Ischemia induced during the brief period allowed rapid mucosal repair and complete recovery of tissue barrier properties during reperfusion. Therefore, reperfusion injury was not observed for this method of ischemic damage in equine colonic mucosa.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Overdose with citalopram is associated with QT prolongation and torsades de pointes, whereas this arrhythmia has not been reported after venlafaxine or mirtazapine overdose.• Uncertainty exists concerning the best means of identifying poisoned patients at greatest risk of arrhythmia, and a nomogram comparing QT and heart rate has recently been proposed based on published cases of torsades de pointes.• Few data are available concerning the performance of the nomogram in patients that present to hospital after antidepressant overdose.
WHAT THIS STUDY ADDS• After antidepressant overdose patients had a broad range of heart rate and QT values, which were below the nomogram in 98% of cases (95% confidence interval 96, 99%).• Citalopram overdose was associated with a higher proportion of patients with QT values above the nomogram than venlafaxine and mirtazapine overdose, especially in those who had low heart rates.• The nomogram allowed discrimination between the different antidepressant agents and may have a role in predicting arrhythmia in clinical practice.
AIMSA QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia.
METHODSA retrospective case control study of patients presenting to hospital after overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary outcome variable was QT higher than the nomogram, and was compared with occurrence of QTc (QT corrected by Bazett's formula) greater than Ն440 ms and QTc Ն500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals.
RESULTSThere were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QTc was Ն440 ms in 23.1% (95% CI 19.8, 26.8%), and QTc was Ն500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be associated with QT higher than the nomogram compared with the other agents (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated with QTc Ն440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013).
CONCLUSIONSThe QT nomogram was associated with a lower false positive rate than widely accepted QTc criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QTc criteria and merits further investigation in a clinical setting.
by short-term hypoxia were followed by intense inflammation associated with epithelial repair during reperfusion. Potential relevance: Equine colonic mucosa subjected to a brief period of ischaemia can repair during reperfusion, despite increased mucosal inflammation.
OBJECTIVE To examine effects of continuous rate infusion of lidocaine on transmural neutrophil infiltration in equine intestine subjected to manipulation only and remote to ischemic intestine. ANIMALS 14 healthy horses. PROCEDURES Ventral midline celiotomy was performed (time 0). Mild ischemia was induced in segments of jejunum and large colon. A 1-m segment of jejunum was manipulated by massaging the jejunal wall 10 times. Horses received lidocaine (n = 7) or saline (0.9% NaCl) solution (7) throughout anesthesia. Biopsy specimens were collected and used to assess tissue injury, neutrophil influx, cyclooxygenase expression, and hypoxia-inducible factor 1α (HIF-1α) expression at 0, 1, and 4 hours after manipulation and ischemia. Transepithelial resistance (TER) and mannitol flux were measured by use of Ussing chambers. RESULTS Lidocaine did not consistently decrease neutrophil infiltration in ischemic, manipulated, or control tissues at 4 hours. Lidocaine significantly reduced circular muscle and overall scores for cyclooxygenase-2 expression in manipulated tissues. Manipulated tissues had significantly less HIF-1α expression at 4 hours than did control tissues. Mucosa from manipulated and control segments obtained at 4 hours had lower TER and greater mannitol flux than did control tissues at 0 hours. Lidocaine did not significantly decrease calprotectin expression. Severity of neutrophil infiltration was similar in control, ischemic, and manipulated tissues at 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE Manipulated jejunum did not have a significantly greater increase in neutrophil infiltration, compared with 4-hour control (nonmanipulated) jejunum remote to sites of manipulation, ischemia, and reperfusion. Lidocaine did not consistently reduce neutrophil infiltration in jejunum.
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