anesthetic management of a patient with mast cell

www.aana.com/aanajournalonline AANA Journal August 2021 Vol. 89, No. 4 307

Mast cell activation syndrome (MCAS) is a relatively new diagnosis for a constellation of symptoms with sometimes devastating results for patients. A 40-year old woman with MCAS underwent arthroscopic repair of her right shoulder, with successful anesthetic man-agement. This case report discusses the basic immu-nologic physiology surrounding this syndrome, myr-iad medications often used by this patient population, and the anesthetic management of this patient. With additional knowledge of this disorder, exposure to

its clinical presentation in the perioperative setting, and anesthetic considerations specific to MCAS, the Certified Registered Nurse Anesthetist will be better equipped to effectively manage the complex require-ments of this patient population.

Keywords: Anesthesiology, cell stabilization, immune hypersensitivity, mast cell activation syndrome, trigger avoidance.

Anesthetic Management of a Patient With Mast Cell Activation Syndrome: A Case Study

Sarah E. Giron, PhD, CRNACrystal D. Trinooson, MS, CRNARana Movahedi, MD

Mast cell activation syndrome (MCAS) is a rare disorder involving the idiopathic activation of morphologically normal mast cells leading to recurrent episodic symp-toms of immunologic activation or ana-

phylaxis.1,2 This syndrome is characterized by a nonspecific clinical presentation involving some combination of integu-mentary, gastrointestinal, cardiovascular, pulmonary, endo-crine, hematologic, and/or neuropsychiatric symptoms that often impedes early diagnosis and treatment.3

Patients with MCAS presenting for surgery and anes-thesia are at high risk of hypersensitivity reactions trig-gered by anesthetic agents, analgesics, neuromuscular blocking agents, anti-infective agents, environmental factors, surgical trauma, and psychological stress. The primary goal of anesthetic management in such patients is to prevent mast cell degranulation.4

This case report presents the successful perioperative management of a patient with known MCAS presenting for orthopedic surgery. The physiology and diagnostic cri-teria for MCAS are briefly reviewed; the clinical summary is evaluated, and a review of available recommendations for treatment and anesthetic management is presented.

Case SummaryA 40-year old woman (82 kg, 180 cm) with right shoul-der instability presented to the preoperative holding area for a right shoulder arthroscopy with repair. Her medical history included MCAS, Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), gas-troparesis, esophagitis, migraine, osteopenia, cervical spine disk herniation (C5-6, C6-7), lumbar spine disk herniation (L4-5), exercise- and stress-induced asthma,

tinnitus, temporomandibular joint (TMJ) stiffness and pain, spontaneous pneumothoraces, and anxiety disorder. Known allergies included ranitidine, hydromorphone, acetaminophen/hydrocodone, penicillins, lamotrigine, trifluridine, risperidone, topiramate, latex, soy, eggplant, gluten, and milk. Preoperative medical clearance had been provided by the patient’s primary medical specialist with a detailed note of recommendations presented by her allergist (Table 1).

The patient’s surgical history included a septoplasty, turbinectomy, and multiple orthopedic procedures; she had also received numerous sympathetic nerve blocks and epidural injections for management of chronic pain. The patient reported no adverse effects following general anesthesia aside from mild nausea and inadequate pain control, and there was no known history of familial anesthesia-related complications.

The patient’s current home medication regimen in-cluded oxycodone (15 mg every 4 hours), hydrocortisone (20 mg daily), tizanidine, erythromycin, lorazepam, lina-clotide, naloxegol oxalate, ondansetron, rifaximin, and cromolyn; inhaled fluticasone and budesonide; topical 2.5% lidocaine-2.5% prilocaine cream, tretinoin cream, and triamcinolone cream. Sumatriptan, ibuprofen, and albuterol were taken as needed. In accordance with her allergist’s recommendations, the patient took 20 mg of cetirizine, 10 mg of famotidine, 200 mg of cromolyn, 50 mg of diphenhydramine, and 20 mg of prednisone on the morning of surgery. Despite known hypersensitiv-ity to ranitidine, famotidine was recommended by the patient’s allergist because it had been safely adminis-tered to the patient during outpatient treatment and on past admissions. (This type of combined antimediator

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approach using H1- and H2-histamine receptor antago-nism and mast cell stabilization is a mainstay of MCAS management and will be examined in greater detail in the Discussion.1,2) Preoperative laboratory results were within normal limits, and a careful review of diagnostic radiologic tests, electrocardiogram, and echocardiogram revealed no abnormal findings.

