Anaesthesia: Physiology and Pharmacology Dr Rob Stephens Consultant in Anaesthesia UCLH Hon Senior Lecturer UCL Thanks to Dr Roger Cordery

Anaesthesia Dr Rob Stephens Physiological and Pharmacological principles Dr Dan Martin Critical Care BREAK Dr Luke Mordecai Acute Pain Management Dr Rob Stephens Physiological and Pharmacological principles Dr Dan Martin Critical Care BREAK Dr Luke Mordecai Acute Pain Management

Introduction Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications

Introduction Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications

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Introduction Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications

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Introduction Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications

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Introduction Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications Website, tutorials, coming to theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills Drug principles + mechanisms Likely postoperative complications

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Introduction 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications

Introduction 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications

Dr Rob Stephens Thanks to Drs James Holding and Maryam Jadidi Dr Rob Stephens Thanks to Drs James Holding and Maryam Jadidi Physiology and …

Contents Introduction Pharmacolgy Physiology CVS, RS, NS, Other Introduction Pharmacolgy Physiology CVS, RS, NS, Other

Pharmacology Contents Introduction – the classical triad Introduction – general principles Hypnotic Agents Neuromuscular Paralysis + Reversal Analgesia Cardiovascular Drugs – up and down Fluids and Gasses are drugs too!

Introduction 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications 12 weeks: Tutorials- booklet Theatre What you can take away from Anaesthesia Acute care (BLS, fluids, pre/postop care, CVS) Physical skills-OSCE Drug principles + mechanisms Likely postoperative complications

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Pharmacology Introduction Anaesthesia ‘classical triad’ Hypnotic agent- unconsciousness Gas or IV Analgesia Neuromuscular Paralysis Induction, Maintenance, Emergence, Recovery Basics of anaesthesia: podcast, download Anaesthesia ‘classical triad’ Hypnotic agent- unconsciousness Gas or IV Analgesia Neuromuscular Paralysis Induction, Maintenance, Emergence, Recovery Basics of anaesthesia: podcast, download

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Introduction - Principles Pharmacokinetics What the body does to the drug Absorption, distribution, metabolism, elimination Pharmacodynamics What the drug does to the body – ie it’s effects CVS, RS, GI, NS, Other, Side effects Pharmacokinetics What the body does to the drug Absorption, distribution, metabolism, elimination Pharmacodynamics What the drug does to the body – ie it’s effects CVS, RS, GI, NS, Other, Side effects

Hand IVI

Typical Anaesthesia Intravenous induction Propofol Short acting opiate - e.g. fentanyl Hypnotic ‘anaesthetic’ - e.g. propofol Set up of anaesthetic maintenance - e.g. sevoflurane vapour in oxygen and air Specific muscle paralysis may be needed Definitive analgesia Anti-emetic Others Intravenous induction Propofol Short acting opiate - e.g. fentanyl Hypnotic ‘anaesthetic’ - e.g. propofol Set up of anaesthetic maintenance - e.g. sevoflurane vapour in oxygen and air Specific muscle paralysis may be needed Definitive analgesia Anti-emetic Others

Hypnosis: Propofol

Giving IV drugs

Hypnosis: Propofol (and others) IV Redistributed out of CNS Wears off quickly – 3-5 minutes Metabolised CVS  MAP = CO x SVR RS  airway and resp depression NS  reflexes, Consciousness pain on injection

Maintenance: Volatiles Air Oxygen Sevoflurane

Maintenance Sevoflurane (‘SEVO’) Used for gaseous induction. Desflurane Isoflurane Gases, inhaled, little metabolised, exhaled CVS: CO x SVR =  MAP RS- irritant, bronchodilate NS - unconsciousness Given with Oxygen /Air /Nitrous Oxide Sevoflurane (‘SEVO’) Used for gaseous induction. Desflurane Isoflurane Gases, inhaled, little metabolised, exhaled CVS: CO x SVR =  MAP RS- irritant, bronchodilate NS - unconsciousness Given with Oxygen /Air /Nitrous Oxide CO x SVR = MAP

Monitoring volatiles live MAC = minimum alveolar concentration

Analgesia – later talk Systemic Simple- paracetamol 1g NSAID – ibuprofen, diclofenac etc Opioids eg morphine 2mg bolus Others – Ketamine Regional – spinal / epidural / blocks Local - infiltration Systemic Simple- paracetamol 1g NSAID – ibuprofen, diclofenac etc Opioids eg morphine 2mg bolus Others – Ketamine Regional – spinal / epidural / blocks Local - infiltration

Muscle Paralysis

Neuromuscular blockers Depolarising Suxamethonium Non-depolarising Atracurium Vecuronium Rocuronium Depolarising Suxamethonium Non-depolarising Atracurium Vecuronium Rocuronium

