General anesthesia

Definition of anesthesia It is a reversable blocking of pain feeling in whole body or in a part of it using pharmacology or other methods

Anesthesia- division Local- regional anesthesia, patient is conscious or sedated General- anesthesia interact with whole body, function of central nervous system is depressed: – Intravenous – Inhalation (volatile) – Combined, balanced

TIVA Total Intra Venous Anaesthesia VIMA Volatile Induction and Maintain Anaesthesia

Parts of general anesthesia Hypnosis- pharmacological sleep, reversable lack of consciousness Analgesia-pain management Areflexio-lack of reflexes Relaxatio musculorum- muscle relaxation, pharmacological reversable neuromuscular blockade

Parts of general anesthesia must be in balance between: Hypnosis (anesthesia) Analgesia Lack of reflexes (muscle relaxation)

Features of General anesthesia 1 Lack of consciousness 2 Pain management 3 Lack of reflexes 4 Neuromuscular blockade

Stages of general anesthesia • Stadium analgesiae (analgesia and sedation stage) • Stadium excitationis (excitation stage) • Stadium anaesthesiae chirurgicae (anesthesia for surgery) • Stadium paralysis respirationis (intoxication, respiratory arrest)

I. Analgesia stage • Patient consciouss • Spontaneus respiration • Reflexes present • Possible small surgery procedures like dressing change in burns II. Excitation stage • Possible uncontrolled movements, vomitings • Increase in respiratory rate III. Anesthesia for surgery • It begins with lack of lid reflex • 4 substages • Airway opening necessary • Possible surgery except for abdominal opening if no relaxants are used • Possible endotracheal intubation IV. intoxication, overdosing • Respiratory arrest • If anesthesia not discontinued possible cardiac arrest

Main reasons for premedication: Anxiolysis lack of of threat Sedation – calming down Amnesia – lack lof memories of perioperative period Methods of general anesthesia OPEN OLD SEMIOPEN USED MOSTLY IN PEDIATRIC ANESTESHIA SEMICLOSED MOST COMMON CLOSED MODERN ANESTESHIA

Stages of general anesthesia Methods of general anesthesia CIRCLE SYSTEM *HIGH FLOW FRESH GAS FLOW > 3 l/min. *LOW FLOW FGF ok. 1l/min. *MINIMAL FLOW FGF ok. 0,5 l/min. Stages of general anesthesia • Introduction to anesthesia (induction) • Maintaining of anesthesia (conduction) • Recovery from anesthesia

Anesthesia agents 1. Inhalation anesthetics (volatile anesthetics) - gases : N2O, xenon - Fluids (vaporisers) 2. Intravenous anesthetics - Barbiturans : thiopental - Others : propofol, etomidat 3. Pain killers - Opioids: fentanyl, sufentanil, alfentanil, remifentanil, morphine - Non Steroid Anti Inflamatory Drugs: ketonal, paracetamol 4. Relaxants - Depolarising : succinilcholine - Non depolarising : atracurium, cisatracurium, vecuronium, rocuronium 5. adiuvants -benzodiazepins: midasolam, diazepam

Volatile vs intravenous anesthesia

Mechanism of action of inhaled anesthetics Reaction depends on concentration. This depends on alveolar (first compartment), blood and brain (central compartment) concentration , (third compartment- other tissue like muscles, fataccumulation effect): – Minute ventilation – Lung blood perfusion – Solubility in tissues MAC-minimal alveolar concentration Concentration in which 50% of anesthetised patients do not react on skin incision Corelation with solubility in fat tissue The lower MAC is the higher strenght of action is

Division of inhalation agents Gases: • N2O – old, weak, used as adiuvant • Xenon – lately introduced 2. Vapors (fluids): • Halothan • Enfluran • Isofluran • Sevofluran • Desfluran

Features of ideal volatile anesthetic Not disturbing smell Fast acting, titrable Low solubility in blood- fast transport to brain Stable when stored, not reacting with other chemicals Non- flamable, non- explosive • Low methabolism in body, fast elimination, no accumulative effect No depressing effect on circulatory and respiratory systems

Nitrous oxide • Old • Weak • Used as adiuvant • Will be removed form medical use up to 2010 Halothan • Used for many years with good effect • First non-flamable volatile fluid anesthetic • MAC high • Depression of circulatory system • May destroy liver • Now-a-days used only in pediatric anesthesia

Isofluran • Disturbing smell • May interact with heart contractivity • Increases relaxation of muscles Desfluran • Very disturbing smell- can not be used for VIMA • Is not methabolised • Very fast acting • May be used for one-day surgery • Expensive, difficult to store (boiling temp. about 20 C) • Modern and widelly used

Sevofluran • Not disturbing smell- may be used for VIMA • Low solubility in blood- fast acting • Does not disturbs airway • May depress circulatory system • Methabolised to Compound A- may be renal toxic (but not confirmed in humans) • May be used in one-day surgery • Modern, and more and more widely used volatile anesthetic

Intravenous anesthesia

TCI (target controlled infusion) TCI is an infusion system which allows the anaesthetist to select the target blood concentration required for a particular effect It allows to control depth of anaesthesia by adjusting the requested target concentration

Instead of setting ml/h or a dose rate (mg/kg/h), the pump can be programmed to target a required blood concentration. Effect site concentration targeting is now included for certain pharmacokinetic models. The pump will automatically calculate how much is needed as induction and maintenance to maintain that concentration.

