Lecture 25- Anaesthetics Flashcards
For patients undergoing surgical or medical procedures, different levels of sedation can provide important benefits to facilitate procedural interventions. These levels of sedation range from anxiolysis to general anesthesia and can create:
- Sedation and reduced anxiety
- Lack of awareness and amnesia
- Skeletal muscle relaxation
- Suppression of undesirable reflexes
- Analgesia
Because no single agent provides all desired objectives….
Anaesthetic techniques can be combines
several categories of drugs are combined to produce the optimum level of sedation required
Preoperative medications provide
anxiolysis and analgesia and mitigate unwanted side effects of the anesthetic or the procedure itself
name 4 preoperative medications
neuromuscular junction blockers enable
endotracheal intubation and muscle relaxation to facilitate surgery.
name 5 analgesics
- acetaminophen
- celexocib
- gabapentin
- ketamine
- opioids
Potent general anesthetic medications are delivered via
inhalation and/or intravenously.
Except for nitrous oxide, inhaled anesthetics are…
inhaled anesthetics are volatile, halogenated hydrocarbons
while intravenous (IV) anesthetics consist of
consist of several chemically unrelated drug classes commonly used to rapidly induce and/or maintain a state of general anesthesia.
name 4 inhaled (volatile) general anaesthetics
- desflurane
- isoflurane
- NO
- sevoflurane
name 4 IV general anaesthetics
local anaesthetics can be
amides or esters
Overall considerations when delivering an anesthetic.
levels of sedation
evels of sedation start with light sedation (anxiolysis) and continue to moderate sedation, then deep sedation, and finally a state of general anesthesia. The hallmarks of escalation from one level to the next are recognized by changes in mentation, hemodynamic stability, and respiratory competency
what is general anaesthesisa
a reversible state of central nervous system (CNS) depression, causing loss of response to and perception of stimuli. The state of general anesthesia can be divided into three stages:
- induction
- maintenance
- recovery.
Induction of general anaesthetics is…..
the time from administration of a potent anesthetic to development of unconsciousness,
- General anesthesia in adults is normally induced with an IV agent like propofol, producing unconsciousness in 30 to 40 seconds.
- Often, an IV neuromuscular blocker such as rocuronium, vecuronium, or succinylcholine is administered to facilitate endotracheal intubation by eliciting muscle relaxation.
maintenance of anaesthesia is…
the sustained period of general anesthesia.
recovery of anaesthesia starts…
After cessation of the maintenance anesthetic drug, the patient is evaluated for return of consciousness.
Inhaled gases are used primarily for
maintenance of anesthesia after administration of an IV drug
inhalation anaesthetics include
nitrous oxide and volatile, halogenated hydrocarbons.
potency in anaestheticsw
MAC is the
median effective dose (ED50) of the anesthetic, expressed as the percentage of gas in a mixture required to achieve that effect.
The more lipid soluble an anesthetic, the
lower the concentration needed to produce anesthesia and, therefore, the higher the potency
Factors that can increase MAC
(make the patient more resistant) include hyperthermia, drugs that increase CNS catecholamines, and chronic ethanol abuse.
Factors that can decrease MAC
(make the patient more sensitive) include increased age, hypothermia, pregnancy, sepsis, acute intoxication, concurrent IV anesthetics, and α2-adrenergic receptor agonists (clonidine and dexmedetomidine).
use of NO and volaltile anaesthetics
Side effect profile of volatile= reduced because MAC is reduced due to addition of NO
Solubility in blood
This is determined by a physical property of the anesthetic called the blood:gas partition coefficient
blood:gas partition coefficient
the ratio of the concentration of anesthetic in the liquid [blood] phase to the concentration of anesthetic in the gas phase when the anesthetic is in equilibrium between the two phases
blood: gas partition coefficient examples
For inhaled anesthetics, think of the blood as a pharmacologically inactive reservoir.
Drugs with low versus high blood solubility differ in their rate of induction of anesthesia. When an anesthetic gas with low blood solubility such as nitrous oxide diffuses from the alveoli into the circulation, little anesthetic dissolves in the blood. Therefore, equilibrium between the inspired anesthetic and arterial blood occurs rapidly with relatively few additional molecules of anesthetic required to raise the arterial anesthetic partial pressure.
