Intensive Care of Emergency Conditions - V. M. Zaporozhan 2006

Brain Edema and Swelling

Brain edema is an increase in brain volume caused by fluid shifting from the vascular bed into brain tissue As a result of oxygen deprivation, hemodynamic instability, Water-electrolyte imbalance, and several other factors.

Brain edema is frequently accompanied by brain Swelling. While edema involves the accumulation of fluid in the extracellular space, swelling is characterized by the binding of water to cellular colloids due to their high hydrophilicity. Evidently, these are different facets or Stages of the same pathophysiological process—cerebral edema and swelling (CES).

In the early stages, CES acts as a protective response to injury, since hyperhydration helps lower toxin concentration. However, disease progression leads to a significant increase in intracranial pressure (ICP) and The Development of brain herniation syndromes. By compressing vital brain centers (such as respiratory and vasomotor centers), this can impair life-sustaining Functions and even result in death, which underscores the urgent need for timely intensive care in CES.

The causes of CES in severe TRAUMATIC BRAIN INJURIES and systemic disorders are most commonly associated with vasogenic brain edema (damage to the Blood-brain barrier) occurring in neuroinfections, Sepsis, hemorrhagic and ischemic strokes. It can also stem from cytotoxic brain edema (hypoxic Cell injury) following cardiac arrest, severe respiratory failure, water intoxication, or renal and hepatic encephalopathy.

The primary trigger for CES across all these conditions is Hypoxia, particularly when combined with elevated carbon dioxide levels. Metabolic Disorders (such as hypoproteinemia), electrolyte imbalances, as well as allergic and infectious states, also play a crucial role in its development. The damaging factors primarily disrupt brain METABOLISM/26.html">Energy Metabolism, forcing a shift toward Anaerobic Respiration. Acute oxygen deprivation and inflammatory processes impair blood-brain barrier permeability, altering the electrolyte balance within Cells and extracellular fluid (transmineralization) and creating a hyperosmotic intracellular environment. As a result, membrane permeability is compromised, cellular oncotic pressure rises, Proteins become denatured, and fluid from the circulating blood infiltrates the brain parenchyma.

Brain edema is classically divided into two main types: generalized and localized.

Generalized edema involves the entire brain and typically develops in the context of intoxications and severe infections. It frequently leads to brain herniation.

Localized edema occurs in association with trauma, space-occupying lesions, and cerebral infarctions, and is less likely to cause significant herniation.

The Clinical presentation of CES depends on the duration, focal localization, severity, and extent of the lesion. Against the backdrop of the underlying disease, patients develop progressive weakness, lethargy, and headaches. Paresis and paralysis appear and worsen, and papilledema develops. As the edema extends toward the Brainstem, seizures occur, along with deepening lethargy, somnolence, cardiovascular and respiratory dysfunction, and The Emergence of pathological Reflexes.

To a large extent, the clinical picture is driven by brain displacement and entrapment, manifesting as brainstem and Midbrain compression syndromes.

Midbrain compression is typically characterized by oculomotor crises with pupillary dilation and fixed gaze, increased Muscle tone, tachycardia, blood pressure fluctuations, and hyperthermia. Brainstem compression leads to Vision loss, mydriasis, anisocoria, and vomiting. Symptoms of cerebellar herniation include bradycardia, bradypnea, sudden vomiting, dysphagia, and paresthesias in the shoulders and arms. Nuchal rigidity is a frequent early sign that often appears before other symptoms. The most critical and ominous sign of herniation is sudden respiratory arrest.

The displacement of brain tissue relative to the rigidly fixed structures of the cranial vault (the dural folds of the falx cerebri and tentorium cerebelli) leads to The formation of brain herniations (tissue protrusion).

