Fine tuning of neurointensive care in aneurysmal subarachnoid hemorrhage: From one-size-fits-all towards individualized care

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of acute brain injury with high mortality and burden of neurological sequelae. General management aims at early aneurysm occlusion to prevent re-bleeding, cerebrospinal fluid drainage in case of increased intracranial pressure and/or acute hydrocephalus, and cerebral blood flow augmentation in case of delayed ischemic neurological deficits. In addition, the brain is vulnerable to physiological insults in the acute phase and neurointensive care (NIC) is important to optimize the cerebral physiology to avoid secondary brain injury. NIC has led to significantly better neurological recovery following aSAH, but there is still great room for further improvements. First, current aSAH NIC management protocols are to some extent extrapolated from those in traumatic brain injury, notwithstanding important disease-specific differences. Second, the same NIC management protocols are applied to all aSAH patients, despite great patient heterogeneity. Third, the main variables of interest, intracranial pressure and cerebral perfusion pressure, may be too superficial to fully detect and treat several important pathomechanisms. Fourth, there is a lack of understanding not only regarding physiological, but also cellular and molecular pathomechanisms and there is a need to better monitor and treat these processes. This narrative review aims to discuss current state-of-the-art NIC of aSAH, knowledge gaps in the field, and future directions towards a more individualized care in the future.

Keywords: Aneurysmal subarachnoid hemorrhage; Multimodal monitoring; Neurointensive care; Precision medicine.

Fig. 1

Physiological pathways, pathomechanisms, and management options to optimize cerebral energy metabolism in aSAH. The figure describes the different pathways to ensure cerebral energy metabolism. In the CBF pathway, MAP and ICP determine CPP, which together with the cerebral autoregulation determine CBF. In the oxygenation pathway, pO₂ and HgB determine the CaO₂, which together with CBF constitute the CDO₂. In the nutrient pathway, CaGlc and CaLac are defined as the arterial content of these metabolites, which together with CBF determine CDGlc and CDLac. CDGlc, CDLac, and CDO₂ are necessary for the cerebral production of energy, which takes place in the cytosol and mitochondria of the brain cells. Several pathomechanisms may interfere with each step, which can be addressed to some extent with specifically targeted management strategies, as suggested in the figure. AR = Autoregulation, aSAH = Aneurysmal subarachnoid hemorrhage, CaGlc = Arterial content of glucose, CaLac = Arterial content of lactate, CaO₂ = Arterial content of oxygen, CBF = Cerebral blood flow, CDGlc = Cerebral delivery of glucose, CDLac = Cerebral delivery of lactate, CDO₂ = Cerebral delivery of oxygen, CSD = Cortical spreading depolarization, EP = Epilepsy, FiO₂ = Fraction of inspired oxygen, Hgb = Hemoglobin, HHH = Hemodilution, hypertension, and hypervolemia, ICP = Intracranial pressure, MAP = Mean arterial blood pressure, pO₂ = Partial pressure of oxygen, RBCT = Red blood cell transfusion.

Fig. 2

Illustration of a multimodality monitoring case in an aSAH patient. The figure shows an example of multimodality monitoring in aSAH at our center. This aSAH patients was unconscious, intubated, and mechanically ventilated and had therefore received an EVD (∗) for ICP monitoring and cerebral microdialysis (∗∗) for energy metabolic monitoring. Xe-CT imaging was conducted during NIC to estimate global and focal CBF. In addition, CDO₂ could be calculated based on CBF and the concurrent CaO₂. This type of MMM setup can be used to diagnose the specific cause for imminent cerebral energy metabolic failure, by evaluating concurrent global/focal cerebral ischemia and CDO₂. As illustrated, there is significant regional CBF variation, which limits the global validity of focal monitors such as the microdialysis. aSAH = Aneurysmal subarachnoid hemorrhage, CBF = Cerebral blood flow, CaO₂ = Arterial content of oxygen, CDO₂ = Cerebral delivery of oxygen, EVD = External ventricular drainage, MMM = Multimodality monitoring, NIC = Neurointensive care, Xe-CT = Xenon-enhanced computed tomography.

Fig. 3

CPP in relation to clinical outcome in TBI and SAH. The figure illustrates the combined effect of “insult” duration and intensity on clinical outcome. Red and blue color indicate unfavorable and favorable clinical outcome, respectively, in a subset of TBI (n = 441) and aSAH (n = 449) patients treated at our center. The patients were managed with similar treatment targets (CPP ≥60 mmHg) and the graphs illustrate that aSAH patients may benefit from much higher CPP-targets than TBI patients. aSAH = aneurysmal subarachnoid hemorrhage. CPP = Cerebral perfusion pressure. TBI = Traumatic brain injury.

Fig. 4

A–B. Key concepts in cerebral pressure autoregulation and autoregulatory-oriented therapy. Fig. 4A illustrates four examples of different cerebral pressure autoregulatory status. The blue curve shows the classic “Lassen curve” with a plateau of stable CBF over a broad range of CPPs. Cerebral ischemia occurs at the lower end of autoregulation when the cerebral vessels are already maximally dilated and then become pressure passive below this CPP-value. Similarly, cerebral hyperemia occurs as CPP surpasses the upper end of the autoregulatory plateau, when the capacity for further cerebral vasoconstriction is exceeded, and CBF again follows CPP passively. The yellow curve shows a right-shifted curve with preserved plateau range, which could be the case for patients with pre-ictal chronic arterial hypertension. The green curve illustrates a case with right-shifted and narrowed plateau, which may occur with cerebral vasospasm with increased vasoconstriction and reduced capacity for vasodilation. Hence, both the yellow and green curves illustrate two cases with increased susceptibility for cerebral ischemia despite “normal” CPP. The red curve illustrates a case with totally lost capacity to autoregulate, where CBF completely depends on CPP. Fig. 4B illustrates how the capacity for cerebral pressure autoregulation curve may be continuously monitored with PRx plotted against CPP for the last 4 h, in order to detect CPPopt. CPPopt reflects the plateau phase of CBF, i.e. the nadir of the U-shaped PRx/CPP curve. However, in cases with lost capacity to autoregulate, e.g. with high PRx and without the U-shaped curve, CPPopt cannot be detected. CBF = Cerebral blood flow, CPP = Cerebral perfusion pressure, CPPopt = Optimal CPP, PRx = Pressure reactivity index.