Current advances in neurocritical care

Abstract

This review summarizes the current research advances and guideline updates in neurocritical care. For the therapy of ischemic stroke, the extended treatment time window for thrombectomy and the emergence of novel thrombolytic agents and strategies have brought greater hope for patient recovery. Minimally invasive hematoma evacuation and goal-directed bundled management have shown clinical benefits in treating cerebral hemorrhage. In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), early lumbar drainage can reduce the risk of infarction. Decompressive craniectomy for severe traumatic brain injury has also obtained high-quality evidence support. However, multimodal brain monitoring strategies for patients with traumatic brain injury need further optimization. For patients with cardiac arrest, extracorporeal cardiopulmonary resuscitation can reduce in-hospital mortality and improve long-term neurological prognosis. For neurocritical care patients, abundant high-quality studies have emerged in areas including multimodal neuromonitoring, hemodynamic management, airway management and respiratory therapy, and antiepileptic treatment. In 2023, the guidelines for aSAH have been updated for the first time in the past decade, aiming to provide evidence-based practice recommendations for clinical care. Chinese expert consensuses have also been formulated to guide analgesia and sedation for neurocritical care patients and developed a set of medical quality indicators on neurocritical care, which will enhance standardization and homogenization improvement in neurocritical care quality.

Introduction

Neurocritical care patients are those suffering from primary or secondary neurological diseases, with existing or potential organ dysfunction, requiring intensive medical monitoring and treatment. The key diseases include intracerebral hemorrhage (ICH), ischemic stroke, traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and cardiac arrest (CA). Endovascular therapy (EVT) and thrombolytic therapy for ischemic stroke have long been the research hotspots. In the past 2 years, trials extending the treatment time window for thrombectomy and the emergence of new thrombolytic drugs and regimens have brought more hope to patients. For ICH, minimally invasive hematoma evacuation and bundled goal-directed therapies incorporating blood pressure lowering, glycemic control, fever management, and reversal of anticoagulation have shown surprising clinical benefits. For severe TBI (sTBI), decompressive craniectomy remains a research focus. Additionally, high-quality studies have emerged in acute critical care areas such as multimodal neuromonitoring, airway and respiratory management, and antiepileptic management. Several major neurocritical care guidelines and consensus statements were released, with the American Heart Association (AHA)/American Stroke Association (ASA), Neurocritical Care Society (NCS), and the Neurocritical Care Expert Committee of the Chinese Medical Association Neurosurgery Society independently publishing updated aneurysmal subarachnoid hemorrhage (aSAH) guidelines or consensus statements. The National Center for Healthcare Quality Management in Neurological Diseases also updated the “Chinese Expert Consensus on Sedation and Analgesia for Neurocritical Care Patients.” This article reviews the research hotspots and important guideline updates in the neurocritical care field.

Update in Diagnosis and Treatment of Neurocritical Diseases

Update in ischemic stroke

Stroke is one of the leading causes of disability and death, with acute ischemic stroke (AIS) comprising approximately 80% of all stroke cases. The crucial aspect of treating AIS is to reopen the blocked vessel timely to salvage the ischemic hemidiaphragm. Intravenous thrombolysis has been established as an effective early revascularization treatment.^[1,2] Subsequent EVT studies have consistently shown that mechanical thrombectomy offers significant benefits for patients with AIS caused by large vessel occlusion in the anterior circulation. In recent years, numerous high-quality research findings in EVT and intravenous thrombolysis have emerged, providing substantial evidence for the precise diagnosis and treatment of ischemic stroke.^[[3], [4], [5], [6]^] This discussion focuses on the latest research advancements in the field of ischemic stroke.

EVT for ischemic stroke

The ANGEL-ASPECT^[7] and SELECT2^[8] trials expanded the application of EVT to patients with large infarct cores and extended the treatment time window. The ANGEL-ASPECT involved patients with anterior circulation acute large-vessel occlusion within 24 h and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3–5 or an infarct-core volume of 70–100 mL. At 90 days, the efficacy of EVT was observed to be superior to that of drug therapy alone in terms of the modified Rankin Scale (mRS) distribution.

