Hydroelectrolytic syndromes in neuroanesthesia and neurocritical care

Abstract

Electrolyte disorders are pivotal determinants of morbidity and mortality in neurocritical care and exacerbated by acute brain injury, neuroendocrine dysfunction, and therapeutic interventions. This narrative review synthesized contemporary evidence on the pathophysiology, diagnosis, and management of hydroelectrolytic disturbances in neuroanesthesia and neurocritical populations. Dysnatremias (hyponatremia and hypernatremia) are prevalent with emerging data challenging historical correction paradigms: Rapid sodium normalization may reduce mortality without increasing complications. Distinct strategies are required for syndromes of inappropriate antidiuretic hormone secretion (fluid restriction, vaptans) vs cerebral salt wasting (volume resuscitation). Chloride dysregulation, driven by cation-chloride cotransporter imbalances, exacerbates cytotoxic edema and seizures, warranting trials of bumetanide and balanced crystalloids. Hypokalemia, prevalent in traumatic brain injury, demands proactive surveillance to prevent arrhythmias while hyperkalemia management prioritizes membrane stabilization and renal clearance. Hypocalcemia correlates with adverse outcomes in subarachnoid hemorrhage, necessitating timely replacement. Magnesium disorders lack consistent prognostic associations in neurocritical cohorts, contrasting with general critical care. Current evidence underscores the need for individualized, pathophysiology-driven correction, integrating endocrine and neurological principles. Innovations such as point-of-care testing and targeted therapies (e.g., acetate-buffered hypertonic saline) show promise, yet reliance on observational data and preclinical models highlights the urgency for randomized controlled trials. This review advocated for protocolized monitoring, dynamic assessments, and research to define optimal correction thresholds and validate emerging interventions in this high-risk population.

Key Words: Electrolytes; Sodium; Potassium; Magnesium; Calcium; Chloride; Critical care

Core Tip: The aim of the present review was to report the latest evidence on the pathophysiology, diagnosis, approach, and targeted management of electrolyte disorders in neuroanesthesia and neurocritical care. Endocrine, neurological, and resuscitation issues will be treated to provide clinical strategies to mitigate secondary neuronal injury and improve outcomes in these critical patients.

INTRODUCTION

Hydroelectrolytic disorders have been historically described, are prevalent in patients who are critically ill, and can complicate clinical management with an increased morbidity and mortality in intensive care units (ICU)[1-5]. Patients receiving neurocritical care exhibit heightened vulnerability due to acute brain injury (ABI) disrupting systemic homeostasis[6-9]. For instance, dysnatremias occur in 38% of patients who are neurocritical and 50% of neurosurgical cohorts with imbalances linked to adverse outcomes in traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), ischemic stroke, and intracranial hemorrhage (ICH)[10-13].

Neuroendocrine dysfunction exacerbates post-ABI electrolyte instability and up to 49% of patients with moderate-to-severe TBI develop hypopituitarism, impairing hypothalamic-pituitary-adrenal axis regulation of sodium-water balance[14-16]. Clinical conditions such as syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSWS), although sharing overlapping laboratory features, necessitate distinct therapeutic approaches[17]. Key challenges in neurocritical care include impaired consciousness, osmotic therapy, drug-induced electrolyte disturbances, and large-volume resuscitation[4,17,18]. Timely correction of electrolyte imbalances guided by symptom severity and underlying brain injury is critical to optimizing outcomes[19].

Given the critical role of electrolyte balance in neurocritical care and the complex interplay between brain injury and systemic homeostasis, a comprehensive review of the pathophysiology, prevention, and management of these disorders is appropriate. Emerging evidence underscores the need for individualized treatment protocols guided by dynamic biomarkers such as natriuretic peptides or urinary chloride excretion and targeted strategies to mitigate secondary neuronal injury and improve outcomes in this vulnerable patient population[19,20].

The aim of the present review was to report the latest evidence on relevance, pathophysiology, diagnosis, prevention, and targeted management of electrolyte disorders in neuroanesthesia and neurocritical care. Endocrine, neurological, and resuscitation issues will be treated to provide clinical strategies to mitigate secondary neuronal injury and improve outcomes in these critical patients.

SODIUM DISORDERS

Dysnatremias (hyponatremia and hypernatremia) are prevalent in neurocritical care, affecting up to 49% of patients in the ICU and independently worsen outcomes in TBI, ICH, SAH, and ischemic stroke[7,9,12,20]. Their management is complicated by neuroendocrine dysfunction, osmotic therapies, and direct brain injury, necessitating etiology-specific correction to mitigate morbidity and mortality[14,21].

