Global research trends in microbiome-gut-brain axis during 2009-2018: a bibliometric and visualized study.

BACKGROUND: The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated. This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009-2018). METHODS: The current study uses the Scopus for data collection. We used the key terms "microbiome-gut-brain axis" and its synonyms because we are concerned with MGBA per se as a new concept in research rather than related topics. A VOSviewer version 1.6.11 was used to visualize collaboration pattern between countries and authors, and evolving research topics by analysis of the term co-occurrence in the title and abstract of publications. RESULTS: Between 2009 and 2018, there were 51,504 published documents related to the microbiome, including 1713 articles related to the MGBA: 829 (48.4%) original articles, 658(38.4%) reviews, and 226 (13.2%) other articles such as notes, editorials or letters. The USA took the first place with 385 appearances, followed by Ireland (n = 161), China (n = 155), and Canada (n = 144).The overall citation h-index was 106, and the countries with the highest h-index values were the USA (69), Ireland (58), and Canada (43). The cluster analysis demonstrated that the dominant fields of the MGBA include four clusters with four research directions: "modeling MGBA in animal systems", "interplay between the gut microbiota and the immune system", "irritable bowel syndrome related to gut microbiota", and "neurodegenerative diseases related to gut microbiota". CONCLUSIONS: This study demonstrates that the research on the MGBA has been becoming progressively more extensive at global level over the past 10 years. Overall, our study found that a large amount of work on MGBA focused on immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders. Despite considerable progress illustrating the communication between the gut microbiome and the brain over the past 10 years, many issues remain about their relevance for therapeutic intervention of many diseases.

Delayed onset of liver injury after intentional chloroform overdose: a case report and literature review.

Chloroform is a recognised cause of acute liver injury, although now rarely encountered in clinical practice. We present a case of inhalational chloroform self-poisoning in a 47-year-old man that presented to hospital initially with reduced conscious level and later developed acute liver injury that was treated with intravenous acetylcysteine. This paper reviews the existing literature and presents a summary of the mechanisms of chloroform hepatotoxicity. Published cases show that there is a characteristic delay of 24 to 48 hours between chloroform exposure and elevation of liver transaminase activity. Therefore, clinicians need to provide an appropriate duration of monitoring in order to detect the occurrence of this important toxic effect.

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose.

BACKGROUND: The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. METHOD: A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. RESULTS: From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. CONCLUSION: Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge.

Development and validation of a computerized algorithm for International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).

STUDY DESIGN: Validation study. OBJECTIVES: To describe the development and validation of a computerized application of the international standards for neurological classification of spinal cord injury (ISNCSCI). SETTING: Data from acute and rehabilitation care. METHODS: The Rick Hansen Institute-ISNCSCI Algorithm (RHI-ISNCSCI Algorithm) was developed based on the 2011 version of the ISNCSCI and the 2013 version of the worksheet. International experts developed the design and logic with a focus on usability and features to standardize the correct classification of challenging cases. A five-phased process was used to develop and validate the algorithm. Discrepancies between the clinician-derived and algorithm-calculated results were reconciled. RESULTS: Phase one of the validation used 48 cases to develop the logic. Phase three used these and 15 additional cases for further logic development to classify cases with 'Not testable' values. For logic testing in phases two and four, 351 and 1998 cases from the Rick Hansen SCI Registry (RHSCIR), respectively, were used. Of 23 and 286 discrepant cases identified in phases two and four, 2 and 6 cases resulted in changes to the algorithm. Cross-validation of the algorithm in phase five using 108 new RHSCIR cases did not identify the need for any further changes, as all discrepancies were due to clinician errors. The web-based application and the algorithm code are freely available at www.isncscialgorithm.com. CONCLUSION: The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. SPONSORSHIP: This study is sponsored by the Rick Hansen Institute and supported by funding from Health Canada and Western Economic Diversification Canada.

International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

International standards for neurological classification of spinal cord injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

Citalopram and cardiac toxicity.

PURPOSE: Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity. METHODS: Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose. RESULTS: The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease. CONCLUSIONS: A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods.

Variability of antimicrobial prescribing in patients with acute cellulitis.

