Clinical bottom line
Mast Cell Activation Syndrome (MCAS) presents unique perioperative challenges due to unpredictable mast cell mediator release triggered by anesthetic agents, surgical stress, or other stimuli. Current evidence, largely from case reports and expert consensus, suggests that careful preoperative assessment, avoidance of known mast cell triggers, and readiness for rapid intervention with antihistamines and epinephrine are critical to minimizing intraoperative anaphylactoid reactions and postoperative complications. While high-quality controlled trials are lacking, anesthesiologists should consider MCAS a potential risk factor for perioperative hypersensitivity reactions and tailor anesthetic plans accordingly.
What the evidence shows
MCAS is characterized by inappropriate mast cell activation leading to episodic symptoms such as flushing, hypotension, bronchospasm, and anaphylaxis. The pathophysiology involves aberrant release of histamine, tryptase, prostaglandins, and other mediators, which can be triggered perioperatively by medications, mechanical stimuli, or stress (KILIÇ et al., 2026; KUTLUĞ ŞEYHAN et al., 2026).
Richter et al. (2017) reported successful anesthetic management of a patient with possible MCAS undergoing pulmonary embolectomy. The team employed preoperative antihistamine prophylaxis and avoided known mast cell degranulators, resulting in an uneventful intraoperative course. This case underscores the importance of individualized anesthetic planning and vigilance for signs of mast cell activation.
Delayed diagnosis of MCAS can negatively impact quality of life and complicate perioperative care due to unrecognized hypersensitivity risks (Suman et al., 2025). Awareness and early identification of MCAS features allow for preemptive measures, including premedication with H1 and H2 blockers, corticosteroids, and availability of emergency medications such as epinephrine.
There is no consensus on a standardized anesthetic regimen for MCAS patients, but avoidance of known triggers such as morphine, neuromuscular blocking agents with high histamine release potential, and certain antibiotics is advised (KILIÇ et al., 2026). Regional anesthesia may be preferable when feasible, as it may reduce systemic mediator release.
Caveats and uncertainty
The evidence base for anesthetic management in MCAS is limited primarily to case reports and expert opinion; no randomized controlled trials or large cohort studies exist. The heterogeneity of MCAS presentations and diagnostic criteria complicates generalization of findings. Furthermore, the rarity and underdiagnosis of MCAS mean many anesthesiologists may not recognize the syndrome preoperatively.
The efficacy of prophylactic regimens remains unproven in controlled settings, and the optimal combination and timing of antihistamines, corticosteroids, and other agents are not established. Additionally, the risk of perioperative mast cell activation varies widely among patients, making risk stratification challenging.
How this may change practice
Anesthesiologists should maintain a high index of suspicion for MCAS in patients with histories of unexplained anaphylaxis, flushing, or multisystem allergic symptoms. Preoperative evaluation should include detailed allergy and symptom histories, and consultation with allergists or immunologists may be warranted.
Perioperative plans should prioritize avoidance of known mast cell triggers and incorporate prophylactic antihistamines and corticosteroids as appropriate. Anesthesia teams should prepare for rapid recognition and treatment of mast cell mediator release, including ready availability of epinephrine and airway management resources.
This approach may reduce perioperative morbidity in MCAS patients, improve patient safety, and enhance outcomes. Future research is needed to develop evidence-based guidelines and standardized protocols for anesthetic management in this population.