GENERAL ANESTHESIA

Prof. Dr. Tatang Bisri, dr., SpAnKNA Department of Anesthesiology & ICU Medical Faculty University of Padjadjaran Hasan Sadikin Hospital

General anesthesia
A reversible state of unconsciousness

produced by anesthetic agent, with loss of sensation of pain over the whole body. Reversible irregular CNS depression. General anesthetic drugs are administered by inhalation, intravenously, intramuscularly, orally, rectally.

The order of descending depression of the CNS

Cortical and psychic centers Basal ganglia and cerebellum

Spinal cord
Medullary centers

Anesthetic drugs
Volatile anesthetic inhalation :

Halogen hydrocarbon (halothane) Halogen ether: enflurane, isoflurane, desflurane, sevoflurane Gas anesthetic inhalation : cyclopropane, N2O, ethylene. Intravenous : thiopental, propofol, ketamine, etomidate, diazepam, midazolam

Concept balanced anesthesia

Component anesthesia Hypnotic Analgesic VIMA Sevo, Iso, Enf, Hal, Desfluran TIVA Propofol, Pento, Ket, Mid

Fentanyl, alf, suf ,Mo, Fentanyl, alf, suf pethidine, remifentanil ,Mo, pethidine, remifentanil

Relaxation

Depol & non depol

Depol & non depol

Indication general anesthesia

Infant and young children. Adult who prefer general anesthesia. Extensive surgical procedures Patient with mental disease Prolonged surgery Patient with a history of toxic or allergic

reaction to local anesthetic drugs Patient on anticoagulant treatment

General anesthesia
Induction inhalation, maintenance

anesthesia with inhalation anesthetic (VIMA). Induction intravenous, maintenance anesthesia with intravenous anesthetic (TIVA). Induction intravenous, maintenance anesthesia with inhalation anesthetic.

General anesthesia technique

Spontaneous breathing Controlled ventilation Face mask Intubation LMA (Laryngeal Mask Airway) COPA (Cuffed Oro Pharyngeal Airway) LSA (Laryngeal Seal Airway)

Techniques of general inhalation anesthesia

Open-drop technique

Insuflation
Ayre T-piece system

System with non-rebreathing valve

Semi closed Closed

Breathing circuit system

Open system

Semi open system

Semi closed system

Closed system

Flow Rate Definition :

Metabolic-flow Minimal-flow Low-flow Medium-flow High-flow : 250 ml/minute : 250 - 500 ml/minute : 500 - 1000 ml/minute : 1-2 liter/minute : 2-4 liter/minute

Advantageous Low-flow anesthesia

Less of anesthesia gas consumption
Less of pollution Heat loss decrease Cost effective

Component anesthesia machine

Gas sources : Oxygen, N2O

Reducing valve or pressure regulator

Flow meter

Vaporizer for halothane, enflurane,

isoflurane, desflurane or sevoflurane. CO2 absorption system (soda lime or bara lime)

Uptake and distribution

Respiration factor Circulation factor Anesthetic gas factor Tissue factor

Respiration factor Inspiration concentration Ventilation effect

Circulation Factor
Solubility (partition coefficient)

Cardiac output
The difference of gas partial pressure

alveoli and vein

Partition coefficient of anesthetic

Anesthetic Blood/gas Brain/blood Tissue/blood
Ether Halothane Enflurane Isoflurane N2O 12.1 2.3 1.8 1.4 0.47 1.1 2.6 2.6 3.7 1.1 0.9 2.5 1.7 4.0 1.2

Anesthetic gas factor

MAC (Minimal Alveolar concentration)

MAC 50, MAC 95

MAC Ei 50, MAC Ei 95

MAC BAR 50, MAC BAR 95

MAC inhalation anesthetic

MAC =minimal alveolar concentration,

in 1 atmosphere, 50% patient without movement in noxious stimuli MAC Ei = concentration of volatile agent permitting laryngoscopy and intubation without untoward movement. MAC BAR = concentration of volatile agent required to block adrenergic response to skin incision

MAC inhalation anesthetic, 40 years old.