The SELECT2 trial design included the patients with a large infarct core volume, with a definition of ASPECTS value of 3–5 or an infarct core volume of at least 50 mL on diffusion-weighted magnetic resonance imaging or computed tomography perfusion. The generalized odds ratio for a shift in the distribution of mRS scores toward better outcomes in favor of thrombectomy was 1.51. In the thrombectomy and medical care groups, 20% and 7% of patients achieved functional independence, respectively. The two groups present a similar mortality. The results showed that the functional efficacy of EVT was superior to medical care, except for the vascular complications.

MR CLEAN-LATE study by Olthuis et al.^[9] was designed to assess the efficiancy and safety of EVT in patients selected for treatment during a later window (6–24 h from symptom onset or last seen well) based on computed tomography angiography demonstrating collateral flow. This study confirmed that EVT is effective and safe for patients in 6–24 h from onset.

The TENSION study by Bendszus et al.^[10] provided robust evidence for EVT in patients with acute anterior circulation large ischemic stroke. This study showed that EVT was associated with improved functional outcomes and reduced mortality in patients with AIS due to occlusion of large vessels that have developed large infarcts when non-contrast computed tomography is used as the primary imaging modality of choice for patients. The IRIS study by Majoie et al.^[11] is a systematic review and meta-analysis of individual participant data, and it was used to determine the non-inferiority of EVT alone vs. intravenous thrombolysis plus EVT. The findings revealed that at 90 days, the median mRS was 3 and 2 in participants who received EVT alone and intravenous thrombolysis plus EVT, respectively (adjusted common odds ratio=0.89, 95% CI: 0.76 to 1.04). The occurrence of ICH was notably lower in the EVT alone group than in the intravenous thrombolysis plus EVT group. No statistically significant variances were found in symptomatic ICH or mortality rates between the two treatment approaches.

These studies provided stronger evidence from evidence-based medicine to support expanding the indications for EVT treatment of ischemic stroke, to guide the selection of treatment regimens, and to enable more individualized treatment approaches.

Thrombolytic therapy for ischemic stroke

The international multicenter CERTAIN study by Warach et al.^[12] compared the incidence of symptomatic ICH caused by 0.25 mg/kg of tenecteplase and alteplase. The group administered with tenecteplase was characterized by older age (P <0.001), a higher proportion of males (P <0.01), elevated National Institutes of Health Stroke Scale scores (P <0.001), and a greater likelihood of undergoing endovascular thrombectomy (P <0.001). The proportion of patients with symptomatic ICH was 1.8% and 3.6% in the tenecteplase and alteplase, respectively (P <0.001). The result shows that tenecteplase may be superior to alteplase in controlling the risk of symptomatic ICH.

Chen et al.^[13] conducted a multicenter randomized controlled trial (RCT) to assess the efficiency and safety of argatroban plus alteplase in the treatment of AIS. At 90 days, 63.8% of participants in the combined treatment group and 64.9% in the alteplase alone group had good functional outcomes (risk difference=−1.0%, 95% CI: −8.1% to 6.1%; risk ratio=0.98, 95% CI: 0.88 to 1.10; P=0.78). The results demonstrated that treatment with intravenous administration of argatroban plus alteplase did not significantly increase the likelihood of achieving a good functional outcome at 90 days compared to using alteplase alone.

These comparisons provided direct evidence for the selection of different thrombolytic regimens, indicating the feasibility of using combined antithrombotic thrombolytic therapy.

Update in ICH

ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma. It is associated with high mortality, with rates reaching up to 50% within 30 days.^[14] Recent advances in the treatment of ICH emphasize the importance of controlling severe hypertension in the acute phase, swiftly reversing anticoagulation, and employing minimally invasive techniques for hematoma removal. Although spontaneous ICH (sICH) comprises <20% of all stroke cases, it remains the deadliest form of stroke and is linked to significant morbidity.^[15] The etiology of ICH is evolving, largely due to the increased use of antiplatelet or anticoagulant medications, which is also a crucial factor in managing sICH in patients undergoing these therapies. This discussion will explore the latest developments in ICH management, focusing on minimally invasive hematoma evacuation, comprehensive management bundle, and treatment of sICH in patients on antiplatelet or anticoagulant therapy.

