Ketamine overdose
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Ketamine Overdose: Risks, Manifestations, and Safety Profile
Introduction to Ketamine Overdose
Ketamine, a dissociative anesthetic, has gained popularity both as a therapeutic agent and a recreational drug. While its medical use is expanding, particularly in mental health and pain management, concerns about overdose and associated risks remain significant. This article synthesizes current research on ketamine overdose, highlighting its clinical manifestations, outcomes, and safety profile.
Clinical Manifestations of Ketamine Overdose
Acute Effects and Symptoms
Ketamine overdose can lead to a range of acute symptoms. Common manifestations include prolonged sedation, respiratory depression, and neuropsychiatric effects such as hallucinations and irrational behavior2 5. In children, inadvertent overdoses have resulted in prolonged sedation and brief respiratory depression, though no long-term adverse outcomes were noted2. Similarly, in palliative care settings, overdoses have led to self-limited physiological and psychological reactions without severe consequences3.
Chronic Effects and Complications
Chronic use of ketamine, particularly in recreational settings, can result in more severe complications such as cystitis and cholangiopathy5. These conditions are typically reversible with abstinence and appropriate medical management. Additionally, long-term use can impair verbal information processing and induce schizophrenic-like symptoms6.
Epidemiology and Risk Factors
Prevalence and Demographics
Ketamine misuse is prevalent among certain demographics, including party drug users and individuals with access to the drug, such as medical and veterinary professionals6. A systematic review reported 312 overdose cases and 138 deaths, with most incidents involving males aged 2 to 65 years1. Polysubstance use was a significant factor in over half of these cases, increasing the risk of severe outcomes1 4.
Therapeutic vs. Recreational Use
In therapeutic settings, particularly for depression and pain management, ketamine is considered safe when used appropriately. No overdose or death cases were reported in these contexts, underscoring its safety profile under medical supervision1. However, recreational use, especially in combination with other central nervous system depressants, poses significant risks, including respiratory depression and increased hospitalizations4.
Safety Profile and Management
Wide Safety Margin
Despite the potential for overdose, ketamine has a wide safety margin. Studies have shown that even significant overdoses, such as those occurring in emergency departments or palliative care, often result in manageable symptoms without long-term adverse effects2 3. This suggests a relatively high threshold for severe toxicity, particularly in controlled environments.
Management of Overdose
Management of ketamine overdose primarily involves supportive care. Benzodiazepines are recommended to manage agitation and neuromuscular activity5. For chronic complications like cystitis and cholangiopathy, a multidisciplinary approach including pharmacotherapy and, if necessary, surgical interventions is advised5.
Conclusion
Ketamine overdose presents a complex clinical picture with a range of acute and chronic effects. While its therapeutic use is generally safe, recreational misuse, especially in combination with other substances, significantly increases the risk of severe outcomes. Clinicians must remain vigilant, but the high safety margin of ketamine in controlled settings should not deter its appropriate medical use. Further research is needed to fully understand the long-term implications of ketamine use and to develop strategies to mitigate the risks associated with its misuse.
Sources and full results
Most relevant research papers on this topic
Overdoses and deaths related to the use of ketamine and its analogues: a systematic review
Ketamine use as medicine is considered safe, but recreational use may pose risks, while its therapeutic use as an antidepressant is considered safe.
Systematic ReviewInadvertent ketamine overdose in children: clinical manifestations and outcome.
Inadvertent ketamine overdose in children treated in the emergency department resulted in prolonged sedation and brief respiratory depression, but no adverse outcomes were observed.
Highly CitedIatrogenic Oral Ketamine Overdose in Palliative Care.
Ketamine is an effective pain treatment with a wide safety profile, but iatrogenic overdose is a risk, especially in palliative care settings with multiple drugs and potential interactions.
Case ReportComment on ‘Characteristics of poisonings involving ketamine in the United States, 2019–2021’
Ketamine use is riskier when combined with other central nervous system depressants, and its use is more common when combined with other psychopharmacological therapies.
Literature ReviewThe clinical toxicology of ketamine
Ketamine toxicity is a common issue in recreational drug use, with a history of overdose and death in the United States.
Systematic ReviewThe health and psycho-social consequences of ketamine use
Ketamine use is relatively safe and does not pose a significant public health risk, but individual harm minimisation strategies should be observed.
Characteristics of poisonings involving ketamine in the United States, 2019–2021
Ketamine poisonings have increased in recent years, with polydrug use, particularly with opioids or GHB, being a particular risk factor for more serious adverse effects.
Observational Study
Very Rigorous JournalThe effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders
Acute ketamine administration in rodents leads to increased dopamine levels in the brain, potentially impacting psychiatric disorders like substance abuse and schizophrenia.
Meta-Analysis
Rigorous JournalHighly CitedKetamine: an update on its abuse.
Ketamine abuse can alter brain functions and cause psychological addiction, while also causing gastrointestinal and urinary tract toxicity.
Highly CitedPredictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children.
High intravenous doses, administration to children younger than 2 years or aged 13 years, and coadministered anticholinergics or benzodiazepines are significant predictors of airway and respiratory adverse events during ketamine sedation in the emergency department.
Meta-AnalysisHighly Cited