Week 1 - Neurophysiology for Anesthesia Flashcards
What is the purpose of Anesthesia?
To reduce anxiety – Anxiolysis
To relieve pain – Analgesia
To provide a stable surgical field – Paralysis
To produce Hypnosis (don’t want awareness)
Autonomic supression
Somatic suppression
Physiologic Patterns of Sleep and Wake
Wakefulness: norepinephrine, histamine, serotonin, dopamine, orexin
Non REM Sleep: firing decreases
REM Sleep: firing virtually quiescent
Anesthesia Affect on Sleep
Anesthetic effect on the thalamus resemble the naturally occurring thalamocortical inhibition characteristic of NREM sleep
Somnogens reduce amount of GA needed
Adenosinergic Antagonists increase amount of GA needed
Sites in the brain where anesthesia affects sleep
Thalamic Sites: during NREM sleep and anesthesia, the cortex is deprived of input (Thalamic Gates)
Hypothalamic Sites: histaminergic and orexenergic neurons in the hypothalamus stimulate the thalamus
Brainstem Sites: Locus Ceruleus, Mesopontine Tegentum, and VLPO stabilization
Limbic System: Hippocampus, medial septum, amygdala
Chemicals that Act at Synapses as Neurotransmitters (Table 3-2)
Glutamate — Oxytocin — Acetylcholine — Cholecystokinin — Norepinephrine — Gastrin — Glycine — GABA — Endorphins — Dopamine — Serotonin — Epinephrine — Histamine — Substance P — Vasopressin — Prolactin — Glucagon — Vasoactive intestinal Peptide
Inotropic Receptors vs Metabotropic Receptors
Ionotropic: ligand-gated ion channels that pass + or - ions and excite or inhibit
Metabotropic: can be excited or inhibited by the same neurotransmitter depending on which type of G-protein is coupled to the transmitter
Glutamate?
Excitatory in the brain and spinal cord
KA, AMPA, NMDA ionotropic receptors
NDMA blocked by Mg at normal extracellular levels
Open NMDA allow Ca into the cell
GABA
Inhibitory primarily in the brain
GABAa - ionotropic (Chloride/Bicarb)
GABAb - metabotropic open K+ channels
Glycine
Inhibitory primarily in the spinal cord
Requires 3 glycine to activate Chloride channels
It is a co-agonist at the NMDA receptor
What type of receptors are the Acetylcholine Receptors in the CNS?
Nicotinic are ionotropic
Muscarinic are G protein coupled
ACh regulated wakefulness, attention, learning, and motivation
What is critical in memory formation and storage?
Alteration in the strength of neuronal connections
Phases of memory
Short-Term Memory - seconds to hours
Long-Term Memory - hours to months
Long-Lasting (months to lifetime)
What phase of memory do Benzodiazepines and IV Anesthetics affect?
Primarily long term memory storage or retrieval
At what MAC do volatile agents impair memory formation?
25% to 50%
What is Long Term Plasticity and what inhibits it?
A form of synaptic plasticity important in memory formation
Inhibited by barbiturates, benzodiazepines, propofol, and Isoflurane
What is a BIS monitor and its limitations?
Algorithmic EEG analysis – range 0-100
General Anesthesia = 40-60
Gives an indication of how “deep” under anesthesia the pt is
Limitations of a BIS monitor
Ketamine and N2O increase BIS (False high)
Neuromuscular blockers decrease BIS in awake pts (False low)
Multiple BIS sensors on same pt give different values
Low BIS values may result in a reduction in delivered anesthesia concentration and resulting awareness
Types of Procedures with Incidence of Awareness
Highest in OB
General Surgery with ETT (1%)
Cardiac Surgery (pure narcotic)
Trauma (shock and severe injury does not equal unconsciousness)
Reasons for Intraoperative Awareness
Equipment Failure Inadequate Anesthesia Patient Factors (age, health status, alcohol/drug use, obesity, pharmacokinetic/pharmacodynamic) Inability to assess depth of anesthesia Inappropriate anesthesia technique
Likely times for recall in anesthesia
Preinduction (light induction for various reasons)
After Intubation (paralyzed but not anesthetized)
Intraoperative (light anesthesia w/ paralysis, wakeup test well tolerated)
Postoperative (residual paralysis during emergence)
What are Guedels Signs and Stages?
