Improvement in post-hemispherotomy cerebral salt-wasting syndrome following intubation: A case report

Abstract

Cerebral salt-wasting syndrome (CSWS) is characterized by renal sodium loss following intracranial disorders, leading to hyponatremia, reduced extracellular volume, and dehydration. The mechanisms underlying CSWS remain unclear. To date, no reports have described the coexistence of arginine vasopressin deficiency (AVPD), also known as central diabetes insipidus (cDI), and CSWS following hemispherotomy. We report a case of cDI and CSWS occurring after hemispherotomy, in which CSWS improved following intubation. A 7-month-old girl with right hemimegalencephaly and cortical dysplasia underwent hemispherotomy. On postoperative day (POD) 1, AVPD was diagnosed and treated with intravenous AVP. By POD 3, she developed CSWS, characterized by increased urinary sodium excretion, decreased serum sodium levels, dehydration, polyuria, and negative fluid balance. Notably, CSWS improved markedly after intubation on POD 5. However, within one day of extubation, CSWS recurred on POD 8. Her condition gradually improved between POD 8 and POD 14. She is currently clinically stable, with her AVPD well-controlled. Conclusion: AVPD and CSWS can co-occur after hemispherotomy, even without hypothalamic-pituitary involvement. The improvement and recurrence of CSWS associated with intubation and extubation suggest that positive end-expiratory pressure may represent a novel therapeutic strategy for CSWS.

Highlights

● First report of CSWS recurrence triggered by extubation after hemispherotomy.

● Intubation with PEEP contributed to improvement of severe CSWS.

● Coexistence of CSWS and AVPD may complicate perioperative management.

Introduction

Cerebral salt-wasting syndrome (CSWS) is an electrolyte imbalance characterized by renal sodium loss, leading to hyponatremia and hypovolemia. CSWS typically occurs within the first week after subarachnoid hemorrhage, trauma, or brain surgery and improves gradually after 3–4 wk (1,2,3).

The pathophysiological mechanisms underlying CSWS remain unclear. CSWS-induced hyponatremia results from excessive renal sodium loss and is accompanied by dehydration. The hypersecretion of brain and atrial natriuretic peptides (BNP and ANP, respectively), which are key markers in the laboratory diagnosis of CSWS, may contribute to decreased aldosterone levels and consequent renal sodium loss (4, 5). ANP and BNP are endogenous peptides activated in response to atrial and ventricular volume or pressure expansion. ANP is secreted by the atria, while BNP originates from the ventricles; both promote vasodilation and natriuresis. Their hemodynamic effects are mediated through reductions in cardiac preload and afterload, leading to decreased ventricular filling pressures.

Functional hemispherotomy is a surgical procedure designed to disconnect the outer cortex of one cerebral hemisphere from the opposite hemisphere and brainstem. The goal is to isolate abnormal brain activity in one hemisphere in order to control severe seizures (6). Known reversible complications include bleeding, fever, infection, ipsilateral vascular ischemia, and incomplete transection of neural pathways (7). Arginine vasopressin deficiency (AVPD), also known as central diabetes insipidus, is a rare complication of hemispherotomy (6, 8, 9).

Here, we report a rare case of CSWS occurring with AVPD after functional hemispherotomy for hemimegalencephaly and discuss the possible effect of intubation on CSWS.

Case Report

A 7-mo-old girl with right hemimegalencephaly and cortical dysplasia (Figs. 1A, B) was admitted for vertical parasagittal hemispherotomy (Figs. 1C, D). At birth, she required therapeutic hypothermia for severe neonatal asphyxia and developed generalized tonic-clonic seizures during rewarming. Subsequently, multiple anticonvulsants were administered but were ineffective. Hemispherectomy was therefore planned at 7 mo of age.

Fig. 1.

Magnetic resonance imaging (MRI) scans of the brain. Contrast-enhanced T1- and T2-weighted MRI scans were obtained preoperatively at (A) 11 d of age and (B) at 6 mo of age B, and (C, D) postoperatively at 1 mo.

On postoperative day (POD) 1, she presented with polyuria of 3,407 mL/m², a plasma sodium level of 165 mEq/L, calculated plasma osmolality of 349.3 mOsm/kg, and urine osmolality of 86 mOsm/kg. Based on these findings, AVPD was diagnosed, and intravenous arginine vasopressin (AVP) therapy (0.1 mIU/kg/h) was initiated 19 hours after surgery, with good response. On POD 2, she was extubated due to stable respiratory status, and her plasma sodium level remained at 150 mEq/L. On POD 3, the patient’s urine volume increased from 1,180 mL/m² to 4,000 mL/m². Her urine sodium concentration rose from 24 mEq/L to 245 mEq/L, while her plasma sodium level declined from 150 mEq/L to 125 mEq/L. At this time, her serum creatinine was 0.2 mg/dL, and the estimated glomerular filtration rate (eGFR), calculated using the modified Schwartz formula, was 141.8 mL/min/1.73 m², indicating preserved renal function. A weight loss of 135 g (1.5% of body weight) was noted from POD 3 to POD 4. She was diagnosed with CSWS based on renal sodium loss, resulting in hyponatremia, dehydration, increased urine output, and negative fluid balance. A central nervous system infection was considered unlikely because the patient remained afebrile and her C-reactive protein value was low (0.2–0.7 mg/dL); thererfore, no cerebrospinal fluid examination or imaging study was performed. Her hyponatremia did not respond to AVP treatment (maximum dose 0.28 mIU/kg/h), and her plasma sodium level dropped as low as 119 mEq/L despite administration of 10% hypertonic saline (Fig. 2a). During this hyponatremic episode, simultaneous polyuria and negative fluid balance were observed, indicating that neither excessive desmopressin administration nor syndrome of inappropriate antidiuretic hormone secretion (SIADH) was responsible.

