Apex Unit 7 Flashcards Neuro
Name 4 types of glial cells and describe the function of each.
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List the name and function of the 4 lobes of the cerebral cortex.
Frontal – contains the motor cortex
Parietal – contains somatic sensory cortex
Occipital – contains vision cortex
Temporal – contains auditory cortex and speech centers
Wernicke’s area = understanding speech
Broca’s area = motor control of speech
Name the 12 cranial nerves.
Mnemonic: On Occasion Our Trusty Truck Acts Funny Very Good Vehicle Any How
What cranial nerves provide motor control of the eyes? How does each nerve contribute to the eye’s movement?
What bedside tests are used to assess the cranial nerves?
CN 1- 6
What bedside tests are used to assess the cranial nerves? CN 7-12
Which cranial nerve resides in the central nervous system? What is the implication of this?
With the exception of the optic n. (CN II), all of the cranial nerves are part of the peripheral nervous system. This means that the optic n is the only cranial nerve that is surrounded by the dura.
Because the optic nerve is part of the CNS, it is bathed by CSF. If you inject local anesthetic into the optic nerve during regional anesthesia of the eye, you will have a big problem.
What is tic douloureux? What cranial nerve contributes to this problem?
Tic douloureux (trigeminal neuralgia CN V) causes excruciating neuropathic pain in the face.
What is Bell’s palsy?
What cranial nerve contributes to this problem?
Bell’s palsy results from injury to the facial n. (CN VII).
This causes ipsilateral facial paralysis
What is the function of CSF, and where is it located?
The cerebrospinal fluid cushions the brain, provides buoyancy, and delivers optimal conditions for neurologic function. It is located in the:
Ventricles (left lateral, right lateral, third, and fourth)
Cisterns around the brain
Subarachnoid space in brain and spinal cord
What regions of the brain are NOT protected by the blood-brain-barrier?
The blood brain barrier separates the CSF from the plasma. It has tight junctions that restrict pass of large molecules and ions.
The BBB is not present at the chemoreceptor trigger zone, posterior pituitary gland, pineal gland, choroid plexus, and parts of the hypothalamus.
What is the normal volume and specific gravity of CSF?
CSF volume = 150 mL
Specific gravity = 1.002 - 1.009
Describe the production, circulation, and absorption of CSF.
CSF production: Ependymal cells of the choroid plexus at a rate of 30 mL/hr
Circulation: Remember - Love My 3 Silly 4 Lorn Magpies (match to image)
Reabsorption: Venous circulation via the arachnoid villi in the superior sagittal sinus.
What is the formula for cerebral blood flow? What are the normal values for global, cortical, and subcortical flow?
What are the 5 determinants of cerebral blood flow?
- Cerebral metabolic rate for oxygen (CMRO2)
- Cerebral perfusion pressure
- Venous pressure
- PaCO2
- PaO2
What is the normal value for CMRO2? What factors cause it to increase? To decrease?
CMRO2 describes how much O2 the brain consumes per minute. The reference value is 3.0 – 3.8 mL/O2/100g brain tissue/min.
Decreased by hypothermia (7% per 1 degree decrease), halogenated anesthetics, propofol, etomidate, and barbiturates.
Increased by hyperthermia, seizures, ketamine, and nitrous oxide.
What is the formula for cerebral perfusion pressure? What is normal?
CPP = MAP - ICP (or CVP) whichever is higher
The cerebral vasculature autoregulates its resistance (vessel diameter) to provide a constant cerebral perfusion pressure of 50 – 150 mmHg.
This ensures a relatively stable blood flow and confers protection against swings in blood pressure.
Autoregulation is influenced by products of local metabolism, myogenic mechanisms, and autonomic innervation.
Notice that 50 – 150 is cerebral perfusion pressure and NOT mean arterial pressure. This is an important point. To ensure a CPP of 50 mmHg, MAP must be 60 – 65 mmHg if ICP is in the normal range of 10 – 15 mmHg. If ICP is elevated, cerebral perfusion requires a higher mean arterial pressure.
What are the consequences of a CPP that exceeds the limits of autoregulation (too high and too low)?
List 4 conditions that reduce CPP as a function of increased venous pressure.
A high venous pressure decreases cerebral venous drainage and increases cerebral volume. This creates a backpressure to the brain that reduces the arterial/venous pressure gradient (MAP – CVP).
Conditions that impair venous drainage include:
Jugular compression secondary to improper head positioning
Increased intrathoracic pressure secondary to coughing or PEEP
Vena cava thrombosis
Vena cava syndrome
What is the relationship between PaCO2 and CBF? What physiologic mechanism is responsible for this?
There is a linear relationship between PaCO2 and CBF.
The pH of the CSF around the arterioles controls cerebral vascular resistance.
At a PaCO2 of 40 mmHg, CBF is 50 mL/100 g brain tissue/min.
At what PaCO2 does maximal cerebral vasodilation occur? How about maximal cerebral vasoconstriction?
For every 1 mmHg increase (or decrease) in PaCO2, CBF will increase (or decrease) by 1 – 2 mL/100g brain tissue/min.
Maximal vasodilation occurs at a PaCO2 of 80 – 100 mmHg.
Maximal vasoconstriction occurs at a PaCO2 of 25 mmHg.
