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Abstract

The most important diagnostic factor in uncovering a toxic etiology for delirium or critical illness is the clinician's openness to the possibility of its existence. Therefore, a consulting psychiatrist, already prepared to perform the detail-oriented work of sorting out behavioral manifestations of disease, can be a vital asset at the bedside if also attuned to the role of purposeful, accidental, and iatrogenic exposures in the intensive care unit. This article summarizes the presentation, evaluation, and treatment of toxidromes relevant to the work of acute psychosomatic medicine.

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... Given the complexity of the clinical scenario, it is ideal to have a toxicology specialist to guide the identification of the agents involved (6). Interventions aimed at emerging physiological needs are the cornerstone of treatment, and in this clinical setting, not only detailed evaluation is required, but also constant reevaluation (5). ...
... An x-ray can be done to evaluate for iron and lead poisoning, an abdominal and pelvic tomography can be conducted to evaluate caustic poisoning, packaged medications, and foreign bodies (criminal behaviors), and a simple skull tomography can be implemented for making alternative diagnoses in terms of chain inhibitor poisoning transporter of electrons that produce heart attacks in the area of the basal ganglia. But, in general terms, they are not a priority (5). ...
... The implementation of early support therapies has a positive impact on both in-hospital stay, as well as in costs of care and mortality (5). It is considered essential to carry out an orderly approach to the patient taking into account the maintenance of the airway, oxygen therapy and permanent observation of the respiratory muscles' activity, and to perform early orotracheal intubation if the respiratory failure is detected. ...
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Introduction: A high percentage of patients who survived poisoning will be transferred to the Intensive Care Unit (ICU) to continue their management in relation to the severity of the poisoning, and possible complications that arise in this scenario. The clinical results will depend on several factors, such as the ingested dose, the characteristics of the substance, the time of medical attention, and the pre-existing state of health of the patient. Objective: To review the clinical behavior of poisonings in the critically ill patient. Recent findings: The data bases that yielded relevant bibliographical results were Web of Sciences, Scopus, PubMed, SciELO, and bibliographic references published between 2012 and 2020 were chosen. Conclusions: The clinical behavior of poisonings in the critically ill patient is atypical. The intensivist must have an in-depth knowledge of the behavior and pathophysiology of the toxins since making a medical diagnosis on the stage of the critically ill patient is challenging. The integration of all possible medical tools is required to achieve this in the absence of clinical history, and the implementation of early management strategies is necessary to reach physiological restoration by using a continuous evaluation approach. The severity of poisoning in the critically ill patient demands interdisciplinary management that includes assessment by Clinical Toxicology.
... Although several features of opioid toxicity overlap with sedative or hypnotic toxicity, the former typically causes pinpoint pupils, which we did not see in this patient. 1 Serotonin syndrome and neuroleptic malignant syndrome (NMS) can both present with altered mental status and autonomic instability. 1 Serotonin syndrome is characterized by acute onset, hyperreflexia and myoclonus, while NMS occurs over days, classically with lead-pipe rigidity. 1 Anticholinergic toxicity presents with agitated delirium, hyperthermia, mydriasis, dry skin and mucous membranes, and urinary retention. ...
... 1 Serotonin syndrome and neuroleptic malignant syndrome (NMS) can both present with altered mental status and autonomic instability. 1 Serotonin syndrome is characterized by acute onset, hyperreflexia and myoclonus, while NMS occurs over days, classically with lead-pipe rigidity. 1 Anticholinergic toxicity presents with agitated delirium, hyperthermia, mydriasis, dry skin and mucous membranes, and urinary retention. ...
... 1 Serotonin syndrome and neuroleptic malignant syndrome (NMS) can both present with altered mental status and autonomic instability. 1 Serotonin syndrome is characterized by acute onset, hyperreflexia and myoclonus, while NMS occurs over days, classically with lead-pipe rigidity. 1 Anticholinergic toxicity presents with agitated delirium, hyperthermia, mydriasis, dry skin and mucous membranes, and urinary retention. whole bowel irrigation, which is considered in toxic ingestions of drugs in sustained-release preparations, for drugs not adsorbed by activated charcoal, or for removal of packets of illicit drugs. ...
... Patients can be exposed to potential toxins or xenobiotics accidentally or intentionally, and favorable outcomes are reliant on early recognition and early treatment [1]. Often, history is limited or unreliable, and a high index of suspicion is the most important diagnostic factor in uncovering a toxic etiology [2]. Table 1 lists clinical features that should prompt the clinician to a potential toxic ingestion. ...
... Table 1 lists clinical features that should prompt the clinician to a potential toxic ingestion. Substance or environmental toxicity is sometimes not considered because of impairments in communication due to age, language barriers, underlying CNS disease, or manifestations of the toxic exposure [2]. Additionally, iatrogenic toxicity is often overlooked by treating physicians. ...
... These findings represent direct physiological manifestations of the agents responsible providing clues to the identity of the xenobiotic. Although not all presentations fall neatly into a particular toxidrome, recognizing the dominant features can be important diagnostic and therapeutic starting points [2]. Therapies targeted towards the offending xenobiotic are key to reversal of the patients presenting toxicological delirium. ...
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Purpose of Review Delirium secondary to a toxic ingestion is a common presentation in the emergency department. The offending drug is often unknown, and history is often limited, making identification of the culprit xenobiotic difficult. We present a review of commonly ingested drug overdoses and toxidromes to assist in rapid diagnosis and treatment of these clinically challenging patients. Recent Findings There is a frequent overlap in the clinical presentation of many toxic ingestions. Key physical exam, electrocardiographic, and toxic-metabolic findings can help identify these drugs and direct early therapy. There are limited randomized controlled trials for many treatment strategies in the intoxicated patient, but recent large observational and meta-analysis have improved the understanding and utility of common antidotes. Summary Early identification of the correct toxidrome and offending agent is important to initiate life-saving treatment. Early involvement of local toxicologists is essential to assist in management of these patients.
... 11,12 Many specific antidotes for common household poisons can be given in a timely manner if a toxidrome based on the presenting symptomatology can be identified. 13,14 However, it should be noted that polydrug overdose may cause confusing symptoms and the toxic effects of poisons may have delayed manifestations due to delayed absorption, volume distribution effects or time-lag for conversion to an active metabolite. 14,15 The purpose of this article is to provide an updated narrative review on various toxidromes and their respective antidotes ISSN: 1740-4398 REVIEW -Paediatric toxidromes drugsincontext.com ...
