Case Summary

A 59-year-old male sustained a nasal bone fracture when an axe accidentally struck the nasal bridge. He was scheduled to undergo nasal bone reduction and fixation under general anesthesia. The anesthetic plan was designed with a multimodal approach, integrating agents with well-defined molecular pharmacology and ensuring meticulous airway protection.

Yilmaz and colleagues emphasize that safe anesthetic management of nasal fractures requires balancing airway strategy with hemodynamic stability and inflammation control (1).

Drugs Administered and Molecular Mechanisms

Premedication with glycopyrrolate (0.2 mg IV) provided antisialagogue effects by antagonizing muscarinic M1 and M3 receptors, thereby inhibiting the Gq-mediated IP3/DAG pathway and reducing glandular secretions (2). Midazolam (1 mg IV) was administered for anxiolysis and sedation through its action as a positive allosteric modulator of GABA-A receptors, enhancing chloride influx and promoting neuronal hyperpolarization (3).

Analgesia was achieved with fentanyl (100 mcg IV), a potent μ-opioid receptor agonist that activates Gi proteins, leading to reduced cAMP, inhibition of calcium influx, and promotion of potassium efflux, thereby suppressing nociceptive transmission (4). Dexamethasone (8 mg IV) was included for its anti-inflammatory effect via glucocorticoid receptor activation, nuclear translocation, and upregulation of anti-inflammatory proteins such as annexin-1, alongside suppression of pro-inflammatory cytokines (5).

Induction was achieved with propofol (150 mg IV), which enhances chloride channel opening at GABA-A receptors while also suppressing NMDA receptor currents, producing hypnosis and amnesia (6). Neuromuscular blockade was provided with atracurium (40 mg IV), a non-depolarizing nicotinic receptor antagonist that prevents acetylcholine-induced endplate depolarization, undergoing metabolism via Hofmann elimination, making it independent of renal or hepatic clearance (7).

Adjunctive sedation and sympatholysis were achieved with dexmedetomidine (30 mcg IV), an α2-adrenoceptor agonist that inhibits norepinephrine release from the locus coeruleus through Gi-mediated signaling (8). Magnesium sulfate (1 g IV) provided additional analgesic benefit by non-competitively antagonizing NMDA receptors and limiting central sensitization through blockade of calcium entry via voltage-gated channels (9). Postoperative analgesia was supported with paracetamol (1 g IV), a weak CNS COX-2 inhibitor that reduces PGE2 synthesis (10), and diclofenac (100 mg PR), a non-selective COX inhibitor that suppresses prostaglandin-mediated pain and inflammation (11).

Airway Strategy

Nasal intubation was avoided because of the risk of cribriform plate fracture and potential intracranial passage of the tube. On a molecular level, manipulation of the traumatized nasal mucosa could expose submucosa and activate platelet aggregation through collagen–GPVI interactions, promoting thromboxane A2 and thrombin generation. Additionally, the nasal mucosa exhibits vascular fragility due to high vascular endothelial growth factor (VEGF) receptor expression (12).

Oral intubation was chosen instead, with the tube secured at the left angle of the mouth to allow surgical access. This positioning minimized pressure-induced ischemia and avoided mast cell activation that could trigger local inflammation.

Intraoperative Molecular Physiology

Pain transmission from the nasal mucosa is carried via the ophthalmic and maxillary branches of the trigeminal nerve (cranial nerve V). Nociception was modulated at multiple levels: fentanyl inhibited presynaptic calcium entry in the dorsal horn, dexmedetomidine reduced norepinephrine-mediated arousal through the locus coeruleus, magnesium blocked NMDA-mediated central sensitization, and both propofol and midazolam enhanced GABA-A receptor activity within the ascending reticular activating system, providing sedation and hypnosis (13).

Extubation Strategy

Extubation was planned only when the patient was fully awake to mitigate the risks of sympathetic surge and airway compromise. Emergence is associated with catecholamine release (norepinephrine and epinephrine) and coughing or vomiting, which can increase intranasal pressure and precipitate bleeding. Dexmedetomidine attenuated these responses by reducing sympathetic outflow via α2 receptors in the brainstem (14).

Awake extubation ensured recovery of pharyngeal tone through hypoglossal nerve activity and restoration of upper airway reflexes such as glottic closure and swallowing. This approach minimized the risk of aspiration and hypoxia that may occur if anesthetics continued to exert residual GABA-A and NMDA receptor effects (15).

Postoperative Considerations

Postoperatively, dexamethasone continued to suppress pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α, thereby limiting edema and pain (16). Paracetamol and diclofenac reduced central and peripheral nociceptor sensitization through suppression of PGE2. Magnesium provided a sustained NMDA-blocking effect that contributed to opioid-sparing analgesia.

Care was taken to avoid direct mask pressure over the nasal site. Excessive compression could cause ischemia with hypoxia-inducible factor-1α (HIF-1α) upregulation, promote leukocyte adhesion through ICAM-1 expression, and trigger mast cell degranulation with histamine and bradykinin release, all of which would worsen swelling and discomfort (17).

References

1. Yilmaz Y, Altun H, Arslan IB. Management of nasal bone fractures. J Craniofac Surg. 2020;31(1):e70–e73.
2. Song CW et al. Pharmacological basis of anticholinergics. Pharmacol Ther. 2019;203:107395.
3. Rudolph U, Möhler H. GABAA receptor subtypes: therapeutic potential. Trends Pharmacol Sci. 2004;25(9):446-454.
4. Pasternak GW. Molecular biology of opioid analgesia. J Pain Symptom Manage. 2005;29(5 Suppl):S2–S9.
5. Barnes PJ. How corticosteroids control inflammation. Br J Pharmacol. 2006;148(3):245-254.
6. Trapani G et al. Propofol in anesthesia. Curr Med Chem. 2000;7(2):249-271.
7. Hunter JM. New neuromuscular blocking drugs. Br J Anaesth. 1996;77(5):541-549.
8. Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology. 2000;93(5):1345-1349.
9. Fawcett WJ et al. Magnesium: physiology and pharmacology. Anaesthesia. 1999;54(8):767-783.
10. Bertolini A et al. Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006;12(3-4):250-275.
11. Vane JR, Botting RM. Mechanism of NSAIDs. Am J Med. 1998;104(3A):2S–8S.
12. Schick B et al. Vascularization and angiogenic growth factors in nasal mucosa. Eur Arch Otorhinolaryngol. 2001;258(5):246-250.
13. Yaksh TL, Wallace MS. Opioids, analgesia, and pain management. In: Brunton LL, et al., eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill; 2018.
14. Abdelmalak B, Mekhail M. Perioperative airway management of patients undergoing nasal surgery. Anesth Clin. 2010;28(2):281-297.
15. Bekker A et al. The use of dexmedetomidine in awake extubation. Anesth Analg. 2004;98(2):590-592.
16. Duffy DJ et al. Role of PGE2 and cytokines in inflammation. Br J Pharmacol. 2011;164(4):894-908.
17. Mahajan A et al. Nasal surgery: anesthesia implications. Anesth Essays Res. 2014;8(1):15-23.