Hyponatremia

Relevance: Hyponatremia (Na⁺ < 135 mmol/L) is often described as the most frequent electrolyte abnormality in patients who are neurocritical with a prevalence of 30% in hospitalized patients and nearly 50% in the ICU[10-12]. Etiologies in this population include SIADH and CSWS and require specific therapeutic strategies[17]. Early identification and tailored treatment are critical to reduce complications and improve prognosis.

Pathophysiology/diagnosis: In SIADH persistent vasopressin release despite hypo-osmolality results in free water retention, hemodilution, and hyponatremia. It is characterized by hypertonic urine (> 100 mOsm/kg) and elevated urinary sodium (> 40 mmol/L) due to suppressed renin-angiotensin-aldosterone system activity. There is water retention without clinical volume overload due to compensatory sodium excretion. Triggers include cerebral edema, increased intracranial pressure, and endocrine disturbances[17]. The CSWS arises from renal sodium loss causing hypovolemia and secondary hyponatremia. Mechanisms involve brain injury-induced natriuretic peptide release and sympathetic activation. Patients may exhibit hypovolemia although assessment is challenging in this population.

Biochemically, CSWS shares hyponatremia and elevated urinary Na⁺ with SIADH but demonstrates less concentrated urine osmolality[17]. Fluid restriction or vasopressin antagonists are indicated for SIADH, whereas volume expansion and sodium repletion are required for CSWS. Misdiagnosis risks worsening hypovolemia and cerebral hypoperfusion[17,19]. Additional contributors include diuretics, antidepressants, glucocorticoid deficiency, and excessive hypotonic fluid resuscitation[18].

Diagnostic workup (Table 1) requires confirming true hypotonicity (serum osmolality < 280 mOsm/kg) and excluding pseudohyponatremia[19]. Differentiating CSWS from SIADH hinges on volume status assessment, which is often obscured by altered consciousness, sedation, or mechanical ventilation. While hypovolemia (tachycardia, hypotension) may indicate CSWS and euvolemia/hypervolemia aligns with SIADH, clinical evaluation alone is unreliable. SIADH features inappropriately concentrated urine and elevated urinary sodium due to renin-angiotensin-aldosterone system suppression. CSWS similarly shows elevated urinary sodium but less concentrated urine. Biochemical overlap necessitates adjunctive testing, such as natriuretic peptide measurement or saline infusion trials, where transient Na+ improvement supports CSWS and no response favors SIADH[17]. A medication review is critical as diuretics, antidepressants (e.g., selective serotonin reuptake inhibitor, tricyclics), and antiepileptics (e.g., carbamazepine) are common contributors[18]. Additional etiologies include glucocorticoid deficiency and excessive hypotonic resuscitation[19].

Table 1 Hyponatremia syndromes and laboratory workup.

Etiology	Volume status	Serum osmolality (mOsm/kg)	Urine osmolality	Urine Na+	Other features
SIADH	Euvolemic	↓ (< 280)	↑ (> 100 mOsm/kg, often > serum)	↑ (> 40 mEq/L)	↓ Serum uric acid; high FeUA before correction (> 11%) that normalizes after correction (4%-11%)
Cerebral salt wasting	Hypovolemic	↓ (< 280)	↑ (> 100, less concentrated than SIADH)	↑ (> 40 mEq/L)	↑ natriuretic peptides; persistent high FeUA (> 11%) even after Na+ correction
Diuretic-induced	Hypovolemic	↓ (< 280)	Variable (often ↑)	Variable (> 20 mEq/L)	History of loop or thiazide use; UNa interpretation may be confounded by recent diuretics
Excess hypotonic fluids	Euvolemic or hypervolemic	↓ (< 280)	↓ (< 100 mOsm/kg)	↓ (< 30 mEq/L)	Large-volume hypotonic IV fluids or low-solute intake (e.g., beer potomania)
Adrenal insufficiency	Euvolemic	↓ (< 280)	↑ (> 100 mOsm/kg)	↑ (> 40 mEq/L)	↓ Cortisol; hyponatremia resistant until glucocorticoid replaced

Confirm true hypotonic hyponatremia with serum osmolality < 280 mOsm/kg and rule out pseudohyponatremia. Volume status (clinical exam, hemodynamics) plus urine indices (osmolality, Na⁺) are essential to distinguish syndrome of inappropriate antidiuretic hormone secretion (euvolemic, concentrated urine, high urine Na) from cerebral salt wasting syndrome (hypovolemic, similar labs but with hypovolemia signs). Iatrogenic contributors (diuretics, hypotonic fluids) and endocrine causes (adrenal insufficiency) must always be considered. Continuous monitoring and tailored therapy (fluid restriction or vaptans for syndrome of inappropriate antidiuretic hormone secretion vs volume/sodium repletion for cerebral salt wasting syndrome) are critical. FeUA: Fractional excretion of uric acid; IV: Intravenous; SIADH: Syndrome of inappropriate antidiuretic hormone secretion; UNa: Urine Na.

