UBP 6.7 (Short Form): Neuro – Cerebellar Tumor

Question 1

What is von Willebrand’s disease (vWD)?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 1

Von Willebrand’s disease is the most common inherited coagulation disorder,

caused by qualitative or quantitative defects of von Willebrand factor (vWF) in the plasma.

vWF plays an important role in both primary hemostasis and coagulation by –

• mediating platelet adhesion to the subendothelial surface of blood vessels
  
  • (via the GPIb receptor),
• facilitating platelet-to-platelet aggregation
  
  • (via the GPIIb/IIIa receptor), and
• functioning as a carrier protein and stabilizer for factor VIII
  
  • (complexes with factor VIII to form VIII:C; prolongs the circulation time of VIII:C).

While there are at least 50 genetic variations of vWD, there are three principle subtypes.

Type I vWD, the most common (80-85%) and mildest form of the disease, represents a quantitative defect in plasma vWF levels (impaired release from endothelial cells, but stores are normal), leading to a clinical picture consistent with an abnormality of primary hemostasis (i.e. mucocutaneous bleeding, menorrhagia, gastrointestinal bleeding, gingival bleeding, and easy bruising).

Type II vWD (20-30% of patients with vWD) represents a variety of qualitative defects in plasma vWF, with some mutations affecting vWF’s interactions with platelets and others affecting its interaction with factor VIII.

• There are four subtypes of Type II vWD (2A, 2B, 2N, 2M), with
  
  • Type 2B vWD leading to a consumptive thrombocytopenia (defect in primary hemostasis), and
  • Type 2N vWD leading to severely reduced factor VIII activity (defect in coagulation).

Type III vWD, the most severe and rare form of the disease, is characterized by extremely low levels of plasma vWF, leading to severe bleeding secondary to abnormalities in both primary hemostasis and coagulation (hemarthrosis, severe mucosal bleeding, muscle hematomas, severe bleeding with surgery).

Question 2

The family is not sure of the patient’s specific type of vWD or past treatment.

How would you evaluate her coagulation status?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 2

I would perform a history, physical, and chart review to help identify –

• the type and severity of vWD;
• previous transfusion requirements; and
• episodes of abnormal bleeding, such as
  
  • easy bruising, hematomas, epistaxis, menorrhagia, and gingival, traumatic, or perioperative bleeding.

I would then order a CBC, platelet count, bleeding time, PT, and PTT, –

• recognizing that mild disease will likely produce near-normal studies, with severe disease resulting in prolonged bleeding, thrombocytopenia, and a prolonged PTT, depending on the type of disease.

Given the severity of this patient’s condition and the urgency of the case, I would NOT delay treatment to obtain studies designed to confirm and diagnose the type of vWD, such as –

• vWF antigen,
• vWF activity (ristocetin cofactor or collagen binding activity),
• factor VIII coagulant activity, and
• vWF multimer distribution by electrophoresis.

Rather, I would anticipate the possibility of significant bleeding and ensure the availability of blood products, DDAVP, cryoprecipitate, FFP, and Humate P (a purified commercial preparation of factor VIII-vWF concentrate containing large vWF multimers).

Question 3

Is prophylactic DDAVP indicated for this case?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 3

Considering the significant risk of bleeding associated with this major surgery, and assuming I have been unable to identify the patient’s specific subtype of vWD, –

I would provide prophylactic vWF replacement with either –

cryoprecipitate or Humate P (less risk of transfusion-related infections with Humate P).

While DDAVP (desmopressin), a synthetic analogue of vasopressin that stimulates the release of vWF from endothelial cells, is effective first-line therapy for many patients with Type I vWD (about 80% of patients with vWD respond well),

it provides little to no response in patients with Type 2A, Type 2M, and Type 3 vWD, and will lead to thrombocytopenia in patients with Type 2B vWD.

The lack of a consistent response, a limited duration of action (6-12 hours), and the potential for tachyphylaxis, render treatment with DDAVP inadequate for surgical prophylaxis during major surgery where it is critical to control the patient’s bleeding tendency.

Clinical Note:

• To provide prophylaxis for major surgery, it is recommended to –
  
  • obtain initial vWF:RCo and factor VIII levels of >/= 100 IU/dL.
• Subsequent dosing should maintain vWF:RCo and factor VIII levels above a trough of 50 IU/dL for at least 7-10 days following surgery.

Question 4

Would you lower her blood pressure prior to surgery?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 4

Recognizing that this patient’s decreased level of consciousness, papilledema, headache, and nausea are suggestive of severely elevated intracranial pressures and reduced cerebral perfusion, and

keeping in mind that cerebral perfusion pressure is equal to the mean arterial pressure minus the intracranial pressure (CPP = MAP - ICP),

I would be very concerned that reducing her blood pressure may lead to worsening cerebral ischemia.