... 13,14 However, it should be noted that polydrug overdose may cause confusing symptoms and the toxic effects of poisons may have delayed manifestations due to delayed absorption, volume distribution effects or time-lag for conversion to an active metabolite. 14,15 The purpose of this article is to provide an updated narrative review on various toxidromes and their respective antidotes ISSN: 1740-4398 REVIEW -Paediatric toxidromes drugsincontext.com available in most emergency departments and critical care units for paediatric poisoning. ...
Article
Background: Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration of an antidote specific for the poison is essential for the management of children with suspected poisoning. This is a narrative review on antidotes for toxidromes in paediatric practice. Methods: A literature search was conducted on PubMed with the keywords "antidote", "poisoning", "intoxication", "children" and "pediatric". The search was customized by applying the appropriate filters (species: humans; age: birth to 18 years) to obtain the most relevant articles for this review article. Results: Toxidrome recognition may offer a rapid guide to possible toxicology diagnosis such that the specific antidote can be administered in a timely manner. This article summarizes toxidromes and their respective antidotes in paediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are discussed. Antidotes are only available for a limited number of poisons responsible for intoxication. Antidotes for common poisonings include N-acetyl cysteine for paracetamol and sodium thiosulphate for poisoning by cyanide. Conclusion: Poisoning is a common cause of paediatric injury. Physicians should be familiar with the recognition of common toxidromes and promptly use specific antidotes for the management of childhood toxidromes.
... Acetylcysteine is also part of the treatment of Amanita mushroom poisonings [37]. A patient presenting with a life-threatening toxidrome or in a severe condition who requires advanced life-saving therapies should be treated in an intensive care unit [38]. ...
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Background: Acute poisoning is a frequent emergency and a significant health concern in the pediatric population. The pattern of acute intoxication differs between countries and within each country. Poisoning depends on many factors. It can be divided into two categories (accidental and intentional), and each one has its own characteristics. Aim of the study: This study aimed to analyze and discuss the overall patterns of accidental and intentional poisoning among children and adolescents. Material and methods: A systematic literature search was conducted using Google Scholar, Elsevier, and the PubMed database. The following keywords were used: “acute poisoning”, “pediatric poisoning”, “intentional poisonings”, “unintentional poisonings”, and “suicide attempts”. Results: A total of 38 articles were included in the review. Half had been published in the last five years. The analysis focused on the characteristics of the materials and methods, results, and conclusions sections of each study. Conclusions: Unintentional poisonings dominate among younger children, with a slight male predominance. They usually occur at home and occasionally lead to severe harm or even death. The most common causes of intoxication in this population are medications and household products. The majority of poisonings among adolescents are intentional suicide attempts. Among older children, over-the-counter analgesics are the most common cause of acute poisoning. Accidental poisoning can be avoided by providing preventive educational programs to guardians and replacing potentially toxic household products with safer ones. The prevention of intentional poisoning should be based on a community support system and behavioral programs. Healthcare professionals should be familiar with poisoning and be aware of the different patterns of intoxication according to age and gender.
... Сьогодні провідними токсикологічними школами США та країн Європейського Союзу переглядаються рекомендації з клінічної практики щодо гострих отруєнь наркотичними та психотропними речовинами (НПР) із метою визначення тих, що можуть бути покладені в основу нових діагностичних підходів з оцінки пацієнта та протоколів лікування. Пошук нових підходів знаходить відображення в сучасній науковій літературі [4][5][6][7][8]. ...
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Background. Poisoning by addictive and psychotropic substances is one of the main reasons for the admission of patients to emergency departments in most countries of the world. The purpose of this study was to investigate the current structure of toxic syndromes in patients with acute poisoning and to analyze existing approaches to the diagnosis of addictive and psychotropic substance poisoning based on the syndromic approach. Materials and methods. Medical data of 2987 patients treated with the diagnosis: “Acute drug poisoning” (ICD-10: T40.0-T40.3) in the Kyiv Toxicological Center were studied. Laboratory studies of addictive and psychotropic substances in the biological environment were performed using immunochromatographic analysis (rapid tests) and chromate-mass spectrometry (device Aligent 6850/5973N, column HP-5MS). Statistical analysis was performed using the program Statistica 12.6 (Windows 10/7). Results. According to the Center for Mental Health and Monitoring of Drugs and Alcohol of the Ministry of Health of Ukraine in 2018, the most common substances that result in abuse were: alcohol — 14.6 %, cannabis — 2.8 %, opioids — 2.1 %, sedative agents — 1.1 %, solvents — 0.9 %, amphetamine-type stimulants — 0.2 %, cocaine — 0.1 %, and hallucinogens — 0.1 %. The range of substances that caused severe poisoning in adults in 2016–2020 represented by: ethanol — 29.2 %, opioids — 42.3 %, cannabinoids — 8.4 %, sedative agents and hypnotics — 9.5 %, cocaine, and stimulants, inclu-ding caffeine — 7.4 %, hallucinogens — 5.5 %, solvents — 2.1 %. The following toxidromes were diagnosed: sedative in 46.3 % of patients, opioid — 37.6 %, sympathomimetic — 17.7 %, anticholinergic — 9.5 %, serotonin — 0.4 %, and syndrome of inappropriate diuretic hormone secretion (SIADH) — 0.2 %. During the study period, the number of combined poisonings increased 1.8 times (from 20.5 to 37.1 %), and among the combinations of addictive and psychotropic substances, the most common are methadone + ethanol, methadone + benzodiazepines, methadone + amphetamine, opioids + cocaine + ethanol, opioids + cannabis, as well as other combinations involving methamphetamine, hallucinogens, analgesics. Clinical diagnosis of combined poisonings is difficult, miosis may be absent in tramadol and meperidine poisoning, in cases of combined use of opioids and stimulants, or extremely severe cases, when the patient shows signs of deep post-hypoxic encephalopathy. Modern synthetic opioids (fentanyl and buprenorphine analogues) significantly outweigh the toxic effects of heroin, so there is a fairly common approach to using higher initial doses of naloxone in the treatment of such overdoses. However, approaches to the use of naloxone differ in various scientific sources. The practical experience in the Kyiv Toxicological Center proves that treatment can be started with standard doses of naloxone and quickly increased in the absence of side effects (agitation, convulsions, pulmonary edema). Given the fact that modern test systems are aimed at finding a small range of narcotic and psychotropic substances and do not determine their concentration, considerable attention should be paid to clinical diagnosis based on the definition of pathological symptoms and syndromes. Since the main target for narcotic and psychotropic substances is the nervous system, the identification of biomarkers of its dysfunction at different levels is key in the diagnosis of poisoning. Based on certain biomarkers, an understanding of the existing toxic syndrome (toxidrome) is