A. Mortality rate in an established case is very high
B. Rhabdomyolysis is one of the diagnostic criteria
C. Tachycardia is an early sign of this syndrome
D. Cardiac dysfunction is very common in this condition
100. A patient is undergoing resection of a supratentorial brain tumor. He is normocarbic,
and his mean blood pressure is 70 mm Hg. Administration of which of the following
is most likely to decrease cerebral blood volume?
A. Nitrous oxide at 0.5 minimum alveolar concentration (MAC)
101. Which of the following classes of drugs is most likely to be responsible for an
anaphylactic reaction during general anesthesia?
A. Neuromuscular-blocking drugs
1. D. Clearance of drugs that are mainly metabolized in the liver is a function of the
amount of drug brought into the liver by its blood flow multiplied by ability of the
hepatocytes to clear the blood of that drug. For drugs that have a high extraction
ratio, the liver removes the entire drug entering the liver in one pass. Lidocaine and
propranolol are examples of this kind of clearance. Alfentanil, on the other hand, has
a low extraction ratio, and liver blood flow does not really affect its clearance.
Instead, it is the intrinsic ability of the liver to clear the blood of this drug that
determines alfentanil’s clearance. Cytochrome P450 system can metabolize a wide
variety of drugs by a single group of enzymes.
2. D. Many patients believe that they are allergic to local anesthetic. Questioning
them about it is important; otherwise, options for safe delivery of anesthesia can get
challenging. Dentists usually add epinephrine to the local anesthetic to decrease the
bleeding associated with the dental procedure. If any epinephrine gets access to the
vascular system, it can cause transient tachycardia and hypertension that patient may
describe as palpitations, flushing, and dizziness. If labeled as an allergic reaction, it
may limit anesthetic options for the patient in the future. In an emergent situation
where a spinal anesthetic could have been possible, one may have to utilize general
anesthesia and risk airway complications. It is important to elucidate the real allergic
reaction for an elective case by subjecting the patient to allergy testing. Serum testing
is available. Skin testing is not indicated because of the risks involved. Most of the
allergic reactions observed with local anesthetics are not due to the local anesthetic
molecule but either to para-aminobenzoic acid, a metabolite of ester local
anesthetics, or to methylparaben and metabisulphite, which are both preservatives.
True type 1 allergic reaction with local anesthetic is extremely rare but will present
as anaphylaxis with hypotension and respiratory symptoms. Vasovagal response
usually manifests as pale skin with very low heart rate and blood pressure. Although
this patient did have light-headedness, she also had flushing and palpitation which is
not consistent with vasovagal reaction.
3. D. Effect of sympathomimetic drugs on the mean arterial blood pressure is
mediated through their effect on the adrenergic receptors they stimulate. Ultimate
effect is generated through complex interaction of different factors based on baseline
sympathetic tone, patient’s volume status, and condition of the heart. Although
isoproterenol increases contractility through its action on β2
receptors in big vascular beds like muscle, causing vasodilatation and
decreasing the systemic vascular resistance. So despite increasing contractility of the
heart and increasing the cardiac output, the mean arterial blood pressure can decrease
with administration of this drug. Other medications increase the mean arterial blood
pressure by their effect on α1 and β1
4. D. All of these catecholamines cause stimulation of β1
cardiac contractility, but norepinephrine also has a very strong effect on α1
thus increasing afterload to such a degree that cardiac output may actually decrease
after administration of this drug.
Cardiac output = Systemic blood pressure/Systemic vascular resistance
According to this formula, systemic vascular resistance (SVR) is inversely related to
cardiac output; thus, an increase in the SVR may decrease the cardiac output. Other
drugs have more effect on cardiac contractility than on SVR, and thus, cardiac output
increases with their administration.
