August 5, 2025 • 45 mins
Continue your journey to mastering anaesthesia—one chapter at a time.
In this episode, Dr. J.R. Decker reads and discusses Chapter 8 (Part 3) of Morgan & Mikhail’s Clinical Anesthesiology (7th Edition).
Follow as you read along to strengthen your foundations in anaesthesia, one clear and engaging session at a time.
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Episode Transcript
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(00:01):
Morgan and Mikhail's Clinical Anesthesiology, 7th Edition,
Chapter 8, Part 3. Anaesthetic neuroprotection and
cardiac preconditioning Althoughinhalational agents have been
(00:26):
suggested as contributing to neurotoxicity, they have also
been shown to provide both neurologic and cardiac
protective effects against ischemia reperfusion injury.
(00:48):
Ischemic preconditioning impliesthat a brief ischemic episode
protects a cell from future, more pronounced ischemic events.
Various molecular mechanisms have been suggested to protect
(01:09):
cells preconditioned either through ischemic events or
secondary to pharmacologic mechanisms, such as through the
use of inhalational anaestheticsin the heart.
Preconditioning in part arises from actions at adenosine
(01:34):
triphosphate, that is ATP sensitive.
Potassium channels K ATP. The exact mechanism of
anaesthetic preconditioning is likely to be multifocal and
includes the opening of KATP channels, resulting in less
(01:59):
mitochondrial calcium ion concentration and reduction of
reactive oxidin species production.
Ros production. Ros contributes to cellular
injury. Anaesthetic preconditioning may
(02:24):
be the result of increased production of antioxidants
following initial anaesthesia exposure.
Additionally, excise T3 NMDA receptors are linked to the
development of neuronal injury. NMDA antagonists such as the
(02:53):
noble anaesthetic gas xenon havebeen shown to be
neuroprotective. Xenon has an anti apoptotic
effect that may be secondary to its inhibition of calcium ion
influx following cell injury. As with neurotoxicity, the role
(03:23):
of inhalational anaesthetics in tissue protection is the subject
of ongoing investigation. Studies have demonstrated
beneficial effects of inhalational anaesthetics in
coronary artery bypass surgery. Additionally, inhalational
(03:48):
anaesthetics may offer protection against inflammatory
lung injury. Anaesthetic Immunomodulation.
Inhaled anaesthetics have been shown to have immunosuppressive
(04:13):
effects. Although immunosuppression may
be desirable in inflammatory conditions, for example lung
inflammation, it may prove deleterious in patients
undergoing cancer therapy. As a consequence, avoidance of
(04:36):
inhalational anaesthetics have been suggested by some in favour
of intravenous agents, that is, other than opioids in the
perioperative management of patients with cancer.
(04:56):
Minimum alveolar concentration 6.
The Mac of an inhaled anaesthetic is the alveolar
concentration that prevents movement in 50% of patients in
(05:20):
response to a standardised stimulus, for example surgical
incision. Mac is a useful measure because
it mirrors brain partial pressure, allows comparisons of
(05:40):
potency between agents, and provides a standard for
experimental evaluations. Nonetheless, it should be
remembered that this is a medianvalue with limited usefulness in
managing individual patients, particularly during times of
(06:06):
rapidly changing alveolar concentrations, for example,
induction and emergence. Next, we get to Table 8-3,
showing the properties of moderninhalation and aesthetics under
(06:32):
the following titles. Agent Structure.
MEC Percentage and vapour pressure.
Kindly pause this recording to go through this table.
The Mac values of anaesthetic combinations are roughly
(06:58):
additive. For example, a mixture of 0.5
Mac of nitrous oxide that is 53%and 0.5 MEC of isofluorine that
is 0.6% produces the same likelihood that movement in
(07:24):
response to a surgical incision will be suppressed as 0.1 MEC of
isofluorine that is 1.2% or zeropoint OR or one sorry let's take
it again will be suppressed as one MEC of isoflorane that is
(07:47):
1.2% or one MEC of any other single agent.
In contrast to CNS depression, the degree of myocardial
depression may not be equivalentat the same MEC. 0.5 MEC of
(08:13):
halothane causes more myocardialdepression than 0.5 MEC of
nitrous oxide. MEC represents only one point on
the concentration response curve.
It is the equivalent of a medianeffective concentration, that is
(08:38):
EC50. MEC multiplies.
MEC multiples are clinically useful if the concentration
response calls of the anaesthetics being compared are
parallel, nearly linear and continuous for the effect being
(09:03):
predicted. Roughly 1.3 MEC of any of the
volatile anaesthetics. For example, for halothene, 1.3
* 0.75% which is equal to 0.97% has been found to prevent
(09:26):
movement in about 95% of patients.
That is an approximation of the EC950 point 3 to 0.4.
MEC is associated with a weakening from anaesthesia.
That is MEC awake when the inhaled drug is the only agent
(09:52):
maintaining anaesthetic, which is a rare circumstance.
Mac can be altered by several physiological and
pharmacological and pharmacologic variables shown in
Table 8-4. One of the most striking is the
(10:19):
6% decrease in Mac per decade ofeach.
Regardless of volatile anaesthetic.
