Intraarterial Nimodipine Versus Induced Hypertension for Delayed Cerebral Ischemia: A Modified Treatment Protocol

Abstract

Background: Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking. We investigated the effects of a classical (iHTN+IAN) and modified (IAN only ) treatment protocol for refractory DCI in an observational study. Methods: Rescue treatment for DCI was initiated with iHTN (target >180 mm Hg systolic) and escalated to IAN in refractory cases. Until July 2018, both iHTN and IAN were offered in cases refractory to iHTN alone. After protocol modification, iHTN target was preemptively lowered to >120 mm Hg when IAN was initiated (IAN only ). Primary outcome was noradrenaline demand. Secondary outcomes included noradrenaline-associated complications, brain tissue oxygenation, DCI-related infarction and favorable 6-month outcome (Glasgow Outcome Scale 4–5). Results: N=29 and n=20 patients were treated according to the classical and modified protocol, respectively. Protocol modification resulted in a significant reduction of noradrenaline demand (iHTN+IAN 0.70±0.54 µg/kg per minute and IAN only 0.26±0.20 µg/kg per minute, P <0.0001) and minor complications (15.0% versus 48.3%, unadjusted odds ratio, 0.19 [95% CI, 0.05–0.79]; P <0.05) with comparable rates of major complications (20.0% versus 20.7%, odds ratio, 0.96 [0.23–3.95]; P =0.95). Incidence of DCI-related infarction (45.0% versus 41.1%, odds ratio, 1.16 [0.37–3.66]; P =0.80) and favorable clinical outcome (55.6% versus 40.0%, odds ratio, 1.88 [0.55–6.39]; P =0.32) were similar. Brain tissue oxygenation was significantly higher with IANonly (26.6±12.8, 39.6±15.4 mm Hg; P <0.01). Conclusions: Assuming the potential of iHTN to be exhausted in case of refractory hypoperfusion, additional IAN may serve as a last-resort measure to bridge hypoperfusion in the DCI phase. With close monitoring, preemptive lowering of pressure target after induction of IAN may be a safe alternative to alleviate total noradrenaline load and potentially reduce complication rate.

Optimal Cerebral Perfusion Pressure and Brain Tissue Oxygen in Aneurysmal Subarachnoid Hemorrhage

“…30,31 In contrast, in a setting with induced hypertension and vasodilation together, we found that a higher pressure target (>180 mmHg systolic) corresponded to even lower PbtO 2 values than a lower pressure target (>120 mmHg systolic). 32 As a future prospect, analyzing the relationship of deltaCPP and PbtO 2 during phases with induced hypertension may delineate an upper limit of autoregulation, and give insight into the oxygen-plus that can or cannot be expected by hypertensive treatment.…”

Nimodipine vs. Milrinone – Equal or Complementary Use? A Retrospective Analysis

“…Secondary systemic distribution of the vasodilator often increases the vasopressor demand to counteract this effect peripherally ( 16 ). Weiss et al ( 17 ) investigated the potential of induced hypertension vs. continuous intra-arterial nimodipine infusion as a rescue treatment for DCI. In the latest guidelines, induced hypertension is the recommended primary rescue therapy and intra-arterial spasmolysis is an adjunct with the weaker recommendation.…”

Treating Delayed Cerebral Ischemia: Should We Focus on Blood Pressure or Vasodilatation?

“…Weiss et al, 18 describe that although IAN was locally administered, it often resulted in hypotension, relative to the standard of care goal of systolic blood pressure >180 mm Hg, or absolute hypotension, related to the systemic vasodilatory effects of nimodipine. The reduced blood pressure, compared with the threshold set, required a high dose of vasoactive drips (mainly norepinephrine).…”

“…In the current issue of Stroke , Weiss et al 18 published a retrospective analysis of a pre/post change in their usual care protocol. In the original clinical protocol, all patients with clinical DCI or high-risk patients (for examples those with perfusion deficit on CT-perfusion, or a significant reduction in partial pressure of brain tissue oxygen—P ti O 2 ) were treated with induced hypertension.…”

“…16 A combined approached was previously described in which the microcatheter is left in one or more of the cerebral arteries, while vasodilators such as nimodipine, are infused intraarterially in a continuous fashion for multiple days. 15,17 In the current issue of Stroke, Weiss et al 18 published a retrospective analysis of a pre/post change in their usual care protocol. In the original clinical protocol, all patients with clinical DCI or high-risk patients (for examples those with perfusion deficit on CT-perfusion, or a significant reduction in partial pressure of brain tissue oxygen-P ti O 2 ) were treated with induced hypertension.…”