General anaesthesia
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This document discusses general anaesthetics. It begins by defining general anaesthetics as drugs that produce reversible loss of consciousness and sensation, including pain, reflexes, and mobility. It then covers various topics related to general anaesthetics, including historical uses, mechanisms of action, stages of anaesthesia, inhalational agents like ether, nitrous oxide, and halothane, and intravenous agents like thiopentone sodium. The ideal properties of anaesthetics are discussed. Inhalational agents have advantages like rapid induction but also risks like flammability, while intravenous agents allow rapid induction and recovery but are only suitable for short procedures.
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General anaesthesia
- 1. General Anaesthetics DR. MAYUR CHAUDHARI ASSISTANT PROFESSOR DEPARTMENT OF PHARMACOLOGY GOVERNMENT MEDICAL COLLEGE, SURAT
- 2. Objectives Terminologies Stages of anaesthesia Inhalational Anaesthetics Intravenous Anaesthetics Preanaesthic Medication
- 3. General Anaesthetics Drugs Which Produce Reversible Loss of consciousness and all sensation Loss of sensation – Pain Unconsciousness and amnesia Immobility and Muscle relaxation Loss of reflexes
- 5. Some Strange Methods Strangulation Cerebral Concussion Applying Cold or compression Alcohol Plants
- 6. Time Line 1799 – Davy 1818 – Michael Faraday 1844 – Horace wells 1846 – William TG Morton 1847 – John Snow and John Sympson 1956 – Charles Suckling
- 7. Mechanism of action Main Sites of action are Cortex, Thalamus and Hippocampus. Can also act at Peripheral Sensory Nerves, Spinal Cord, Brain Stem
- 8. Molecular Mechanism Chloride Channel GABA-A Receptor Complex Glycine gated chloride channel Neuronal Nicotinic receptors Antagonizing NMDA receptors
- 9. Minimum Alveolar Concentration (MAC) Measure of Potency of inhalational General anaesthetic agent Lowest Concentration in alveoli To produce immobility in 50 % subjects In response to painful stimuli. Correlation with oil/gas partition Coefficient Reflect capacity of anaesthetic to enter into CNS
- 10. MAC : Practically Alveolar concentrations can be monitored continuously by measuring end-tidal anesthetic concentration using spectrometry End point (immobilization) – can me measured. Other end points – Verbal commands or memory etc.
- 11. MAC Premedication with CNS depressant lowers MAC When combination is used MAC is additive DRC of inhaled anesthetic is steep Concentration exceeding 1.5 MAC are not used 2-3 MAC is lethal Patient wakes up when concentration falls to 0.4 MAC
- 12. Guedel’s Stages of Anaesthesia Guedel in 1920 described with ether Descending depression of CNS. Higher to lower areas of brain are involved. Vital centers located in medulla are paralyzed last. In spinal cord lower segments are affected earlier than the higher segments.
- 13. Stage I – Analgesia Starts with inhalation up to loss of consciousness Can Hear, See and Dream like state Reflexes and respiration normal Minor Operations can be carried out
- 14. Stage II - Excitement Delirium and combative behavior Rise and irregularity in BP and Respiration Chance of laryngospasm Pupils dilated No procedure is carried out in this stage
- 15. Stage III – Surgical Anaesthesia Onset of regular respiration to cessation of spontaneous breathing Phase1: Roving eyeballs. Phase2: Loss of corneal and laryngeal reflexes. Phase 3: Pupil starts dilating and light reflex is lost. Plane 4: Intercostal paralysis, shallow abdominal respiration, dilated pupil. Muscle tone decreases, BP falls, HR increases with weak pulse, respiration decreases
- 16. Stage IV – Medullary Paralysis Cessation of breathing to failure of circulation Death. Dilated Pupil, Flabby muscles Thready or imperceptible Pulse Low BP
- 18. Observations Eyelash reflex and swallowing movement present – Stage I Loss of response to painful stimuli – Stage III Light Anaesthesia – Reflex increase in respiration, BP on Incision, Resistance to intubation, Coughing, Vomiting, Laryngospasm Deep Anaesthesia - Fall in BP, Cardiac and respiratory depression
- 19. Phases of Anaesthesia Induction: Beginning of administration of anaesthesia to the development of surgical anaesthesia Maintenance: Sustaining the state of anaesthesia. Recovery: At the end of surgical procedure administration of anaesthetic is stopped and consciousness regains
- 20. Pharmacokinetics
- 21. Pharmacokinetics Depth of anaesthesia depends on Potency of the agent (MAC) and Partial Pressure (PP) attained in the brain. Induction and recovery depends on rate of change of PP in brain.