formed. Today, opioids play a key role in morbidity and mortality from drug poisoning in Ukraine. A threatening trend in recent years is the increase in the proportion of combined poisonings by opioids and other substances, which complicates the determination of the toxidrome. It is important to note that the “fashion” for the use of combinations of narcotic drugs and psychotropic substances among drug users is constantly changing, so doctors try to regularly update information on available drugs and psychotropic substances in the region, which are popular among consumers and characteristic manifestations of poisoning. The universal approach ABCDE should be used in cases where there are no specific tests for toxic substances, and because more than a third of positive tests show the presence of two or more xenobiotics. Conclusions. Identification of toxidrome is important from the standpoint of diagnosis and treatment of acute poisoning. Many researchers note that its importance exceeds the value of rapid tests to determine the toxic substance, and the patient’s vital signs and careful examination are the best clues for choosing treatment tactics. In cases of combined poisoning with drugs or psychotropic substances, or in situations where it is not possible to conduct rapid testing of the patient’s urine for toxic substances, it is necessary to approach the use of antidotes (naloxone) with caution. It is important to remember that the object of medical intervention in any poisoning is the patient, not the toxin or the results of laboratory tests, which do not always correctly indicate the poison. Pharmacological interventions in the treatment of a patient with acute addictive or psychotropic substance poisoning should be aimed at correcting the underlying pathological syndrome (if possible), taking into account not to exacerbate its manifestations, but rather to minimize its severity and duration.
... Several drugs such as acetaminophen, anesthetics and some cardiotoxins, β-adrenergic blockers, calcium channel blockers, digitalis glycosides, iron, isoniazid, methotrexate, neuroleptics, sulfonylureas, insulin, tricyclic antidepressants (and related compounds with sodium channel blocking properties), valproic acid, anticoagulants could be the cause of toxidromes [7,8]. ...
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Is there a relationship between toxidromes and multimorbidity? Does multimorbidity cause worse outcomes by toxidromes? this editorial evaluates all these and other aspects of a clinical concern which is far away from being fully understood.
... Rationale No published study of sufficient quality has provided conclusive evidence for the contribution of PCC and expert centres to the improvement of the management of patients with pharmaceutical or recreational drug poisoning, whether in terms of toxin identification or expected morbidity and mortality. Note that, in terms of identification of the suspected toxin: (1) due to the detailed knowledge of clinical toxicology (toxidromes), these expert centres can help to identify the class of toxins consumed [29]; (2) as in other countries [30], the dedicated and trained pharmacists of PCCs are able to identify medication tablets marketed in France 24 h a day, 7 days a week; and (3) PCC/expert centres work in collaboration with laboratories able to identify the possible presence of a toxic substance (tablet or liquid) within a package. In terms of morbidity and mortality, it should be noted that: (1) consultation of a PCC could reduce the length of hospital stay (probably by recommending earlier discharge from hospital than that envisaged in the absence of PCC opinion) [31][32][33]; and (2) PCC/expert centres can rapidly guide clinicians concerning the indications for antidotes, toxin elimination methods and the indications for exceptional techniques (ECMO). ...
Article
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Background Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. Methods A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d’Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology. Results The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. Conclusions The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N -acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.
... The administration of 25-50 mg/Kg during 5-30 minutes also allowed a favourable evolution [26]. In fact, the recommended dose for children is 25-50 mg/Kg intravenous infusion for 30-60 minutes, followed by an intravenous infusion of 10-20 mg/Kg/hour [27][28]. ...
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Introduction Acute pesticides poisonings is a serious public health problem in Algeria. The indication of oximes in the treatment of poisoning by cholinesterase inhibitors pesticides is still controversial in practice, although it seems theoretically interesting because of the reversibility of the toxic-cholinesterase binding and the atropine-like effect. The interest of oximes in the management of cholinesterase inhibitors pesticides poisoning will be discussed through the study of the observation of 4 patients received at University Hospital Center of Oran (Algeria). Observations and discussion The study of the 4 observations enabled us to highlight the following points. For collapsed cholinesterase activity levels, it is better to administrate the highest recommended doses of Pralidoxime immediately, this will allow a rapid regeneration of an important fraction of inhibited cholinesterase activity, process which is concentration-dependent. Early intake of Pralidoxime with continuous injections appeared to have resulted in a rapid and favourable evolution. The use of oximes in carbamate poisoning is still debatable and needs further research. Conclusion In view of the data presented, oximes retain their place in the treatment of acute intoxication with cholinesterase inhibitors. Their indication should be discussed for each case taking into account the anamnesis, clinical presentation and level of cholinesterase activity.
... Half-life of opioid agents.46,47 ...
Article
Background: Opioids are natural, semisynthetic, or synthetic substances that act on opioid receptors in the central nervous system. Clinically, they are prescribed for pain management. Opioid overdose (OOD) occurs when the central nervous system and respiratory drive are suppressed because of excessive consumption of the drug. Symptoms of OOD include drowsiness, slow breathing, pinpoint pupils, cyanosis, loss of consciousness, and death. Due to their addictive potential and easy accessibility opioid addiction is a growing problem worldwide. Emergency medical services and the emergency department often perform initial management of OOD. Thereafter, some patients require intensive care management because of respiratory failure, metabolic encephalopathy, acute kidney injury, and other organ failure. Areas of uncertainty: We sought to review the literature and present the most up-to-date treatment strategies of patients with acute OOD requiring critical care management. Data sources: A PubMed search was conducted to review all articles between 1950 and 2017 and the relevant articles were cited. Results & conclusions: Worldwide, approximately 69,000 people die of OOD each year, and approximately 15 million people have opioid addiction. In the United States, death from OOD has increased almost 5-fold from 2001 to 2013. OOD leading to intensive care unit admission has increased by 50% from 2009 to 2015. At the same time, the mortality associated with these admissions has doubled. The management strategies include airway management, use of reversal agents, assessing and treating coingestions and associated complications, treatment of opioid withdrawal with alpha-agonists, and psychosocial support to help with opiate addiction and withdrawal. This warrants awareness among clinicians regarding the adverse effects associated with opioid use, management strategies, and calls for a multidisciplinary approach to treating these patients.
