INTRAVENOUS INDUCTION AGENT by Dr Deepak kalyani hospital


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Dr deepak nirwal Kalyani hospital kiratpur bijnor up


By: vinijoshi22 (77 month(s) ago)


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CONTENT 12/12/2013 2


HISTORY WILLIAM HARVEY describe the complete and continuous intravascular circuit in 1628. ALEXANDER WOOD invented a hollow needle and glass syringe in 1855. In 1872 PIERRE ORE’ perform first intravenous surgical anaesthesia by injecting chloral hydrate ADOLF VON BAEYER discovered first barbiturate , barbituric acid in 1864. 12/12/2013 3


HISTORY 12/12/2013 4



What are i.v. induction agent ?:

What are i.v. induction agent ? Agent cause a rapid reversible loss of consciousness. TIME :- “one arm-brain (A→B)circulation time” this time also depend on cardiac output and ejection fraction . normal A → B circulation time is 15-20 sec. They are used: To induce anaesthesia prior to other drugs being given to maintain anaesthesia. To maintain anaesthesia for longer procedures by intravenous infusion. To provide sedation. Use for day care / short / opd procedure . 12/12/2013 6

what happens to a bolus of IV induction drug ? from induction to wake up: -:

what happens to a bolus of IV induction drug ? from induction to wake up: - 12/12/2013 7


CARDIAC OUTPUT DISTRIBUTION ORGAN PERFUSION % CARDIAC OUTPUT ML/MIN 1. Coronary 5 250 2. Cerebral 15 750 3. Splanchnic 25 1250 4. Renal 22 1100 5. Cutaneous 8 400 6. Muscular 17 850 7. Other regions 8 400 Total Systemic Circ. 100 5000 C0 % T. B. WT % VRG 75 9 MUSCLE 18 50 FAT 5 19 12/12/2013 8



PowerPoint Presentation:

12/12/2013 10 Single bolus continuous infusion pharmacokinetics

induction dose depend on :

induction dose depend on Several factors :- Route of administration Age ( ↓ with age ) Lean body mass ( fat free ) (muscular > fatty ) ↓ in low cardiac output state( body compensate to accordingly to maintain cerebral perfusion ) ↓ in Hypoprotenemia ( nutritional, nephropathy , PIH ) 12/12/2013 11

PowerPoint Presentation:

12/12/2013 12


IDEAL ANAESTHETIC PROPERTIES Rapid onset and offset Analgesia at subanesthetic dose Minimal cardio respiratory depression No emetic effect No excitatory and emergence phenomenon No interaction with N-M blocking agent No pain on injection No venous squealae ( venous thrombosis) No toxic effect on other organs No release of histamine ( bronchospasm ) Water soluble formulation and long self life No hypersensitivity No stimulation of porphyria No adrenocortical suppression 12/12/2013 13

How do they work?:

How do they work? Major inhibitory Neuro-transmitter in the CNS = GABA Active GABA A receptor => Cl - influx => Hyperpolarisation Propofol & barbiturates slow GABA A receptor dissociation Benzodiazepines increase GABA A to receptor coupling Ketamine acts at NMDA receptor These effects lead to sedative & hypnotic effects 12/12/2013 14


Pharmacodynamics Increasing dose => sedation => hypnosis All iv anesthetics affect other organ systems Potential for respiratory depression Potential for CVS depression Potential for altered CBF/ICP Hypovolemia => severe hemodynamic effects seen due to decreased blood pool Use lower doses! 12/12/2013 15



SODIUM THIOPENTAL (STP) ralph and lundy:

SODIUM THIOPENTAL (STP) ralph and lundy Rapid onset and rapid offset , no excitatory effect . Yellow amorphous powder , in atmosphere of nitrogen Diluted to 2.5 % solution ,can be stored for 48 hr ↓refrigerator , Concentration >5 % cause pain Highly Alkaline pH 10.5, contain 6 % NaHCO3 ↓ in alkalinity cause ppt of solution , so avoid to dilute in acidic solution , RL . Co-adm of vec, atra , midaz , alfentanil form ppt in I.V. line and occlude the vein . 12/12/2013 17

PowerPoint Presentation:

Main Effects DOSE :- 3-5 mg/kg effective plasma conc. 15µg/ml. Drug Induction Dose (mg/kg) * † Onset (sec) Intravenous Maintenance Infusion Thiopental in adult 3-4 mg/kg 10-30 sec 50-100 mg every 10-12 min Children 5-6 mg / kg 10- 20 sec 12/12/2013 18

