Acknowledgments
The authors would like to thank their colleague William Young MD who was responsible for much of the original text of this chapter.
Interventional neuroradiology (INR) is the discipline that uses endovascular procedures to treat vascular conditions of the central nervous system. Other names for the field are neurointerventional surgery, surgical neuroangiography, and endovascular neurosurgery. INR is firmly established in the management of cerebrovascular disease, a watershed event perhaps being the International Subarachnoid Aneurysm Trial, which provided level 1 evidence that aneurysm coiling has advantages over surgical clipping of intracranial aneurysms.
The discussion in this chapter emphasizes perioperative and anesthetic management strategies to optimize conditions for therapeutic interventions, to prevent complications and to minimize their effects if they occur. We further assume that the primary imaging technology is catheter angiography, although magnetic resonance imaging may one day augment this practice. Planning of the anesthetic and perioperative management is predicated on an understanding of the goals of the therapeutic intervention and anticipation of potential problems.
The anesthetic concerns of particular importance for INR procedures are (1) maintaining the patient’s immobility during the procedure to facilitate imaging and to prevent intervention- related complications; (2) either enabling rapid recovery from anesthesia at the end of the operation to facilitate neurologic examination and monitoring or providing for intermittent evaluation of neurologic function during the procedure; (3) managing anticoagulation; (4) treating and managing sudden unexpected procedure-specific complications during the procedure, such as hemorrhage or vascular occlusion, which may involve manipulating systemic blood pressure; (5) guiding the medical management of critical care patients during transport to and from radiology suites; and (6) recognizing self- protection issues related to radiation safety. ,
Preoperative planning and patient preparation
Patients for NIR procedures range from healthy outpatients coming for diagnostic NIR procedures to the critically ill, unresponsive patients from the intensive care unit with devastating intracranial bleeds. Procedures may be elective or emergent, such as treatment of acute ischemic strokes. Thus, the preoperative planning may vary significantly from patient to patient.
Baseline blood pressure and cardiovascular reserve should be assessed carefully. This almost axiomatic statement is particularly important for several reasons. Blood pressure manipulation is commonly required, and treatment-related perturbations should be anticipated. Therefore, a clear sense of the patient’s baseline blood pressure needs to be established. One must keep in mind that “autoregulation” as presented in the textbooks is a description of a population; individual patients are likely to vary considerably, a concept based on the historical observations that underlie our modern notions of autoregulatory behavior. , To state the issue another way: when looking at the usual autoregulation curve, one should bear in mind that each point on that curve has a 95% confidence interval (CI) associated with it in both x and y directions. For most procedures, beat-to-beat blood pressure monitoring is useful, considering the rapid time constants in this setting for changes in systemic or cerebral hemodynamics.
Preoperative administration of calcium channel blockers for prophylaxis for cerebral ischemia may be used and can affect hemodynamic management. In addition, these agents or transdermal nitroglycerin are sometimes used to lower the chance of catheter-induced vasospasm.
Radiologic contrast media are well known to cause allergic reactions. There seems to be no difference between the older and newer agents in their propensity to cause anaphylactoid reactions. However, newer agents provide a much lower osmolar load and, therefore, preserve intravascular volume in the event of an allergic crisis. The newer agents are also less neurotoxic than the older, high osmolar contrast agents.
The patient’s previous experience with radiologic imaging that may have included administration of contrast agents should be inquired about. As intraprocedural systemic heparinization is commonly used in INR, protamine sulfate is also often used to reverse the anticoagulant effect of heparin. Protamine is also known to cause allergic reactions. In the history, items of interest include prior anticoagulation, coagulation disorders, protamine allergy (related items include protamine insulin use, fish allergy, and prior vasectomy), recent steroid use, and contrast agent reactions (including general atopy and iodine/shellfish allergies).
Patients who give a history of significant contrast agent reactions can be treated with steroids, antihistamines and H2 blockers prior to the procedure. The treatment of severe allergic response is reviewed in general textbooks and prominently features use of adrenergic agonists, such as epinephrine (adrenaline).
