Targeted temperature management in brain edema

Targeted temperature management is a treatment strategy to lower core body temperature to achieve neuroprotection or reduce elevated intracranial pressure. Therefore, it has been increasingly used in the neurointensive care unit to manage various types of acute neurologic injuries.Current Concepts: Targeted temperature management can be divided into three distinct phases, including induction, maintenance, and rewarming, and each phase has risks and predictable complications. In patients with acute neurocritical illnesses, including traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage, and ischemic stroke, brain edema is a potentially life-threatening complication as it raises the intracranial pressure, leading to brain herniation and permanent neurological damage. In this sense, targeted temperature management can be considered the final strategy for medical treatment for controlling an intracranial pressure crisis in patients with severe brain injury.Discussion and Conclusion: In the neurointensive care unit, applying targeted temperature management to patients with severe brain injuries may be challenging. Targeted temperature management in critically ill neurological patients is associated with an increased risk of systemic complications, as hypothermia is prolonged, requiring a comprehensive patient-by-patient assessment of the advantages and disadvantages of treatment. Except for cerebral pressure management, analyses of targeted temperature management in patients with traumatic brain injury and subarachnoid hemorrhage remain controversial regarding its effect on prognosis. Targeted temperature management should be reserved for selective patients, and further studies are needed to improve the efficacy of hypothermia for individual conditions, including intracerebral hemorrhage and ischemic stroke.

Management of adverse effects in hyperosmolar therapy of brain edema

Mannitol and hypertonic saline are the most frequently used hyperosmolar agents to treat cerebral edema resulting from acute brain injury. However, there are several issues with using hyperosmolar therapies. Here, we focus on the potential adverse effects of hyperosmolar therapies and practical tips to overcome these issues in the neurointensive care unit.Current Concepts: Among the hyperosmolar agents used, mannitol may decrease intravascular volume and pose a potential risk of acute kidney injury for patients. Complications associated with using hypertonic saline include the risk of central pontine myelinolysis, coagulopathy, electrolyte imbalances, metabolic acidosis, and pulmonary edema. In addition, prolonged use of hypertonic saline increases the risk of hyperchloremic metabolic acidosis, which may be overcome with the concomitant use of sodium acetate.Discussion and Conclusion: Several laboratory variables were monitored in the neurointensive care unit to limit and possibly detect early complications related to hyperosmolar therapies. When using hyperosmolar agents, including mannitol and hypertonic saline, for therapeutic purposes in patients with cerebral edema, determining whether to use peripheral or central lines and determining the appropriate rate and infusion dose can minimize their adverse effects. Clinicians need to be aware of the potential adverse events of administering hyperosmolar agents.

Hyperosmolar therapy for regulation of cerebral edema and intracranial pressure

Hyperosmolar therapy is an essential treatment method for increased intracranial pressure and cerebral edema. Mannitol and hypertonic saline are frequently used in clinical practice; however, more helpful recommendations are needed for the optimal management of cerebral edema in terms of the choice, dosage, and timing of these medications. This study aimed to introduce the characteristics and relative strengths of two agents, i.e., mannitol and hypertonic saline, and review clinical data supporting their use in various diseases.Current Concepts: Hyperosmolar therapy reduces intracranial pressure by removing water from the brain tissue and transferring it to the vascular space by creating an osmotic gradient. Mannitol improves cerebral blood flow by reducing the hematocrit, decreasing blood viscosity, and increasing deformability of red blood cells. Hypertonic saline increases intravascular volume, transiently increases cardiac output, and improves tissue oxygen partial pressure in the brain. Hypertonic saline has several advantages over mannitol, including quicker onset and longer-lasting reduction in intracranial pressure. However, no significant differences are noted in clinical, functional outcomes, or mortality between the two treatment agents.Discussion and Conclusion: Both mannitol and hypertonic saline are effective in reducing increased intracranial pressure. Clinicians should be able to select an appropriate agent in different clinical situations based on available evidence and patients’ individual medical conditions.