Depending on the localization, herniation may occur in several clinical variants:

— subfalcine herniation (herniation of the medial cerebral hemisphere under the falx cerebri), which can compress the anterior and posterior cerebral Arteries, leading to ischemic stroke manifested by contralateral leg weakness and impaired bladder control;

— uncal (transtentorial) herniation, in which the uncus cerebri shifts into the tentorial notch, compressing the Oculomotor nerve and displacing the cerebral peduncles; it is characterized by ipsilateral mydriasis with an unreactive pupil and contralateral hemiparesis (though ipsilateral hemiparesis is occasionally possible);

— central transtentorial herniation, involving the downward Displacement of the Diencephalon relative to the tentorium cerebelli, accompanied by a depressed level of consciousness ranging from stupor to coma, along with respiratory disturbances (most commonly Cheyne-Stokes breathing); pupillary constriction is typical, but light reflex is preserved for a prolonged period;

— tonsillar herniation (herniation of the cerebellar Tonsils through the foramen magnum) with compression of the Medulla Oblongata and the development of Cushing's triad (respiratory depression, arterial Hypertension, bradycardia), culminating in cardiorespiratory collapse.

Depression of consciousness is best evaluated using the Glasgow Coma Scale (see Table 2).

CES should be suspected in any patient presenting with unexplained loss of consciousness, seizures, or hyperthermia, particularly in the presence of severe systemic disease. Furthermore, no episode of hypoxia—regardless of its duration—passes without consequence for the brain, as recurrent, even brief, hypoxic episodes can cause lasting brain damage.

Computed tomography (CT) is the diagnostic method of choice for CES, enabling the rapid detection of intracranial mass effects and the Assessment of the brain parenchyma, ventricular system, subarachnoid cisterns, and sulci.

Continuous ICP monitoring confirms the Diagnosis of brain edema and allows clinicians to track the efficacy of intensive care management.

Lumbar puncture is contraindicated in CES due to the high risk of brain herniation. Notably, neither a normal CT scan nor the absence of papilledema can rule out the presence of brain edema.

All intensive care measures and therapies employed to manage brain edema can be broadly divided into three main categories.

The first category comprises general resuscitation measures and supportive care utilized in critical conditions of various etiologies. These include maintaining adequate mechanical ventilation and optimal oxygenation (PO₂^>70 mmHg), supporting systemic blood pressure and circulating blood volume, controlling psychomotor agitation, seizures, pain, and nociceptive responses, and maintaining normal body Temperature.

The second category includes targeted therapies specific to patients with CES, such as elevating the HEAD AND TORSO by raising the head of the bed to an angle of 30–45° (provided the patient is hemodynamically stable with adequate circulating blood volume), alongside The Use of moderate hyperventilation, osmotic and non-osmotic Diuretics, and corticosteroids.

Combating hypoxia is one of the most critical elements in the therapy of brain edema. In acute brain swelling (ABS), neuronal hypoxia occurs under conditions of normal partial pressure of oxygen in the blood, whereas hypoxemia leads to cell death. Therefore, it is imperative to ensure adequate mechanical ventilation by any means necessary, combined with active Oxygen therapy and a fully patent airway. At the slightest threat of asphyxia, mechanical ventilation is recommended.

In cases of ABS, The Cardiovascular system must be closely monitored, and appropriate symptomatic therapy administered.

Dehydration therapy is carried out using various Methods. Today, mannitol is considered one of the most effective treatments for intracranial hypertension and ABS. A bolus administration of mannitol at 0.25–1.0 g/kg is recommended, as it offers advantages over continuous infusion. The clinical effect manifests 15–30 minutes after drug administration and lasts for 1.5–6 hours. It should be emphasized that the use of mannitol requires continuous monitoring of plasma osmotic parameters—osmolality and its components, namely sodium, glucose, and blood urea nitrogen. In hypernatremic hyperosmolarity (osmolality >320 mOsm/kg H₂O or hypernatremia >155 mmol/L), the use of mannitol is not recommended. Its administration requires simultaneous monitoring and replenishment of circulating blood volume (CBV) to the level of normovolemia. The potential Adverse effects of mannitol must be taken into account, such as an increase in intracranial pressure (the "rebound phenomenon") due to its ability to penetrate the extracellular space of the brain and cause water accumulation along an osmotic gradient, especially with prolonged use of high doses.

Saluretics provide a rapid effect, most commonly furosemide, administered at a dosage of 3–5 mg/(kg·day). It circulates in the blood for 4 hours. The initial dose should be at least 10 mg.