Prevention/targeted management: Management requires a tailored approach to mitigate neurologic complications (e.g., seizures, coma) while avoiding osmotic demyelination syndrome. Urgency depends on severity and symptom acuity with initial efforts focused on discontinuing causative medications or correcting pituitary dysfunction[3,4]. For hypervolemic hypotonic hyponatremia (e.g., SIADH), fluid restriction remains the mainstay of therapy. Refractory cases may benefit from vasopressin antagonists (vaptans) to enhance free water excretion. Hypovolemic hyponatremia, such as CSWS, mandates both sodium and volume repletion[17]. Severe or symptomatic cases, particularly those with cerebral edema or life-threatening manifestations, require hypertonic saline resuscitation[19].

Challenging the “slow-correction mantra”: Emerging evidence challenges traditional approaches advocating slow hyponatremia correction. A recent meta-analysis demonstrated that rapid correction (≥ 8-10 mmol/L per day) of severe hyponatremia correlates with reduced in-hospital and 30-day mortality, shorter hospital stays, and no increased osmotic demyelination syndrome risk[22]. Similarly, a recent retrospective cohort reported lower mortality in patients in the ICU with severe sodium deficits (≤ 120 mmol/L) undergoing rapid correction (> 8 mmol/L per day) without significant neurological complications[23]. Both studies highlighted the need to reevaluate guidelines based on low-quality evidence although limitations like observational designs and undetermined chronicity warrant cautious interpretation and further research[22,23].

Hypernatremia

Relevance: Hypernatremia (Na⁺ > 145 mmol/L) disrupts neuronal osmotic balance, causing cellular dehydration, cerebral edema, and neurological deterioration (encephalopathy, seizures, coma). It affects 16%-40% of patients with TBI, 26% of patients with ICH, and 20%-30% of patients with SAH with ICU prevalence reaching 49%[6,8,10,12,20]. ICU-acquired hypernatremia independently increases mortality by 28% and prolongs ICU stays by 40%[18,19]. The etiology includes osmotic therapies (e.g., mannitol, hypertonic saline; 60% of cases) and central diabetes insipidus (15%-28% post-TBI)[6,14-16]. Disease-specific mechanisms, such as disrupted thirst regulation in TBI, further exacerbate risks.

Pathophysiology/diagnosis: Hypernatremia reflects a relative free-water deficit, generating extracellular hyperosmolality that draws water out of neurons, causing shrinkage, synaptic disruption and even capillary tears. Over hours to days cells accumulate organic osmolytes (e.g., taurine, betaine) to restore volume, but in acute cases (< 48 h) this adaptation is insufficient. Overly rapid sodium correction can precipitate cerebral edema. When hypernatremia persists beyond 48 h, cerebral blood flow falls by roughly 20%, compounding injury in patients with acute brain insults[4,24].

Hypernatremia diagnostic work up (Table 2) starts by confirming hypernatremia and assessing serum osmolality to confirm hypertonicity[4,24]. Volume status classification commonly relies on clinical history, physical exam, and ancillary testing[19]. Hypovolemic hypernatremia involves disproportionate total body water loss, whereas euvolemic cases reflect isolated total body water depletion. Hypervolemic hypernatremia, the least common form, results from excess sodium retention. Urinary sodium and osmolality refine etiology. Low urinary sodium (< 30 mmol/L) suggests extrarenal water loss or renal free water loss with preserved sodium reabsorption, while elevated levels indicate renal sodium wasting (e.g., osmotic diuresis, nephrogenic diabetes insipidus)[4,24]. Low urine osmolality supports diabetes insipidus, often observed post-TBI or hypothalamic-pituitary injury[14-16]. Iatrogenic causes, such as osmotic therapy for cerebral edema, should be evaluated[18]. Differentiating acute from chronic hypernatremia is critical to guide management.

Table 2 Hypernatremia syndromes and laboratory workup.