- 22. Factors affecting PP of anaesthetic
- 23. 1. PP of anaesthetic in the inspired gas Higher the inspired gas tension more anaesthetic will be transferred to the blood. Induction can be hastened by administering the GA at high concentration in the beginning.
- 24. 2.Pulmonary Ventilation Delivery of GA to alveoli depends on ventilation Hyperventilation – More delivery per minute Hypoventilation – Opposite effect
- 25. 3. Alveolar Exchange The GAs diffuse freely across alveoli, but if alveolar ventilation and perfusion are mismatched the attainment of equilibrium between alveoli and blood delayed Induction and recovery both are slowed.
- 26. Solubility of anaesthetic in blood Determined by Blood: Gas Partition coefficient Lower the blood : gas co-efficient – faster the induction and recovery – Nitrous oxide. Higher the blood : gas co-efficient – slower induction and recovery – Halothane.
- 28. 5. Solubility of anaesthetic in tissues It determines its concentration in that tissue equilibrium. Most of GAs are equally soluble in tissue as in blood Lipid soluble more rapidly enter and slowly leave adipose tissue
- 29. 6. Cerebral blood flow Highly perfuse so quick entry, Hasten by CO2 inhalation (cerebral vasodilatation) CO2 causes hyperventilation
- 30. Elimination Mostly through lungs in unchanged form. Channel of absorption (lungs) become channel of elimination Enter and persists in adipose tissue for long periods – high lipid solubility and low blood flow. They are not metabolized except Halothane
- 31. Second gas effect The ability of the large volume uptake of one gas (first gas) to accelerate the rate of rise of the alveolar partial pressure of a concurrently administered companion gas (second gas) is known as the second gas effect.
- 32. Diffusion Hypoxia Diffusion hypoxia is a decrease in PO2 usually observed as the patient is emerging from an inhalational anesthetic where nitrous oxide (N2O) was a component. The rapid outpouring of insoluble N2O can displace alveolar oxygen, resulting in hypoxia. All patients should receive supplemental O2 at the end of an anesthetic and during the immediate recovery
- 34. Ideal For Patient Pleasant, nonirritating, no nausea or vomiting. Induction and recovery should be fast with no after effects
- 35. Ideal for Surgeon Adequate analgesia, immobility and muscle relaxation. Noninflammable and nonexplosive
- 36. Ideal for Anaesthetic Easy, Controllable and Versatile Wide margin of safety. Potent so that low concentrations are needed. Rapid adjustments in depth of anaesthesia should be possible. Cheap, stable and easily stored. Not react with rubber tubing or soda lime.
- 37. Classification Inhalational Gas Volatile Liquid Intravenous Faster Acting Slower Acting
- 38. Inhalational Gas – Nitrous Oxide Volatile Liquids Ether Halothane Isoflurane Desflurane Sevoflurane
- 39. Intravenous Faster Acting Thiopentone Sodium Methohexitone Propofol Etomidate Slower Acting Diazepam Lorazepam Ketamine Fentanyl
- 40. Ether Colorless, highly volatile liquid with a pungent odor. Boiling point – 35ºC Produces irritating vapors and are inflammable and explosive. 85 to 90 percent is eliminated through lung and remainder through skin, urine, milk and sweat. Can cross the placental barrier.
- 41. Ether: Advantages Can be used without complicated apparatus. Potent anaesthetic and good analgesic. Muscle relaxation. Wide safety of margin. Respiratory stimulation and Broncho dilatation. Does not sensitize the heart to adrenaline Can be used in delivery. Less likely hepatic or nephrotoxicity.
- 42. Ether: Disadvantages Inflammable and explosive. Slow induction and unpleasant -atropine. Slow recovery – nausea & vomiting Cardiac arrest. Convulsion in children. Cross tolerance – ethyl alcohol.
- 43. Ether: Precaution Should not be used in Hot environment Electro cautery should not be used
- 44. Nitrous Oxide Non inflammable, nonexplosive, colorless and odorless gas Weak and low efficacy anaesthetic Produces Light anaesthesia
- 45. Nitrous Oxide: Advantages Quick and pleasant induction and recovery Strong analgesic action even at low concentration Requirement of toxic anaesthetic agent can be reduced No Nausea and vomiting Non toxic to liver kidney and brain
- 46. Nitrous oxide: Disadvantages Costly Supplementation required No muscle relaxation Diffusion Hypoxia
- 47. Nitrous Oxide: Use As an adjuvant with other agents Obstetrics and terminal illness – 50% + O2 Maintenance anaesthesia – 30 to 60%
- 48. Nitrous Oxide: Precautions Should always be used with 30% Oxygen Should be avoided in patient with collection of air in pleural, pericardial or peritoneal space. On Prolonged use – Bone marrow depression Megaloblastic Anaemia
- 49. Halothane Fluorinated volatile liquid with sweet odour, non-irritant non- inflammable and supplied in amber coloured bottle. Potent anaesthetic, 2-4% for induction and 0.5-1% for maintenance. Boiling point - 50ºC 60 to 80% eliminated unchanged. 20% retained in body for 24 hours and metabolized.