The ENRICH study by Pradilla et al.^[16] was a multicenter, adaptive RCT aimed at comparing the efficacy and safety of early (within 24 h) minimally invasive parafascicular surgery (MIPS) in improving outcomes for patients with ICH. The results showed that the MIPS group had significantly lower mRS compared to the control group. Meanwhile, minimally invasive surgery did not increase hematoma volume or 30-day post-operative mortality rates. Minimally invasive surgery can safely and efficiently improve neurological function in patients with ICH. It provided evidence supporting the further promotion of MIPS treatment, but further analysis is needed to determine whether it suits different bleeding locations.

The INTERACT-3 study by Ma et al.^[17] was an international multicenter RCT aimed at evaluating the efficacy of a goal-directed bundle in improving outcomes for patients with ICH. The results showed that the incidence of neurological dysfunction was lower in the care bundle group significantly, but overall mortality and disability rates remained high. The study confirmed that a goal-directed bundle can improve neurological function in patients with ICH.

The DASH study by Desborough et al.^[18] was a phase 2, randomized, placebo-controlled, multicenter feasibility trial. This study aimed to assess the feasibility of randomizing participants with sICH treated with antiplatelet drugs to receive desmopressin or placebo, respectively, to reduce the effect of antiplatelet drugs. The results showed that 22% of patients in the desmopressin group and 37% of patients in the placebo group died or were dependent on others for daily activities on day 90 (mRS >4). The rates of serious adverse events were 44% and 48% in the desmopressin and placebo groups, respectively. Thus, the findings support the conduct of a well-defined trial to determine whether desmopressin can improve prognosis in patients with ICH treated with antiplatelet drugs.

The COCROACH study by Al-Shahi Salman et al.^[19] was a prospective meta-analysis. The safety and efficiency of oral anticoagulation for the main adverse cardiovascular incident in patients with atrial fibrillation (AF) and sICH are uncertain. So, this study aims to evaluate the effects of initiating vs. avoiding oral anticoagulation in patients with sICH and AF. The results suggest that in patients with AF and sICH, the effect of oral anticoagulation on the risk of stroke or cardiovascular death (overall and in subgroups), hemorrhagic major adverse cardiovascular events, and functional outcomes is uncertain. Oral anticoagulation reduces the incidence of the main adverse cardiovascular incidents, which can help to guide clinical practice in treating and preventing such incidents.

Update in aSAH

aSAH is associated with high rates of mortality and disability. The primary complications following aSAH are rebleeding and delayed cerebral ischemia (DCI), making it crucial to prevent rebleeding, cerebral vasospasm, and DCI. Cerebral vasospasm, caused by an excessive volume of blood in the basal cisterns, is believed to be a leading cause of DCI. However, the effectiveness of ventricular or lumbar drainage in improving patient outcomes remains controversial. In 2023, the Earlydrain study provided new evidence in this field.

The EARLYDRAIN study by Wolf et al.^[20] was a multicenter RCT to evaluate the long-term impact of early lumbar drainage on patients with aSAH. The results showed that early lumbar drainage significantly reduced the risk of poor prognosis (mRS 4–6) and the occurrence of DCI when compared to standard care. The study also monitored drainage-related complications, and only in one patient did the gradient of intracranial pressure (ICP) readings increase by >5 mmHg between the external ventricular drain and the lumbar drain, making it impossible to continue the lumbar drainage. These results underscore the importance of prophylactic lumbar drainage in aSAH patients to mitigate infarction burdens upon discharge and improve outcomes at the 6 months. The study advocates for incorporating lumbar drainage alongside standard care protocols.

Update in sTBI

sTBI, defined as Glasgow Coma Scale (GCS) ≤8, is associated with high mortality and poor functioning. Apart from treatment bundles based on ICP monitoring, brain tissue oxygen pressure (PbtO₂) can provide valuable information for clinicians.^[21] At the 2019 Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC), experts proposed to simultaneously monitor PbtO₂ and ICP in patients with sTBI.^[22] Moreover, it is important to explore whether combining PbtO₂ monitoring with ICP monitoring improves patient outcomes. Decompressive craniectomy is considered a last-resort and effective treatment for sTBI patients with refractory intracranial hypertension (RIH) when dehydration and diuresis fail to reduce ICP. However, its association with improved outcomes remains unclear. New advancements in the practice of decompressive craniectomy were listed as follows.