Mac is relatively unaffected by specie, sex or duration of
(10:41):
anaesthesia. Further, as noted earlier, Mac
is not altered after spinal cordtransaction in rats, leading to
the hypothesis that the site of anaesthetic inhibition of mutual
(11:01):
responses lies in the spinal cord.
Table 8-4 is next talking about factors affecting Mac with the
(11:21):
following headings, the variableeffects on MEC and comments.
The variables, I'll just go through them quickly.
(11:45):
Just the headings, Temperature, age, alcohol, anaemia, P,
AO2PAC, O2, thyroid, blood pressure, electrolytes,
(12:14):
pregnancy and drugs. Kindly pause this recording to
go through this table. It's hyphen for clinical
(12:42):
pharmacology of inhalation anaesthetics.
Nitrous oxide Physical properties.
Nitrous oxide that is N2O or laughing gas is colourless and
(13:09):
essentially odourless. Although non explosive and non
flammable, nitrous oxide is as capable as oxygen of supporting
combustion. Unlike the potent volatile
(13:30):
agents, nitrous oxide is a gas at room temperature and ambient
pressure. It can be kept as a liquid under
pressure because it's critical temperature, that is, the
(13:51):
temperature at which a substancecannot be kept as a liquid
irrespective of the pressure applied, lies above room
temperature. Nitrous oxide is a relatively
inexpensive anaesthetic. However, concerns regarding its
(14:15):
safety have led to continued interest in alternatives such as
xenon. As noted earlier, nitrous oxide,
like xenon, is an NMDA receptor antagonist.
(14:38):
Next we get to Table 8-5, talking about the advantages and
disadvantages of xenon anaesthesia.
Kindly pause this recording to go through this table.
(15:02):
Effects on organ Systems A cardiovascular nitrous oxide
tends to stimulate the sympathetic nervous system.
Thus, even though nitrous oxide directly depresses myocardial
(15:23):
contractility in vitro, arterialblood pressure, cardiac output,
and heart rate are essentially unchanged or slightly elevated
in vivo. Because of its stimulation of
catecholamines, myocardial depression may be unmasked in
(15:48):
patients with coronary artery disease or severe hypovolemia.
Constriction of pulmonary vascular smooth muscle increases
pulmonary vascular resistance, which results in a generally
(16:08):
modest elevation over right ventricular end diastolic
pressure. Despite vessel constriction of
cutaneous vessels, peripheral vascular resistance is not
significantly altered. Next we get to Table 8-6 talking
(16:37):
about the clinical pharmacology of inhalational anaesthetics.
Kindly pause this recording to go through this very important
Table 8-6. B Respiratory nitrous oxide
(17:02):
increases respiratory rate, thatis tachypnea, and decreases
tidal volume as a result of CNS stimulation.
The net effect is a minimal change in minute ventilation and
resting arterial PCO. 2 hypoxic drive The ventilator response to
(17:32):
arterial hypoxia that is mediated by peripheral
chemoreceptors in the carotid bodies is markedly depressed by
even small amounts of nitrous oxide.
C Cerebral By increasing CBF andcerebral blood volume, nitrous
(18:02):
oxide produces a mild elevation of intracranial pressure.
Nitrous oxide also increases cerebral oxygen consumption,
that is, CMRO 2. Concentrations of nitrous oxide
(18:22):
below MEC may provide analgesia in dental surgery, labour,
traumatic injury, and minor surgical procedures.
D Neuromuscular. In contrast to other inhalation
(18:48):
agents, nitrous oxide provides no significant muscle
relaxation. In fact, at high concentrations
in hyperbaric chambers, nitrous oxide causes skeletal muscle
(19:09):
rigidity. Nitrous oxide does not trigger
malignant hypothermia. E Renal nitrous oxide seems to
decrease kidney blood flow by increasing renal vascular
(19:31):
resistance. This leads to decreased
glomerular filtration rate and urinary output.
F Hepatic Hepatic blood flow probably falls during nitrous
(19:54):
oxide anaesthesia, but to a lesser extent than with volatile
agents. G Gastrointestinal The use of
nitrous oxide in adults increases the risk of post
(20:16):
operative nausea and vomiting. Presumably as a result of
activation of the chemoreceptor trigger zone and the vomiting
centre in the medulla. Biotransformation and toxicity.
(20:41):
During emergence, almost all nitrous oxide is eliminated by
exhalation. A small amount diffuses out
through the skin. Biotransformation is limited to
the less than 0.01% that undergoes reductive metabolism
(21:06):
in the gastrointestinal tract byanaerobic bacteria. 7 By
irreversibly oxidising the cobalt atom in vitamin B12,
nitrous oxide inhibits enzymes that are vitamin B12 dependent.
(21:35):
These enzymes include methioninesynthesis, which is necessary
for myelin formation, and thyme thymidilate synthesis, which is
necessary for DNA synthesis. Prolonged exposure to
(21:57):
anaesthetic concentrations of nitrous oxide can result in bone
marrow depression, that is, megaloblastic anaemia, and even
neurologic deficiencies, that is, peripheral neuropathies.
(22:18):
However, administration of nitrous oxide for bone marrow
harvest does not seem to affect the viability of bone marrow
mononuclear cells. Because of possible teratogenic
effects, nitrous oxide is often avoided in pregnant patients who
(22:45):
are not yet in the third trimester.