5. B. Effect of norepinephrine is on α1
receptors and systemic vascular resistance,
and thus on systemic mean arterial blood pressure may be so pronounced that there
may be a decrease in heart rate secondary to baroreceptor response. It does increase
the likelihood of cardiac dysrhythmias in the presence of some older anesthetics like
halothane as well as in hypoxia and hypercarbia.
receptors causes inhibition of release of norepinephrine, thus
decreasing the activity of the sympathetic nervous system. Hypotension and
bradycardia are side effects that sometimes limit the use of medications like
clonidine and dexmedetomidine. In the past, these drugs were used mainly as
antihypertensives, but applications based on their sedative, anxiolytic, and analgesic
properties are becoming increasingly common. Dry mouth may also result from the
7. C. Labetalol is a competitive antagonist at the α1 and β adrenergic receptors. It is a
useful agent in the perioperative period because vasodilatation caused by α1
blockade is not accompanied with tachycardia with its attendant risks. It is a
particularly useful drug in hypertensive patient with diagnosis of aortic dissection as
it decreases the sheer force across the dissection. It does not cross the placenta and
does not decrease the uterine blood flow even when patient is hypotensive, so it is
used in obstetric patients with preeclampsia to control their blood pressure.
Clonidine is a stimulant of α2
receptors, thus decreasing sympathetic activity, and its
long-term administration leads to up regulation of adrenergic receptors. Sudden
withdrawal of this medication leads to overactivity of the sympathetic system and a
β-blocker antagonist is very helpful in controlling the manifestations of this
overactivity. Abnormalities of cardiac conduction system are a relative
contraindication to the administration of labetalol as it may worsen the degree of
8. D. Although all of these medications may be useful in the event of anaphylaxis
during a general anesthetic, epinephrine is considered to be the drug of choice and is
indicated as the first line of treatment. Dose depends on the severity of the reaction
and may be anywhere from 10 μg to 1 mg if cardiac arrest develops. Its α1 action
counteracts the severe vasodilatation, which is the hallmark of this condition. Its β2
action helps treat bronchoconstriction while β1 action helps support the cardiac
-blockers are also indicated in the treatment of anaphylaxis and
help mitigate the effects of type 1 antigen antibody reaction on mast cells and other
mediators, causing vascular dilatation and increased capillary permeability, but their
actions are neither as rapid nor as profound as epinephrine. Steroids stabilize the cell
membranes of mast cells and eosinophils, thus decreasing the intensity of the
immunologic response, but their action takes 4 to 6 hours to develop, and there is
little evidence to support the use of steroids for the acute treatment of anaphylaxis.
9. C. Etomidate actually causes a decrease in the seizure threshold, and is thus useful
in cases of electroconvulsive therapy for severe depression. Spontaneous movements
characterized as myoclonus occur in more than 50% of patients receiving etomidate
and may be associated with seizure-like activity on the EEG. Another side effect is
an increased incidence of nausea and vomiting in the postoperative period. It does
not cause histamine release in contrast to thiopental, which has been shown to release
10. C. Ketamine differs from other induction agents used in contemporary practice of
information from the RES to cerebral cortex) from the limbic cortex (which is
involved with the awareness of sensation). In sharp contrast to other anesthetic
agents, it increases blood pressure, heart rate, and cardiac output by central
stimulation of sympathetic system and inhibition of uptake of norepinephrine. In the
same vein, its effect on the ventilator drive and airway reflexes is minimal, if any. It
is an excellent bronchodilator and analgesic. Thiopental, propofol, and etomidate, on
the other hand, may be anti-analgesic.
11. B. Phenelzine inhibits monoamine oxidase, an enzyme that metabolizes
catecholamines, allowing their levels to build up in the adrenergic neurons. Ephedrine
has both direct and indirect actions on adrenergic system. Indirect action involves
release of exaggerated amounts of norepinephrine from the adrenergic neurons
leading to catastrophic increase in blood pressure. More direct-acting medication like
phenylephrine is a better choice in a patient using monoamine oxidase inhibitors.