Cerebral perfusion pressure optimization for the regulation of brain edema and intracranial pressure

Increased intracranial pressure (ICP) is a pathological condition associated with severe neurological conditions in patients with acute brain injuries. Managing increased ICP based on optimal cerebral perfusion pressure (CPP) is crucial for improving outcomes.Current Concepts: Cerebral autoregulation, the intrinsic ability to maintain stable cerebral blood flow across a wide range of CPP, is impaired in several brain injuries. CPP, the difference between the mean arterial pressure and the ICP, is a critical factor in maintaining cerebral blood flow. Therefore, optimal CPP is important in managing patients with acute brain injuries. In addition, monitoring cerebral autoregulation and its response to pathological derangements can help diagnose, manage, and predict acute brain injury outcomes. Goal-directed therapy using cerebral autoregulation is beneficial in managing patients with ICP elevation. If blood pressure is excessively low in a patient with elevated intracranial pressure, a treatment to increase blood pressure should be considered as a first step, called optimizing cerebral perfusion pressure. However, if CPP is excessively high in a patient with elevated ICP, a treatment to lower CPP by controlling blood pressure to an appropriate level to prevent worsening of edema due to hyperperfusion should be considered.Discussion and Conclusion: Monitoring cerebral autoregulation to guide optimal management of increased ICP based on optimal CPP may be helpful in goal-directed therapy and improving prognosis among patients with acute brain injuries.

Assessment of increased intracranial pressure in patients with brain injury

Monitoring and managing elevated intracranial pressure (ICP) is one of the core topics in neurocritical care. Although invasive methods are regarded as standard means, the recent development of non-invasive monitoring devices help clinicians handle ICP issues without additional risks of device-related complications.Current Concepts: According to the Monro–Kellie hypothesis, any brain injury that can cause a mass effect will lead to ICP elevation. Therefore, an ICP surge beyond the capacity of a compensatory reserve will decrease cerebral blood flow and may end up causing secondary brain damage. Indications for invasive ICP monitoring may vary according to the underlying conditions or the severity of brain damage. Regardless, ICP monitoring is considered when there is a risk of ICP elevation. In addition to pressure monitoring, external ventricular drainage catheters are used therapeutically to drain cerebrospinal fluid to reduce ICP. Several ICP monitoring probes are available based on pressure measurement types. Recently, non-invasive ICP monitoring methods have been developed and are increasingly used in patients with severe brain injuries. Pulsatility index from transcranial Doppler ultrasonography, quantitative pupillary light reflex from an automated pupillometer, and optic nerve sheath diameter using ultrasonography are commonly used surrogates for ICP surges in neurointensive care units.Discussion and Conclusion: ICP monitoring is essential for managing patients with severe brain injuries. Understanding the differences among the ICP monitors and determining the appropriate methods for ICP monitoring is necessary for optimizing patients’ care in the neurocritical care unit.

Basic principle in the management of brain edema and elevated intracranial pressure

Brain edema is a well-recognized pathophysiological secondary change after primary brain injury. The mechanism of brain edema may differ based on the types of brain edema. However, numerous ion channels are involved in its development and are therefore currently a hot target for anti-edema therapy. Here, this paper reviews the clinically important differences among the types of brain edema and a step-wise management strategy for brain edema and elevated intracranial pressure (ICP).Current Concepts: Brain edema can be classified as cytotoxic, ionic, vasogenic, and interstitial edema. Although the underlying mechanisms may differ among the various types of brain edema, multiple ion channels and the integrity of tight junctions are associated with the development of brain edema. If brain edema aggravates, the intracranial volume expands and leads to an elevation of ICP. A basic principle in the management of ICP includes proper positioning, screening for a need for extraventricular drainage, proper sedation, transient hyperventilation, assessing the intracranial water status with the serum sodium level, optimization of cerebral perfusion pressure, hyperosmolar therapy, targeted temperature management, and induction of a pharmacological coma with sedatives.Discussion and Conclusion: Stepwise treatment strategies are recommended in the management of patients with ICP crisis. Based on the principle, detailed management plans need to be adjusted based on the status of an individual patient.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke

Background@#Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. @*Methods@#We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. @*Results@#Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92–1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27–1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68–1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68–1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89–1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01–10.74, P < 0.001). @*Conclusion@#Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

2022 Update of the Korean Clinical Practice Guidelines for Stroke: Antithrombotic Therapy for Patients with Acute Ischemic Stroke or Transient Ischemic Attack / 대한뇌졸중학회지

Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.