Volatile anesthetic
Halothane Enflurane Isoflurane Desflurane Sevoflurane N2O

MAC
0,72 1.68 1.12 6.0 2.05 105.2

Factors influencing or not influencing MAC

MAC decreased MAC unchanged
Increasing age CNS depressant: alcohol, barbiturate, lidocaine, benzodiazepine, narcotic Duration of anesthesia Gender Species Hypertension Hypocarbia

MAC increased
Alcoholism chronic Hyperthermia > 42 Hypercarbia Anemia

Tissue factor
Tissue rich vessel : brain, heart,

endocrine, kidney. Intermediate : muscle, skin. Fat. Tissue poor vessel : ligament, tendon.

General anesthesia planning

Pre operative visit

Premedication
Anesthesia technique : General,

Regional anesthesia Intraoperative Postoperative

Anesthesia technique :
General anesthesia
Airway controlled

Induction
Maintenance anesthesia

Analgesia
Muscle relaxation

Intraoperative
Monitoring Patient position Crystalloid and colloid Special technique

Postoperative Post operative pain treatment Send patient to Ward or ICU

Balance anesthesia
Anesthesia Drugs component Hypnotic Pentothal, Propofol, Enflurane, Isoflurane, Sevoflurane Analgesic Pethidine, Morphine, Fentanyl, Sufentanil, Remifentanil Relaxation Succ choline, Atracurium, Cisatracurium, Pancuronium

Intravenous anesthetic
Pentothal Propofol Etomidate

Midazolam
Diazepam

Ideal intravenous anesthetic

Water soluble

Non irritation
No anta analgesic effect

Rapid and smooth Induction

Cardiovascular stable in clinically dose

Resume: Effect anesthetic non volatile to organ system

Drug
Thiopentone Diazepam Midazolam Meperidine Morphine Fentanyl Ketamine Propofol

HR
0/ 0

MAP
* *

Vent

Bdil
0 0 * * 0 o

Resume: Effect anesthetic non volatile to CNS

Drug Thiopentone Diazepam Midazolam Meperidine Morphine Fentanyl Ketamine Propofol CBF CMRO2 ICP

Comparative properties of intravenous anesthetics

Thiopen Ketamin Propof
Aqueous solution Available in solution Pain on injection Venous thrombosis + + -

Diazep Midaz
+

+
-

+
+ -

+
+ +

+
-

Comparative properties of intravenous anesthetics

Thiopen Ketamin Propof
Rapidly acting Smooth induction Respiratory depression Cardiovasc depression + ++ + ++ + + + + ++

Diazep Midaz
+ +/+ +/+/-

Comparative properties of intravenous anesthetics

Thiopen Ketamin Propof
Rapid recovery Smooth recovery Suitable for infusion Interaction with relaxant + +/+ + +/-

Diazep Midaz
-

Choice of anesthetic inhalation

Cardio pulmonal effect

Product degradation with soda lime

What metabolites ?

How much metabolism?

Ideal anesthetic inhalation

Pleasant odor and non irritation Low solubility No organ toxic Side effect cardiovascular and respiration minimal CNS effect reversible without stimulant activity Effective in high O2 concentration Boiling pressure and boiling point can delivered by vaporizer standard

Interaction with Sodalime

Anesthetic Halothane degradation Product BCDFE organ Toxicity Nephrotoxic clinical Relevancy Non identified to data

Enflurane
Isoflurane Desflurane Sevoflurane

CO
CO CO Compound A Compound B

Nephrotoxic

Non identified to date

Physicochemical properties
Halothane Odor + Irritating to Resp system Solubility 2,35 MAC 0,76 Metabolism 17-20% Metabolites F, Cl, Br, TFA BCDFE, CDE, CTE, DBE Enfl + 1,91 1,68 2,4% F, CDA Isofl + 1,4 1915 <0,2% F, TFA Desfl + 0,42 6,0 0,02% F, TFA +

Sevo

0,63 2,05 <5% F, HFIP

New Trend in General Anesthesia

VIMA (Volatile Induction and Maintenance

of Anesthesia) Fast-Track Anesthesia Low-flow Anesthesia Low-cost Anesthesia Single-breath induction (Rapid induction)

Cardiovascular effect of Volatile inhalational anesthetics

Variable Blood pressure Vascular resistance Cardiac output Cardiac contraction CVP Heart rate Sensitization of the heart to epinephrine 0 = No change (<10%) = increase Halothane N/C 0 = Variable change Enflurane Isoflurane 0 0 0?

