose homeostasis. Secretion of which involves a cholinergic pathway. Anticholinergic agent like atropine could act as a competitive antagonist of acetylcholine at muscarinic receptors. This review explores studies that assess the role of atropine in GLP-1 secretion. We selected published original articles from PubMed, Science Direct, The Cochrane Library, Trip, Google and the reference lists of the selected articles. Reporting was done according to the PRISMA statement. Relevant standard and previously published tools were used to assess the risk of bias of the selected articles. Twelve articles out of 185 search results fulfilled the review criteria. Eight were in vivo studies (six animal and two human studies), three were ex vivo studies and one was an in vitro study. Animal studies had rats, mice, pigs and monkeys as the subjects. Human studies involved healthy men and women. Majority of the studies reported an atropine-mediated attenuation of GLP-1 secretion and postprandial secretion of GLP-1 was mainly affected. However, atropine failed to significantly affect GLP-1 secretion when dipeptidyl peptidase-4 (DPP-4) enzyme was inhibited.
Topics: Adult; Animals; Atropine; Dipeptidyl Peptidase 4; Female; Glucagon-Like Peptide 1; Humans; Male; Mice; Postprandial Period; Rats; Swine
PubMed: 31446595
DOI: 10.1007/s11356-019-06227-2 -
Clinical Case Reports Nov 2019Clozapine is considered the golden standard in the treatment of therapy-resistant schizophrenia; however, it associated with bothersome side effects such as sialorrhea....
Clozapine is considered the golden standard in the treatment of therapy-resistant schizophrenia; however, it associated with bothersome side effects such as sialorrhea. Current evidence suggests that the sublingual use of atropine seems to be safe and effective and could be considered as a first-line treatment of clozapine-induced sialorrhea.
PubMed: 31788260
DOI: 10.1002/ccr3.2431