Premedication & Sedation 2024 PDF

P R E M E D I C AT I O N & S E D AT I O N Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia 27th September 2024 LEARNING OBJECTIVES Be able to: Outline the different reasons for premedication before induction of general anaesthes...

P R E M E D I C AT I O N & S E D AT I O N Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia 27th September 2024 LEARNING OBJECTIVES Be able to: Outline the different reasons for premedication before induction of general anaesthesia Explain the rationale and patient safety considerations for the use of sedation versus general anaesthesia Describe the pharmacology of commonly used sedative drugs and opioids used in contemporary veterinary anaesthesia Explain the principles of neuroleptoanalgesia as applied to premedication and sedation in veterinary practice SOME DEFINITIONS PREMEDICATION: administration of medication(s) before anaesthesia ANXIOLYSIS: state of mental calm & relaxation, decrease in locomotor activity, reduced anxiety, lack of concern for the surrounding environment, response to stimuli if stimulated SEDATION: state of mental calm, sleepiness, disinterest in the environment, poorer responsiveness to stimuli compared to an anxiolytic NARCOSIS: Sedation produced by opioids NEUROLEPTOANALGESIA: Joint administration of a sedative drug and an opioid analgesic especially for relief of surgical pain S E D AT I O N V S G E N E R A L A N A E S T H E S I A ( G A ) SEDATION GA Control of the airways X V (regurgitation/aspiration) Ability to ventilate X V Monitoring > Difficult, “incomplete” V Local blocks administration > Difficult ? V Time Can be > time consuming Can be time consuming Additional notes Minor procedures in healthy patients  Often deep sedation required Often patient is noise/touch/light sensitive Sudden arousal possible Level of pain? Sedation is NOT quicker & safer! W H Y P R E M E D I C AT E ? Decrease anxiety, stress & catecholamines release Patient & staff welfare Facilitate handling Facilitate IV catheter placement Pre-emptive analgesia Balanced anaesthesia:↓ anaesthetic drugs required & related side-effects (i.e., MAC sparing effect) Promote smooth induction, maintenance & recovery phase Decrease Autonomic Nervous System (ANS) activation during surgery P R E M E D I C AT I O N O P T I O N S Acepromazine https://picryl.com/media/questions- Alpha-2 agonists demand-doubts-emotions-2ea8c6 Benzodiazepines Opioids Ketamine (discussed in the injectable agents lecture)  ACEPROMAZINE Phenothiazines class SC/IM/IV/PO Licensed in dogs/cats/horses Unpredictable sedative?? Especially in Combine with other drugs Slow onset of action (up 30-40’ IM) Long duration: 4-6h (up to 8 h?) No reversal Dose: 5-10 mcg/kg IV up to 20 -30 mcg/kg IM Highly protein bound Liver metabolism, urinary & faeces excretion Cross BBB, placenta (lipophilic) ACEPROMAZINE ACEPROMAZINE SYNCOPE Careful with hypovolemic animals (decreased cerebral perfusion→ fainting) Breeds with high vagal tone/bradycardia (I.e. boxers, brachycephalic breeds…) ANTI-ARRHYTHMIC effect? ↓ incidence catecholamine-induced arrhythmias in dogs anaesthetised with barbiturates & halothane COLLIES & SHEPHERDS with MDR-1 gene mutation Prolonged & profound sedation Image from: https://www.preciousgemminis.com/mdr 1.html ACEPROMAZINE PRO CONVULSANT EFFECT? ACEPROMAZINE PRIAPISM RISK (stallions)? ALPHA-2 ADRENERGIC RECEPTOR AGONISTS Activation of central & peripheral pre & post- synaptic alpha 2 receptors Effects also on alpha1 & Imidazoline receptors  Central Nervous System Cerebral cortex Locus coeruleus & Rostroventral lateral medulla (area of SNS outflow) ↓ noradrenaline release, ↓ neurotransmission → Sedation, some cardiovascular effects Image from: Zhou and Zhao, J Anesth Clin Res 2014, 5:10 DOI: 10.4172/2155-6148.1000457 Spinal (analgesia, muscle relaxation)  Peripheral Nervous System  ≠ Organs ALPHA-2 ADRENERGIC RECEPTOR AGONISTS MEDETOMIDINE & DEXMEDETOMIDINE (dog, cat) XYLAZINE (horse, cattle) DETOMIDINE (horse, cattle) ROMIFIDINE (horse) ZENALPHA (dog) ≠ selectivity of ≠ alpha 2 agonists Drug α2:α1 selectivity ratio Xylazine 160 : 1 Detomidine 260 : 1 (Dex)Medetomidine 1620 : 1 Romifidine 340 : 1 Medetomidine: = mixture of Levomedetomine & Dexmedetomidine (active entianomer) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS SC, IM, IV, Oral transmucosal, Nasal, Intra-rectal, Intra-vaginal… Short onset (1-2’ IV- 15/20’ IM) Administered as bolus/constant rate infusion (CRI) Duration of action: drug dependent (~ 30- 120’) Dose related effect Synergism with opioids & benzodiazepines (to decrease side effects) Decrease dose of induction/inhalational agents (MAC sparing effect) Analgesia duration?? Liver metabolism, urine excretion ALPHA 2 ADRENERGIC RECEPTOR AGONISTS GENERAL EFFECTS ALPHA-2 ADRENERGIC RECEPTOR AGONISTS CARDIOVASCULAR EFFECTS CARE if cardiovascular disease or sick patients  A N TA G O N I S T S O F A L P H A - 2 A D R E N E R G I C RECEPTOR AGONISTS  ATIPAMEZOLE: Dex/Medetomidine Can be used also with xylazine & detomidine Sedation & analgesia are both antagonised No IV unless CPR Muscle tremors, excitement, tachycardia, hypotension, panting, vomiting  YOHIMBINE  TOLAZOLINE  VATINOXAN (MK-467) no cross BBB, reversal of cardiovascular effects only BENZODIAZEPINES DIAZEPAM & MIDAZOLAM Diazepam licensed (dog, cat, horse) Midazolam licensed (horse) Schedule IV drug IV, IM (midazolam only) Dose: 0.1-0.4mg/kg IV Hepatic metabolism (active metabolites) Duration: 1-4h Midazolam, 4-12h Diazepam? Hepatic necrosis (cats) Renal and biliary excretion Antagonist: Flumazenil BENZODIAZEPINES MECHANISM of ACTION GABA A receptors Image from: GABA Receptors (diff.org) Image from: Mota, Alberto & Nascimento, Gyzelle & Pereira, Gabriel. (2022). ACUPUNCTURE AS A COMPLEMENTARY ALTERNATIVE IN THE TREATMENT OF ANXIETY: A LITERATURE REVIEW. Journal Health and Technology - JHT. 1. e1216. 10.47820/jht.v1i2.16. BENZODIAZEPINES OPIOIDS Interaction with opioid receptors: mu(μ), kappa (κ), & delta (δ) Primary endogenous ligands: β-Endorphin (μ receptor), leucine- & methionine-enkephalin (κ receptor), dynorphin A (δ receptor) Dose response relationship: Image from: Yamaoka & Auckburally (2013) Analgesia in veterinary patients- opioids (part 1) The veterinary nurse: volume 4, issue 10 OPIOIDS: EFFICACY VS POTENCY Equal Efficacy, ≠ potency Image from: Image from: https://step1.medbullets.com/pharmacology/107007/efficacy-vs- https://ketaminenightmares.com/pex/saqs/pharmacology/pharmacodynamics/2020B11 potency _dose_response_curves_opioids.htm OPIOIDS IV, IM, SC, poor availability PO, transdermal, transmucosal (OTM) Hepatic metabolism (remifentanil: plasma esterases) Excretion: urine & bile OPIOIDS MECHANISM of ACTION PRESYNAPTIC POST-SYNAPTIC Image from: In utero and Postnatal Oxycodone Exposure: Implications for Intergenerational Effects - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Simplified-mechanism-of-action-of-opioids-using-morphine- as-an-example-of-an-opioid_fig3_355422924 OPIOIDS Receptors located all around the body Species & individual differences Image from: De Rosa, Giannatiempo , Charlier et others (2023). Pharmacological