Abstract

Background: Diabetes insipidus (DI) is a rare entity in neuroanesthesia, most often encountered in the context of hypothalamic–pituitary surgeries. Its occurrence during the intraoperative period, outside of any manipulation of this region, is exceptional and may delay diagnosis.

Case Description: We report the case of a 54-year-old female patient who underwent surgery for a cerebellopontine angle schwannoma and developed signs of DI early during the intraoperative period, even before any surgical incision. No usual contributing factors were identified. The favorable outcome following cessation of propofol infusion suggests a probable role of this agent in the development of this disorder.

Conclusion: This case illustrates an atypical but important complication to be aware of in anesthesia. The sudden onset of polyuria during surgery, even outside of hypothalamic–pituitary procedures, should prompt consideration of DI, especially in the presence of potentially triggering pharmacological agents.

Keywords: Diabetes insipidus, Neurosurgery, Polyuria, Propofol

INTRODUCTION

Diabetes insipidus (DI) is a water balance disorder characterized by the kidneys’ inability to concentrate urine, leading to polyuria (>40 mL/kg/24 h in adults) and plasma hyperosmolality. DI may be of central origin, due to a deficiency in vasopressin secretion, or nephrogenic, resulting from impaired renal responsiveness to the hormone. The distinction is classically based on the response to a desmopressin test: A marked improvement in urine output and concentration suggests a central form, whereas an incomplete response points toward peripheral resistance.

Commonly reported causes include hypothalamic–pituitary surgeries or trauma, certain endocrine disorders, and the use of mannitol or other hyperosmolar agents. In the intraoperative setting, DI is a rare event, yet its occurrence can acutely disrupt fluid and electrolyte homeostasis.

We report here a case of intraoperative DI most likely attributed to the administration of propofol, occurring prior to any direct neurosurgical manipulation. This case raises several questions regarding the role of propofol in vasopressin regulation and highlights the need for appropriate anesthetic management.

CASE PRESENTATION

We report the case of a 54-year-old female patient with a history of ovarian cancer, treated with total hysterectomy, bilateral salpingo-oophorectomy, and para-aortic lymph node dissection. She was scheduled for resection of a cerebellopontine angle tumor, suspected to be an acoustic schwannoma.

Clinically, she presented with signs of intracranial hypertension, a peripheral vestibular syndrome on the side of the lesion, and ipsilateral sensorineural hearing loss. There was no reported history of polyuria–polydipsia syndrome.

The diagnosis was supported by brain magnetic resonance imaging, which revealed a well-defined, ovoid extra-axial mass in the right cerebellopontine angle, measuring 40 × 28 × 31 mm. The lesion exerted a mass effect on the pons, the right superior and middle cerebellar peduncles, and the adjacent cerebellar parenchyma, which was displaced but not infiltrated. There was no evidence of intra-cochlear or intravestibular involvement, nor any abnormal signal or contrast enhancement within the cerebellar parenchyma [ Figure 1 ].

Figure 1:

Brain magnetic resonance imaging coronal T1-weighted images with contrast enhancement.

In the operating room, the patient was placed on a surgical table, monitored by five-lead electrocardiography, heart rate, respiratory rate, pulsed oxygen saturation, and non-invasive blood pressure. A peripheral venous catheter is placed in the upper limb. General anesthesia was chosen as the main anesthetic technique. After verifying the vital constants of the patient, anesthetic induction was performed using remifentanil (1 µg/kg over 2 min), propofol (3 mg/kg), and cisatracurium (0.15 mg/kg). After intubation, mechanical ventilation was adjusted to have the end-tidal carbon dioxide between 30 and 35 mmHg. An ultrasound-guided central venous catheter in the supraclavicular area, a radial arterial catheter (monitoring invasive blood pressure), a thermal probe, and a bladder catheter were placed. Anesthesia was maintained using: Propofol (6 mg/kg/h), remifentanil (0.1–0.5 µg/kg/min), and cisatracurium (0.12 mg/kg/h). We then monitored the depth of anesthesia using bispectral index. The patient was positioned in the left lateral decubitus position. Shortly after surgical positioning, and even before any incision was made, significant polyuria was observed, reaching 4 mL/kg/h. The urine was clear [ Figure 2 ], with a urine specific gravity (USG) of 1.005. Laboratory tests revealed a serum sodium level of 146 mmol/L, potassium at 4 mmol/L, chloride at 105 mmol/L, blood glucose at 7 mmol/L, and plasma osmolality of 300 mOsm/L. No hyperosmolar agents (such as hypertonic saline solution or mannitol) had been administered, and neither diuretic use nor hyperglycemia was a contributing factor.

Figure 2:

Appearance of the urine collected before desmopressin administration.

DI was suspected. In the absence of an obvious cause, symptomatic treatment was initiated with sublingual administration of 120 µg of desmopressin and hydroelectrolytic compensation with 4.5% saline solution. A moderate decrease in urine output to 3 mL/kg/h was noted, without improvement in USG, prompting the administration of a second identical dose of desmopressin.

The surgery lasted 7 h without further incident. At the end of the procedure, urine output remained at 3 mL/kg/h, with a serum sodium level of 142 mmol/L, potassium at 3.5 mmol/L, and chloride at 108 mmol/L. The partial response to desmopressin suggested a possible nephrogenic origin of the DI. The patient was transferred to the postoperative neurocritical care unit and was extubated after 2 h. The same hydroelectrolytic measures were continued. A gradual normalization of urine output was observed within 24 h.

A comprehensive evaluation of pituitary function was conducted postoperatively. The hormonal assessment revealed no abnormalities in the anterior pituitary axes, and no signs of chronic or structural pituitary dysfunction were identified. The transient nature of the symptoms and the absence of recurrence following the discontinuation of propofol, without further need for desmopressin, support the hypothesis of a functional and reversible form of DI rather than a lesion-induced deficiency of vasopressin secretion.