THIOPENTAL Old, one of the first used intravenous anesthetics Depressing effect on circulatory system May be used in patients with ASA 1

Ketamine Only intravenous anesthetic which has good analgesia effect Does not depress circulatory nor respiratory function Used in children, and in emergency and diseaster medicine Gives night mare dreams in adult patients

Propofol Very good anesthetic for induction and maintaince of anesthesia with no accumulation effect Titrable May be used in short procedures – titrated do not effect circulatory and respiratory system in important manner Good for sedation, brain protecting effect May be used in TCI

Opioids fentanyl, alfentanil, sufentanil, remifentanil May be used for induction and maintain of anesthesia in repeated bolus or continuous infusion technique Sedative effect In high doses may be used alone for so called opioid anesthesia- formerly used in cardioanesthesia- very stable circulatory effect

Muscle rigidity in high doses Post-Operative Nausea and Vomitings Compications of use Respiratory depression Muscle rigidity in high doses Post-Operative Nausea and Vomitings Accumulation effect after prolonged administration (except for remifentanil)

No accumulation effect after prolonged Remifentanil T1/2 3-5 min Methabolised by non-specific tissue esterases- methabolism is not altered by renal or liver function No accumulation effect after prolonged

BENZODIAZEPINES Used in anesthesia: Diazepam Midazolam Used as adiuvants for premedication

MUSCLE RELAXANTS

1.nondepolarising- 2.depolarising- Division of relaxants depending on mechanism of action 1.nondepolarising- combine with receptor for Ach like antagonists- they are fake mediators do not cause muscle contractation but block access to receptors for Ach 2.depolarising- they combine with receptors for Ach and cause contractation of muscle but they stay connected with receptor blocking access to it for Ach. They act like agonists.

Nondepolarising agents d-tubocurine – oldest deliverate of curarine – alcuronium -pancuronium – cheap and still used – pipercuronium – vercuronium – atracurium – cisatracurium – mivacurium -rocuronium

Division of nondepolarising relaxants due to Chemical structure: AMINOSTEROIDS Pankuronium( Pavulon ) Pipekuronium( Arduan ) Rapakuronium ( Raplon ) Rokuronium ( Esmeron ) Wekuronium ( Norcuron )

Benzylizochinolons Miwakurium( Mivacron ) Cisatrakurium( Nimbex ) Atrakurium(Trakurium)

Division of nondepolarising relaxants due to time of action: Short acting < 3 min: still searching Midle time <60 min: mivacurium, atracurium, cisatracurium, rocuronium, vecuronium Long acting > 60 min: pancuronium, pipecuronium

Atracurium Elimination non-enzymatic, independent of renal and liver function, Hoffman elimination- hydrolisis Releases histamine Acts about 30 min Cisatracurium One of stereoisomers of atracurium, Do not release histamine Acts about 60 min

Rocuronium Fast acting- time to 100% supresion 60 sec. Do not release histamine Acts about 60 min Is methabolised in liver- disfunction of liver may alter elimination Mivacurium Releases histamine Acts about 15-20 min – used for short procedures Methabolised by plasma esterases

Reverse of neuromuscular blockade Neostigmine, piridostigmine- blockers of acetylocholinesterase Must be given toghether with atropine to avoid bradycardia caused by activation of perisympatic system Depolarising agents Only one: chlorsuccinilocholine – It is methabolised by pseudocholinesterase - Causes many complications, has many contraindications – Indications: Rapid sequence induction: full stomach, suspected difficult intubation because it acts very fast < 30 seconds and short < 3 min

Complications of general anesthesia Respiratory: residual relaxants/opioids action Circulatory Neurological: residual anesthetics/opioids action Post-Operative Nausea and Vomitings

Mortality connected with anesthesia 0,05 0,05 - 4/10000 GA 2 2 - 16 % of of surgical surgical patients patients 80 % is is caused caused by by human human mistakes Major causes of deaths Airway obstruction Difficult and and unefficient intubation Insufficient ventillation

Haemodynamic instability Aspiration Aspiration Toxity of drugs drugs Other causes of mortality and morbidity Anoxia Haemodynamic instability Aspiration Aspiration Toxity of drugs drugs mostly inhalation agents Anaphylaxia and and drug interations