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Anaesthesia and orphan disease

Rapid sequence induction in systemic mastocytosis

Unterbuchner, Christoph; Hierl, Marina; Seyfried, Timo; Metterlein, Thomas

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European Journal of Anaesthesiology: March 2017 - Volume 34 - Issue 3 - p 176-178
doi: 10.1097/EJA.0000000000000568
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Systemic mastocytosis is a rare mast cell activation disorder with a prevalence of 1 : 364 000.1 This orphan disease is characterised by an abnormal accumulation of clonal mast cells in various organs and tissues. Clinical signs range from a mild course to life-threatening cardiovascular collapse because of mast cell activation that may be induced spontaneously or by external triggers.2 Systemic mastocytosis is considered a high risk for general anaesthesia.1

Written informed consent for publication was obtained from the patient.

We report on a 45-year-old man (57 kg, 180 cm, ASA III) undergoing emergency laparotomy because of small bowel ileus. The patient also had bronchial asthma, tachyarrhythmia, polyneuropathy, residual left-sided brachiofacial hemiparesis, generalised epilepsy and depression as well as indolent systemic mastocytosis with splenomegaly, osteoporosis, recurrent syncope, diarrhoea and generalised urticaria with recurrent flushes. Allergy testing in 2012 showed type I hypersensitivity to dimenhydrinate, clonidine, diazepam as well as wasp and bee venom. Tests with muscle relaxants were negative. The patient's medication consisted of duloxetine, lamotrigine, amitryptiline, pantoprazole, tamsulosin, bisoprolol, beclomethasone/formoterol, salbutamol, cetirizine, cromolyn sodium and etoricoxib. General anaesthesia with propofol, sufentanil and rocuronium 6 years previously had been uneventful.

Preoperative echocardiography and ECG yielded normal results. SpO2 was 96%. Physical examination of the immobilised patient showed hemiparesis, a distended and painful abdomen as well as brown maculopapular lesions on the thorax and the abdomen. White blood cell count showed leucocytosis (15.6 × 109 l−1), thrombocytopenia (148 × 109 l−1) and C-reactive protein of 68 mg dl−1. The plasma level of tryptase was moderately elevated at 17 ng ml−1 (retrospective assay, reference range of concentration according to the institutional laboratory <11 ng ml−1, fluorescence immunoassay, Phadia, Uppsala, Sweden). All other parameters were within the normal range.

In the operation room, 1000 ml of secretions were aspirated through a nasogastric tube. Thereafter, a radial arterial line and a central venous line were inserted. Vital parameters were continuously monitored, and an antihistamine prophylaxis specific for mastocytosis [6 mg of dimetindene (H1 blocker), 50 mg of ranitidine (H2 blocker) and 100 mg of prednisone) was administered intravenously. After 45-degree head-up positioning and removal of the nasogastric tube, preoxygenation was performed with oxygen (FiO2: 1.0) for 4 min with a positive end-expiratory pressure (5 cmH2O). Rapid sequence induction was induced without mask ventilation with a bolus dose of sufentanil 50 μg (0.9 μg kg−1), propofol 150 mg (2.6 mg kg−1) and rocuronium 60 mg (1.1 mg kg−1) in a rapid sequence. Sixty seconds after the injection of the muscle relaxant, tracheal intubation was performed without any problems. Use of succinylcholine was avoided because of immobilisation, hemiparesis and mastocytosis. General anaesthesia was maintained by applying propofol 5 to 8 mg kg−1 h−1 and sufentanil as necessary. The application of both norepinephrine (0.1 to 0.25 μg kg−1 min−1) and balanced electrolyte solution administered intravenously were used as necessary. Antibiotic therapy consisted of 2 g of ceftriaxone and 600 mg of metronidazole. Laparotomy showed adhesions causing small bowel obstruction and minor necrosis of the mucosal layer. The lesions and the necrotic tissue were resected, and primary staple anastomosis was carried out.

Every 60 s (s), the train-of-four ratio (TOFR) (60 mA square wave stimuli, 0.2 ms; frequency 2 Hz) was measured with uncalibrated acceleromyography (TOF-Watch SX acceleromyograph, Organon Ltd., Dublin, Ireland) at the adductor pollicis muscle of the immobilised right arm with a hand adapter (Hand Adapter; Organon Ltd.). To achieve a moderate neuromuscular block (T1 to T4) during laparotomy, further small doses of rocuronium were administered (cumulative dose: 80 mg). At the end of surgery (duration: 145 min), moderate residual neuromuscular block (return of T2) was reversed with 120 mg of sugammadex (2.1 mg kg−1) to a TOFR of 100% within 150 s. The patient was extubated and transferred to the intensive care unit without any problems. No clinical episode of mast cell degranulation was observed. Blood samples taken 30 min after the induction of anaesthesia and 30 min after the application of sugammadex showed slightly but irrelevantly increased tryptase levels (retrospective assays, 18 ng ml−1 vs. 20 ng ml−1, reference <11 ng ml−1).

