What the Anesthesiologist Should Know before the Operative Procedure

The sitting position for posterior cranial fossa and posterior cervical spine surgery facilitates surgical access. However, the sitting position is associated with the potential for serious complications. The sitting position provides excellent surgical exposure, particularly for the midline lesions, improves cerebral venous decompression, promotes gravity drainage of blood and cerebrospinal fluid (CSF) from the operative field, and lowers intracranial pressure (ICP). Hence, there is less blood in the operative field, and perioperative blood loss and transfusion requirements may decrease.

The advantages for the anesthesiologist include better access to the patient’s airway, chest wall, and arms; ability to observe the patient’s face for cranial nerve monitoring; less facial swelling; and decreased intrathoracic pressure, providing improved ventilation.

Despite these advantages, a number of complications are associated with the sitting position, including hemodynamic instability, venous air embolism (VAE) with the possibility of paradoxical air embolism (PAE), pneumocephalus, macroglossia, and quadriplegia. Some of these complications are not exclusive to the sitting position but occur more frequently in the sitting position.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

Surgical procedures in the sitting position are usually elective, which allow the anesthesiologist to have sufficient time to evaluate and prepare the patients for the surgery, such as preoperative evaluation for a patent foramen ovale (PFO).

2. Preoperative evaluation

Baseline neurological and physical status, particularly cardiovascular and cerebrovascular systems, should be assessed to identify contraindications to the sitting position. The presence of a right-to-left intracardiac, such as a PFO or pulmonary shunt is considered an absolute contraindication, given the potential risk for PAE.

3. What are the implications of co-existing disease on perioperative care?

Co-existing diseases that affect perioperative care include diseases of the cardiovascular, pulmonary, renal-gastrointestinal, neurologic, and endocrine systems.

b. Cardiovascular System

Acute/unstable conditions

Perioperative evaluation

– This should seek to identify the presence of a PFO and uncontrolled hypertension and determine the patient’s volume status. The preoperative screening for a PFO may be performed by a bubble study via transesophageal echocardiography (TEE) or transcranial Doppler (TCD).

Perioperative risk reduction strategies

– The presence of a PFO is considered an absolute contraindication to the sitting position and surgery should be performed with an alternative position. For patients with uncontrolled hypertension, cardiovascular consultation should be obtained, and surgery should be delayed. Hypovolemia can result in hypotension when the patient is placed in the sitting position. Therefore, preoperative hypovolemia should be corrected.

Baseline coronary artery disease or cardiac dysfunction – goals of management

Perioperative evaluation:

– This should determine the presence and severity of baseline cardiac disease, patient’s functional capacity, current medications, history of pacemaker or implantable cardioverter defibrillator (ICD), and associated diseases, such as cerebrovascular disease, diabetes mellitus, and renal impairment.

Perioperative risk reduction strategies

– Perioperative cardiovascular consultation should be obtained. In patients with poor or unknown functional capacity, preoperative cardiac testing may be required.

c. Pulmonary

COPD

Perioperative evaluation

– History should determine the severity of the disease, frequency of exacerbation, supplement oxygen use, hospitalization, history of intubation, signs of infection such as change in amount or color of sputum, medication, and coexisting cardiac disease.

– Physical examination should focus on the quality of breath sound, air movement, and the presence of wheezing, rhonchi, and rales. Chest radiography may be useful in detecting infection or lung bullae. Arterial blood gas is useful to establish baseline oxygenation, carbon dioxide, and acid-base balance. EKG may reveal right ventricular hypertrophy.

Perioperative risk reduction strategies

– The aim is to prevent perioperative bronchospasm and reduce postoperative pulmonary complications. Smoking should be discontinued at least 2 months before the surgery.

– Bronchospasm should be treated. If pulmonary infection is present, consider delaying surgery and administering antibiotic therapy. Start preoperative lung expansion maneuvers education. Bronchodilators and inhaled steroid should be continued on the day of surgery. For patients receiving chronic oral steroid therapy, supplemental doses of steroid may be needed.

Reactive airway disease (asthma)

Preoperative evaluation

– The preoperative history should determine the severity of the disease, recent exacerbation, hospitalization, intubation, and current therapy. The physical examination should focus on detecting signs of acute exacerbation and active lung infection. A chest X-ray may be useful for evaluating infection, air trapping, and pneumothorax. Pulse oxymetry is useful in determining oxygen saturation. In severe cases, arterial blood gas analysis may be necessary.