PURPOSE: Clinical guidelines concerning treatment of infection are incorporated into prescribing formularies and antimicrobial stewardship policies. The extent to which these influence prescribing is uncertain. In this study, we sought to examine antimicrobial prescribing patterns in patients with cellulitis. METHODS: Consecutive adults admitted to hospital due to acute cellulitis between 2008 and 2010 were studied. Data collected were clinical and laboratory markers of sepsis, antimicrobial agent, route of administration, number of i.v. dosages, duration of antimicrobial treatment, and hospital length of stay. Three groups were defined by prescribing that was (i) identical to formulary, (ii) modified appropriately due to microbiological data or prior drug allergy, and (iii) nonformulary prescribing. Comparisons were made between groups using Mann-Whitney tests. RESULTS: There were 306 patients: 167 men (54.6%), median age 66 (range 18-100) years. Prescribing was consistent with formulary recommendations in 253 (82.7%), modified appropriately in 24 (7.8%), and nonformulary in 29 (9.5%). Median [interquartile range (IQR)] duration of hospital stay was 5 (3-8), 7 (5-9, P = 0.026), and 7 (5-14, P = 0.0006) days, and overall duration of antimicrobial therapy was 12 (9-16), 13 (8-15), and 15 (12-19, P = 0.0479) days, respectively. No differences were observed in clinical or laboratory markers of sepsis. CONCLUSIONS: Prescribing patterns accorded with prevailing guidelines in the majority of patients. Nonetheless, there was nonformulary prescribing in 10% of patients, and this could not be explained by clinical or laboratory measures of disease severity. Further work is needed to explore the factors that contribute to nonformulary prescribing in this group of patients.

Patterns of admissions in an acute medical unit: priorities for service development and education.

An Acute Medical Unit has recently been established at York Hospital. The present study sought to characterise the case mix of acutely unwell medical patients to allow identification of priorities for ongoing service development and to assess educational opportunities for trainees in the region. Data were collected for 16001 admission episodes between January 2010 and April 2011 inclusive. These allowed characterisation of the case mix, and identified key priorities where clinical pathway do not yet exist, namely heart failure, urinary tract infection, and acute diarrhoea. Good educational opportunities exist for most aspects of the Acute Medicine curriculum; several weaknesses were identified, and trainees might address these by undertaking a specific period of specialty training in endocrinology and neurology.

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut-brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut-brain axis. AIM: To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field. METHODS: The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000-2019. VOSviewer software was used for data visualization. RESULTS: A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS (r = 0.951, P < 0.001). The United States was the most prolific country with 449 (24%) publications, followed by the United Kingdom (n = 176, 9.4%), China (n = 154, 8.2%), and Italy (n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters: (1) The gut-brain axis related to IBS; (2) Clinical trials related to IBS and the microbiome; (3) Drug-mediated manipulation of the gut microbiome; and (4) The role of the altered composition of intestinal microbiota in IBS prevention. CONCLUSION: This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

Evaluation of a QT nomogram for risk assessment after antidepressant overdose.

AIMS: A 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. METHODS: A 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 QT(c) (QT corrected by Bazett's formula) greater than ≥440 ms and QT(c) ≥500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals. RESULTS: There were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QT(c) was ≥440 ms in 23.1% (95% CI 19.8, 26.8%), and QT(c) was ≥500 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 QT(c) ≥440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013). CONCLUSIONS: The QT nomogram was associated with a lower false positive rate than widely accepted QT(c) criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QT(c) criteria and merits further investigation in a clinical setting.

Variability in the quality of overdose advice in Summary of Product Characteristics (SPC) documents: gut decontamination recommendations for CNS drugs.

AIMS: Deliberate self-poisoning is a major cause of morbidity and mortality. The Summary of Product Characteristics (SPC) document is a legal requirement for all drugs, and Section 4.9 addresses the features of toxicity and clinical advice on management of overdose. The quality and appropriateness of this advice have received comparatively little attention. METHODS: Section 4.9 of the SPC was examined for all drugs in the central nervous system (CNS) category of the British National Formulary. Advice concerning gut decontamination was examined with respect to specific interventions: induced vomiting, oral activated charcoal, gastric lavage, and other interventions. Data were compared with standard reference sources for clinical management advice in poisoning. These were graded 'A' if no important differences existed, 'B' if differences were noted but not thought clinically important, and 'C' if differences were thought to be clinically significant. RESULTS: SPC documents were examined for 258 medications from 67 manufacturers. The overall agreement was 'A' in 23 (8.9%), 'B' in 28 (10.9%) and 'C' in 207 (80.2%). Discrepancies were due to inappropriate recommendation of induced emesis in 21.7% (95% confidence interval 17.1, 27.1), gastric lavage in 38.4% (32.7, 44.4), other gut decontamination in 5.8% (3.6, 9.4) and failure to recommend oral activated charcoal in 57.4% (51.1, 63.4). CONCLUSIONS: Gut decontamination advice in SPC documents with respect to CNS drugs was inadequate. Possible reasons for the observed discrepancies and ways of improving the consistency of advice are proposed.

Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit.

BACKGROUND: Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. METHODS: This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. RESULTS: Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. CONCLUSIONS: Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.

Interpretation of clinical guidelines for poisoned patients: positive and negative effects of standard phrases used in TOXBASE.

INTRODUCTION: Electronic information sources are increasingly relied upon for clinical management advice. TOXBASE is a standardised online resource that offers clinical advice on the management of poisoned patients and is the first point of contact between clinicians and the National Poisons Information Service in the United Kingdom. Advice is delivered using a series of standard phrases. The present study examined how healthcare professionals interpret the phrases and studied their impact on clinical decision-making. METHODS: A structured prospective written questionnaire was offered to healthcare staff in the Lothian region, and an electronic questionnaire issued to TOXBASE users across the United Kingdom. Participants were asked to respond to a variety of scenarios representing acutely poisoned patients. Clinical management advice was offered via TOXBASE using a variety of standard phrases, and participants were asked to express the likelihood that they would then administer gut decontamination treatment. RESULTS: There were 70 respondents to written questionnaires, and 119 respondents to the electronic version. Phrases that included didactic instructions, for example 'give', 'contraindicated', 'do' and 'perform' were associated with strongly positive or strongly negative responses. In contrast, advice that consisted of open phrases such as 'consider', 'benefit uncertain', and 'few data' were associated with inconsistent responses. CONCLUSION: Didactic words and phrases are associated with more consistent interpretation and response than open-ended words and phrases. The choice of words and phrases used in electronic systems can have an independent impact on clinical decision-making and require further consideration.

Self-poisoning in older adults: patterns of drug ingestion and clinical outcomes.

BACKGROUND AND AIMS: self-poisoning accounts for a substantial proportion of acute medical hospital presentations, but has been poorly characterised in older adults. This study sought to determine the agents ingested by older adults presenting to hospital after drug overdose, and to compare clinical outcomes to younger patients. METHODS: a retrospective observational study of patients admitted via the emergency department due to drug overdose between 2004 and 2007. RESULTS: during the study period, there were 8,059 admissions, including 4,632 women (57.5%). This included a subgroup of 361 patients (4.5%) who were >60 years of age. This subgroup was more likely to require hospital stay >1 night, odds ratio (95% confidence interval) = 4.3 (3.6-5.5, P < 0.0001), transfer to a critical care area = 3.8 (1.1-13.0, P = 0.0340) and had higher mortality = 4.8 (1.1-22.1, P = 0.0463). A higher proportion of older patients required transfer to a psychiatric unit (P < 0.0001) or to a general medical ward (P < 0.0001) than younger adults. CONCLUSIONS: older adults that presented to hospital after drug overdose had ingested different drugs than younger patients, possibly due to different prescribing patterns, and had a poorer outcome. The use of drugs associated with significant toxicity should be avoided in older patients at risk of self-harm.

Acute caffeine ingestion: clinical features in patients attending the emergency department and Scottish poison centre enquiries between 2000 and 2008.

BACKGROUND AND AIMS: Little information is available regarding the healthcare burden associated with deliberate caffeine ingestion. The present study sought to establish the impact of caffeine ingestion on hospital attendances and Poisons Centre enquiries in Scotland. METHODS: Retrospective analyses of clinical data from patients attending the Royal Infirmary of Edinburgh after acute caffeine ingestion, and TOXBASE enquiries from Scotland regarding caffeine poisoning between 2000-2008 inclusive. Cochran-Armitage trend tests were used to evaluate changes in annual admissions and TOXBASE enquiries. RESULTS: There were 43 hospital attendances due to deliberate caffeine ingestion, representing 0.2% of all poisoning cases. The median (interquartile range) stated dose was 1040 mg (600-1500 mg). Minor gastrointestinal symptoms were common, and no patient developed features of severe toxicity. There were 1418 enquiries to TOXBASE concerning caffeine poisoning, representing 0.2% of all poisoning enquiries from Scotland. The proportions of hospital admissions and TOXBASE enquiries due to caffeine ingestion have remained constant. CONCLUSION: Caffeine ingestion is uncommon, and results in only a small number of hospital attendances and Poisons Centre enquiries. In contrast to patterns reported elsewhere, the prevalence of caffeine abuse has not increased in Scotland over recent years.

