Ketamine; history and role in anesthetic pharmacology

Ketamine (Ket) was developed in 1962 as a less hallucinogenic and shorter acting agent than phencyclidine. It was given to humans for the first time in 1964. However, Ket produces several adverse reactions such as raised intracranial and blood pressures along with seizures, and patients still show low acceptance due to hallucinations. As new volatile and intravenous anesthetic agents with good emergence and favorable side effect profiles were developed, Ket use markedly decreased. In the 1990s, as the ultrashort-acting opioid remifentanil was developed, high dose opioid could be used to reduce surgical stress in highly invasive procedures. However, high dose opioids can produce hyperalgesia and acute tolerance. As Ket can exert anti-hyperalgesic actions, the clinical use of low dose Ket has been reconsidered. Other beneficial effects of Ket such as; analgesia, anti-shock in hemorrhagic and septic insults, anti-inflammatory effects, anti-tumor effects, brain and spinal cord neuroprotection, and bronchodilation, have all been reported. Moreover, this anesthetic agent at low dose has been recently recognized to possess anti-depressive actions. This diverse profile extends Ket far beyond anesthesia practice and the operating room.