What is the relationship between CMRO2 and CBF?
As a general rule:
Things that increase the amount of O2 the brain uses (CMRO2) tend to cause cerebral vasodilation (increased CBF). Examples include hyperthermia or ketamine.
Things that decrease the amount of O2 the brain uses (CMRO2) tend to cause cerebral vasoconstriction (decreased CBF). Examples include hypothermia, propofol, and thiopental.
Halogenated anesthetics are an exception - the decouple the relationship between CMRO2 and CBF. Said another way, they reduce CMRO2, but they cause cerebral vasodilation. This explains why a patient with intracranial hypertension is better served with TIVA.
How do acidosis and alkalosis affect CBF?
Respiratory acidosis increases CBF.
Respiratory alkalosis decreases CBF.
Metabolic acidosis or alkalosis do not directly affect cerebral blood flow. This is because H+ does not pass through the blood brain barrier. A compensatory change in minute ventilation can, however, affect CBF.
How does PaO2 affect CBF?
A PaO2 below 50 – 60 mmHg causes cerebral vasodilation and increases CBF.
When PaO2 is above 60 mmHg, it does not affect cerebral blood flow.
What is the normal intracranial pressure? What values are considered abnormal?
Intracranial pressure is the supratentorial CSF pressure.
Normal ICP is 5 - 15 mmHg.
Cerebral hypertension occurs if ICP > 20 mmHg.
When is ICP measurement indicated?
What is the gold standard for measurement?
ICP measurement is indicated with a Glasgow Coma Scale score < 7.
An intraventricular catheter is the gold standard for ICP measurement. ICP can also be measured with a subdural bolt or a catheter placed over the convexity of the cerebral cortex.
List the signs and symptoms of intracranial hypertension.
- Headache
- N/V
- Papilledema (swelling of the optic nerve)
- Focal neurologic deficit
- Decreased LOC
- Seizure
- Coma
Discuss the Monroe-Kellie hypothesis.
- The brain lives in a rigid, bony box. Within this box, there are 3 components: brain, blood, and CSF.
- The Monroe-Kellie hypothesis describes the pressure-volume equilibrium between the brain, blood, and CSF within the confines of the cranium. It says that an increase in one of the components must be countered with a decrease in one or both of the others. If not, then pressure inside the cranium will rise.
What is Cushing’s triad? What is the clinical relevance of this reflex?
Cushing’s triad indicates intracranial hypertension. It includes:
- Hypertension
- Bradycardia
- Irregular respirations
Increased ICP reduces CPP. In an effort to preserve cerebral perfusion, blood pressure increases. Hypertension activates the baroreceptor reflex, leading to bradycardia. Compression of the medulla causes irregular respirations.
Name 4 areas where brain herniation can occur.
Brain herniation can occur at any of these 4 locations:
- Herniation of the cingulate gyrus under the falx.
- Herniation of contents over the tentorium cerebelli (transtentorial herniation).
- Herniation of the cerebellar tonsils through the foramen magnum.
- Herniation of contents through a site of surgery or trauma.
How does hyperventilation affect CBF? What is the ideal PaCO2 to achieve this effect?
CO2 dilates the cerebral vessels → ↓ cerebral vascular resistance → ↑ CBF → ↑ ICP.
Hyperventilation (PaCO2 30-35 mmHg) constricts the cerebral vessels → ↑ cerebral vascular resistance → ↓ CBF → ↓ ICP.
Lowering PaCO2 < 30 mmHg increases the risk of cerebral ischemia due to vasoconstriction and shifting the oxyhemoglobin dissociation curve to the left (this reduces oxygen offloading).
How do nitroglycerine and nitroprusside affect ICP?
These agents are cerebral vasodilators. By increasing CBF (volume of blood in the brain), they increase ICP.
How does head position affect ICP?
Head elevation > 30 degrees facilitates venous drainage away from the brain.
Neck flexion or extension can compress the jugular veins, reduce venous outflow, increase CBV, and increase ICP.
Head down positions increase CBV and ICP.
How does mannitol reduce ICP?
What problems can arise when mannitol is used in this way?
Osmotic diuretics (mannitol 0.25 - 1.0 g/kg) increases serum osmolarity and “pulls” water across the blood brain barrier towards the bloodstream.
- If the blood brain barrier is disrupted, mannitol enters the brain and promotes cerebral edema!
- Mannitol transiently increases blood volume, which can increase ICP and stress the failing heart.
Describe the anterior and posterior circulation of the brain. Where do these pathways converge?
The cerebral circulation can be divided into 2 separate circulations: anterior and posterior. They converge at the circle of Willis.
Anterior Circulation
- The internal carotid arteries supply the anterior circulation. They enter the skull through the foramen lacerum.
- Aorta → Carotid a. → Internal carotid a. → Circle of Willis → Cerebral hemispheres
Posterior Circulation
- The vertebral arteries supply the posterior circulation. They enter the skull through the foraman magnum.
- Aorta → Subclavian a. → Vertebral a.→ Basilar a. → Posterior fossa structures and cervical spinal cord
Describe the anatomy of the circle of Willis.
The anterior and posterior circulations converge at the circle of Willis. The primary function of the circle of Willis is to provide redundancy of blood flow in the brain. If one side of the circle becomes occluded, then the other side should theoretically be able to perfuse the affected areas of the brain.