Etiology	Volume status	Urine osmolality	Urine Na+	Key lab/clinical features
Extrarenal water losses	Hypovolemic	High (> 450 mOsm/kg)	Low (< 30 mEq/L)	↑ BUN/Cr ratio, hypotension/tachycardia, clinical signs of volume depletion
(Fever, hyperventilation, GI losses, drains, wounds)
Osmotic diuresis	Hypovolemic	High (> 300 mOsm/kg)	High (> 30 mEq/L)	Polyuria, osmotic diuresis; mannitol-induced free-water loss
(Mannitol, diuretics)
Central diabetes insipidus	Euvolemic	Low (< 200 mOsm/kg)	Low (< 30 mEq/L)	Polyuria (> 200 mL/hour), polydipsia, ↑ serum Na+, responds to desmopressin
Nephrogenic diabetes insipidus	Euvolemic	Low (< 200 mOsm/kg)	Variable (< 30 mEq/L)	Polyuria, ADH-resistance; no response to desmopressin
Hypertonic saline infusion	Hypervolemic	High (> 450 mOsm/kg)	High (> 30 mEq/L)	Positive fluid balance, volume overload, exogenous Na+ load (3%-23.4% NaCl)
Exogenous sodium load	Hypervolemic	High (> 450 mOsm/kg)	High (> 30 mEq/L)	Iatrogenic Na+ gain (bicarbonate drips, enteral salt), often with ↑ chloride
(NaHCO3, salt tablets)

Serum osmolality is invariably high (> 295 mOsm/kg) in true hypernatremia. Differentiation hinges on volume status (clinical exam, hemodynamics) and urinary indices (urine osmolality, urine Na⁺) to guide targeted therapy. ADH: Antidiuretic hormone; BUN: Blood urea nitrogen; Cr: Creatinine; GI: Gastrointestinal.

Prevention/targeted management: Management of hypernatremia requires an individualized approach guided by volume status, etiology, and neurological context. The primary goal is gradual normalization of serum sodium while avoiding complications such as cerebral edema. Serial sodium monitoring is critical to prevent overcorrection[19,24]. Fluid selection depends on volume status. Hypotonic solutions correct free water deficits in patients who are euvolemic or resuscitated hypovolemic. Isotonic solutions restore intravascular volume in hypovolemia before addressing residual deficits[24,25]. Enteral free water is preferred for patients with intact gastrointestinal function to minimize solute load. In hypovolemic hypernatremia initial resuscitation with isotonic fluids precedes gradual free water replacement[4,24,25]. Patients who are euvolemic require free water replacement via enteral or hypotonic fluids alongside investigation of underlying causes such as diabetes insipidus[4,16,24,25]. Hypervolemic hypernatremia, the least common form, mandates sodium/fluid restriction, loop diuretics, or dialysis[24]. For iatrogenic hypernatremia in cerebral edema, hypertonic saline maintains serum sodium at 145-155 mmol/L to achieve osmotic therapy[3,24]. Assessment of intracranial pressure and neurological status is essential[5,24].

Challenging the “slow-correction mantra”: Current evidence questions historical guidelines for slow hypernatremia correction. Two studies linked slower correction rates ≤ 0.5 mmol/L/hour) and persistent hypernatremia to increased mortality[26,27]. Accordingly, a recent study reported that accelerated correction was not associated with any increase in neurological complications, whereas a later, larger retrospective cohort (n = 4265) reported that correction rates above 0.5 mmol/L/hour were linked to reduced mortality without additional adverse effects[28,29].

Potassium disorders

Relevance: Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L while hyperkalemia commonly refers to a concentration above 5.0 mmol/L[3,30]. Potassium disturbances are highly prevalent in neurocritical care with reported rates for the need of potassium supplementation in up to 75% of patients within 5 days postinjury in TBI and hyperkalemia occurring in 1.9% of patients with TBI, 17.8% of trauma cases within 12 h, and 18.8% of general ICU admissions[3,5,31,32]. Both hypokalemia and hyperkalemia are independently linked to increased morbidity and mortality via proarrhythmic effects, neuromuscular impairment, and exacerbation of cerebral dysregulation[30-33].

Pathophysiology: Hypokalemia often arises from surgical stress, hormonal dysregulation, and therapies such as mannitol-induced osmotic diuresis, loop diuretics, exogenous insulin, and catecholamine surges[5,31,34]. These factors drive renal potassium wasting and intracellular shifts via Na⁺/K⁺-adenosine triphosphatase activity, particularly following pituitary or hypothalamic surgery in which transient adrenal insufficiency and fluid redistribution exacerbate depletion[30,33]. The resultant hypokalemia destabilizes neuromuscular excitability, predisposing to diaphragmatic weakness, respiratory failure, and arrhythmias in patients with autonomic instability while impairing renal concentration and worsening polyuria in those with diabetes insipidus[35].

Molecularly, intracellular potassium depletion promotes caspase activation and neuronal apoptosis, exacerbating secondary injury[33]. Hyperkalemia, though less frequent, stems from impaired renal clearance, acidosis, rhabdomyolysis, or excessive supplementation[3,30]. Perioperative succinylcholine use in patients with denervation-related acetylcholine receptor upregulation can precipitate acute episodes[30,36]. Elevated extracellular potassium depolarizes membranes, triggering arrhythmias, flaccid paralysis, and central nervous system effects such as seizures, disrupted astrocytic buffering, and compromised cerebral autoregulation, intensifying secondary injury. Both disorders independently elevate morbidity and mortality through pro-arrhythmic effects, neuromuscular dysfunction, and cerebral dysregulation[3,35].