The patient’s renal function should be evaluated before the procedure due to nephrotoxicity of the contrast agents.
Patients coming from intensive care units may be intubated, mechanically ventilated and have an intra-arterial catheter and/or an extra ventricular device (EVD) in place. Hemodynamic, ventilator and EVD management of these patients should be clearly discussed with the ICU team before the procedure.
A number of considerations regarding the anesthetizing location should be borne in mind. Both wall and tank oxygen should be available. All the usual anesthetizing location considerations should be provided, including adequate lighting, electrical power, and ready access to a phone line (dedicated if at all possible). The access to emergency equipment must be proximate and immediate. One configuration of a modern neuroradiology suite and associated images is shown in Fig. 14.1 . Magnetic resonance imaging and conventional angiography units are sometimes combined in one setting ( Fig. 14.2 ).
A fundamental knowledge of radiation safety is essential for all staff members working in an INR suite as well as a critical part of preoperative planning. It is reasonable to assume that the X-ray machine is always on. There are three sources of radiation in the INR suite: direct radiation from the X-ray tube, leakage (through the collimators’ protective shielding), and scatter radiation (reflected from the patients and the area surrounding the body part to be imaged). The amount of exposure decreases proportionally to the inverse of the square of the distance from the source of radiation (inverse square law). Digital subtraction angiography delivers considerably more radiation than fluoroscopy.
Optimal protection involves the use of lead aprons, thyroid shields, eye protection, and radiation exposure badges. The lead aprons should be periodically evaluated for any cracks in the lead lining that may allow accidental radiation exposure. Movable lead glass screens may provide additional protection for the anesthesia team. Clear communication between the INR and anesthesia teams is also crucial for limiting radiation exposure. With proper precautions, the anesthesia team should be exposed to far less than the annual recommended limit for health care workers.
Anesthetic Technique
Choice of Anesthetic Technique
The choice of anesthetic technique varies among centers, with no clear superior method, and generally follows the dictates of the well-described considerations for operative neuroanesthesia. At UCSF we typically provide monitored anesthesia care (MAC, sedation) to patients undergoing diagnostic angiography as long as the patients are cooperative and can remain still during image acquisition. Patients receiving therapeutic intervention involving intracranial blood vessels and patients undergoing spinal angiography typically receive general anesthesia (GA).
Secure intravenous (IV) access should be available with adequate extension tubing to allow drug and fluid administration at maximal distance from the image intensifier during fluoroscopy. Access to intravenous or arterial catheters and EVDs can be difficult when the patient is draped with the arms restrained at the sides. Primary anesthetic or vasoactive agent infusions should be given through proximal ports with minimal dead space.
Monitoring
In addition to the standard monitors specified by the American Society of Anesthesiologists, capnography sampling via the sampling port of the nasal cannula is used during IV sedation.
For intracranial procedures and postoperative care, beat-to-beat arterial pressure monitoring and blood sampling can be facilitated by the placement of an intra-arterial catheter. A side port of the femoral artery introducer sheath can also be used, but the sheath is usually removed immediately after the procedure. In a patient who requires continuous blood pressure monitoring or frequent blood sampling postoperatively, it is convenient to have a separate radial arterial catheter. Electrophysiologic monitoring is not commonly used.
With a coaxial or triaxial catheter system, arterial pressure at the carotid artery, the vertebral artery, and the distal cerebral circulation can be measured. Pressures in these distal catheters usually underestimate systolic and overestimate diastolic pressure; however, mean pressures are reliable. Bladder catheters assist in fluid management as well as patient comfort; a significant volume of heparinized flush solution and radiographic contrast agent may be used. Sodium bicarbonate infusions are used to reduce potential renal injury, especially in patients with abnormal renal function. The infusion is typically started before the procedure, and continued till after the end of procedure.
EVDs should be monitored and drained as discussed with the primary care team.