Sodium thiopental effect on central nervous system :

Sodium thiopental effect on central nervous system 12/12/2013 19


CNS 12/12/2013 20 Act on GABA a receptor lead to Cl influx – hyperpolarisation of cell membrane - ↑threshold of excitability of post synaptic neuron . This is highly lipid soluble drug cross BBB – fast onset of axn AT plasma pH around 50 % unionized drug ; in acidosis condition unionized % ↑; dose requirement ↓ Dose dependent↓ CBF, ↓ ICP, ↓ CMRO 2 CPP= (MAP-ICP ) but { ↓ICP > ↓MAP } ; CPP preserve

CNS effect (dose and rate of inj dependent):

CNS effect (dose and rate of inj dependent) 12/12/2013 21 Sedation and loss of consciousness retrograde amnesia and depression of vasomotor centre. Induction and maintenance of anaesthesia Rate of adm α onset Termination of effect take 5-10 min to awake ( after bolus ) Awakening depend on :- Volume of distribution Plasma concentration Redistribution and Clearance Alteration in metabolism CNS sensitivity ↑ with age


CNS 12/12/2013 22 Pupil and eye :- initially pupil contract but then dilate . Pupillary response is lost with surgical anaesthesia .loss of eyelash reflex is commonly used as endpoint for adequate induction dose . Following traumatic brain injury, infusion of thiopental to produce a “barbiturate coma” lowers intracranial pressure and may improve neurological outcome. Anticonvulsant property Thiopental have no analgesic action and may be antianalgesic in low dose . Burst suppression of EEG can be induced with high doses when used in treatment of status epilepticus or intractable rise in ICP following head injury .

IOA with STP:- rapid onset and rapid offset :

IOA with STP:- rapid onset and rapid offset 12/12/2013 23

Management of Intra arterial injection of thiopental :

Management of Intra arterial injection of thiopental Stop injection immediately ,leave the canula insitu , and dilute with immediate inj of saline Give intra-arterial inj of LA + vasodilator Lidocaine 50 mg ( 5 ml of 1 %) + phenoxybenzamine ( α blocker)0.5 mg bolus or 50-200 µg/min infusion. Consider systemic papaverine 40-80 mg Consider sympathetic block ( brachial plexus block or stellate ganglion block ) Start i.v heparin infusion Give intra arterial hydrocort Postpone surgery Consult vascular surgeon 12/12/2013 24


REDISTRIBUTION 12/12/2013 25




CVS 12/12/2013 27 First effect dose dependent peripheral vasodilatation - ve inotropic effect - ↓ Ca to myocardial fiber ↓BP ↓ CO (↓venous return , vasodilatation, -ve inotropic effect , ↓CNS symp outflow ) Tachycardia ( 10-36 %) Via baroreceptor mediated symp reflex in response to ↓ CO & BP CAD patient on induction ↑HR - ↑myocardial demand of O2 ECG changes :-prolonged QT , flattened T wave ,vent arrhythmia eg - acidotic patient ,long term dialysis , Cirrhosis




RESPIRATORY SYSTEM :- 12/12/2013 29 Dose related resp depression ,peak resp depression after (1-1.5 min) after adm of bolus dose . More susceptible patient ch lung disease , Airway obst Apnea :- transient apnea for 25 sec only in 20 % cases. Double apnea :- 1 st during adm of drug > transient >after 4-5 breath 2 nd apnea last for longer period .during this period ventilation must be assessed – controlled ventilation . ↓minute ventilation , ↓ sensitivity to raised CO2 Airway reflexes preserved not suitable for LMA insertion ,may cause coughing and laryngospasm C/I in St. asthmaticus


STP IN OBS 12/12/2013 30 When choosing an induction agent, the primary goals are as follows: (1) to preserve maternal blood pressure, cardiac output, and uterine blood flow; (2) to minimize fetal and neonatal depression; and (3) to ensure maternal hypnosis and amnesia.