Prevention/targeted management: Management of potassium disorders (Table 3) in this population demands proactive surveillance and tailored strategies[3,30]. For hypokalemia, prevention prioritizes minimizing iatrogenic losses (e.g., diuretics, mannitol, insulin) and frequent electrolyte monitoring[3,30]. Oral potassium chloride is preferred for replacement, reserving intravenous administration with central access and continuous electrocardiogram monitoring for severe deficits. A target serum potassium of 4.0-4.5 mmol/L optimizes arrhythmic risk reduction and neuromuscular function[3,31]. Hyperkalemia management begins with membrane stabilization (calcium gluconate), followed by intracellular redistribution (insulin-glucose, beta-agonists, or bicarbonate in acidosis). Elimination strategies (e.g., diuretics, resins, or dialysis) are guided by renal function and severity[3,30]. Perioperatively, non-depolarizing neuromuscular blockers could replace succinylcholine in patients who are at-risk[36]. Serial point-of-care testing enables rapid detection and mitigation of acute shifts[3,30].

Table 3 Potassium disorders correction.

Disorder	Treatment category	Agent	Dose/Route	Notes
Hypokalemia	Oral repletion	Potassium chloride	20-40 mEq per dose, 2-3 times/day	High bioavailability; GI side effects at higher doses
	IV repletion (peripheral)	Potassium chloride in D5W or NS	10 mEq in 100 mL, infused ≤ 10 mEq/hour	Must dilute to minimize phlebitis
	IV repletion (central)	Potassium chloride in D5W or NS	20 mEq in 100 mL, infused ≤ 20 mEq/hour (up to 40 mEq/hour in arrest)	ICU monitoring; higher rates only in life-threatening situations
Hyperkalemia	Membrane stabilization	Calcium gluconate (10% solution)	1 g IV over 5-10 minutes	Repeat every 5-10 minutes if ECG changes persist; central line preferred
	Intracellular shift	Insulin + dextrose	10 U regular insulin IV + 25 g dextrose	Lowers K+ in 10-20 minutes; monitor blood glucose
	Intracellular shift	Salbutamol (β2-agonist)	10-20 mg nebulized or 5-10 μg IV	Onset about 30 min; watch for tachycardia
	Intracellular shift	Sodium bicarbonate	50 mEq IV	Particularly if metabolic acidosis present
	Renal elimination	Furosemide	20-40 mg IV	Requires adequate renal function and volume status
	Dialytic removal	Hemodialysis or CRRT	-	Definitive in severe or refractory cases
	Gastrointestinal binding	SPS	15-30 g PO or PR	Erratic onset, GI side effects, risk of colonic necrosis
	Gastrointestinal binding	SZC	10 g PO	Onset about 1 h; better tolerated than SPS

GI: Gastrointestinal; D5W: 5% dextrose in water; NS: Normal saline; ICU: Intensive care unit; ECG: Electrocardiogram; CRRT: Continuous renal replacement therapy; SPS: Sodium polystyrene sulfonate; PO: By mouth; PR: Per rectum; SZC: Sodium zirconium cyclosilicate; IV: Intravenous.

Magnesium disorders

Relevance: Hypomagnesemia (Mg²⁺ ≤ 1.7 mg/dL) affects 33.6% of patients with intracerebral hemorrhage on admission and 41.9% of neurosurgical ICU cohorts. In ICH low magnesium correlates with higher ICH scores, increased systolic blood pressure, intraventricular hemorrhage, and lower Glasgow Coma Scale scores[37,38]. Hypermagnesemia (Mg²⁺ > 2.5 mg/dL) occurs in up to 27.6% of neurosurgical ICU admissions[38]. Contrary to general critical-care data in which hypomagnesemia predicts worse morbidity, neurocritical cohorts do not consistently demonstrate associations between magnesium extremes and mortality, modified Rankin Scale outcomes, or ICU length of stay[35,37,38]. This divergence may reflect transient, peri-injury shifts in magnesium homeostasis, or unique neurospecific adaptive mechanisms[37].