General Anesthesia
The primary reasons for employing general anesthesia in INR are to minimize motion artifacts, to improve the quality of the image and to reduce catheter-induced complications. Normocapnia or modest hypocapnia consistent with the safe conduct of positive-pressure ventilation should be maintained, unless intracranial pressure is a concern. The specific choice of anesthesia may be guided primarily by other cardiovascular and cerebrovascular considerations and typically follow general neuroanesthesia principles. There is no clear superiority of one modern anesthetic over another in terms of pharmacologic protection against neuronal injury. Total intravenous anesthetic techniques, or combinations of inhalational and intravenous methods, may optimize rapid emergence. An argument could be made for avoiding nitrous oxide because of the possibility of introducing air emboli into the cerebral circulation and also because of reports that this agent worsens outcome after experimental brain injury.
It is important to distinguish between the two general settings in which hyperventilation is used in anesthetic practice. First, it is used to treat intracranial hypertension. Hyperventilation is an important mainstay in the management of an intracranial catastrophe to acutely reduce cerebral blood volume ( Box 14.1 ). PaCO 2 management should aim at normocapnia or mild hypocapnia to the extent consistent with the safe conduct of positive-pressure ventilation. If a patient has increased intracranial pressure, prophylactic mild hypocapnia may be indicated during the induction and maintenance of anesthesia. Patients who have been hyperventilated in the ICU before the procedure, and patients who may be spontaneously hyperventilating secondary to cerebral injury should have their pCO 2 maintained at or below pre-procedure levels.
* These are only general recommendations and drug doses. They must be adapted to specific clinical situations and in accordance with a patient’s preexisting medical condition. In some cases of asymptomatic or minor vessel puncture or occlusion, less aggressive management may be appropriate.
Initial Resuscitation
Communicate with endovascular therapy team. Assess the need for assistance; call for assistance. Secure the airway and ventilate with 100% O 2 .
Determine whether the problem is hemorrhagic or occlusive:
Hemorrhagic: Immediate heparin reversal (1 mg protamine for each 100 units of heparin given) and low normal mean arterial pressure.
Occlusive: Deliberate hypertension, titrated to findings of neurologic examination, angiography, or physiologic imaging studies or to clinical context.
Further Resuscitation
PaCO 2 manipulation consistent with clinical setting; otherwise normocapnia. Mannitol 0.5 g/kg, rapid IV infusion.
Titrate IV agent to electroencephalographic burst suppression.
Consider ventriculostomy for treatment or monitoring of increased intracranial pressure. Consider anticonvulsant.
There are some special circumstances for which induced hypercapnia may be indicated, such as embolization of extracranial vascular malformations, which drain into the intracranial venous system. In these cases, induction of hypercapnia can promote high venous outflow from the cerebral venous system and help minimize the risk of inadvertent movement of embolic material into the intracranial compartment (discussed later).
Intravenous Sedation
For cases managed with an unsecured airway, routine evaluation of the potential ease of laryngoscopy in an emergency situation should take into account that direct access to the airway may be limited by table or room logistics. Recent pterional craniotomy can sometimes result in impairment of temporomandibular joint mobility.
For IV sedation cases, careful padding of pressure points and working with the patient to obtain a final comfortable positioning may assist in the patient’s ability to tolerate a long period of lying supine and motionless, decreasing the requirement for sedation, anxiolysis, and analgesia. The possibility of pregnancy in women and a history of adverse reactions to radiographic contrast agents should be explored.
Intravenous sedation in aneurysm management is used most often for patients coming for diagnostic angiography or interim follow-up angiography to assess the necessity for re-treatment after primary coiling. If further treatment is indicated or the patient is not able to stay still during image acquisition, the technique can be converted to general anesthesia. The goals of anesthetic choice for intravenous sedation are to alleviate pain, anxiety, and discomfort, and allow rapid recovery. There may be some discomfort associated with injection of contrast media into the cerebral arteries (burning) and with distention or traction on them (headache). A long period of lying motionless can also cause significant discomfort.