Therefore, while hypertension could potentially lead to hyperemia, increased cerebral blood flow (CBF), and increased ICP (increased CBF → increased CBV → increased ICP),

I would NOT treat her hypertension at this time.

My concern is that lowering the MAP of a patient with elevated ICP and/or altered cerebral autoregulation (potentially abolished or rightward shifted secondary to tumor effects or chronic hypertension, respectively), prior to undergoing a procedure in the sitting position, could contribute to decreased cerebral perfusion pressure and worsening cerebral ischemia.

Rather, with this concern in mind, I would take immediate steps to reduce her intracranial pressure prior to initiating any treatment to lower her blood pressure.

Question 5

Aren’t you concerned that her high blood pressure will result in increased intracranial pressure (ICP), placing the patient at increased risk of brain herniation?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 5

Recognizing that CBF becomes pressure dependent with mean arterial pressures above the range of autoregulation or when autoregulation is abolished or dysfunctional (which is often the case in regions of the brain surrounding a mass due to inflammation, ischemia, and high tissue pressure gradients),

I am concerned that her hypertension could lead to hyperemia and increased CBF, with resultant increases in cerebral blood volume and ICP.

Nevertheless, I am also concerned that reducing her blood pressure places her at risk for cerebral ischemia.

Therefore, prior to lowering her blood pressure, I would attempt to lower her ICP by one or more of the following methods:

1. hyperventilate the patient to a PaCO2 of about 30 mmHg;
2. ensure unobstructed venous drainage and elevating the head to 30º to facilitate venous drainage;
3. administer mannitol (the increase in osmolarity draws water from the extravascular brain tissue) and/or a diuretic (particularly useful for hypervolemic patients or those who will not tolerate mannitol – CHF or nephrotic syndrome);
4. administer a corticosteroid, which is thought to reduce ICP by stabilizing capillary membranes around the brain tumor (vasogenic cerebral edema often develops around tumors) and/or decreasing CSF production;
5. administer a cerebral vasoconstricting anesthetic, such as propofol or thiopental (this would be done at induction); and
6. ask the surgeon to consider performing a ventriculostomy to allow for the drainage of CSF (and provide a means of direct ICP measurement).

Moreover, I would avoid factors that could further increase ICP or decrease cerebral perfusion, such as –

• hypoventilation (hypercapnia), sympathetic stimulation (light anesthesia, especially during laryngoscopy), hypotension (i.e. induction, sitting position, excessive anesthesia), and hypervolemia.

My treatment goals throughout this period of time would be to maintain adequate cerebral perfusion pressure while avoiding ICP-induced brain herniation.

Question 6

Could you just quickly place a lumbar subarachnoid catheter to drain some CSF and reduce her ICP?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 6

The placement of a lumbar subarachnoid catheter would facilitate the indirect measurement of her ICP and allow for the removal of CSF, which may reduce her ICP.

However, the measurement of lumbar CSF pressure may not accurately reflect ICP due to the natural compartmentalization of the intracranial vault and/or mass-induced obstruction of CSF flow between the cranial and spinal compartments.

Moreover, in the setting of non-communicating hydrocephalus, the withdrawal of CSF via the lumbar catheter may result in decreased CSF pressures below the foramen magnum, without producing a concomitant drop in intracranial pressures.

The subsequent development of a pressure gradient between the cranial and spinal compartments in a patient who already has severely elevated intracranial pressures could result in tonsillar herniation.

Since the pressure measurements of a lumbar subarachnoid catheter are less reliable, and recognizing that patients with a posterior fossa tumor are at increased risk for noncommunication hydrocephalus (obstruction of the CSF outflow through the 4^th ventricle),

I would prefer a ventricular catheter to a lumbar subarachnoid catheter, if possible.

Question 7

How does hyperventilation decrease ICP?

What would be your target PaCO2?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 7

The decrease in PaCO2 that occurs with hyperventilation leads to a higher CSF pH around the walls of arterioles, which in turn leads to arteriolar vasoconstriction, reduced CBF, reduced CBV, and, finally, lower ICP (the opposite occurs with increases in PaCO2 and a reduction in CSF pH).

In fact, between PaCO2 tensions of 20-80 mmHg, CBF changes at a rate of 1 mL/100 g per minute for every 1 mmHg change in a PaCO2.