On physical examination, the patient was found to be agitated but alert and fully oriented; her vital signs were within normal limits. Palpation of peripheral pulses dem-onstrated a regular heart rate; auscultation found all lung fields clear with no adventitious breath sounds. Results of the airway examination revealed a small mouth opening of 2 finger breadths, limited atlanto-occipital range of motion, Mallampati score of 3, and ability to protrude the mandible despite a history of TMJ symptoms. Dentition was grossly intact with no loose teeth or removable dental appliances reported. According to the patient, she had had nothing to eat or drink for more than 8 hours.

Following a careful review of allergist recommenda-tions and a thorough discussion of anesthetic risks, benefits, and options with the patient, informed consent was obtained for an interscalene block with continuous infusion catheter and a general anesthetic. A 20-gauge peripheral intravenous (IV) line was inserted in the left antecubital vein, oxygen (O2) therapy was initiated through a nasal cannula, and standard noninvasive moni-tors were applied to the patient. Before the interscalene block and continuous infusion catheter placement, the procedure site was confirmed to be the right side and procedural sedation was administered; total doses were 4 mg IV of midazolam and 50 μg IV of fentanyl. (The administration of benzodiazepines as a premedication before general anesthesia may confer some protection against anxiety-mediated mast cell degranulation. This benefit must be evaluated against the risk of heavy sedation, particularly in those patients receiving early-generation antihistamines.5)

Sterile preparation of the operative side was achieved with chlorhexidine topical solution, which was well tolerated. A SonoLong Echo E-Cath (Pajunk) 18-gauge catheter was inserted with continuous ultrasound guid-ance for nerve localization. Then 0.5% ropivacaine, 20 mL, was injected, with intermittent aspiration during administration. Ropivacaine was selected for its onset, analgesic duration, and provision of differential sensory-motor blockade. (Like other amide local anesthetics, ropivacaine is generally well tolerated and less likely to contribute to mast cell activation than ester local anesthetics.5,6) No blood was aspirated, and no pain or paresthesias were reported on injection. There were no symptoms of intraneural or IV injection and the patient tolerated the procedure well.

The patient was taken to the operating room and stan-dard monitors were applied. The patient was preoxygen-

ated using 8 L of O2 via face mask. A smooth IV induction was accomplished using 2% lidocaine, 100 mg IV; propo-fol, 200 mg IV; and rocuronium, 70 mg IV per surgeon request. (Recent studies have indicated that amides gener-ally have a low incidence of adverse reactions in patients with mast cell disorders. Lidocaine, in particular, is well-tolerated and may even modulate immune responses.5) Following loss of lash reflex, the eyes were secured with paper tape, and manual mask ventilation was easily achieved with low peak airway pressures.

With use of in-line cervical spine stabilization, a video-assisted laryngoscope (C-Mac, Karl Storz) was utilized. A 7.0-mm oral endotracheal tube was placed, with a Cormack-Lehane grade 1 view; bilateral breath sounds were auscultated, end-tidal carbon dioxide was noted, and the tube was secured at 21 cm at the teeth. General anesthesia was maintained with 60% fraction of inspired oxygen (Fio2) and 1.9% to 2.2% sevoflurane, using volume control ventilation. Clindamycin, 900 mg IV, was initiated as a preincision antibiotic. A 20-gauge left radial arterial line (Arrow, Teleflex) was placed with sterile technique in

Timing InterventionDay before surgery • Cetirizine, 20 mg in morning and 20 mg

at night• Famotidine, 10 mg in morning and 10

mg at night• Cromolyn, 200 mg 4 times a day• Prednisone, 20 mg in morning and 20

mg at night

Day of surgery Two hours before surgery:• Cetirizine, 20 mg• Famotidine, 20 mg• Prednisone, 20 mg• One hour before: Diphenhydramine, 50

mg IV (or orally unless contraindicated)

Intraoperative (after oropharyngeal intubation)

As needed:• Epinephrine IV, subcutaneous• Albuterol, ipratropium nebulized• Vasoactive agents: dopamine,

norepinephrine, vasopressin• Diphenhydramine, 50 mg IV• Methylprednisolone, 125 mg IV/IM

every 6 h as needed• Muscle relaxants, NSAIDs, morphine,

and codeine should be used with caution• Avoid vancomycin

Postoperative • Cetirizine, 20 mg twice daily• Famotidine, 10 mg orally twice daily• Prednisone, 20 mg orally twice

daily (can discontinue after day 1 if hemodynamically stable)