A variety of sedation regimens is available, and specific choices are based on the experience of the practitioner and the goals of anesthetic management. Common to all intravenous sedation techniques is the potential for upper airway obstruction. However, light levels of sedation that provide anxiolysis are usually optimal as the patients need to stay still and hold their breath during image acquisition. At UCSF we frequently use small doses of midazolam and fentanyl for sedation during NIR procedures. Placement of a nasopharyngeal airway may cause troublesome bleeding in anticoagulated patients and is generally avoided.
Dexmedetomidine is a newer agent that may have applicability in the INR setting. It is a potent, selective alpha2 adrenoceptor agonist with sedative, anxiolytic, and analgesic properties. Dexmedetomidine is especially noteworthy for its ability to produce a state of patient tranquility without depressing respiration. However, like other sedatives, dexmedetomidine-induced sedation may cause upper airway obstruction. More importantly, there is a tendency for patients managed with dexmedetomidine to have relatively low blood pressure in the postoperative recovery period. Because patients with aneurysmal subarachnoid hemorrhage (SAH) may be critically dependent on the adequacy of collateral perfusion pressure, regimens that may result in blood pressure decreases should be used with great caution.
Anticoagulation
Heparin
Careful management of coagulation is required to prevent thromboembolic complications during and after the procedure. Generally, after a baseline activated clotting time is obtained, intravenous heparin (approximately 70 units/kg) is given to a target prolongation of 2 to 3 times the baseline value. Then heparin can be given continuously or as an intermittent bolus with hourly monitoring of activated clotting time. For the occasional case of refractoriness, adequate anticoagulation, switching from bovine to porcine heparin, or vice versa, should be considered. If antithrombin III deficiency is suspected, administration of fresh frozen plasma may be necessary.
Direct Thrombin Inhibitors
Heparin-induced thrombocytopenia is a rare but important adverse event in heparin anticoagulation. Development of heparin-dependent antibodies after initial exposure leads to a prothrombotic syndrome. In high-risk patients, direct thrombin inhibitors can be applied, with the realization that adverse events are inherent to their use, such as anaphylaxis. Direct thrombin inhibitors inhibit free and clot-bound thrombin, and their effect can be monitored by either an activated partial thromboplastin time or activated clotting time. Lepirudin and bivalirudin, a synthetic derivative, have half-lives of 40 to 120 minutes and about 25 minutes, respectively. Because these drugs undergo renal elimination, dose adjustments may be needed in patients with renal dysfunction. Argatroban is an alternative agent that undergoes primarily hepatic metabolism. One report has described bivalirudin as a potential alternative to heparin during INR procedures for intravenous anticoagulation and intra-arterial thrombolysis.
Antiplatelet Agents
Although still controversial in the acute setting, antiplatelet agents (aspirin, the glycoprotein IIb/IIIa receptor antagonists, and the thienopyridine derivatives) are increasingly being used for cerebrovascular disease management and may be of use for acute treatment of thromboembolic complications. Abciximab (ReoPro) has been used to treat thromboembolic complications. Activation of the platelet membrane glycoprotein IIb/IIIa leads to fibrinogen binding and is a final common pathway for platelet aggregation. Abciximab, eptifibatide, and tirofiban are glycoprotein IIb/IIla receptor antagonists. The long duration and potent effect of abciximab also increase the likelihood of major bleeding. The smaller-molecule agents, eptifibatide and tirofiban, are competitive blockers with shorter half-lives of about 2 hours. Thienopyridine derivatives (ticlopidine and clopidogrel) bind to the platelet’s adenosine diphosphate receptor, permanently altering the receptor; therefore, the duration of action is the lifespan of the platelet. Clopidogrel is commonly added to the antiplatelet regimen for procedures that require placement of devices (eg, stents, coiling or stent-assisted coiling) primarily in patients who have not had an acute event, such as those with unruptured aneurysms. Patients who are expected to receive stents, should be pretreated with antiplatelet agents, because of the potential risk of thrombus formation on the stent.