However, it is important to keep in mind that this effect may be attenuated by the vasodilating or vasoconstricting effects of anesthetic agents (volatile agents are cerebral vasodilators and propofol/barbiturates are cerebral vasoconstrictors) and/or the active transport of bicarbonate ions into or from the CSF to normalize CSF pH.

The latter process occurs in about 6-12 hours into or from the CSF to normalize CSF pH.

The latter process occurs in about 6-12 hours, limiting the usefulness of hyperventilation as a long-term treatment option for elevated intracranial hypertension.

Moreover, the abrupt discontinuation of profound hyperventilation could potentially lead to a rebound increase in ICP.

–

Therefore, when employing hyperventilation as a treatment modality, I would attempt to lower the patient’s PaCO2 to around 30 mmHg (possibly 25 mmHg if I believed that cerebral herniation was imminent).

Further reductions in PaCO2 may provide little benefit while, at the same time, placing the patient at increased risk of cerebral ischemia (this is a theoretical risk) and other complications associated with respiratory alkalosis (i.e. prolonged opioid-induced respiratory depression).

Question 8

On exam, you hear a midsystolic click and systolic ejection murmur, and note premature ventricular contractions at a rate of about 3 per minute.

What pre-operative cardiac workup would you require?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 8

The auscultatory findings of midsystolic click and the late systolic murmur along with PVC’s on ECG are consistent with mitral valve prolapse associated with mitral valve regurgitation.

In the absence of symptoms, such as syncope, chest pain, and fatigue, these findings would not normally warrant further cardiac workup.

However, in this case, cardiac echocardiography would be desirable for several reasons:

1. to determine the severity of the mitral valve prolapse and regurgitation of this patient who is unable to discuss recent symptomatology;
2. to determine if there are any atrial thrombi present in this patient who is most likely taking propranolol for dysrhythmia control; and
3. to rule out a patent foramen ovale in this patient who will be at increased risk of experiencing an air embolism when undergoing craniotomy in the sitting position.

In fact, the presence of a patent foramen ovale is a relative contraindication to the performance of a craniotomy in the sitting position, due to the potential for paradoxical embolism to the coronary or cerebral circulations.

If, however, the emergent nature of the patient’s condition did not allow for further preoperative cardiac evaluation, I would proceed with the case and discuss alternative patient positioning with the surgeon (i.e. lateral decubitus, prone, park bench, or supine).

Question 9

Would you order any premedication?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 9

Given the emergent nature of this case, I would consider this patient to have a full stomach.

Therefore, I would administer metoclopramide and an H2-receptor antagonist to reduce the risk of aspiration pneumonitis.

Considering the patient’s signs and symptoms consistent with increased ICP (headache, nausea, imbalance, and papilledema) in conjunction with his worsening mental status, I would avoid:

1. central nervous system depressants (i.e. benzodiazepines), which could confound my ability to assess further mental status changes, and
2. opioids, which could lead to hypoventilation, hypercapnia, and further increases in ICP.

I would, however, continue her propranolol and consider the administration of a corticosteroid to reduce ICP and/or decrease CSF production.

Question 10

What are the current recommendations for perioperative antibiotics in someone with mitral valve prolapse?

(A 24-year-old female presents for emergent craniotomy and resection of a cerebellar tumor in the sitting position. She has a history of progressive headache, nausea, and imbalance over the previous two months; over the last 24 hours she has become obtunded and confused. Past medical history is significant for depression, mitral valve prolapse, and Von Willebrand’s disease. Severe papilledema is noted on physical exam. She is currently taking propranolol and zoloft. VS: HR = 58, BP = 188/94 mmHg, RR = 10, Temp = 36.4ºC. CT scan shows a large posterior fossa mass with compression of the 4th ventricle.)

Answer 10

According to the revised American Heart Association guidelines from 2007, MVP is no longer an independent indication for endocarditis antibiotic prophylaxis.

Rather, prophylaxis is more reasonably reserved for patients with cardiac conditions that are associated with the greatest risk for adverse outcomes from infective endocarditis (IE).

These conditions include:

1. a prosthetic cardiac valve or prosthetic material used for valve repair;
2. a previous occurrence of IE;
3. unrepaired cyanotic congenital heart disease;
4. the 6 month postoperative period following a repaired congenital heart defect using prosthetic material or a device;
5. repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or device (which inhibits endothelialization); and
6. cardiac transplantation recipients who develop cardiac valvulopathy.

The new guidelines now emphasize prophylaxis for those conditions associated with the highest risk for adverse outcomes from IE versus those associated with the highest lifetime risk of acquisition of IE.

Although MVP is not an independent indication for antibiotic prophylaxis, I would administer antibiotics to this patient for meningitis prophylaxis and to prevent surgical infection.