Glycerol at a dose of 1–2 g/kg is increasingly used in the Treatment of ABS. It is prescribed orally mixed with fruit juices, or administered via a gastric tube in unconscious patients. Glycerol is effective as an antihypertensive agent, can be administered repeatedly, and its anti-edematous effect is independent of diuresis.

One of the drawbacks of dehydration therapy is hemoconcentration, which impairs blood rheology and contributes to the development of thromboembolic complications. Consequently, in cases of cerebral blood flow disorders, the use of direct anticoagulants is recommended, particularly low-molecular-weight heparins (fraxiparine, clexane, etc.). Hemodilution also improves microcirculation, but it may lower oncotic pressure, potentially exacerbating brain edema. Therefore, erythrocytapheresis is considered more appropriate—namely, the exfusion of 400–800 mL of blood, after which the plasma is returned to the patient, while THE RED BLOOD cells are subsequently used to compensate for blood loss during surgery, etc.

To increase the oncotic pressure of the blood, a 20% albumin solution or a hypertonic solution of dry plasma (50 or 100 g of dry plasma dissolved in 25 or 50 mL of sterile pyrogen-free water, respectively) is administered.

The use of corticosteroids, which primarily normalize cell membrane function and reduce the permeability of cerebral capillary walls, is effective in bacterial and fungal meningitis, as well as most viral encephalitides (data are controversial regarding herpetic encephalitis). Specifically, in viral encephalitis, their administration is recommended not only intravenously but also endoluminally. In metabolic encephalopathies (hepato-renal failure, Reye's syndrome), the efficacy of corticosteroids has not been proven. Dexamethasone is most commonly used intravenously at a dose of 4–16 mg 4 times a day, or, according to another recommendation, 20–40 mg/day, gradually tapering the dose over 4–6 days. Prolonged use of these drugs carries the risk of developing certain complications, such as gastrointestinal bleeding, arterial hypertension, water-electrolyte balance disorders, and suppression of the body's immunological activity.

The third group comprises so-called "aggressive" treatment methods that require additional medical equipment and expertise. The inherent risks compel physicians to use these methods only when ongoing treatment proves ineffective. This group includes: barbiturate coma, hyperventilation, hypothermia, and the so-called "triple-H" therapy (hypertension + hypervolemia + hemodilution). Prospective randomized clinical trials have demonstrated that the use of high-dose barbiturates in ABS (pentobarbital at 10 mg/kg every 30 minutes or 5 mg/kg every hour, pre-divided into 3 doses or via continuous infusion at 1 mg/(kg·h), and sodium thiopental, which is recommended for intravenous drip infusion at 1–2 mg/(kg·h), since higher doses causing deep anesthesia do not improve treatment outcomes but threaten marked arterial hypotension, reduced cerebral blood flow, and bronchopulmonary complications) not only helps reduce intracranial pressure but also lowers mortality among patients in whom Other Methods of lowering intracranial pressure have failed. Barbiturates must not be used in the presence of arterial hypotension and a fully replete CBV. Conversely, the adverse effects of barbiturates can be mitigated by maintaining CBV and correcting systemic blood pressure through the infusion of adrenomimetics (dopamine, dobutamine).

Prophylactic use of hyperventilation ($p_{\text{CO}_2}$ down to 25–30 mm Hg, preferably moderate down to 35 mm Hg) requires rigorous monitoring of blood gas composition, as it can lead to impaired cerebral perfusion. Prolonged (exceeding 24 hours) and deep hyperventilation ($p_{\text{CO}_2} < 25$ mm Hg) in the absence of intracranial hypertension is particularly dangerous. Deep hyperventilation (as a therapy of last resort) may be applied in the event of a sharp deterioration in neurological status if intracranial hypertension does not respond to sedation, muscle relaxation, ventricular CSF drainage, or osmodiuretics, and is classified as an "aggressive" treatment method. The development of cerebral ischemia resulting from hyperventilation can be assessed by measuring the arteriovenous oxygen difference in draining blood (Internal jugular vein bulb) or by studying cerebral blood flow. Moderate hyperventilation is particularly effective in children, where short sessions are capable of lowering intracranial pressure without additional interventions.