Reversal of Anticoagulation
At the end of the procedure or at occurrence of hemorrhagic complication, heparin anticoagulation may be reversed with protamine. Because there is no specific antidote for the direct thrombin inhibitors or the antiplatelet agents should reversal be indicated, biologic half-life is one of the major considerations in drug choice, and platelet transfusion is a nonspecific therapy. There is no currently available accurate test to measure platelet function in patients taking the newer antiplatelet drugs. Desmopressin (DDAVP) has been reported to shorten the prolonged bleeding time of individuals taking antiplatelet agents, such as aspirin and ticlopidine. There are also increasingly more reports on the use of specific clotting factors, such as recombinant factor VIIa and factor IX complex, to rescue severe life-threatening bleeding, including intracranial hemorrhage uncontrolled by standard transfusion therapy. The safety and efficacy of these coagulation factors remain to be investigated.
Preoperative planning and patient preparation
Patients for NIR procedures range from healthy outpatients coming for diagnostic NIR procedures to the critically ill, unresponsive patients from the intensive care unit with devastating intracranial bleeds. Procedures may be elective or emergent, such as treatment of acute ischemic strokes. Thus, the preoperative planning may vary significantly from patient to patient.
Baseline blood pressure and cardiovascular reserve should be assessed carefully. This almost axiomatic statement is particularly important for several reasons. Blood pressure manipulation is commonly required, and treatment-related perturbations should be anticipated. Therefore, a clear sense of the patient’s baseline blood pressure needs to be established. One must keep in mind that “autoregulation” as presented in the textbooks is a description of a population; individual patients are likely to vary considerably, a concept based on the historical observations that underlie our modern notions of autoregulatory behavior. , To state the issue another way: when looking at the usual autoregulation curve, one should bear in mind that each point on that curve has a 95% confidence interval (CI) associated with it in both x and y directions. For most procedures, beat-to-beat blood pressure monitoring is useful, considering the rapid time constants in this setting for changes in systemic or cerebral hemodynamics.
Preoperative administration of calcium channel blockers for prophylaxis for cerebral ischemia may be used and can affect hemodynamic management. In addition, these agents or transdermal nitroglycerin are sometimes used to lower the chance of catheter-induced vasospasm.
Radiologic contrast media are well known to cause allergic reactions. There seems to be no difference between the older and newer agents in their propensity to cause anaphylactoid reactions. However, newer agents provide a much lower osmolar load and, therefore, preserve intravascular volume in the event of an allergic crisis. The newer agents are also less neurotoxic than the older, high osmolar contrast agents.
The patient’s previous experience with radiologic imaging that may have included administration of contrast agents should be inquired about. As intraprocedural systemic heparinization is commonly used in INR, protamine sulfate is also often used to reverse the anticoagulant effect of heparin. Protamine is also known to cause allergic reactions. In the history, items of interest include prior anticoagulation, coagulation disorders, protamine allergy (related items include protamine insulin use, fish allergy, and prior vasectomy), recent steroid use, and contrast agent reactions (including general atopy and iodine/shellfish allergies).
Patients who give a history of significant contrast agent reactions can be treated with steroids, antihistamines and H2 blockers prior to the procedure. The treatment of severe allergic response is reviewed in general textbooks and prominently features use of adrenergic agonists, such as epinephrine (adrenaline).
The patient’s renal function should be evaluated before the procedure due to nephrotoxicity of the contrast agents.
Patients coming from intensive care units may be intubated, mechanically ventilated and have an intra-arterial catheter and/or an extra ventricular device (EVD) in place. Hemodynamic, ventilator and EVD management of these patients should be clearly discussed with the ICU team before the procedure.
A number of considerations regarding the anesthetizing location should be borne in mind. Both wall and tank oxygen should be available. All the usual anesthetizing location considerations should be provided, including adequate lighting, electrical power, and ready access to a phone line (dedicated if at all possible). The access to emergency equipment must be proximate and immediate. One configuration of a modern neuroradiology suite and associated images is shown in Fig. 14.1 . Magnetic resonance imaging and conventional angiography units are sometimes combined in one setting ( Fig. 14.2 ).