STP IN OBS 12/12/2013 31


STP INDICATION CONTRAINDICATION IOA Control convulsive state ↓ ICP neuroprotection Absolute contraindication COPD Severe asthma Porphyria Previous hypersensitivity Allergic to sulphur Precaution stenotic valvular Disease Severe hepatic disease Renal impairment 12/12/2013 32


THIOPENTAL ADVANTAGE :- Rapid induction Don’t sensitize myocardium to adrenaline No nausea and vomiting Other uses Anticonvulsant In psychiatric patient Narcoanalysis DISADVANTAGE :- Pharyngeal and laryngeal reflex persist →apnea – controlled ventilation Resp depression Hypotension Poor analgesic and muscle relaxant Gangreen and necrosis Shivering and delirium 12/12/2013 33

KETAMINE HCl 1965 (corseen & domino ):

KETAMINE HCl 1965 ( corseen & domino ) 12/12/2013 34 2 isomer S (+) & R(-) , S is 3 times more potent


KETAMINE 12/12/2013 35 Ketamine is a phencyclidine derivative Rapid onset 30-60 sec ; high lipid soluble ( 5× thiopental ) Hypnosis ,amnesia Dissociative anaesthesia , intense analgesic ( SOMATIC > VISCERAL ), ,rapid clearance Cardio stimulation property Minimal effect on resp system Sympathomimetic effect IOA choice for ASA – IV and hemodynamic compromised state the possibility of emergence delirium limits the clinical usefulness of ketamine. Ketamine has advantages over Propofol and etomidate in being water soluble


MOA OF KETAMINE NMDA Receptors antagonist :- Opioid Receptors:- Muscarinic Receptors:- The fact that ketamine produces anticholinergic symptoms (emergence delirium, Bronchodilation, sympathomimetics action) suggests that an antagonist effect of ketamine at muscarinic receptors is more likely than an agonist effect. Sodium Channels:- Consistent with its mild local anesthetic-like properties, ketamine interacts with voltage-gated sodium channels sharing a binding site with local anesthetics. 12/12/2013 36


DOSES PURPOSE DOSE Induction of general anesthesia * 0.5-2  mg/kg IV 4-6  mg/kg IM Maintenance of general anesthesia 0.5-1 mg/kg IV with N 2 O 50% in O 2 15-45  µg/kg/min IV with N 2 O 50-70% in O 2   30-90 µg/kg/min IV without N 2 O Sedation and analgesia 0.2-0.8 mg/kg IV over 2-3 min   2-4 mg/kg IM Preemptive/preventive analgesia 0.15-0.25 mg/kg IV Intra thecal ketamine 0.5-0.75 mg/kg 12/12/2013 37

PowerPoint Presentation:

Simulated time course of plasma levels of ketamine after an induction dose of 2 mg/kg. Plasma levels required for hypnosis and amnesia during surgery are 0.7 to 2.2 µg/mL, with awakening usually occurring at levels less than 0.5 µg/ mL. THERAPEUTIC RANGE Action last for 10-15 min Therapeutic range in adult (2.2-0.7 µg/ml) In children (0.8 to 4 µg/mL). 12/12/2013 38

IOA with ketamine :

IOA with ketamine 12/12/2013 39

CNS effect of Ketamine:

CNS effect of Ketamine 12/12/2013 40

CNS effect with ketamine :

CNS effect with ketamine 12/12/2013 41 ↑CMRO2, ↑ ICP(d/t ↑symp tone ), ↑ IOT, ↑ CBF (↑CBF> ↑CMRO2) Dissociative anaesthesia ( cataleptic state ) Corneal , cough , swallow reflex +nt Amnesia not prominent as compare with BZD ↑muscle tone , purposeless movement , Ө wave on EEG , petit mal type seizure activity in hippocampus Primary site of axn in CNS thalamoneocortical projection syst . Depress cortical and thalamus function Stimulate limbic and hippocampal function


EMERGENCE EFFECT :- 12/12/2013 42 Associated with vivid dreaming , sense of floating of body, illusion , ext sensory experience , excitement , confusion , euphoria , fear . Occur with ketamine due to depression of auditory and visual relay nuclei . The loss of skin and musculoskeletal sensations results in a decreased ability to perceive gravity, thereby producing a sensation of bodily detachment or floating in space. These feature last for 1 hr Factor affecting emergence reaction Age ( adult > child ) Gender( female > male ) Dose (↑) Concurrent drug ( BZD priming 5 min before ketamine ) Preop counseling