Nitrous oxide may also alter theimmunologic response to
infection by affecting chemotaxis and motility of
polymorphonuclear leukocytes. Contraindications Although
(23:13):
nitrous oxide is relatively insoluble in comparison with
other inhalation agents, it is 35 times more soluble than
nitrogen in blood. Thus, it tends to diffuse into
(23:34):
air containing cavities more rapidly than nitrogen is
absorbed by the bloodstream. For instance, if a patient with
100 mil pneumatorax inhales 50% nitrous oxide, the gas content
(23:58):
of the pneumatorax will tend to approach that of the
bloodstream. Because nitrous oxide will
diffuse into the cavity more rapidly than the air that is
principally nitrogen diffuses out.
(24:21):
Sorry, because nitrous oxide will diffuse into the cavity
more rapidly than the air that is principally nitrogen diffuses
out. The pneumothorax expands until
it contains roughly 100 mills ofair and 100 mills of nitrous
(24:42):
oxide. If the walls surrounding the
cavity are rigid, pressure risesinstead of volume.
Examples of conditions in which nitrous oxide might be hazardous
include venous or arterial air embolism, pneumothorax, acute
(25:08):
intestinal obstruction with boreal distention, intracranial
air that is pneumocephalus following dural closure or
pneumoencephalography, pulmonaryair CIS, intraocular air
(25:30):
bubbles, and tympanic membrane grafting.
Nitrous oxide will even diffuse into tracheal tube coughs,
increasing the pressure against the tracheal mucosa.
(25:54):
Obviously, nitrous oxide is of limited value in patients
requiring increased inspired oxygen concentrations drug
interactions. Because the high Mac of nitrous
(26:18):
oxide prevents its use as a complete general anaesthetic, it
is frequently used in combination with a more potent
volatile agents. The addition of nitrous oxide
decreases the requirements of these other agents.
(26:41):
That is, 65% nitrous oxide decreases the MEC of the
volatile anaesthetics by approximately 50%.
Although nitrous oxide should not be considered a benign
carrier gas, it does attenuate the circulatory and respiratory
(27:07):
effects of volatile anaestheticsin adults.
The concentration of nitrous oxide flowing through a
vaporizer can influence the concentration of volatile
anaesthetic delivered. For example, decreasing nitrous
(27:30):
oxide concentration, that is, increasing oxygen concentration,
increases this concentration of volatile agents despite a
constant vaporizer setting. This disparity is due to the
(27:50):
relative solubilities of nitrousoxide and oxygen in liquid
volatile anaesthetics. The second gas effect was
discussed earlier. Nitrous oxide is an ozone
depleting gas with greenhouse effects.
(28:16):
Sorry, let's take it again. Nitrous oxide is an ozone
depleting gas with greenhouse effects.
Halothane physical properties. Halothane is a halogenated
(28:43):
arcane carbon. Fluoride bonds are responsible
for its non flammable and non explosive nature.
Effects on organ systems A cardiovascular A dose dependent
(29:13):
reduction of arterial blood pressure is due to direct
myocardial depression. Two point O Mac of halothane in
patients not undergoing surgery results in a 50% decrease in
(29:36):
blood pressure and cardiac output.
Cardiac depression from interference with sodium calcium
exchange and intracellular calcium utilisation causes an
increase in right atrial pressure.
(30:00):
Although halothane is a coronaryartery vasodilator, coronary
blood flow decreases because of the drop in systemic arterial
pressure. Adequate myocardial perfusion is
(30:21):
usually maintained as myocardialoxygen demand also drops.
Normally, hypotension inhibits baroreceptors in the aortic arc
and carotid bifurcation, causinga decrease in vagal stimulation
(30:47):
and a compensatory rise in heartrate.
Halothene blunts this reflex. Slowing of sinoatrial node
conduction may result in a junctional rhythm or bradycardia
(31:11):
In infants. Halothane decreases cardiac
output by a combination of decreased heart rate and
depressed myocardial contractility.
Halothane sensitises the heart to the arythmogenic effects of
(31:34):
epinephrine, so doses of epinephrine above 1.5 micrograms
per kilogramme should be avoided.
Although organ blood flow is redistributed, systemic vascular
resistance is unchanged. B Respiratory hallucine
(32:04):
typically causes rapid shallow breathing.
The increased respiratory rate is not enough to counter the
decreased tidal volume, so alveolar ventilation drops and
resting PA CO2 is elevated. The APNIC threshold, the highest
(32:31):
PA CO2 at which a patient remains APNIC, also rises
because the difference between it and resting PA CO2 is not
altered by general anaesthesia. Similarly, halothane limits the
(32:53):
increase in minute ventilation that normally accompanies a rise
in PA CO2. Halothane's ventilatory effects
are probably due to central, that is medullary depression and
peripheral, that is intercostal muscle dysfunction mechanisms.
(33:20):
These changes are exaggerated bypre-existing lung disease and
attenuated by surgical stimulation.
The increase in PA CO2 and the decrease in intrathoracic
pressure that accompanies spontaneous ventilation with
(33:42):
halothane partially reverse the depression in cardiac output,
arterial blood pressure, and heart rate described above.
The hypoxic Dr is severely depressed by even low
concentrations of halothine, that is 0.1 MEC.