By contrast, anesthetic gases with high blood solubility, such as isoflurane, dissolve more fully in the blood; therefore, greater amounts of gas and longer periods of time are required to raise blood partial pressure. This results in longer periods for induction, recovery, and time to change in depth of anesthesia in response to changes in the drug concentration. The solubility in blood is ranked as follows: isoflurane > sevoflurane > nitrous oxide > desflurane.
Nitrous oxide
unable to create a state of general anesthesia.
Nitrous oxide does not depress respiration, and maintains cardiovascular hemodynamics as well as muscular strength. Nitrous oxide can be combined with other inhalational agents to establish general anesthesia, which lowers the required concentration of the combined volatile agent. This gas admixture further reduces many unwanted side effects of the other volatile agent that impact cardiovascular output and cerebral blood flow.
IV anesthetics
- cause rapid induction of anesthesia often occurring in 1 minute or less.
- It is the most common way to induce anesthesia before maintenance of anesthesia with an inhalation agent.
- IV anesthetics may be used as single agents for short procedures or administered as infusions (TIVA) to help maintain anesthesia during longer surgeries.
- In lower doses, they may be used solely for sedation.
name 3 Intravenous general anaesthetics
Propofol (rapid), Barbiturates (rapid), Ketamine (slower).
Propofol
Propofol [PRO-puh-fol] is an IV sedative/hypnotic used for induction and/or maintenance of anesthesia. It is widely used and has replaced thiopental as the first choice for induction of general anesthesia and sedation. Because propofol is poorly water soluble, it is supplied as an emulsion containing soybean oil and egg phospholipid, giving it a milklike appearance.
Barbiturates
Thiopental [THYE-oh-PEN-tahl] is an ultra–short-acting barbiturate with high lipid solubility. It is a potent anesthetic but a weak analgesic. Barbiturates require supplementary analgesic administration during anesthesia.
Benzodiazepines
The benzodiazepines are used in conjunction with anesthetics for sedation and amnesia. The most commonly used is midazolam [meh-DAZ-o-lam]. Diazepam [dye-AZ-uh-pam] and lorazepam [lore-AZ-uh-pam] are alternatives. All three facilitate amnesia while causing sedation, enhancing the inhibitory effects of various neurotransmitters, particularly GABA.
Opioids
a short-acting anti-NMDA receptor anesthetic and analgesic, induces a dissociated state in which the patient is unconscious (but may appear to be awake) with profound analgesia.
Ketamine
a short-acting anti-NMDA receptor anesthetic and analgesic, induces a dissociated state in which the patient is unconscious (but may appear to be awake) with profound analgesia.
local anaesthetics
block nerve conduction of sneosry impulses from the peripherp-y to the CNS
- sodium ion channels are blocked to prevent AP conduction
delivery techniques of local anaesthetics
elivery techniques include topical administration, infiltration, and perineural and neuraxial (spinal, epidural, or caudal) blocks.
The most widely used local anesthetics are
bupivacaine [byoo-PIV-uh-cane], lidocaine [LYE-doe-cane], mepivacaine [muh-PIV-uh-cane], ropivacaine [roe-PIV-uh-cane], and tetracaine [TET-truh-cane].
why are local anaesthetics delivered with adrenaline (epinephrine)
Local anesthetics cause vasodilation, which leads to a rapid diffusion away from the site of action and short duration when these drugs are administered alone. By adding the vasoconstrictor epinephrine, the rate of local anesthetic absorption and diffusion is decreased. This minimizes systemic toxicity and increases the duration of action.
Anesthetic Adjuncts
Adjuncts are a critical part of the practice of anesthesia and include drugs that affect
- gastrointestinal (GI) motility
- Post operative nasea and vomiting (PONV)
- anxiety
- analgesia.
Adjuncts are used in collaboration to help make the anesthetic experience safe and pleasant.
GI medication adjuncts
aim to reduce gastricic acidity in the event of aspiration
- H2 receptor antagonists e.g. ranitine
- PPI e.g. omeprazole
risk factors for PONV
Risk factors for PONV include
- female gender, nonsmoker
- use of volatile and nitrous anesthetics
- duration of surgery
- postoperative narcotic use
drugs used to prevent PONV
- 5-HT3 receptor antagonists e.g. ondastron
- glucocorticoid dexamethasone
Anxiety medications
Anxiety is a common part of the surgical experience.