• Cromolyn, 200 mg 4 times daily• Diphenhydramine, 50 mg orally every 6

h as needed

Table 1. Sample of Patient Instructions From Allergist Managing MCASAbbreviations: IM, intramuscular; IV, intravenous; MCAS, mast cell activation syndrome; NSAIDs, nonsteroidal anti-inflammatory drugs.


one attempt, and a transparent dressing was applied.The patient was then positioned in the left lateral

decubitus position with an axillary roll and vacuum-packed bean bag for immobilization. Head and neck stabilization and neutrality were maintained throughout. (Immobilization of the cervical spine during endotrache-al intubation and patient positioning is a critical tenet of anesthesia management for patients with known cervical spine defects and for those whose comorbid connective tissue disease places them at high risk of atlantoaxial and craniocervical instabilities.7 Recent studies have found a possible association between connective tissue diseases, particularly joint hypermobility variants, and mast cell disorders.8 Furthermore, if cervical manipulation con-tributes to the local activation of afferent neurons, the release of inflammatory neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and pituitary adenylate cyclase activating polypeptide can stimulate activation and degranulation of adjacent mast cells.9)

A stress dose of methylprednisolone, 125 mg IV, was administered; a surgical pause was completed; and surgery commenced without issue. (The prophylactic administration of corticosteroids can help modulate immune responses to perioperative mast cell activation triggers by decreasing mediator release, producing pulmo-nary vasoconstriction, reducing bronchial hyperreactivity, inhibiting inflammatory cell recruitment, and mitigating bronchial smooth muscle contraction.10 Furthermore, the administration of stress doses of corticosteroids is known to mitigate the risk of adrenal insufficiency associated with long-term corticosteroid use.5,10)

Approximately 30 minutes after incision, the patient was repositioned to the supine position for surgical expo-sure and prophylaxis against pressure-mediated mast cell activation. Again, cervical spine stability was maintained and adhesive goggles were applied over the paper tape for additional ocular protection. (Despite the protection it confers against pressure-mediated injury and immune ac-tivation, intraoperative position alteration can be a criti-cal event because of the risk it poses for friction-mediated mast cell degranulation as well as orthostatic intolerance, particularly in patients such as this with a comorbid di-agnosis of POTS.11,12 A series of studies have examined the role of mast cell activation in cutaneous flushing during POTS episodes and have even posited a triad relationship between POTS, EDS, and MCAS.13 Further research is needed to clarify this potential relationship and the clinical impact on diagnosis and treatment of each syndrome.) The patient tolerated positioning well with no clinical evidence of tachycardia or autonomic dysfunction; electrocardiography showed normal sinus rhythm throughout the case, vital signs were stable, and lung compliance was maintained as evidenced by ade-quate measured tidal volumes, peak inspiratory pressures

ranging from 16 to 18 cm H2O throughout the case, and a grossly normal expiratory plateau of the end-tidal cap-nography waveform.

On surgical closure, ondansetron (4 mg IV) was ad-ministered and 3/4 train-of-four (TOF) twitches were measured with a left ulnar peripheral nerve stimulator. Sugammadex, 180 mg (2.2 mg/kg) IV, was administered to reverse neuromuscular blockade. Before tracheal extubation, 4/4 TOF twitches and sustained 5-second tetanus at 50 Hz were exhibited, spontaneous adequate tidal volumes and respiratory rate were present, the oropharynx was suctioned, and the patient was able to follow commands. After extubation criteria were met, the patient was extubated easily and was transported to the postanesthesia care unit (PACU) in stable condition with 6 L of O2 via face mask. Total operative time was 2 hours, 9 minutes to complete a right shoulder hemiarthroplasty with arthroscopic débridement. The total estimated blood loss for the case was 50 mL; total IV fluid adminis-tered was 1,000 mL of 0.9% sodium chloride.

On arrival to the PACU, the patient was noted to be awake and conversing clearly; bilateral lungs were auscultated to be clear, vital signs remained stable, and the patient denied pain or nausea. Following surgical assessment of the operative arm for motor and sensory function, a continuous infusion of 0.2% ropivacaine was initiated through the right interscalene catheter for post-operative pain control at a rate of 4 mL/h. Early recovery was uneventful, and the patient was later discharged home without clinical evidence of mast cell activation during her perioperative course. However, due to subop-timal pain control later in the hospital course, the patient had a longer than anticipated length of stay.

