Opioid-free, multimodal neuroanaesthesia using ketamine–lignocaine–dexmedetomidine in a patient with pituitary macroadenoma and endocrine dysfunction

Dear Editor,

Compression of normal pituitary tissue by large adenomas may result in partial or complete panhypopituitarism, with dysfunction of the hypothalamic–pituitary–thyroid axis significantly influencing perioperative stress responses and haemodynamic stability.[1] Uncontrolled hypothyroidism further increases anaesthetic risk by reducing cardiac output, impairing ventilatory drive, altering drug metabolism, and increasing sensitivity to sedatives and opioids. These effects assume particular relevance in neurosurgical patients, where maintenance of cerebral perfusion, haemodynamic stability, and early post-operative neurological assessment are essential.[2]

Opioid-free anaesthesia (OFA) has emerged as an alternative strategy to mitigate opioid-related adverse effects such as respiratory depression, delayed emergence, and post-operative nausea and vomiting. The ketamine–lignocaine–dexmedetomidine (KeLiDex) combination provides effective multimodal analgesia, anaesthetic-sparing effects, and haemodynamic stability while preserving respiratory function.[3] We report the successful use of a KeLiDex-based OFA technique in a patient with pituitary macroadenoma, partial hypopituitarism, and uncontrolled hypothyroidism undergoing transnasal transsphenoidal excision.

A 63-year-old male patient (weight 50 kg) presented with headache, progressive blurring of vision, and vomiting for one and a half months. He was a recently diagnosed hypertensive on regular medication with adequate blood pressure control. Imaging revealed a pituitary macroadenoma measuring 3.5 × 3.1 × 2.8 cm involving the sellar and suprasellar regions, with bilateral encasement of the internal carotid arteries and associated partial hypopituitarism [Figure 1]. The patient was receiving oral thyroxine 75 μg once daily and hydrocortisone 15 mg twice daily for the past 6 days. Relevant laboratory parameters are summarised in Table 1. The parameters were consistent with partial hypopituitarism. In view of uncontrolled hypothyroidism and the associated neuroendocrine risk, an OFA technique was planned.

Figure 1.

Sagittal T1-weighted magnetic resonance imaging (MRI) of the brain demonstrating a well-defined sellar–suprasellar lesion causing elevation of the optic chiasm

Table 1.

Summary of pre-operative endocrine evaluation

Parameters		Value		Reference range
Serum cortisol		2.03 µg/dL		6.02-18.4 µg/dL
TSH		25.12 microIU/mL		0.27-4.20 micro IU/mL
Total T3		1.15 ng/mL		0.80-2.00 ng/mL
Total T4		3.97 µg/dL		5.10-14.10 µg/dL
LH		1.62 mIU/mL		1.70-8 mIU/mL
FSH		3.61 mIU/mL		1.5-12.4 mIU/mL
Prolactin		37.92 ng/mL		4.6-21.4 ng/mL
IGF1		19 ng/mL		75-212 ng/mL

TSH: Thyroid stimulating hormone; T3: Triiodothyronine; T4: Thyroxine; FSH: Follicle stimulating hormone; LH: Luteinising hormone; IGF1: Insulin-like growth factor1

Standard American Society of Anesthesiologists monitoring was instituted. A KeLiDex bolus comprising ketamine 0.5 mg/kg, lignocaine 1.5 mg/kg, and dexmedetomidine 1 μg/kg was administered intravenously over 10 minutes. Anaesthesia was induced with propofol 50 mg and vecuronium 5 mg, followed by tracheal intubation using an 8.0-mm cuffed endotracheal tube. Anaesthesia was maintained with a continuous KeLiDex infusion (ketamine 0.5 mg/kg/h, lignocaine 0.5 mg/kg/h, and dexmedetomidine 0.5 μg/kg/h), prepared in a single syringe, along with an oxygen–air mixture with a fraction of inspired oxygen of 0.5. Multimodal analgesia was supplemented with ultrasound-guided right femoral nerve (10 mL of 0.25% bupivacaine) and lateral femoral cutaneous nerve block (5 mL of 0.25% bupivacaine) for fascia lata graft harvest, and bilateral infraorbital nerve blocks for nasal and midfacial analgesia using bupivacaine 0.25% 2.5 mL on each side post-induction.

Intra-operative haemodynamics remained stable throughout the 3-hour procedure. The KeLiDex infusion was discontinued 10 minutes before skin closure. The total dose of ketamine, lignocaine, and dexmedetomidine administered throughout the case was 100 mg, 150 mg, and 125 µg, respectively. The patient regained consciousness within 15–20 minutes and was extubated uneventfully in the operating theatre. The Glasgow Coma Scale score in the post-extubation period was E4V5M6. The patient did not develop any post-operative delirium. The modified Brice questionnaire, administered at 30 minutes and again at 24 hours post-extubation, revealed no evidence of intra-operative awareness or recall. The patient was transferred to the intensive care unit for overnight observation.

Pituitary macroadenomas commonly present with mass effect and visual disturbances, and trans nasal trans sphenoidal (TNTS) surgery has evolved as the standard minimally invasive approach. From a neuroanaesthesia perspective, panhypopituitarism presents significant perioperative challenges due to impaired stress hormone responses and altered cardiovascular physiology. Cortisol deficiency predisposes patients to hypotension and reduced responsiveness to catecholamines, while thyroid hormone deficiency further compromises cardiovascular function, ventilatory drive, and drug pharmacokinetics, potentially delaying emergence.[4] These endocrine derangements necessitate meticulous perioperative planning and judicious anaesthetic drug selection.

In this context, OFA offers distinct advantages by avoiding opioid-induced respiratory depression and delayed emergence, thereby facilitating early neurological assessment following TNTS surgery. The KeLiDex combination provides balanced hypnosis, analgesia, and sympatholysis while maintaining stable cerebral and systemic haemodynamics. As adrenaline-soaked nasal pledgets are routinely used during TNTS surgery, the ketamine bolus dose was deliberately reduced to mitigate exaggerated sympathetic responses due to systemic adrenaline absorption.

Bispectral index monitoring was not employed in the present case because neuronavigation was performed during the initial phase, which made its application technically challenging. However, post-operative assessment using the modified Brice questionnaire suggested no recall of intra-operative events. The role of OFA and green anaesthesia in neurosurgery remains underexplored; however, multimodal, opioid-sparing strategies such as KeLiDex-based techniques appear promising in reducing opioid-related adverse effects, facilitating early neurological evaluation, and minimising environmental impact. This case adds to the growing body of evidence supporting the feasibility of OFA in carefully selected neurosurgical patients.

Disclosure of use of artificial intelligence (AI)-assistive or generative tools

These tools were not used.

Author contributions

GS, SKS, SB: Concept and design; GS, SS: Acquisition, analysis, interpretation of data; GS, SB, SS: Drafting of the manuscript; GS, SKS: Critical review of the manuscript for important intellectual content; SKS: Overall supervision.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.