= 10-20% = 20decrease 40% decrease

Clinical pharmacology of Inhalational anesthetics : Respiratory

N2O
Tidal volume Resp rate PaCO2 resting

Halo

Enflur

Isoflu

Sevoflu

Clinical pharmacology of Inhalational anesthetics : CNS

N2O Halo Enflur Isoflu Sevoflu

CBF ICP CMRO2 Seizure

Clinical pharmacology of Inhalational anesthetics

N2O
HBF Nondep blockade Metabolism 0.004

Halo
15-20

Enflur Isoflu Sevoflu

2.5 0.2 2-3

Kuliah ke-2

Narcotic analgesic ideal :

Wide margin of safety Fast onset of action Short duration of action Easier analgesia controlled Strong analgesic no histamine release Non active metabolite

Opiate in Anesthesia
1. Premedication 2. Induction Anesthesia 3. Narcotic anesthesia 4. A part of balanced anesthesia 5. Adjuvant in regional anesthesia 6. Neurolept anesthesia 7. Post operative pain relief

Narcotic effect :

Bradycardia : central vagotonic effect, SA & AV node depression Respiratory depression : respiratory rate, rhythm, Response CO2, Minute Volume, Tidal Volume Muscle stiffness Nausea vomiting cause by stimulation CTZ, GIT mobility, decrease gastric mobility, increased gastric volume

Clinical Doses of Narcotics

Drug
Morphine Meperidine Fentanyl Sufentanil Alfentanil

i.v dose
0.05-0.3 mg/kg 0.5-1 mg/kg 1-5 ug/kg 10-40 ug/kg 30-80 ug/kg

Onset (min)
5-10 5-10 2 <1 <1

Approximate duration
3-5 h 2-3 h 45 min 2 h < 30 min < 60 min

Muscle relaxant
Very useful in general anesthesia.

laryngoscopy and intubation more

easier and avoid injury Muscle relaxation very useful during surgery and controlled ventilation

Ideal muscle relaxant

Non depolarization Rapid onset, short duration of action Rapid recovery, high potency non cumulative, metabolite non active No cardiovascular effect No histamine release Counteract with anticholinesterase

Mechanism neuromuscular blockade

Competitive block : non-depol, avoid

AcCh access to receptor. Depolarization block : depol, depolarization as AcCh but permanent Deficiency block: influence syntesis and release AcCh: Procaine, toxin botulinus, Ca decrease, Mg increase.
Morgan GE, Mikhail MS. Clinical Anesth, 1996

Terminology in muscle relaxant

ED 50 : dose what can paralyzed 50%

muscle strength ED 90 : dose what can paralyzed 90% muscle strength. Onset : interval between start of injection until maximal effect

Table 1. Depolarizing and nondepolarizing muscle relaxant

Depolarizing Short-acting Succinylcholine Decamethonium

Nondepolarizing Long-acting Tubocurarine Metocurine Doxacurium Pancuronium Pipecuronium Gallamine Intermediate-acting Atracurium Vecuronium Rocuronium Short-acting Mivacurium

Nondepolarizing drug
Do not produce muscular fasciculation

Effect are decreased by

anticholinesterase agent, depolarizing agent, lowered body temperature, epinephrine, acetylcholine Effect are increased by non-depolarizing drugs, volatile anesthetic .

Depolarizing drugs
Produce muscular fasciculation .

