Ketamine Diazepam

The inhalation anesthesia is not practical for a toxicologist working on series of animals. We made a study of ERG under anesthesia obtained with diazepam-ketamine or demetomidine. Anesthetic drugs are used intramuscularly or intravenously for toxicology studies. 

Anticonvulsant drugs such as carbamazepine, diazepam, valproic acid, and phenobarbital also slightly increased the duration of the initial AD. However, the effects of these drugs on the other associated seizure events were quite different from PCP and ketamine. The effects of carbamazepine and diazepam, typical of the four compounds, are illustrated in figure 4. These compounds either suppressed the rebound spiking (diazepam, valproic acid, and phenobarbital) or lengthened the total seizure duration with no rebound suppression (carbamazepine). 

PCP, 15 mg/kg, and ketamine, 40 mg/kg, elevated the threshold for eliciting hippocampal afterdischarge (prekindling) by 61 percent and 267 percent, respectively (table 2). Valproic acid and carba-mazepine also elevated the threshold. In contrast, phenobarbita 1 and diazepam had no effect on the prekindling afterdischarge threshold, even at doses capable of altering the AD. 

The most serious disadvantage to the use of ketamine is its propensity to evoke excitatory and hallucinatory phenomena as the patient emerges from anesthesia. Patients in the recovery period may be agitated, scream and cry, hallucinate, or experience vivid dreams. These episodes may be controlled to some extent by maintaining a quiet reassuring atmosphere in which the patient can awaken or if necessary by administering tran-quilizing doses of diazepam. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

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. 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

Ketamine often causes emergence delirium and disturbing dreaming. Benzodiazepines are often co-adminis-tered to attempt to manage this. The optimal dose of diazepam to add to ketamine-fentanyl field anaesthesia has been assessed in a randomized double-blind study in 400 patients from Vanuatu the optimal dose was 0.1 mg/ kg (436). 

Grace RF. The effect of variable dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia. Anaesthesia 2003 58 904-10. 

Tachycardia and hypertension are common after anesthetic induction with ketamine, although the hypertension can be limited by the addition of diazepam (10). Nodal dysrhythmias can also occur (11). Because of possible... 

Zsigmond EK, Kothary SP, Kumar SM, Kelsch RC. Counteraction of circulatory side effects of ketamine by pretreatment with diazepam. Clin Ther 1980 3(l) 28-32. 

There are reports that diazepam can produce paradoxical excitability immediately after i.v. administration to humans and small animals. Although this paradoxical effect is not well described in horses, diazepam should be administered with caution to mature horses when used as a sole agent. It can be used as the sole agent for sedation and restraint in young foals. Diazepam is recommended for i.v. use at doses of 0.02-0.1 mg/kg. Diazepam is primarily used in adult horses to provide muscle relaxation and for its anticonvulsant effect prior to anesthetic induction with ketamine. Diazepam (0.04 mg/kg) reduces the MAC of halothane by approximately 29% (Matthews et al 1990). Diazepam is considered the acute treatment of choice for status epilepticus in all species (see Ch. 9). Diazepam (0.02-0.04 mg/kg) is an appetite stimulant in horses, although its effect is of short duration (Brown et al 1976). 

Artru A A 1990 Hypocapnia and diazepam reverse and midazolam or fentanyl attenuates ketamine induced Increase of cerebral blood volume and/or cerebrospinal fluid pressure. In Domino E F (ed) Status of ketamine in anesthesiology. NPP Books, Ann Arbor, Ml, p. 119 Aurich C, Aurich J E, Klug E 1993 Naloxone affects gastrointestinal functions and behaviour in horses. Deutsche Tierarztiiche Wochenschrift 100 314-315 Ballard S, Shults T, Kownacki A A et al 1982 The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse. 

American Journal of Veterinary Research 61 1579-1586 Nolan A, Reid J, Welsh E et al 1996 Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine a pharmacokinetic study. Research in Veterinary Science 60 262-266 Norman W M, Court M H, Greenblatt D J 1997 Age-related changes in the pharmacokinetic disposition of diazepam in foals. American Journal of Veterinary Research 58 878-880... 

No effective treatment is known. Drugs that counteract the effect of glycine on neuronal cells, such as strychnine, diazepam, and dextromethorphan, could bring mild benefits in milder forms of the condition. Ketamine, an anesthetic blocker of the N-methyl-n-aspartate (NMDA) receptor channel, brought a partial improvement of neurological symptoms and EEG findings m some patients, but their developmental milestones were delayed. 

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