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KETAMINE MODERATOR: Dr. D.MADHUSUDHAN REDDY D.A. PRESENTER : Dr. V.SUJATHA P.G

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Page 1: Ketamine Ppt

KETAMINE

MODERATOR: Dr. D.MADHUSUDHAN REDDY D.A.PRESENTER : Dr. V.SUJATHA P.G

Page 2: Ketamine Ppt

HISTORY

It was synthesized as Ketalar by Stevens ,in 1962.

First used in humans by Corsen and Domino in

1965.

First used- American soldiers during Vietnam War.

Released for civilian use in 1970.

In recent past its use on humans dramatically

curtailed emergence phenomena including

out-of-body experiences in clinical practice.

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Physical & Chemical Properties

It is phencylidine derivative {2-(O-chlorophenyl)-2-methylamino

cyclohexanone}. Mol wt =238 pH =3.5 to 5.5 Freely water soluble pKa =7.5

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PHARMACOLOGY There is a chiral centre with two optical

isomers (enantiomers)

Ketamine has a high lipid solubility (5–10 times that of thiopental)

crosses the blood-brain barrier faster.

It undergoes demethylation and hydroxylation of the cyclohexanone ring.

The metabolites are conjugated to water soluble glucoronide derivatives and excreted in the urine.

Norketamine has 20–30% of the activity of the parent compound.

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Isomers The chiral centre of the cyclohexanone

ring permits the existence of two enantiomers.

S-(+)-ketamine has greater affinity than R (-) ketamine at phencyclidine binding sites on the NMDA receptor.

There are no significant differences in pharmacokinetic properties between enantiomers and the racemic mixture.

S-(+)-ketamine has twice as potent as the racemic mixture in producing anaesthesia and analgesia, and thrice as potent as R-( - ) ketamine

Page 9: Ketamine Ppt

The recovery time is reduced with S (+)

ketamine compared with the racemic mixture.

smaller dose of S-(+)-ketamine is required for

anaesthesia, there are less psychological side-

effects.

Coupled with the quicker recovery, patient

acceptance of S-(+)-ketamine is greater.

S-(+)ketamine is significantly more expensive

than the generic, racemic ketamine.

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PHARMACKINETICS Onset of action:

IV <30 seconds IM/ rectal 3 – 4 minutes

Peak effects: IV 1minute IM/ rectal 5 – 20 minutes Orally 30 minutes

Duration of action: IV 5 - 15minute IM/ rectal 12 – 25 minutes Epidural 4 hours

Metabolism: Demethylation & hydroxylation by hepatic CYP One of the produced metabolites is active

Norketamine (Metabolite I) Has a potency of 30% of the parent drug &

longer half-life

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PHARMACODYNAMICS Dosing:

Sedation/Analgesia IV: 0.5 – 1.0 mg/kg IM/ rectal: 2.5 – 5.0 mg/kg Orally: 5 – 6 mg/kg

Induction IV: 1.0 – 2.5 mg/kg IM/ rectal: 5 – 10 mg/kg

Infusion 15-80 mcg/kg/min

Augment with midazolam IV 1 -2 mg Epidural/ Caudal

0.5 mg/kg Dilute in saline or local anesthetic (1

mL/kg)

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Site of action: Thalamoneocortical projection. Depresses the thalamus, stimulates part of limbic system

(Hippocampus) Causes functional disorganization of

nonspecific pathways in mid brain and thalamus

Medullary reticulary formation is depressed

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Mechanism of action acts on the central nervous system and has local

anaesthetic properties. Its effects are mediated primarily by

noncompetitive antagonism at the N-methyl-D aspartate(NMDA) receptor Ca+2 channel pore.

NMDA channel block appears to be the primary mechanism of the anaesthetic and analgesic action of ketamine (at the CNS and also at spinal cord receptors).

It reduces the presynaptic release of glutamate. The S (+) enantiomer has a three- to four-fold

greater affinity for the NMDA receptor than the R(-) form.

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Other mechanisms of action of ketamine

Include interaction with opioid receptors,

With a preference for mu and kappa

receptors;.

