Basic principles of anaesthesia Małgorzata Cyran

General anaesthesia The main objective of general anaesthesia is to allow the performance of surgical procedures. General anaesthesia consists of several components which can be obtained with the use of various substances.

These components are: loss of consciousness and amnesia (intravenous and inhaled/volatile anaesthetics), analgesia (opioids), disabling or reduction of the physiological somatic, visceral-somatic and autonomic responses to noxious stimuli, muscle flaccidity (muscle relaxants)

Components of general anaesthesia are: • unconsciousness (hypnosis) • pain relief/ loss of response to pain (analgesia) • skeletal muscle relaxation (relaxatio) • loss of motor reflexes (areflexia)

The stages of general anaesthesia Induction Maintenance phase Emergence from anaesthesia

Inhaled anaesthetics They are introduced through the lungs and distributed to the various tissues of the body by blood

The ideal volatile anaesthetic: provides fast and pleasant induction (falling asleep) and emergence from anaesthesia (waking up), good controllability - the ability to quickly change the depth of anaesthesia, sufficiently strong analgesic effect, inhibition of reflexes and skeletal muscle paralysis, a wide margin of safety, lack of toxicity at clinical doses, low cost

Inhaled anaesthetics do not meet all the requirements so an ideal anaesthetic doesn’t exist! time of induction of anaesthesia is extremely long and is accompanied by a period of arousal, for obtaining a sufficient depth of anaesthesia it is often necessary to use concentrations that lead to unwanted side effects, especially cardiovascular, most of the inhaled anaesthetics are combined with other intravenous drugs as a component in combined anaesthesia

Inhaled anaesthetics at a room temperature they remain in a volatile (nitrous oxide) or liquid state (isoflurane, desflurane, sevoflurane), those remaining in a liquid state must first be converted into steam to be implemented through the lungs, this is done with special evaporators, by which you can supply the anaesthetic in a specific concentration, Nitrous oxide does not require evaporator (can be given from a gas cylinder or a central supply)

Volatile anaesthetics are always introduced as a mixture containing other gases: air, O2, N2O or O2. The total pressure of this mixture of gases is the total sum of the partial pressures of all the gases present in the mixture. The level of the partial pressure of the inhaled anaesthetic determines the speed of reaching a state of equilibrium between the concentration of an anaesthetic in the breathing air and the concentration in blood.

The absorption of anaesthetic in the lungs depends on: The solubility of the anaesthetic in the blood, Cardiac output, The difference between the partial pressures of alveolar air and blood in the pulmonary veins

Distribution of the anaesthetic The amount of anaesthetic that is taken up by various tissues from the blood depends on: the solubility of an anaesthetic in the tissue, the blood supply, the difference between the partial pressures of an volatile anaesthetic.

Rate of anaesthetics’ elimination: 1. nitrous oxide 2. desflurane 3. sevoflurane 4. isoflurane The longer time of anaesthesia using a highly soluble anaesthetic, the slower the elimination through the lungs and the waking up period.

MAC Minimum alveolar concentration (MAC 50) is a concentration of an inhaled anaesthetic in the lungs that is needed to prevent motor response in 50% of subjects in response to a surgical (pain) stimulus. The lower the value of the MAC is, the greater the potency of an anaesthetic. The administration of 70% nitrous oxide can reduce MAC by half.

Factors affecting the MAC age (age reduces the need for an anaesthetic), lower body temperature, hypothermia - reduces MAC, pregnancy - reduces MAC, opioids- reduce MAC sedative and hypnotic agents - reduce MAC chronic alcohol abuse - increases MAC fever - increases MAC

Isoflurane molecular weight 184.5 Da boiling temperature of 48.5 C vapor pressure at 20C at 238 mm Hg partition coefficient blood / gas 1.4 MAC value 1.28 in 100% O2, 0.56% N2O 70

Isoflurane heart rate under isoflurane is variable, mean arterial pressure is decreased, myocardial contractility - negative inotropic effect, cardiac output remains unchanged or reduces the consumption of oxygen by the myocardium enhances the effects of muscle relaxants