(34:12):
Halothine is a potent bronchodilator as it may reverse
asthma induced bronchospasm. This action is not inhibited by
beta hydrogenergic blocking agents.
(34:34):
Halothine attenuates airway reflexes and relaxes bronchial
smooth muscle by inhibiting intracellular calcium
mobilisation. Halothine also depresses the
clearance of mucus from the respiratory tract that is MUCO
(34:58):
ciliary function promoting post operative hypoxia.
Anatelectasis. C Cerebral By dilating cerebral
vessels, halothen lowers cerebral vascular resistance and
(35:22):
increases cerebral blood volume and CBF autoregulation.
The maintenance of constant CBF during changes in arterial blood
pressure is blunted. Concomitant rises in
(35:43):
intracranial pressure can be prevented by establishing
hyperventilation before administration of halothane.
Cerebral activity is decreased, leading to
electroencephalographic slowing and modest reductions in
(36:07):
metabolic oxygen requirements. D Neuromuscular halothine
relaxes skeletal muscle and potentiates non depolarizing
neuromuscular blocking agents that is Nmbas.
(36:32):
Like the other potent volatile anaesthetics, it is a trigger
for malignant hypothermia. E Renal halothen reduces renal
blood flow, glomerular filtration rate and urinary
(36:57):
output. Part of this decrease can be
explained by a fall in arterial blood pressure and cardiac
output. Because the reduction in renal
blood flow is greater than the reduction in glomerular
(37:17):
filtration rate, the filtration fraction is increased.
Preoperative hydration limits these changes.
F Hepatic halothine decreases hepatic blood flow in proportion
(37:44):
to the depression of cardiac output.
Hepatic artery vasospasm has been reported during halothine
anaesthesia. The metabolism and clearance of
some drugs, for example, fentanyl, fenitol, verapamil
(38:07):
seem to be impaired by halothine.
Other evidence of hepatic cellular dysfunction includes
sulfo, bromo, phalene, BSP dye retention, and minor liver
(38:27):
transaminase. Elevate elevations,
biotransformation and toxicity Halothane is oxidised in the
liver by a particular ISO enzymeof CYP that is 2.
(38:50):
EI to its principal metabolite, trifluoroacetic acid.
In the absence of oxygen, reductive metabolism may result
in a small number of hepatotoxicend products that covalently
(39:11):
bind to tissue macromolecules. This is more apt to occur
following enzyme induction by chronic exposure to
barbiturates. 8 Post operative hepatic dysfunction has several
(39:35):
causes. Viral hepatitis, impaired
hepatic perfusion, Pre-existing liver disease.
Hepatocytes, Hypoxia. Sepsis, hemolysis.
(40:01):
Benign post operative intrahepatic Cholestasis and
drug induced hepatitis. Halothane hepatitis is extremely
rare. Patients exposed to multiple
(40:26):
halothane anaesthetics at short intervals, middle-aged obese
women and persons with a familiar predisposition to
halothin toxicity or a personal history of toxicity are
considered to be at increased risk.
(40:53):
Signs are mostly related to hepatic injury such as increased
serum alanine and aspartate transferase, elevated bilirubin
that is leading to jaundice and encephalopathy.
(41:18):
The hepatic lesion seen in humans.
Sentry. Lobular necrosis also occurs in
rats pretreated with an enzyme inducer that is phenobarbital
and exposed to halothane under hypoxic conditions.
(41:44):
Fio 2 less than 14%. This halothane hypoxic model
implies hepatic damage from reductive metabolites or
hypoxia. Other evidence points to an
(42:08):
immune mechanism. For instance, some signs of the
disease indicate an allergic reaction, for example,
eosophilia, rash, eosinophilia rash, fever and do not appear
(42:32):
until a few days after exposure.Furthermore, an antibody that
binds to hepatocytes previously exposed to halothine has been
isolated from patients with halothine induced hepatic
(42:55):
dysfunction. These antibody response may
involve liver microsomal proteins that have been modified
by trifluoroacetic acid as the triggering antigens, that is,
trifluoroacetylated liver proteins such as microsomal
(43:20):
carboxyless esterase, microsomalcarboxyl lesterase.
Other inhibitional agents that undergo oxidative metabolism can
likewise lead to hepatitis. However, newer agents undergo
(43:46):
little to no metabolism and therefore do not form
trifluoroacetic acid protein adducts or produce the immune
response leading to hepatitis Contra indications.
(44:11):
It is prudent to withhold halothane from patients with
unexplained liver dysfunction following previous anaesthetic
exposure. Halothane, like all inhalational
(44:33):
anaesthetics, should be used with care and only in
combination with modest hyperventilation in patients
with intracranial mass lesions because of the possibility of
intracranial hypertension secondary to increased cerebral
(44:56):
blood volume and blood flow. Hypovolemic patients and some
patients with severe reductions in left ventricular function may
not tolerate halothenes. Negative iodotrophic effects.
(45:20):
Sensitization of the heart to catecholamines limits the
usefulness of halothenes when exogenous epinephrine is
administered, for example, in local anaesthetic solutions or
in patients with fail chromo cytoma drug interactions.
(45:50):
The myocardial depression seen with halothane is exacerbated by
beta adrenergic blocking agents and calcium channel blocking
agents. Tricyclic antidepressants and
monoamine oxidase inhibitors have been associated with
(46:12):
fluctuations in blood pressure and arrhythmias, though neither
represents an absolute Contra indication.