DISCUSSION

The diagnosis of DI was made based on the combination of sudden intraoperative polyuria, hypotonic urine (USG 1005), and plasma osmolality of 300 mOsm/L. Usual causes of intraoperative polyuria (hyperglycemia, diuretics, and hyperosmolar agents such as mannitol or hypertonic saline solution) were ruled out. The occurrence of this condition in a surgical context where the hypothalamus was not manipulated suggests a non-lesional origin. The early onset, preceding any surgical stimulation, points toward a pharmacological cause.

The involvement of propofol, used both for induction and maintenance, was considered. Several clinical observations have suggested a link between propofol and the occurrence of transient DI, whether central[ 1 , 2 , 4 ] or peripheral.[ 5 ] In central forms, propofol may inhibit the release of vasopressin from the magnocellular neurons in the hypothalamus. A potential action on gamma aminobytyric acid (GABA) circuits regulating the supraoptic nucleus, through potentiation of GABA-A, has been proposed as a plausible mechanism.[ 2 , 4 ] In fact, in the hypothalamus, the magnocellular neurons of the supraoptic nucleus (SON) are responsible for the synthesis and release of vasopressin (antidiuretic hormone, ADH). These neurons are tightly regulated by a network of local interneurons, among which GABAergic (gamma-aminobutyric acid-releasing) neurons play a key inhibitory role. GABA acts predominantly via GABA-A receptors, which are ligand-gated chloride channels. When activated, these receptors induce hyperpolarization of the magnocellular neurons, thereby decreasing their firing rate and suppressing vasopressin release.

Propofol is known to potentiate GABA-A receptor-mediated transmission, thereby enhancing the inhibitory GABAergic tone within the SON. This potentiation leads to a transient decrease in the excitability of vasopressin-secreting neurons, resulting in reduced ADH release. This effect is reversible upon discontinuation of the anesthetic agent, which explains the transient nature of the central diabetes insipidus observed in some cases.

Furthermore, the anesthetic agents used in this case, including opioids, neuromuscular blockers, antibiotics, and halogenated agents, are routinely administered in other surgical procedures performed in our institution, such as abdominal and orthopedic surgeries, without any reported cases of intraoperative DI. The main distinguishing feature in the anesthetic protocol for this neurosurgical procedure was the use of propofol for maintenance, whereas sevoflurane is typically used in other surgeries. This observation, while not establishing causality, strengthens the hypothesis of a potential role of propofol in the development of transient DI in our patient.

In our case, in the absence of a significant correction of diuresis despite two doses of desmopressin, the hypothesis of nephrogenic DI was considered. It is well known that vasopressin exerts its antidiuretic effect by binding to the V2 receptor on the principal cells of the collecting duct, inducing the insertion of aquaporin-2 (AQP2) into the apical membrane.[ 3 ] Impairment of this mechanism can lead to resistance to vasopressin, clinically manifested as an incomplete response to desmopressin, as observed with our patient.

Van Decar et al.[ 5 ] described similar cases of intraoperative DI with partial or absent response to desmopressin, suggesting a direct toxic effect of propofol on vasopressin intracellular signaling pathways or AQP2. These observations support the idea of a transient pharmacological mechanism, without lasting structural damage.

In the series by Soo et al.,[ 4 ] spontaneous normalization of diuresis was observed after cessation of propofol, without the need for prolonged treatment. Our observation confirms this transient nature: urine output gradually normalized over the first 24 postoperative hours, reinforcing the triggering role of propofol.

The management of intraoperative DI relies on two main approaches: Correcting the functional vasopressin deficiency using desmopressin and replacing fluid losses to prevent hydropyelectrolytic disturbances. In our case, the sublingual administration of two doses of desmopressin (120 µg each) led to a partial reduction in urine output. The persistence of high urinary flow, with a constant specific gravity of 1005, suggests only a partial response. This situation required fluid replacement with 4.5% isotonic saline to prevent hypernatremia and hypovolemia.

Although confirmatory testing or animal experiments were not performed in this case, the hypothesis linking propofol to transient DI is supported by temporal associations and previous clinical observations. Animal models or experimental studies would be valuable to confirm the pathophysiological mechanisms involved. The absence of structural abnormalities in the hypothalamic-pituitary region, alongside a rapid resolution of symptoms upon discontinuation of propofol, strengthens the likelihood of a functional, transient mechanism rather than a chronic or structural pituitary pathology.

To conclude, although a causal relationship cannot be definitively established, the temporal association observed in our case, combined with previously reported similar observations, suggests that propofol may play a role in triggering DI in susceptible individuals.

CONCLUSION

Intraoperative DI is a rare but potentially serious complication, and its prompt recognition is essential to avoid severe hydro-electrolytic imbalances. This case illustrates a probable link between propofol and a transient inhibition of the vasopressinergic axis, involving both central and peripheral mechanisms. Particular vigilance is warranted during surgery in the presence of unexplained polyuria. Further studies are needed to understand better the interactions between anesthetic agents and water balance regulation, and to refine prevention and treatment strategies for this atypical complication.

Ethical approval:

Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

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3. Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: From molecules to medicine. Physiol Rev. 2002. 82: 205-44

4. Soo J, Gray J, Manecke G. Propofol and diabetes insipidus. J Clin Anesth. 2014. 26: 679-83

5. Van Decar LM, Reynolds EG, Sharpe EE, Harbell MW, Kosiorek HE, Kraus MB. Perioperative diabetes insipidus caused by anesthetic medications: A review of the literature. Anesth Analg. 2022. 134: 82-9