Perioperative risk reduction strategies

– The goal of management is to avoid perioperative bronchospasm, which can be provoked by a number of factors, such as airway procedures and histamine release medications.

– Bronchodilators and inhaled steroid should be continued on the day of surgery. A perioperative oral steroid for 3 to 5 days may be beneficial for patients who are not at baseline condition. If respiratory tract infection is present, consider delaying surgery. For patients on chronic steroid therapy, supplementation of steroid may be necessary.

d. Renal-GI:

Perioperative evaluation

– Perioperative evaluation of patients with renal insufficiency should focus on renal function, volume, and electrolyte status, as well as associated cardiovascular and other coexisting diseases, medication, and dialysis.

– In patients on hemodialysis, the site of arteriovenous fistula should be identified and blood pressure and venous access should be avoided in that arm.

Perioperative risk reduction

– The primary goal of management for patients with renal insufficiency is to preserve renal function by hydration fluid, diuretics (mannitol, furosemide), and low-dose dopamine and avoiding nephrotoxic agents.

– In patients receiving hemodialysis, dialysis should be performed and electrolytes should be obtained within 24 hours prior to surgery. Postoperative fluid administration and electrolytes will dictate the need for postoperative dialysis.

e. Neurologic:

Acute issues: preoperative evaluation

– This should determine the presence of intracranial hypertension, neurologic deficits, and medication, including steroids, diuretics, and anticonvulsants.

– Neurologic assessment comprises of mental status, respiratory pattern, sensory and motor function, cranial nerves function, and signs of cerebella dysfunction. The preoperative CT scan or MRI can identify the presence of obstructive hydrocephalus. In such cases, treatment such as ventricular drainage and hyperosmolar therapy with mannitol and diuretics can be initiated preoperatively.

Chronic disease: preoperative evaluation

– This evaluation of patients with cerebrovascular disease involves neurological and cardiovascular evaluation. The etiology of stroke, neurological deficit, and treatment, particularly anticoagulant and antiplatelet drugs, should be determined. The patient with severe cerebrovascular disease should be considered a relative contraindication to the sitting position.

f. Endocrine:

Perioperative evaluation

– Diabetes mellitus, especially type II, is a common endocrine disease. The preoperative evaluation of diabetes should focus on control of blood glucose and end-organ damage, including cardiovascular, renal, and neurological systems. The control of blood glucose can be determined by the glycosylated hemoglobin (HbA1c) level. The preoperative EKG, chest radiography, blood glucose, BUN, creatinine, and electrolytes are recommended.

Perioperative risk reduction strategies

– There are several perioperative blood glucose management regimens; however, the primary goals are to avoid hypoglycemia, hyperglycemia, ketoacidosis, and hyperosmolar state. Intensive insulin therapy or tight control aims to keep plasma glucose between 80 to 120 mg/dL, whereas conventional regimen aims to keep plasma glucose below 220 mg/dL. During the perioperative period, blood glucose should be monitored closely and efforts should be made to prevent both hypoglycemia and hyperglycemia.

g. Additional systems/conditions that may be of concern in a patient undergoing this procedure and relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

The patient is usually in a modified sitting (semirecumbent) rather than classical sitting position. The head is fixed with a three-pin head holder, with neck flexed, and the head holder should be attached to the back of the table.

The patient’s legs should be elevated, with knees flexed, to promote venous return and to avoid sciatic nerve injury. The arms should be padded and should rest on the abdomen. Pressure points such as elbows, heads of fibula, and heels should be padded.

4. What are the patient's medications and how should they be managed in the perioperative period?

Most medications for treatment should be continued on the day of the surgery. However, some of these medications should be discontinued before the surgery due to the side effects. A careful medication history should be obtained, including non-prescribed medications, vitamins, and herbal supplement.

h. Are the medications commonly seen in patients undergoing this procedure, and for which should there be greater concern?

Antihypertensive drugs

Diuretics can cause electrolyte imbalance, resulting in arrhythmia. Patients who receive β-blockers may experience bradycardia and fail to increase heart rate in response to blood loss. Calcium channel blockers may cause hypertension, especially when combined with β-blockers. ACE inhibitors or angiotensin II antagonists (AIIAs) are associated refractory hypotension, especially when combined with diuretics.