Effect are increased by

anticholinesterase agent, Acetylcholine, hypothermia Effect decrease with non-depolarizing relaxant drugs, anesthetic inhalation Dose Succ choline : 1 mg/kg BW

Table 9 - 5. Conditions causing susceptibility to succiniylcholine-induced hyperkalemia.

Burn injury Massive trauma Severe intra-abdominal infection Spinal cord injury Encephalitis Stroke Guillain-Barre syndrome Severe Parkinsons disease Tetanus Prolonged total body immobilization Ruptured cerebral aneurysm Polyneuropathy Closed head injury Near drowning Hemorrhagic shock with metabolic acidosis Myopathies ( eg, Duchenness dystrophy )

Table 9 - 6. A summary of the pharmacology of nondepolarizing muscle relaxant

Relaxant Tubocurarine Metocurine Atracurium Mivacurium Doxacurium Pancuronium Pipecuronium Vecuronium Rocuronium
1 2

Metabolism Insignificant Insignificant +++ +++ Insignificant + + + Insignificant

Primary Excretion Renal Renal Insignificant Insignificant Renal Renal Renal Biliary Biliary

Onset ++ ++ ++ ++ + ++ ++ ++ +++

Duration +++ +++ ++ + +++ +++ +++ ++ ++

Histamine Release +++ ++ + + 0 0 0 0 0

Vagal Blockade 0 0 0 0 0 ++ 0 0 +

Relative Potency1 1 2 1 2.5 12 5 6 5 1

Relative Cost2 Low Moderate High Moderate High Low High High High

For example, pancuronium and vecuronium are five times more potent than tubocurarine or atracurium Based on average wholesale price per 10 mL; does not necessarily reflect duration and potency Onset : + = slow; ++ = moderately rapid; +++ = rapid Duration : + = short; ++ = intermediate; +++ = long Histamine release : 0 = no effect; + = slight effect; ++ = moderate effect; +++ marked effect Vagal blockade : 0 = no effect; + = slight effect; ++ = moderate effect

Choice of anesthesia technique depend on:

Patient condition Skill anesthetist

Skill surgeon
Hospital socio economy

Problem during induction of anesthesia

Main problem : airway

Sign of partial obstruction : snoring,

crowing, gargling, wheezing, chest retraction, cyanosis Sign of total obstruction : air flow from nose/mouth negative, supraclavicular retraction, intercostal retraction, cyanosis

Other problem during induction

Respiratory depression Cough Larynx spasm Mucus and saliva vomiting

Airway controlled
Without equipment : Triple mannuver

Safar With equipment: OPA (Oro Pharyngeal Airway) NPA (Naso Pharyngeal Airway) LMA ( Laryngeal Mask Airway) ETT (Endo Tracheal Tube)

Indication Intubation
Head and neck surgery

Difficult airway
Thoracotomy

Laparotomy
Lateral position Prone position Controlled ventilation

Technique laryngoscopy
Head position

Insertion laryngoscope blade

Visualization epiglottis

Lift epiglottis
View larynx and surrounding structure

Advantages Endotracheal intubation

Ensures a patent airway

Normal anatomic dead space (75 ml) is

decreased to 25 ml. Ventilation can be assisted or controlled Possibility of aspiration diminished drastically Suctioning of the lung is facilitated

Disadvantages endotracheal intubation Increases resistance to respiration Trauma to the lips, teeth, nose, throat, larynx.

Complication Intubation
Teeth rupture

Mouth bleeding
Endobronchial intubation

Oesophageal intubation
Sore throat Hypertension Arrhythmias

Induction technique
Mask induction / inhalation Intravenous Intra muscular

Per rectal

Mask Induction with Sevoflurane

Gradual Induction Single Breath Induction Triple Breath Induction (Multiple Breath Induction) Fast technique with Single Breath Induction, without cough, breath holding, spasm larynx.

Gradual Induction

Classic method for Mask Induction. To decrease respiratory tract irritation and non pungent odor no need for Sevoflurane. Combined with N2O or Oxygen 100%. Concentration Sevo increase 0.5-1,5 vol% every 2-3 breath until anesthesia adequate. Commonly reach in 60-90 seconds with Sevo 7%.