In recent years, interest has resurfaced in the use of hypothermia as a method to lower intracranial pressure and increase the brain's tolerance to ischemia and hypoxia. Hypothermia reduces the metabolic oxygen demand of cells. The simplest method is head cooling (ice cap). Hypothermia combines very well with neuroplegia, for which droperidol or aminazine is used. Sodium oxybutyrate (GHB) and seduxen are also effective, as they additionally act as cerebral protectants during oxygen deprivation.

The approach to intensive care regimens in ABS is undergoing significant revision; in particular, the advisability of using diuretics is being debated. Experience from leading neurosurgical centers indicates that the foundation of intensive care for brain edema must be the maintenance of normal Blood Circulation in the cerebral basin. Consequently, the primary factor in treating ABS is maintaining adequate hemodynamics through the use of novel natural or synthetic catecholamines (dopamine, dobutamine) at a dose of 2–20 mcg/(kg·min), as well as microcirculation-improving agents (heparin, trental, agapurin, etc.).

Despite some differences in the Pathogenesis of brain edema across various diseases, treatment is conducted according to General Principles. Traditional conservative therapy methods—including the use of osmodiuretics and saluretics, hyperventilation, maintenance of adequate cerebral perfusion, normalization of water-electrolyte balance, and Hyperbaric Oxygenation (Table 11)—are complemented by novel approaches, among which is blood ultrafiltration. The experience of L. P. Chepky (1998) demonstrated that 1–3 sessions are often sufficient to significantly reduce or completely resolve edema. Furthermore, a single session successfully removes 1 to 6 liters of ultrafiltrate without causing hemoconcentration or hemodynamic disturbances, which in this case is attributed to the fluid shift from intracellular and interstitial spaces into the vascular bed.

The accumulation of $\text{Ca}^{++}$ ions in the neuronal Cytoplasm also contributes to the development of ABS. This is particularly relevant in cases of brain trauma, but also holds some significance in meningoencephalitis. The activation of Ca-dependent phospholipase $\text{A}_2$ leads to the release of arachidonic acid from membrane Phospholipids, which upon oxidation promotes the accumulation of BIOLOGICALLY ACTIVE SUBSTANCES (Prostaglandins, thromboxane, Leukotrienes) that increase blood-brain barrier permeability and foster brain edema. Therefore, the administration of calcium channel blockers with cerebral effects is well-founded. These include nimodipine (nimotop), administered via slow intravenous drip twice daily at 10 mg for 7–10 days. For the same purpose, the administration of magnesium sulfate (5–10 mL of a 25% solution intravenously 2–4 times a day) and lidocaine (0.5–1.0 mg/kg) is proposed.

To protect against free radicals generated during Lipid Peroxidation that promote brain edema, antioxidants are recommended: tocopherol acetate at 500 mg/day, ceruloplasmin at 1000 mg/day, emoxitin at 10–15 mg/(kg·day), as well as the kallikrein inhibitor aprotinin (contrykal, gordox, trasylol) at 60,000 IU/day and inotropic agents (piracetam, nootropil).

Class="center">Table 11. Main therapeutic measures in ABS (according to L. P. Chepky, 1998)

References

1. Zavgorodny, V. L., Nalapko, Y. I., & Mamchur, S. Y. Algorithms of intensive care in diseases and INJURIES OF THE brain / Ed. by I. P. Shlapak. — Luhansk: Yantar, 2002. — 144 p.

2. Cherniy, I. I., Kardash, A. M., Gorodnik, G. A., & Drobotko, V. F. Diagnosis and treatment of cerebral edema and swelling / Ed. by I. I. Cherniy. — K.: Zdorovya, 1997. — 227 p.

3. Svadovsky, A. I. Traumatic brain edema // Neurotraumatology: Handbook / Ed. by A. N. Konovalov, L. B. Likhterman, A. A. Potapov. — M.: IPC VAZAR-FERRO, 1994. — P. 132–134.

4. Starchenko, A. A. Clinical neuroresuscitation: A reference guide / Ed. by V. A. Khilko. — St. Petersburg: Saint Petersburg Medical Publishing House, 2002. — 665 p.

5. Cherniy, V. I. Posthypoxic encephalopathy. — K.: Zdorovya, 1997. — 336 p.