Benzodiazepines also elicit anterograde amnesia, which can help promote a more pleasant surgical experience.
Regarding levels of sedation, which one applies to loss of perception and sensation to painful stimuli?
A. Anxiolysis
B. General anesthesia
C. Moderate sedation
D. Deep sedation
Correct answer = B. Anxiolysis is a state of relaxation, but consciousness remains. General anesthesia is a total loss of perception and sensation to stimuli. Moderate sedation maintains mentation with adequate airway and respiratory competency. Deep sedation has some response to stimuli, but respirations may be inadequate.
13.2. Which of the following decreases minimum alveolar concentration (MAC)?
A. Hyperthermia
B. Cocaine intoxication
C. Pregnancy
D. Chronic ethanol abuse
Correct answer = C. Pregnancy is the only choice that decreases minimum alveolar concentration. All the other options increase MAC.
Which one of the following is a potent intravenous anesthetic and analgesic?
A. Propofol
B. Midazolam
C. Ketamine
D. Fentanyl
Correct answer = C. Ketamine is unique in its blockage of NMDA receptors, yielding both potent anesthetic and analgesic properties. Propofol is a potent anesthetic but a weak analgesic. Benzodiazepines such as midazolam have little analgesic effect, but can be a potent anesthetic at high doses. Fentanyl is a potent analgesic.
A 23-year-old patient with a history of severe postoperative nausea and vomiting is coming in for plastic surgery. Which anesthetic drug would be best to use for maintenance in this situation?
A. Isoflurane
B. Sevoflurane
C. Nitrous oxide
D. Propofo
Correct answer = D. A propofol infusion (TIVA) anesthetic would be best for this patient with a history of postoperative nausea and vomiting. Propofol is the only anesthetic listed with antiemetic properties. Both fluorinated hydrocarbons (isoflurane and sevoflurane) and nitrous oxide are linked to nausea and vomiting during surgery.
Anaesthetic technique can be combined
Conscious sedation
use of small amounts of anaesthetic or benzodiazepines to produce a ‘sleepy-like’ state (maintain verbal contact but feel comfortable
general anaesthetics either
Inhalational or ‘Volatile’ General Anaesthesia.
Via the lungs via a vaporiser
Guedels signs illustrate the
stages of anaethesia
stage 1
analgesia and consciouness
stage 2
unconscious, breathing erratic but delirium could occur, leading to an excitement phase
stage 3
surgical anaesthesia, with four levels descriving increasing depth until breathing weak
stage 4
respiratorey paralysis and death
Anaesthetic potency is measured by MAC or minimum alveolar concentration
- [Alveolar] (at 1atm) at which 50% of subjects fail to move to surgical stimulus (unpremedicated breathing O2/air)
- At equilibrium [alveolar] = [spinal cord]
- Anatomical substrate for MAC is spinal cord
- In animal models if section cord (i.e., remove connection to the brain) MAC is unchanged.
Total intravenous anaesthesia (TIVA)
can be defined as a technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide.
How Do We Describe Intravenous Anaesthetic Potency ?
main molecular targets of interest
general anaesthetic molecular target
Common ‘Anaesthetic’ theme : GABAA receptors
- GABAA receptors critical target for anaesthetics
- Major inhibitory transmitter
- Ligand Gated Ion Channel (Cl- conductance)- reduce likelihood of AP
- Potentiate GABA activity
- Anxiolysis
- Sedation
- Anaesthesia
With the exception of ……,….. and …… all anaesthetics potentiate GABAA mediated Cl- conductance to depress CNS activity.
Xe,N2O and ketamine
NMDA receptors probable other site
In the brain consciousness is (simplistically) a balance between
excitation (Glutamate) and inhibition (GABA).
Anaesthetics modulate this balance.
Parts of the brain involved with anaesthetic action
-
Reticular formation (hindbrain, midbrain and thalamus) depressed. Connectivity lost.
- Reticular system often called “activating system” due to ability to increase arousal.
- Thalamus transmits and modifies sensory information.
- Hippocampus depressed (memory).
- Brainstem depressed (respiratory and some CVS).
- Spinal cord-depress dorsal horn (analgesia) and motor neuronal activity (MAC).
Local and regional anaesthetics
Local Anaesthetics e.g.
Lidocaine, Bupivacaine, Ropivacaine and Procaine.
