2. What are i.v induction drugs?
Drugs,when given intravenously in an appropriate dose,cause rapid loss of
consciousness.
Rapid onset:Often described as occurring within"ONE ARM-
BRAINCIRCULATION TIME”
The time taken for the drug to travel from the site of injection (usually the
arm)to the brain,where they have their effect.
3. History
HEXOBARBITAL:The first ultra short acting barbiturateThe first
successful i.v anesthetic
Introduced by Weese in Germany in 1932.
THIOPENTAL:Introduced in 1935 by Lundy in Minnesota &Waters in
Wisconsin.
Thiopental-widely accepted because of lack of excitatory
myoclonicmovements seen with hexobarbitone
4. PROPOFOL-launched in 1986 under the brand name DIPRIVAN
KETAMINE-was first synthesized in 1962 by Calvin StevensFirst human use
was in 1969.
METHOHEXITAL-a shorter-acting barbiturate with central nervous system-
stimulating properties,was introduced in 1956 for electroconvulsive therapy
(ECT).
5. USES of Intravenous anesthetics
Induction and maintenance of anesthesia
As a sole anesthetic for short procedures
Intravenous infusion-to maintain anesthesia for
longer procedures
e.g.TIVA(Total intravenous anesthesia)
To provide sedation in places like ICU
6. From induction to wake up:what happens to
abolus of IV induction drug?
Bolus of i.v induction agent enters blood stream
A percentage of drug is bound to plasma proteins &the rest is
UNBOUND(protein binding depends on lipid solubility °ree of ionization)
The drug is carried in the Venous blood to the right side of the heart.
7. Drug reaches Left side of the heart through pulmonary
circulation
Systemic circulation
High proportion of initial bolus is delivered to CEREBRAL
CIRCULATION(as majority of cardiac output is diverted to
brain,liver &kidney)
8. The drug then passes along a concentration gradient from
the blood into the brain.
The rate of this transfer is dependent on a number of factors:
the arterial concentration of the unbound free drug
the lipid solubility of the drug
the degree of ionization.
Unbound,lipid soluble,unionized molecules cross the blood
brain barrier the quickest.
9. Drug starts exerting its effect once it penetrates CNS tissue
Each drug acts at a specific receptor (e.g GABA-A,NMDA
and Ach receptors)
The drug then starts to diffuse in to other tissues that do not
have such a richblood supply(e.g Skeletal muscle)
10. This secondary tissue uptake,causes the plasma
concentration to fall,allowing drug to diffuse out of the CNS
down the resulting reverse concentration gradient
This initial REDISTRIBUTION-leads to the rapid wake up
seen after a singledose of an induction drug
Metabolism and plasma clearance have a much less
important role following a single bolus,but are more important
following infusions and repeat doses of a drug.
11. Drug distribution in various tissues against time
following an i.v bolus of thiopental
12. How is this different in states of reducedcardiac
output?
When cardiac output is reduced(Shock,Elderly)the body compensates by
diverting an increased proportion of the cardiac output to the cerebral
circulation,as preservation of cerebral blood flow in these situations is
important.
A greater proportion of any given drug will enter the cerebral circulation
As a result,the dose of induction drug must always be reduced.
Since global cardiac output is reduced,the time taken for an induction drug
toreach the brain and exert its effect is prolonged*
Key to SAFE INDUCTION:SLOW titration of a REDUCED dose of drug
13. Properties of an IDEAL induction agent
Physical properties
Water soluble & stable in solution
Stable on exposure to light
Long shelf life
No pain on intravenous injection
Painful when injected into an artery
Non-irritant when injected subcutaneously
Low incidence of thrombophlebitis
Cheap
14. Pharmacokinetic properties
Rapid onset in one arm-brain circulation time
Rapid redistribution to vessel rich tissue
Rapid clearance and metabolism
No active metabolites
15. Pharmacodynamic properties
High therapeutic ratio(ratio of toxic dose:minimally effective dose )
Minimal cardiovascular and respiratory effects
No histamine release/hypersensitivity reactions
No emetic effects
No involuntary movements
No emergence nightmares
No hang over effect
No adrenocortical suppression
Safe to use in porphyria
16. Classification
The commonest drugs currently in use can be classified according to
theirchemical structure and include:
Barbiturates-THIOPENTAL,METHOHEXITAL
Phenols -PROPOFOL
Imidazoles -ETOMIDATE
Phencyclidines -KETAMINE
Benzodiazepines-MIDAZOLAM,DIAZEPAM,LORAZEPAM
Others-Dexmedetomidine
17. They can also be classified based on the onset of their action as:
Rapidly acting(within one arm brain circulation time)-
Thiopentone,Propofol,Etomidate
Slow acting (those that take longer than one arm-brain circulation
time)-Ketamine,Midazolam
18. EXTRA POINTS
α half life denotes time taken to redistribute the drug from central
compartment to peripheral tissues.