Neuromuscular blockers Depolarising Suxamethonium 2x Ach molecules Activates receptor Non-depolarising – competitive vs ACh Atracurium Vecuronium Rocuronium Depolarising Suxamethonium 2x Ach molecules Activates receptor Non-depolarising – competitive vs ACh Atracurium Vecuronium Rocuronium

Nicotinic ACh Receptor

intubation

Reversal of Paralysis Neostigmine Blocks cholinesterase Stimulates nicotinic and muscarinic Given with an anticholinergic Sugammadex Neostigmine Blocks cholinesterase Stimulates nicotinic and muscarinic Given with an anticholinergic Sugammadex

Uppers Anti-muscarininc cholinergics Atropine Glycopyrulate μg Symatheto-mimetics  1 agonists Phenylepherine Metaraminol Ephedrine mixed  and  adreno agonist Anti-muscarininc cholinergics Atropine Glycopyrulate μg Symatheto-mimetics  1 agonists Phenylepherine Metaraminol Ephedrine mixed  and  adreno agonist MAP = CO x SVR  1  2 11

Downers More anaesthetic or opiate / analgesia Short acting  -blockers (labetalol, esmolol) Short acting  blockers GTN Clonidine -  2 agonist clonidine More anaesthetic or opiate / analgesia Short acting  -blockers (labetalol, esmolol) Short acting  blockers GTN Clonidine -  2 agonist clonidine MAP = CO x SVR

Antiemetics

General- Hydrate, anxiety, gastric decompress Cyclizine anti-histamine S/E – tachycardia and other anti-cholinergic effects Ondansatron5-HT 3 receptor antagonists S/E – constipation + long QT Prochlorperazine (‘Stematil’) – DA and mACh receptor antagonist S/E – extrapyramidal Dexamethasone glucocorticoid S/E – deranged glucose control General- Hydrate, anxiety, gastric decompress Cyclizine anti-histamine S/E – tachycardia and other anti-cholinergic effects Ondansatron5-HT 3 receptor antagonists S/E – constipation + long QT Prochlorperazine (‘Stematil’) – DA and mACh receptor antagonist S/E – extrapyramidal Dexamethasone glucocorticoid S/E – deranged glucose control

Fluids and Gasses are drugs too! Oxygen is a ‘drug’ Intravenous fluids- ward -NICE guidelines Colloids Crystalloids Blood and products Articles on website / Oxygen is a ‘drug’ Intravenous fluids- ward -NICE guidelines Colloids Crystalloids Blood and products Articles on website /

Contents Introduction Pharmacolgy Anaesthetic/ Hypnotic Agents Neuromuscular Paralysis & Reversal Analgesia Others, CVS, Gasses, Fluids Physiology Dr ABCD CVS, RS, NS, Other Introduction Pharmacolgy Anaesthetic/ Hypnotic Agents Neuromuscular Paralysis & Reversal Analgesia Others, CVS, Gasses, Fluids Physiology Dr ABCD CVS, RS, NS, Other

CVS physiology O 2 + C 6 H 12 O 6 CO 2 + H 2 O ATP O 2 delivery =Amount of O 2 to tissues per minute =Cardiac Output x O 2 content of blood x HR x SV Hb x Sa0 2 x constant

CVS physiology MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia HR x SV Vaso-? constricted ? Dilated

CVS physiology: Heart Heart pumps blood (0 2 ) from lungs to tissues then back to heart / lungs (C0 2 ) SV Preload / Contractility / Hr / Afterload Work =0 2 needs  Rate Contractility Preload & Afterload Heart pumps blood (0 2 ) from lungs to tissues then back to heart / lungs (C0 2 ) SV Preload / Contractility / Hr / Afterload Work =0 2 needs  Rate Contractility Preload & Afterload

CVS effects.. Anxiety, illness, walking to theatre, pain Induction of general anaesthesia or onset of epidural/ spinal anaesthesia Cardiovascular - active drugs Intubation Surgical stimulation / trauma Haemorrhage Extubation Pain ?Recovery or complication Anxiety, illness, walking to theatre, pain Induction of general anaesthesia or onset of epidural/ spinal anaesthesia Cardiovascular - active drugs Intubation Surgical stimulation / trauma Haemorrhage Extubation Pain ?Recovery or complication

Cardiovascular changes ‘artists impression’ version often filled in!