Pathophysiology: Magnesium seems to have an important role in vascular tone, neuronal excitability, and cerebral blood flow[30,37]. Hypomagnesemia exacerbates hypertension in ICH leading to arterial tone elevation, potentially driving hematoma expansion. Its association with intraventricular hemorrhage and depressed consciousness positions hypomagnesemia as a biomarker of disease severity rather than a direct outcome determinant[37]. In SAH hypomagnesemia correlates with higher World Federation of Neurological Societies scores and ventricular blood volume although trials of therapeutic magnesium infusions for vasospasm prevention have shown no clear benefit, likely due to non-targeted administration[39,40]. The neuroprotective roles of magnesium are context-dependent with early administration trials demonstrating no stroke outcome improvement[30,40]. Hypermagnesemia, typically from excessive supplementation (e.g., eclampsia protocols), risks hypotension and respiratory depression but appears to be tolerated in mild neurosurgical cases without renal impairment[3,35].

Prevention/targeted management: Symptomatic or severe hypomagnesemia warrants intravenous magnesium sulfate repletion[19,30]. Continuous infusions are used off-label for vasospasm prophylaxis although efficacy remains unproven. Oral repletion is reserved for patients who are stable[19,30]. Concurrent correction of hypokalemia and hypocalcemia is critical due to the role of magnesium in renal potassium retention and parathyroid hormone secretion[30,37]. Hypermagnesemia management includes discontinuing exogenous sources and administering calcium gluconate for cardiac stabilization[30]. Severe hypermagnesemia with renal failure may require loop diuretics or hemodialysis[19,30]. In neurocritical settings protocols must balance the theoretical neuroprotection of magnesium against risks of overcorrection with close monitoring during prolonged infusions. Serial serum magnesium assays are essential, particularly in renal dysfunction or high-dose therapy[19,30] (Table 4).

Table 4 Magnesium disorders correction.

Disorder	Treatment	Dose/route	Notes
Hypomagnesemia	IV magnesium sulfate	1-2 g IV over 1 hour, then 4-8 g IV over 12-24 h; in emergencies (e.g., torsades) 1-2 g IV over 15 min	Use central access for prolonged high-dose infusion; monitor serum Mg 2 h after start of infusion due to renal losses; faster infusion (e.g., in TdP) may be warranted
	Oral magnesium	Magnesium oxide or lactate 300-600 mg (12-25 mmol) PO 2-4 times daily	Use in mild, asymptomatic cases with intact GI tract; bioavailability limited; avoid if significant GI intolerance
Hypermagnesemia	Remove exogenous sources	Discontinue all magnesium-containing meds/infusions	Necessary first step; review all sources (IV fluids, TPN additives, supplements)
	Calcium gluconate	1-2 g IV over 5-10 min	Stabilizes cardiac membrane in severe elevations (> 4 mg/dL) or ECG changes; repeat PRN
	Loop diuretics + IV fluids	Furosemide 20-40 mg IV once, with isotonic saline bolus	Promotes renal Mg excretion; ensure adequate volume status; monitor electrolytes and renal function
	Hemodialysis	Standard-dialyze against low-Mg/zero-Mg bath	Reserved for refractory or life-threatening hypermagnesemia in renal failure

ECG: Electrocardiogram; GI: Gastrointestinal; IV: Intravenous; PO: By mouth; PRN: As needed; TPN: Total parenteral nutrition; TdP: Torsades de Pointes.

Calcium disorders

Relevance: Hypocalcemia (total calcium < 8.5 mg/dL or ionized < 1.15 mmol/L) is prevalent in this population and correlates with adverse outcomes[5,41-43]. In a cohort of patients with SAH, 60.7% presented with hypocalcemia at admission and was associated with higher mortality (40.1% vs 26.7%), poorer functional outcomes (61.7% vs 42.9%), and increased inotropic requirements (33.3% vs 21.9%) compared with patients who were normocalcemic[42]. While hypocalcemia incidence in general ICUs is 20%, neurocritical cohorts demonstrate heightened susceptibility due to associated dysregulation. Hypercalcemia (total calcium > 10.5 mg/dL or ionized 1.28 mmol/L) is rare in this setting with limited characterization; broader critical care etiologies such as malignancy or hyperparathyroidism remain dominant[30,42].

Pathophysiology: Calcium homeostasis is involved in neuronal excitability, coagulation, and cardiovascular stability. Hypocalcemia could exacerbate secondary brain injury in SAH by impairing coagulation, increasing hematoma volume, and acute hydrocephalus risk[5,41-43]. Reduced myocardial calcium availability compromises contractility and is associated with a higher inotrope use while hypocalcemia-induced vascular smooth muscle contraction could elevate systemic blood pressure[42]. Dynamic ionized calcium fluctuations during SAH complications (e.g., vasospasm) independently predict mortality and is linked to neuroinflammatory/oxidative pathways[43]. Hypercalcemia, though rare in ABI, may shorten QT intervals (predisposing to arrhythmias) and induce neuropsychiatric symptoms[30,35]. Both hypocalcemia and hypercalcemia disrupt cerebral autoregulation although direct mechanistic evidence in this population remains limited.