β-half-life denotes redistribution of the drug from the muscle group to less
vascular tissues.
γ-half life denotes elimination of the drug from the body.
The patient wakens from anaesthesia when the plasma concentration
reduces at the end of alpha half life even though it is not eliminated from the
body.
20. PROPOFOL
Chemical Structure-2,6 Di isopropyl phenol
Availablity-Single-patient use vials of 200 mg of propofol per 20 mL,500 mg
of propofol per 50 mL
1 or 2%aqueous emulsion(tiny fat droplets in suspension,hence the white
colour)
Highly lipid soluble Contains-
10%Soybean oil,
1.2%Egg Lecithin and
2.25%Glycerol(an osmotic agent)
21. Propofol
The emulsion is an excellent medium for bacterial growth
EDTA or Sodium Benzoate are added to impede bacterial growth
Propofol causes pain in injection
PROPOFOLLIPURO-preparation of propofol containing both long &medium
chain triglycerides in 1:1 ratio.Reduces pain on injection
FOSPROPOFOL-A water soluble methylphopshorylated prodrug of propofol
No Pain on injection.But slow onset of action
22. Propofol
Physicochemical &pharmacokinetic properties
pKa-11
Volume of distribution-4.6 L/Kg
Clearance-25 ml/Kg/min
Protein binding-98%
Water solubility-No
pH 7.0-8.5
23. Propofol
Mechanism of action-Activation of chloride channels of GABA receptors
thus enhancing inhibitory synaptic transmission.It also inhibits NMDA
subtypeof glutamate receptors.
Onset of action-One arm brain circulation time(15 -20 seconds)
Duration of action-3 to 5 min when given i.v
Half life:
a half life-3-5 min
β half life-20-50 min
y half life-200-500 min
24. Propofol
Context sensitive half time:Appox.10 minutes when infused
for less than 3 hours &less than 40 minutes when infused for
upto 8 hours
Elimination:Propofol is metabolized by conjugation to
glucuronide&sulfate by liver.
Propofol also undergoes Extra hepatic metabolism in
kidneyand lungs (30%)
25. PROPOFOL:Effects on the body
CNS:Dose dependent depression of CNS
End point for induction-Loss of response to verbal
commands
Can be used an anti-convulsant
Reduces Cerebral metabolic rate
Reduces Cerebral blood flow through auto-regulation
Reduces Intracranial pressure
Can cause some involuntary movements during induction
26. PROPOFOL
CVS:Causes hypotension due to peripheral vasodilatation
The fall in blood pressure is dose dependent and is most
marked in theelderly and in shocked patients.
This can be minimized by slow injection-avoiding inadvertent
overdose.
RS:Causes transient apnea
Obtunds airway reflexes well
GIT:Propofol has antiemetic properties
27. Propofol:Uses,Dose &Route
Induction of anaesthesia:2-2.5 mg/Kg in adults;2.5-3 mg/Kg in children
Maintenance of anaesthesia:At a dose of 50-150μg/Kg/min
Conscious sedation:@50-75μg/Kg/min
Sole anaesthetic for short procedures e.g.Cardioversion
Very useful in Day care anaesthesia and surgery
Useful in patients susceptible to Malignant hyperthermia
Can be used as an Anticonvulsant
28. PROPOFOL
Total intravenous anaesthesia (TIVA):A plasma concentration of 2.5 to
8μg/ml is required.
This can be achieved as follows-1 mg/Kg bolus→10 mg/kg/hr for 10 min —
8mg/kg/hr for next10 minutes6 mg/kg/hr thereafter.→
This is expected to give a plasma conc.of propofol of 3 μg/ml.
Sedation of critically ill patient in ICU:1-3 mg/kg/hr.
Can also be used as antipruritic &antiemetic:10-20 mg boluses every 5-10
minutes
Safe in patients susceptible to porphyrias.
