The clinical toxicology of ketamine.

INTRODUCTION: Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug. OBJECTIVES: To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity. METHODS: Both OVID MEDLINE (January 1950-April 2023) and Web of Science (1900-April 2023) databases were searched using the term "ketamine" in combination with the keywords "pharmacokinetics", "kinetics", "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". Furthermore, bibliographies of identified articles were screened for additional relevant studies. These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant. Those excluded were other animal investigations, therapeutic human clinical investigations, commentaries, editorials, cases with no clinical relevance and post-mortem investigations. EPIDEMIOLOGY: Following its introduction into medical practice in the early 1970s, ketamine has become a popular recreational drug. Its use has become associated with the dance culture, electronic and dubstep dance events. MECHANISM OF ACTION: Ketamine acts primarily as a non-competitive antagonist on the glutamate N-methyl-D-aspartate receptor, causing the loss of responsiveness that is associated with clinical ketamine dissociative anaesthesia. PHARMACOKINETICS: Absorption of ketamine is rapid though the rate of uptake and bioavailability is determined by the route of exposure. Ketamine is metabolized extensively in the liver. Initially, both isomers are metabolized to their major active metabolite, norketamine, by CYP2B6, CYP3A4 and CYP2C9 isoforms. The hydroxylation of the cyclohexan-1-one ring of norketamine to the three positional isomers of hydroxynorketamine occurs by CYP2B6 and CYP2A6. The dehydronorketamine metabolite occurs either by direct dehydrogenation from norketamine via CYP2B6 metabolism or non-enzymatic dehydration of hydroxynorketamine. Norketamine, the dehydronorketamine isomers, and hydroxynorketamine have pharmacological activity. The elimination of ketamine is primarily by the kidneys, though unchanged ketamine accounts for only a small percentage in the urine. The half-life of ketamine in humans is between 1.5 and 5 h. CLINICAL FEATURES: Acute adverse effects following recreational use are diverse and can include impaired consciousness, dizziness, irrational behaviour, hallucinations, abdominal pain and vomiting. Chronic use can result in impaired verbal information processing, cystitis and cholangiopathy. DIAGNOSIS: The diagnosis of acute ketamine intoxication is typically made on the basis of the patient's history, clinical features, such as vomiting, sialorrhea, or laryngospasm, along with neuropsychiatric features. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively. MANAGEMENT: Treatment of acute clinical toxicity is predominantly supportive with empiric management of specific adverse effects. Benzodiazepines are recommended as initial treatment to reduce agitation, excess neuromuscular activity and blood pressure. Management of cystitis is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery. Management of cholangiopathy may require pain management and, where necessary, biliary stenting to alleviate obstructions. Chronic effects of ketamine toxicity are typically reversible, with management focusing on abstinence. CONCLUSIONS: Ketamine is a dissociative drug employed predominantly in emergency medicine; it has also become popular as a recreational drug. Its recreational use can result in acute neuropsychiatric effects, whereas chronic use can result in cystitis and cholangiopathy.

The potential impact of future climate change on the production of a major food and cash crop in tropical (sub)montane homegardens.

Tropical agroforestry systems support the wellbeing of many smallholder farmers. These systems provide smallholders with crops for consumption and income through their ecological interactions between their tree, soil, and crop components. These interactions, however, could be vulnerable to changes in climate conditions; yet a reliable understanding of how this could happen is not well documented. The aim of this study is to understand how tree-soil-crop interactions and crop yield are affected by changes in climate conditions, which has implications for recognising how these systems could be affected by climate change. We used a space-for-time climate analogue approach, in conjunction with structural equation modelling, to empirically examine how warmer and drier climate conditions affects tree-soil-crop interactions and banana yield in Mt. Kilimanjaro's homegarden agroforest. Overall, the change in climate conditions negatively affected ecological interactions in the homegardens by destabilizing soil nutrient cycles. Banana yield, however, was mainly directly influenced by the climate. Banana yields could initially benefit from the warmer climate before later declining under water stress. Our findings imply that under increasingly warmer and drier climate conditions, homegarden agroforestry may not be a robust long-term farming practice which can protect smallholder's wellbeing unless effective irrigation measures are implemented.

The clinical toxicology of sodium hypochlorite.

INTRODUCTION: Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach. OBJECTIVE: The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning. METHODS: PubMed was searched from January 1950 to June 2018 using the terms "Hypochlorite", "Sodium Hypochlorite", "Sodium Oxychloride", "Hypochlorous Acid", "Bleach", "Chlorine Bleach", in combination with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant. EPIDEMIOLOGY: There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012-2016. Mechanisms of toxicity: Hypochlorite's potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin. Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia. Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage. Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns. Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways. Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur. DIAGNOSIS: The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis. MANAGEMENT: Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally. CONCLUSIONS: Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.

Duck shooting injuries in Southland, New Zealand.

Duck shooting is a common sport in New Zealand. The opening weekend is anticipated and celebrated, often with significant alcohol intake which is cause for concern, and potentially very dangerous. Hunters are annually warned about the dangers. There have been few duck shooting incidents which lead to injury or death. In the last decade two duck shooters in New Zealand have been killed, while 16 suffered non fatal gunshot injuries. We present a series of injuries identified during the 2012 duck shooting season in Southland Province.

