What are the signs and symptoms of ketamine toxicity, abuse, and withdrawal?

Signs and Symptoms of Ketamine Toxicity, Abuse, and Withdrawal

Acute Ketamine Toxicity

Ketamine toxicity primarily manifests as neuropsychiatric disturbances, cardiovascular stimulation, and respiratory effects, with treatment focusing on supportive care and benzodiazepines for agitation. 1, 2

Neuropsychiatric Effects

• Dissociative symptoms including disorientation, altered consciousness, feelings of floating, detachment, and being "spaced out" occur commonly, particularly at higher doses 1, 3
• Emergence reactions occur in 10-30% of adults, manifesting as vivid dreams, hallucinations, delirium, and floating sensations 4, 5
• Psychotomimetic effects include dysphoria, anxiety, insomnia, and flashback phenomena, especially prominent in patients over 10 years of age 1
• Impaired consciousness, dizziness, and irrational behavior are typical acute presentations 2
• Amnesia for the time during which the drug exerts its action is characteristic 4

Cardiovascular Effects

• Dose-dependent increases in heart rate, blood pressure, and cardiac output occur through sympathetic nervous system stimulation 6, 1, 4, 5
• Tachycardia and arrhythmias can develop 1
• This makes ketamine particularly dangerous for individuals with pre-existing ischemic heart disease, cerebrovascular disease, or hypertension 4, 5

Respiratory and Other Physical Effects

• Increased upper airway secretions can lead to severe dyspnea or a sense of "suffocation," particularly when combined with other secretion-increasing agents 1
• Sialorrhea (excessive salivation) and laryngospasm may occur 2
• Emesis occurs in approximately 6.7-19.4% of patients, more prevalent at higher doses and with increasing age 1
• Abdominal pain and vomiting are common acute complaints 2

Management of Acute Toxicity

• Benzodiazepines are the first-line treatment to reduce agitation, excess neuromuscular activity, and blood pressure 2
• Treatment is predominantly supportive with empiric management of specific adverse effects 2
• Continuous monitoring must include vital signs, airway status, and CNS symptoms 1
• Average recovery time after IV ketamine is approximately 84 minutes (range: 22-215 minutes) 1

Ketamine Abuse Patterns

Ketamine has become a popular recreational drug associated with dance culture and electronic music events, producing reinforcing effects through dopaminergic mechanisms. 2, 7

Abuse Characteristics

• Ketamine produces a variety of symptoms including anxiety, dysphoria, disorientation, insomnia, flashbacks, hallucinations, and psychotic episodes 3
• The drug has significant reinforcing effects, hypothesized to occur through blockade of NMDA receptors on GABA neurons, leading to disinhibition of dopaminergic neurons and increased dopamine release 7
• Ketamine has been used as a "date-rape drug" due to its sedative and amnestic properties, with effects occurring within 20 minutes and lasting up to 3 hours 4
• The drug can be detected in urine for 24-72 hours after ingestion 4

Chronic Abuse Effects

Urological Complications

• Cystitis is the most common chronic effect, presenting with lower urinary tract symptoms 2, 8, 9
• Renal failure has been reported in severe cases 9
• Management is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery 2

Hepatobiliary Complications

• Cholangiopathy can develop with chronic use 2, 8
• Abnormal liver function tests, choledochal cysts, and dilations of the common bile duct have been described 8
• S-ketamine has been shown to be hepatotoxic in vitro 8
• Management may require pain control and biliary stenting to alleviate obstructions 2

Gastrointestinal Effects

• Epigastric pain and impaired gallbladder activity occur with chronic use 8, 9
• Gastric pathology has been noted in chronic users 8

Neurocognitive Effects

• Disrupted learning and memory processing is a long-term consequence of ketamine use 7
• Impairment of verbal information processing occurs with chronic use 2
• Persistent dissociative, depressive, and delusional thinking has been reported 8
• Ketamine alters brain networks affecting the prefrontal cortex, hippocampus, and mesolimbic pathway, which are vital for decision-making, memory, and reward processing 10

Ketamine Withdrawal Syndrome

A withdrawal syndrome with psychotic features has been described following discontinuation of long-term ketamine use, though specific withdrawal symptoms are less well-characterized than for other substances. 3

Withdrawal Characteristics

• Ketamine dependence and tolerance are possible following prolonged administration 3
• Psychotic features can accompany withdrawal from chronic ketamine use 3
• The neuroadaptive changes during withdrawal involve glutamate and dopamine neurotransmitter systems 10
• Low-dose ketamine can alter cortisol secretion and cause HPA axis dysregulation 10

Treatment Approach

• Abstinence from ketamine is considered the mainstay of treatment and may reduce the adverse effects of chronic use 2, 8
• Chronic effects of ketamine toxicity are typically reversible with cessation 2
• Specialized urine drug testing may be required to detect use, as not all point-of-care screens include ketamine 8
• Ketamine should be prescribed and administered with caution due to abuse potential 3

Critical Clinical Pitfalls

• Death from direct pharmacologic effects appears rare, but disinhibition and altered sensory perceptions put users at risk of environmental harm 8
• Ketamine has been implicated in nonconsensual sexual intercourse due to its amnestic properties 8
• The therapeutic value of ketamine for psychiatric disorders faces the major challenge that it owns significant reinforcing and toxic effects 7
• Not recognizing chronic urological and hepatobiliary complications can lead to permanent organ damage if abstinence is not achieved 2, 8