Stage I Analgesia or Disorientation
Stage II Excitement or Delirium
Stage III Surgical Anesthesia
Stage IV Overdose
Guedels Signs and Stages - Stage I
Analgesia or Disorientation
From beginning of induction of anesthesia to loss of consciousness
Guedels Signs and Stages - Stage II
Excitement or Delirium
From loss of consciousness to onset of automatic breathing
Eyelash reflex disappears but other reflexes remain intact, pupils dilated but reactive, tearing, coughing, vomiting and strugglilng may occur; respiration can be irregular with breath-holding
Guedels Signs and Stages - Stage III
Surgical Anesthesia
Begins with onset of regular respiratory pattern and ends with loss of respiration
Guedels Signs and Stages - Stage III Phane I
Onset of automatic respiration to cessation of eyeball movements
Eyelid reflex is lost, swallowing reflex disappears, marked eyeball movement may occur but conjunctival reflex is lost at the bottom at the bottom of the plane
Guedels Signs and Stages - Stage III Phane II
Cessation of eyeball movements to beginning of paralysis of intercostal muscles
Laryngeal reflex is lost although inflammation of the upper resp tract increases reflex irritability, corneal reflex disappears, secretion of tears increases, respiration is automatic and regular, movement and deep breathing as a response to skin simulation disappears
Guedels Signs and Stages - Stage III Phane III
From beginning to completion of intercostal muscle paralysis
Diaphragmatic respiration persists but there is progressive intercostal paralysis, pupils dilated and light reflex is abolished. Laryngeal reflex lost in plane II can still be initiated by painful stimuli arising from the dilatation of anus or cervix.
Desired plane for surgery when muscle relaxants were not used
Guedels Signs and Stages - Stage III Plane IV
From complete intercostal paralysis to diaphragmatic paralysis (apnea)
Guedels Signs and Stages - Stage IV
From stoppage of respiration till death
Anesthetic overdose causes medullary paralysis with respiratory arrest and vasomotor collapse
Pupils are widely dilated and muscles are relaxed
Pros and Cons of Guedels Signs and Stages
Good indicators of narcosis
Provide greater knowledge about the level of anesthesia (MAC provides boundaries)
Are important to know physiologic loss of reflexes related to level of anesthesia
Do NOT work well when using opioids and muscle relaxants
What rate does a resting brain consume oxygen?
3.5 mL oxygen per 100g of brain tissue per minute (50mL/min)
Receives 12-15% of cardiac output
What function is the brain’s energy utilized for?
Approx 60% of brain’s energy consumption is used to support electrophysiologic function (Maintenance of transmembrane ionic gradients (Na/K pump)
Synthesis, storage, release and reuptake of neurotransmitters)
Remainder of energy is used to maintain cellular homeostasis
Energy Requirements of the Brain
Requires oxygen and glucose for sustained function
Glucose regenerates ATP by oxidative metabolism
Has insignificant glycogen storage - dependent on constant supply (maintained by adequate blood flow)
What arteries supplies cerebral blood flow
Internal carotid and vertebral arteries
What do the vertebral arteries form?
The single basilar artery
What arteries form the circle of Willis?
Internal carotid arteries Anterior Cerebral Anterior Communicating Posterior Communicating Posterior Cerebral Basilar
What contains most of the cerebral blood volume?
Dural Sinuses
Passive recipient of “regulated” arterial inflow
What is the normal cerebral metabolic rate (CMRO2)?
Remains stable between 3.0 and 3.8 mL /100g/min
What is the global CBF at normocarbia?
45 to 65 mL /100g/min
What is CBF-CMRO2 Coupling?
Blood flow is increased to areas of increased CMRO2 and vice versa
(normal brain will self regulate delivery of blood to areas that need it)
When is CMRO2 decreased?
During sleep and coma
When is CMRO2 increased?
Sensory stimulation
Mental tasks
Epileptic activity
How does Hypothermia affect CMRO2?
It decreases by 6% to 7% for each 1 degree C reduction in temperature
Can cause complete suppression of EEG at 18 to 20 degrees C
Decreases rate of energy utilization associated with both electrophysiological function and maintenance of cellular integrity
How does Hyperthermia affect CMRO2?
Between 37C and 42C both CBF and CMRO increase
Above 42*C a dramatic reduction in CMRO occurs (indicated threshold for the toxic effect of hyperthermia that may occur as a result of protein degradation
What happens to EEG waves as body temperature decreases?
EEG waves flatten
How to anesthetics affect CMRO2?
In general anesthetics decrease it with the exceptions of Ketamine and Nitrous Oxide
Increasing plasma concentrations of anesthetics beyond the level of initial EEG suppression does not further decrease CMRO
What are the primary factors controlling CBF in the normal brain?
Carbon Dioxide (central)
Oxygen (peripheral)
Cerebral Perfusion Pressure
How does PaCO2 affect CBF?