Neostigmine for Treating Acute Colonic Pseudo-Obstruction in Neurocritically Ill Patients

Background@#and PurposeAcute colonic pseudo-obstruction (ACPO) is a common but understudied complication in neurocritically ill patients. The acetylcholinesterase inhibitor neostigmine can be used to treat ACPO in patients who do not respond to conventional treatment. This study investigated the effectiveness and adverse events when using neostigmine to manage ACPO in neurocritically ill patients. @*Methods@#This retrospective study investigated patients with ACPO who were treated using neostigmine in the neurological intensive-care units at two centers between March 2017 and August 2020. Neostigmine was administered intravenously or subcutaneously (at doses ranging from 0.25 mg to 2 mg) according to the protocols at the two centers. The outcomes were bowel movements and the changes in colon diameters on abdominal radiographs. Safety events such as bradycardia, vomiting, salivation, and sweating were evaluated. @*Results@#This study included 31 subjects with a mean age of 46.8 years (65.4% males). All patients had a bowel movement at a median of 120 minutes after administering neostigmine. The colon diameter decreased by a median of 17.5 mm (paired t-test: p<0.001) regardless of the dose and treatment protocols. Multilevel analysis confirmed that the mean colon diameter decreased from 66 mm pretreatment to 47.5 mm posttreatment (p<0.001), with an intraclass correlation coefficient of 13%. Three patients (9.7%) exhibited hypersalivation, sweating, bradycardia, and vomiting. Bradycardia (heart rate, 42 beats/minute) occurred in one patient (3.2%), and was successfully managed by injecting atropine. @*Conclusions@#Neostigmine injection is a safe and effective treatment option for ACPO in neurocritically ill patients who fail to respond to conservative management.

Neostigmine for Treating Acute Colonic Pseudo-Obstruction in Neurocritically Ill Patients

Background@#and PurposeAcute colonic pseudo-obstruction (ACPO) is a common but understudied complication in neurocritically ill patients. The acetylcholinesterase inhibitor neostigmine can be used to treat ACPO in patients who do not respond to conventional treatment. This study investigated the effectiveness and adverse events when using neostigmine to manage ACPO in neurocritically ill patients. @*Methods@#This retrospective study investigated patients with ACPO who were treated using neostigmine in the neurological intensive-care units at two centers between March 2017 and August 2020. Neostigmine was administered intravenously or subcutaneously (at doses ranging from 0.25 mg to 2 mg) according to the protocols at the two centers. The outcomes were bowel movements and the changes in colon diameters on abdominal radiographs. Safety events such as bradycardia, vomiting, salivation, and sweating were evaluated. @*Results@#This study included 31 subjects with a mean age of 46.8 years (65.4% males). All patients had a bowel movement at a median of 120 minutes after administering neostigmine. The colon diameter decreased by a median of 17.5 mm (paired t-test: p<0.001) regardless of the dose and treatment protocols. Multilevel analysis confirmed that the mean colon diameter decreased from 66 mm pretreatment to 47.5 mm posttreatment (p<0.001), with an intraclass correlation coefficient of 13%. Three patients (9.7%) exhibited hypersalivation, sweating, bradycardia, and vomiting. Bradycardia (heart rate, 42 beats/minute) occurred in one patient (3.2%), and was successfully managed by injecting atropine. @*Conclusions@#Neostigmine injection is a safe and effective treatment option for ACPO in neurocritically ill patients who fail to respond to conservative management.