What are the side effects of increased ketamine use?

Side Effects of Increased Ketamine Use

Increased ketamine use is associated with dose-dependent adverse effects including psychotomimetic symptoms (dysphoria, hallucinations, anxiety), increased upper airway secretions, emesis, cardiovascular stimulation, and with chronic high-dose use, hepatotoxicity, uropathy, and cognitive impairment. 1

Acute Side Effects During Clinical Administration

Psychotomimetic and Psychiatric Effects

• Patients receiving ketamine may experience psychotomimetic side effects including dysphoria, nightmares, hallucinations, anxiety, disorientation, insomnia, flashback, and feelings of floating, detachment and being "spaced out." 2, 1
• These effects are especially prominent at higher ketamine doses and occur more frequently in patients over 10 years of age (35.7% recovery agitation in patients >10 years versus 5.7% in younger patients). 2
• The psychotropic effects are typically mild and transient when ketamine is used in clinical settings, and can be attenuated with benzodiazepine co-administration. 3, 4

Respiratory Effects

• Ketamine increases upper airway secretions, which can lead to severe dyspnea or a sense of "suffocation," particularly when used concomitantly with other agents that increase secretions. 2
• Atropine or glycopyrrolate can attenuate these secretory effects. 2
• Respiratory depression and apnea may occur with overdosage or rapid administration, requiring assisted or mechanical ventilation. 1
• Prolonged apnea and respiratory distress have been documented in experimental settings, particularly with combined chemical exposures. 2

Gastrointestinal Effects

• Emesis is a common adverse effect, occurring in approximately 6.7-19.4% of patients, and is more prevalent at higher ketamine doses and with increasing patient age. 2, 5, 6
• Nausea and vomiting are dose-dependent side effects. 2, 6

Cardiovascular Effects

• Ketamine causes dose-dependent increases in heart rate, blood pressure, and cardiac output through sympathetic nervous system stimulation. 5, 7
• Tachycardia and arrhythmias can occur. 2
• Hypotension may paradoxically occur in critically ill or septic patients despite ketamine's typical sympathomimetic effects. 7
• Use should be avoided in patients with ischemic heart disease, cerebrovascular disease, or hypertension. 5, 7

Recovery and Sedation Effects

• Mild recovery agitation occurs in approximately 17.6% of patients, with moderate-to-severe agitation in about 1.6%. 5
• Recovery agitation is associated with higher ASA status (>I) and decreasing age. 2, 5
• Average recovery time after IV ketamine is approximately 84 minutes (range: 22-215 minutes). 5

Chronic High-Dose Use Effects

Hepatotoxicity

• Hepatotoxicity is common after high-dose ketamine, is dose-dependent, and is usually transient. 6
• Close monitoring of hepatic function is mandatory during prolonged ketamine administration. 3, 6

Urological Complications

• High-dose ketamine-induced uropathy is a potential adverse effect, particularly documented in recreational users. 6
• Bladder and renal complications are significant risks with prolonged, high-dose exposure. 3

Cognitive and Neurological Effects

• Recurrent high-dose ketamine misuse or abuse may be associated with memory and/or attention impairment. 1
• Long-term recreational ketamine use (mean 2.4 g/day for 2-9.7 years) is associated with lower gray matter volume, less white matter integrity, and lower functional thalamocortical and corticocortical connectivity. 8
• These structural and functional neuroanatomical changes may explain long-term cognitive side effects including memory impairment and executive dysfunction. 8
• Persistent psychotypical behavior and memory defects have been documented with chronic abuse. 3

Dependence and Withdrawal

• Physical dependence has been reported with prolonged use of ketamine, particularly with frequent use (more than weekly) of large doses over extended periods. 1
• Withdrawal symptoms include craving, fatigue, poor appetite, and anxiety. 1
• Tolerance develops with prolonged use, requiring higher doses to achieve the same effect. 1

Special Populations and Considerations

Pediatric Patients

• Safety and effectiveness in pediatric patients below age 16 have not been established by the FDA. 1
• Juvenile animal studies demonstrate that ketamine administration during rapid brain growth causes widespread neuronal and oligodendrocyte cell loss, alterations in synaptic morphology, and neurogenesis changes. 1
• The window of vulnerability correlates with the third trimester through approximately 3 years of age in humans. 1

Geriatric Patients

• Dose selection should be cautious in elderly patients, starting at the low end of the dosing range due to decreased hepatic, renal, or cardiac function. 1

Abuse Potential

• Ketamine is a Schedule III controlled substance with recognized abuse potential. 1
• Individuals with a history of drug abuse or dependence are at greater risk for ketamine abuse and misuse. 1

Clinical Monitoring Requirements

When administering ketamine, continuous monitoring must include: 5

• Vital signs (oxygen saturation, heart rate, blood pressure)
• Airway status
• CNS symptoms
• Hepatic function with prolonged use
• Renal function with prolonged use
• Assessment for abuse potential