The affinity of ketamine for these

receptors is 10 times less than that for

the NMDA channel,

Naloxone does not antagonize the

analgesic effects of Ketamine

Page 17: Ketamine Ppt

ketamine has an antagonistic interaction

with

monoaminergic, muscarinic, and nicotinic

receptors.

ketamine produces anticholinergic

symptoms (e.g. tachycardia and

bronchodilatation).

Ketamine at high doses has local anaesthetic

properties through its ability to inhibit

neuronal sodium channels

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“DISSOCIATIVE ANESTHETIC” Ketamine produces the ‘dissociative’ anaesthetic

state that has been described as functional and electrophysiological dissociation between the thalamo-neocortical and limbic systems

Produces an atypical behavioral state. State of sedation Immobility Amnesia Marked analgesia Feeling of dissociation from the environment Without true unconsciousness

Page 19: Ketamine Ppt

CNS effects The EEG demonstrates a dominant theta

activity with abolition of alpha rhythm. The unique clinical state produced by

ketamine is typically a state of catalepsy in which the eyes remain open with a slow nystagmic gaze, whereas the corneal and light reflexes remain intact.

Varying degrees of hypertonus and occasional purposeful movements unrelated to painful stimuli are noted in the presence of adequate surgical anaesthesia.

excitatory activity in both the thalamus and limbic systems without clinical evidence of seizure activity after ketamine administration.

Page 20: Ketamine Ppt

Ketamine has anticonvulsive and even neuroprotective properties.

Analgesia occurs at considerably lower blood concentrations than does the loss of consciousness..

Ketamine increases cerebral metabolism, cerebral blood flow , and intracranial pressure, cerebral O2 consumption.

Pupillary dilatation, nystagmus, salivation, and lacrimation are common,

Intra occular pressure rises

Increased skeletal muscle tone with coordinated but purposeless movements of arms , legs, trunk and head

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Emergence reactions Psychic sensations after ketamine emergence can be

alterations in mood state and body image, floating sensations, vivid dreams or illusions, and occasional frank delirium.

These dreams and illusions usually disappear on full wakening.

The incidence of psychic effects is approximately 5–30%. A higher incidence is associated with factors such as

increasing age, female gender, patients who normally dream, rapid intravenous administration, and large doses.

Ketamine has been observed to activate psychoses in patients with schizophrenia.

Premedication can attenuate psychic reactions: midazolam (0.07–0.1 mg /kg), diazepam (0.15– 0.3 mg /kg), and lorazepam (2–4 mg) i.v.

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Cardiovascular effects

Stimulates CVS and associated with tachycardia,

increased blood pressure, SVR and PVR and increased

cardiac output and myocardial O2 consumption.

centrally mediated sympathetic response ..

Ketamine has a direct myocardial depressant effect, in

presence of sympathetic depression.

It is possible to reduce the undesirable cardiovascular

effects by giving Ketamine as a continuous infusion

and use of a benzodiazepine.

ketamine inhibits intraneuronal uptake of

noradrenaline

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Cardiovascular effects Drug of choice in congenital heart

disease Increases SVR and CO Does not worsen RIGHT to LEFT

shunt Correction of fallots tetralogy CVS effects are supressed by

Benzodiazepines, Clonidine , fentanyl and Volatile anaesthetics

Page 24: Ketamine Ppt

Respiratory effects

Ketamine has minimal effect on central

respiratory drive,

A transient decrease in ventilation can occur

after bolus administration.

Ketamine is a bronchial smooth muscle relaxant,

so it has a special role in intractable asthma.

It improves pulmonary compliance and is as

effective as halothane in preventing

bronchospasm..

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Ketamine increases salivary secretions, which can

produce potential problems in children by causing upper

airway obstruction.

Although swallowing, cough, sneeze, and gag reflexes

are relatively intact with ketamine, silent aspiration can

occur.

Laryngospasm is frequent

laryngospasm during ketamine sedation is usually

caused by stimulation of the vocal cords by

instrumentation or secretions.

Secretions can be reduced by giving glycopyrrolate

premedication.

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Effects on other systems Ketamine has not been shown to have any

adverse effects on hepatic and renal systems.

Intraocular pressure is slightly increased after Ketamine administration.

Ketamine produces an increase in muscle tone and sometimes muscle spasms, although it has been safely used in myopathies and malignant hyperthermia.

Variable effects on uterine tone have been reported.

Other effects include emesis, transient rash, and agitation.