A fundamental knowledge of radiation safety is essential for all staff members working in an INR suite as well as a critical part of preoperative planning. It is reasonable to assume that the X-ray machine is always on. There are three sources of radiation in the INR suite: direct radiation from the X-ray tube, leakage (through the collimators’ protective shielding), and scatter radiation (reflected from the patients and the area surrounding the body part to be imaged). The amount of exposure decreases proportionally to the inverse of the square of the distance from the source of radiation (inverse square law). Digital subtraction angiography delivers considerably more radiation than fluoroscopy.
Optimal protection involves the use of lead aprons, thyroid shields, eye protection, and radiation exposure badges. The lead aprons should be periodically evaluated for any cracks in the lead lining that may allow accidental radiation exposure. Movable lead glass screens may provide additional protection for the anesthesia team. Clear communication between the INR and anesthesia teams is also crucial for limiting radiation exposure. With proper precautions, the anesthesia team should be exposed to far less than the annual recommended limit for health care workers.
Anesthetic Technique
Choice of Anesthetic Technique
The choice of anesthetic technique varies among centers, with no clear superior method, and generally follows the dictates of the well-described considerations for operative neuroanesthesia. At UCSF we typically provide monitored anesthesia care (MAC, sedation) to patients undergoing diagnostic angiography as long as the patients are cooperative and can remain still during image acquisition. Patients receiving therapeutic intervention involving intracranial blood vessels and patients undergoing spinal angiography typically receive general anesthesia (GA).
Secure intravenous (IV) access should be available with adequate extension tubing to allow drug and fluid administration at maximal distance from the image intensifier during fluoroscopy. Access to intravenous or arterial catheters and EVDs can be difficult when the patient is draped with the arms restrained at the sides. Primary anesthetic or vasoactive agent infusions should be given through proximal ports with minimal dead space.
Monitoring
In addition to the standard monitors specified by the American Society of Anesthesiologists, capnography sampling via the sampling port of the nasal cannula is used during IV sedation.
For intracranial procedures and postoperative care, beat-to-beat arterial pressure monitoring and blood sampling can be facilitated by the placement of an intra-arterial catheter. A side port of the femoral artery introducer sheath can also be used, but the sheath is usually removed immediately after the procedure. In a patient who requires continuous blood pressure monitoring or frequent blood sampling postoperatively, it is convenient to have a separate radial arterial catheter. Electrophysiologic monitoring is not commonly used.
With a coaxial or triaxial catheter system, arterial pressure at the carotid artery, the vertebral artery, and the distal cerebral circulation can be measured. Pressures in these distal catheters usually underestimate systolic and overestimate diastolic pressure; however, mean pressures are reliable. Bladder catheters assist in fluid management as well as patient comfort; a significant volume of heparinized flush solution and radiographic contrast agent may be used. Sodium bicarbonate infusions are used to reduce potential renal injury, especially in patients with abnormal renal function. The infusion is typically started before the procedure, and continued till after the end of procedure.
EVDs should be monitored and drained as discussed with the primary care team.
General Anesthesia
The primary reasons for employing general anesthesia in INR are to minimize motion artifacts, to improve the quality of the image and to reduce catheter-induced complications. Normocapnia or modest hypocapnia consistent with the safe conduct of positive-pressure ventilation should be maintained, unless intracranial pressure is a concern. The specific choice of anesthesia may be guided primarily by other cardiovascular and cerebrovascular considerations and typically follow general neuroanesthesia principles. There is no clear superiority of one modern anesthetic over another in terms of pharmacologic protection against neuronal injury. Total intravenous anesthetic techniques, or combinations of inhalational and intravenous methods, may optimize rapid emergence. An argument could be made for avoiding nitrous oxide because of the possibility of introducing air emboli into the cerebral circulation and also because of reports that this agent worsens outcome after experimental brain injury.