Antiplatelet and anticoagulant drugs

Patients who receive antiplatelet or anticoagulant drugs may have an increased risk of bleeding and may require transfusion. Perioperative transfusion of 2 to 5 units of platelet concentrates may be required to return platelet function to an adequate level. Emergency reversal of oral anticoagulant could be achieved by administering vitamin K therapy with fresh frozen plasma, prothrombin complex concentrates (PCCs) or recombinant factor VIIa (rfVIIa).

Oral hypoglycemic drugs

Patients who receive oral hypoglycemic drugs may develop perioperative hypoglycemia.

Steroids

Possible side effects of steroids include electrolyte imbalance, hyperglycemia, delayed wound healing, infection, and hypothalmic-pituitary-adrenal axis (HPAA) suppression.

Herbal

Garlic, ginseng, ginger, and gingko are commonly used herbals. All of them may interfere with platelet function, particularly when combined with NSAIDs or Warfarin, and may increase the risk of bleeding. Ginseng also has hypoglycemic effects and may cause intraoperative hypoglycemia, especially in patients who receive oral hypoglycemic drugs.

i. What should be recommended with regard to continuation of medications taken chronically?

Cardiac medications

– This includes antihypertensive medications and diuretics, should be continued on the day of surgery except AIIAs, which depend on the individual patient.

Pulmonary

– Asthma medication, including inhaled and oral steroids, should be continued on the day of surgery. Supplemental dose of steroid may be needed in patients who receive chronic steroid therapy.

Renal

– Diuretics should be continued on the day of the surgery.

Neurologic

– Antiseizure medications should be continued on the day of the surgery.

Antiplatelet and anticoagulant

– Aspirin usually can be continued on the day of the surgery. Plavix (Clopidogrel) should be discontinued 7 days before the surgery, and platelets may need to be given prior to surgery, Warfarin (Coumadin) should be discontinued 4 days before the surgery.

Psychiatric

– Monoamine oxidase inhibitors (MAOIs) should be discontinued at least 2 to 3 weeks before surgery.

Oral hypoglycemic drugs

These should be discontinued on the day of the surgery.

Herbals and nonvitamin supplements

– These should be discontinued 7 days before the surgery.

Vitamins and iron

– These should be discontinued on the day of the surgery.

j. How To modify care for patients with known allergies –

A careful history and medical record review is important to identify patient risk factors or history of allergy. The key to management is to avoid all the known trigger agents.

k. Latex allergy: If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

If latex allergy is suspected, scheduling the surgery as the first case of the day is recommended.

The operating room (OR) should be latex free and labeled as a latex-free OR. All staff should wash hands thoroughly and must wear nonpowdered, nonlatex gloves. All medical products should be made of nonlatex materials. There should be a latex allergy resuscitation cart available in or near the OR. All drugs should be in glass ampules, and all the syringes with latex-free plungers. Prophylacic steroids or H1 and H2 receptor antagonists are not recommended.

l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics]

Cefazolin is the prophylactic antibiotic of choice for craniotomy, but if the patient has ß-lactam allergy, Clindamycin 600-900 mg or Vancomycin 1 g intravenously is the alternative antibiotic.

m. Does the patient have a history of allergy to anesthesia?

Malignant hyperthermia

Documented

– Avoid all trigger agents such as succinylcholine and inhalational agents:

Proposed general anesthetic plan: General anesthesia with total intravenous anesthesia (TIVA) technique is safe. The anesthetic machine should be cleansed by a fresh gas flow 10 L/min for 5 minutes and using a disposable circuit. All the vaporizers should be removed and the soda lime should be changed. MH cart with dantrolene should be available for immediate use.

Family history or risk factors for MH

– If the patient has a family history or risk factors for malignant hyperthermia, anesthesia should be given in the same fashion as known malignant hyperthermia patient.

Local anesthetics/ muscle relaxant

If the patient has a history of allergy to local anesthetics or muscle relaxants, all such drugs must be avoided. If the patients had an unexplained reaction during the previous anesthesia, anesthesia should be given without muscle relaxant in a latex-free environment.

5. What laboratory tests should be obtained and has everything been reviewed?

The preoperative laboratory tests should be obtained based on the patient’s age and medical condition.