The OXY-TC study by Payen et al.^[23] was an RCT aimed at evaluating the role of PbtO₂ monitoring in improving neurological outcomes for TBI patients. The results showed that combined ICP and PbtO₂ monitoring did not improve neurological function scores and increased the incidence of probe-related complications. The results indicated that compared to ICP monitoring alone, combined PbtO₂ monitoring did not reduce the incidence of sequelae or improve prognosis in TBI patients, which may be related to the effects of comprehensive management measures. This suggests that multimodal brain monitoring strategies need further optimization to clarify which patient subgroups are more suitable for multimodal monitoring.

The RESCUE-ASDH study by Hutchinson et al.^[24] was an international multicenter RCT aimed at comparing the treatment effects of decompressive craniectomy (bone flap not replaced) and craniotomy (bone flap replaced) in acute subdural hematoma (aSDH) surgery. The results showed no statistically significant difference in the extended Glasgow Outcome Scale (GOSE) scores between the two groups, but the decompressive craniectomy group had lower rates of secondary surgery and infection than the craniotomy group, suggesting that decompressive craniectomy may have a safety advantage but did not improve long-term neurological function. The study indicated that for aSDH patients with a bone flap >11 cm, there was no difference in the therapeutic effect between decompressive craniectomy and craniotomy, but the former may be safer.

In terms of drug therapy for sTBI patients, a study by PATCH-Trauma Investigators and the ANZICS Clinical Trials Group et al.^[25] found that prehospital intravenous tranexamic acid after trauma could reduce the 28-day mortality rate among patients with major trauma and suspected trauma-induced coagulopathy, but had no significant improvement in neurological function recovery at 6 months, suggesting the need to optimize the use strategy of this drug further.

Update in post-CA

CA has remained a serious public health issue for decades. The primary factor influencing outcomes after CA is hypoxic-ischemic brain damage (HIBI),^[26] and temperature control plays a key component after CA. Investigating the role of targeted temperature management (TTM) in the recovery of brain function is essential for improving the prognosis of patients.

Life support and brain protection for post-CA patients have also been a sustained hotspot. Low et al.^[27] published a systematic review and meta-analysis on the benefits of using extracorporeal cardiopulmonary resuscitation (ECPR) compared to conventional cardiopulmonary resuscitation (CCPR) in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) cases. The results showed that ECPR was associated with a significantly reduced in-hospital mortality rate. When considering only IHCA, patients receiving ECPR had lower in-hospital mortality rates than those receiving CCPR, whereas when considering OHCA only, the difference was not statistically significant. ECPR correlated with improved short-term and long-term survival rates coupled with favorable neurological outcomes. Additionally, the survival rates at 30 days, 3 months, 6 months, and 1 year of follow-up were increased in patients receiving ECPR. These results emphasize that ECPR, in contrast to CCPR, lowers in-hospital mortality rates and enhances long-term neurological outcomes and survival rates following CA, especially for IHCA patients. Therefore, eligible patients with IHCA may be considered for ECPR.

The TTM2 study by Lilja et al.^[28] aimed to evaluate the impact of targeted hypothermia management vs. targeted normothermia management on functional outcomes, emphasizing social participation and cognitive function in survivors 6 months after OHCA. A total of 836 survivors participated in the follow-up. The results demonstrated no significant differences in functional outcomes focusing on social participation (GOSE score, Montreal Cognitive Assessment [MoCA], and Symbol Digit Modalities Test [SDMT]) between groups. Limitations in social participation (GOSE score <7) were prevalent regardless of the intervention. Of the 599 participants who underwent both MoCA and SDMT, 353 (59%) had cognitive impairment. This study focusing on social participation and cognitive function as outcome measures in comatose patients after OHCA targeted hypothermia treatment did not result in better functional outcomes compared to normothermia treatment. Many survivors failed to resume their pre-arrest behaviors and characters, and mild cognitive impairment was common.

