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1. Etomidate , ketamine
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab. DCA,
Dip. Software statistics-
PhD ( physiology), IDRA

2. Etomidate
• Etomidate is an imidazole derivative whose
structure is unlike that of any other anesthetic
• it is ionized and water soluble at acidic pH and
lipid soluble at physiologic pH.
• It is supplied as a 0.2% solution in 35%
propylene glycol.

3. Preparation
• emulsion preparation with medium chain
triglycerides and soyabean oil (Etomidate-
Lipuro®).
• Ampoules contain 20 mg of etomidate in 10
mL (2 mg mL–1).
• The pH of the propylene glycol solution is 8.1.

4. Carbon between two nitrogen is
imidazole

5. Pharmacokinetics
• After an induction dose of 0.3 mg/kg, loss of
consciousness and recovery will be similarly
rapid, as with thiopental and propofol.
• Redistribution –
• Hepatic esterases – carboxylic acid to excrete
in the urine
• T-half – 3-5 hours
• 78 % protein bound

6. What is special ?
• Etomidate works via GABA A receptors to
produce rapid onset of unconsciousness
• No analgesia
• No suppression of autonomic reflexes
• But myoclonic jerks

7. • Respiratory depression as thio
• Few episodes of apnea +
• At the typical induction dose of 0.3 mg/kg, it
has little effect on arterial or venous vascular
tone or on cardiac contractility.
• What is the reason ??
• Not known

8. • Etomidate is a popular choice for induction of anesthesia
in patients compromised by cardiac dysfunction or
hypovolemia
• Hemodynamic stability after induction with etomidate is
superior to that of any alternative method of induction
• Does not release histamine
• Inpatients with atopy a big OK
• Can we use routinely then ??

9. Side effects
• High incidence of nausea and vomiting
• 30 %
• Increased observation of myoclonus
• 40 %
• Pain on injection
• 80 %
• Emergence phenomena
• Routine use ?

10. Adrenal suppression
• At clinically relevant concentrations, etomidate inhibits
the mitochondrial CYP isozyme (CYP11B) responsible for
catalyzing the 11β-hydroxylation reaction in cortisol
synthesis
• Even a single dose does
• But clinical relevance ?
• Out of common use

11. • Evolving septic shock ??
• As infusions in coronary case ??
• Etomidate + glucocorticoid ?? Use
• Porphyria ??

12. • Significant hemolysis may occur in patients with
fragile red cells, for example spherocytosis or post
transfusion, or by interaction with other drugs or
diseases causing hemolysis
Due to propylene
glycol

13. Newer horizons
• Methoxy carbonyl etomidate (MOC-
etomidate) and carboetomidate
• Anesthetic action
• Hemodynamic stability
• Hemolysis -- no
• But no adrenal suppression ??
• Future

14. Ketamine

15. • Phencyclidine
• Cyclohexamine
• Ketamine
1960
1970

16. Chemistry
• It is a weak base with a pKa of 7.5 and is supplied in solution
as the hydrochloride salt.
• The 3 concentrations available—10 mg/mL, 50 mg/mL, and
100 mg/ml
• Ketamine is compatible in solution with atropine or
glycopyrrolate, with which it is often mixed.
• The commercial preparations of ketamine contain a racemic
mixture of its 2 isomers.
• S ketamine is available in europe

17. Images taken from the internet for closed academic purpose only

18. Pharmacokinetics
• Within a minute – action
• Redistribution
• Elimination itself in around 4 hours
• Ketamine
– Liver---
– Diazepam competitively inhibits N-demethylation of
ketamine, decreasing its hepatic clearance
• Nor ketamine
– Glucuronide metabolites to the kidney
Tolerance may occur in burn patients receiving more than
two short-interval exposures to ketamine.

19. NMDA antagonism
No
GABA A

20. Other mild actions
• σ receptors
• Sodium receptors as local anesthetic
• Some muscarinic action

21. Pharmacodynamics
• Ketamine produces dose-dependent CNS depression leading
to a so-called dissociative ( dissociated from surroundings)
anesthetic state characterized by profound analgesia and
amnesia, even though patients may be conscious and
maintain protective reflexes.(catalepsy)
• The proposed mechanism for this cataleptic state includes
• electro physiologic inhibition of thalamocortical pathways
stimulation of the limbic system.

22. Dosage – hypnotic
• Intravenous dose 1-2 mg /kg – 30 seconds
• IM dose 4-8 mg / kg –2 – 4 minutes
• Return of consciousness is around 10 – 20 minutes
• burn dressing changes, débridements, and skin-
grafting procedures.
• The excellent analgesia and ability to maintain
spontaneous ventilation in an airway that might
otherwise be altered by burn-scar contractures are
important advantages of ketamine in these patients.

23. Other uses
• Ketamine 0.5 – 1 mg / kg / hour in
Refractory status epilepticus
• 2 -4 mg / kg – used in infants
• But attenuation of pain and stress response
may not efficient in kids
• Caudal adjuvant 1 mg /kg – apoptosis risk ??