29. PROPOFOL:Adverse effects &Caution
Hypotension
Allergic reaction to Egg protein
Pain on injection(can be reduced with lignocaine 20 mg added to 20ml )
Caution in patients who are hypovolemic
Susceptible to growth of micro-organisms:Tubings and unused propofol
injectable emulsions should be discarded after 12 hours.
Can cause involuntary epileptiform movements.
30. Propofol Infusion Syndrome
Occurs due to prolonged infusion in small children and infantsUsually when
used in excess of 4 mg/kg/hr for>48 hours
Propofol interferes with mitochondrial mechanisms
Features:METABOLIC ACIDOSIS,hyperkalemia,RHABDOMYOLYSIS,Renal
failure,hepatomegaly,cardiac failure(RBBB &asystole)Hyperlipidemia.
Management:Cardiorespiratory support
Hemodialysis.
31. BARBITURATES
Barbiturates-broadly classified as
a)Thiobarbiturates:Sulphur at C2 e.g.Thiopental,thiamylal
b)Oxybarbiturates:Oxygen at C2 e.g.Methohexital
Formulated as racemic mixtures of their water soluble sodium salts
Use“Sodium carbonate”to maintain alkaline pH 10-11
High alkalinity-Severe tissue damage (intra arterial injections)
Precipitation of drugs that are weak bases(vecuronium)
32.
33. Thiopentone Sodium
Ultra-short acting barbiturate
Available as Hygroscopic,pale YELLOW powder
Ampoules commonly contain-500mg or 1000mg of sodium thiopental +
6%sodium carbonate in an inert atmosphere of nitrogen.
(to prevent precipitation of insoluble acid form of barbiturate by atmospheric CO2)
Reconstituted with 20ml of water-2.5%solution(25mg/ml)with a pH of 10.8.
The alkaline solution is bacteriostatic and safe to keep for 48 hours
34. Thiopentone Sodium
Mechanism of action:
Mainly through interaction with inhibitory neurotransmitter-GABA in CNS
GABAA receptor has 5 glycoprotein subunits
Activation of GABAA receptor
Increase in transmembrane Chloride channel conductance
Hyperpolarization of post-synaptic neurons
“FUNCTIONAL INHIBITION OF POST-SYNAPTIC NEURONS”
35. Thiopentone Sodium-Uses &Dose
Always given intravenously (i.v)
Can be given through rectal route for sedation,but
theabsorption is erratic.
For induction of anaesthesia:4-5 mg/Kg in adults.
Children require slightly higher doses (5-6 mg/Kg)due to
larger volume of distribution(Vd)
36. Thiopentone Sodium-Uses &Dose
Status Epilepticus-Single bolus of 3-5 mg/Kg to treat an
episode ofconvulsion f/b INFUSION(3-5mg/Kg/hr)in status
epilepticus refractory to conventional treatment.
Cerebral protection-Bolus of 3 mg/Kg followed by an
infusionof 5-6 mg/Kg/hr to protect ischemic brain in
neurosurgical patients
37. Thiopentone Sodium
Onset of action:One arm-brain circulation time (15-20 sec)
Duration of action:
a Half life -10 min
β Half life -45 min
γ Half life -6-20 hrs
Elimination:Metabolized by LIVER &excreted by KIDNEY
Clearance:3.4 ml/Kg/min
Volume of distribution:2.5 liters/Kg
38. Thiopentone Sodium
Following repeated doses or infusions of thiopental,metabolism follows
zero order kinetics i.e.,a constant amount of drug is being eliminated per
unit time,irrespective of the plasma concentration.
Some drugs are metabolized by frst order kinetics;a constant fraction of
drug is eliminated per unit time,i.e.dependent on plasma concentration.