- 50. Halothane: Advantages Quick and pleasant induction and recovery Non Inflammable – Electro cautery safe Non Irritant – No effect on secretion, Bronchospasm, Nausea and vomiting Potent bronchodilator – Preferred in asthmatics Do not react with Soda lime
- 51. Halothane: Disadvantages Costly, Special Apparatus required Poor Analgesic and Poor muscle relaxant Sensitize heart to CAs – arrhythmias Cerebral vasodilator – Increase ICT induces Microsomal enzymes in patients and exposed persons
- 52. Halothane on Uterus Relaxation of uterine smooth muscle Useful for manipulation of position of foetus in perinatal period Helpful in delivery of placenta postnatally Not useful as analgesic or anaesthetic during labour
- 53. Halothane: Adverse effects Halothane Hepatitis ( 1:10000) Malignant Hyperthermia Patient with abnormal RyR1 calcium channel at SR. Massive Ca++ released – Persistent Muscle contraction, Heat. Treatment – Rapid Cooling, Bicarbonate, 100% O2 + IV dantrolene
- 54. Halothane: Precaution Proper History regarding exposure Repeated use should be avoided
- 55. Enflurane Causes Hypotension with minimal effect on heart Does not sensitize to CAs Significant Muscle relaxation Respiratory depression is more ↑ ICT, ↓ O2 consumption of cerebrum, Produce convulsions Less chances of hepatotoxicity Can produce malignant hyperthermia Same effect on uterus
- 56. Isoflurane Isomer of Enflurane and have similar properties but slightly more potent. Intermediate onset induction
- 57. Isoflurane: Advantages Rapid induction and recovery Good muscle relaxation Good coronary vasodilatation Less Myocardial depression No renal or hepatotoxicity Low nausea and vomiting No dilatation of pupil and no loss of light reflex in deep anaesthesia No seizure and preferred in neurosurgery Uterine muscle relaxation
- 58. Isoflurane: Disadvantages Pungent and respiratory irritant Special apparatus required Respiratory depression Maintenance only, no induction ß adrenergic receptor stimulation Costly
- 59. Sevoflurane Rapid induction and recovery Non irritant and Pleasant – Children Bronchodilator – Asthmatics Hypotension without tachycardia- MI or IHD patients Weak muscle relaxant
- 61. Thiopentone Sodium Ultrashort acting Barbiturate – 5to 10 minutes Onset with in arm to brain circulation time – 12 seconds Dose – 3-5mg/kg , repeated as per requirement (Max – 1gm) T1/2 – 9 hours
- 63. Thiopentone: Advantages Rapid induction, rapid Recovery No CNS Excitement Patient Directly goes into Surgical anaesthesia
- 64. Thiopentone: Disadvantages No Analgesic, rather Hyperalgesic No Muscle Relaxant Action Ultrashort – Short procedure only
- 65. Thiopentone: Adverse Effects Apnoea, Hypotension Pain, Necrosis and gangrene if accidently injected into artery Shivering Delirium during recovery
- 66. Thiopentone: Contraindications Acute Intermittent porphyria –LMN Paralysis Poor GC, Shock Crush injury ↑ ICT, IOT, Eye injury Psychiatric patient
- 67. Thiopentone: Use For Induction and ET intubation with muscle relaxant Endoscopies with short acting muscle relaxant ECT Short Surgical procedures Status epilepticus
- 68. Objective Intravenous general Anaesthetics Administration of drugs for anaesthesia Preanaesthetic Medication Complication of General anaesthesia
- 69. Etomidate Wide safety margin Preferred in patient with poor cardiac function Duration of action – 5 to 10 minutes Metabolized in liver , excreted through kidney and bile
- 70. Etomidate: Advantages Rapid induction Does not sensitize myocardium to adrenaline No nausea and vomiting Non-explosive and non-irritant Short operations (alone)
- 71. Etomidate: Disadvantages Involuntary movements during induction Post operative Nausea and Vomiting On Prolonged use- Suppression of adrenal cortex, Hypotension, electrolyte imbalance and oliguria Not used in Status epilepticus – Proconvulsant Poorly soluble in water- Solution prepared in Propylene Glycol
- 72. Propofol Rapid Induction and Rapid recovery One Dose – 4 minutes, t1/2 45 minutes Recovery after multiple dose is much faster Extensively metabolized 88% of an administered dose appears in the urine Metabolized by hepatic conjugation of the inactive glucuronide metabolites