Fig. 2.

Serum sodium levels, urine sodium levels, and the dosage of arginine vasopressin (AVP) treatment over time. On postoperative (POD) 1, arginine vasopressin deficiency (AVPD) was diagnosed, therefore AVP therapy (0.1 mIU/kg/h) was initiated. The maximum dosage of intravenous AVP therapy was 0.5 mIU/kg/h on POD 9, and the minimum was 0.05 mIU/kg/h on POD 6. A: On POD 2, the patient was extubated. Within one day after extubation, cerebral salt-wasting syndrome (CSWS) was diagnosed. Her hyponatremia did not respond to AVP treatment; therefore the dosage of AVP was increased from 0.1 mIU/kg/h to 0.28 mIU/kg/h. B: On POD 5, CSWS significantly improved following intubation. The dosage of AVP was gradually reduced from 0.28 mIU/kg/h to 0.05 mIU/kg/h. C: On POD 7, she was extubated again. Within one day after extubation, CSWS recurred on POD 8. The dosage of AVP was increased from 0.05 mIU/kg/h to 0.5 mIU/kg/h. D: CSWS gradually improved between POD 8 and POD 14 without positive end-expiratory pressure treatment. The dosage of AVP was reduced from 0.5 mIU/kg/h to 0.2 mIU/kg/h. POD, postoperative day; AVPD, central diabetes insipidus; CSWS, cerebral salt-wasting syndrome; PNa, plasma sodium concentration; DI, diabetes insipidus; UNa, urine sodium concentration.

On POD 5, she was transferred to the pediatric intensive care unit in our hospital following re-intubation to secure her airway. Cerebral computed tomography revealed no significant changes. Although the same sodium load and infusion volume were maintained, her urine volume began to decrease markedly within 3 hours of intubation, and her urine sodium concentration dropped from 257 mEq/L to below 10 mEq/L. This change was interpreted as an improvement in CSWS. The AVP dosage was gradually reduced from 0.28 to 0.1 mIU/kg/h, and hypertonic saline administration was discontinued 9 hours after transfer. On POD 7, her condition remained stable, and she was extubated, while treatment for AVPD was continued (Fig. 2b). Plasma renin activity and the aldosterone were measured to assess her volume status. On POD 7, during a stable, post-extubation period, the values were normal (renin: 0.7 ng/mL/h; aldosterone: 67.5 ng/dL), indicating the absence of hypovolemia. On POD 8, 24 h after extubation, the patient’s urine volume began to increase again, despite an increase in the AVP dosage from 0.1 to 0.5 mIU/kg/h. By POD 9 (48 h after extubation), her serum sodium level had decreased from 141 to 121 mEq/L, and her urine sodium level had increased from < 10 mEq/L to 236 mEq/L. She also exhibited a negative fluid balance, with weight loss of 108 g (1.1% body weight) per day. Therefore, the recurrence of CSWS was diagnosed (Fig. 2c). During this period, serum human atrial natriuretic peptide (HANP) and NT-proBNP levels were elevated (HANP; 714 pg/mL, NT-proBNP; 1030 pg/mL). Ten percent hypertonic saline was administered from POD10. On POD 12, following the CSWS recurrence and re-intubation, her plasma renin activity and aldosterone increased markedly (renin: 23 ng/mL/h; aldosterone: 2020 ng/dL), indicating significant hypovolemia and further corroborating the diagnosis of CSWS. Mechanical ventilation was begun using the synchronized intermittent mandatory ventilation with pressure support (SIMV + PS) mode with PEEP 5 cmH₂O. Following re-intubation, her serum sodium gradually normalized. As the sodium concentration improved, the hypertonic saline and AVP dose were gradually decreased from POD 14 (Fig. 2D). This clinical course was interpreted as CSWS improvement. On POD 20, the intravenous AVP was replaced with 27 µg/d oral desmopressin acetate. The patient is now clinically well, with her AVPD under control. Nine months after the surgery, the hyperintensity of the posterior pituitary gland was detectable on a T1-weighted image on magnetic resonance imaging, suggesting that her AVPD may have been transient.

Statement of ethics

We state that the subject and his parents have given their written informed consent to publish their case, in accordance with the Declaration of Helsinki.