Chapter
Since the early days of mankind, humans have used chemicals from a wide range of origins for psychic changes, whether for religious, occupational or recreational purposes. Among the most widely used illicit substances on the planet, according to the United Nations Office on Drugs and Crime (UNODC), are Cannabis sativa, amphetamines, cocaine, opiates, ecstasy and heroin. These are responsible for the dependence of millions of people. Thus, this review is about chemical dependence with a focus on the mechanism of molecular interaction, metabolism and its consequent symptomatology manifested during drug withdrawal, as well as the current pharmacological treatments used during its manifestation and the search to increase pharmacotherapeutic arsenal against this pathology.KeywordsAmphetamine Cannabis sativa Lysergic Acid DiethylamideCocaineChemical dependencyWithdrawal syndrome
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Segunda edición del libro "Compendio de psiquiatría clínica" de la Asociación Iberolatinoamericana de Neurociencias y Psiquiatría (AILANCYP).
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Equine toxicologic emergencies are relatively uncommon but can cause significant morbidity and mortality in a group of comanaged horses. The field veterinarian's role is to triage the situation, as well as the individual animal. Individual patient stabilization should focus on support of essential organ functions, providing time for treatments to have an effect or for elimination of the toxicant. Decontamination procedures can follow patient stabilization, if appropriate. Antidotes are often not available or feasible for equine intoxications. The field veterinarian should emphasize triage and stabilization before referral and on-site identification and collection of diagnostic samples to support the diagnosis.
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While antipsychotic medications have long been associated with anticholinergic effects, asenapine has been purported to have no capacity for muscarinic cholinergic antagonism based on in vitro studies. Research in rat brain tissue has yielded different results, with one study finding more cholinergic M1-5 binding in the medial prefrontal cortex, dorsolateral frontal cortex and hippocampal CA1 and CA3 areas than would be predicted from in vitro findings. Moreover, it is structurally similar to other anticholinergic antipsychotics such as loxapine and, to a lesser degree, quetiapine, olanzapine and clozapine. This case report describes the anticholinergic toxidrome in a patient treated with benztropine and paroxetine at stable doses, with the emergence of the toxidrome after upward titration of asenapine. A broad differential was considered. With further consideration of the history, time-course, clinical features and physical examination, the presentation is most indicative of the anticholinergic toxidrome. Although not employed, physostigmine, the antidote for anticholinergic delirium, could help to differentiate this toxidrome and serve as a diagnostic and therapeutic intervention. We have presented this case to highlight the importance for clinicians to integrate history and bedside examination data with principles of pharmacology. In particular, asenapine should be added to the list of compounds with recognized anticholinergic potential.
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Acute intoxications account for a significant proportion of the patient population in intensive care units and sedative medications, ethanol, illicit drugs, inhalable poisons and mixed intoxications are the most common causes. The aim of this article is to describe biomarkers for screening and diagnosis of acute intoxications in critically ill patients. For this purpose, a survey of the relevant literature was conducted, and guidelines, case reports, expert assessments, and scientific publications were reviewed. In critical care it should always be attempted to identify and quantify the poison or toxin with the assistance of enzyme immunoassay (EIA), chromatography, and mass spectrometry techniques and this section is critically appraised in this publication. The principles for anion gap, osmol gap and lactate gap and their usage in intoxications is shown. Basic rules in test methodology and pre-analytics are reviewed. Biomarkers in general are presented in part one and biomarkers for specific intoxications including ethanol, paracetamol, cardiovascular drugs and many others are presented in part two of these publications.
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Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. It is also the most common psychiatric syndrome found in the general hospital setting, its prevalence surpassing better known psychiatric disorders. This article reviews the published literature on delirium and addresses the epidemiology, known etiologic factors, presentation and characteristics of delirium, while emphasizing what is known about treatment strategies and prevention. Given increasing evidence that delirium is not always reversible and the many sequelae associated with its development, physicians must do everything possible to prevent its occurrence or shorten its duration, by recognizing its symptoms early, correcting underlying contributing causes, and using treatment strategies proven to help recover functional status.
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Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central toxicity and adverse psychological effects during late adulthood and senescence of adults who receive prolonged courses of amphetamine treatment are warranted. Finally, identification of the biological factors that confer risk and those that offer protection is also needed to better specify the parameters of safe, long-term, therapeutic administration of amphetamines to adults.
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A case of propoxyphene hydrochloride (Darvon) poisoning was unresponsive to therapeutic doses of naloxone hydrochloride in a 2 1/2-year-old girl. Following prolonged coma and artificial ventilation for three hours, the patient responded immediately to the intravenous administration of 2 mg of naloxone hydrochloride, which is 20 times the manufacturer's recommended dosage. Naloxone is the agent of choice in reversing the effects of narcotics and synthetic opiate derivatives, such as propoxyphene and pentazocine. The manufacturer's present recommended dosage may not be sufficient to reverse the effects of large narcotic ingestions. We therefore recommend that if there is no response within two minutes of the initial 0.01 mg/kg dosage of naloxone hydrochloride, a second dose 0.1 mg/kg (ten times the manufacturer's suggested dose) be given.