To our knowledge, this is the first report about the use of high-dose rocuronium and sugammadex in rapid sequence induction in a patient with systemic mastocytosis. Mastocytosis is subdivided into a benign cutaneous form and a systemic form with a high risk for general anaesthesia.1,2 A total of 10% of patients with cutaneous mastocytosis have systemic involvement with mast cell hyperplasia in various tissues, such as skin, bone marrow, liver, spleen and the gastrointestinal tract.1 Episodic symptoms such as flushing, pruritus, headache, palpitations, abdominal pain, diarrhoea, bronchospasm and systemic cardiovascular collapse can occur spontaneously or may be triggered by external factors (surgery, inflammation or anaesthesia).1,2 Intravenously administered drugs have the unpredictable potential of mast cell degranulation, liberating mediators such as histamine, tryptase, interleukins, TNF-α, proteinases and lipid-mediators.1 The cumulative prevalence of anaphylaxis in mastocytosis has been reported to be 49% in adults and 9% in children.1 Particularly neuromuscular blocking agents have the major side effects of both immune (IgE-related) and non-immune anaphylaxis (non-receptor G-protein mediated) with consecutive systemic mast cell activation.2 The rate of anaphylaxis due to atracurium (1 : 22 451) in the general population is almost 10-fold lower than anaphylaxis caused by succinylcholine (1 : 2080) and rocuronium (1 : 2499).3 High-dose rocuronium of 1.2 mg kg−1 did not provoke any significant non-immunological increase in plasma histamine levels and is not categorised as an initiator of mast cell activation. In contrast, atracurium and mivacurium have shown the highest unspecific histamine release.4,5 Succinylcholine is an empirically known mast cell activator and should be avoided in patients with systemic mastocytosis.5 Moreover, succinylcholine was contraindicated in our patient because of his prolonged immobilisation and hemiparesis that include the risk of hyperkalaemia with cardiac arrhythmia.6 Despite the risk of anaphylaxis, we used the rapid onset of high-dose rocuronium for rapid sequence induction because of its uneventful administration 6 years ago and a negative allergy test for muscle relaxants 4 years previously. If no rapid onset of relaxation is required, cis-atracurium and vecuronium would be the relaxants of choice because of the low potential for mast cell mediator release.5 Nonetheless one should keep in mind that a previous uneventful use of a drug like rocuronium is absolutely no guarantee that it can be reused without any risk of mast cell activation. Moderate residual neuromuscular block was reversed with sugammadex because of the depth of the block, asthma as a contraindication for neostigmine and possible mast cell activation by neostigmine.7,8 The incidence of anaphylactic reactions to sugammadex was estimated to be 1 : 34 483.9

The recommended strategy for perioperative mastocytosis management is avoiding mast cell-activating triggers and drugs (Table 1)2,5,8 as well as perioperative continuation of mast cell stabilisation medication (cromolyn sodium and glucocorticoids).2,5,8 Prophylactic application of H1 and H2 blockers are also recommended on the evening before surgery and 30 to 60 min before the induction of anaesthesia to antagonise the effects of mast cell mediators.2,5,8 Furthermore, application of glucocorticoids as anti-inflammatories and mast cell stabilisers should be considered.5 In the case of cardiovascular collapse, the drug of choice should be adrenaline because of its cardiovascular effects and its ability to prevent further mast cell degranulation. Perioperative monitoring of the plasma level of tryptase is recommended to assess mast cell activation.5,8 In the retrospectively conducted fluorescence immunoassay, our patient had slightly but not relevantly elevated tryptase levels before surgery. This finding showed that no relevant mast cell mediator release was triggered after the application of rocuronium and sugammadex.

Table 1
Table 1:
Drug recommendations for general anaesthesia in patients with mastocytosis

In conclusion, use of high-dose rocuronium for rapid sequence induction and sugammadex for reversing moderate residual paralysis combined with antihistamine prophylaxis may be a well tolerated strategy for patients with systemic mastocytosis. Sugammadex may also be an option for reversing vecuronium-induced residual paralysis in systemic mastocytosis.

Acknowledgements relating to this article

Assistance with the case report: none.

Financial support and sponsorship: none.

Conflicts of interest: none.


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