Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model

Abstract

Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty‐nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT‐SNP group) or saline placebo (IT‐saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT‐saline group, the IT‐SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P <0.05) monitored on the cerebral cortex during the 5‐hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude‐integrated electroencephalography. Repeated‐measures analysis of variance revealed significant group–time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post–restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long‐term neurologic outcomes.

Assessment of the Effects of Sodium Nitroprusside Administered Via Intracranial Subdural Catheters on the Cerebral Blood Flow and Lactate Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy in a Pig Cardiac Arrest Model

“…In the previous study, intrathecal drug administration took place 30 minutes post‐ROSC, and cerebral perfusion was quantified by visualizing microcirculation on the cerebral cortex surface and determining the microvascular flow index, number of perfused microvessels, and arteriole diameter. 14 Despite these methodological differences, our cerebral perfusion measurement findings agreed with those of the previous study. Administering SNP into the subarachnoid space led to an immediate increase in CBF (including cortical GM CBF, subcortical WM CBF, and GM+WM CBF) and pial arteriole diameter in the current and previous studies, respectively, and the effects were sustained for a minimum of 2 hours.…”

“…The SNP dose in the present study was identical to that in a previous study. 14 All other investigators were blinded to group assignment. A 20‐gauge catheter was then inserted through each burr hole into the subarachnoid space for intrathecal drug administration.…”

“…The sample size for this study was calculated based on the microvascular flow index data (mean±SD, 2.79±0.26) of a previous study, 14 where the microvascular flow index values were 2.61±0.27 and 2.96±0.08 in the saline and SNP groups, respectively, and the intragroup variance was 0.04. We calculated that 6 animals would be needed per group to reach a power of 80% at α=0.05 and thus included 8 animals per group to minimize the impact of possible data loss.…”

“…It bypasses systemic circulation and facilitates ready access of a high concentration of vasodilator drugs to the spastic vessels on the surface of the brain, thus resulting in enhanced therapeutic efficacy and a reduction in adverse effects associated with systemic administration, such as arterial hypotension. In a previous study using a porcine cardiac arrest model, 14 sodium nitroprusside (SNP) introduced into the subarachnoid space through intracranial subdural catheters during the early post‐ROSC period effectively improved the pial microcirculation and cerebral cortex tissue oxygenation. This intervention alleviated post‐ROSC cerebral cortical hypoperfusion and decreased the duration of exposure to cortical tissue hypoxia.…”

“…Conversely, intravenous administration of SNP led to profound hypotension and failed to improve pial microcirculation and tissue oxygenation. 14 However, the efficacy of this SNP treatment for improving deep‐brain CBF was undetermined, because the cerebral perfusion measurements were limited to the surface of the cerebral cortex. To determine the potential applicability of the abovementioned treatment for postischemic cerebral hypoperfusion, the impact of the SNP treatment on the deeper cerebral structures as well as the pathophysiologic significance of postischemic cerebral hypoperfusion need to be investigated.…”