Hemoglobin levels with complete blood count should be obtained due to the potential blood loss.
Electrolytes should be obtained if the patient is receiving steroid or diuretic therapy or if the patient is vomiting.
Coagulation panel.
Imaging: Bubble studies either with TEE or TCD should be obtained to screen for the presence of a PFO.
Other tests: Glucose should be obtained if the patient is receiving steroid therapy or has diabetes.

Intraoperative Management: What are the options for anesthetic management and how do I determine the best technique?

Goals of anesthetic management

Facilitate surgical access.
Maintain cardiovascular and respiratory stability.
Maintain cerebral perfusion pressure.

These goals can be achieved by general anesthesia with endotracheal tube, controlled ventilation technique.

6. What is the author's preferred method of anesthesia technique and why?

Premedication: Premedication should be avoided in patients with elevated ICP or hydrocephalus. Steroid and anticonvulsant therapy should be continued on the day of the surgery.

Inhalation versus intravenous: In patients with elevated ICP, invasive arterial blood pressure monitoring should be established before induction and intubation because hypertension during induction and intubation can lead to increased cerebral blood volume and increased ICP.

There is no evidence that one anesthetic drug is better than another. Choice of anesthetic drugs may be affected by the use of electrophysiology monitoring during the surgery. Although N2O has no effect on the incidence or severity of VAE, N2O should be avoided because of its ability to diffuse into and expand air bubbles and the risk of VAE.

General monitoring and monitoring for VAE: In addition to standard American Society of Anesthesiology (ASA) monitors, invasive arterial blood pressure monitoring is recommended for beat-to-beat blood pressure monitoring and for blood gas analysis and blood glucose monitoring during craniotomy.

The transducer should be placed at skull base level to monitor cerebral perfusion pressure (CPP). Additional monitoring for detecting of VAE includes precordial Doppler ultrasonography, expired CO2 (ETCO2) monitoring, expired N2 (ETN2) monitoring, pulmonary artery (PA) catheter, and TEE.

TEE is the most sensitive monitor for detecting air in the right atrium and is the only monitor that can detect PAE in the left atrium. However, it is invasive and prolonged use may cause postoperative airway swelling and obstruction.

Precordial Doppler ultrasonography is the most sensitive of the commonly available devices for detecting intracardiac air. Precordial Doppler in combination with ETCO2 is the current standard monitoring for VAE. The Doppler probe should be placed at the middle third on the right side of the sternum. The position of the probe can be confirmed by injecting 0.25 to 0.5 mL CO2 or 5 mL saline through a right heart catheter and listening for characteristic Doppler signal.

Expired gas monitor and PA catheters are less sensitive. VAE is associated with a sudden decrease in ETCO2 and the presence of the ETN2. PA pressure increases due to pulmonary hypertension caused by VAE.

A right heart catheter is essential for surgery performed in the sitting position, as a means to recover the entrained air from the right side of the heart. Aspiration of air is not only a treatment but also confirms the diagnosis of VAE. It is recommended that all patients undergoing surgery in the sitting position should have a right heart catheter.

Formaximum recovery of entrained air, a multi-orifice catheter is required. The ideal location of the multi-orifice catheter is 2 cm below the junction, between the superior vena cava and the right atrium. The catheter position can be confirmed by intravascular EKG, a chest X-ray, or by withdrawing from the right ventricle while monitoring intravascular pressure. Due to elevated ICP in some patients, which makes the head-down position for internal jugular access impossible, and because of the risk of hematoma from access to the internal jugular vein, some anesthesiologists may prefer to insert the right heart catheter through the brachial vein.

What prophylactic antibiotics should be administered?

Cefazolin 1-2 g intravenous should be given within 1 hour prior to surgical incision. If the patient has ß-lactam allergy, Clindamycin 600-900 mg or Vancomycin 1 g intravenously are alternative antibiotics. If there is known history of MRSA, Vancomycin 1 g intravenously is recommended (SCPI 2007 recommendations).

What are the most common intraoperative complications and how can they be avoided and/or treated?

Intraoperative complications associated with the sitting position are hemodynamic instability, venous air embolism (VAE) with the possibility of paradoxical air embolism (PAE), and pneumocephalus.