Isoflurane reduces blood flow to the kidneys, decreases glomerular filtration rate and urine output no negative effect on the liver, has an irritating smell: apnea and coughing, can trigger malignant hyperthermia

Desflurane Molecular weight 168 Da the smell of acrid, irritating the airways boiling temperature of 22.8 C vapor pressure at 20 ° C is 664 mm Hg partition coefficient blood / gas 0.42 value of the MAC50 6-9% vol. 100% O2 2.5-3.5% in 70% N2O

Desflurane the smallest partition coefficient blood / gas from all the volatile anaesthetics increased heart rate decreases the vascular resistance of the peripheral circulation and causes vasodilatation, in a healthy person has a weak negative inotropic effect decreases blood pressure expanding effect on the coronary arteries irritates the respiratory system during induction of anaesthesia (cough, laryngospasm, increased secretion) is NOT suitable for the introduction of inhaled anaesthesia in children nor in adults

Desflurane intensifies the effects of muscle relaxants > 1 MAC increases cerebral blood flow no toxic effect on the liver requires a special evaporator can trigger malignant hyperthermia high usefulness in the low-flow or minimal-flow anaesthesia

Sevoflurane colourless, flammable liquid with a mild ether odour, the molecular weight of 200.06 Da boiling point at 58.5 C partition coefficient blood / gas 0.69 MAC value 2.05% by volume in 100% O2, 0.66% by volume to 70% N2O

Sevoflurane pretty good controllability 3-5% metabolised in the liver reacts with the absorber lime and forms a compound A - nephrotoxic substance cause weak or no changes in the heart rate peripheral vasodilation, reduced vascular resistance hypotension negative inotropic effect

Sevoflurane Sevoflurane is suitable for inhaled induction of anaesthesia in children (and adults) enhances the effect of muscle relaxants can cause malignant hyperthermia reduces the oxygen consumption by the brain

Nitrous oxide (N2O) physical state at room temperature - gas partition coefficient blood / gas 0.47 The value of the MAC 104 is a weak anaesthetic, is used as an additive to other anaesthetics the maximum concentration of nitrous oxide should not exceed 70% !!!

Nitrous oxide negative inotropic effect the impact on a healthy person is very weak and clinically insignificant does not cause muscle relaxation can lead to megaloblastic anaemia diffuses in body cavities filled with air: air-filled loops of bowel eg. the obstruction, pneumothorax, emphysema, middle ear, air-filled tube cuff,

Nitrous oxide the only volatile anaesthetic with an analgesic effect!!! diffusion hypoxia while emerging from anaesthesia

Halothane colourless liquid with a very pleasant smell sensitive to light coefficient blood / gas 2.5 does not irritate the respiratory tract a long waking-up period 20% of halothane is metabolised by the liver inhibits the secretion in the airways

Halothane reduces airway resistance in patients with spastic states of the bronchi by the inhibition of contraction and by promoting the relaxation of bronchi muscles, has a strong depressing effect on myocardial contractility decreases blood pressure, can cause bradycardia can cause ectopic arrhythmias: even ventricular fibrillation increased cerebral blood flow and increased intracranial pressure decreases gastrointestinal motility post- halothane liver failure

Intravenous Anaesthetics

Propofol fast and short acting anaesthetic without analgesic effect, use: an introduction to anaesthesia, TIVA, sedation for diagnostic procedures, sedation for patients requiring intensive supervision (ICU) insoluble in water, emulsion of soybean oil; white colour dose of 2-2.5 mg / kg painful during the injection

Propofol sedation by binding to the B subunit of the GABA A receptor decrease in blood pressure a decreased cardiac output causes transient apnea bounds to plasma proteins in 98%

Thiopental belongs to barbiturates a temporary decrease of blood pressure increased heart rate negative inotropic effect on the heart muscle can cause abnormal heart rhythm suppresses the respiratory centre - apnea