Prevention/targeted management: Hypocalcemia management prioritizes intravenous calcium replacement, calcium gluconate for symptomatic or severe cases (ionized Ca²⁺ < 0.9 mmol/L), and calcium chloride in emergencies[44]. Prophylactic calcium supplementation is advised for patients who are high-risk (e.g., massive transfusion recipients) with continuous infusions for refractory cases[30,44]. Hypercalcemia requires volume resuscitation, loop diuretics in hypervolemia or when hypovolemia has been corrected, and bisphosphonates to inhibit osteoclast activity. Serial ionized calcium monitoring is recommended as corrected calcium formulas lack reliability in critical illness[30,38,44,45].

Chloride disorders

Relevance: Hyperchloremia (Cl^- > 110 mmol/L) is prevalent in this population with the incidence escalating during hospitalization[46,47]. Among patients who were critically ill after experiencing a stroke, the prevalence increased from 8.6% at admission to 17.0% within 72 h, peaking at 22.2% in cohorts[46]. Mortality correlates strongly with severity. Patients with peak Cl^- ≥ 139.7 mmol/L exhibited 90% in-hospital mortality vs 42% in those < 110 mmol/L[47]. In TBI and ICH hypertonic saline administration drives the incidence[48]. Each 5 mmol/L Cl^- increase independently elevates risks of acute kidney injury, in-hospital mortality, and 3-month mortality in patients who experienced stroke[46-48]. Hypochloremia remains understudied, underscoring the dominance of hyperchloremia in chloride-related morbidity[5].

Pathophysiology: Chloride homeostasis is essential for neuronal activity and cerebral edema regulation[35,49]. Dysregulated cation-chloride cotransporters (CCC) elevate intraneuronal Cl^-, converting gamma-aminobutyric acid inhibition to depolarization and hyperexcitability, a mechanism implicated in phenobarbital-resistant neonatal seizures and post-injury epileptogenesis[49]. Cytotoxic edema stems from CCC-mediated Cl^- and water influx during ischemia or trauma, amplified by matrix metalloproteinase-driven extracellular matrix degradation that shifts Cl^- into neurons[50]. Systemically, hyperchloremia reduces the strong ion difference, inducing metabolic acidosis with downstream impairments in myocardial contractility, renal perfusion, and cerebral oxygen delivery[47,48]. These dual neurotoxic and systemic effects establish chloride dysregulation as a central driver of multiorgan dysfunction in this population[5,49].

Prevention/targeted management: Prevention and treatment focus on minimizing chloride load. Balanced crystalloids reduce hyperchloremia risk compared with normal saline (Table 5)[3,47]. In SAH acetate-buffered hypertonic saline mitigates cerebral edema without exacerbating chloride imbalances[47]. Pharmacologically, bumetanide (Cl^- importer inhibitor) lowers intraneuronal Cl^-, restoring gamma-aminobutyric acid inhibition and reducing seizure burden in neonatal and TBI models[49]. Adjunctive matrix metalloproteinase inhibitors may attenuate extracellular Cl^- shifts by preserving sulfated glycosaminoglycans although clinical validation is pending[49]. Serial chloride monitoring during hypertonic saline therapy is critical with protocols advocating chloride-restricted fluids and diuretics for levels ≥ 110 mmol/L[47]. Emerging biomarkers, such as urinary chloride excretion, may refine risk stratification while renal protection strategies mitigate bidirectional Cl^--acute kidney injury interactions[47,48]. Individualized fluid regimens and CCC-targeted therapies represent promising avenues to improve outcomes in chloride-sensitive populations[49].

Table 5 Calcium disorders correction.

Disorder	Medication	Dosing/infusion	Route	Key notes
Hypocalcemia	Calcium gluconate	1-2 g (10-20 mL of 10% solution) over 10-20 min; repeat as needed	IV	Preferred for mild-moderate hypocalcemia; monitor ECG during infusion
	Calcium chloride	1 g (10 mL of 10% solution) over 5-10 minutes	IV (central line preferred)	Reserved for severe/acute hypocalcemia (e.g., tetany, arrhythmias); risk of tissue necrosis if extravasated
	Oral calcium	1-4 g elemental calcium daily (e.g., calcium carbonate 500-1500 mg TID)	PO	For mild/asymptomatic hypocalcemia; combine with vitamin D in chronic cases
	Calcitriol	0.25-2 µg/day	PO/IV	Enhances intestinal calcium absorption; used in chronic hypocalcemia or renal failure
	Magnesium sulfate	1-2 g over 1 h (if hypomagnesemic)	IV	Corrects hypomagnesemia to restore PTH function
Hypercalcemia	Isotonic saline	1-2 L bolus, then 150-300 mL/hour	IV	First-line for volume resuscitation and calciuresis; avoid in heart failure
	Furosemide	20-40 mg every 4-6 h (after rehydration)	IV	Enhances calcium excretion; avoid in hypovolemia
	Zoledronic acid	4 mg over ≥ 15 min	IV	Bisphosphonate for malignancy or severe hypercalcemia; peak effect at 48-72 h
	Pamidronate	60-90 mg over 2-24 h	IV	Alternative bisphosphonate; adjust dose for renal impairment
	Calcitonin	4-8 units/kg every 6-12 h	SC/IM	Rapid calcium reduction (4-6 h); tachyphylaxis limits use to 48 h
	Denosumab	120 mg weekly × 1-3 doses	SC	For refractory hypercalcemia (e.g., malignancy); inhibits RANKL
	Prednisone	20-40 mg/day	PO	For hypercalcemia due to vitamin D toxicity or granulomatous diseases