EMERGENCE EFFECT 12/12/2013 43




CARDIO-VASCULAR SYSTEM 12/12/2013 45 Sympathomimetic action ↑BP, ↑HR , ↑ CO ↑ SBP is 20 to 40 mm Hg, with a slightly increase in DBP, increases progressively during the first 3 to 5 minutes after an intravenous injection of ketamine and then decreases to predrug levels over the next 10 to 20 minutes. ↑ myocardial O2 demand – provided by adequate CO &↓ coronary vascular resistance . These effect are more apparent in 1 st bolus dose than 2 nd dose . Ketamine ↑ pul artery pressure – caution use in left side stenotic valvular lesion . Tachycardia and hypertension by ketamine can be prevented by premedication with BZD or continuous inhalational agent Cautiously use in IHD Useful in pt of cong heart Ds even in whom propensity for R-L shunt exist




RESP….. 12/12/2013 47 Min effect on central resp drive Transient (1-3 ) min ↓ in minute ventilation Large dose produce apnea Bronchial muscle relaxant { when given in patient of bronchospasm – pul compliance increased } Bronchodilation make this a potentially useful drug for the rapid intravenous induction of anesthesia in patients with asthma. Ketamine as effective as halothane Resp problem in children are due to ↑ secretion ( salivation )-cause upper airway obstruction – laryngospasm Increase pul artery pressure Preserve cough and upper airway reflex so not useful with LMA


KETAMINE IN OBS 12/12/2013 48 When choosing an induction agent, the primary goals are as follows: (1) to preserve maternal blood pressure, cardiac output, and uterine blood flow; (2) to minimize fetal and neonatal depression; and (3) to ensure maternal hypnosis and amnesia.


KETAMINE IN OBS 12/12/2013 49


KETAMINE ADVANTAGE increase HR,BP,CO In asthmatic For short procedure Combination with BZD can use in cardiac catheterization and angiography . In OPD surgical procedure Good analgesic property DISADVANTAGE limb movement and Nystagmus Emergence phenomenon in 50 % Hypertensive Increased ICP , IOT , Uterine stimulation Schizophrenia , psychosis Poor muscle relaxation 12/12/2013 50


KETAMINE INDICATION CONTRAINDICATION 12/12/2013 51 CVS except IHD and Resp disorder Hemodynamic compromised ( pericarditis , cardiac temponade , CM , shock ) Traumatic and septic shock As component in TIVA with midaz and propofol provide better hemodynamic stability In cancer patient , neuropathy Phantom or ischaemic limb pain Fibromyalgia , visceral pain Migraine ↑ ICP , SOL brain Large size Infarct Ophthalmic injury IHD Vascular aneurysm Schizophrenia

PROPOFOL kay and rolly in 1977:

PROPOFOL kay and rolly in 1977 12/12/2013 52

Propofol :

Propofol 12/12/2013 53 Most frequently use I.V. anaesthetic drug today Milky white ; pH 7.0 - 8.5 ; isotonic to plasma Fospropofol prodrug Stable at room temp ; not light sensitive Dilution :- water insoluble ; compatible in DNS Dilution cause cracking of emulsion , spontaneous degradation Concern regarding microbial growth in emulsion – disodium edetate (0.005%) added to retard the bact. growth Sedation in and outside of OT Concern regarding induction and emergence myoclonic ,jerk Painful injection in small vessel take care of it .

PROPOFOL 2,6 –di-isopropylphenol :

PROPOFOL 2,6 –di-isopropylphenol Rapid onset 15-45 sec and offset , rapid offset even after prolonged infusion ( small context sensitive half time ) Metabolize in liver with Glucuronide and sulfate conjugation . Extra hepatic metabolism + lung ; inactive metabolite Mainly excreted by kidney Propofol causes the most marked fall in blood pressure of all the induction drugs. This is mainly due to systemic vasodilatation. There may be an accompanying slight increase in heart rate. The fall in blood pressure is dose dependent and is most marked in the elderly and in shocked patients. This can be minimized by slow injection – avoiding inadvertent overdose. 12/12/2013 54

PROPOFOL effect after single bolus dose :

PROPOFOL effect after single bolus dose 12/12/2013 55

Context(duration)-sensitive Half-Time:

Context(duration)-sensitive Half-Time Time required for central compartment blood concentration to fall by half as a function of the duration of an infusion i.e time taken for plasma concentration to fall to half its value when infusion is stopped . 12/12/2013 56

Different formulation :