The combination of halothane andaminophylline has resulted in
ventricular arrhythmias. Yeah.
Morgan and Mikhail's Clinical Anesthesiology, 7th Edition,
Chapter 8, Part 3. Anaesthetic neuroprotection and
cardiac preconditioning Althoughinhalational agents have been
(00:26):
suggested as contributing to neurotoxicity, they have also
been shown to provide both neurologic and cardiac
protective effects against ischemia reperfusion injury.
(00:48):
Ischemic preconditioning impliesthat a brief ischemic episode
protects a cell from future, more pronounced ischemic events.
Various molecular mechanisms have been suggested to protect
(01:09):
cells preconditioned either through ischemic events or
secondary to pharmacologic mechanisms, such as through the
use of inhalational anaestheticsin the heart.
Preconditioning in part arises from actions at adenosine
(01:34):
triphosphate, that is ATP sensitive.
Potassium channels K ATP. The exact mechanism of
anaesthetic preconditioning is likely to be multifocal and
includes the opening of KATP channels, resulting in less
(01:59):
mitochondrial calcium ion concentration and reduction of
reactive oxidin species production.
Ros production. Ros contributes to cellular
injury. Anaesthetic preconditioning may
(02:24):
be the result of increased production of antioxidants
following initial anaesthesia exposure.
Additionally, excise T3 NMDA receptors are linked to the
development of neuronal injury. NMDA antagonists such as the
(02:53):
noble anaesthetic gas xenon havebeen shown to be
neuroprotective. Xenon has an anti apoptotic
effect that may be secondary to its inhibition of calcium ion
influx following cell injury. As with neurotoxicity, the role
(03:23):
of inhalational anaesthetics in tissue protection is the subject
of ongoing investigation. Studies have demonstrated
beneficial effects of inhalational anaesthetics in
coronary artery bypass surgery. Additionally, inhalational
(03:48):
anaesthetics may offer protection against inflammatory
lung injury. Anaesthetic Immunomodulation.
Inhaled anaesthetics have been shown to have immunosuppressive
(04:13):
effects. Although immunosuppression may
be desirable in inflammatory conditions, for example lung
inflammation, it may prove deleterious in patients
undergoing cancer therapy. As a consequence, avoidance of
(04:36):
inhalational anaesthetics have been suggested by some in favour
of intravenous agents, that is, other than opioids in the
perioperative management of patients with cancer.
(04:56):
Minimum alveolar concentration 6.
The Mac of an inhaled anaesthetic is the alveolar
concentration that prevents movement in 50% of patients in
(05:20):
response to a standardised stimulus, for example surgical
incision. Mac is a useful measure because
it mirrors brain partial pressure, allows comparisons of
(05:40):
potency between agents, and provides a standard for
experimental evaluations. Nonetheless, it should be
remembered that this is a medianvalue with limited usefulness in
managing individual patients, particularly during times of
(06:06):
rapidly changing alveolar concentrations, for example,
induction and emergence. Next, we get to Table 8-3,
showing the properties of moderninhalation and aesthetics under
(06:32):
the following titles. Agent Structure.
MEC Percentage and vapour pressure.
Kindly pause this recording to go through this table.
The Mac values of anaesthetic combinations are roughly
(06:58):
additive. For example, a mixture of 0.5
Mac of nitrous oxide that is 53%and 0.5 MEC of isofluorine that
is 0.6% produces the same likelihood that movement in
(07:24):
response to a surgical incision will be suppressed as 0.1 MEC of
isofluorine that is 1.2% or zeropoint OR or one sorry let's take
it again will be suppressed as one MEC of isoflorane that is
(07:47):
1.2% or one MEC of any other single agent.
In contrast to CNS depression, the degree of myocardial
depression may not be equivalentat the same MEC. 0.5 MEC of
(08:13):
halothane causes more myocardialdepression than 0.5 MEC of
nitrous oxide. MEC represents only one point on
the concentration response curve.
It is the equivalent of a medianeffective concentration, that is
(08:38):
EC50. MEC multiplies.
MEC multiples are clinically useful if the concentration
response calls of the anaesthetics being compared are
parallel, nearly linear and continuous for the effect being
(09:03):
predicted. Roughly 1.3 MEC of any of the
volatile anaesthetics. For example, for halothene, 1.3
* 0.75% which is equal to 0.97% has been found to prevent
(09:26):
movement in about 95% of patients.
That is an approximation of the EC950 point 3 to 0.4.
MEC is associated with a weakening from anaesthesia.
That is MEC awake when the inhaled drug is the only agent
(09:52):
maintaining anaesthetic, which is a rare circumstance.
Mac can be altered by several physiological and
pharmacological and pharmacologic variables shown in
Table 8-4. One of the most striking is the
(10:19):
6% decrease in Mac per decade ofeach.
Regardless of volatile anaesthetic.
Mac is relatively unaffected by specie, sex or duration of
(10:41):
anaesthesia. Further, as noted earlier, Mac
is not altered after spinal cordtransaction in rats, leading to
the hypothesis that the site of anaesthetic inhibition of mutual
(11:01):
responses lies in the spinal cord.