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Introduction: This is the 33rd Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of 1 January 2015, 55 of the nation’s poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 9.52 [7.40, 13.6] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. Methods: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. Results: In 2015, 2,792,130 closed encounters were logged by NPDS: 2,168,371 human exposures, 55,516 animal exposures, 560,467 information calls, 7657 human confirmed nonexposures, and 119 animal confirmed nonexposures. US PCs also made 2,695,699 follow-up calls in 2015. Total encounters showed a 3.42% decline from 2014, while health care facility (HCF) human exposure cases increased by 5.09% from 2014. All information calls decreased by 15.5% but HCF information calls increased 2.67%, and while medication identification requests (Drug ID) decreased 31.7%, human exposures reported to US PCs were essentially flat, increasing by 0.149%. Human exposures with less serious outcomes have decreased 2.95% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.34% per year since 2000. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.1%), household cleaning substances (7.54%), cosmetics/personal care products (7.41%), sedatives/hypnotics/antipsychotics (5.83%), and antidepressants (4.58%). Sedative/Hypnotics/Antipsychotics exposures as a class increased the most rapidly (2597 calls (11.4%)/year) over the last 14 years for cases showing more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (13.6%), household cleaning substances (11.2%), analgesics (9.12%), foreign bodies/toys/miscellaneous (6.45%), and topical preparations (5.33%). Drug identification requests comprised 35.0% of all information calls. NPDS documented 1831 human exposures resulting in death with 1371 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in calls involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, viral, bacterial, venomous, chemical agent, or commercial product), the identification of events of public health significance, resilience, response and situational awareness tracking. NPDS is a model system for the real-time surveillance of national and global public health.
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Introduction: Dexmedetomidine may help physicians target a low level of sedation. Unfortunately, the impact of dexmedetomidine on major endpoints remains unclear in intensive care unit (ICU). Material and methods: To evaluate the association between dexmedetomidine use with efficacy and safety outcomes, two reviewers independently identified randomized controlled trials comparing dexmedetomidine with other sedative agents in non-post-cardiac surgery critically ill patients in the PubMed and Cochrane databases. Random effects models were considered if heterogeneity was detected using the DerSimonian and Laird estimation method. Statistical heterogeneity between results was assessed by examining forest plots, confidence intervals (CI) and by using the I(2) statistic. The risk of bias was assessed using the risk of bias tool. Results: This meta-analysis included 1994 patients from 16 randomized controlled trials. Comparators were lorazepam, midazolam and propofol. Dexmedetomidine was associated with a reduction in ICU length of stays (WMD=-0.304; 95% CI [-0.477, -0.132]; P=0.001), mechanical ventilation duration (WMD=-0.313, 95% CI [-0.523, -0.104]; P=0.003) and delirium incidence (RR=0.812, 95% CI [0.680, 0.968]; P=0.020). Dexmedetomidine is also associated with an increase in the incidence of bradycardia (RR=1.947, 95% CI [1.387, 2.733]; P=0.001) and hypotension (RR=1.264; 95% CI [1.013, 1.576]; P=0.038). Conclusions and relevance: In this first meta-analysis including only randomized controlled trials related to ICU patients, dexmedetomidine was associated with a 48h reduction in ICU length of stay, mechanical ventilation duration and delirium occurrence despite a significant heterogeneity among studies. Dexmedetomidine was also associated with an increase in bradycardia and hypotension.
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We comprehensively reviewed published literature to determine whether it supported the link between corrected QT (QTc) interval prolongation and torsade de pointes (TdP) for the 11 second-generation antipsychotics and seven second-generation antidepressants commonly implicated in these complications. Using PubMed and EMBASE, we identified four thorough QT studies (one each for iloperidone, ziprasidone, citalopram, and escitalopram), 40 studies specifically designed to assess QTc interval prolongation or TdP, 58 publications based on data from efficacy and safety trials, 18 toxicology studies, and 102 case reports. Thorough QT studies, QTc prolongation-specific studies, and studies based on efficacy and safety trials did not link drug-associated QTc interval prolongation with TdP. They only showed that the drugs reviewed caused varying degrees of QTc interval prolongation, and even that information was not clear and consistent enough to stratify individual drugs for this risk. The few toxicology studies provided valuable information but their findings are pertinent only to situations of drug overdose. Case reports were most informative about the drug-QTc interval prolongation-TdP link. At least one additional well established risk factor for QTc prolongation was present in 92.2 % of case reports. Of the 28 cases of TdP, six (21.4 %) experienced it with QTc interval <500 ms; 75 % of TdP cases occurred at therapeutic doses. There is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision and broaden its scope to better understand the factors that facilitate or attenuate progression of drug-associated QTc interval prolongation to TdP.
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Context: Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. Objective: To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Methods: Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Results: Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia. Neuroimaging may demonstrate leukoencephalopathy in these cases. Acute exposures improve with cessation of exposure. Electrolyte and fluid replacement will improve metabolic acidosis. Arrhythmias are precipitated via catecholamine surge, and beta blockers are presumed protective. Aspiration of hydrocarbons causes a potentially fatal pneumonitis. Symptoms may include cough, wheezing respiratory distress, and hypoxia. Bilateral interstitial infiltrates may be delayed for several hours after the development of pneumonitis. Treatment consists of supportive care, supplemental oxygen, and may require intubation and admission to an intensive care unit in severe cases. Unfortunately, aspiration pneumonitis remains a leading cause of poisoning mortality in children. Dermal exposure can cause dermatitis, chemical burns, and defatting injury. Oral exposure can cause local irritation as well as vomiting, diarrhea, and abdominal pain. Conclusion: Acute hydrocarbon exposure can result in a wide array of pathology, such as encephalopathy, pneumonitis, arrhythmia, acidosis, and dermatitis. Intentional inhalational and accidental ingestion exposures with aspiration lead to the greatest morbidity and mortality.
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For centuries, 'khat sessions' have played a key role in the social and cultural traditions among several communities around Saudi Arabia and most East African countries. The identification of cathinone as the main psychoactive compound of khat leaves, exhibiting amphetamine-like pharmacological properties, resulted in the synthesis of several derivatives structurally similar to this so-called natural amphetamine. Synthetic cathinones were primarily developed for therapeutic purposes, but promptly started being misused and extensively abused for their euphoric effects. In the mid-2000's, synthetic cathinones emerged in the recreational drug markets as legal alternatives ('legal highs') to amphetamine, 'ecstasy', or cocaine. Currently, they are sold as 'bath salts' or 'plant food', under ambiguous labels lacking information about their true contents. Cathinone derivatives are conveniently available online or at 'smartshops' and are much more affordable than the traditional illicit drugs. Despite the scarcity of scientific data on these 'legal highs', synthetic cathinones use became an increasingly popular practice worldwide. Additionally, criminalization of these derivatives is often useless since for each specific substance that gets legally controlled, one or more structurally modified analogs are introduced into the legal market. Chemically, these substances are structurally related to amphetamine. For this reason, cathinone derivatives share with this drug both central nervous system stimulating and sympathomimetic features. Reports of intoxication and deaths related to the use of 'bath salts' have been frequently described over the last years, and several attempts to apply a legislative control on synthetic cathinones have been made. However, further research on their pharmacological and toxicological properties is fully required in order to access the actual potential harm of synthetic cathinones to general public health. The present work provides a review on khat and synthetic cathinones, concerning their historical background, prevalence, patterns of use, legal status, chemistry, pharmacokinetics, pharmacodynamics, and their physiological and toxicological effects on animals and humans.
