Is the Combination of alpha2 Agonist-Ketamin Suitable for Human Anaesthesia?

Overview

An alpha2 agonist-ketamine combination is often used in veterinary anaesthesiology for anaesthetizing or immobilizinglaboratory or domestic animals or animals reared in zoos.Depending on the dose ketamine has sedative, analgetic, psychomimetic, cataleptic and anaestetic effects. It stimulatesblood circulation. It does not significantly alter the pattern of breathing. Alpha2 agonists include xylazine and recentlymedetomidine. They have a significant sympatholytic effect and lower noradrenaline level in the CNS by 75%. They reduceheart frequency by sympatholytic effect and stimulation of the vagus nerve and invoke a drop in blood pressure.Medetomidine has a hypnotic and anaesthetic effect in larger doses. Breathing is slightly influenced when clinical dosesare used. Xylazine or medetomidine reduce the dose of ketamine by 40–60%, induce muscle relaxation and reduce theoccurrence of psychomotor symptoms after ketamine. From the clinical point of view, breathing is not significantlyinfluenced with this combination, cardiovascular stability is good. The possibility of using specific alpha2 antagonistagonists – atipamezol is the advantage. In the 1990s, a right-handed isomers of ketamine and medetomidine started to beused in the humaneanaesthesiology.Since 2000 dexmedetomidine has been registered as Precedex by Abbott Laboratories.Data on the use of an alfpha2 agonist – ketamine combination in humane anaesthesiology are rather scare. Lävenen andcoll. (1995) gave dexmedetomidine in a pre-medication dose of 2.5 µg.kg-1 i. m. The intravenous ketamine dose could bereduced by 50%. At the same time the occurrence of psychomimetic symptoms was reduced too. According to ourpreliminary results with intravenous combination of midazolam with ketamine, dexmedetomidine at doses of 1 µg.kg-1 i. v.causes a marked reduction of the ketamin dosage and the occurrence of psychomimetic effects. The reduction of theketamine dose during surgery was pronounced in the range of 60–70%. Advantages of the triple combination were veryconvincing, especially in dental surgery. Dexmedetomidine markedly reduces ketamine dosage and the subsequentreduction of the undesirable efects (esp.psychomimetic). It markedly potentiates hypnotic effect of ketamine and midazolamand analgetic effect of ketamin. Midazolammarkedly reduces the occurrence of psychomimetic effects after ketamine.Whencombined with dexmedetomidine, it markedly reduces the stimulatory effects of ketamine on the circulation. The triplecombination has no clinically significant effects on respiration. Dexmedetomidine with midazolam protect against neurotoxiceffects of ketamine and reduce the increased sympathetic tone caused by its administration. Psychomotor recoveryafter the triple combination is fast. There is a possibility to use specific antagonists flumazenil and atipamezol.The questionremains whether the above mentioned triple combination could be used in a disastermedicine for patients with hypovolemia or in a haemorrhagic shock. In our preliminary experimental trials on rabbits we demonstrated that the medetomidine-ketaminecombination during a haemorrhagic shock (central arterial pressure 40 mm Hg after a three hour period) had thehighest survival rate. It was demonstrated in the tests on piglets that infusion of medetomidine with ketamine increasesblood pressure in a haemorrhagic shock. However, further experiments are necessary to elucidate the role of medetomidine-ketamine combination in clinical anaesthesiology and emergency medicine.

Key words:
alpha2 agonist – ketamin – benzodiazepins