ECG: Electrocardiogram; IM: Intramuscular; IV: Intravenous; PO: By mouth; PTH: Parathyroid hormone; SC: Subcutaneous; TID: Three times a day; RANKL: Receptor activator of nuclear factor kappa-B ligand.

CONCLUSION

This narrative review synthesized over 60 years of evidence on electrolyte disorders in neurocritical care, emphasizing their pathophysiological complexity and clinical implications. Electrolyte imbalances in this population are not mere biochemical deviations but pivotal drivers of morbidity and mortality, exacerbated by ABI, neuroendocrine dysregulation, and therapeutic interventions. Timely recognition and tailored correction are critical to mitigating secondary neuronal injury and optimizing outcomes.

Existing literature predominantly outlines electrolyte disturbances in general critical care with limited focus on the neurocritical setting where ABI disrupts homeostasis, amplifying vulnerability. Reports illustrating the complexity of managing one or more electrolyte disturbances in patients receiving neurocritical care help elucidate the unique challenges of treatment in this population. For instance a case report demonstrated the diagnostic and therapeutic challenges in a patients receiving neurosurgical care for SAH in which hyponatremia, hypokalemia, and polyuria arose from overlapping salt-wasting nephropathy and primary polydipsia. This report highlighted the critical role of individualized pathophysiology-driven management in complex cases[50,51]. Recent advancements challenge historical correction paradigms, such as rapid sodium normalization improving survival without increasing neurological complications, and reframe hyperchloremia as a modifiable risk factor through targeted therapies. These insights extend beyond neurocritical care. Patients in the cardiac ICU may benefit from strategies to mitigate hyperchloremic acidosis while general ICUs could adopt rapid sodium correction protocols validated in neurological cohorts. Conversely, neurospecific findings, such as the lack of efficacy of magnesium in preventing vasospasm, caution against extrapolating data to non-neurological contexts.

As a narrative synthesis this review prioritized conceptual integration over systematic rigor, which may have introduced selection bias. Key studies were included based on clinical relevance, potentially omitting granular data from narrower populations. Emerging information such as the growing support for faster sodium correction rates in severe dysnatremias, directed interventions (like vaptans for SIADH or acetate-buffered hypertonic saline), the time incidence of potassium disorders in ABI, the research on chloride-directed therapies, the knowledge gap in magnesium impact, and its context-sensitive neuroprotective effects emerged as critical findings of this review.

Future studies should prioritize randomized controlled trials comparing targeted therapies, such as vaptans in SIADH vs volume resuscitation in cerebral salt wasting, using biomarker-stratified designs to address diagnostic uncertainty. Multidisciplinary collaboration (e.g., integrating neurology, nephrology, and bioinformatics) and precision medicine approaches (e.g., dynamic biomarker-guided protocols) are essential to address heterogeneity in neurocritical populations and optimize individualized care pathways.

This article had several limitations. First, as a narrative synthesis potential selection bias and exclusion of non-English studies may have limited comprehensiveness. Second, physiological evidence and rationale often derives from preclinical models, necessitating cautious clinical interpretation. Third, therapeutic recommendations often rely heavily on observational studies, highlighting the need for randomized controlled trials.

Electrolyte management in neurocritical care demands individualized, pathophysiology-driven approaches to reduce morbidity, mortality, and long-term disability while prioritizing patient-centered outcomes such as functional recovery and quality of life. While innovations in monitoring and targeted therapies show promise, gaps in high-quality evidence persist. Future research should prioritize defining optimal correction thresholds that balance efficacy with risk mitigation, validate directed interventions and specific agents, and integrate neuroendocrine assessments into electrolyte protocols. Translational success will hinge on multidisciplinary collaboration to align biomarker-driven precision medicine with patient-centric endpoints, ensuring innovations directly improve survivorship and neurological outcomes in this vulnerable population.