Table 8-4 is next talking about factors affecting Mac with the
(11:21):
following headings, the variableeffects on MEC and comments.
The variables, I'll just go through them quickly.
(11:45):
Just the headings, Temperature, age, alcohol, anaemia, P,
AO2PAC, O2, thyroid, blood pressure, electrolytes,
(12:14):
pregnancy and drugs. Kindly pause this recording to
go through this table. It's hyphen for clinical
(12:42):
pharmacology of inhalation anaesthetics.
Nitrous oxide Physical properties.
Nitrous oxide that is N2O or laughing gas is colourless and
(13:09):
essentially odourless. Although non explosive and non
flammable, nitrous oxide is as capable as oxygen of supporting
combustion. Unlike the potent volatile
(13:30):
agents, nitrous oxide is a gas at room temperature and ambient
pressure. It can be kept as a liquid under
pressure because it's critical temperature, that is, the
(13:51):
temperature at which a substancecannot be kept as a liquid
irrespective of the pressure applied, lies above room
temperature. Nitrous oxide is a relatively
inexpensive anaesthetic. However, concerns regarding its
(14:15):
safety have led to continued interest in alternatives such as
xenon. As noted earlier, nitrous oxide,
like xenon, is an NMDA receptor antagonist.
(14:38):
Next we get to Table 8-5, talking about the advantages and
disadvantages of xenon anaesthesia.
Kindly pause this recording to go through this table.
(15:02):
Effects on organ Systems A cardiovascular nitrous oxide
tends to stimulate the sympathetic nervous system.
Thus, even though nitrous oxide directly depresses myocardial
(15:23):
contractility in vitro, arterialblood pressure, cardiac output,
and heart rate are essentially unchanged or slightly elevated
in vivo. Because of its stimulation of
catecholamines, myocardial depression may be unmasked in
(15:48):
patients with coronary artery disease or severe hypovolemia.
Constriction of pulmonary vascular smooth muscle increases
pulmonary vascular resistance, which results in a generally
(16:08):
modest elevation over right ventricular end diastolic
pressure. Despite vessel constriction of
cutaneous vessels, peripheral vascular resistance is not
significantly altered. Next we get to Table 8-6 talking
(16:37):
about the clinical pharmacology of inhalational anaesthetics.
Kindly pause this recording to go through this very important
Table 8-6. B Respiratory nitrous oxide
(17:02):
increases respiratory rate, thatis tachypnea, and decreases
tidal volume as a result of CNS stimulation.
The net effect is a minimal change in minute ventilation and
resting arterial PCO. 2 hypoxic drive The ventilator response to
(17:32):
arterial hypoxia that is mediated by peripheral
chemoreceptors in the carotid bodies is markedly depressed by
even small amounts of nitrous oxide.
C Cerebral By increasing CBF andcerebral blood volume, nitrous
(18:02):
oxide produces a mild elevation of intracranial pressure.
Nitrous oxide also increases cerebral oxygen consumption,
that is, CMRO 2. Concentrations of nitrous oxide
(18:22):
below MEC may provide analgesia in dental surgery, labour,
traumatic injury, and minor surgical procedures.
D Neuromuscular. In contrast to other inhalation
(18:48):
agents, nitrous oxide provides no significant muscle
relaxation. In fact, at high concentrations
in hyperbaric chambers, nitrous oxide causes skeletal muscle
(19:09):
rigidity. Nitrous oxide does not trigger
malignant hypothermia. E Renal nitrous oxide seems to
decrease kidney blood flow by increasing renal vascular
(19:31):
resistance. This leads to decreased
glomerular filtration rate and urinary output.
F Hepatic Hepatic blood flow probably falls during nitrous
(19:54):
oxide anaesthesia, but to a lesser extent than with volatile
agents. G Gastrointestinal The use of
nitrous oxide in adults increases the risk of post
(20:16):
operative nausea and vomiting. Presumably as a result of
activation of the chemoreceptor trigger zone and the vomiting
centre in the medulla. Biotransformation and toxicity.
(20:41):
During emergence, almost all nitrous oxide is eliminated by
exhalation. A small amount diffuses out
through the skin. Biotransformation is limited to
the less than 0.01% that undergoes reductive metabolism
(21:06):
in the gastrointestinal tract byanaerobic bacteria. 7 By
irreversibly oxidising the cobalt atom in vitamin B12,
nitrous oxide inhibits enzymes that are vitamin B12 dependent.
(21:35):
These enzymes include methioninesynthesis, which is necessary
for myelin formation, and thyme thymidilate synthesis, which is
necessary for DNA synthesis. Prolonged exposure to
(21:57):
anaesthetic concentrations of nitrous oxide can result in bone
marrow depression, that is, megaloblastic anaemia, and even
neurologic deficiencies, that is, peripheral neuropathies.
(22:18):
However, administration of nitrous oxide for bone marrow
harvest does not seem to affect the viability of bone marrow
mononuclear cells. Because of possible teratogenic
effects, nitrous oxide is often avoided in pregnant patients who
(22:45):
are not yet in the third trimester.