Different formulation 12/12/2013 57 By the removal of Cremophor consists of 1% (wt/ vol ) Propofol 10% soybean oil 2.25% glycerol 1.2% purified egg phosphatide To prevent microbial growth in the emulsion, disodium edetate (0.005%) was added as a retardant of bacterial growth. If a dilute solution of propofol is required, it is compatible with 5% dextrose in water. fospropofol (Aquavan)soon going to be approved by FDA, a phosphorylated prodrug of Propofol,


DOSES OF PROPOFOL CLINICAL USE DOSE Induction of general anesthesia 1-2.5 mg/kg IV dose reduced with increasing age the induction dose in 2 yr (2.9 mg/kg) and 6-12 yr (2.2 mg/kg ). Maintenance of general anesthesia 100-200  µg/kg/min IV with out N 2 O or an opiate 50-150  µg/kg/min IV combined with N 2 O or an opiate Sedation( with little analgesic and amnesic ) 25-75 µg/kg/min IV; conscious sedation Antiemetic 10-20 mg IV, can repeat every 5-10 min or start infusion of 10 µg/kg/min 12/12/2013 58

PowerPoint Presentation:

Simulated time course of whole blood levels of Propofol after an induction dose of 2 mg/kg. Blood levels required for anesthesia during surgery are 2 to 5 µg/mL, with awakening usually occurring at a blood level less than 1.5 µg/mL 12/12/2013 59 Awakening occur



Effect on CNS…..:

Effect on CNS….. 12/12/2013 61 Dose and therapeutic conc dependent action Hypnotic action by enhancing GABA induced chloride current Onset with 2.5 mg/kg 15-30 sec with peak effect in 90-100 sec. Duration of hypnosis 5-10 min depending on redistribution and Vd Subhypnotic dose – sedation and amnesia infusion @2mg/kg/hr Propofol have shown direct depressant effect on neuron of spinal cord sense of well being ( ↑dopamine conc in nucleus accumbence- phenomenon seen in drug abuser and pleasure seeking behavior. Antiemetic action may be explained by ↓in serotonin level .

Effect on CNS…..:

Effect on CNS….. 12/12/2013 62 ↓ ICP , acutely ↓ IOP -(propofol >Thio )effective in preventing raised IOP with scolin and intubation response Neuroprotective role ↓ controversies ;due to antioxidant axn by inhibiting lipid peroxidation Just or 1 hr after to ischemic insult produce reduction in size of infarct at sedation dose @ 25-75 µg/kg/min as compared to awake control with intralipid. Burst suppression @blood level > 8µg/ml –better neurological outcome and less brain injury EEG effect – ( α → ϒ → Ө ) wave Seizure like activity reported mainly on induction and emergence . Dose dependent anticonvulsant activity +nt




CVS…… 12/12/2013 64 On induction dose and rate of adm dependent↓ BP (25-40 %) in comparable dose (propofol >Thiopental) ↓ SBP and DBP , ↓ MAP ↓ CO, ↓ SV , ↓ SVR ( 15-25 %) HR ↓(-10 +_10 % ) to baseline; Propofol either may reset or may inhibit the baroreflex, reducing the tachycardia response to hypotension MAP ↓ ( -10-40 %) Propofol at high concentrations (10 µg/mL) abolishes the inotropic effect of α but not β adrenoreceptor stimulation, and enhances the lusitropic (relaxation) effect of β stimulation CNS induced ↓ sympathetic drive on heart - cardio depression


CVS……. 12/12/2013 65 In patient with valvular lesion ↓( PA and PCWP ) – due to ↓ pre and afterload . cardio depression ( bolus > infusion ) Continuous Infusion cause significant ↓ in myocardial blood flow and oxygen demand For better hemodynamic stability use one or more additive induction agent ( fentanyl , Midazolam )with propofol . Bradycardia-related Death:-Profound bradycardia and asystole after the administration of Propofol despite prophylactic Anticholinergics. thus suggesting that Propofol induce a suppression of sympathetic nervous system activity. The treatment of Propofol-induced bradycardia may require the administration of a β-agonist, such as isoproterenol.