Thiopental dose of 2-5 mg / kg up to 500mg contraindicated in: acute intermittent porphyria and mixed porphyria severe asthma allergy to barbiturates heart failure, acute myocardial infarction pericarditis, cardiac tamponade hypovolemia, shock

Etomidate dose: 0.15-0.3 mg / kg anaesthetic without the analgesic component, myoclonus and can cause dyskinesia (after injection no change in EEG) among intravenous anaesthetics it has the weakest impact on the cardiovascular system recommended in patients at risk, in elderly patients

Ketamine It can be used as individual anaesthetic in small surgical procedures causes dissociate anaesthesia (hypnosis, unconsciousness, hallucinations, catalepsy may cause involuntary movements it may cause strange dreams and visual hallucinations associated with anxiety causes stimulation of the cardiovascular system (tachycardia, increased blood pressure), increases intracranial pressure, Do not use in patients with ischaemic heart disease

Ketamine indications: daily surgical wound treatment/ extensive burn care, in non-cooperating children, patients with shock it can be administered intramuscularly dose: 1-2 mg / kg

Benzodiazepines main effects: calming, anxiolytic, hypnotic, an anticonvulsant They do not provide surgical anaesthesia associated with opioids can lead to severe and prolonged respiratory depression, short-acting: midazolam average long-acting: flunitrazepam long-acting: diazepam

Benzodiazepines Indications: premedication, sedation, induction for the patients “at risk”, supplements the action of opioids and ketamine, anticonvulsant

Benzodiazepines Contraindications: myasthenia gravis hypersensitivity to benzodiazepines acute intoxication with alcohol and hypnotics severe respiratory failure Flumazenil - specific antidote for the benzodiazepines!

Opioids

Opioids Opioid receptors: μ - analgesia (pain relief), respiratory depression, inhibition of intestinal peristalsis κ - dysphoria, miosis and sedation, hallucinations. δ - analgesia, dysphoria and hallucinations.

Opioids Effects: analgesia somnolence euphoria respiratory depression muscle stiffness miosis nausea and vomiting suppression of the cough reflex

Opioids Analgesic potency of the opioid depends on the dose, the concentration of the opioid receptor, pain intensity, and many individual factors and circumstances. Opioids themselves, even at very high doses do not induce unconsciousness in a reliable manner, so they must be associated with an intravenous anaesthetic or sedative-hypnotic substances. Opioids do not cause amnesia.

Opioids Respiratory depression caused by opioids is dose-dependent and reinforced by the lack of stimulation and sleep, or concomitant administration of intravenous anaesthetics and sedatives. Clinical signs of respiratory depression: decreased respiratory rate and minute ventilation, apnea Opioids can increase muscle tension, even their stiffness (muscles of the chest, abdomen and larynx) All opioids in clinical doses cause constriction of the pupils. nausea and vomiting, itching of the skin - a typical side effect

Opioids cause hypotension bradycardia (it can be prevented or reversed by the administration of atropine) constipation (decrease the motility of the gastrointestinal tract) they increase the pressure in the bile ducts (spastic contraction of the sphincter of Oddi)

Fentanyl synthetic opioid μ-receptor agonist 50-100x stronger than morphine endotracheal intubation dose of 1-5 ug / kg combined anaesthesia 0.5 - 2.5 ug / kg approximately every 30 minutes or a continuous infusion of 2-10 ug / kg / h

Alfentanyl tetrazole derivative of fentanyl short-term effect a short treatment (15 min) or an analgesic component of TIVA

Sulfentanyl 7-10x times stronger than fentanyl endotracheal intubation dose of 0.3-1 ug / kg administered as a supplement to combined anaesthesia and in TIVA

Remifentanyl the shortest half life of all the opioids (3-4 min) not cumulative, its effect disappears quickly TIVA the start of the infusion of 0.1 to 0.25 to 0.5 ug / kg / min easy controllability due to the rapid determination of the balance between blood and tissues, 16-30x more potent than alfentanil (comparable to fentanyl)

Naloxone pure opioid antagonist administered to overcome the respiratory depression and limited awareness as a result of a residual activity of the opioids 0.4-0.8 mg, depression subsides after 1-2 min it is advised to administer it in divided doses