Characteristics of local anaesthetics
- Higher lipid solubility higher greater potency
- Dissociation constant (pKa) – time of onset.
- Lower pKa faster onset
- Chemical link – metabolism
- Ester (short acting) or amide (longer acting) link
- Protein binding = longer duration (higher for longer duration)
Local anaesthetic mode of action.
- Block voltage gated sodium channels (molecular drivers of AP)–>therefore reduced AP, reduced neuronal activity
- Uncharged anaesthetic passes plasma membrane, becomes charged and then blocks sodium channel –>prevents sodium transmissionUse dependent block
- The greater the degree to which ion channels are firing, the greater the block
- Adding adrenaline increases duration of action by causing vasoconstriction preventing the local anaesthetic from moving away from the site
Regional anaesthesia
As the name suggests selectively anaesthetising a part of the body.
- Often described as a ‘block’ of a nerve and hence the patient remains awake.
- Uses local anaesthetic and or an opioid.
- Upper extremity (e.g.,); interscalene, supraclavicular, infraclavicular, axillary.
- Lower extremity (e.g.,) ; femoral, sciatic, popliteal, saphenous.
- Extradural (epidural) / Intrathecal / Combined (labour).
Main Anaesthetic Side Effects. (from the very common 1:10 category for GA)
Too many agent specific effects to list and remember polypharmacology !
General anaesthesia
- PONV (opioids)–> post operative nausea and vomiting
- CVS – hypotension
- POCD- post operative cognitive dysfunction (increases with increasing age)
- Chest infection
Local and regional
- Depends on the agent used and usually result from systemic spread (Locals are Na+ channel blockers so cardiovascular toxicity)
Increased general concern re: allergic reactions/anaphylaxis
The more lipid soluble an anesthetic, the
lower the concentration needed to produce anesthesia and, therefore, the higher the potency
what is MAC
median alveolar concentration–> the lower the MAC the higher the potency
concentration of inhaled anesthetic within the alveoli at which 50% of people do not move in response to a surgical stimulus
what can increase MAC
(make the patient more resistant) include hyperthermia and chronic ethanol abuse.
Factors that can decrease MAC
(make the patient more sensitive) include increased age, hypothermia, pregnancy, sepsis, acute intoxication
blood: gas partition coefficient examples: anesthetic gases with high blood solubility
By contrast, anesthetic gases with high blood solubility, such as isoflurane, dissolve more fully in the blood; therefore, greater amounts of gas and longer periods of time are required to raise blood partial pressure. This results in longer periods for induction, recovery, and time to change in depth of anesthesia in response to changes in the drug concentration. The solubility in blood is ranked as follows: isoflurane > sevoflurane > nitrous oxide > desflurane.
IV anesthetics
cause rapid induction of anesthesia often occurring in 1 minute or less.
IV anesthetics may be used as single agents for short procedures or administered as infusions (TIVA) to help maintain anesthesia during longer surgeries.
benzodiazepines e.g. midazolam induce
amnesia and also reduce anxiety
ketamine is both
anaesthetic and analgesic
Propofol is the only anesthetic listed with
antiemetic properties
guedels signs represent
stages of anaethesia
4 stages-> 4th stage need intubation
Total intravenous anaesthesia (TIVA)
A
can be defined as a technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide.
Common ‘Anaesthetic’ theme :
- GABAA receptors
- GABAA receptors critical target for anaesthetics
- Major inhibitory transmitter
- Ligand Gated Ion Channel (Cl- conductance)- reduce likelihood of AP
- Potentiate GABA activity
- Anxiolysis
- Sedation
- Anaesthesia
with sodium channel blockers…
The greater the degree to which ion channels are firing, the greater the block
Adding adrenaline increases duration of action by causing vasoconstriction preventing the local anaesthetic from moving away from the site
main side effects of anaesthetics
PONV (opioids)–> post operative nausea and vomiting
CVS – hypotension
POCD- post operative cognitive dysfunction (increases with increasing age)
Chest infection
Use of Mesna alongside cyclophosphamide
Mesna – thiol group for cytoprotection and polar group – high renal excretion and protection at bladder epithelium – p.o. 2 hours before or i.v. with cyclophosphamide
examples of gram positive bacteria
streptococcus
staphyloccus
examples of gram negative
neisseria gonorrhea
chlamydia trachomatis