RESPIRATORY…… 12/12/2013 67 Profound resp depressant Apnea occur depend on dose , speed of injection, concomitant premedication Occur in 25- 30 % cases ,may last for >30 sec ,may ↑by adding opiate in premedication Apnea risk max in this agent than other Apnea precedes with marked ↓ TV and tachypnoea. A maintenance infusion (100 µg/kg/min) results in a 40% ↓TV and a 20% ↑ RR , Propofol (50 to 120 µg/kg/min) also depresses the Ventilatory response to hypoxia, presumably by a direct action on carotid body chemoreceptor Reduces airway and pharyngeal reflexes- use with LMA Bronchoconstriction ( thiopental > propofol ),Bronchodilation prevent intraop wheeze.


SIDE EFFECT Proconvulsant Activity:-The majority of reported Propofol-induced seizures during the induction of anesthesia or emergence from anesthesia reflect spontaneous excitatory movements of sub cortical origin. Abuse Potential :-Intense dreaming activity, amorous behaviour, and hallucinations have been reported during recovery from the effects of Propofol. Bacterial Growth:-growth of Escherichia coli and Pseudomonas aeruginosa. Pain on Injection:-As little as 0.2 mg/kg of lidocaine (mixed with the propofol) is effective in reducing but not eliminating this discomfort. Mini – Bier Block –apply tourniquet give 1mg /kg of lidocaine 15-20 sec before propofol adm then remove tourniquet 12/12/2013 68


PROPOFOL INFUSION SYNDROME Complication in prolonged infusion patient Propofol infusion syndrome(PIS) in (pediatric > adult) patients receiving prolonged high-dose infusions of Propofol (>75 µg/kg per minute) for longer than 24 hours. Associated with :- metabolic acidosis, lipidaemia, cardiac arrhythmias Unexpected tachycardia Increase mortality 12/12/2013 69


PROPOFOL IN OBS 12/12/2013 70 When choosing an induction agent, the primary goals are as follows: (1) to preserve maternal blood pressure, cardiac output, and uterine blood flow; (2) to minimize fetal and neonatal depression; and (3) to ensure maternal hypnosis and amnesia.


PROPOFOL IN OBS 12/12/2013 71


PROPOFOL ADVANTAGE DISADVANTAGE 12/12/2013 72 Rapid induction Antiemetic effect TIVA Agent of choice for day care surgery Induction apnoea Hypotension Dose dependent bradycardia Dose dependent resp depression Pain during injection  It also is euphorigenic, but does not have residual psychotic effects as does ketamine.


ETOMIDATE 12/12/2013 73


ETOMIDATE Etomidate is a carboxylated imidazole & prepared as a fat emulsion, its effects on GABA A receptors Etomidate A→B circulation time 1 min, The clearance of etomidate is about five times that for thiopental; Likewise, the context-sensitive half-time of etomidate is less likely to be increased by continuous infusion, as compared with thiopental. Etomidate (0.2 to 0.4 mg/kg IV) IOC especially in the presence of an unstable cardiovascular system. Involuntary myoclonic movements are common during the induction due to alterations in the balance of inhibitory and excitatory influences on the thalamocortical tract. Awakening after a single intravenous dose of etomidate is more rapid than after barbiturates. The principal limiting factor in the clinical use of etomidate for the induction of anesthesia is the ability of this drug to transiently depress adrenocortical function. 12/12/2013 74

PowerPoint Presentation:

12/12/2013 75


DRUG DOSES 12/12/2013 76 CLINICAL USE DOSE Induction of general anesthesia 0.2-0.6 mg/kg IV Maintenance of general anesthesia 10 µg/kg/min IV with N 2 O and an opiate Sedation and analgesia Limited to periods of brief sedation because of inhibition of corticosteroid synthesis




CNS… 12/12/2013 78 ↓ CBF , ↓ CMR02 , ↓ ICP Myoclonus (spontaneous movements) occurs in 50% to 80% of patients receiving etomidate in the absence of premedication. etomidate-induced Myoclonus appears to be disinhibition of subcortical structures that normally suppress extra pyramidal motor activity.



CVS ….. :

CVS ….. 12/12/2013 80 CVS:- Cardiovascular stability (minimal changes in heart rate, stroke volume, cardiac output) is characteristic of induction of anesthesia using 0.3 mg/kg IV of etomidate So it may differ from most other intravenous anesthetics in that depressive effects on myocardial contractility are minimal at the concentrations needed for the production of anesthesia.




RESP…… 12/12/2013 82 RESP:- The depressant effects of etomidate on ventilation seem to be less than those of barbiturates, although apnea may occasionally accompany a rapid intravenous injection of the drug.