Induction of anaesthesia Preoperative

Induction of anaesthesia MAP = CO x SVR HR x ↓SV ie vasodilated ↓ ↓ Intervention: Fluids Inotrope Vasopressors Spinal/Epid ural: vasodilates GA: negative inotrope + vasodilates

Surgical stimulation MAP = CO x SVR ↑HR x ↑SV vasocontricts ↑ ↑ +ve inotrope +ve chronotrope vasocontricts Intervention Avoid! Deepen GA Specific Drugs Sympathetic

Surgical stimulation Incision

Cardiovascular Bleeding Less oxygen in blood Less pressure at Atrial and Aortic stretch Sympathetic ++ response (+renal, adrenal) Blood pressure maintained … Less oxygen in blood Less pressure at Atrial and Aortic stretch Sympathetic ++ response (+renal, adrenal) Blood pressure maintained … CO x SVR ↑HR x ↑SV vasocontricts ↑ ↑ +ve inotrope +ve chronotrope vasocontricts

Respiratory Upper – Airway – above vocal cords Lower- Trachea, lungs, muscles Upper – Airway – above vocal cords Lower- Trachea, lungs, muscles

Respiratory- Airway Anaesthesia ‘Obtunds’ airway =“Airway obstruction’ = no airflow = no 0 2 = Badness Anaesthesia ‘Obtunds’ airway =“Airway obstruction’ = no airflow = no 0 2 = Badness

Keep Airway open: Airway manoeuvres (chin lift etc) Airway devices- above vs blow cords Above Vocal Cords eg, gudel, LMA Below Vocal Cords - Into trachea = intubation, paralysis Keep Airway open: Airway manoeuvres (chin lift etc) Airway devices- above vs blow cords Above Vocal Cords eg, gudel, LMA Below Vocal Cords - Into trachea = intubation, paralysis Respiratory- Airway

Anaesthesia Airway Equipment

Guedel / Oro-Pharyngeal Adult male Adult female Guedel size 4 size 3

Laryngeal Mask Airway

Video of LMA insertion

Respiratory- Airway

Respiratory- Lower/ Lungs Spontaneous breathing under anaesthesia vs Ventilated Lungs smaller  depth Drugs  respiratory rate Small airways / Alveolar collapse Can’t cough – secretions = ‘pulmonary shunt (vs deadspace) Hypoxaemia, persists postoperatively Spontaneous breathing under anaesthesia vs Ventilated Lungs smaller  depth Drugs  respiratory rate Small airways / Alveolar collapse Can’t cough – secretions = ‘pulmonary shunt (vs deadspace) Hypoxaemia, persists postoperatively

CT scan of Diaphragm during awake spontaneous breathing

CT scan of Diaphragm during anaesthesia: Atelectasis

Gastrointestinal General Anaesthesia relaxes gastro-oesophageal sphincter Fluid up oesophagus ?into lungs starvation postoperative vomiting Other drugs eg analgesia-opioid constipation- Rx laxatives General Anaesthesia relaxes gastro-oesophageal sphincter Fluid up oesophagus ?into lungs starvation postoperative vomiting Other drugs eg analgesia-opioid constipation- Rx laxatives

Neurology Many Effects GA =drug induced reversable unconsciousness Many reflexes  (airway, gag, CN) Awareness +/- NMJ paralysis Many Effects GA =drug induced reversable unconsciousness Many reflexes  (airway, gag, CN) Awareness +/- NMJ paralysis

Physiology summary MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia RS: upper airway / lower airway MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia RS: upper airway / lower airway HR x SV Vaso-? constricted ? Dilated

Pharmacology Summary Introduction – the classical triad Introduction – general principles Hypnotic Agents- IV and volatile Neuromuscular Paralysis + Reversal Analgesia Cardiovascular Drugs – up and down Fluids and Gasses are drugs too!

General Advice Check out website for lots of material Come to theatre- great teaching Come to theatre- physiology in action Get involved in other areas.. Preassessment, CPEx, Outreach Nurses ICU, pain etc etc Check out website for lots of material Come to theatre- great teaching Come to theatre- physiology in action Get involved in other areas.. Preassessment, CPEx, Outreach Nurses ICU, pain etc etc

Google UCL Anaesthesia Student UCL Anaesthesia Website Google UCL Stephens Thank you

Introduction Anaesthesia is more than Physiology and Pharmacology! Surgery vs Anaesthesia Outside theatre ICU, Pain, CPEx, Obstetrics, Research, Global Health, Extreme Environment, Disaster Medicine Anaesthesia is more than Physiology and Pharmacology! Surgery vs Anaesthesia Outside theatre ICU, Pain, CPEx, Obstetrics, Research, Global Health, Extreme Environment, Disaster Medicine

CVS physiology summary MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia MAP = CO x SVR Pathologies: Low SVR: SepsisAnaphylaxis Low CO: CardiogenicHypovolaemia HR x SV Vaso-? constricted ? Dilated