Zero order kinetics occur when the metabolic pathways become saturated
leading to an accumulation of the active drug and delayed recovery
39. Effects on Body
Central Nervous System:
Dose dependent depression of CNS
End point of induction-Loss of"EYELASH REFLEX"
Reduces CMRO2&CBF thereby reducing ICP
It is a potent anti-convulsant
It is an ANTANALGESIC-decreases the threshold to pain
40. Effect on body
Cardiovascular system:
Causes Hypotension due to peripheral vasodilatation
Causes increase in Heart rate -Baroreceptor reflexmediated
sympathetic stimulation
Higher doses have negative inotropic effect &should be used
with caution in hypovolemic and IHD patients
41. Effect on body
Respiratory system:
Causes transient apnea
Produces dose dependent decrease in both tidal volume &minute
ventilation
The medullary center ventilator responses to both hypoxia
&hypercapnia are reduced
May not obtund airway reflexes well-hence unsuitable for use while
inserting an LMA(can cause coughing &laryngospasm)
Histamine release can occur-can precipitate bronchospasm
42. Thiopentone-Adverse effects
Inadvertent intra-arterial injection of thiopentone-causes intense
spasm
of the artery &therefore must be avoided.If occurs,
a)Stop further injection but keep cannula in place
b)Inject saline into the cannula &flush it
c)Inject through same cannula,preservative free LIGNOCAINE to reduce
pain,PAPAVERINE 40-80 mg to provide local vasodilatation,HEPARIN to
preventthrombus formation
d)Stellate ganglion block or brachial plexus block to achieve
sympatholysis if intensepain &if tissue perfusion is in jeopardy.
43. Thiopentone-Adverse effects
Thiopentone is contraindicated in Patients with PORPHYRIAS
Stimulation of mitochondrial enzyme-“δ Amino levulinic acid
Reductase”,the rate limiting enzyme in porphyrin biosynthesis,can
exacerbate AIP(Acute intermittent porphyria)
Manifestations:
1.Abdominal pain
2.Psychiatric symptoms like hysteria
3.Motor neuropathies.
4.CNS symptoms like seizures,mental status changes,cortical
blindness &coma
44. Thiopentone-Adverse effects
Thiopentone should be avoided in patients with sulpha drug
allergy
Extravasation of thiopentone at i.v site can cause local tissue
destruction
Thiopentone can be used safely in cesarean deliveries
But doses greater than 8 mg/Kg can cause neonatal
depression due to placental transfer of the drug
45.
46. Etomidate
Chemical Structure-Carboxylated IMIDAZOLE ester.
Weak Base &poorly water soluble
Formulated as a Hyperosmotic solution in 35%Propylene glycol*
Prepared as pharmacologically active R(+)isomer
Available as lipid emulsion 10ml at a conc.of 2mg/ml
Pain on injection is common and there is a high rate of thrombophlebitis in the
post operative period.
47. Etomidate
Mechanism of action:Activation of Chloride channels ofGABAA
receptors
Enhancing inhibitory synaptic transmission
Onset of action: One arm-brain circulation time (15-20 sec)
Duration:3-5 minutes when given i.v
Dosage:For induction of anaesthesia 0.2-0.4 mg/Kg i.v
48. Etomidate : Effects on the body
CNS: Dose dependent depression of CNS
Can produce involuntary movements during induction.
Recovery is RAPID due to REDISTRIBUTION.
CVS:IV agent with LEAST cardiovascular depression
Only small reduction in BP&HR-very CARDIOSTABLE Used in
shock,elderly and cardiovascularly compromised patients.
49. Etomidate : Effects on the body
RS: Transient apnea occurs with induction doses.
Can cause cough or hiccups. Hence not ideal for insertion of
supraglottic airway devices*
GIT: Increased incidence of Nausea &Vomiting
Metabolized by hepatic and plasma esterase to yield inactive
metabolites.
Excretion is predominantly urinary and the elimination half life varies
from 1-5 hours.
50. Etomidate : Adverse effects
Pain on iniection & Thrombophlebitis
Recovery is frequently unpleasant and accompanied by nausea and vomiting
Adreno-cortical suppression
Etomidate inhibits 11-β-hydroxylase, an enzyme important in adrenal steroid
production. A single induction dose blocks the normal stress-induced increase in
adrenal cortisol production for4-8 hours, and up to 24 hours in elderly and
debilitated patients.
Continuous infusion of etomidate for sedation in critically ill patients has been
shown to increase mortality.
No increase in mortality has been identified following a single dose during induction
of anesthesia.
51.
52. KETAMINE HYDROCHLORIDE
Chemical Structure-Phencyclidine derivative
AVAILABILTY: vials containing 10 mg/ml&50 mg/ml
Preservative free ketamine is available for use for Central neuraxial
blockade.
Produces DISSOCIATIVE ANAESTHESIA-dissociation between
thalamocortical & limbic systems
Dissociative anaesthesia resembles a cataleptic state in which the eyes
remain open with a slow nystagmus gaze.
53. Structure activity relationships
Presence of asymmetric carbon atom results in the existence of two
OPTICAL ISOMERS of ketamine: S(+)&R(-)forms.