Limitation of etomidate :

Limitation of etomidate Etomidate causes adrenocortical suppression by producing a dose-dependent inhibition of the conversion of cholesterol to cortisol . 12/12/2013 83


AGENT OF CHOICE 12/12/2013 84


I.V. INDUCTION AGENTS Properties PROPOFOL (178) THIOPENTAL (264) KETAMINE (237.5) chemistry ALKYLPHENOL THIOBARBITURATE ARYLCYCLOHEXYLAMINE consistency Emulsion milky white Sodium salts( 6 % sod carbonate) Yellow amorphous powder Clear aqueous solution solubility Lipid soluble Lipid soluble Lipid soluble pH 7 10.5 of 2.5 % 3.5 - 5.5 % pKa 11 7.6 7.5 Unionized % 99.97% 61% 55.7% Onset One arm -brain time 15-30 sec 10-15 sec 30-60 sec Peak 90-100 sec 90-100 sec 90-100 sec Awakening 5-10 min 5-10 min 10-20 min Rapid fall in plasma conc. after single bolus Redistribution & elimination Redistribution Redistribution 12/12/2013 85


I.V. INDUCTION AGENTS PROPERTIES PROPOFOL THIOPENTAL KETAMINE Protein binding 98% 85% 60% Metabolism and excretion LIVER Glucuronide & sulfate kidneys LIVER Oxidation N – dealkylation Desulfuration Destruction of barbituric acid ring Excretion by kidney and bile LIVER Norketamine Hydroxynorketamine Excreted in kidneys Metabolite Inactive Pentobarbital Norketamine 20-30 % Extrahepatic metabolism lung Absent Absent Clearance 20-30 ml/kg/min 3-4 ml/kg/min 12-14 ml/kg/min 12/12/2013 86


I.V INDUCTION AGENT PROPERTIES PROPOFOL THIOPENTAL KETAMINE Context sensitive half time ( for infusion lasting upto 8 hrs <40 min <150 min <40 min MOA GABA GABA NMDA (thalamocortical & limbic system Induction 1-2.5 mg/kg 3-5 mg / kg adult , 5-6mg/kg in children, 6-7 mg/kg in infant 0.5-2 mg /kg Maintenance 50-150 µg/kg/min + 15-45 µg/kg/min Sedation 25-75 µg/kg/min 0.2-0.8 mg/kg Analgesia 25-75 µg/kg/min IV; conscious sedation -- 0.2-0.8 mg/kg 12/12/2013 87


I.V INDUCTION AGENT PROPERTIES PROPOFOL THIOPENTAL KETAMINE Neuroprotective Reduce infarct size when adm immediately or 1 hr after ischemic insult ↓ o2 demand Preserve CPP Robin hood phenomenon Free radical scavenging Improve perfusion in incomplete cerebral ischemia Dissociative anaesthesia - -- + Emergence reaction + -- + Upper airway reflexes -- -- + Salivation and lacrimation -- -- ++ antiemetic + -- -- Sk muscle tone -- -- ↑ Nystagmus -- -- + 12/12/2013 88


I.V INDUCTION AGENT PROPERTIES PROPOFOL THIOPENTAL KETAMINE BP ↓(25-40)% ↓ ↑ HR N/↓ ↓(10-36)% ↑ CO ↓ ↓ ↑ CMRO2 ↓ ↓ ↑ CBF ↓ ↓ ↑ ICP ↓ ↓ ↑ IOP ↓ ↓ ↑ Apnea ++ dose dependent (25-30%) ++ Higher dose Minute ventilation ↓ ↓ ↓ Bronchodilatation + -- + Anticonvulsant + + -- Antipruritic + -- -- Chronic refractory headache + -- -- 12/12/2013 89


I.V INDUCTION AGENTS PROPERTIES PROPOFOL THIOPENTAL KETAMINE Pain on injection ++ + -- Hypotension ++ + -- Apnea ++ + +/- Bronchospasm -- + -- Allergic rxn + + -- Thrombophelbitis + ++ -- 12/12/2013 90

Cases for choice of agent :

Cases for choice of agent 12/12/2013 91

Case -1 :