Skeletal muscle relaxants cause reversible flaccid paralysis of skeletal muscles paralysis occurs as a result of the inhibition of the transfer of potentials in a neuromuscular junction Depolarising and non-depolarising They are used to facilitate endotracheal intubation and to improve operating conditions the duration of the paralysis depends on the substance used

Depolarising block caused by succinylcholine, it binds to presynaptic and postsynaptic receptors motor end-plate is permanently depolarised and there is a flaccid paralysis of the muscles succinylcholine increases muscle fasciculations (due to presynaptic effects) precurarisation - providing a small dose of non-depolarising muscle relaxant before succinylcholine

Suxamethonium after the administration - max. effect after 60-90 sec; duration of aprox. 5 min slightly releases histamine can cause cardiac arrhythmias: sinus bradycardia, nodal rhythm, ventricular arrhythmias endotracheal intubation dose of 1 mg / kg the shortest-acting muscle relaxant should not be used in children indicated in suspected difficult intubation

Suxamethonium Contraindications: atypical cholinesterase acquired deficiency of pseudocholinesterase severe hyperkalemia multi-organ trauma, prolonged immobilization burns malignant hyperthermia myotonia, muscular dystrophies

Suxamethonium Side effects: bradycardia hypotonia increased salivation increased secretion in the airways increased tension of the gastrointestinal tract Symptoms tend to occur mainly after multiple injections. For this reason, you should not repeat injection of succinylcholine!

Non-depolarising block non-depolarising agents compete with acetylcholine for the subunit ⍺ of the choline receptor, they do not have agonist activity, long-acting: pancuronium; average duration of acting: vecuronium, rocuronium, atracurium, cis- atracurium, short-acting: mivacurium nondepolarizing agents can release histamine from the mast cells the impact on the cardiovascular system: tachycardia, arrhythmias, hypotension

Atracurium endotracheal intubation dose: 0.3-0.6 mg / kg distribution route of elimination: Hofmann elimination, independent of the liver and kidney metabolism releases histamine acting time of 20-30 min

Cis-atracurium endotracheal dose: 0.15-0.2 mg / kg Five times stronger than atracurium releases far less histamine than atracurium Hofmann elimination does not accumulate acting time: about 45 minutes

Mivacurium the shortest-acting non-depolarising skeletal muscle relaxant endotracheal intubation dose: 0,2-0,25 mg / kg not suitable for rapid intubation releases histamine acting time: 15-20 min liver failure extends the acting time

Rocuronium it has the fastest onset time endotracheal intubation dose: 0.6 -1.2 mg / kg satisfactory conditions for intubation after 60-150 s liver failure extends the acting time it can be used for rapid intubation acting time: 45 min

Vecuronium endotracheal intubation dose 0,08-0,1 mg / kg it does not release histamine distribution mainly in the liver acting time: 20-30 min

Pancuronium endotracheal intubation dose of 0.08-0.12 mg / kg duration of action of more than 45 min only long-term surgeries, procedures, after which the extubation is not planned/needed side effects: tachycardia, increased salivation, prolonged exposure

Neostigmine an acetylcholinesterase inhibitor inhibits the activity of acetylcholinesterase by increasing the amount of acetylcholine in the synaptic cleft dose should not exceed 0.07 mg / kg severe side effects: bradycardia, bronchospasm, stimulation of the gastrointestinal motility and increased salivary secretion and contraction of the bladder, miosis to weaken the adverse effects of the muscarinic acetylcholinesterase inhibitors an anticholinergic agent (eg. atropine) should be given at the same time

Sugammadex eliminates the effect of rocuronium and vecuronium, The minimum dose of 2mg / kg immediate elimination of the effect 16 mg / kg

Bibliography: Anestezjologia. Larsen Tom. 1 R. Larsen wyd Bibliography: Anestezjologia. Larsen Tom.1 R. Larsen wyd. III polskie, red. A. Kübler rok wydania: 2013

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