Nitrous oxide may also alter theimmunologic response to
infection by affecting chemotaxis and motility of
polymorphonuclear leukocytes. Contraindications Although
(23:13):
nitrous oxide is relatively insoluble in comparison with
other inhalation agents, it is 35 times more soluble than
nitrogen in blood. Thus, it tends to diffuse into
(23:34):
air containing cavities more rapidly than nitrogen is
absorbed by the bloodstream. For instance, if a patient with
100 mil pneumatorax inhales 50% nitrous oxide, the gas content
(23:58):
of the pneumatorax will tend to approach that of the
bloodstream. Because nitrous oxide will
diffuse into the cavity more rapidly than the air that is
principally nitrogen diffuses out.
(24:21):
Sorry, because nitrous oxide will diffuse into the cavity
more rapidly than the air that is principally nitrogen diffuses
out. The pneumothorax expands until
it contains roughly 100 mills ofair and 100 mills of nitrous
(24:42):
oxide. If the walls surrounding the
cavity are rigid, pressure risesinstead of volume.
Examples of conditions in which nitrous oxide might be hazardous
include venous or arterial air embolism, pneumothorax, acute
(25:08):
intestinal obstruction with boreal distention, intracranial
air that is pneumocephalus following dural closure or
pneumoencephalography, pulmonaryair CIS, intraocular air
(25:30):
bubbles, and tympanic membrane grafting.
Nitrous oxide will even diffuse into tracheal tube coughs,
increasing the pressure against the tracheal mucosa.
(25:54):
Obviously, nitrous oxide is of limited value in patients
requiring increased inspired oxygen concentrations drug
interactions. Because the high Mac of nitrous
(26:18):
oxide prevents its use as a complete general anaesthetic, it
is frequently used in combination with a more potent
volatile agents. The addition of nitrous oxide
decreases the requirements of these other agents.
(26:41):
That is, 65% nitrous oxide decreases the MEC of the
volatile anaesthetics by approximately 50%.
Although nitrous oxide should not be considered a benign
carrier gas, it does attenuate the circulatory and respiratory
(27:07):
effects of volatile anaestheticsin adults.
The concentration of nitrous oxide flowing through a
vaporizer can influence the concentration of volatile
anaesthetic delivered. For example, decreasing nitrous
(27:30):
oxide concentration, that is, increasing oxygen concentration,
increases this concentration of volatile agents despite a
constant vaporizer setting. This disparity is due to the
(27:50):
relative solubilities of nitrousoxide and oxygen in liquid
volatile anaesthetics. The second gas effect was
discussed earlier. Nitrous oxide is an ozone
depleting gas with greenhouse effects.
(28:16):
Sorry, let's take it again. Nitrous oxide is an ozone
depleting gas with greenhouse effects.
Halothane physical properties. Halothane is a halogenated
(28:43):
arcane carbon. Fluoride bonds are responsible
for its non flammable and non explosive nature.
Effects on organ systems A cardiovascular A dose dependent
(29:13):
reduction of arterial blood pressure is due to direct
myocardial depression. Two point O Mac of halothane in
patients not undergoing surgery results in a 50% decrease in
(29:36):
blood pressure and cardiac output.
Cardiac depression from interference with sodium calcium
exchange and intracellular calcium utilisation causes an
increase in right atrial pressure.
(30:00):
Although halothane is a coronaryartery vasodilator, coronary
blood flow decreases because of the drop in systemic arterial
pressure. Adequate myocardial perfusion is
(30:21):
usually maintained as myocardialoxygen demand also drops.
Normally, hypotension inhibits baroreceptors in the aortic arc
and carotid bifurcation, causinga decrease in vagal stimulation
(30:47):
and a compensatory rise in heartrate.
Halothene blunts this reflex. Slowing of sinoatrial node
conduction may result in a junctional rhythm or bradycardia
(31:11):
In infants. Halothane decreases cardiac
output by a combination of decreased heart rate and
depressed myocardial contractility.
Halothane sensitises the heart to the arythmogenic effects of
(31:34):
epinephrine, so doses of epinephrine above 1.5 micrograms
per kilogramme should be avoided.
Although organ blood flow is redistributed, systemic vascular
resistance is unchanged. B Respiratory hallucine
(32:04):
typically causes rapid shallow breathing.
The increased respiratory rate is not enough to counter the
decreased tidal volume, so alveolar ventilation drops and
resting PA CO2 is elevated. The APNIC threshold, the highest
(32:31):
PA CO2 at which a patient remains APNIC, also rises
because the difference between it and resting PA CO2 is not
altered by general anaesthesia. Similarly, halothane limits the
(32:53):
increase in minute ventilation that normally accompanies a rise
in PA CO2. Halothane's ventilatory effects
are probably due to central, that is medullary depression and
peripheral, that is intercostal muscle dysfunction mechanisms.
(33:20):
These changes are exaggerated bypre-existing lung disease and
attenuated by surgical stimulation.
The increase in PA CO2 and the decrease in intrathoracic
pressure that accompanies spontaneous ventilation with
(33:42):
halothane partially reverse the depression in cardiac output,
arterial blood pressure, and heart rate described above.
The hypoxic Dr is severely depressed by even low
concentrations of halothine, that is 0.1 MEC.
(34:12):
Halothine is a potent bronchodilator as it may reverse
asthma induced bronchospasm. This action is not inhibited by
beta hydrogenergic blocking agents.