Which population of stroke patients should receive a thrombolytic agent?
The type of CVA must be determined prior to treatment, because a thrombolytic should NOT be given to a patient with hemorrhagic stroke. Since the etiology of CVA cannot be determined by clinical criteria alone, the patient should receive an emergent non-contrast CT.
- If treatment can begin < 3 hours after the onset of symptoms, the patient with an ischemic CVA should receive an intravenous thrombolytic such as recombinant tissue plasminogen activator (tPA).
- Aspirin is an acceptable alternative if tPA cannot be administered.
What is the relationship between hyperglycemia and cerebral hypoxia?
During cerebral hypoxia, glucose is converted to lactic acid. Cerebral acidosis destroys brain tissue and is associated with worse outcomes. Monitor serum glucose and treat hyperglycemia with insulin.
Think about this when administering IV fluids that contain dextrose.
In the context of cerebral aneurysm, how is transmural pressure calculated?
An increased transmural pressure predisposes the aneurysm to rupture. As the vessel bursts, blood flows into the subarachnoid space.
We like to think of MAP as the pressure pushing outwards against the aneurysmal sac and ICP as the counter pressure that pushes against it. In essence, ICP creates a tamponade effect. Using this model, it’s easy to see that the risk of rupture is increased by hypertension and/or an acute reduction in ICP (opening of the dura).
What is the most common clinical finding in a patient with subarachnoid hemorrhage? What are the other s/sx?
The most common in a patient with SAH is an intense headache that is often described as the “worst one in my life.”
Consciousness is lost about 50% of the time, and other s/sx include focal neurologic deficits, N/V, photophobia, and fever. Meningismus (signs of meningitis) occurs as blood spreads throughout and irritates the subarachnoid space. Furthermore, blood can block CSF flow, causing obstructive hydrocephalus and increasing ICP.
What is the most significant source of morbidity and mortality in the patient with SAH?
Cerebral vasospasm is a delayed contraction of the cerebral arteries. It can lead to cerebral infarction and is the most significant source of morbidity and mortality in the patient with SAH.
Free hemoglobin that is in contact with the outer surface of the cerebral arteries increases the risk of vasospasm. Indeed, there is a positive correlation between the amount of blood observed on CT and the incidence of vasospasm.
How do you treat the patient with an intracerebral bleed who is on warfarin?
Warfarin can be reversed with FFP, prothrombin complex concentrate, and/or recombinant factor VIIa.
Vitamin K is not the best option for acute warfarin reversal.
When is the incidence of cerebral vasospasm?
When is it most likely to occur?
It occurs in about 25% of patients following SAH
and is most likely 4 - 9 days following SAH.
What is the treatment for cerebral vasospasm?
Triple H therapy (hypervolemia, hypertension, and hemodilution to Hct 27 - 32%) is the standard of care for vasospasm following SAH. Liberal hydration supports blood pressure and CPP. It also creates a state of hemodilution, which reduces blood viscosity and cerebrovascular resistance. Together these improve cerebral blood flow.
Nimodipine is the only calcium channel blocker shown to reduce morbidity and mortality associated with vasospasm. Interestingly, it does not actually relieve the spasm, but instead it increases collateral blood flow.
During endovascular coil placement for a cerebral aneurysm, the aneurysm ruptures. What is the best treatment at this time?
Patients who undergo endovascular coiling require heparinzation during the procedure.
If the aneurysm ruptures during the procedure, you should give protamine (1 mg of protamine per 100 U of heparin administered). MAP should be lowered into the low/normal range.
While it wasn’t cited in our references, adenosine can be given to temporarily arrest the heart, so the interventional radiologist can control the bleeding.
Be able to calculate the Glasgow coma scale.
The GCS provides an objective assessment of neurologic status. A GCS < 8 is consistent with traumatic brain injury.
How do you treat the patient with an intracerebral bleed who is on clopidogrel?
Clopidogrel, aspirin, or both can be reversed with platelet transfusion. There is also evidence of reversal with recombinant factor VIIa.
What are 2 common ways of reducing ICP that should specifically be avoided in the patient with a traumatic brain injury?
There are 2 things you should specifically avoid in the patient with TBI:
- Hyperventilation can worsen cerebral ischemia in patients with TBI. Hyperventilation is only indicated as a temporary measure to acutely reduce ICP.
- Steroids worsen neurologic outcome.
Is nitrous oxide safe in the patient with a traumatic brain injury?
Other injuries, such as pneumothorax, may only become evident after anesthetic induction and positive pressure ventilation. Nitrous oxide can rapidly expand a pneumothorax or cause pneumocephalus. Do not use it in the patient with TBI.
Compare and contrast the 5 types of seizures.
Compare and contrast the 5 types of seizures.
What is the relationship between etomidate and seizures?
Etomidate commonly causes myoclonus. This is not associated with increased EEG activity in patients that do not have epilepsy.
In patients with seizure disorders, etomidate (or methohexital or alfentanil) increases EEG activity and can be used to help determine the location of seizure foci during cortical mapping.
Describe the pathophysiology of Alzheimer’s disease.