Advances in Critical Care Management of Neurocritical Care Patients

Monitoring of neurocritical care patients

Recently, bedside multimodal neuromonitoring technology has garnered significant attention because of its role in assessing fluctuations in intracranial conditions and tracking treatment responses. This technology holds promise in detecting neurological deterioration in patients with neurocritical illnesses before clinical symptoms manifest. Exploring the potential of multimodal neuromonitoring to enhance patient outcomes and functional recovery is crucial. A notable advancement revealed the relationship between the Neurological Pupil index (NPi) and the prognosis of patients with severe non-hypoxic acute brain injury (ABI).

The ORANGE study by Oddo et al.^[29] was an international, multicenter, prospective, observational cohort study designed to investigate the relationship between the NPi and the outcomes in participants with ABI. A total of 514 patients from 18 countries were included, with 40,071 NPi measurements. Among them, 47% (n=241) had at least one documented NPi abnormality, which was linked to adverse neurologic outcomes and in-hospital mortality. The study indicated that NPi has statistical significance for neurological prognosis and mortality in ABI patients. Pupillometry assessment, as a non-invasive, dynamic monitoring indicator, can help in the clinical evaluation of disease progression trends and improve treatment efficacy.

Hemodynamic management in neurocritical care patients

Despite the effectiveness of EVT in AIS due to large vessel occlusion, there are still opportunities to further optimize clinical outcomes. Concerns regarding hemorrhagic transformation due to elevated cerebral perfusion pressure have led to the hypothesis that reducing blood pressure after successful reperfusion could mitigate cerebral hemorrhagic complications. Both low- and high-baseline systolic blood pressure (SBP) have been linked to poor function outcomes at 3 months.^[30] The current clinical guidelines from the AHA/ASA^[31] and the European Stroke Organisation^[30] recommend maintaining blood pressure <185/105 mmHg as well as avoiding drops in SBP <130 mmHg. In this context, two randomized clinical trials present findings on intensive blood pressure control strategies after successful EVT.

The OPTIMAL-BP study by Nam et al.^[32] showed that compared to conventional blood pressure management targets (140–180 mmHg), patients who underwent “intensive” blood pressure management (target <140 mmHg) within 24 h after surgery had a lower proportion of functional independence at 3 months than the conventional management group, but no significant differences in the incidence of sICH and stroke-related mortality between the two groups.

On the other hand, the BEST-II study by Mistry et al.^[33] compared three different SBP management targets (<140 mmHg, <160 mmHg, and <180 mmHg), and the results present that the <140 mmHg group had the smallest infarct volume, but no significant differences in functional prognosis among the three groups. This study suggested that while there is currently no evidence that lower blood pressure targets are harmful, the likelihood of benefit is also low. The OPTIMAL-BP study indicated that excessive blood pressure lowering may be unfavorable, but the BEST-II study cannot completely rule out the potential benefits of blood pressure lowering. Future high-quality clinical studies are needed to investigate the optimal range for blood pressure management further.

Airway management and respiratory therapy in neurocritical care patients

Airway management constitutes a critical aspect of basic treatment for all critically ill patients, as improper handling can directly jeopardize patient lives. Neurocritical care patients, in particular, face an increased risk of airway-related complications due to various factors such as central respiratory dysfunction, swallowing impairment, airway obstruction, and respiratory insufficiency. The timing of weaning and extubation in neurocritical care patients remains a subject of debate. However, a recently updated series of studies offers valuable insights that can assist neurocritical care unit (NCU) physicians in determining the appropriate timing for weaning and extubation in such patients.

Freund et al.^[34] conducted a multicenter RCT exploring the impact of withholding tracheal intubation vs. routine practice of tracheal intubation on clinical outcomes in comatose patients with acute poisoning. The results found that the group where tracheal intubation was withheld experienced better outcomes concerning in-hospital mortality, intensive care unit (ICU) stay, and overall hospital stay compared to the control group. These results suggest that in comatose patients suspected of acute poisoning, adopting a conservative approach of withholding intubation may confer clinical benefits. The optimal strategy of weaning and extubation in sTBI patients still needs more evidence. Rabinstein et al.^[35] systematically evaluated the current literature and proposed recommendations for screening criteria and procedures for weaning and extubation. First, the stability of the neurological system should be confirmed, followed by an evaluation of whether the patient meets weaning readiness criteria. After successful weaning, the patient should be further evaluated to determine if they meet the extubation criteria. The extubation can be considered if hemodynamic stability is achieved and perfusion is maintained during spontaneous breathing. Before weaning, and even before extubation attempts, alertness is not mandatory, but higher levels of alertness increase the likelihood of extubation success. Additionally, airway protection should be evaluated, and laryngeal edema should be prevented. The more severe the impairment responsiveness degree is, the more careful evaluation is needed regarding the amount of oral secretions (especially tracheobronchial secretions) and the preservation of gag and cough reflexes.