12. A. Flumazenil is useful as a specific reversal agent for benzodiazepine overdose. It
has minimal intrinsic activity on this receptor, but because of similarity in the
chemical structure, it acts as a competitive antagonist in the presence of agonist at
the receptor site. Duration of action is short (60–90 minutes), so repeated doses or
infusion is required if recurrence of sedation is desired. Reversal of benzodiazepine
action does not lead to cardiovascular side effects or evidence of acute stress
response. It does not have any effect on opioid receptor, so is not useful to reverse
respiratory depression caused by narcotic overdose.
13. C. Although most common route of administration of midazolam in anesthesia is
intravenous, this drug can be given via many routes. Midazolam oral suspension is
used routinely in pediatric anesthesia. Intramuscular injection can be painful, but
intranasal route utilizing mucosal atomization device may be useful to treat seizure
activity. Bioavailability of sublingual midazolam is much better than orally
administered drug. Exposure of the acidic midazolam preparation to the physiologic
pH of blood causes a change in the ring structure that renders the drug more lipid
soluble, thus speeding its passage across the blood–brain barrier. There is no
preparation available for transcutaneous delivery of this drug in comparison to
14. A. Since local anesthetics are weak bases, they exist largely in the ionic form,
making it difficult for them to cross the cell membrane, thus delaying their local
anesthetic action. Addition of sodium bicarbonate promotes nonionized fraction of
local anesthetic, promoting more rapid onset of its action. Depending on the amount
injected, the local pH may increase, but effect on the intracellular pH is minimal, if
15. B. Cocaine inhibits reuptake of catecholamines into preganglionic nerve terminal; it
has a sympathomimetic effect, causing tachycardia, hypertension, pupillary dilatation,
and increased skin temperature. Chronic use may lead to cardiomyopathy and
depletion of catecholamine stores with unpredictable manifestations during
16. D. There are important differences between the two classes of local anesthetics.
Ester local anesthetics are metabolized by plasma cholinesterase, and so patients
with atypical variety of enzyme is liable to develop local anesthetic toxicity because
of slow metabolism. They are metabolized to para-aminobenzoic acid (PABA), and
individuals known to have allergy to this substance should not be given ester kind of
local anesthetic. Commercial multidose preparations of amides often contain
methylparaben, which has a chemical structure similar to that of PABA. This
preservative may be responsible for most of the rare allergic responses to amide
agents. Amide local anesthetics are metabolized by liver, and decreased liver blood
have amide structure in their molecule, except cocaine.
17. D. Ropivacaine is less lipid soluble, and thus less potent than bupivacaine. For a
given dose, the sensory block is more than the motor block. Part of the reason
ropivacaine may be less cardio toxic than bupivacaine is that it causes
vasoconstriction in the tissues, thus decreasing the rate of absorption into systemic
Enantiomers are stereoisomers that exist as mirror images. Enantiomers have
identical physical properties except for the direction of the rotation of the plane of
the polarized light. Ropivacaine is an S-enantiomer of mepivacaine and bupivacaine.
18. C. Oxygen demand of the myocardium increases with increase in heart rate and
blood pressure. Esmolol will decrease both the heart rate and blood pressure rapidly,
thus decreasing the oxygen demand. Hydralazine will decrease the blood pressure but
may make the tachycardia worse. Same is true for nitroprusside. Shivering increases
oxygen demand and needs to be treated promptly. Application of warming blanket
may be effective if patient is hypothermic, but it may take a while for the body
temperature to improve. It may not be effective in this patient if his temperature is
normal and if the mechanism of shivering involves inhibition of thermoregulatory
mechanisms of the body by the residual anesthetic.
Esmolol is a short-acting β-blocker that will decrease the heart rate and
myocardial contractility through its inhibition of β1
receptors, thus decreasing the
myocardial oxygen demand. Improved heart rate will also help with improved supply
of oxygen to the myocardium by increasing the diastolic time during which most of
the left-ventricular myocardium gets its oxygen.
19. C. Local anesthetics exert their electrophysiologic effects by blocking sodium ion
conductance. This effect is primarily mediated by interaction with specific receptors
that are within the inner vestibule of the sodium ion channel.
