Dear Editor,

Dexamethasone is frequently administered perioperatively for post-operative nausea-vomiting prophylaxis and cerebral edema in neurosurgical cases. Its potent effects include near-total suppression of the hypothalamic-pituitary-adrenal (HPA) axis, regulated by negative feedback. However, the duration of suppression and consequences of short-term exogenous steroid administration remain unclear. Prior research suggests rapid HPA feedback, as administering corticosteroids shortly before exposing individuals to stressors leads to reduced adrenocorticotropic hormone secretion.

A 9-year-old, 20 kg female with a midline posterior fossa lesion was posted for midline sub-occipital craniotomy and lesion decompression [ Figure 1 ]. Her preoperative assessment revealed no congenital abnormalities, allergies, or medical comorbidities. On the morning of surgery (5 am), the child received intravenous (IV) pantoprazole 20 mg and 8 mg dexamethasone per the neurosurgeon’s order. Induction was with weight-appropriate doses of fentanyl, sodium thiopentone, and vecuronium, followed by tracheal intubation.

Figure 1:

A well-defined extra-axial midline posterior fossa lesion along the vermis. The lesion demonstrated (a) hyperintense signal on sagittal T2W imaging, (b) no significant post contrast enhancement on sagittal T1W scan, (c) no hydrocephalus, (d) incomplete suppression of signal on T2-FLAIR sequences, (e) with diffusion restriction on DWI, and (f) low ADC signal. T2W: T2 weighted, T1W: T1 weighted, FLAIR: Fluid-attenuated inversion recovery, DWI: Diffusion-weighted imaging, ADC: Apparent diffusion coefficient.

Post induction (5–6 h after dexamethasone), the child developed resistant hypotension, with blood pressure (BP) dropping from 121/86 mmHg (post-intubation) to 74/40 mmHg, while heart rate (HR) consistently stayed within 10–20% of baseline (90 beats/min) [ Figure 2 ]. With the BP drop exceeding 20% from baseline (ward BP as reference), the child was given 250 mL isotonic saline followed by 3 mg mephentermine boluses. Despite these interventions, no improvement was observed. Until this point, no significant blood loss had occurred, and allergic reactions were ruled out (no rashes, airway pressure changes, capnography alterations, and normal levels of tryptase). Point-of-care testing and arterial blood gas indicated normal hemoglobin and lactate levels. The positive pressure variation was measured which was below 12–13 throughout. Air embolism was also ruled out as hypotension set in before the start of surgery or pinning. A low-dose noradrenaline infusion was initiated to maintain BP within 20% of ward values. As a last resort, IV hydrocortisone 2 mg/kg was administered. Following this, BP improved significantly, and vasopressors could be tapered [ Figure 2 ]. Subsequently, no hypotension was observed during tumor handling. BP remained stable postoperatively till discharge, with normal hemoglobin and hematocrit.

Figure 2:

Intraoperative hemodynamic chart illustrating persistent hypotension followed by blood pressure stabilization on steroid administration (blue arrow represents time point of steroid administration, ARTsys: Systolic arterial blood pressure, HR: Heart rate).

The patient’s resistant hypotension unresponsive to standard fluid and vasopressor administration, led to the administration of a steroid bolus. The prompt response to the exogenous steroid suggests a possible link between the high preoperative dexamethasone dose, suppressing the intact HPA axis, and increased cortisol demand due to surgical stress. Other potential causes of hypotension, including anemia, blood loss, air embolism, fluid depletion, and anaphylaxis, were ruled out.

These findings emphasize that resistant perioperative hypotension can occur not only with chronic steroid use but also after a single high steroid dose. Risk factors for HPA suppression post-steroid administration include cumulative duration of use, long-acting agents, and parenteral administration. Despite dexamethasone’s 4-h elimination half-life, its biologically extended half-life exceeds 36 h[ 1 ], and in severe illness, patients may fail to mount an appropriate cortisol response to stress.[ 6 ] Supporting this hypothesis, a study in adults explored the HPA axis suppression duration post a standard antiemetic dexamethasone dose (4–8 mg) where significant cortisol suppression peaked 24 h later. By the end of 8 h, cortisol levels had decreased to 4.04% of baseline.[ 3 ] Another study reported a 50% reduction in cortisol levels at 2 h and 75% by the end of 4 h with an 8 mg dose.[ 5 ]

The mechanism of glucocorticoid-related HPA suppression has two stages: an early acute phase and a later delayed phase (from inhibition of gene transcription factors). The acute phase starts soon after glucocorticoid administration, while the delayed phase occurs 2–20 hours later, potentially lasting days. This explains why HPA axis suppression can occur after high doses, even with intact negative feedback, and is not entirely uncommon after a single dose.[ 4 ] In pediatric neurosurgery, it is advised to use IV hydrocortisone stress therapy throughout the procedure, regardless of baseline cortisol levels.[ 2 ]

Thus, a single high perioperative steroid dose may lead to HPA axis suppression, causing resistant hypotension in pediatric neurosurgical cases. We hypothesize severe intraoperative hypotension in our case resulted from the large dexamethasone dose, but formal HPA axis testing could not confirm this.

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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.

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References

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2. Claude F, Ubertini G, Szinnai G. Endocrine disorders in children with brain tumors: At diagnosis, after surgery, radiotherapy and chemotherapy. Children (Basel). 2022. 9: 1617

3. Elston MS, Conaglen HM, Hughes C, Tamatea JA, Meyer-Rochow GY, Conaglen JV. Duration of cortisol suppression following a single dose of dexamethasone in healthy volunteers: A randomised double-blind placebo-controlled trial. Anaesth Intensive Care. 2013. 41: 596-601

4. Nicolaides NCPavlaki ANMaria Alexandra MAChrousos GP. Glucocorticoid therapy and adrenal suppression. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279156 [Last accessed on 2024 Apr 01].

5. Shilo S, Rösler A. Single intravenous bolus of dexamethasone for the differential diagnosis of Cushing’s syndrome. J Pediatr Endocrinol Metab. 1995. 8: 27-33

6. Téblick A, Gunst J, Van den Berghe G. Critical illness-induced corticosteroid insufficiency: What it is not and what it could be. J Clin Endocrinol Metab. 2022. 107: 2057-64