Key findings include the development of diffuse beta amyloid rich plaques and neurofibrillary tangles in the brain.
Consequences of plaque formation include:
- Dysfunctional synaptic transmission. This is most noticeable in nicotinic Ach neurons.
- Apoptosis (programmed cell death)
What class of drugs is used to treat Alzheimer’s disease? How do they interact with succinylcholine?
Treatment for Alzheimer’s disease is palliative and aims to restore the concentration of Ach. This is accomplished with cholinesterase inhibitors, such as tacrine, donepezil, rivastigmine, and galantamine.
Cholinesterase inhibitors increase the duration of action of succinylcholine, although the clinical significance of this is debatable.
Describe the pathophysiology of Parkinson’s disease.
In the patient with Parkinson’s disease, the dopaminergic neurons in the basal ganglia are destroyed.
What drugs increase the risk of extrapyramidal s/sx in the patient with Parkinson’s disease?
Drugs that antagonize dopamine should be avoided. Examples include:
- Metoclopramide
- Butyrophenones (haloperidol & droperidol)
- Phenothiazines (promethazine)
What is the most common eye complication in the perioperative period? What is the most common cause of vision loss?
Corneal abrasion is the most common eye complication.
Ischemic optic neuropathy is the most common cause of vision loss.
Describe the pathophysiology of ischemic optic neuropathy.
ION is a consequence of ischemia of the optic nerve. The most likely explanation is that venous congestion in the optic canal reduces perfusion pressure. Increased intraabdominal and/or intrathoracic pressure can also increase intraocular pressure.
Ocular Perfusion Pressure = MAP - Intraocular Pressure
The central retinal and posterior ciliary arteries are at highest risk because they are “watershed” areas - they lack anastomoses with other arteries. A rise in intraocular pressure can compress these vessels, which reduces oxygen delivery to the retina.
What surgical procedure presents the most significant risk of ION? What are other procedure and patient risk factors?
ION is most common after spinal surgery in the prone position.
Discuss the blood flow to the spinal cord.
The spinal cord is perfused by:
- 1 Anterior spinal artery (anterior 2/3 of spinal cord)
- 2 Posterior spinal arteries (posterior 1/3 of spinal cord)
- 6 – 8 Radicular arteries
What is the most important radicular artery? Which spinal segment does it typically enter the spinal cord?
The artery of Adamkiewicz is the most important radicular artery.
Along with the anterior spinal artery, the artery of Adamkiewicz supplies the anterior cord in the thoracolumbar region. It most commonly originates between T11-T12.
Envision the anatomy of the spinal cord and spinal nerve in cross section.
The spinal cord links the peripheral nerves to the brain.
- Sensory neurons from the periphery via the dorsal nerve root.
- Motor and autonomic neurons exit via the ventral nerve root.
Describe the organization of the 3 neuron pathway common to the spinal tracts.
Each Pathway Consists of Three Neurons
- The first order neuron links the peripheral nerve to the spinal cord or brainstem.
- The second order neuron links the spinal cord or brainstem to a subcortical structure.
- The third order neuron links the subcortical structure to the cerebral cortex.
Compare the structure and function of the dorsal column with the spinothalamic tract.
Dorsal column - Medial lemniscal system:
- Transmits mechanoreceptive sensations: fine touch, proprioception, vibration, and pressure.
- Capable of two point discrimination – a high degree of localizing the stimulus.
- Consists of large, myelinated, rapidly conducting fibers.
- Transmits sensory information faster than the anterolateral system.
- Think of this as a more evolved system.
Anterolateral System - Spinothalamic Tract:
- Transmits: pain, temperature, crude touch, tickle, itch, and sexual sensation.
- Two point discrimination is not present.
- Consists of smaller, myelinated, slower conducting fibers.
- Think of this as a more primitive system.
What bedside exam can assess the integrity of the corticospinal tract? How do you interpret it?
The corticospinal tract is the most important motor pathway. This pathway is often referred to as the pyramidal tract. All of the other motor pathways outside of the corticospinal (pyramidal) tract are known collectively as the extrapyramidal tract.
The Babinski test is a method to test the integrity of the corticospinal tract. A firm stimulus is applied to the underside of the foot yields the following responses.
- Normal response: Downward motion of all the toes.
- Upper motor neuron injury: Upward extension of the big toe with fanning of the other toes.
- Lower motor neuron injury: No response.
Contrast the presentation of upper- vs lower motor neuron injury.
The upper motor neurons begin in the cerebral cortex and end in the ventral horn of the spinal cord, while the lower motor neurons begin in the ventral horn and end at the neuromuscular junction.
- Upper motor neuron injury presents with hyperreflexia and spastic paralysis.
- Lower motor neuron injury presents with impaired reflexes and flaccid paralysis.
Discuss the pathophysiology of neurogenic shock.
Pathophysiology of Neurogenic Shock:
- Impairment of cardioaccelerator fibers (T1-T4) → unopposed cardiac vagal tone → bradycardia & reduced inotropy
- Decreased SNS tone → vasodilation → venous pooling → decreased CO and BP
- Impairment of sympathetic pathways from hypothalamus to blood vessels → inability to vasoconstrict or shiver → hypothermia
- Hypothermia is the result of the inability of the cutaneous vasculature to vasoconstrict, causing a redistribution of blood flow towards the periphery and allowing more heat to escape from the body.