Single-Breath Induction

Priming circuit with N2O 60% + Sevo 8% 30 seconds. Ask patient for maximal expiration (until residual volume) face mask . Ask patient inspiration maximal (vital capacity), keep 20 seconds, then normal breathing. After eyelash reflex negative, Sevo turn to 2%.

Triple Breath Induction

A variation

from Single Breath Induction Ask patient 3 times deep breath. Difference with Single Breath, no breath holding. Commonly patient sleep, in 2-3 breathing.

WHY VIMA???
intravenous induction, ex: Propofol : rapid

and smooth induction, but need vein access first, hypotension, apnoe. Pediatric anesthesia commonly by VIMA. More advantages than intravenous induction, maintenance inhalation.

How to maintain anesthesia ?

Maintenance anesthesia depend on

deep of anesthesia to reach adequate anesthesia. Commonly with inhalation anesthetic 0.5-1 MAC depend on type of surgery, spontaneous breathing or controlled. To reduce vol% (MAC) : add N2O or Fentanyl.

Sign of deep anesthesia

PRST Score (balanced anesthesia)

Guedel sign (ether anesthesia)

PRST Score (score 2-4: adequate

anesthesia) P = Systolic arterial pressure (mmHg) R = rate (heart rate) S = sweat/ lacrimation T = tear

PRST Scoring indexes for Balanced anesthesia

Index Systolic arterial pressure (mmHg) Heart rate (beats/min) Condition Less than control + 15 Less than control + 30 More than control +30 Less than control + 15 Less than control + 30 More than control +30 Nil Skin moist to touch Visible beads of sweat No excess tears when eyelids open Excess teas visible when eyelids open Tears overflow from closed eyelid Score 0 1 2 0 1 2 0 1 2 0 1 2

Sweat

Tears or Lacrimation

Extubation
After adequate ventilation

In deep anesthesia or after patient awake

Clear airway Oxygen 100% after and before extubation Send to RR or ICU depend on patient

condition

Factor which influence total anesthetic inhalation : 1. Constanta 2. Fresh gas flow 3. Volume % (MAC) 4. Length of surgery
Total anesthetic inhalation = constanta x fresh gas flow (ml) x vol % x time (minute)

If length of surgery 2 h, total Sevoflurane :

Induction first 30 second Fresh gas x 1/183 flow (ml) 6000 x 1/183 3 minute for intubation : 6000 x 1/183 3 minute start for low-flow : 3000 x 1/183 second 3 minute: 1000 x 1/183 Operation 2 hours : 1000 x 1/183 Total Sevoflurane 11,6 ml

x Vol %
x 8%

x time (minute) x 0,5 = 1,3 x 3

x 3 x 3

x 2%
x 3% x 1% x 1%

= 1,9
= 1,4 = 0,5

x 120 = 6,5

TIVA CONTINU
Propofol 6-10 mg/kg/h + Vecuronium 0.1 mg/kg/h + Fentanyl 2 ug/kg

Pentotal 1-3 mg/kg/h + Vecuronium 0.1 mg/kg/h + Fentanyl 2 ug/kg

Ketamine 2 mg/kg/h + Vecuronium 0.1 mg/kg/h + Diazepame 0.25 mg/kg Midazolam 50 ug/kg/h + Ketamine 2 mg/kg/h + Atracurium 0,25 mg/kg/h

Relaxation
Drug ED95 (mg/kg) Recommended Infusion rate intubating dose for steady state (mg/kg) blockade (mg/kg/h) 0.3-0.6 0.005-0.008 0.08-0.1 0.25 0.032 0.078

Atracurium 0.21 Pancuronium 0.067 Vecuronium 0.043

Drugs

Protein binding Lipid solubility

Morphine Pethidine Fentanyl Sufentanil Alfentanil

++ +++ +++ ++++ ++++

+ ++ ++++ ++++ +++

Note : + = very low; ++ = low; +++ = high ++++ = very high

Morgan GE. Clinical Anesthesiology, 1996.