20. D. Local anesthetics decrease the rate of depolarization of the cell membrane when
a nerve impulse arrives and changes the resting membrane potential of the neuron.
Normally, this potential is −90 mV inside the cell. When an impulse reaches the cell,
it increases the inflow of sodium into the cell, causing this potential to move toward a
positive value. If this change is enough to reach a critical level called the threshold
potential, an action potential is generated; otherwise, the impulse dies down. Local
anesthetics decrease the rate of change of this potential so that it does not reach the
threshold level. They do not change the threshold potential or resting membrane
21. D. Lipid solubility of a local anesthetic is directly proportional to its potency. It is
ordinarily expressed as a partition coefficient, which is determined by comparing the
solubility in aqueous phase, generally water or buffered solution. Since the site of
action of the anesthetic molecule is inside the nerve cell, higher the proportion of
neutral base or the unionized form, higher the lipid solubility and higher the potency.
Ionization makes it more resistant to enter the cell and decreases its potency.
It is important to appreciate that measures of anesthetic activity may be affected
by the in vitro and in vivo system in which these effects are determined. For
example, tetracaine is 20 times more potent than bupivacaine when studied in
isolated nerve tissue but has equivalent potency compared with bupivacaine when
tested in intact in vivo systems. The effect actually may vary even in different areas
of the body like epidural space vs. peripheral nerve block because of secondary
effects such as the inherent vasoactive properties of the anesthetic.
22. A. Infiltration of local anesthetic in peripheral tissues is different from injection
into a nerve sheath for a peripheral nerve block. Duration of anesthesia after
infiltration is much less than after a nerve block. Anesthesia after ropivacaine and
bupivacaine lasts 4 to 8 hours, while lidocaine is effective only from 1 to 2 hours.
Mepivacaine is in between with duration of action from 90 to 180 minutes.
23. D. Use of many local anesthetics for spinal anesthesia is still evolving. Lidocaine
was introduced into clinical practice in 1946. It was commonly used for spinal
anesthesia until reports of transient neurologic symptoms (TNS) started appearing in
the literature. Incidence of TNS is relatively high with up to one-third of patients
complaining of pain and dysesthesia 12 to 24 hours after the surgery. Although
symptoms are transient, pain sometimes is so severe that it may exceed the pain of
surgery and may necessitate readmission into the hospital. This issue has raised
questions regarding the advisability of continued use of lidocaine for spinal
24. A. If central nervous system toxicity was to happen from slow absorption of local
anesthetic or injection into a vein, symptoms are usually milder to begin and escalate
finally to the seizure level. Early symptoms of local anesthetic toxicity may manifest
as circumoral numbness, metallic taste in the mouth, and tremors. As the serum
levels of the local anesthetic increase further, seizure may result due to excitation of
some focus in the central nervous system. Further increase in these levels leads to
depression of the nervous system manifesting as lethargy and coma.
Direct injection into a nerve usually causes a shooting pain along the length of
the nerve with involuntary withdrawal of the limb in an awake patient, not a seizure.
It is recommended to avoid performance of a nerve block under general anesthesia so
that patient could point to this, and thereby avoidance of nerve injury. Treatment is
supportive. Specific treatment for the seizure is either benzodiazepine or barbiturates
that increase the seizure threshold. It is important to control the seizure because
intense muscular activity increases oxygen utilization and carbon dioxide production,
causing both metabolic as well as respiratory acidosis. If the dose of bupivacaine
that gained access to vascular system is high, the major danger is cardio toxicity that
is made much worse and is extremely difficult to treat in the presence of acidosis.
25. D. It is recommended that the needle used for interscalene block should be of
appropriate length for the given patient. Nerve roots in this region are very
superficial and if a longer needle is used, a medially directed needle may end up in
either epidural or intrathecal space leading to high epidural or intrathecal block
respectively. This usually presents as catastrophic hypotension, respiratory distress
followed by cardiovascular collapse depending on the dose injected. Seizure is not a
presentation of high epidural or intrathecal injection. Higher protein-binding
decreases the chance of neurotoxicity by decreasing the free fraction of the drug
available for absorption into the circulation.