Treatments and Therapeutic Drug Monitoring in Patients with Chronic Pain. Pharmaceutics. OPIOIDS OPIOIDS Reduction pain perception ANALGESIA DORSAL HORN Reduce excitatory  Transduction neurotransmitter release  Transmission Hyperpolarization post  Modulation synaptic membrane ROSTRO-VENTRAL  Perception MEDULLA & PAG PERIPHERAL NOCICEPTORS Activation of descending inhibitory pathways Inhibition of ascending nociceptive input Opioid induced HYPERALGESIA OPIOIDS MORPHINE Mu agonist Histamine release Emetic (esp IM/SC) Epidural (preservative free) Urinary retention Pruritus Horses Controlled drug (schedule II) OPIOIDS METHADONE Full mu(μ) agonist NMDA receptor antagonist Analgesia  Not very sedative (apart from sick & very young patients) Potency: ~ to morphine Duration of action 3-4h Dose 0.1-0.5mg/Kg IV/IM/SC/transmucosal Controlled drug (schedule II) Licensed (dog, cat) OPIOIDS FENTANYL µ agonist Potency: 100 x morphine Onset: 1-2 mins Short Duration: 20 mins Bolus (1-2 mcg/kg) + Constant rate infusion (CRI) (5 -10 mcg/kg/hr) IV or transdermal patches Respiratory depression Controlled Drug (schedule II) Licensed in dogs OPIOIDS BUPRENORPHINE Mu(μ) partial agonist Weak kappa (κ), & delta (δ) antagonist High affinity binding to the receptors Onset of action: 30 min Long duration of action (6-8h) Analgesic effect (moderate) Mild respiratory & cardiovascular effects, less nausea/vomiting Dose 0.01-0.02mg/Kg IM/IV/SC/OTM Controlled drug (schedule III) Licensed in dog, cat, horse OPIOIDS PETHIDINE or MEPERIDINE mu(μ) agonist ONLY IM administra on → Histamine release (IV) 1/10th morphine’s potency Sedation & analgesia Some anticholinergic activity Dose 3.5- 10mg/kg IM Duration of action: 1-2h Pain on injection Controlled drug (Schedule II) Licensed in dog, cat & horse OPIOIDS BUTORPHANOL mu(μ) antagonist, kappa (κ) agonist Sedation  Antiemetic Antitussive Analgesic? (some birds spp, reptiles, horses) Duration: controversial Dose: 0.1 - 0.5 mg/kg IV/IM/SC (dogs & cats) 0.05 - 0.2 mg/kg IV (horses) Horses: Increase locomotor activity, ataxia, excitement Controlled drug (schedule III) It can be used to reverse mu-agonists MDR1 mutation (collies & shepherds) profound prolonged sedation A D J U N C T S TO P R E M E D I C AT I O N TRAZODONE Anxiolytic/sedative Tricyclic antidepressant Serotonin reuptake inhibitors (SSRIs) Serotonin receptors antagonist Histamine 1 & α1-adrenergic receptors antagonist (sedative-hypnotic effect) 3-7 mg/kg PO SID/BID/TID 1-2h before travelling Serotonin syndrome A D J U N C T S TO P R E M E D I C AT I O N GABAPENTIN  Neuropathic pain/ seizures Blockage of Ca2+ channels presynaptic neurons →↓ Ca2+ influx→ ↓ excitatory neurotransmitters Side effects: Sedation, ataxia, vomiting, diarrhoea, increased appetite? 100 mg/cat 1-2h before veterinary visit  HOW TO CHOOSE THE PERFECT DRUG C O M B I N AT I O N F O R YO U R PAT I E N T ? Anaesthetic protocol should be TAILORED to YOUR PATIENT’s NEEDS! Dosages reported on leaflets and many formularies can be quite high! Some considerations: Species Patient: aggressive/ anxious? old/ young? Many different options (e.g.,): Which procedure? Duration? Level of pain elicited? Opioid alone as sedative/ analgesic Which effects do you wish to achieve? Opioid + sedative (i.e. medetomidine/acp) Is your patient cardio-vascularly stable? Opioid + Sedative + Ketamine Are there any other comorbidities (including pain)? IV/ IM/SC/OS administration? → effect on dose, dura on Calculate dose based on lean body weight & allometric scaling REFERENCES THANK YOU FOR YOUR AT T E N T I O N. ANY QUESTIONS?