DiscussionMast cells are a critical component of the immune response, playing a major role in immunoglobulin E (IgE)–mediated acute hypersensitivity and anaphylactic reactions.8 They also help promote the expression of immunoregulatory proteins and serve a complex role in delayed hypersensitivity.8,14 Mast cells originate in the bone marrow from the same stem cells that give rise to basophils; they then travel through the systemic blood and lymphatic circulation in a precursor form before settling in the peripheral tissues and differentiating. The proliferation and maturation of mast cells are thought to be influenced by a number of cytokines (small pro-teins used by the immune system in cellular signaling), particularly stem cell factor (SCF), which binds the CD117 tyrosine kinase transmembrane receptor (c-KIT) to promote “homing” of immature mast cells from bone marrow and peripheral blood to specific tissues.8,15 The local environments of specific tissues interact with the immature mast cells to promote unique phenotypical traits in the mature mast cells that will support various


functions, including immune mediation, angiogenesis, tissue healing, blood-brain barrier support, and phagocy-tosis.8,16,17 The influence of certain tissues on the traits of homed mast cells is a current topic of interest in the potential relationship between EDS and MCAS.8

The surface of mature mast cells is heavily coated with Fc ε-receptors (FcεRI) that preferentially bind the crystallizable fragment regions of antibodies and have a high affinity for IgE at their α subunit.18 When IgE binds with an antigen at the α subunit of FcεRI, the β and γ subunits activate a special sequence contained in their cytoplasm to trigger an immune-mediated mast cell acti-

vation16,18,19 (Figure 1). This sequence, immunoreceptor tyrosine-based activation motif (ITAM), provides signal-ing capability for the FcεRI.19 Furthermore, the β subunit of FcεRI plays an important role in stabilizing the antigen-IgE complex to enhance the positive feedback immune response.20 The activation of the ITAM on the β subunit stimulates spleen tyrosine kinase (SYK) to augment mast cell degranulation, a process by which mast cells release histamine. Increased SYK then stimulates cytokine pro-duction and (via downstream second messengers) re-cruits T-cell immunity19,20 (Figure 2). This leads to an unchecked cascade of immune-mediated hypersensitivity

Figure 1. Mast Cell ActivationAbbreviations: c-KIT, CD117 tyrosine kinase transmembrane receptor; FcεRI, Fc ε-receptor; IgE, immunoglobulin E; ITAM, immunoreceptor tyrosine-based activation motif; SCF, stem cell factor; SYK, spleen tyrosine kinase; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α.


responses ranging from local tissue edema, headache, diarrhea, urticaria, and cutaneous flushing to vascular permeability, widespread vasodilation, bronchoconstric-tion, and cardiovascular collapse.11,14

Toll-like receptors (TLRs) on the mast cell surface may cause a direct immune response if bound to bacteria or viruses. Further investigative work on the unique role of TLRs has demonstrated that they use cell signaling to either augment or inhibit mast cell degranulation in various types of peripheral mast cells.21 The binding of SCF to c-KIT also stimulates a series of signal transduc-tion pathways that activate mast cell degranulation and

attenuate the response of mature mast cells.15 Although mast cells play an integral role in immune-mediated pro-cesses, they may also degranulate in direct response to toxins, venoms, hormones, and physical stimuli such as thermal or friction tissue injury1,22 (see Figure 2).

Mast cell activation triggers the exocytotic release of presynthesized inflammatory mediators from the cyto-plasm of the cell, including proteases, heparin, cytokines, tumor necrosis factor-α (TNF-α), histamine, and sero-tonin.16,17,23 Mast cell activation also triggers synthesis of platelet activating factor, prostaglandins, leukotrienes, thromboxanes, and other vasoactive substances.16,17,24

Figure 2. Mast Cell DegranulationAbbreviations: c-KIT, CD117 tyrosine kinase transmembrane receptor; FcεRI, Fc ε-receptor; IgE, immunoglobulin E; ITAM, immunoreceptor tyrosine-based activation motif; SCF, stem cell factor; SYK, spleen tyrosine kinase; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α.