Pharmacological effects and safety monitoring of anabolic androgenic steroid use: differing perceptions between users and healthcare professionals.

BACKGROUND: Androgenic anabolic steroids (AASs) have a number of licensed clinical indications but are also subject to abuse within the body building community. They have a number of potentially important adverse pharmacological effects, and users require health monitoring, including selected laboratory investigations. The extent to which AAS users are able to seek medical supervision and the ability of healthcare providers to respond to the needs of users is uncertain. The present study sought to ascertain how AAS abusers interact with healthcare providers, and self-reported knowledge among doctors regarding the healthcare effects and need for monitoring of AAS users. METHODS: Questionnaires were administered, and there were 216 respondents among AAS users and 134 doctors. RESULTS: A high proportion of AAS users cited various barriers to accessing healthcare, including 136 of 189 (72%) that reported a fear of reproach, and 107 of 194 (55%) that had avoided seeking medical advice; 137 of 193 respondents (71%) did not disclose AAS use to healthcare professionals. Doctors across a broad range of seniority stated a lack of knowledge of AASs; 130 (97%) had received no formal training, and 109 (82%) did not know which blood tests could be used for safety monitoring. CONCLUSIONS: The present study has highlighted some perceptions among the body-building community that create obstacles to them accessing appropriate safety monitoring while using AASs. Doctors may not have adequate knowledge of AASs, which may prevent them giving accurate and complete information. Further work is needed to address the barriers of communication between users and health professionals in order to facilitate better healthcare monitoring and drug safety.

Does the patient history predict hepatotoxicity after acute paracetamol overdose?

BACKGROUND: Initial management of patients who were presented to hospital after acute paracetamol overdose depends on the suspected amount ingested and more than 12 g is potentially fatal. However, the validity of this approach has received comparatively little attention. METHODS: The present study is sought to establish whether the stated paracetamol dose might predict systemic exposure and risk of hepatotoxicity. A prospective observational study of consecutive patients presenting to the Emergency Department due to acute paracetamol overdose was performed. Serum paracetamol concentrations between 4 and 15 h post-ingestion were compared with the Rumack-Matthew '200-line' nomogram, and hepatotoxicity was defined by prothrombin time ratio >1.3 or alanine transaminase > or =1000 U/l. RESULTS: There were 987 patients, and the stated quantity of paracetamol ingested was 0-12 g in 475 (48.1%), >12 g in 349 (35.4%) and unknown in 163 (16.5%). Ingestion of >12 g was associated with paracetamol concentration above the '200-line' in 31.8% (95% CI 27.1-36.9%) vs. 3.2% (1.9-5.2%), P < 0.0001 by chi2 proportional test, and associated with hepatotoxicity in 6.9% (4.6-10.1%) vs. 1.3% (0.5-2.8%), P = 0.0001. CONCLUSION: Therefore, ingestion of >12 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.

Predictive factors for generalized seizures after deliberate citalopram overdose.

AIMS: Seizures are a recognized complication of citalopram overdose. The present study sought to establish risk factors for seizures in this high-risk patient group, including stated dose ingested, co-ingested drugs or ethanol, and electrolyte disturbances. METHODS: A retrospective casenote review was carried out of patients who attended the Emergency Department due to citalopram overdose between January 2000 and July 2007 inclusive. Stepwise logistic regression analysis considered age, gender, stated citalopram dose, acute ethanol consumption, co-ingested drugs, administration of activated charcoal, and hyponatraemia. RESULTS: There were 241 patients (177 women), and the median (interquartile range) stated citalopram dose was 300 mg (200 to 600 mg). Generalized seizures occurred in 18 patients (7.5%). Logistic regression analysis found co-ingested tricyclic antidepressants or venlafaxine predicted seizures with odds ratio = 15 (95% confidence interval 3, 75). In the absence of co-ingested drugs, the minimum citalopram dose associated with seizures was 400 mg. Odds ratio for seizures = 1.1 (95% confidence interval 1.0, 1.2) for every 100 mg increment in citalopram dose. Seizures were associated with a greater need for invasive ventilatory support, higher creatine kinase activity, and prolonged hospital stay. CONCLUSIONS: Generalized seizures are an important manifestation of citalopram toxicity, and cannot be explained solely by electrolyte disturbances or co-ingestion of other drugs or ethanol. The strongest predictors of seizures in this patient series were ingestion of high citalopram dosages and co-ingestion of drugs capable of lowering seizure threshold.

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose.

PURPOSE: Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. METHODS: This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. RESULTS: Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). CONCLUSIONS: Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.