Most frequently used preparation of ketamine -Racemic mixture
S(+)ketamine produces (when compared to R(-)form):
a)More intense analgesia
b)More rapid metabolism &thus recovery
c)Less salivation
d)Lower incidence of emergence reactions
Preservative used -BENZETHENIUM CHLORIDE
54.
55. Mechanism of action:
a)Inhibits N-methyl-D-aspartate (NMDA)receptors which have been activated
by Glutamate,an excitatory neurotransmitter.
b)Also inhibits SEROTONIN &MUSCARINIC receptors
c)It is an agonist of μ type of opioid receptors
Onset of action:30-60 sec when given i.v,5 min when given i.m&25-45 min
when given orally
Duration of action:10-15 min when given i.v(a half life-10-15 min, γ half life-2-
3 hours)
KETAMINE HYDROCHLORIDE
56. Induction of anaesthesia:1-2 mg/Kg.
Particularly useful in a)Bronchial asthma- Bronchodilatory effect
b)Tetralogy of fallot- Maintains SVR(systemic vascular resistance)
c)Hypovolemic patients.
Analgesia:0.5 mg/Kg bolus followed by infusion @3μg/Kg/min*
Premedication:I.m-3-5 mg/Kg(onset time-5 min),Nasal-3-6 mg/Kg(onset
time-5 min),Orally-3-10 mg/Kg(onset-20-45 min)
KETAMINE :Uses,Dose &Route
57. As a Bronchodilator: for treatment of Status asthmaticus @30-
40μg/Kg/min
As a sole anesthetic for short procedures-Can be given as infusion
@15-45μg/Kg/min with 50%Nitrous oxide
@30-90 μg/Kg/min without Nitrous oxide
POINTS TO REMEMBER WITH USE OF KETAMINE:
*Ketamine can produce “Hallucinations &Increase in secretions” Hence
ketamine administration should be preceded by a benzodiazepine like
midazolam &an anti-sialo gogue like Glycopyrrolate.
KETAMINE :Uses,Dose &Route
58. Central Nervous system:
Produces "Dissociative anaesthesia“ resembling a cataleptic state.
Causes Functional &Electrophysiological dissociation of Thalamocortical
system(depressed)from Limbic system(stimulated).
This produces intense analgesia &amnesia as the sensory impulses from the
body do not reach the cortex.
Increases CMRO2,CBF and thereby increases Intracranial pressure. Also
increases the intraocular pressure.
KETAMINE :Effects on the body
59. Cardiovascular system:DUAL EFFECT
a)HYPERTENSION &TACHYCARDIA-by indirect stimulation of
sympathetic system causing release of catecholamines.
b)In larger doses or patients with depressed sympathetic system, can
cause hypotension due to direct myocardial depression
Respiratory system: Very good BRONCHODILATOR, But does not
obtund airway reflexes well.
GIT: Increases secretions especially Salivary &bronchial
KETAMINE :Effects on the body
60. Hallucinations : also called “Emergence reactions”
Occur due to ketamine induced depression of auditory and visual
relay nuclei, leading to misperception/misinterpretation of auditory
and visual stimuli.
Muscle rigidity due to increased muscle tone
Hypertension and tachycardia.
KETAMINE :Adverse effects
61.
62. Midazolam Hydrochloride
Chemical Nature-Water soluble Benzodiazepine with an IMIDAZOLE ring in its
structure, that accounts for stability in aqueous solutions & rapid metabolism.
The solubility of midazolam is pH dependent.
At pH 3.5,imidazole ring is open →WATER SOLUBLE.
At body pH imidazole ring closes
LIPID SOLUBLE →RAPID ONSET
Availability:5 ml vials containing 1 mg/ml&1 ml ampoules containing 5 mg/ml*
It doesn't cause pain on injection.
63.
64. Midazolam Hydrochloride
Mechanism of action: Activation of Chloride channels of GABA receptors
enhancing inhibitory synaptic transmission.
Onset of action:30-60 seconds
Duration of action:1 hour when given i.v
*Elimination: Metabolized in liver by hydroxylation &conjugation,
The metabolite “HYDROXYMIDAZOLAM” has no clinically significant side
effects.