It is important to distinguish between the two general settings in which hyperventilation is used in anesthetic practice. First, it is used to treat intracranial hypertension. Hyperventilation is an important mainstay in the management of an intracranial catastrophe to acutely reduce cerebral blood volume ( Box 14.1 ). PaCO 2 management should aim at normocapnia or mild hypocapnia to the extent consistent with the safe conduct of positive-pressure ventilation. If a patient has increased intracranial pressure, prophylactic mild hypocapnia may be indicated during the induction and maintenance of anesthesia. Patients who have been hyperventilated in the ICU before the procedure, and patients who may be spontaneously hyperventilating secondary to cerebral injury should have their pCO 2 maintained at or below pre-procedure levels.
* These are only general recommendations and drug doses. They must be adapted to specific clinical situations and in accordance with a patient’s preexisting medical condition. In some cases of asymptomatic or minor vessel puncture or occlusion, less aggressive management may be appropriate.
Initial Resuscitation
Communicate with endovascular therapy team. Assess the need for assistance; call for assistance. Secure the airway and ventilate with 100% O 2 .
Determine whether the problem is hemorrhagic or occlusive:
Hemorrhagic: Immediate heparin reversal (1 mg protamine for each 100 units of heparin given) and low normal mean arterial pressure.
Occlusive: Deliberate hypertension, titrated to findings of neurologic examination, angiography, or physiologic imaging studies or to clinical context.
Further Resuscitation
PaCO 2 manipulation consistent with clinical setting; otherwise normocapnia. Mannitol 0.5 g/kg, rapid IV infusion.
Titrate IV agent to electroencephalographic burst suppression.
Consider ventriculostomy for treatment or monitoring of increased intracranial pressure. Consider anticonvulsant.
There are some special circumstances for which induced hypercapnia may be indicated, such as embolization of extracranial vascular malformations, which drain into the intracranial venous system. In these cases, induction of hypercapnia can promote high venous outflow from the cerebral venous system and help minimize the risk of inadvertent movement of embolic material into the intracranial compartment (discussed later).
Intravenous Sedation
For cases managed with an unsecured airway, routine evaluation of the potential ease of laryngoscopy in an emergency situation should take into account that direct access to the airway may be limited by table or room logistics. Recent pterional craniotomy can sometimes result in impairment of temporomandibular joint mobility.
For IV sedation cases, careful padding of pressure points and working with the patient to obtain a final comfortable positioning may assist in the patient’s ability to tolerate a long period of lying supine and motionless, decreasing the requirement for sedation, anxiolysis, and analgesia. The possibility of pregnancy in women and a history of adverse reactions to radiographic contrast agents should be explored.
Intravenous sedation in aneurysm management is used most often for patients coming for diagnostic angiography or interim follow-up angiography to assess the necessity for re-treatment after primary coiling. If further treatment is indicated or the patient is not able to stay still during image acquisition, the technique can be converted to general anesthesia. The goals of anesthetic choice for intravenous sedation are to alleviate pain, anxiety, and discomfort, and allow rapid recovery. There may be some discomfort associated with injection of contrast media into the cerebral arteries (burning) and with distention or traction on them (headache). A long period of lying motionless can also cause significant discomfort.
A variety of sedation regimens is available, and specific choices are based on the experience of the practitioner and the goals of anesthetic management. Common to all intravenous sedation techniques is the potential for upper airway obstruction. However, light levels of sedation that provide anxiolysis are usually optimal as the patients need to stay still and hold their breath during image acquisition. At UCSF we frequently use small doses of midazolam and fentanyl for sedation during NIR procedures. Placement of a nasopharyngeal airway may cause troublesome bleeding in anticoagulated patients and is generally avoided.
Dexmedetomidine is a newer agent that may have applicability in the INR setting. It is a potent, selective alpha2 adrenoceptor agonist with sedative, anxiolytic, and analgesic properties. Dexmedetomidine is especially noteworthy for its ability to produce a state of patient tranquility without depressing respiration. However, like other sedatives, dexmedetomidine-induced sedation may cause upper airway obstruction. More importantly, there is a tendency for patients managed with dexmedetomidine to have relatively low blood pressure in the postoperative recovery period. Because patients with aneurysmal subarachnoid hemorrhage (SAH) may be critically dependent on the adequacy of collateral perfusion pressure, regimens that may result in blood pressure decreases should be used with great caution.