- 73. Propofol: Advantages Inducing agent, Maintenance Agent Suppression of laryngeal reflex – Endotracheal intubation Antiemetic and anticonvulsant action Safe in pregnancy, can cross placenta Suitable for OPD Anaesthesia
- 74. Propofol: Disadvantages Induction Apnoea Hypotension Bradycardia Dose dependent respiratory depression Pain during injection: local anaesthetic combination
- 75. Benzodiazepines PAM, Induction, Maintenance and Supplementation Conscious Sedation Produce Sedation, Amnesia, and Unconsciousness in 5 minutes No Respi/ CVS Depression. Preferred for Endoscopies, Cardiac Catheterization, Angiographies, Local/ regional Anaesthesia, Fracture Setting Balanced Anaesthesia
- 76. Ketamine Dissociative anaesthesia Commonly used as IV, IM, Oral, Rectal can also be given Induction, Maintenance Large Volume of Distribution, rapid Clearance Metabolized in liver and excreted through Kidney and Bile
- 77. Ketamine: Advantages Effect of single dose last for 15 minutes No Vomiting, No Hypotension Little impairment of pharyngeal and laryngeal reflex Bronchodilator – Asthmatics Suitable for patient who lost circulatory volume due to dehydration, Hemorrhage or burns Poor risk and geriatric patient, Poor GC Children – IM, rectal
- 78. Ketamine: Disadvantages No Muscle relaxation ↑ BP, ↑ Cerebral blood flow, ↑ O2 Consumption, ↑ ICT, ↑ IOT Hallucinations, Disorientation, Sensory and perceptual illusions during recovery Involuntary movements
- 79. Ketamine and Pregnancy Contraindicated in pregnancy Oxytocic actionm Dangerous in eclampsia and preeclampsia Can be used for assisted vaginal delivery – Less Foetal and neonatal depression
- 80. Fentanyl Opioid analgesic, given at the start of painful procedures Supplements Anaesthetics in balanced anaesthesia In combination with BZDs – Diagnostic, Angiography and minor procedures in poor risk patients
- 81. Fentanyl: Advantages Patient is conscious- Patient cooperation can be asked Smooth onset and rapid recovery Suppression of vomiting and coughing Less fall in BP and no sensitization to adrenaline
- 82. Fentanyl: Disadvantages Respiratory depression Increase tone of chest muscle Nausea, vomiting and itching during recovery
- 83. Administration of Drugs in Anaesthesia Minimize deleterious effects – Preanaesthetic medication Maintain Physiological homeostasis Better Post anaesthetic outcome
- 84. Preanaesthetic Medication To relieve patients anxiety and apprehension To produce amnesia To prevent and control nausea and vomiting Supplement analgesic, Less anaesthetic required Decrease secretions and Vagal Stimulation Decrease acidity and volume of gastric juice
- 85. Selection of preanaesthetic drug Patient’s mental makeup Anaesthetic agent to be used Type of surgery Presence of preoperative problems
- 86. Antimuscarinics Drugs: Atropine, Glycopyrollate, Hyoscine Decrease salivary and bronchial secretions Prevents laryngospasm, bronchospasm, Nausea and Vomiting Prevent Vasovagal attack, Prevent Bradycardia, Hypotension, Cardiac arrhythmia and arrest Hyoscine – Sedation, amnesia, Antiemetic They ↑ body temperature Produce Pupillary dilation – alter pupil sign
- 87. Benzodiazepines: Diazepam, Lorazepam, Midazolam Anxiolytic Perioperative amnesia Sedative Smooth induction
- 88. Opioid Analgesics: Morphine, Pethidine, Fentanyl √ Good perioperative analgesic √ Sedation and Hypnotic effects x Respi. Depression, Hypotension, Post op Nausea, Vomiting x Constipation, Urinary retention x Asthma can be precipitated x Pupil constricted – Pupillary sign altered
- 89. Neuroleptics: Chlorpromazine, Haloperidol √ Sedation, √ Antianxiety √ Antiemetic x Hypotension x Extrapyramidal Side effects
- 90. Antiemetics: Metoclopramide, Domperidone Prevent Gastric reflux and aspiration pneumonia Antiemetic action in perioperative period Metoclopramide – EP Side effects Promethazine- Antiemetic+ Sedative+ Anticholinergic Promethazine reverses EP Side effects
- 91. Antacids, H2 Blockers, Proton Pump Inhibitors Antacids neutralize gastric acidity, H2 Blockers and Proton Pump Inhibitors decrease acid secretion Useful for emergency surgeries, Prolonged surgeries, CS, Obese Patients Given night before and in the morning Prevent stress ulcers
