Cerebral Vasospasm in Critically III Patients with Aneurysmal Subarachnoid Hemorrhage: Does the Evidence Support the Ever-Growing List of Potential Pharmacotherapy Interventions?

Abstract

The occurrence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a significant event resulting in decreased cerebral blood flow and oxygen delivery. Prevention and treatment of cerebral vasospasm is vital to avert neurological damage and reduced functional outcomes. A variety of pharmacotherapy interventions for the prevention and treatment of cerebral vasospasm have been evaluated. Unfortunately, very few large randomized trials exist to date, making it difficult to make clear recommendations regarding the efficacy and safety of most pharmacologic interventions. Considerable debate exists regarding the efficacy and safety of hypervolemia, hemodilution, and hypertension (triple-H therapy), and the implementation of each component varies substantially amongst institutions. There is a new focus on euvolemic-induced hypertension as a potentially preferred mechanism of hemodynamic augmentation. Nimodipine is the one pharmacologic intervention that has demonstrated favorable effects on patient outcomes and should be routinely administered unless contraindications are present. Intravenous nicardipine may offer an alternative to oral nimodipine. The addition of high-dose magnesium or statin therapy has shown promise, but results of ongoing large prospective studies are needed before they can be routinely recommended. Tirilazad and clazosentan offer new pharmacologic mechanisms, but clinical outcome results from prospective randomized studies have largely been unfavorable. Locally administered pharmacotherapy provides a targeted approach to the treatment of cerebral vasospasm. However, the paucity of data makes it challenging to determine the most appropriate therapy and implementation strategy. Further studies are needed for most pharmacologic therapies to determine whether meaningful efficacy exists.

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

“…Intraarterial papaverine causes vasodilatation, likely related to alteration in cAMP. It can result in transient reversal of cerebral hypoperfusion with improvement in blood flow velocities and CBF . There are significant limitations with its use.…”

“…This antioxidant effect is believed to confer a neuroprotective benefit in aSAH. 82,83 A trial that enrolled 1015 patients randomized to receive tirilazad at 6 mg/ kg/day demonstrated significantly reduced overall mortality (P < .01) and improved clinical outcomes at 3 months compared to patients who received placebo (P < .01). 84 The benefits of treatment with tirilazad were predominantly shown in men rather than in women.…”

“…It can result in transient reversal of cerebral hypoperfusion with improvement in blood flow velocities and CBF. 83,157,158 There are significant limitations with its use. It has a short-lived effect, and patients may require multiple treatments.…”

Clinical warning signs of life-threatening hematochezia in neurosurgical patients with long-term bed rest

“…Vasopressors are commonly used to maintain cerebral perfusion during delayed vasospasm in subarachnoid hemorrhage caused by aneurismal rupture, septic shock, and neurogenic shock. [ 10 , 11 ] Because vasopressors centralize the blood volume and increase blood supply to vital organs such as the brain and heart, they cause splanchnic hypoperfusion, which can exacerbate mesenteric ischemia. [ 9 , 12 ] In patients with multiple trauma in neurosurgical ICU, acute kidney injury due to rhabdomyolysis, acute kidney injury due to use of mannitol to control intracranial pressure, refractory metabolic acidosis, and acute kidney injury in septic conditions may occur.…”

Elevated MFG-E8 in CSF in the Early Stage Indicates Rapid Recovery of Mild Aneurysmal SAH Patients

“…Subarachnoid hemorrhage (SAH) is a type of blood oozing from damaged vessels into the subarachnoid space because of different kinds of brain damage. It is a destructive cerebrovascular disease that affects the cerebral blood perfusion state [ 1 ] and contributes to cerebral vasospasm [ 2 ], early brain injury [ 3 ], chronic cerebral ischemia [ 4 ], and various systemic complications [ 5 ]. These injuries often lead to a poor prognosis [ 6 ].…”