Hemodynamic instability

Placing the anesthetized patients in the sitting position causes pooling of blood in the lower part of the body and decreases venous return and cardiac output, resulting in hypotension and compromise CPP. Techniques to minimize hypotension include adequate hydration, administration of vasopressors, use of elastic stocking or active leg compression, slow incremental adjustment of the table, and adjustment of anesthetic depth. Placement of the invasive atrial pressure transducer at the skull base level can help measure and maintain CPP.

Cardiovascular reflex

Surgical manipulation on or near brain stem, fourth ventricle, cranial nerves may result in sudden and profound cardiovascular changes, such as hypertension and bradycardia. The surgeon should be notified immediately to avoid the manipulation. Bradycardia can be treated with glycopyrolate or atropine.

Venous air embolism (VAE) and paradoxical air embolism (PAE)

VAE can occur when the pressure in the open vein is subatmospheric. Craniotomy in the sitting position is high risk for VAE because the venous sinuses are noncollapsible. The incidence of VAE during sitting craniotomy varies, depending on the detection method. The reported incidence of VAE detected by TEE is 76%. Clinical manifestation depends on volume and rate of air entrainment and the presence of PFO.

A decrease of ETCO2 with presence of nitrogen in the expired gas, an increase of right atrial, and PA pressure may be detected prior to hypotension and hypoxemia. Arterial blood gas analysis may show an increase in PaCO2. Massive air embolism is rare but can cause sudden cardiovascular collapse from right ventricular obstruction.

Management of VAE aims to prevent further air entry, reduce intravascular air, and support cardiovascular and respiratory function. Treatment of VAE includes the following measures:

Notify the surgeons so that they can pack or flood surgical field with saline, apply bone wax, and identify the source of air entrainment.
Discontinue N2O (if being used) and increase FiO2 to 1.
Aspirate the right heart catheter to remove the entrained air.
Intravenous fluid infusion to increase venous pressure.
Provide cardiovascular support with vasopressors and/or inotropes if necessary.
Bilateral jugular vein compression.
Change patient position to head-down position if the proceeding measures fail to prevent further air entrainment.
Position the patient in the left lateral position, which may help localize air into the right atrium and facilitate aspiration through the right heart catheter.

PAE occurs when VAE passes from venous circulation via a PFO to the systematic arterial circulation. PAE may have catastrophic consequences from embolism to cerebral or coronary vessels.

The reported incidence of clinical and TOE detected PAE ranged from 0% to 14%. A study by Mammoto et al. demonstrated that PAE was associated with severe VAE and increased pulmonary artery pressure. This finding suggests that an elevated right heart pressure increases the risk of PAE. Augmented intravenous fluid administration was shown to reduce the pressure gradient between right and left atria; hence, it may prevent PAE. In contrast, the use of PEEP increases the pressure gradient and may increase risk of PAE.

a. Neurologic:

Pneumochephalus: During craniotomy in an upright position, intracranial volume is decreased due to CSF loss, good venous drainage, mannitol administration, and hypocapnia. Drainage of CSF leads to air into the supratentorial space, invert pop bottle mechanism.

Tension pneumocephalus occurs when dura is closed and the patient is returned to the supine position (the head is lowered), CSF and blood return, and the brain re-expands. As a result, the air pocket becomes a mass compressing the brain.

N20 has been implicated as a contributing factor of tension pneumocephalus because it is used to diffuse into and expand an air-filled cavity. However, tension pneumocephalus can occur when N2O is not used. Clinical symptoms include severe headache, confusion, convulsion, and delayed awakening or nonawakening after the surgery and cardiovascular collapse. Diagnosis can be confirmed by CT scan. The treatment is immediately drilling a twist-drill hole and needle aspiration of air.

b. If the patient is intubated, are there any special criteria for extubation?

Like other types of neurosurgery, rapid, smooth emergence from anesthesia without coughing, straining, or hypertension for neurological assessment is desirable.

The decision to extubate at the end of sitting craniotomy depends on general criteria as well as the preoperative neurologic status, the extent and nature of surgery, and the possibility of brain stem injury or edema. As posterior cranial fossa contains respiratory, a circulatory center, and also cranial nerves with their nuclei, injuries to such structures can result in an inability to maintain the airway after extubation or an abnormal respiratory pattern.

The anesthesiologist should discuss plans for the patient’s extubation and postoperative management with the surgeon.

c. Postoperative management

What analgesic modalities can I implement?