- 92. Induction and Maintenance Induction: Thiopentone/ other IV agent Maintenance: 1. N2O + O2+ Ether 2. N20 + O2 + Halothane + SM Relaxant 3. O2 + Halothane + SM relaxant + Analgesic Prevent/ Treat undesired side effects: Anticholinergics, Antiemetics, Analgesics
- 93. After Anaesthesia Oxygen: Prevent Diffusion Hypoxia Neostigmine: Reverse effect of SM relaxant Analgesic: Pain relief postoperatively Antiemetic: to Control vomiting
- 95. During Anaesthesia Bradycardia, Cardiac arrhythmia, Cardiac arrest Hypotension ↑ Salivary and bronchial secretion Respiratory depression, Hypercapnia Aspiration pneumonia Delirium, Convulsions Hypoxia Awareness and recall of events Fire and explosion
- 96. After Anaesthesia Nausea and Vomiting Delayed recovery, Persistent sedation Atelectasis and pneumonia Liver and Kidney damage Delirium Nerve palsy
- 97. Drug Interactions Patient on antihypertensive: fall in BP Neuroleptics, Opioids, Clonidine and MAO Inhibitors potentiate Anaesthetics Halothane sensitize heart to adrenaline Insulin need of diabetic increased
- 98. Summary Stages of Anaesthesia Ether, Nitrous Oxide Second Gas Effect, Diffusion Hypoxia Enflurane, Sevoflurane, Desflurane Thiopentone, Propofol, Ketamine Preanaesthetic Medication
Notes de l'éditeur
- Davy - Ether relieved severe Head ache Faraday – Narcotic effects of ether Horace wells - observed a young man injure his leg without pain while under the influence of nitrous oxide. Morton – First Public demonstration of ether anaesthesia John snow – Popularised chloroform Suckling – Introduced halothane
- Bind With GABA-A receptor protein and facilitate GABAnergic neurotransmission Glycine at spinal cord NMDA – aKetamine, N2o and xenon
- Influence of minute volume on rate of induction is greatest in the case of agents which have high blood solubility because their PP in blood takes a long time to approach the PP in alveoli.
- ratio of the concentration of an anesthetic in the blood phase to the concentration of the anesthetic in the gas phase when the anesthetic is in equilibrium between the two phases.
- Lower anesthetic solubility in blood results in the "blood" compartment becoming saturated with the drug following fewer gas molecules transferred from the lungs into the blood. Once the "blood" compartment is saturated with anesthetic, additional anesthetic molecules are readily transferred to other compartments, the most important one of which is the brain.
- N2O +halothane
- - Significant in case of low cardiopulmonary reserve
- Hepatitis on repeted exposure – occurs after few days- Fever, anorexia, NV, Jaundice and eosinophilia Malignant Hyperthermia – Genetically linked, can also occur with Succinyl choline, Neuroleptics Dandrolene – blocks release of ca++
- Properties are like halothane. Differences are ---
- Ultrashort action – Rapid redistribution in tissues Recovery prolonged on excess administration
- Apnoea, Hypotension when injecting drug rapidly.
- Crush injury – Hyperkalemia, Thiopentone toxicity
- Properties similar to Thiopentone – Dose which produces respi and CVS depression is much higher than anaesthetic dose Action terminates because of redistribution
- Concious Sedation - a technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function Balanced Anaesthesia - A technique of general anesthesia based on the concept that administration of a mixture of small amounts of several neuronaldepressants summates the advantages but not the disadvantages of the individual components of the mixture.
- Patient feels dissociated from the surroundings as well as from own body. There is analgesia, Amnesia, Sedation and patient is immobile
- 15 minutes – Diagnostic and minor surgical procedures, Traumatic wounds, Debridement and dressing, Severe burns, Cardiac catheterization,Angiography Stimulates Sympthetic system – so BP and HR maintained
- Administration of Drugs before anaesthesia to make it more pleasant and safe is known as Preanaesthetic medication
- Mental make up – if unusually anxious patient BZDs are must Anaesthetic- if irritant – atropine Surgery – if vagal nerve involvement might be there
- Instead of halothane Isoflurane, Sevoflurane, Desflurane can be used