How can you differentiate neurogenic shock from hypovolemic shock?
Neurogenic Shock → bradycardia, hypotension, hypothermia with pink, warm extremities (cutaneous vasodilation)
Hypovolemic shock → tachycardia, hypotension, and cool, clammy extremities
Discuss the use of succinylcholine in the patient with spinal cord injury.
Succinylcholine should be avoided 24 hours after injury and should not be used for at least 6 months thereafter (some books say a year).
When does a patient with spinal cord injury become at risk for autonomic hyperreflexia? What factor (other than time) contibutes to this risk?
After the neurogenic shock phase ends (1 – 3 weeks), the body begins to mend itself in a pathologic and disorganized way. There is a return of spinal sympathetic reflexes below the level of injury, however without inhibitory influences that would normally come from above the level of injury, the sympathetic reflexes below the level of injury exist in an overactive state. This places the patient at risk for autonomic hyperreflexia (mass reflex).
While up to 85% of patients with injury above T6 will develop AH, it is very unlikely to occur in patients with injury below T10. The higher the level of injury, the more intense the response.
List 6 situations that can precipitate AH.
- Stimulation of the hollow organs – bladder, bowel, or uterus
- Bladder catheterization
- Surgery - especially cystoscopy or colonoscopy
- Bowel movement
- Cutaneous stimulation
- Childbirth
Discuss the presentation and pathophysiology of autonomic hyperreflexia.
The classic presentation of autonomic hyperreflexia is hypertension and bradycardia.
Stimulation below the level of SCI triggers sympathetic reflex arc that creates a profound degree of vasoconstriction below the level of injury. This activates the baroreceptor reflex in the carotid bodies, which slows the heart rate. The body attempts to reduce afterload with vasodilation above the level of injury.
Other signs and symptoms include:
- Reflex vasodilation above the level of spinal cord injury → nasal stuffiness
- Hypertension → headache and blurred vision
- Malignant hypertension → stroke, seizure, left ventricular failure, dysrhythmias, pulmonary edema, and/or myocardial infarction.
Detail the anesthetic management of the patient with AH.
Even though the patient does not have sensation below the level of SCI, stimulation to the affected areas can elicit autonomic hyperreflexia – prevention is paramount!
- General or spinal anesthesia are the best options.
- An epidural may be used for a laboring mother, however when compared to a spinal anesthetic, an epidural does not inhibit the sacral nerve roots to the same degree.
- Hypertension is best treated with removal of the stimulus, deepening the anesthetic, and a rapid acting vasodilator, such as sodium nitroprusside.
- Bradycardia can be treated with atropine or glycopyrrolate.
- Administration of a positive chronotrope with vasoconstrictive properties will worsen hypertension.
- Adding lidocaine jelly to the cystoscope or Foley catheter does not prevent AH.
- Succinylcholine should be avoided for at least 6 months following SCI.
- AH may present in the postoperative period as the effects of anesthesia wear off; close postoperative monitoring is warranted.
Discuss the pathophysiology of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) causes progressive degeneration of motor neurons in the corticospinal tract. Astrocytic gliosis replaces the affected motor neurons. Both the upper as well as the lower motor neurons are affected.
The etiology is unknown.
Detail the anesthetic management of ALS.
- There is no evidence that supports a clear benefit of any particular anesthetic technique.
- Succinylcholine can cause lethal hyperkalemia. Lower motor neuron dysfunction is associated with the proliferation of postjunctional nicotinic receptors.
- There is increased sensitivity to nondepolarizing neuromuscular blockers.
- Bulbar muscle dysfunction increases the risk of pulmonary aspiration.
- Chest weakness reduces vital capacity and maximal minute ventilation.
- Consider postoperative mechanical ventilation.
Describe the pathophysiology of myasthenia gravis.
Myasthenia gravis is an autoimmune disease. IgG antibodies destroy post-junctional, nicotinic, acetylcholine receptors at the neuromuscular junction. Although Ach is present in sufficient quantity, there aren’t enough receptors to translate the extracellular signal into an intracellular response. This manifests as skeletal muscle weakness.
A key feature of myasthenia gravis is skeletal muscle weakness that becomes worse later in the day or that develops with exercise. Periods of rest allow for recovery of skeletal muscle function.
What surgical procedure can reduce symptoms in the patient with myasthenia gravis?
The thymus gland plays a key role in MG, and thymectomy brings symptom relief to many patients.
- Thymectomy reduces circulating Anti-AchR IgG in most patients.
- Surgical approach may be via median sternotomy or by the transcervical approach.
What does myasthenia gravis affect the pregnant mother and the fetus?
In 1/3 of women, pregnancy intensifies the symptoms of myasthenia gravis.
Anti-AchR IgG antibodies cross the placenta and cause weakness in 15 – 20% of neonates. This can persist up to 2-4 weeks, which is consistent with the half-life of the Anti-AchR IgG antibodies in the neonate’s circulation. These neonates may require airway management.
How can you tell the difference between cholinergic crisis and myasthenic crisis?
Pryidostigmine (an anticholinesterase) is the first line treatment for myasthenia gravis. An overdose can cause cholinergic crisis, which can include skeletal muscle weakness. Since myasthenic crisis also presents with skeletal muslce weakness, it can be difficult to distinguish from cholinergic crisis.