65. Midazolam : Uses,Dose &Route
Induction of anesthesia:0.1-0.2 mg/Kg intravenously
Commonly used to supplement to regional anesthesia for SEDATION
For PREMEDICATION: Midazolam is given in a dose of 0.5 mg/Kg
ORALLY,upto a maximum dose of 10 mg,to easily separate children from
parents. This is usually possible in 15 to 30 minutes
Popular drug for sedating critically ill patients in the ICU as it is
cardiostable.
Also used as an ANTICONVULSANT
66. Midazolam : Effects on the body
CNS: Dose dependent depression of the CNS*
CVS: Relatively CARDIOSTABLE
Doesn't affect Heart rate and Blood pressure much
RS: doesn't produce change in respiration at usual doses
CAUTION: To be used with caution in patients with
HYPOVOLEMIA as it may aggravate hypotension
67. Flumazenil
Competitive benzodiazepine antagonist
*Available in vials containing 0.1 mg/ml Usually given
in 100 μg boluses
Onset of action:2 min
Duration: about an hour
Adverse effects: Nausea, Vomiting, Agitation,
seizures.
68. Dexmedetomidine
Dexmedetomidine is a potent a2 adrenergic agonist.
It is shorter acting than clonidine and much more selective for a2 vs. a1
receptors (dexmedetomidine 5 1620:1; clonidine 220:1).
MECHANISM OF ACTION-
One of the highest densities of a2receptors is located in the pontine locus
ceruleus, an important nucleus mediating sympathetic nervous system
function, vigilance, memory, analgesia, and arousal.
The sedative effects produced by dexmedetomidine are largely due to
inhibition of this nucleus.
69. Dexmedetomidine
Dexmedetomidine, acting on a2 receptors, produces sedation by decreasing
sympathetic nervous system activity and the level of arousal.
The result is a calm patient who can be easily aroused to full consciousness.
Available forms-Dexmedetomidine 50mcg/0.5ml, 100mcg/ml and 200mcg/2ml
70. Dexmedetomidine
Pharmacokinetics
Elimination half-time of dexmedetomidine is 2 to 3 hours
Dexmedetomidine is highly protein bound (.90%) and undergoes extensive
hepatic metabolism.
The resulting methyl and glucuronide conjugates are excreted by the
kidneys.
71. Dexmedetomidine
CLINICAL USES-
Pretreatment with dexmedetomidine
attenuates hemodynamic responses to tracheal intubation, decreases plasma
catecholamine concentrations during anesthesia, decreases perioperative
requirements for inhaled anesthetics and opioids, and increases the likelihood
of hypotension.
72. Dexmedetomidine
Decreases inhalational MAC
In Patients isoflurane MAC was decreased 35% and 48% by dexmedetomidine
plasma concentrations of 0.3 ng/mL and 0.6 ng/mL, respectively
Despite marked dose-dependent analgesia and sedation produced by this
drug, there is only mild depression of ventilation.
73. Dexmedetomidine
Dexmedetomidine in high doses (loading dose of 1 mcg/kg IV followed by 5 to
10 mcg/kg/hour IV) produces total IV anesthesia without associated depression
of ventilation.
The preservation of breathing provides a potential anesthetic technique for
patients with a difficult upper airway.
Addition of 0.5 mcg/kg dexmedetomidine to lidocaine being administered to
produce IV regional anesthesia improves the quality of anesthesia and
postoperative analgesia without causing side effects.
Severe bradycardia may follow the administration of dexmedetomidine and
cardiac arrest has been reported in a patient receiving a dexmedetomidine
infusion as a supplement to general anesthesia.
74. Dexmedetomidine
Postoperative Sedation
Dexmedetomidine (0.2 to 0.7 mg/kg/hour IV) is useful for sedation of postoperative
critical care patients in an ICU environment, particularly when mechanical ventilation
via a tracheal tube is necessary.
dexmedetomidine infusions do not result in clinically significant depression of
ventilation and sedation exhibits some similarity with natural sleep.
Tracheal extubation, dexmedetomidine-sedated patients breathe spontaneously and
appear calm and relaxed.
Because of its sympatholytic and vagomimetic actions, dexmedetomidine may be
accompanied by systemic hypotension and bradycardia.
75. References
Robert K.Stoelting,Simon C Hillier. Pharmacology and
physiology in anesthetic practice.5th Edition.
Morgan &Mikhail's Clinical Anesthesiology.5th Edition.
Ronald D Miller,Elske sitsen,Marije reekers Intravenous
Anesthetics.8th edition.