The release of TNF-α, in particular, triggers a powerful positive inflammatory cascade because of its stimulation of T-cell immunity and its direct potentiation of addi-tional mast cell degranulation14,16 (see Figure 1). The classic example of this cascade is the anaphylactic reac-tion, whereby FcεRI-IgE binding of an allergen potenti-ates massive mast cell degranulation with subsequent lymphocyte, neutrophil, and basophil recruitment.16 The resultant release of histamines, prostaglandins, and other vasoactive mediators contributes to an acute array of car-diovascular, respiratory, integumentary, neuromuscular, and gastrointestinal symptoms.11

Mast cell disorders are often characterized as primary, secondary, or idiopathic in accordance with their patho-physiology. Primary disorders are associated with a defect in mast cell morphology, proliferation, or signaling. They generally involve c-KIT mutations (with or without concomitant genetic mast cell alteration) and abnormal mast cell proliferation and activation; these conditions include mastocytosis, primary monoclonal MCAS, mast cell sarcoma, and chronic eosinophilic leukemia. Because of the unique role of c-KIT in cellular propagation and migration, it is considered a proto-oncogene; any altera-tion in its function may contribute to the development of malignancy.3,11,15,25,26 Additionally, SYK may play a substantial role in the development of lymphomas.20

Clonal mast cell disorders may respond to cytoreduc-tive therapies such as interferon-α (IFN-α), cladribine, hydroxyurea, or tyrosine kinase inhibitors; hematopoietic stem cell transplant is an additional treatment option for patients with mast cell malignancy.25,26 Because primary disorders are characterized by the proliferation of clonal mast cells, they may be more readily diagnosed using lab-oratory analysis. Differential diagnosis is often confirmed with bone marrow aspiration or biopsy of cutaneous lesions.9 Patients with primary disorders often present with periodic symptomatic mast cell degranulation; trig-gering agents are typically unknown and symptoms may include cutaneous flushing, gastrointestinal symptoms, profound hypotension, and cardiovascular collapse.3,25 Mast cell stabilization agents, leukotriene inhibitors, and antimediator agents (epinephrine and antihistamines) are a mainstay of symptom management for all classifications of mast cell disease.27

Secondary disorders are associated with extrinsic activation of healthy mast cells; they often involve un-checked adaptive inflammatory responses (IgE- and non-IgE–mediated reactions, inflammation, and infec-tion) and include immediate hypersensitivity reactions and chronic autoimmune urticaria.3,25 Isolated secondary mast cell disorders generally respond to avoidance of known triggers and management of underlying infection. However, secondary causes may be concomitant with primary or idiopathic causes.2,25

Idiopathic disorders are associated with increased mast

cell activation of unknown etiology despite a full diag-nostic evaluation; these include idiopathic anaphylaxis, idiopathic angioedema, and MCAS.2,3 As with secondary disorders, idiopathic syndromes are generally character-ized by normal proliferation and histologic appearance of mast cells.2 However, idiopathic causes are associated with markedly heightened mast cell activity; mast cells may degranulate in response to even a mild stimulus.6,11,25 MCAS is a disorder of chronic mast cell degranulation that has been described diagnostically only within the past decade.2 Diagnostic characteristics of MCAS include all of the following:

• Recurrent symptoms of mast cell activation in at least 2 distinct organ systems (integumentary involve-ment is common).1,8,25

• Measurably elevated immune mediator activity within 4 hours of mast cell degranulation symptoms in at least 2 episodes,25 with elevation of serum tryptase values 20% above baseline the marker most specific for mast cell activation.

• Measurable reduction in symptoms in response to mass cell membrane stabilizers or other immune me-diator blockade (cromolyn, antihistamines, leukotriene inhibitors).8,25

Laboratory analysis of elevated immune mediator activity has been historically difficult because mast cells may be involved in the activation of a multitude of nonspecific mediators (eg, histamine and its urinary metabolites are also indicative of basophil involvement).9 Furthermore, many of the serum and urine mediators that may serve as specific indexes of mast cell activa-tion are unstable ex vivo.1,24 Unlike mastocytosis, MCAS typically does not present with chronically heightened baseline tryptase levels.6,25 Elevated 24-hour urinary metabolites of mast cell mediators (histamine, prosta-glandins, leukotrienes) are less specific indicators of mast cell activation; they may also be measurably elevated in the setting of basophil activation, inflammatory bowel disease, and histamine intolerance due to exogenous his-tamine toxicity or reduced diamine oxidase function.11,28