The diagnosis is made by administering 1 – 2 mg IV edrophonium, otherwise known as the “Tensilon test.”
- If muscle weakness is made worse, then the patient has cholinergic crisis (treatment = anticholinergic).
- If there is an improvement in muscle strength, then the patient had an exacerbation of myasthenic symptoms (treatment = anticholinesterase, immunosuppression, plasmapheresis).
How do patients with myasthenia gravis respond to neuromuscular blockers?
Because there is a reduction in the number of nicotinic receptors (type-m) at the neuromuscular junction, patients with myasthenia gravis have an increased sensitivity to non-depolarizing NMBs and a resistance to succinylcholine.
Remember that volatile anesthetics cause skeletal muscle relaxation by acting in the ventral horn of the spinal cord. In many cases, this eliminates the need for neuromuscular blockers.
Why are patients with myasthenia gravis prone to aspiration?
Bulbar muscle weakness (mouth and throat) manifests as difficulty handling oral secretions. This increases the risk of pulmonary aspiration.
Describe the pathophysiology of Eaton-Lambert syndrome.
Eaton-Lambert syndrome is caused by IgG mediated destruction of the presynaptic voltage-gated calcium channel at the presynaptic nerve terminal.
When the action potential depolarizes the nerve terminal, Ca+2 entry into the presynaptic neuron is limited, thereby reducing the amount of Ach that is released into the synaptic cleft.
The postsynaptic nicotinic receptor is present in normal quantity and functions normally.
Compare and contrast myasthenia gravis to Eaton-Lambert syndrome in terms of pathophysiology, common co-morbidities, and response to neuromuscular blockers/reversals.
Describe the pathophysiology of Guillain-Barre syndrome.
Guillain-Barre Syndrome (acute idiopathic polyneuritis) is characterized by an immunologic assault on myelin in the peripheral nerves. The action potential can’t be conducted, so the motor endplate never receives the incoming signal.
It usually persists for ~ 2 weeks and ends with full recovery in ~ 4 weeks.
Discuss the presentation of Guillain-Barre syndrome.
A flu-like illness usually precedes paralysis by 1-3 weeks.
S/sx include:
- Flaccid paralysis begins in the distal extremities and ascends bilaterally towards the proximal extremities, trunk, and face.
- Intercostal muscle weakness impairs ventilation.
- Facial and pharyngeal weakness causes difficulty swallowing
- Sensory deficits include: paresthesias, numbness, and/or pain.
- Autonomic dysfunction is common: tachycardia or bradycardia, hypertension or hypotension, diaphoresis or anhidrosis, and orthostatic hypotension.
What is familial periodic paralysis and how can the 2 variants of this disease be distingushed from each other?
Familial periodic paralysis are two distinct disease processes that are characterized by acute episodes of skeletal muscle weakness that is accompanied by either hypo- or hyperkalemia.
- Hypokalemic periodic paralysis is diagnosed if skeletal muscle weakness follows a glucose-insulin infusion. The patient becomes weak after the serum K+ is reduced.
- Hyperkalemic periodic paralysis is diagnosed if skeletal muscle weakness follows oral potassium administration. The patient becomes weak after the serum K+ is increased.
What drugs should be avoided in the patient with each type of familiar periodic paralysis? How about temperature?
Acetazolamide is the treatment for both forms of this disease. It creates a non-anion gap acidosis, which protects against hypokalemia. It also facilitates renal potassium excretion, which guards against hyperkalemia.
*Avoid hypothermia for both hypo- and hyperkalemic periodic paralysis!
Detail the functions of the following receptors in skeletal muscle: nicotinic, dihydropyridine, ryanodine, and SERCA2. Which is dysfunctional in the patient with malignant hyperthermia?
When the T-tubule is depolarized (Ach binds to nicotinic receptor at the NMJ), extracellular Ca+2 enters the myocyte via the dihydropyridine receptor at the T-tubule.
This activates the defective ryanodine receptor (RYR1), which instructs the sarcoplasmic reticulum to release way too much calcium into the cell. You can think of the RyR1 receptor as a Ca+2 faucet that can’t be turned off. Not only is there more Ca+2 to engage with the contractile elements, but the cell attempts to return the excess Ca+2 to the SR via the SERCA2 pump. Both processes consume a substantial amount of ATP, increase oxygen consumption, and increase CO2 production.
When the skeletal myocyte consumes all of its ATP, there is no ATP available to maintain the integrity of cell membranes. As a consequence, they break down and intracellular components (myoglobin and K+) are released into the systemic circulation.
List 8 consequences of too much Ca+2 inside of the skeletal myocyte.
- Sustained muscle contraction
- Accelerated metabolic rate and rapid depletion of ATP
- Increased oxygen consumption
- Increased CO2 and heat production
- Mixed respiratory and lactic acidosis
- Sarcolemma breaks down
- Potassium and myoglobin leak into the systemic circulation
- Rigidity from sustained contraction
Identify 3 conditions that are definitively linked to MH.