26. D. Frequent attempts at aspiration are recommended whenever large dose and
volume of local anesthetic is injected for epidural or peripheral nerve block to avoid
injecting the local anesthetic in the vascular or intrathecal space. Cases of local
anesthetic toxicity have been reported even when aspiration was negative for blood
Addition of a dilute concentration of epinephrine to local anesthetic is helpful as
it may alert the practitioner to inadvertent vascular injection of the local anesthetic
by increase in the heart rate. It also helps delay the systemic absorption of local
anesthetic, thus keeping the maximum serum concentration lower.
It is possible that loss of consciousness is secondary to cardiac arrest, but it
may also be secondary to high-dose CNS toxicity, respiratory arrest, or high
Amiodarone was the drug of choice to treat cardiovascular toxicity of
bupivacaine in the past, but now 20% intralipid has replaced this drug.
Recommended dosage for cardiovascular collapse secondary to bupivacaine toxicity
is 1.5 mL/kg bolus, followed by 0.25mL/kg/min for the next 10 minutes.
Oxygenation, ventilation, and good basic and advanced life support are extremely
essential as bupivacaine toxicity is adversely affected by hypercarbia, acidosis, and
27. D. Neuromuscular-blocking drugs (NMBDs) are highly charged molecules because
of the presence of a quaternary ammonium group in their structure. This makes them
poorly lipid soluble so that they do not cross biologic membranes like blood–brain
barrier, renal tubular epithelium, and placenta. Administration of these drugs thus
does not produce central nervous system effects; renal tubular reabsorption is
minimal, and maternal administration does not adversely affect the fetus. Issue of ion
trapping can only develop if a drug gets trapped in the acidic environment of fetal
blood after it has crossed the placenta.
28. D. Any time prolonged skeletal muscle inactivity or extensive muscle damage
exists, patient may be susceptible to hyperkalemia after the administration of
succinylcholine and is dependent on development of extrajunctional atypical
receptors. In some patients, potassium levels may exceed 10 mEq/L. This can lead to
serious cardiac arrhythmias and even cardiac arrest. The duration of susceptibility to
the hyperkalemic response to succinylcholine is unknown but probably decreases
after 3 to 6 months of denervation injury.
Although cerebral palsy seems to be a muscular problem, consensus is that it is
safe to use succinylcholine for these patients if airway management will be
29. B. Atypical plasma cholinesterase lacks the ability to hydrolyze ester bonds in
drugs such as succinylcholine and remifentanil. Diagnosis of presence of atypical
enzyme can be made by measuring the ability of dibucaine, a local anesthetic, to
inhibit the activity of this enzyme. A normal enzyme gets inhibited the most (80%),
while atypical homozygous type is minimally inhibited (20%). Heterozygous variety
In clinical terms, this leads to prolonged paralysis following administration of
succinylcholine, with duration ranging from 5 to 10 minutes with normal enzyme to
60 to180 minutes for patients having homozygous atypical variety of enzyme.
30. D. Choice of the muscle relaxant for any given anesthetic depends on many factors
like duration of surgical procedure, comorbidities of the patient, required speed of
onset, route of elimination, duration of action, and associated side effects like
tachycardia or hyperkalemia. Out of these factors, the duration of action depends on
the dose, presence of associated conditions like hypothermia, concomitant use of
drugs that influence the muscle relaxation like magnesium or calcium channels
blockers, and the presence of hepatic or renal disease. Intermediate acting
neuromuscular blockers like rocuronium and vecuronium undergo primarily hepatic
metabolism and biliary excretion with minimal renal excretion (10%–25%).