Taran et al.^[36] also conducted a systematic review on extubation issues in neurocritical care patients, including 21 studies with 3274 ABI patients. The findings indicated that the incidence of extubation failure in ABI patients was approximately 25%. Patients who experienced extubation failure exhibited prolonged stay in the ICU and faced elevated mortality. Factors such as advanced age and prolonged mechanical ventilation duration were linked to a heightened risk of extubation failure. Conversely, a reduced risk was associated with the presence of coughing and intact swallowing reflexes on the day of extubation. Other prognostic factors associated with extubation failure included gender, rapid shallow breathing index, arterial oxygen partial pressure (PaO₂)/fraction of inspired oxygen (FiO₂), GCS score on the day of extubation, and GCS-Motor score <5 on the day of extubation. Cough and swallowing were protective factors as well as higher maximal inspiratory pressure and maximal expiratory pressure. Additionally, one-quarter of selected studies found that excessive secretions were the primary reason for reintubation in >50% of patients with extubation failure.

Xu et al.^[37] conducted a prospective, observational study that consecutively enrolled neurocritical care patients with mechanical ventilation for 1 year. They established the STAGE score, a predictive model for extubation outcomes composed of GCS-Motor and airway-protecting functions (swallowing, tongue protrusion, spontaneous cough, and suctioning cough), with a score range of 0–12. The area under the receiver operating characteristics curve for predicting extubation success was 0.72. When patients scored ≥9, the likelihood of successful extubation was extremely high, and immediate extubation was recommended. This scoring system can assist clinicians in making appropriate extubation decisions and reduce adverse outcomes associated with extubation failure and delayed extubation.

Antiepileptic treatment in neurocritical care patients

An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult.^[38] In cerebrovascular disease, the prevalence ranges from 1.3% for ischemic stroke^[39] to 4% for intracerebral or SAH.^[40] Acute symptomatic seizures may indicate an increased risk of subsequent unprovoked seizures.^[41] The SeLECT model included five variables, on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). SeLECT 2.0 refinement of any acute symptomatic seizure into short acute symptomatic seizure and acute symptomatic status epilepticus on the basis of SeLECT. Therefore, the SeLECT 2.0 prognostic model compared the risk of poststroke mortality and epilepsy between different types of acute symptomatic seizures. At the same time, the antiepileptic treatment of neurocritical care patients, especially prophylactic antiepileptic treatment, remains controversial. This prognostic model provides a basis for the use of antiepileptic drugs. Sinka et al.^[41] performed a cohort study examining the association between acute symptomatic seizures following ischemic stroke and patient prognosis. The results showed that stroke patients experiencing status epilepticus had increased mortality and a higher likelihood of developing epilepsy compared to those with short seizures or no seizures. The study also updated the prognostic prediction model SeLECT 2.0, offering insights into the epilepsy risk among high-risk stroke patients. This model can guide decisions regarding the continuation of anti-seizure medication treatment and the frequency of follow-up.