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Indications Aged and poor risk patients

Shock and cardiovascular instability.

Severe dehydration.

Respiratory failure or bronchospasm.

Severe anaemia.

Major thoraco abdominal procedures.

Cardiac tamponade and constrictive pericarditis.

Obstetric patients

Rapid sequence induction

Severe hypovolaemia.

Acute haemorrhage.

Acute bronchospasm.

Low dose for analgesia

Supplement regional technique.

Transient analgesia at the time of delivery.

Adjunct to local or regional anaesthesia

Low dose for sedation and analgesia during the procedure.

Supplement for inadequate block.

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Outpatient surgery

Paediatric anaesthesia

Diagnostic and therapeutic procedures.

Induction of anaesthesia.

Caudal analgesia.

Adult anaesthesia

Brief surgical procedures.

Supplement local or regional technique.

Diagnostic and therapeutic procedures.

Reactive airway disease

Intractable bronchial asthma.

COPD with bronchospasm.

Patients with thermal injuries

Debridement and skin grafting.

Dressing changes

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Postoperative analgesia

As an adjunct with morphine

Recovery room.

Intensive care units.

Procedural sedation in intensive care

Paediatric cannulation, central lines.

Adult central lines, endoscopies, dressing changes.

Developing countries and field hospitals

Chronic pain

For patients in whom airway management may be difficult

Unstable cervical spine.

Trapped casualties.

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Contra indications A high predisposition to laryngospasm or apnoea (e.g.

active pulmonary infection, patients younger than 3 months).

Severe cardiovascular disease, such as angina, heart failure, or malignant hypertension (because of cardiostimulant effects of ketamine, although this is controversial).

CSF obstructive states (e.g. severe head injury, central congenital or mass lesions).

Intraocular pressure pathology (e.g. glaucoma, acute globe injury).

Previous psychotic illness (potential activation of psychoses)

Hyperthyroidism or thyroid medication use (possibility of severe tachycardia or hypertension).

Porphyria (possibility of triggering a porphyric reaction).

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Clinical applications Sedation Ketamine is appropriate for children

undergoing procedures in isolated situations. Emergence reactions in children are less intense, so it can be used for both sedation and general anaesthesia in procedures such as cardiac catheterization , radiotherapy, radiological investigations, and burns dressings.

Generally, sub anaesthetic doses are required for minor procedures.

Ketamine is often combined with premedication (e.g. benzodiazepines) to reduce the dose requirement and emergence reactions, and an antisialogogue (e.g. glycopyrrolate) to reduce salivary secretions.

Page 32: Ketamine Ppt

In both adults and children, ketamine can be used as a supplement (i.v. or i.m.) during regional anaesthesia.

It can also be given via the epidural route as an adjunct to a local anaesthetic to extend the duration of analgesia.

Low-dose ketamine has also been used along with propofol to improve the quality of sedation.

administration of ketamine results in reduced postoperative opioid requirements6 (40–60% on an average).

Ketamine-treated patients also experienced less post operative nausea and vomiting

Page 33: Ketamine Ppt

ADVANTAGES & USES Induction agent of choice for

Asthmatics

Shock

Children as an alternative to inhalational induction.

Constrictive pericarditis, cardiac tamponade, right to left shunt like TOF,

Used as sole agent for minor procedures, burns and dressings

Safely used at remote places since it does not depress respiration and heart

Depressed pts as they have better recovery

In neuromuscular diseases- as a sole anaesthetic

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DISADVANTAGES

Incidence of hallucinations and emergence

reactions is very high

Increased muscle tone

Pharyngeal and respiratory secretions are

increased which can cause laryngospasm

Increases myocardial O2 demand

All pressures – like intra ocular, intra

gastric, intracranial markedly raised

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Ketamine in regional Anaesthesia:Should be preservative free as

Benzethonium is neurotoxic.After caudal or epidural anaesthesiaDuration of analgesia is longerKetamine caudal block is similar to

post OP analgesia of bupivacaine.Chlorobutanol used as preservative for

ketamine is neurotoxic.

Page 36: Ketamine Ppt

References Miller 7th edition Ketamine & Kids an update -

Paediatric anaesthesia 2005, 15:91- 97

Ketamine CEACCP reviews vol 7, no.2,2007.