Ketamine adverse effects

Although ketamine produces direct myocardial depression, it has significant indirect cardiovascular effects through sympathomimetic effects and stimulation of the vasomotor centre. The heart rate and systolic blood pressure increase by 30% and occasionally up to 100%. Owing to the increased cardiac work and myocardial consumption, ketamine adversely affects the balance between myocardial oxygen supply and demand. Consequently, it is not recommended for use as the sole agent in adults with severe cardiovascular disease. However, the same haemodynamic effects, particularly the raised systemic vascular resistance, make the agent particularly suitable for children with cyanotic heart disease. 

Adverse effects noted with the anesthetic use of ketamine include the sudden loss of respiratory function, spasms of the trachea or larynx, and vomiting. Literature on the emergency treatment of ketamine overdose is rare. Clinical recommendations advise making sure the airway is clear, that breathing is continually monitored, and that the heart rate remains steady. 

Although it is a desirable anesthetic in many respects, ketamine has been associated with postoperative disorientation, sensory and perceptual illusions, and vivid dreams (so-called emergence phenomena). Diazepam, 0.2-0.3 mg/kg, or midazolam, 0.025-0.05 mg intravenously, given prior to the administration of ketamine reduces the incidence of these adverse effects. 

There have been several attempts to attenuate the unpleasant psychological adverse effects that occur after sedation with ketamine. 

The pharmacology of ketamine, including its adverse effects, has been reviewed (4), as has the use and adverse effects of 5-ketamine in the intensive care unit (5). 

Oral ketamine is an effective analgesic in patients with chronic pain. In 21 patients with central and peripheral chronic neuropathic pain treated with oral ketamine, the starting dose was ketamine 100 mg/day, titrated upward by 40 mg/day increments every 2 days until a satisfactory effect was achieved, or until adverse effects became limiting (19). Nine patients discontinued ketamine because of intolerable adverse effects, including psychotomimetic symptoms, such as elevator effect or dissociative feelings, somnolence or insomnia, and sensory changes such as taste disturbance and somatic sensations. 

In a study of 21 outpatients with refractory neuropathic pain treated with oral ketamine, 17 reported adverse events (20). The most common were light-headedness, dizziness, tiredness, headache, a nervous floating feeling, and bad dreams. The adverse effects were sufficiently important to prevent ten patients from continuing with the trial. 

Caudal bupivacaine has been successfully combined with clonidine, ketamine, diamorphine, and buprenor-phine, with increased duration of anesthesia and a low incidence of adverse effects (SEDA-20, 124) (SEDA-21,131). 

In a comparison of intrathecal bupivacaine 10 mg and bupivacaine 7.5 mg combined with ketamine 25 mg, in 30 healthy women there was no extension of postoperative analgesia or reduction in postoperative analgesic requirements in those given ketamine (176). Those given ketamine had a shorter duration of motor blockade, but had an increased incidence of adverse effects, and the study was abandoned after 30 patients. 

There was a higher incidence of adverse effects of morphine in patients with renal insufficiency who receive opioids for some time (37), and in patients with hemolytic uremic syndrome who were given ketamine with subcutaneous morphine postoperatively (38). 

Adverse effects of ketamine are that it causes muscle twitching and excessive salivation together with nightmares and hallucinations (apparently less so in children). 

The emergence phenomena described are adverse effects of ketamine. Administration of diazepam immediately prior to ketamine anesthesia reduces the incidence of these effects. The answer is (C). 

Drugs that make the urine alkaline (e.g. sodium bicarbonate, carbonic anhydrase inhibitors) will reduce the elimination of memantine. Memantine should be used with caution with other NMDA antagonists, such as amantadine, ketamine and dextromethorphan, or concurrent use should be avoided, because of the theoretical increased risk of adverse effects. Memantine is predicted to interact with other drugs eliminated by the same renal secretion mechanism, but no important interaction was seen with glibenclamide, hydrochlorothiazide, metformin or triamterene. 

Many case reports avaiiable, S-ketamine, if avaiiabie, may be used at even lower doses, though risk of adverse effects remains... 

In another study, postoperative ketamine as an adjuvant to morphine (1 mg morphine + 5 mg ketamine with a 7-minute lock out time) was associated with fewer adverse effects one patient who received the combination regimen reported lightheadedness, which resolved spontaneously [123 j. 

Ketamine has been traditionally contraindicated in patients with increased ICP or reduced cerebral compliance because it increases CMR02, CBF and ICP. These deleterious effects can be antagonised by the concomitant administration of propofol, or thiopentone, and benzodiazepines. Furthermore, ketamine is an antagonist at the NMDA receptor. Nevertheless, ketamine can adversely affect neurological outcome in the presence of brain ischaemia. 

Subanesthetic low-dose ketamine is thought to cause delirium and disturbing dreaming. A systematic review of NMDA receptor antagonists in preventive analgesia has shown that only one of 20 studies documented adverse psychotomimetic effects attributable to ketamine (435). In that study, ketamine was given by the epidural route in a relatively high dose. 

The effects of a combination of morphine and a subanesthetic dose of ketamine have been studied in 41 patients undergoing thoracotomy in a double-blind, randomized study [131. The addition of ketamine reduced morphine consumption by 45%, achieved equivalent pain management, and was associated with fewer adverse events. 

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