N2O
1.5 time heavier than air

Must be give with O2 100%

Weak anesthetic

Analgesic N2O 20% equal with 15 mg

morphine Dont use in closed system At the end of anesthesia, to prevent diffusion hypoxia O2 100%

Advantages N2O
Rapid induction and recovery

No sensitized myocardium with

catecholamine No irritation respiratory tract Odor pleasant Strong analgesic

Disadvantages N2O
Weak anesthetic

No muscle relaxation effect

Need high concentration oxygen

Possibility aplasia bone marrow

Halothane
A clear, colorless, potent volatile liquid. Metabolism 17-20%

Advantages Halothane Rapid, smooth induction and recovery. Pleasant Non irritating, no secretion Bronchodilator Nonemetic Non flammable and non explosive

Disadvantages Halothane
Myocardial depressant

An arrhythmia producing drug

Sensitizes the myocardial conduction

system to the action of catecholamines A potent uterine relaxant Possible toxic to the liver Shivering during recovery period.

Enflurane
A clear, colorless, stable volatile liquid with

a pleasant ether-like odor. A potent inhalation anesthetic CNS excitation Use of epinephrine : saver than halothane.

Advantages Enflurane
Pleasant Rapid induction and recovery Non-irritating : no secretion Bronchodilator Good muscle relaxation Nonemetic Non flammable and non explosive Compatible with epinephrine

Disadvantages Enflurane
Myocardial depressant

Shivering on emergence
CSF production increase

CNS excitation, in high dose and

hypocarbia.

Isoflurane
A stabe, volatile liquid

A isomer enflurane
Inhalation anesthetic choice for

neurosurgical patient, kidney, liver.

Advantages Isoflurane
Rapid induction of anesthesia and swift

recovery Nonirritating : no secretion Blood pressure remain stable Indicated in poor-risk patient

Disadvantages Isoflurane
Less than halothane and enflurane

Sevoflurane
Inhalation

anesthetic with low solubility (0,63), low MAC (2,05), pleasant odor, no airway irritation, rapid uptake and elimination , cardio vascular stable. Rapid induction, with technique single breath induction, induction time 23 seconds.

Sevoflurane
Drugs of choice for Neuro anesthesia : WCA

2000 Montreal, Canada. Drugs of choice for Pediatric Anesthesia : ESA Barcelona, 1998. ASPA, Singapore, 2000., ESA Sweden 2001. In Sectio Caesarea equal with Isoflurane and spinal anesthesia Reduce sphlannic blood flow, hepatic blood flow lesser than other anesthetic inhalation.

Thiopentone
Blood pressure decrease

Heart rate increase or decrease

Peripheral vasodilatation

Heart contraction depressed

Larynx spasm, bronchus spasm Respiratory depression until apnoea Dose 4-6 mg/kg BW

Relative contraindication thiopentone

Asthma bronchiale

Severe liver disease

Severe kidney disease

Severe anemia
Hypotension Shock

Ketamine

Dissociative anesthetic Delirium Hallucination Increase blood pressure : systolic 23% from base line Increase heart rate Arrhythmias Hypersecretion Dose 1-3 mg/kg I.v or 9-11 mg/kg I.m

Indication and Contraindication Ketamine

Indication : short surgery
Contraindication : Hypertension systolic >

160 mmHg Arrhythmias Heart failure Pharynx and larynx surgery without intubation.

Propofol
New intravenous anesthetic

Fast onset, short duration of action

Accumulation minimal

Fast recovery
Rapid metabolism No complication at site of injection Dose 2-2.5 mg/kg BW

Pharmacology Propofol
No histamine release/reaction anaphylactoid

(chremophor El change with soya bean oil). Perivascular injection, tissue necrosis negative. Injection intra artery : tissue necrosis negative. Effect Propofol to CNS Hypnotic effect 1,8 time pentothal Airway depression > pentothal Anti emetic effect No anti convulsan effect