Sugammadex in systemic mastocytosis

The patient consented to publication and signed the informed consent. We present the case of a 50-year-old woman (184 cm, 66 kg) with American Society of Anesthesiologists (ASA) physical status II, diagnosed with systemic mastocytosis with c‑kit D816 mutation and expression of CD2 and CD25 with cutaneous symptoms (urticaria) and episodes of systemic anaphylaxis. She had been treated with subcutaneous epinephrine at that time. The patient had a personal history of Hashimoto’s thyroiditis and drug-induced hepatitis. In addition, she had previously undergone left parathyroidectomy, subsequently suffering from generalized urticaria associated with nonsteroidal anti-inflammatory drugs (NSAID) in the early postoperative period. The patient had no other medical history. She was scheduled for right hemithyroidectomy to solve a follicular neoplasia of the right thyroid lobe. She did not present predictors of difficult airway management. Her daily medication included sodium cromoglycate 100 mg/4 h and ebastine 20 mg/24 h. Physical examination revealed erythematous lesions on the trunk and lower limbs. The baseline serum tryptase determination was 140 ng · ml⁻¹. The tryptase determination technique was fluoroenzyme immunoassay (immunoCap 250® [Phadia, Uppsala, Sweden]), reference values: 0–11 ng · ml⁻¹.

The patient was evaluated by the allergology department prior to the surgical intervention in order to carry out a multidisciplinary approach to the most appropriate drugs for perioperative management. In this assessment, it was concluded that the only NSAIDs that could be used were paracetamol and celecoxib. In addition, the pertinent recommendations were made in case the patient had to undergo general anesthesia. Thus, she was premedicated with oral prednisone 0.5 mg · kg⁻¹ 1h prior to the surgery, and with intravenous dexchlorpheniramine 5 mg, ranitidine 100 mg, and montelukast 10 mg immediately before anesthetic induction. In addition, midazolam 3 mg was administered in the preanesthesia room. Intraoperative monitoring included electrocardiogram, heart rate (HR), bispectral index (BIS), pulse oximetry (SpO₂), noninvasive blood pressure (NIBP) and train-of-four (TOF). Vital signs at the arrival to the operating room were: NIBP 132/82 mm Hg, HR 90 bpm, SpO₂ 100%. Anesthetic induction was performed with etomidate 0.2 mg · kg⁻¹, remifentanil in continuous perfusion 0.1 mcg · kg⁻¹ · min⁻¹ and rocuronium 0.6 mg · kg⁻¹. Intraoperative maintenance was performed using balanced anesthesia, with desflurane 0.7–0.9 MAC (minimal alveolar concentration) and remifentanil 0.05–0.1 µg · kg⁻¹ · min⁻¹. The patient showed hemodynamic stability, adequate peripheral saturation (SpO₂ 98–100%) and adequate neuromuscular relaxation (TOF 0–1/4) throughout the intraoperative period (length of surgery: 115 min). At the end of the procedure, neuromuscular blockade was reversed with sugammadex 2 mg · kg⁻¹ according to TOF response (TOF 3/4) and the patient was transferred to the intensive care unit (ICU) for postoperative monitoring. Her vital signs at the arrival to the ICU were: NIBP 119/74 mm Hg, HR 72 bpm, SpO₂ 100%. No cutaneous or systemic signs of mast cell release were noticed perioperatively. Postoperative analgesic management was controlled using intravenous paracetamol 1 g/6 h and oral celecoxib 200 mg/24 h.

Blood samples were taken for the determination of serum tryptase in the immediate postoperative period (105 ng · ml⁻¹), and at 2 h (103 ng · ml⁻¹), at 6 h (104 ng · ml⁻¹) and 24 h (105 ng · ml⁻¹) postoperatively. She did not present symptoms associated with her underlying pathology, or postoperative complications, and she was discharged 48 h after surgery.

All studies published up to January 2021 concerning anesthetic management in systemic mastocytosis were included for this systematic review. It was conducted in accordance with current guidelines on systematic literature reviews, and prospectively registered at International prospective register of systematic reviews (PROSPERO:CRD 42021239209). This manuscript adheres to the applicable Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Studies were identified within the electronic databases PubMed and Google Scholar. Search strategy was carried out as follows: in PubMed: systemic mastocytosis[MeSH Terms] OR urticaria pigmentosa[MeSH Terms] AND anesthesia[MeSH Terms], and in Google Scholar: “systemic mastocytosis” OR “urticarial pigmentosa” AND anesthesia OR “general anesthesia” OR “sugammadex” NOT “regional anesthesia”.

All studies published up to January 2021 in English, Spanish, or German were eligible. No type of document restriction was applied, and no methodology filters were used. Titles and abstracts of retrieved papers were screened for relevance. Selection of articles was carried out using predefined screening criteria. Disagreements regarding inclusion were resolved via discussion among the authors.

The reasons for excluding studies were duplicated papers, publications reporting anaphylaxis to sugammadex in patients not suffering from systemic mastocytosis, or patients suffering from systemic mastocytosis for whom sugammadex had not been administered. A flow-chart illustrating the process of study selection is presented in Fig. 1.

Using a predefined data extraction form, data were gathered from individual papers. Any discrepancies in the extracted data were resolved via discussion among authors.

Information obtained from reviews were abstracted in a narrative synthesis. Details obtained from case reports were compared and summarized (Table 1). Data regarding the elevation of tryptase levels after sugammadex administration were ordered numerically, as difference between poststimulus and prestimulus values. As no randomized clinical trials were expected to be identified, data extraction was based on conclusions found in reviews and results reported in case reports.

Only one review of those published regarding anesthetic management in patients with systemic mastocytosis recommends the administration of sugammadex [6]. Although they found no reason to advise against its use in these patients, they acknowledged that there are no data concerning it.

Moreover, in a review on anesthetic recommendations in electroconvulsive therapy in special conditions [7], the use of full-dose rocuronium reversed with sugammadex in short-term procedures is an acceptable alternative for patients with systemic mastocytosis.

In 4 case reports of patients with systemic mastocytosis the use of sugammadex is reported [8‐11]. Two articles justify not using of sugammadex due to its unavailability [12, 13]. In another article, sugammadex is proposed as an acceptable option in pregnant women with mastocytosis, although in the reported case neuraxial anesthesia was used [14].

Only in 2 of the reported cases in which sugammadex was used, was perioperative monitoring of serum tryptases performed. In the article by Unterbuchner et al. the levels of tryptases went from 17 ng · ml⁻¹ preoperatively, to 18 ng · ml⁻¹ (+5.9%) 30 min after the administration of rocuronium and to 20 ng · ml⁻¹ (+11.8% with respect to basal value) 30 min after the administration of sugammadex [8]. In the case reported by Parra et al., the levels of tryptases went from 12 ng · ml⁻¹ preoperatively down to 9 ng · ml⁻¹ (−25%) in the postoperative period, although it is not specified how much time elapsed from the administration of sugammadex to tryptase determination [11]. Figure 2 shows the evolution of the tryptases levels in the two cases referred to, together with the evolution in the case reported in this article.