Anticoagulation
Heparin
Careful management of coagulation is required to prevent thromboembolic complications during and after the procedure. Generally, after a baseline activated clotting time is obtained, intravenous heparin (approximately 70 units/kg) is given to a target prolongation of 2 to 3 times the baseline value. Then heparin can be given continuously or as an intermittent bolus with hourly monitoring of activated clotting time. For the occasional case of refractoriness, adequate anticoagulation, switching from bovine to porcine heparin, or vice versa, should be considered. If antithrombin III deficiency is suspected, administration of fresh frozen plasma may be necessary.
Direct Thrombin Inhibitors
Heparin-induced thrombocytopenia is a rare but important adverse event in heparin anticoagulation. Development of heparin-dependent antibodies after initial exposure leads to a prothrombotic syndrome. In high-risk patients, direct thrombin inhibitors can be applied, with the realization that adverse events are inherent to their use, such as anaphylaxis. Direct thrombin inhibitors inhibit free and clot-bound thrombin, and their effect can be monitored by either an activated partial thromboplastin time or activated clotting time. Lepirudin and bivalirudin, a synthetic derivative, have half-lives of 40 to 120 minutes and about 25 minutes, respectively. Because these drugs undergo renal elimination, dose adjustments may be needed in patients with renal dysfunction. Argatroban is an alternative agent that undergoes primarily hepatic metabolism. One report has described bivalirudin as a potential alternative to heparin during INR procedures for intravenous anticoagulation and intra-arterial thrombolysis.
Antiplatelet Agents
Although still controversial in the acute setting, antiplatelet agents (aspirin, the glycoprotein IIb/IIIa receptor antagonists, and the thienopyridine derivatives) are increasingly being used for cerebrovascular disease management and may be of use for acute treatment of thromboembolic complications. Abciximab (ReoPro) has been used to treat thromboembolic complications. Activation of the platelet membrane glycoprotein IIb/IIIa leads to fibrinogen binding and is a final common pathway for platelet aggregation. Abciximab, eptifibatide, and tirofiban are glycoprotein IIb/IIla receptor antagonists. The long duration and potent effect of abciximab also increase the likelihood of major bleeding. The smaller-molecule agents, eptifibatide and tirofiban, are competitive blockers with shorter half-lives of about 2 hours. Thienopyridine derivatives (ticlopidine and clopidogrel) bind to the platelet’s adenosine diphosphate receptor, permanently altering the receptor; therefore, the duration of action is the lifespan of the platelet. Clopidogrel is commonly added to the antiplatelet regimen for procedures that require placement of devices (eg, stents, coiling or stent-assisted coiling) primarily in patients who have not had an acute event, such as those with unruptured aneurysms. Patients who are expected to receive stents, should be pretreated with antiplatelet agents, because of the potential risk of thrombus formation on the stent.
Reversal of Anticoagulation
At the end of the procedure or at occurrence of hemorrhagic complication, heparin anticoagulation may be reversed with protamine. Because there is no specific antidote for the direct thrombin inhibitors or the antiplatelet agents should reversal be indicated, biologic half-life is one of the major considerations in drug choice, and platelet transfusion is a nonspecific therapy. There is no currently available accurate test to measure platelet function in patients taking the newer antiplatelet drugs. Desmopressin (DDAVP) has been reported to shorten the prolonged bleeding time of individuals taking antiplatelet agents, such as aspirin and ticlopidine. There are also increasingly more reports on the use of specific clotting factors, such as recombinant factor VIIa and factor IX complex, to rescue severe life-threatening bleeding, including intracranial hemorrhage uncontrolled by standard transfusion therapy. The safety and efficacy of these coagulation factors remain to be investigated.
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