Because of the nonspecific nature of presenting symp-toms and the comparatively recent introduction of diag-nostic criteria, the actual incidence of MCAS is not widely known. A recent combined retrospective and prospective cohort study evaluated the population characteristics of patients with MCAS. The findings indicated that MCAS is most prevalent in white females whose presenting symp-toms commonly included fatigue, diffuse pain, presynco-pal or syncopal episodes, and headache. Unfortunately, the median time from self-reported onset of symptoms to diagnosis was 30 years.29 Diagnosis may be complicated by the complex and nonspecific nature of the symptoms, the episodic nature of clinical presentation, and the lack of reliable serologic indicators outside the immediate flare.30,31 Patients may be markedly disabled during


episodes, leading to a delay in seeking treatment; by the time they present for care, their baseline tryptase values are often within normal limits. Furthermore, emergency medical treatment during acute anaphylaxis may focus on symptom management and identification of triggering agents without focus on a global diagnosis.4,32

The anesthetic management of the patient with MCAS spans a vast range of clinical symptoms and incorporates the basic therapeutic considerations of this disease: (1) highly individualized care to avoid known triggers and (2) prevention of mast cell mediator proliferation.9,33

Patients typically are receiving a plethora of medications,

which must be continued perioperatively and incorpo-rated into the anesthetic plan (Table 2). With a dearth of randomized controlled studies on which to base clinical decisions, the anesthetist is forced to rely on case reports and observational studies in the MCAS population. To date, no therapeutic trials exist and no guidelines are available on the anesthetic management of patients with MCAS.26,27,32,33

The avoidance of known mast cell activation triggers is one of the primary considerations in the perioperative care of the patient with MCAS. A detailed history is para-mount to safe anesthetic management, as well as close

MCAS symptom TreatmentAnesthetic

considerationsCardiovascular Hypotension Syncope Tachycardia Lightheadedness Angina pectoris

Emergent: EpinephrineProphylactic:H1-antihistaminesAntileukotrienesOmalizumabNitratesCalcium channel blockersVenom immunotherapy if appropriate

Fluid replacement may be indicated in the setting of massive vasodilatation and acute refractory hypotension to help preserve circulating volume. Make emergency medications readily available for any anesthetic involving a patient with MCAS.

Cutaneous Flushing Pruritus Urticaria Angioedema

H1- and H2-antihistaminesKetotifenAspirin or NSAIDsa

Emergent intubation may be indicated to protect the airway in patients with angioedema. Have fiberoptic bronchoscopy and/or video laryngoscopy readily available to avoid airway trauma or further edema.

Gastrointestinal Cramping Diarrhea Nausea/vomiting GERD Colicky gastric pain Biliary colic

Local thermal treatmentH2-antihistaminesCromolynProton pump inhibitorsGlucocorticoidsScopolaminePolyethylene glycol

Localized abdominal application of heat has been shown to activate heat receptors that competitively interfere with nociceptive pain.35 However, avoid systemic hyperthermia, which can trigger mast cell degranulation.

Respiratory Throat swelling Wheezing Shortness of breath

AntileukotrienesInhaled corticosteroids for asthma

When possible, use MAC anesthesia to avoid airway manipulation. Have advanced airway equipment and breathing treatments readily available.

Musculoskeletal Bone pain Arthralgia Osteoporosis Muscle pain Neuropathic pain Fibromyalgia

Calcium/vitamin D supplementationBisphosphonatesAspirin or NSAIDsa

Opioidsa H1-antihistaminesAvoid massage

Avoid tourniquets when appropriate and possible. Treat pain with previously used modalities or per specialist recommendations.

Neurologic Migraine Trigeminal neuralgia

Acetaminophen or NSAIDsTriptansPotassium supplementation

Administer adequate perioperative fluids. Start home medications as soon as possible.

Genitourinary Renal colic

Scopolamine Avoid meperidine.

Oropharyngeal Sore throat

H1-antihistamines Carefully and gently manipulate oropharynx during intubation. Use MAC when appropriate.

Table 2. Medications Used for Treatment of MCASAbbreviations: GERD, gastroesophageal reflux disease; MAC, monitored anesthesia care; MCAS, mast cell activation syndrome; NSAIDs, nonsteroidal anti-inflammatory drugs.aAssess for tolerability before administering.


collaboration with any allergist or immunology specialist involved in the patient’s care. Continuation of baseline therapy of antimediators, mast cell stabilizing agents, and leukotriene inhibitors is critical for safe anesthetic management.1 Premedication with histamine antagonists and corticosteroids may be warranted; close consultation with the patient’s immunologist will help provide clini-cal guidance for preoperative optimization and manage-ment.1,5 Unless there is a known history of hypersensitiv-ity reaction during a prior anesthetic, prescreening with a skin test is not recommended, but obtaining a baseline tryptase level may be helpful.32 The patient in this case reported a constellation of food allergies, which were easily avoided; latex and penicillin use was avoided peri-operatively, and 900 mg of clindamycin was administered before the incision. Of note, patient records indicated that clindamycin had been safely administered to the

patient in the past, with no unfavorable sequelae.Pain is also a known trigger of mast cell activation.