Many of the long-acting neuromuscular blockers are excreted by the kidney, and
their use in patients with renal failure may lead to prolonged neuromuscular
blockade. Pancuronium is one of these long-acting agents, and 80% of its
administered dose is excreted by the kidney. As discussed in the previous question,
succinylcholine is metabolized by the plasma cholinesterase and only a fraction of
the administered dose reaches the neuromuscular junction.
31. A. Onset and duration of action are largely dependent on the dose administered.
Although smaller doses can be effective, the recommended intubating dose is usually
two to four times higher than ED95
. This provides a higher incidence of better and
earlier intubating conditions than would be possible with ED95
to longer duration of action so that the return of the first twitch on train of four, a
prerequisite before a reversal agent can be administered, is delayed.
32. A. Anticholinesterases are used to reverse the effects of nondepolarizing
neuromuscular-blocking agents (NMBDs). Selection of these drugs depends on many
factors. One of the considerations is the ability of the selected drug to cross the
blood–brain barrier. As NMBDs do not cross the blood–brain barrier, there is no
effect on the central nervous system. Using an anticholinesterase with only peripheral
action thus makes sense because central nervous system side effects of a drug like
physostigmine can be avoided. These effects can be very pronounced in elderly
patients, leading to confusion and agitation in the recovery room. Neostigmine and
pyridostigmine, with their quaternary ammonium structure and consequent inability to
cross the blood–brain barrier, are thus preferred agents to reverse the actions of
NMBDs than physostigmine which crosses that barrier readily. Same principle
applies to anticholinergic agents that are administered along with anticholinesterase
drug to counteract the surge of acetylcholine causing bradycardia. Atropine and
scopolamine, with their tertiary character, may cross the blood–brain barrier and may
cause central nervous system effects. Glycopyrrolate, on the other hand, has
quaternary structure and lacks central nervous system effects and has largely
replaced atropine for blocking the adverse muscarinic effects.
33. D. Administration of anticholinesterase agent leads to accumulation of
acetylcholine, manifesting increased cholinergic actions in the body. Vagal
stimulation causes bradycardia and, if not antagonized by concomitant administration
of a cholinergic agent, may lead to cardiac standstill. Antisialagogue actions of these
agents are also helpful in reducing the excessive salivation induced by
parasympathetic overactivity of acetylcholine generated by inhibition of
cholinesterase. Disruption of gastrointestinal anastomosis is another consideration,
secondary to increased peristalsis of the bowel. Cholinergic activity may also lead to
bronchospasm and not bronchodilation.
34. C. Impulses generated by the nerve stimulator are standardized to ensure
uniformity of monitoring. Out of the different patterns described in the question, only
the characteristic of train of four is correct. Although this mode is used more often in
modern clinical practice of anesthesia, in fact the absence of fade—a hallmark of
nondepolarizing block—is a more reliable indicator of reversal of neuromuscular
blockade with tetanic or double-burst stimulation. A depolarizing block is
characterized by absence of fade but takes on characteristics of a nondepolarizing
block if enough depolarizing agent is administered.
35. D. Many physiologic factors and anesthetic and nonanesthetic drugs interact with
nondepolarizing muscle relaxants (NDMRs). Volatile and local anesthetics
potentiate, while depolarizing muscle relaxants antagonize the effects of these drugs.
Intravenous anesthetic agents do not have any appreciable muscle-relaxant effect in
normal doses. Aminoglycoside antibiotics potentiate the effects of NDMRs, while
penicillin, cephalosporins, erythromycin, and tetracycline are devoid of
neuromuscular effects. Streptomycin belongs to aminoglycoside family, and thus
augments the effects of NDMRs.
36. C. Induction of anesthesia in a patient with severe valvular stenosis can lead to
decreased ventricular filling secondary to vasodilatation and decreased venous
return. Increase in the heart rate is very poorly tolerated as the ventricular filling is
impaired because of decreased diastolic time. In the presence of normal ejection
fraction, augmentation of cardiac contractility with administration of milrinone,
epinephrine, or dobutamine may not be needed. Administration of phenylephrine will
Comments
Post a Comment
اكتب تعليق حول الموضوع