Discussion

Herein, we described the clinical course of a patient with a rare combination of AVPD and CSWS; to the best of our knowledge, this combination has not previously been reported following hemispherotomy. In the present case, CSWS developed twice during the treatment of AVPD and significantly improved following intubation. In contrast, CSWS gradually worsened after extubation.

The reason for significant improvement in CSWS immediately following intubation remains unclear. The precise pathophysiology of CSWS is still not fully understood; however, increased activation of natriuretic factors, such as ANP and BNP, may play an important role (5, 10, 11). In our case, plasma renin activity and aldosterone were normal on POD 7, when CSWS improved during intubation with PEEP. In contrast, both hormones were markedly elevated on POD 12 following extubation and the CSWS recurrence. This pattern corresponded to the physiological distinction between the improvement phase of CSWS during intubation with PEEP and the recurrence phase following extubation. Recent reviews have also emphasized the importance of distinguishing CSWS from SIADH, especially in the context of severe brain injury, where the two conditions may present with similar clinical features (12).

Mechanical ventilation with PEEP induces hemodynamic changes, including decreased venous return, increased right ventricular pressure, and decreased left ventricular filling volume. Shirakami et al. (13) reported that mechanical ventilation with PEEP resulted in decreased plasma ANP and BNP levels. PEEP, a common component of mechanical ventilation, prevents alveolar collapse at the end of expiration and improves oxygenation. It also influences hemodynamics by reducing venous return and modifying atrial wall stretch, potentially altering the secretion of natriuretic peptides. Although primarily used for respiratory support, the impact of PEEP on fluid and electrolyte balance, particularly through suppression of ANP and BNP secretion, warrants further investigation in neurosurgical and endocrine contexts. It is possible that decreased ANP and BNP secretion following intubation contributed to the improvement of CSWS. In contrast, extubation has been shown to increase plasma ANP and BNP levels (4, 13), which may exacerbate or trigger CSWS, as observed in our patient. Although ANP and BNP were not measured immediately before or after the start of mechanical ventilation, their level increased during the CSWS recurrence on POD 9 following extubation. Specifically, the patient’s serum HANP and NT-proBNP were markedly elevated (HANP: 714 pg/mL; NT-proBNP: 1030 pg/mL), thus supporting the hypothesis that natriuretic peptide activation may have contributed to the CSWS recurrence. These findings highlight the potential role of natriuretic peptides in the pathophysiology of CSWS and underscore the need for serial hormonal assessments in future cases. Indeed, elevated BNP levels have been associated with brain injury and postoperative hyponatremia and may serve as useful markers for distinguishing CSWS from SIADH, particularly in neurosurgical patients (5).

AVPD after surgery, typically associated with hypothalamic-pituitary lesions, generally occurs within 24–48 h postoperatively and may develop as early as several hours after brain surgery (14,15,16). In our patient, AVPD developed within several hours of surgery. This type of surgery-related AVPD can be transient or permanent (9). The pathophysiology is presumed to involve direct or indirect partial destruction of the hypothalamus during surgical manipulation, disruption of its blood supply, or hypothalamic dysfunction resulting from increased intracranial pressure, edema, or vasospasm (17, 18). Although a phase of SIADH may follow the initial AVPD phase after surgery (19, 20), our patient did not develop SIADH but instead developed CSWS.

In our case, increasing the dose of l-deamino-8- D-arginine vasopressin (DDAVP) did not improve serum sodium level during the CSWS phase. Sodium is passively reabsorbed in the proximal convoluted tubules (responsible for 60–70% of filtered water reabsorption), via osmotic gradients created by active sodium and chloride transport. Although final urine volume is regulated by AVP acting on the collecting ducts, only 4–10% of filtered water is reabsorbed at this site. In CSWS, impaired sodium and water reabsorption is believed to occur at the proximal tubules, which is the primary site of reabsorption. Therefore, as expected, the main pathophysiology during the CSWS period in this case was not improved by DDAVP.

To the best of our knowledge, this is the first report of CSWS development in a patient with AVPD after hemispherotomy. CSWS development in patients with AVPD is rare and has been described in only a few pediatric cases (2, 21). Two recent reviews on CSWS with AVPD identified central nervous system infection as the most common underlying cause, accounting for 35–44% of cases, followed by hypoxic-ischemic events, head injury, and spontaneous intracranial hemorrhage (2, 21). In addition, simultaneous occurrence of AVPD and CSWS has only rarely been described following neurosurgery for brain tumors (14, 22). Depending on the timing of each condition, serum sodium levels may appear normal, leading to delayed diagnosis. CSWS associated with brain injury has been increasingly described in recent literature, with case-based reviews emphasizing its diagnostic complexity and the need for early intervention (12). Indeed, CSWS in patients with AVPD has also been associated with a high mortality rate (2, 16, 21).

In conclusion, intubation and extubation may have contributed to the improvement and recurrence of CSWS in our case, respectively. These findings suggest that respiratory support with PEEP may represent a novel therapeutic strategy for managing CSWS. Further prospective studies are warranted to clarify the precise role of PEEP in modulating natriuretic peptide levels and improving sodium balance in patients with CSWS.

Conflict of interests

The authors have no conflicts of interest to declare.