Cattle associated trauma--a one year prospective study of all injuries.

AIM: To prospectively study all types and frequency of injuries resulting from direct contact with cattle in an occupational setting. METHODS: Prospective evaluation of all injuries due to direct contact with cattle presenting to the Emergency Department (ED) of a rural District General Hospital over a one year period. RESULTS: Injuries related to cattle were a common reason for presentation to the ED. Some clear patterns of injury were noted. Injuries to the upper extremity were particularly common, especially the hand and wrist and were associated with particular activities and mechanisms. Truncal injuries were less common but do have the potential for serious morbidity and mortality as noted in previous studies. CONCLUSIONS: Injuries related to direct contact with cattle are common. We noted an as yet unreported common pattern of injury to the hands of workers kicked whilst handling cattle at milking time. We also noted the previously recognized potential for serious injury due to more proximal body trauma whilst working with large animals. Whilst there is some work available pertaining to injury prevention in this industry, our study demonstrates a need for further work to be done to minimize and prevent future injuries.

Cannabinoid hyperemesis presenting to a New Zealand hospital.

Cannabis use is common among the general population in many areas of the world and cannibis is readily available in much of New Zealand. We report an unusual complication of chronic cannabis use which has recently been described overseas. Cannabinoid hyperemesis with abnormal bathing behaviour is a syndrome of episodic cyclic vomiting, often associated with relief being obtained by hot water bathing or showering. Underlying the disorder is the chronic use of cannabis. The proposed mechanism of the syndrome is accumulation of cannabis metabolites in the brain. Abstaining from cannabis use is likely to prevent ongoing recurrences. Although there have been limited reports in the medical literature, it is likely that the syndrome is commoner than previously recognised and the presentation could easily be confused with psychiatric illness or cyclic vomiting syndromes.

Comparison of CD-Rom and Internet access to clinical information.

INTRODUCTION: The New Zealand National Poisons Centre has developed an extensive clinical poisons information database, TOXINZ. This resource was originally provided on a CD-Rom, and in 2002 made accessible solely via the Internet (www.toxinz.com). It was unknown whether users would prefer the CD-Rom or Internet version to access the same information. METHODS: In September 2003 a total of 100 questionnaires were mailed to the emergency departments of 15 hospitals to be answered by medical and nursing staff utilizing the Internet version of TOXINZ. The results were then compared with a nearly identical questionnaire conducted in the same way in the same hospitals when only the CD-Rom database version was available. RESULTS: There was a 79% response rate with both medical and nursing staff rating the poisons management recommendations highly when accessed both on CD-Rom and Internet. Statistically significant differences (p<0.05, Mann-Whitney U-test) identified the Internet accessed database as: supplying better visual aids, being more repetitive, harder to search, and more difficult to print. CONCLUSION: Those developing Internet accessible databases for a healthcare environment are encouraged to incorporate robust search functionality, mobility solutions, and an ability to integrate with other healthcare applications.

Compliance with poisons center referral advice and implications for toxicovigilance.

BACKGROUND: When Poisons Information, or Poisons Control Centers (PCC) give directive advice in response to general public calls it is usually assumed that the advice will be followed, but it is difficult to measure the actual compliance of callers to a PCC. Epidemiological data regarding the incidence of poisoning incidents (Toxicovigilance) often utilizes reports of calls to a PCC. METHODS: Retrospective review of advice given to all callers to the New Zealand National Poisons Centre (NZNPC) from a defined area for the calendar year 2001. Callers to the NZNPC telephone hotlines who were advised to attend or not to attend the hospital Emergency Department (ED) were subsequently matched with actual ED visits. RESULTS: The compliance rate for those advised to attend the ED was 76.1%, whereas those advised not to attend had a compliance rate of 98.7%. The overall compliance rate was 94.1%. Of the patients presenting to the ED with a potential poisoning, only 10.2% were referred by the PCC. The callers referred by PCC and direct ED visitors appeared to differ in some respects. CONCLUSIONS: Compliance with PCC telephone advice is similar to the compliance rates in many other health interventions. Comparisons between populations calling a PCC and those self-presenting to an ED show that PCC data may not reflect the true burden of poisoning to health care systems.

Clinical utility of an electronic poisons information and clinical decision support tool.

The objective of the study was to assess the use of a computer toxicology database/clinical decision aid by clinical practitioners. The study investigated the sources that Emergency Department (ED) personnel use to obtain toxicology information and performed a quality audit of the current database. A questionnaire survey of ED staff was used in departments with access to the New Zealand Poisons Centre Substance Database (NZSD), a toxicology CD ROM computer database. Outcome measures were reported use of alternative data sources when managing clinical toxicology presentations and the qualities of the NZSD. Computer databases are commonly used for the management of clinical toxicology cases and the toxicology computer database/clinical decision aid studied is well accepted and used in Emergency Medicine practice. The users of the NZSD assessed the usability and quality of the information of the database.