24. Which is the end point ?
• Loss of eye lash reflex
• Apnea
• Verbal contact.
• Not clearly defined

25. Pharmacodynamics
• Opioid tolerance reversed
• it increases CMRO2, CBF, and ICP
• Propofol prior is useful in blunting ICP increase
• No protection against brain ischemia
• EEG -fast β activity (30 to 40 Hz) followed by moderate-
voltage θ activity, mixed with high-voltage δ waves
recurring at 3- to 4-second intervals.
No iso electric
EEG –
Cant monitor
EEG

26. RS
• Ketamine has well-characterized broncho dilatory
activity.- no ventilatory drive effect
• In the presence of active bronchospasm, ketamine is
considered to be the IV induction agent of choice.
Ketamine has been used in subanesthetic dosages to
treat persistent bronchospasm in the OR and ICU.
• Increase secretions– ( glyco as additive)
• Airway reflexes preserved but -----

27. • Effective intravenous ketamine anesthesia
permits high inspired oxygen concentrations
• Functional residual capacity, minute volume,
tidal volume, and the coordinated
contribution of intercostal muscle function to
inspiration are maintained

28. CVS
• Ketamine has prominent cardiovascular-stimulating
effects secondary to direct stimulation of the
sympathetic nervous system. Ketamine is the only
anesthetic that actually increases peripheral arteriolar
resistance.
• As a result of its vasoconstrictive properties, ketamine
can reduce the magnitude of redistribution hypothermia
Hypovolemic ok ---- but no use in
sympathetically exhausted patients

29. Other clinical pearls
• Rapid Sequence Intubation of the Shock Patient
• In sub hypnotic doses (0.15-0.3 mg/kg), ketamine is
commonly used for monitored anesthesia care.
• It produces profound analgesia without the concurrent
ventilatory depression produced by opioids
• Children

30. • Anesthetic doses of ketamine increase uterine
tone and the intensity of uterine contraction
• We have a case of atonic PPH and hypotension
• The ideal drug would be ??

31. All routes
• IV
• IM
oral
• Nasal
• Rectal
• Epidural
• Intra thecal
• IVRA
• Adjuvant to blocks

32. • Ketamine is commonly used, either alone or in
combination with midazolam, as an oral medication
in children, especially as the sole agents for
conscious sedation for a short but noxious procedure
• No iv line also is OK
• No pain on injection

33. Side effects
• high incidence of psychomimetic reactions (namely,
hallucinations, nightmares, altered short-term memory,
and cognition) during the early recovery period.
• Usually 10 – 20 %
• The incidence of these reactions is dose-dependent and
can be reduced by co administration of benzodiazepines,
barbiturates, or propofol
• ( upto 75 % described )

34. Emergence phenomena
• Start from one hour after recovery
• One third of adults
• Adults and women higher
• Many times pleasant in children
• Previous psychological problems
• Atropine increases
• Benzodiazepines decrease
• Promethazines
Music
makes it
pleasant

35. Eye and MH
• A parallel increase in intraocular pressure may
be detrimental in patients with open eye
injuries or glaucoma, or during vitreo retinal
surgery
• Ketamine has been safely used for patients
with malignant hyperthermia and acute
intermittent and variegate porphyria.

36. Heart , TCADs and ketamine
• ketamine can produce adverse effects when
administered in the presence of tricyclic
antidepressants because both drugs inhibit
norepinephrine reuptake and could produce severe
hypotension, heart failure, and/or myocardial
ischemia

37. Resurgence
• Low doses
• Anesthetic adjuvant
• Analgesia
• Spinal comfort
• Post operative pain reduction
• Ketamine is effective in decreasing the incidence of
emergence agitation in children undergoing dental
repair under sevoflurane general anesthesia.

38. Intranasal ketamine
• attenuates pain in the emergency room in children and
adults.
• also reduces the severity of pain in migraine.
• Wink et al reported a 29-year-old woman with autism
who was treated with intranasal ketamine (20–60 mg) on
12 dosing occasions across 6 weeks.
• She showed improvements in mood, social interactions,
flexibility, tolerance of changes in routine, motivation,
and concentration.

39. • Rectal Ketamine, 10 mg/kg, has a delayed
onset but is as effective as 1 mg/kg midazolam
for sedating healthy children before general
anesthesia.
• Anesthesiology. 1992 Jan;76(1):28-33.
• Oral ketamine preanesthetic medication in
children- 6 mg / kg

40. • Long-term ketamine subcutaneous
continuous infusion in neuropathic cancer
pain. 150 mg / day tapered
• subcutaneous injection of low dose ketamine
at the incision site to reduce cesarean section
pain.( 0.5 mg / kg )

41. Epidural PCEA
• A combination of low-dose epidural ketamine and
morphine results in effective postoperative analgesia
and also reduces morphine requirement, thereby
decreasing morphine-related side-effects.

44. Nerve blocks
• Addition of 2 mg / kg – possible improvement
in block characters after supra clavicular nerve
blocks
• Ketamine as an adjuvant in sympathetic blocks
for management of central sensitization
following peripheral nerve injury

45. IVRA or sublingual or local
• 0.5 mg/kg of body weight ketamine to
lignocaine for IVRA improves quality of
anesthesia and perioperative analgesia
without causing side effects.
• Better than dexmed in a few studies
• ------------------------------------------------------
• Sublingual ketamine 25 mg for chronic
neuropathic pain
• Ketamine ointment for neuropathic pain

46. Summary
• Etomidate – imidazole
• GABA A -0.3 MG/ KG- iv
• Thio like
• Nausea, myoclonus pain
• Hemodynamics
• Adrenal suppression
• Phencyclidine
• Dissociative , analgesia
• Increase cmro2, EEG ?
• 1-2 mg/ kg , NMDA ant.
• Subanesthetic doses
• All routes
• Sympathetic stimulation
• Bronchospasm ,
• emergence
• IOP, ICP, IHD, HT -- ??
• PPH !!