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Acetaminophen poisoning remains one of the more common drugs taken in overdose with potentially fatal consequences. Early recognition and prompt treatment with N-acetylcysteine can prevent hepatic injury. With acute overdose, the Rumack-Matthew nomogram is a useful tool to assess risk and guide management. Equally common to acute overdose is the repeated use of excessive amounts of acetaminophen. Simultaneous ingestion of several different acetaminophen-containing products may result in excessive dosage. These patients also benefit from N-acetylcysteine. Standard courses of N-acetylcysteine may need to be extended in patients with persistently elevated plasma concentrations of acetaminophen or with signs of hepatic injury.
Article
Serotonin syndrome (SS) is becoming a more frequent diagnosis in the intensive care unit (ICU). We sought to determine the clinical presentation, drug exposures, and outcomes of SS in critically ill patients. A retrospective study of 33 consecutive ICU patients with SS between March 2007 and March 2012 in ICUs in a large teaching hospital. SS was defined using the Hunter Serotonin Toxicity Criteria. Seventeen patients (52 %) were admitted for mental status changes, including seven patients (21 %) with drug overdose and four cases (12 %) in which SS was considered the primary admission diagnosis. In 13 patients (39 %) the features of SS developed only after a mean of 6.8 ± 9 days of hospitalization. Most received multiple serotonergic drugs upon diagnosis (median three drugs, range 1-5). Antidepressants were the serotonergic medications most often used before admission, and opioids (principally fentanyl) and antiemetics were the most frequently prescribed new serotonin-enhancing medications. Altered mental status was present in all patients and myoclonus, rigidity, and hyperreflexia were the most prevalent examination signs. All but one patient had documented recovery. The mean time to neurological improvement was 56 ± 5 h, but ranged from 8 to 288 h. There were no cases of renal failure related to rhabdomyolysis, or death or persistent disability caused by SS. SS in the ICU occurs most often because of exposure to multiple serotonergic agents. Continuation of antidepressants plus the addition of opioids and antiemetics during hospitalization are most commonly responsible for this complication.
Article
Background and purpose: To assess MRI patterns and associated clinical outcome in adults with global hypoxic-ischemic injury. Materials and methods: In order to identify the patients with evidence of global hypoxic-ischemic injury, we retrospectively searched our radiology information system for reports of brain MRI studies from 01/01/2004 to 12/31/2010, containing the keywords - "hypoxia", "hypoxic", "anoxia" and "anoxic". A board certified neuroradiologist visually inspected the corresponding MR images for the presence, location and extent (focal versus diffuse) of ischemic findings. Clinical data for these patients was collected from the electronic medical records, including mechanism of the hypoxic-ischemic injury, and clinical outcome was measured using modified Rankin Scale (mRS). Results: Review of radiology reports identified 151 cases, of which 64 patients remained after exclusion of normal studies ("no hypoxia" in the report), pediatric patients and patients with remote perinatal hypoxia. Five patients had relatively favorable clinical outcome (mRS of 1 to 3) and 59 had poor outcome (mRS of 4 to 6). Patterns associated with relatively favorable clinical outcome were: a) watershed pattern and b) basal ganglia without cortical involvement. Patterns associated with poor clinical outcome were: a) diffuse cortical and deep grey matter pattern, with and without perirolandic sparing; (b) medial occipital with perirolandic involvement; c) precentral gyrus involvement; d) diffuse white matter involvement; e) brainstem involvement; f) cerebellar involvement and g) hippocampal involvement. Conclusion: The vast majority of patients with MRI patterns of hypoxic-anoxic injury have a poor clinical outcome, independently of the observed pattern, with the only relative exception being the watershed pattern and the basal ganglia pattern without cortical involvement.
Article
Prolongation of the corrected QT (QTc) interval is a key issue for patients who receive psychotropic medications. Such patients may have baseline clinical risk factors for QTc prolongation, and many psychotropic medications may further prolong this interval. This has great clinical relevance, as QTc prolongation is linked with dangerous arrhythmias, especially torsades de pointes (TdP). We summarize current literature regarding appropriate methods of calculating the QTc interval, the association of the QTc interval with TdP, and risk factors for QTc prolongation. We then review connections between psychiatric medications and QTc prolongation, with a specific focus on antidepressants and antipsychotics. QTc interval prolongation is an established, though imperfect, risk marker for TdP. There are no well-controlled studies that assess the risk of TdP associated with psychotropic agents. There are limited data that selective serotonin reuptake inhibitors (SSRIs) as a class are linked to QTc prolongation; citalopram appears more likely than others to induce this phenomenon. Among antipsychotics, thioridazine remains the agent most associated with QTc prolongation; intravenous haloperidol also appears to carry an increased risk. Of the atypical antipsychotics, ziprasidone appears most likely to prolong the QTc interval. The majority of patients in need of psychotropic medications display few risk factors for QTc prolongation and should be considered to be at low risk for TdP. The frequency of cardiac monitoring for patients receiving psychiatric medications should be individually determined, based on the prescribed agent(s) and additional risk factors for TdP.
Article
Objective: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. Methods: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. Conclusion: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.
Article
Non-perinatal hypoxic-ischaemic encephalopathy (HIE) has varying anatomical patterns dependent on the type of insult, the degree and duration of cerebral hypoxia, or presence and degree of hypoperfusion. Profound insults can affect the entire cerebral cortex or just the perirolandic cortex, the cerebellum and the deep grey matter structures. Less severe insults may affect only the watershed regions. The objective of this article is to review the anatomical patterns of non-perinatal HIEs by MRI.
