Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

Abstract

Background. During hypertensive therapy for post-subarachnoid hemorrhage (SAH) symptomatic vasospasm, norepinephrine is commonly used to reach target blood pressures. Concerns over aggravation of vasospasm with norepinephrine exist. Objective. To describe norepinephrine temporally related deterioration in neurological examination of two post-SAH patients in vasospasm. Methods. We retrospectively reviewed two charts of patients with delayed cerebral ischemia (DCI) post-SAH who deteriorated with norepinephrine infusions. Results. We identified two patients with DCI post-SAH who deteriorated during hypertensive therapy with norepinephrine. The first, a 43-year-old male presented to hospital with DCI, failed MABP directed therapy with rapid deterioration in exam with high dose norepinephrine and MABP of 140–150 mm Hg. His exam improved on continuous milrinone and discontinuation of norepinephrine. The second, a 39-year-old female who developed DCI on postbleed day 8 responded to milrinone therapy upfront. During further deterioration and after angioplasty, norepinephrine was utilized to drive MABP to 130–140 mm Hg. Progressive deterioration in examination occurred after angioplasty as norepinephrine doses escalated. After discontinuation of norepinephrine and continuation of milrinone, function dramatically returned but not to baseline. Conclusions. The potential exists for worsening of DCI post-SAH with hypertensive therapy directed by norepinephrine. A potential role exists for vasodilation and inotropic directed therapy with milrinone in the setting of DCI post-SAH.

Fluctuations in Moyamoya Vasculopathy Associated with Basedow Disease Depending on Thyroid Hormone Status

“…It is hypothesized that the activation of sympathetic nerves through hyperthyroidism induces vasospasm. Cerebral arteries are innervated by sympathetic nerves containing noradrenaline and 5-hydroxytryptamine, and excess catecholamine levels or sensitivity due to thyrotoxicosis can lead to vasospasm [11]. Moreover, vascular contractile responses to norepinephrine were greater in large vessels than in small ones [12].…”

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage

“…Indeed, several in vitro studies using a rat model reported discrepant findings, which indicated that HIF inhibition per se has been associated with improved blood-brain barrier 34,35 In contrast, the therapeutic efficacy of MIL infusion with and without intravenous sedation in patients following SAH has been established in several clinical settings including SAH. 6,11,14,[29][30][31][32][33] Thus, the timing, severity, and sustainability of HIF-1α upregulation and its downstream transcriptional effects may also be pursued in translational studies using genetically modified mice [36][37][38] to identify more promising preventive or prophylactic interventions against post-SAH DCI.…”

“…In the clinical setting, however, the infusion of catecholamines such as noradrenaline and dobutamine may have limited effects and may aggravate cardiac failure due to massive stress hormone release, so‐called ‘catecholamine surge’ or ‘adrenergic storm’ caused by severe acute brain injury . There are also concerns of cerebral vasoconstriction even with the use of the most reliable vasopressor noradrenaline . The phosphodiesterase‐III inhibitor milrinone (MIL) may be an alternative option when inotropes are required but dobutamine is contraindicated due to tachycardia, left ventricular outflow obstruction or neurogenic cardiomyopathies …”

“…9,10 There are also concerns of cerebral vasoconstriction even with the use of the most reliable vasopressor noradrenaline. 11 The phosphodiesterase-III inhibitor milrinone (MIL) may be an alternative option when inotropes are required but dobutamine is contraindicated due to tachycardia, left ventricular outflow obstruction or neurogenic cardiomyopathies. 1,[12][13][14] We hypothesized that application of MIL to the isoflurane postconditioning strategy may have potential beneficial effects on post-SAH EBI to stabilize the CBF and improve the outcome.…”

The Risk of Milrinone Use in Severe Neurological Insult and Stunned Myocardium

“…One patient's exam improved after starting milrinone and stopping norepinephrine, while the second patient deteriorated clinically in spite of milrinone. Again, hypotension and tachycardia were not mentioned as side effects, and patients did not have preexisting cardiac problems [8].…”