MH is definitively linked to only three other co-existing diseases:
- King-Denborough syndrome
- Central core disease
- Multiminicore disease
*Some texts list Evans myopathy as the third disease that is definitively linked to MH. Our list came from Nagelhout, and its also what’s listed on the MHAUS website.
MH is NOT linked to these conditions:
- Duchenne muscular dystrophy (see below)
- Becker muscular dystrophy
- Neuroleptic malignant syndrome
- Myotonia congenita
- Myotonic dystrophy
- Osteogenesis imperfecta
Duchenne muscular dystrophy is associated with an MH-like condition characterized by rhabdomyolysis. It is possible that halogenated agents and succinylcholine can initiate this MH-like syndrome in the patient with DM, so it is prudent to avoid these agents. Dantrolene does not treat this condition.
List 6 conditions that are NOT definitively linked to MH.
MH is NOT linked to these conditions:
- Duchenne muscular dystrophy (see below)
- Becker muscular dystrophy
- Neuroleptic malignant syndrome
- Myotonia congenita
- Myotonic dystrophy
- Osteogenesis imperfecta
Duchenne muscular dystrophy is associated with an MH-like condition characterized by rhabdomyolysis. It is possible that halogenated agents and succinylcholine can initiate this MH-like syndrome in the patient with DM, so it is prudent to avoid these agents. Dantrolene does not treat this condition.
What is the most sensitive indicator of MH?
What is the time course of the other s/sx?
The most sensitive indicator is an EtCO2 that rises out of proportion to minute ventilation. MH can occur as late as 6 hours after exposure to a triggering agent.
What is the difference between trismus and malignant hyperthermia? How should you proceed if the patient presents with either condition?
Trismus and masseter muscle rigidity are two entities that exist on a continuum.
- Trismus describes a tight jaw that can still be opened.
- Masseter muscle rigidity describes a jaw that cannot be opened.
Trismus is a normal response to succinylcholine, so it’s ok to proceed with surgery if trismus occurs in isolation. Even so, it’s probably wise to convert to a non-triggering agent.
Masseter muscle rigidity complicates airway management. Spasm is due to increased Ca+ in the myoplasm. Since this site of action is distal to the neuromuscular junction, a neuromuscular blocker will not relax the jaw. If the patient experiences masseter muscle rigidity, assume MH until proven otherwise.
What is the definitive test for susceptibility to malignant hyperthermia?
Anyone who has experienced MH or masseter spasm should be referred for a halothane contracture test for diagnosis. Although this is the definitive test for diagnosis, it only has an 80% specificity, so there is a risk of a false-negative result.
How does dantrolene treat MH? What are its most common side effects?
Dantrolene is classified as a muscle relaxant. It has two mechanisms of action:
- It halts Ca+2 release from the RyR1 receptor
- It prevents Ca+2 entry into the myocyte, which reduces the stimulus for calcium-induced calcium release
The most common side effects are muscle weakness and venous irritation.
How is dantrolene formulated?
How is it prepared?
Each vial contains 20 mg of dantrolene + 3 g of mannitol. The vials must be reconstituted with preservative free water.
NaCl introduces additional solute, which prolongs the time required for dantrolene to dissolve into the diluent. Coming from someone who has experience with this, mixing dantrolene is a chore. Enlist help early. Warming the diluent will make the process much faster.
How do you treat MH?
- Discontinue the triggering agent.
- Administer 100% oxygen at > 10 L/min.
- Administer dantrolene (or Ryanodex) 2.5 mg/kg IV and repeat q 5-10 min.
- Hyperventilate.
- Correct lactic acidosis w/ sodium bicarbonate.
- Treat hyperkalemia (CaCl 5-10 mg IV and insulin 0.15 units/kg + D50 1 mL/kg).
- Protect against dysthymias (class I agents: lidocaine 2mg/kg or procainamide 15 mg/kg).
- Maintain urine output (IV hydration, mannitol 0.25 g/kg, furosemide 1mg/kg).
- Cool the patient until temperature drops below 38 degrees C (cold IVF, cold fluid lavage, ice packs).
- Monitoring coagulation (DIC is a late complication and signals impending demise).
*Calcium channel blockers should not be given with dantrolene, because dangerous hyperkalemia will result.
Describe the pathophysiology of Duchenne muscular dystrophy.
Dystrophin is a critical structural component of the cytoskeleton of skeletal and cardiac muscle cells. It helps anchor actin and myosin to the cell membrane. The absence of dystrophin destabilizes the sarcolemma during muscle contraction and increases membrane permeability.
The absence of dystrophin allows extrajunctional receptors to populate the sarcolemma. This predisposes these patients to hyperkalemia following succinylcholine administration. Indeed, succinylcholine sports a black box warning that details the risk of cardiac arrest and sudden death secondary to hyperkalemia in children with undiagnosed skeletal muscle myopathy. Classic teaching suggests that DM increases the risk of malignant hyperthermia, however a more recent meta-analysis refutes this claim.
How does Duchenne muscular dystrophy affect pulmonary function?
Kyphoscoliosis (restrictive lung disease) → decreased pulmonary reserve → increased secretions and risk of pneumonia
Respiratory muscle weakness
How does Duchenne muscular dystrophy affect cardiac function? What EKG findings might you expect?
Cardiac Considerations
- Degeneration of cardiac muscle → reduced contractility, papillary muscle dysfunction, mitral regurgitation, cardiomyopathy, and congestive heart failure.