Inadequate postoperative pain control can cause agitation and hypertension, resulting in intracranial edema and hemorrhage. However, side effects of opioids (particularly long-acting ones) such as respiratory depression and nausea/vomiting also have negative effects on the patient’s neurological status. Thus, the goal of postoperative pain therapy is to have adequate analgesia with minimal side effects from analgesic drugs.

At present, there are no treatment guidelines for postoperative pain control. Adequate analgesia can be provided with continuous intravenous infusion of short-acting opioids, such as remifentanil or fentanyl. Morphine can be titrated to individual patient’s need or with patient-controlled analgesia (PCA) with careful monitoring. Nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol may be added to reduce the need for opioids. However, NSIADs may increase the risk of postoperative bleeding. Scalp blocks with bupivacaine or ropivacaine have been demonstrated to be effective in reducing early postoperative pain and analgesic drugs.

What level of bed acuity is appropriate?

Because of the small size of posterior fossa and its important contents, complications such as hemorrhage or swelling can lead to brain stem compression and herniation. Therefore, postoperative monitoring and care in ICU is recommended.

What are common postoperative complications and ways to prevent and treat them?

Macroglossia: Upper airway obstruction following surgery in the sitting position can occur due to swelling of pharyngeal structures, including soft palate, posterior pharyngeal wall, and base of tongue. Excessive neck flexion with the presence of foreign body, such as in the oropharyngeal airway or TEE in lengthy procedures, promotes obstruction of venous and lymphatic drainage of these structures, leading to swelling and macroglossia. It is advisable to maintain at least two fingerbreadth’s distance between the mandible and the sternum to prevent extreme neck flexion.

Quadriplegia: There have been reports of quadriplegia following surgeries in the sitting position. Although the pathogenesis remains uncertain, some mechanisms have been hypothesized. Flexion of head and neck during the sitting position may cause overstretching or compression of the cervical spinal cord. In addition, hypotension secondary to positioning in combination with extreme neck flexion may compromise spinal cord perfusion.

What's the Evidence?

Fischer, SP, Bader, AM, Sweitzer, B, Miller, RD. “Preoperative evaluation”. Miller's Anesthesia. 2010. (This book provides current knowledge and practices in the field of anesthesia.)

Strendel, R, Gramm, HJ, Schroder, K, Lober, C, Brock, M. “Transcranial Doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position”. Anesthesiology . vol. 93. 2000. pp. 971-5.

Schneider, B, Zienkiewcz, T, Jansen, V. “Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings”. Am J Cardiol . vol. 77. 1996. pp. 1202-9.

Gildenberg, PL, O’Brien, RP, Britt, WJ, Frost, EA. “The efficacy of Doppler monitoring for the detection of venous air embolism”. J Neurosurg . vol. 54. 1981. pp. 75-8.

Mirski, MA, Lele, AV, Fitzsimmons, L. “Diagnosis and treatment of vascular air embolism”. Anesthesiology. vol. 106. 2007. pp. 164-7.

Palmon, SC, Moore, LE, Lundberg, J, Toung, T. “Venous air embolism: a review”. J Clin Anesth. vol. 9. 1997. pp. 251-7.

Tinker, JH, Gronert, GA, Messick, JM, Michenfelder, JD. “Detection of air embolism, a test for positioning of right atrial catheter and Doppler probe”. Anesthesiology . vol. 43. 1975. pp. 104-6.

Maroon, JC, Albin, MS. “Air embolism diagnosed by Doppler ultrasound”. Anesth Analg . vol. 53. 1974. pp. 399-402.

Colley, PS, Pavlin, EG, Groepper, J. “Assessment of a saline injection test for location of a right atrial catheter”. Anesthesiology. vol. 50. 1979. pp. 258-60.

Bunegin, L, Albin, MS, Helsel, PE, Hoffman, A, Hung, TK. “Positioning the right atrial catheter: a model for reappraisal”. Anesthesiology. vol. 55. 1981. pp. 348-8. (These articles provide evidence regarding various methods for detection of VAE.)

Mirski, MA, Lele, AV, Fitzsimmons, L. “Diagnosis and treatment of vascular air embolism”. Anesthesiology. vol. 106. 2007. pp. 164-77. (This article provides prevention and management for VAE.)

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