Article
To examine the impact of delirium during intensive care unit stay on long-term health-related quality of life and cognitive function in intensive care unit survivors. Prospective 18-month follow-up study. Four intensive care units of a university hospital. A median of 18 months after intensive care discharge, questionnaires were sent to 1,292 intensive care survivors with (n = 272) and without (n = 1020) delirium during their intensive care stay. The Short Form-36v1, checklist individual strength-fatigue, and cognitive failure questionnaire were used. Covariance analysis was performed to adjust for relevant covariates. Of the 915 responders, 171 patients were delirious during their intensive care stay (median age 65 [interquartile range 58-85], Acute Physiology and Chronic Health Evaluation II score 17 [interquartile range 14-20]), and 745 patients were not (median age 65 [interquartile range 57-72], Acute Physiology and Chronic Health Evaluation II score 13 [interquartile range 10-16]). After adjusting for covariates, no differences were found between delirium and nondelirium survivors on the Short Form-36 and checklist individual strength-fatigue. However, survivors who had suffered from delirium reported that they made significantly more social blunders, and their total cognitive failure questionnaire score was significantly higher, compared to survivors who had not been delirious. Survivors of a hypoactive delirium subtype performed significantly better on the domain mental health than mixed and hyperactive delirium patients. Duration of delirium was significantly correlated to problems with memory and names. Intensive care survivors with delirium during their intensive care unit stay had a similar adjusted health-related quality of life evaluation, but significantly more cognitive problems than those who did not suffer from delirium, even after adjusting for relevant covariates. In addition, the duration of delirium was related to long-term cognitive problems.
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Methamphetamine abuse has reached epidemic proportions in the United States. The repetitive use of methamphetamine causes massive and sustained elevations in central monoamines. These elevations, particularly in dopamine, can cause changes in the function of the central nervous system that can manifest as a variety of neurologic disorders. This article focuses on these disorders, such as neurocognitive disorders and mental illness, including drug-induced psychosis; motor disorders, including the possible risk of Parkinson's disease, the development of choreoathetoid movements, and punding; and changes in the physical appearance of the methamphetamine users, including dental caries.
Article
As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.
Article
Our objective was to summarize and critically review data on the prevalence of posttraumatic stress disorder (PTSD) in general intensive care unit (ICU) survivors, risk factors for post-ICU PTSD and the impact of post-ICU PTSD on health-related quality of life (HRQOL). We conducted a systematic literature review using Medline, EMBASE, Cochrane Library, CINAHL, PsycINFO and a hand-search of 13 journals. Fifteen studies were eligible. The median point prevalence of questionnaire-ascertained "clinically significant" PTSD symptoms was 22% (n=1,104), and the median point prevalence of clinician-diagnosed PTSD was 19% (n=93). Consistent predictors of post-ICU PTSD included prior psychopathology, greater ICU benzodiazepine administration and post-ICU memories of in-ICU frightening and/or psychotic experiences. Female sex and younger age were less consistent predictors, and severity of critical illness was consistently not a predictor. Post-ICU PTSD was associated with substantially lower HRQOL. The prevalence of PTSD in ICU survivors is high and negatively impacts survivors' HRQOL. Future studies should comprehensively address how patient-specific factors (e.g., pre-ICU psychopathology), ICU management factors (e.g., administration of sedatives) and ICU clinical factors (e.g., in-ICU delirium) relate to one another and to post-ICU PTSD. Clinicians caring for the growing population of ICU survivors should be aware of PTSD risk factors and monitor patients' needs for early intervention.
Article
To demonstrate the efficacy of flumazenil in reversing the sedative action of midazolam in ventilated intensive care patients. Prospective, double-blind randomized study. ICU of a tertiary, university-affiliated teaching hospital. Thirty ICU patients requiring artificial ventilation for greater than 12 hrs were studied. All patients received a midazolam infusion for sedation. Twenty-nine patients received supplementary narcotics. At the end of the sedation period, either flumazenil or placebo was administered to all the patients in a double-blind, randomized fashion, and the effects were observed. Sedation levels were measured hourly during the infusion; at the end of the infusion; and at 5, 15, 30, 60, and 120 mins after cessation of the midazolam infusion. Midazolam concentrations in serum were measured at the time of cessation of the midazolam infusion and at 30, 60, and 120 mins later. Reversal of sedation was observed in 14 of 15 patients who received flumazenil, and resedation occurred in seven of these patients. Reversal was not seen in any of the patients who received placebo. Midazolam serum concentrations were similar in both groups. Flumazenil in a dose of 0.15 mg is a safe drug that reverses the sedative effect of midazolam.
Article
Five to six subjects ingested doses of controlled-release physostigmine salicylate tablets (9, 12, and 15 mg) followed by sequential blood drawing for measurement of plasma physostigmine concentrations and percentage of acetylcholinesterase (AChE) inhibition. Both plasma physostigmine concentrations and percentage of AChE inhibition demonstrated dose proportionality to three doses of ingested drug. Plasma physostigmine concentrations correlated with percentage of AChE inhibition across time by dose and across all doses and subjects tested. These data should be helpful to physicians in adjusting physostigmine dosing, enabling them to use the relatively simple and widely available AChE assay to approximate plasma physostigmine concentrations.
Article
Cocaine abuse has been implicated as a cause of death due to sudden cardiac arrest. We examined the hemodynamic and electrophysiological effects of cocaine administered as a series of 5-mg/kg i.v. boluses coupled with a continuous infusion in anesthetized dogs. Sodium bicarbonate (50 meq i.v.) was administered as a potential antidote in 11 of 15 dogs, and intravenous 5% dextrose was given in the remaining four. In a dose-dependent fashion, cocaine significantly decreased blood pressure, coronary blood flow, and cardiac output; increased PR, QRS, QT, and QTc intervals and sinus cycle length; and increased ventricular effective refractory period and dispersion of ventricular refractoriness. No afterdepolarizations were noted in the monophasic action potential recording. Nonsustained monomorphic ventricular tachycardia occurred spontaneously in two dogs, and sustained ventricular tachycardia could be induced by programmed stimulation at the end of the dosing protocol in five of 11 animals. Sodium bicarbonate promptly decreased cocaine-induced QRS prolongation to nearly that measured at baseline but had no effect on the other electrocardiographic or hemodynamic variables. In one dog, sodium bicarbonate administration was associated with reversion of ventricular tachycardia to sinus rhythm. We conclude that high-dose cocaine possesses negative inotropic and potent type I electrophysiological effects. Sodium bicarbonate selectively reversed cocaine-induced QRS prolongation and may be a useful treatment of ventricular arrhythmias associated with slowed ventricular conduction in the setting of cocaine overdose.