Therefore, an adequate analgesic plan must be discussed with the patient and surgical service preoperatively and implemented during planned procedures. Remifentanil, alfentanil, fentanyl, oxycodone and ketamine are rec-ommended analgesics; morphine and codeine should be avoided if possible due to their impact on me-diator release.9,26,32,34 The anesthetist should be aware that opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) can also trigger MCAS events, so a thorough preoperative assessment and plan for pain control are essential.9,26 In this case report, the patient underwent a regional nerve block with catheter placement for periop-erative pain control to limit the administration of narcotic analgesics. The intraoperative and immediate postop-erative periods were successfully managed with a mul-timodal analgesic plan and continuous infusion through the regional block catheter. However, due to suboptimal pain control later in the hospital course, the patient had a longer than anticipated length of stay.

Highly attentive hemodynamic management is foun-dational to anesthetic management of all patients. There are currently no consensus data for specific perioperative monitoring in patients with MCAS, but the use of arterial blood pressure monitoring or noninvasive continuous he-modynamic devices may provide early awareness of hypo-tension due to mast cell degranulation or other intraopera-tive factors. Hemodynamic instability should be managed aggressively with vasoactive support; epinephrine is the agent of choice if mast cell involvement is suspected.11 Because of the risk of mast cell degranulation with ex-tremes of temperature, normothermia should be carefully maintained.1 Core temperature monitoring at the distal esophagus, nasopharynx (at appropriate depth) or pulmo-nary artery (if pulmonary artery access is warranted) may provide the most reliable data to assist in maintaining nor-mothermia.36,37 If nasopharyngeal monitoring is employed, it should be used with great care to mitigate the risk of local trauma and potential mast cell activation. Alternatively, a core approximate site such as the bladder may be used.36 Skin temperature monitoring should be used with caution because of the potential for unreliable data.

The nature of symptoms of mast cell activation episodes often precludes early identification in the perioperative setting. Headache, loss of concentration, peripheral vasodi-lation and cutaneous flushing, urticaria, and gastrointesti-nal symptoms are often present in mild mast cell degranu-lation events.1,2 These events may be difficult to identify when the patient is under general anesthesia. However, ongoing cutaneous assessment may help promote early identification of urticaria, flushing, and rashes if surgical positioning and draping allows. Attentive monitoring of peak airway pressure and lung compliance measures is also essential for early identification and treatment of airway

Drug classDrugs with high risk Alternativesa

Anesthetics MethohexitalPhenobarbitalThiopental

PropofolKetamineEtomidateMidazolamTIVA/sevoflurane26

Muscle relaxants AtracuriumMivacuriumRocuroniumb

CisatracuriumVecuroniumPancuronium

Antibiotics CefuroximeFluoroquinolonesVancomycin

Agents administered in previous therapies with no reaction

Anticonvulsants CarbamazepineTopiramate

Clonazepam

Opioids MeperidineMorphineCodeine

RemifentanilAlfentanilFentanylOxycodone

Other analgesics Acidic NSAIDs (eg, acetaminophen and ibuprofen)b

Acetaminophenb

Local anesthetics ArticaineTetracaineProcaine

Amides such as bupivacaine5

Plasma substitutes

Hydroxyethyl starch Albumin0.9% Normal salineLactated Ringer’s solution

Cardiovascular drugs

ACE inhibitorsβ-Blockers

Angiotensin II blockersCalcium channel blockersIvabradine

Table 3. Drugs Associated With High Risk of Release of Mediators From Mast Cells and Their AlternativesAbbreviations: ACE, angiotensin-converting enzyme; NSAIDs, nonsteroidal anti-inflammatory drugs; TIVA, total intravenous anesthetic.a Any injectables containing ethanol should be avoided.4b Assess for tolerability before administering.(Adapted from: Molderings et al.33)