Updates in Guideline and Consensus

Update of aSAH guidelines

After 11 years, the AHA/ASA has updated the “Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage.” ^[42] The 2023 guidelines focus on the comprehensive management of aSAH, including natural history and outcomes, clinical manifestations and diagnosis, systems of care, prevention of rebleeding, surgical and endovascular treatment options for ruptured cerebral aneurysms, and management of medical complications. Meanwhile, the “Guidelines for Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage” updated by the NCS in the same year^[43] focuses on the management of patients with aSAH within NCU. Regarding blood pressure management, the NCS guidelines no longer recommend specific blood pressure targets before aneurysm treatment, and the AHA/ASA guidelines also do not recommend target values before aneurysm treatment. Both the AHA/ASA and NCS guidelines recommend close monitoring of volume status and maintaining euvolemia, avoiding large-volume fluid administration. Neither the AHA/ASA nor NCS guidelines recommend using statins, magnesium, or anti-fibrinolytic agents to improve prognosis. The AHA/ASA guidelines newly recommend the use of multimodal monitoring modalities, such as continuous electroencephalogram (cEEG) monitoring, invasive monitoring of brain tissue oxygenation, lactate/pyruvate ratio, and glutamate, for high-grade patients with aSAH. The AHA/ASA guidelines suggest that in patients with symptomatic vasospasm, it may be reasonable to elevate SBP values to reduce the progression and severity of DCI. However, the NCS guidelines do not recommend or against increasing blood pressure and cardiac output to prevent and treat DCI. Both the AHA/ASA and NCS guidelines recommend early use of nimodipine, which helps to prevent DCI and improve functional outcomes. The AHA/ASA guidelines indicate that prophylactic use of phenytoin is not only ineffective in reducing the incidence but is also associated with higher disability and mortality rates. Anti-seizure medications for >7 days were ineffective in reducing the risk of future SAH-associated seizures in patients who had already experienced seizures and who had no prior history of epilepsy. Beyond treatment, the AHA/ASA guidelines strongly emphasize healthcare system accessibility and patient availability, highlighting the importance of neurocritical care bundled monitoring models, adequate and qualified professional nursing staff, and interdisciplinary collaboration, all of which are closely related to patient outcomes. At the same time, functional assessment and exercise guidance should be strengthened for post-operative recovery patients with aSAH, and high-risk factors for recurrent aSAH should be evaluated, with enhanced follow-up.

Update of Chinese expert consensus on sedation and analgesia for neurocritical care patients

In 2023, the National Center for Healthcare Quality Management in Neurological Diseases released an updated version of the Chinese expert consensus on sedation and analgesia for neurocritical care patients (2023),^[44] which was based on the first consensus published in 2013. The new consensus has been updated in five domains such as the goal of analgesia and sedation for neurocritical care patients, monitoring during analgesic and sedative therapy, analgesic and sedative medications selection, and the application in RIH and TTM. The 2023 consensus clarifies the neuroprotective effects of analgesic and sedative therapy for neurocritical care patients, including controlling ICP, maintaining cerebral perfusion, inhibiting the sympathetic nervous system, controlling seizures, and preventing/reducing secondary brain injury. However, for patients with intracranial hypertension (IH) and hemodynamic instability or at a stage where the diagnosis is still unclear, analgesic and sedative therapy may exacerbate or mask the condition. In such cases, the treatment strategy for IH should weigh the pros and cons and adopt a stratified comprehensive management approach. Regarding the choice of sedation depth, the principle should be to prioritize pain relief and pursue light sedation. The choice of sedation depth needs to be weighed based on the patient's condition and dynamic assessment. In situations such as the use of neuromuscular blocking agents, status epilepticus, patient-ventilator dyssynchrony, strict immobilization, and strong suspicion of IH or unstable organ function, NCU patients should consider adopting a deep sedation strategy. Regarding whether NCU patients should undergo a neurological wake-up test (NWT), the 2023 consensus indicates that it is warranted to consider NWT for NCU patients to evaluate neurological function, but the timing of NWT should be balanced against risks and benefits. NWT should be avoided when patients are in severe conditions such as obvious hyperthermia, status epilepticus, and/or receiving barbiturate treatment, or with solid suspicion of IH. The 2023 consensus also details the selection of analgesic and sedative medications for NCU patients, introducing the characteristics, main advantages and disadvantages, and precautions for different populations of commonly used drugs. The consensus states that analgesic and sedative therapy should be continued during RIH and TTM in neurocritical care patients, but more evidence needs to be accumulated. Attention should be paid to adverse drug reactions, and due to pharmacokinetic changes, short-acting drugs may be more suitable.