Article
A 13-year-old girl familially predisposed to affective disorders had a mixed bipolar disorder after ingesting eight 60 mg pseudoephedrine pills. The patient was misdiagnosed as having pseudoephedrine-induced organic mood disorder until recurrence of symptoms necessitated rehospitalization seven months after the initial episode.
Article
To the Editor.— The letter of Feldman and Behar1 describes the withdrawal of a patient dependent on 1600 mg of diphenhydramine hydrochloride per day. As far as I am aware it is the first report of abuse of diphenhydramine as found in Sominex 2, an over-the-counter sleep aid, and thus alerts the physician to the potential for abuse of this drug. I disagree, however, with the authors' statement that "increased defecation was the only cholinergic rebound effect noted even with rapid tapering." They also point out that "this patient did display moderate irritability and restlessness as the drug use was stopped" and insomnia characterized by "getting up and lying down repeatedly." The authors described this as a bedtime ritual of such magnitude that it led to the patient signing out on day 15 "following a disagreement with the staff over his bedtime behavior." This behavior resembles the akathisialike syndrome reported
Article
There is a need for a rapid predictor of potential clinical severity to guide therapy in patients with an acute overdose of tricyclic antidepressant drugs. We performed a prospective study of 49 such patients to observe the associations among serum drug levels, maximal limb-lead QRS duration, and the incidence of seizures and ventricular arrhythmias. Patients were divided into two groups on the basis of maximal limb-lead QRS duration. Group A (13 patients) had a duration of less than 0.10 second, and Group B (36 patients) had a QRS duration of 0.10 second or longer. No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. Serum drug levels failed to predict the risk of seizures or ventricular arrhythmias accurately. Seizures occurred at any QRS duration of 0.10 second or longer (P less than 0.05), but ventricular arrhythmias were seen only with a QRS duration of 0.16 second or longer (P less than 0.0005). We conclude that determination of the maximal limb-lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants. Serum drug levels are not of predictive value.
Article
Physostigmine is a commonly used therapy for the anticholinergic manifestations of tricyclic antidepressant (TCA) overdose. We describe two patients with TCA toxicity who developed asystole following the administration of physostigmine to treat seizures.
Article
The mechanism by which decongestants produce their action is activation of postjunctional alpha-adrenergic receptors found on precapillary and postcapillary blood vessels of the nasal mucosa. Activation of these receptors by either direct binding of the sympathomimetic agent to the binding site of the receptor, or by the enhanced release of norepinephrine produces vasoconstriction. Such vasoconstriction decreases blood flow through the nasal mucosa and results in shrinkage of this tissue. Decongestants can be administered topically, directly onto the nasal mucosa, or orally. Prolonged topical administration may produce rebound congestion. Oral decongestants can affect the cardiovascular, urinary, central nervous, and endocrine systems. Overdose can produce medically significant increases in blood pressure as well as central nervous system stimulation.
Article
In the assessment and management of the potentially poisoned patient with altered consciousness, the most consequential and controversial interventions occur during the first 5 minutes of care. In this review article, the risks and benefits of standard diagnostic and therapeutic interventions are presented to guide clinicians through this critical period of decision making. Data for discussion were obtained from a search of English-language publications referenced on MEDLINE for the years 1966 to 1994. Older literature was included when pertinent. Search terms included poisoning, overdose, toxicity, naloxone, glucose, thiamine, and flumazenil. Only large trials were used for determinations of diagnostic utility and efficacy. Small trials, case series, and case reports were reviewed extensively for adverse effects. Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcome. Analysis favors empirical administration of hypertonic dextrose and thiamine hydrochloride to patients with altered consciousness. Although rapid reagent test strips can be used to guide this therapy, they are not infallible, and they fail to recognize clinical hypoglycemia that may occur without numerical hypoglycemia. Administration of naloxone hydrochloride should be reserved for patients with signs and symptoms of opioid intoxication. Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.
Article
On the basis of case reports and small non-comparative series it has been suggested that thioridazine has greater cardiotoxicity in overdose. Limited evidence also suggests an increased association with sudden death in therapeutic doses. The aim of our study is to examine the clinical and electrocardiographic features associated with neuroleptic poisoning and compare thioridazine with other neuroleptics. Consecutive adult patients with neuroleptic poisoning presenting to metropolitan hospitals in Newcastle between 1987 and 1993 were studied. The main outcome measures examined were ECG changes (QRS, QT and QTc intervals), arrhythmias, seizures, degree of sedation, heart rate and blood pressure. Two-hundred ninety-nine patients had ingested thioridazine (104), chlorpromazine (69), trifluoperazine (36), pericyazine (35), haloperidol (33), prochlorperazine (18), fluphenazine (8), or other neuroleptics (7). Sixteen patients had ingested more than one neuroleptic and were excluded from comparative analysis. Thioridazine was more likely to cause tachycardia (odds ratio 1.7, 95% CI 1.1-2.9, p = 0.03), a prolonged QT interval (odds ratio 5.2, 95% CI 1.6-17.1, p = 0.006), prolonged QTc > 450 ms1/2 (odds ratio 4.7, 95% CI 2.7-7.9, p = 0.001), a widened QRS (> 100 ms) (odds ratio 3.1, 95% CI 1.5-6.3, p = 0.001) and arrhythmias (odds ratio infinity, 95% CI 2.4- infinity, p = 0.004). There were no significant differences in the odds of coma (odds ratio 0.5 (0.2-1.5)), hypotension (odds ratio 0.9 (0.4-1.9)) or seizures (odds ratio 3.9 (0.3-43.5)). Adjustment for age, sex, dose ingested and co-ingestion of tricyclic antidepressants or lithium had no major effect on the odds ratios observed.(ABSTRACT TRUNCATED AT 250 WORDS)