- Signs of cardiomyopathy include resting tachycardia, jugular venous distension, S3/S4 gallop, and displacement of the point of maximal impulse.
- The gold standard of cardiac evaluation is echocardiogram.
EKG Changes
- Impaired cardiac conduction → sinus tachycardia and short PR interval.
- Scarring of the posterobasal aspect (back/bottom) of the left ventricle manifests as increased R wave amplitude in lead 1, and deep Q waves in the limb leads.
What is the Cobb angle, and what is its significance?
The Cobb Angle describes the magnitude of the spinal curvature.
Describe Cobb angle and its significance?
Contrast the early and late complications of scoliosis.
Scoliosis alters thoracic geometry, which compresses the lungs and creates a restrictive ventilatory defect. One side of the thorax becomes smaller than the other.
List 3 ways rheumatoid arthritis affects the airway.
What is the most common airway complication of rheumatoid arthritis? What is its clinical significance?
Atlantoaxial subluxation is the most common airway complication of RA.
This is due to weakening of the transverse axial ligament, which allows the odontoid to directly compress the spinal cord at the level of the foramen magnum. The patient is at risk for quadriparesis or paralysis.
As an aside, patients with Down syndrome are also at risk for AO subluxation.
Discuss the pathophysiology of rheumatoid arthritis.
Rheumatoid arthritis is an autoimmune disease that targets the synovial joints. There is also widespread systemic involvement due to infiltration of immune complexes into the small and medium arteries leading to vasculitis. Cytokines (TNF and interleukin-1) play a central role in the pathogenesis of RA.
The hallmark of RA is morning stiffness that generally improves with activity. The joints are painful, swollen, and warm. Other symptoms include weakness, fatigue, and anorexia. Lymph node enlargement in the cervical, axillary, and epitrochlear regions may be noted as well. This condition is 2 – 3 times more common in women.
Using a systems approach, list the complications of rheumatoid arthritis.
airway,pulm, cardiac, heme
Using a systems approach, list the complications of rheumatoid arthritis.
Describe the pathophysiology of systemic lupus erythematosus.
Systemic lupus erythematosus is an autoimmune disease characterized by the proliferation of antinuclear antibodies. SLE affects nearly every organ system, and most of the consequences are the direct result of antibody induced vasculitis and tissue destruction.
Using a systems based approach, list the complications of systemic lupus erythematosus.
SLE is a disease that targets young women (~1:1000). The most common problems of SLE are polyarthritis and dermatitis. Arthritis can affect any joint, but it generally does not involve the spine.
Only 33 – 50% of these patients develop the malar “butterfly” rash.
What drugs can exacerbation SLE?
Exacerbation of SLE can occur as a result of stress or drug exposure. Drug induced lupus generally persists for several weeks to months and presents with mild symptoms of arthralgia, anemia, leukopenia, and fever. Here are the most common offenders:
P = Pregnancy
I = Infection
S = Surgery
S = Stress
E = Enalapril
D = D-penicillamine
C = Captopril
H = Hydralazine
I = Isoniazid
M = Methyldopa
P = Procainamide
*The mnemonic “PISSED CHIMP” will help you remember this list.
What is the relationship between SLE and antiphospholipid syndrome?
Patients with SLE are prone to developing antiphospholipid antibodies. Although the aPTT is prolonged, these patients are prone to a state of hypercoagulability and thrombosis. They are at risk for stroke, DVT, and pulmonary embolism.
Pregnant patients with SLE are at higher risk.
Discuss the pathophysiology of myotonic dystrophy.
Myotonic dystrophy is characterized by a prolonged contracture after a voluntary contraction. This is the result of dysfunctional calcium sequestration by the sarcoplasmic reticulum. Contractions can be so severe that they interfere with ventilation and intubation.
What 3 things can increase the risk of contractures in the patient with myotonic dystrophy?
There are 3 things that increase risk of contractures:
- Succinylcholine
- Reversal of NMB with anticholinesterases (theoretical)
- Hypothermia (shivering → sustained contractions)
Discuss the pathophysiology of Marfan syndrome.
Marfan syndrome is an autosomal dominant trait (not acquired). It is a connective tissue disorder that’s associated with an elevated risk of aortic dissection, mitral valve prolapse, mitral regurgitation, and aortic insufficiency.
Dissection of the ascending aorta can extend into the pericardium, and this increases the risk of cardiac tamponade. Remember Beck’s triad? (JVD, hypotension, and muffled heart tones).
As an aside, spontaneous pneumothorax is a very common complication in the patient with Marfan syndrome.
Discuss the pathophysiology of Ehlers-Danlos syndrome.
Ehlers-Danlos syndrome is an inherited disorder of procollagen and collagen. There are several types, but only type IV is associated with blood vessel rupture (think AAA).
Arguably the most important thing to remember about Ehlers-Danlos syndrome is that there is an increased bleeding tendency. This is the result of lack of blood vessel integrity and not coagulopathy. Since hematoma is a common complication, we tend to avoid regional anesthesia and IM injections. Invasive line placement or trauma during airway management pose a threat as well.
Pneumothorax is also a common complication, so be careful with the peak inspiratory pressure.