(34:34):
Halothine attenuates airway reflexes and relaxes bronchial
smooth muscle by inhibiting intracellular calcium
mobilisation. Halothine also depresses the
clearance of mucus from the respiratory tract that is MUCO
(34:58):
ciliary function promoting post operative hypoxia.
Anatelectasis. C Cerebral By dilating cerebral
vessels, halothen lowers cerebral vascular resistance and
(35:22):
increases cerebral blood volume and CBF autoregulation.
The maintenance of constant CBF during changes in arterial blood
pressure is blunted. Concomitant rises in
(35:43):
intracranial pressure can be prevented by establishing
hyperventilation before administration of halothane.
Cerebral activity is decreased, leading to
electroencephalographic slowing and modest reductions in
(36:07):
metabolic oxygen requirements. D Neuromuscular halothine
relaxes skeletal muscle and potentiates non depolarizing
neuromuscular blocking agents that is Nmbas.
(36:32):
Like the other potent volatile anaesthetics, it is a trigger
for malignant hypothermia. E Renal halothen reduces renal
blood flow, glomerular filtration rate and urinary
(36:57):
output. Part of this decrease can be
explained by a fall in arterial blood pressure and cardiac
output. Because the reduction in renal
blood flow is greater than the reduction in glomerular
(37:17):
filtration rate, the filtration fraction is increased.
Preoperative hydration limits these changes.
F Hepatic halothine decreases hepatic blood flow in proportion
(37:44):
to the depression of cardiac output.
Hepatic artery vasospasm has been reported during halothine
anaesthesia. The metabolism and clearance of
some drugs, for example, fentanyl, fenitol, verapamil
(38:07):
seem to be impaired by halothine.
Other evidence of hepatic cellular dysfunction includes
sulfo, bromo, phalene, BSP dye retention, and minor liver
(38:27):
transaminase. Elevate elevations,
biotransformation and toxicity Halothane is oxidised in the
liver by a particular ISO enzymeof CYP that is 2.
(38:50):
EI to its principal metabolite, trifluoroacetic acid.
In the absence of oxygen, reductive metabolism may result
in a small number of hepatotoxicend products that covalently
(39:11):
bind to tissue macromolecules. This is more apt to occur
following enzyme induction by chronic exposure to
barbiturates. 8 Post operative hepatic dysfunction has several
(39:35):
causes. Viral hepatitis, impaired
hepatic perfusion, Pre-existing liver disease.
Hepatocytes, Hypoxia. Sepsis, hemolysis.
(40:01):
Benign post operative intrahepatic Cholestasis and
drug induced hepatitis. Halothane hepatitis is extremely
rare. Patients exposed to multiple
(40:26):
halothane anaesthetics at short intervals, middle-aged obese
women and persons with a familiar predisposition to
halothin toxicity or a personal history of toxicity are
considered to be at increased risk.
(40:53):
Signs are mostly related to hepatic injury such as increased
serum alanine and aspartate transferase, elevated bilirubin
that is leading to jaundice and encephalopathy.
(41:18):
The hepatic lesion seen in humans.
Sentry. Lobular necrosis also occurs in
rats pretreated with an enzyme inducer that is phenobarbital
and exposed to halothane under hypoxic conditions.
(41:44):
Fio 2 less than 14%. This halothane hypoxic model
implies hepatic damage from reductive metabolites or
hypoxia. Other evidence points to an
(42:08):
immune mechanism. For instance, some signs of the
disease indicate an allergic reaction, for example,
eosophilia, rash, eosinophilia rash, fever and do not appear
(42:32):
until a few days after exposure.Furthermore, an antibody that
binds to hepatocytes previously exposed to halothine has been
isolated from patients with halothine induced hepatic
(42:55):
dysfunction. These antibody response may
involve liver microsomal proteins that have been modified
by trifluoroacetic acid as the triggering antigens, that is,
trifluoroacetylated liver proteins such as microsomal
(43:20):
carboxyless esterase, microsomalcarboxyl lesterase.
Other inhibitional agents that undergo oxidative metabolism can
likewise lead to hepatitis. However, newer agents undergo
(43:46):
little to no metabolism and therefore do not form
trifluoroacetic acid protein adducts or produce the immune
response leading to hepatitis Contra indications.
(44:11):
It is prudent to withhold halothane from patients with
unexplained liver dysfunction following previous anaesthetic
exposure. Halothane, like all inhalational
(44:33):
anaesthetics, should be used with care and only in
combination with modest hyperventilation in patients
with intracranial mass lesions because of the possibility of
intracranial hypertension secondary to increased cerebral
(44:56):
blood volume and blood flow. Hypovolemic patients and some
patients with severe reductions in left ventricular function may
not tolerate halothenes. Negative iodotrophic effects.
(45:20):
Sensitization of the heart to catecholamines limits the
usefulness of halothenes when exogenous epinephrine is
administered, for example, in local anaesthetic solutions or
in patients with fail chromo cytoma drug interactions.
(45:50):
The myocardial depression seen with halothane is exacerbated by
beta adrenergic blocking agents and calcium channel blocking
agents. Tricyclic antidepressants and
monoamine oxidase inhibitors have been associated with
(46:12):
fluctuations in blood pressure and arrhythmias, though neither
represents an absolute Contra indication.
The combination of halothane andaminophylline has resulted in
ventricular arrhythmias. Yeah.
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