PaCO2 is the most potent physiologic determinant of CBF
CBF varies directly with PaCO (directly proportionate between 20 and 80) (Double CO2 - CBF doubles vice versa)
CBF changes 1 to 2 mL/100g/min for each 1 mmHg change in PaCO around normal PaCO
Above 80 = maximum vasodilation
Below 20 = maximal vasoconstriction
What happens to CMRO2 when there is a PaCO greater than 80?
a reduction in CMRO occurs reflecting the anesthetic effect of extreme hypercarbia (why pts become unresponsive)
How long to changes in CBF last?
CBF returns to normal over a period of 6 to 8 hours
How does PaO2 below 60 affect CBF?
Below a PaO2 of 60, CBF increases rapidly
“Oxygen Sensor” - located in the rostral ventrolateral medulla (stimulation results in an increase in CBF and not in CMRO)
Increased PaO has little effect on CBF
What range of cerebral perfusion pressure is CBF constant (Autoregulation)?
50 mmHg to 150 mmHg
CPP = MAP - ICP or CVP (whichever is greater)
What happens when CPP is above 150 mmHg?
it results in hypertensive encephalopathy due to BBB disruption, edema, and ischemia
What happens when CPP is below 50 mmHg?
it results in maximal vasodilation and CBF becomes pressure dependent
What direction does hypertension shift the curve?
To the Right
Limits the safe level for reduction CPP
Following successful treatment of HTN, curve returns to control levels
What is Cerebral Steal?
Stealing of blood from one area of the brain to another
In ischemic brain regions, blood vessels are maximally dilated - if vasodilation occurs due to hypercapnia or other reasons, the normal adjacent brain regions get vasodilated and receive an increased flow - Stealing flow from the ischemic area that needs it
What is Inverse Cerebral Steal?
Robin Hood effect
Vasoconstriction caused by hypocapnia or an anesthetic agent such as Sodium-Thiopental causes an increase in blood flow to ischemic regions
How do benzodiazepines affect CBF and CMRO2?
All cause a reduction in CBF due to a decrease in CVR and CMRO2
Induction dose of midazolam (0.15mg/kg) causes 40% decrease in CBF
Fall in CBF not associated with any cerebral ischemia
Flumazenil reverses these effects and may increase CBF and CMRO2
How do barbiturates affect CBF and CMRO2?
Decrease in both CBF and CMRO
Incremental doses of pentathol may decrease CBF and CMRO by 55-60%
Has a direct vasoconstrictive effect (appears to be due to influx of calcium into VSM)
How does Propofol affect CBF and CMRO2?
Decreases both CBF and CMRO
May also decrease ICP particularly when combined with hyperventilation
No direct cerebral vascular effects (affects the vessels that supply the brain instead)
May cause hypotension which can cause decreased CPP
How does Etomidate affect CBF and CMRO2?
Decreases both CBF and CMRO
Causes minimal hemodynamic suppression, even in high doses
High incidence of myclonus
Causes adrenal cortical suppression
How does Ketamine affect CBF and CMRO2?
Causes significant increase in CBF and ICP but has lesser effects of CMRO
Should be avoided in pts at risk of high ICP
How does Nitrous Oxide affect CBF and CMRO2?
Has little effect on CMRO
When used alone with oxygen it is a potent vasodilator and may increase ICP
When combined with barbiturates, narcotics, volatile agents, or hypocarbia it has little or no effect on CBF and ICP
How do volatile anesthetics affect CBF and CMRO2?
All cause a dose related increase in CBF and a decrease in CMRO
How do volatile anesthetics affect cerebral autoregulation?
Dose-dependent depression of cerebral autoregulation
As does gets higher autoregulation decreases eventually going away
How does Halothane affect ICP?
It is a potent cerebral vasodilator and can cause increased ICP (hyperventilation to CO2 of 25 will abolish this effect)
potential for halothane induced cerebral toxicity with end expiration concentrations exceeding 2.3%
How does Enflurane affect CMRO?
it is less potent cerebral vasodilator than halothane but is more potent suppressor of CMRO
when administered at concentrations greater than 1.5 MAC it has a capacity to induce seizures (especially when combined with hypocapnia)
How does Isoflurane affect CBF and CMRO2?
Least potent cerebral vasodilator and the Most potent depressant of CMRO (when compared to halothane/enflurane)
Does not increase CBF at doses less than 1 to 1.5 MAC
How does Desflurane affect CBF and CMRO2?
In clinically used concentrations in humans it does not adversely affect ICP
Dose dependent increase in CBF and decrease in CMRO at least up to 2 MAC (same as isoflurane)
Has advantage of rapid onset and emergence
How does Sevoflurane affect CBF and CMRO2?
It causes little to no increase in ICP at concentrations up to 1.5 MAC
Cerebral autoregulation has been found to be intact at concentrations below 1 MAC
There is no evidence of acute tolerance or cerebral toxicity after prolonged exposure to higher concentrations
What kind of amnesia do benzodiazepines produce?
Anterograde Amnesia
