Kmin

Uses

Kmin is recommended for:

• As the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Kmin is best suited for short procedures and it can be used with additional doses, for longer procedures.
• For the induction of anesthesia prior to the administration of other general anesthetic agents.
• To supplement low-potency agents, such as nitrous oxide.

Kmin is also used to associated treatment for these conditions: General Anesthesia, Induction and Maintenance of General Anesthesia

How Kmin works

Kmin interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.

Dosage

Kmin dosage

Adult:General Anesthesia-

• IV Induction: 1-4.5 mg/kg single dose
• IM Induction: 6.5-13mg
• IV Infusion: 1-2mg/kg at 0.5mg/kg/min

Maintenance:

The maintenance dose should be adjusted according to the patient's anesthetic needs and whether an additional anesthetic is employed. Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia.Rapid sequence Intubation, Induction - 2mg/kg IV

Pediatric:

General Anesthesia:

• IV Induction: 1-2 mg/kg IV; range: 4-13 mg/kg
• IM Induction: 5-10 mg/kg; range: 0.5-4.5 mg/kg
• Maintenance: 0.01-0.03 mg/kg/min continuous IV infusion

Maintenance:

The maintenance dose should be adjusted according to the patient's anesthetic needs and whether an additional anesthetic is employed. Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia.

Rate of Administration: It is recommended that ketamine should be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.

The 100 mg/ml concentration of ketamine should not be injected intravenously without proper dilution. It is recommended the drug be diluted with an equal volume of either Sterile Water for Injection, USP, Normal Saline, or 5% Dextrose in Water.

Reconstitutions

To prepare a dilute solution containing 1 mg of ketamine per ml, aseptically transfer 10 ml (50 mg per ml vial) to 500 ml of Dextrose Injection, 5% or Sodium Chloride Injection, 0.9% and mix well. The resultant solution will contain 1 mg of ketamine per ml.

Side Effects

Emergence reactions (e.g. vivid dreams, hallucinations, confusion, irrational behaviour); increased muscle tone sometimes resembling seizures; temporary HTN and tachycardia, hypotension, bradycardia, arrhythmias, apnoea, laryngospasm, resp depression, diplopia, nystagmus, nausea, vomiting, lacrimation, hypersalivation, raised intraocular and CSF pressure, transient rash and pain at inj site, cystitis.

Toxicity

Preclinical studies related to the blocking of NMDA receptors have shown an increase in apoptosis in the developing brain which results in cognitive deficits when used for longer than 3 hours. Toxicity studies regarding carcinogenesis have not been performed. Regarding mutagenesis and fertility, ketamine showed to be clastogenic and to not have effects on fertility.

Precaution

Patient with cardiac decompensation, chronic alcoholic or acutely alcohol-intoxicated patients, pre-anaesth elevated CSF pressure, globe injuries, increased intraocular pressure (e.g. glaucoma), neurotic traits or psychiatric illness (e.g. schizophrenia, acute psychosis), acute intermittent porphyria, seizures, hyperthyroidism, pulmonary or upper resp infection, intracranial mass lesions, head injury, or hydrocephalus, hypovolaemia, dehydration, cardiac disease esp coronary artery disease (e.g. CHF, myocardial ischaemia, MI). Pregnancy and lactation.

Interaction

Prolonged recovery time with barbiturates or narcotics. May potentiate neuromuscular blocking effects of atracurium and tubocurarine including resp depression with apnoea. May increase risk of bradycardia, hypotension or decreased cardiac output with halogenated anaesthetics. May potentiate CNS depression and risk of resp depression with CNS depressants (e.g. phenothiazines, sedating H1-blockers, skeletal muscle relaxants). May antagonise hypnotic effect of thiopental. May increase risk of HTN with thyroid hormones. May increase risk of hypotension with antihypertensive agents. Reduction in seizure threshold resulting in unpredictable extensor-type seizures when given concurrently with theophylline.

Food Interaction

• Avoid alcohol.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of ketamine.

Use in combination may result in additive central nervous system (CNS) depression and
GENERALLY AVOID: Coadministration of oral ketamine with grapefruit juice may significantly increase the plasma concentrations of S(+) ketamine, the dextrorotatory enantiomer of ketamine.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Inhibition of hepatic CYP450 3A4 may also contribute.

When a single 0.2 mg

In addition, the elimination half-life of S(+) ketamine increased by 24% with grapefruit juice, and the ratio of the main metabolite norketamine to ketamine was decreased by 57%.

The pharmacodynamics of ketamine were also altered by grapefruit juice.

Specifically, self-rated relaxation was decreased and performance in the digit symbol substitution test was increased with grapefruit juice, but other behavioral or analgesic effects were not affected.

MANAGEMENT: Patients receiving ketamine should not drink alcohol.

Caution is advised when ketamine is used in patients with acute alcohol intoxication or a history of chronic alcoholism.

Following anesthesia with ketamine, patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination, such as driving or operating hazardous machinery, for at least 24 hours and until they know how the medication affects them.

Patients treated with oral ketamine should also avoid consumption of grapefruit and grapefruit juice during treatment.

Otherwise, dosage reductions of oral ketamine should be considered.

Kmin Hypertension interaction

[Major] The use of ketamine is contraindicated in patients whom a significant elevation of blood pressure would constitute a serious hazard.

It is recommended to monitor cardiac function continually during a procedure in patients with hypertension or cardiac decompensation.

Kmin Drug Interaction

Major: lorazepam, lorazepam, diphenhydramine, diphenhydramine, clonazepam, clonazepam, pregabalin, pregabalin, quetiapine, quetiapine, alprazolam, alprazolamModerate: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, duloxetine, duloxetineUnknown: cholecalciferol, cholecalciferol, ondansetron, ondansetron

Kmin Disease Interaction

Major: hypertensionModerate: alcoholism

Volume of Distribution

The apparent volume of distribution of the central compartment and at steady-state are 371.3 ml/kg and 4060.3 ml/kg, respectively.

Elimination Route

Kmin absorption is very rapid and the bioavailability is around 93%. After the first pass metabolism, only 17% of the administered dose is absorbed. It distributes very rapidly and presents a distribution half-life of 1.95 min. The Cmax levels at peak reach 0.75 mcg/ml in plasma and 0.2 mcg/ml in cerebrospinal fluid.

Half Life

The reported half-life in preclinical studies for ketamine is 186 min.

Clearance

The clearance rate of ketamine is high and of around 95 L/h/70kg.

Elimination Route

Pharmacokinetic studies have resulted in the recovery of 85-95% of the administered dose in urine mainly in the form of metabolites. Some other routes of elimination of ketamine are bile and feces. When administered intravenously the resultant recovery is distributed by 91% of the administered dose in urine and 3% in feces.

Pregnancy & Breastfeeding use

Pregnancy: The safe use of ketamine in pregnancy has not been established, and such use is not recommended.

Lactation: Kmin is likely to be excreted in breast milk and therefore breastfeeding should be discontinued when ketamine is in use.

Contraindication

CV disease including severe HTN; patients with increased intraocular or CSF pressure.

Acute Overdose

Symptoms: Resp depression.

Management: Employ supportive ventilation. Mechanical support of respiration is preferred to admin of analeptics.

Storage Condition

Storage Conditions

Store between 20-25° C.

Innovators Monograph

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