involvement, as is chest auscultation, if feasible.2

Many aspects of surgery induce mast cell medi-ator release, as do common anesthetic medications. Anesthesia, extreme temperatures, psychological stress or anxiety, pain, mechanical trauma (including applica-tion of tourniquets), friction injury (often associated with positioning or adhesive placement and removal), ischemia-reperfusion injury, and excessive skin pressure can all activate mast cell mediators.9,27,32 A summary of common anesthetic drugs that activate mast cell media-tors are listed in Table 3. Because many of the agents as-sociated with anesthetic management can induce mast cell activation, current literature recommends premedi-cating with an antihistamine and a corticosteroid.9,26,32 Both a forced warm air blanket and fluid warmer were utilized to maintain a stable normothermic state and to prevent rapid patient cooling intraoperatively. In this case report, coordination with the surgical team allowed for the intraoperative repositioning of the patient to avoid excessive skin pressure and to maximize surgical site ex-posure. Positioning changes should always be conducted with careful ongoing attention to hemodynamic status due to the risk for friction-mediated mast cell activation or profound hypotension (possibly immune-mediated in these patients, but orthostatic intolerance may also be present in those with certain comorbid conditions).13,28

Preoperative consultation with the surgical team revealed that anticipated blood loss would be minimal, so no ad-ditional IV access was obtained.

Anaphylaxis can be common in the MCAS population, with reactions ranging from cutaneous findings to cardio-vascular collapse.32 Intravenous or intramuscular (IM) epinephrine, antihistamines, and corticosteroids should be readily available to administer during any anesthetic management of the patient with MCAS.26,32 Omalizumab, an IgE antagonist, may also benefit the patient with MCAS in anaphylaxis by preventing IgE-mediated mast cell degranulation.26 The anesthetist should also keep in mind that agents with an increased propensity to cause anaphylaxis in the general population (latex, muscle relaxants and antibiotics) need not be avoided in the patient with MCAS unless a previously documented reac-tion has occurred.32

Furthermore, some antihistamines can cause QT pro-longation, so caution is warranted when administering other medications or agents that prolong the QT interval. If anaphylaxis does occur in the patient with MCAS, the causative agent should immediately be stopped in ac-cordance with current recommendations. Antihistamines (preferably IV diphenhydramine) and corticosteroids such as methylprednisolone should be administered for the treatment of both mild and severe hypersensitivity re-actions.32-34 Epinephrine is the mainstay of management for anaphylaxis; IV administration is preferred in most cases, but intramuscular injection may mitigate delays

in treatment if the event is triggered before IV access has been established.11 Placement of a secure airway is paramount if not already in place at the time of the ana-phylactoid reaction; inhaled β2-agonists may confer some benefit as a secondary approach.5,11,33 Fluid administra-tion is also a critical aspect of anaphylaxis management. When hemodynamic stability has been achieved, mea-surement of serum tryptase level is of diagnostic benefit if collected within 30 to 120 minutes after the event.5

This case exemplifies the careful history taking, com-prehensive physical evaluation, interdisciplinary commu-nication, and multimodal anesthetic management needed to avoid mast cell activation in a patient with MCAS. Further study is indicated to identify additional serologic markers of mast cell activation, as the limited diagnostic window and nonspecific nature of tryptase and urine me-diators impede their diagnostic value. The development of additional treatment options is also paramount for pro-viding ongoing mast cell stabilization, reduction in the scope of mast cell degranulation, and interference with the physiological activity of released mediators. Global awareness of this disorder and its diagnostic criteria may aid in earlier diagnosis and treatment.25 Of particular in-terest to the anesthetist is the development of published guidelines for the anesthetic management of MCAS and other mast cell disorders.

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AUTHORSSarah E. Giron, PhD, CRNA, has been a clinical and didactic educator in nurse anesthesia since 2005. She is currently a full-time faculty member of the Kaiser Permanente School of Anesthesia in Pasadena, California, and practices at the South Bay Kaiser Permanente facility in Harbor City, California.

Crystal D. Trinooson, MS, CRNA, is a staff nurse anesthetist at Keck Medical Center of the University of Southern California.

Rana Movahedi, MD, is an associate clinical professor at the University of California, Los Angeles, where she teaches clinical and didactic regional anesthesia. She completed her residency at Cedars-Sinai Medical Center, Los Angeles, California, and her fellowship at the Hospital for Special Surgery, New York, New York.

DISCLOSURESName: Sarah E. Giron, PhD, CRNAContribution: This author made significant contributions to the concep-tion, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author.Disclosures: None.Name: Crystal D. Trinooson, MS, CRNAContribution: This author made significant contributions to the concep-tion, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author.Disclosures: None.Name: Rana Movahedi, MDContribution: This author made significant contributions to the concep-tion, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author.Disclosures: None.The authors did discuss off-label use within the article. Disclosure state-ments are available for viewing upon request.

anesthetic management of a patient with mast cell

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