Quality control indicators of neurocritical care in China

As a cross-discipline at the junction of Neurological Sciences and Critical Care Medicine, it faces challenges such as uneven resource distribution, diverse practitioner backgrounds, and significant disparities in treatment concepts and diagnostic and treatment levels nationwide. Given the current situation, the Neurocritical Care Working Group of the National Center for Healthcare Quality Management in Neurological Disease in China organized specialists in the field of neurocritical care to develop the “Quality Control Indicators in Neurocritical Care” adopting the Modified Delphi Method. The indicator collection is made up of 23 indicators, divided into process indicators, readmission indicators, and key disease indicators (Figure 1). The set of medical quality control indicators for neurocritical care constructed in this study will serve as the first reference monitoring system for quality improvement in neurocritical care. Continuous monitoring of the system will allow longitudinal and cross-sectional comparisons. Cross-sectional comparison can find differences between different regions and hospitals, while longitudinal comparison can track changes in the same indicators over time. According to the previous investigation results of this indicator set in China, some indicators showed great progress such as rate of consciousness assessment, venous thromboembolism (VTE) evaluation, and sedation and pain assessment. Nevertheless, some indicators, such as the rate of delirium assessment, still need improvement.^[45] Continuous monitoring and targeted training programs based on this indicator set will enhance standardization and homogenization improvement in neurocritical care quality.

Figure 1.

Quality control indicators of neurocritical care in China.

*The outcome indicators can be objectively captured through the HQMS.

CAUTI: Catheter-associated urinary tract infections; CRBSI: Catheter-related bloodstream infection; DAMA: Discharge rate against medical advice; EEG: Electroencephalogram; GCS: Glasgow Coma Scale; HQMS: Hospital quality monitoring system; ICP: Intracranial pressure; NCU: Neurocritical care unit; SAT: Spontaneous awakening trial; SBT: Spontaneous breathing trial; TCD: Transcranial Doppler; VAP: Ventilator-associated pneumonia; VTE: Venous thromboembolism.

Outlook for the neurocritical care

The field of neurocritical care witnessed several high-quality studies and the release of several important guideline updates, though some unresolved issues remain. For ischemic stroke, EVT, thrombolytic therapy, and optimal blood pressure targets at different stages will continue to be research hotspots going forward. For hemorrhagic stroke, minimally invasive surgery has shown promise in improving outcomes for patients with ICH, but further analysis is needed to determine its suitability across different bleeding locations. Goal-directed care bundled incorporating protocols have also shown significant improvement in neurological function, and standardized, bundled management of neurocritical care patients is a topic worth exploring further. For aSAH patients, early lumbar drainage has been shown to improve prognosis, but its advantages still need to be further confirmed by large-sample RCTs. As for the outcome of sTBI patients, biomarkers, imaging evaluation, bioinformatics analysis, and artificial intelligence (AI) models may be valuable tools to develop.

Beyond the key diseases, management of neurocritical care patients has also been a hot topic of discussion for researchers, with new advances in multimodal neuromonitoring, airway and respiratory management strategies, and antiepileptic treatment, particularly prophylactic antiepileptic treatment regimens. However, more evidence needs to be accumulated regarding the value of monitoring indicators, airway management strategies, and the long-term effects of antiepileptic treatment. The critical care management of neurocritical care patients is closely related to prognosis, but due to the significant heterogeneity of patients, with differences across disease types and lesion locations, more in-depth stratified research is still needed. With the rapid development of AI and large language models may also play a greater role in this field. Furthermore, with advances in technology, cutting-edge techniques such as inflammation modulation, gene editing, stem cell therapy, arousal therapy, neuroplasticity mechanism research, and brain-computer interfaces have shown promise in animal studies and may accelerate translation to clinical applications in the future.

In summary, the neurocritical care field has experienced rapid advancements, resulting in substantial progress and the establishment of a more robust evidence-based medicine framework. This advancement sets the stage for improved precision in diagnosis and treatment approaches. However, to enhance overall patient prognosis and quality of life, more high-quality, large-sample studies are needed to refine the formulation and adjustment of treatment strategies, as well as the selection of drugs and monitoring indicators.

CRediT authorship contribution statement

Yuqing Chen: Writing – original draft. Shuya Wang: Methodology. Shanshan Xu: Resources. Ningyuan Xu: Writing – review & editing. Linlin Zhang: Writing – review & editing. Jianxin Zhou: Supervision.

Managing Editor: Jingling Bao/Zhiyu Wang