Case -1 A patient with intestinal obstruction requires an emergency laparotomy. Which induction drug would you use? Any patient with intestinal obstruction must be assumed to have a potentially full stomach. Traditionally a rapid sequence induction would be performed with preoxygenation , cricoid pressure, thiopental and suxamethonium. Thiopental is chosen due to its rapid, well defined onset at a predetermined dose. This is also the method of choice of induction for caesarean section. 12/12/2013 92

Case -2:

Case -2 A patient a history of throat cancer has signs of respiratory distress and marked stridor requires a tracheostomy. Which IV induction drug would you use? IV induction drugs and muscle relaxants should be avoided in this case due to their respiratory depressant properties. It may not be possible to perform facemask ventilation should this patient become apnoeic. Inhalational induction with halothane or Sevoflurane should be employed. 12/12/2013 93

Case - 3:

Case - 3 A patient requires a burns dressing change. Which induction drug would you use? Ketamine is an ideal drug to be used for minor procedures. For burns dressing changes, a sub-anaesthetic dose can be used. It will provide sedation and analgesia, preserving the protective airway reflexes. Ketamine is often combined with benzodiazepine premedication to reduce the dose requirement and emergence reactions, and sometimes an anti-sialagogue (e.g. glycopyrrolate, glycopyrronium bromide) to reduce airway secretions. 12/12/2013 94

Case -4 :

Case -4 A patient with a history of heart failure requires a general anaesthetic. Which induction drug would you choose? drug of choice would be etomidate due to its limited effect on the cardiovascular system. However some anaesthetists avoid etomidate all together due to its effect on steroid synthesis. Ketamine could also be considered due to its relative cardiovascular stability. Propofol and thiopental are also options, but potentially cause more cardiac depression. The important issue is that which ever induction drug is used, the lowest possible dose is given, it is given slowly and it is titrated to effect. Intra-arterial blood pressure monitoring should be considered if available. 12/12/2013 95

Case – 5 :

Case – 5 A patient with porphyria comes for an inguinal hernia repair and is requesting a general anaesthetic. Which induction drug would you use? The porphyrias are a group of disease characterised by overproduction and excretion of porphyrins (intermediate compounds produced during haemoprotein synthesis). Acute attacks may be precipitated by drugs, stress, infection, alcohol, pregnancy and starvation. Propofol would be the ideal induction drug to use in this case – being safe to use in patients with porphyria. Thiopental and etomidate should be avoided as they can precipitate a porphyric crisis. 12/12/2013 96

Case -6 :

Case -6 An adult patient requires sedation on the intensive care unit. Which of the induction drugs would be appropriate to run as an infusion? A propofol infusion would be appropriate. Midazolam could also be given in addition, or as an alternative to propofol. Thiopental should be avoided due to accumulation, and etomidate should be avoided due its effect on adrenal steroid hormone synthesis. 12/12/2013 97


TIVA AND TCI 12/12/2013 98


TIVA 12/12/2013 99 TIVA is technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide. Reason of popularity Firstly modern drugs like Propofol and the newer synthetic, short acting opioids make them very suitable for administration by continuous infusion.  new concepts in pharmacokinetic modelling and advances in computer technology have allowed the development of sophisticated delivery systems which make control of anaesthesia given by the intravenous route.


TIVA 12/12/2013 100 Drug suitable for TIVA:- Rapid onset and rapid offset Not accumulative – small steady state volume of distribution Drug unsuitable for TIVA:- Having accumulative effect Affective organ function


TIVA 12/12/2013 101 Think for FAST HUG in ICU for patient on prolonged infusion Feeding, Analgesia, Sedation, Thromboembolic prophylaxis, Head of bed elevation, Ulcer prophylaxis Glyemic control

PROPOFOL advantage in TIVA:

PROPOFOL advantage in TIVA 12/12/2013 102 Predictable and extremely clear headed awakening , so useful in neurosurgery Rapid emergence , esply when used with remifentanil Low incidence in PONV compared with volatile anaesthesia Safe in patient susceptible to malignant hyperthermia Paralysis not always required when used with fentanyl - avoiding reversal agent Can be used when anaesthetized patient need to be transferred B/W radiology and OT

Disadvantage of Propofol TIVA:

Disadvantage of Propofol TIVA 12/12/2013 103 Propofol expensive than volatile used in low flow Needs electrical power and infusion devices Need experience to run smoothly there is risk of awareness if I.V. disconnected or blocked There is no direct monitoring of plasma concentration like end tidal concentration in volatile anaesthetic .

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Thursday, December 12, 2013 104

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