Case report
Anaphylactic risk due to systemic mastocytosis: Perioperative management in cardiac surgery
Riesgo anafiláctico por mastocitosis sistémica: manejo perioperatorio en cirugía cardíaca
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"apellidos" => "Planas Roca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cirugía Cardíaca, Hospital Universitario de la Princesa, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Riesgo anafiláctico por mastocitosis sistémica: manejo perioperatorio en cirugía cardíaca" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Mastocytosis is a heterogeneous group of rare myeloproliferative diseases that are caused by pathological growth and accumulation of mast cells, which can manifest cutaneously or systemically.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Under normal conditions, mast cells participate in the body's immunological and inflammatory response. The cytoplasm of the mast cell contains chemical mediators that can be released in certain clinical situations or by the action of certain drugs, and can cause excessive degranulation. This causes acute or chronic symptoms, which vary in their severity from mild to severe, and can even be life-threatening. Patients with mastocytosis may present erythema, itching, nausea, diarrhoea, dyspepsia, muscle and bone pain, osteoporosis, hypotonia, tachycardia, headaches, fatigue, depression, anxiety or, in extreme cases, anaphylaxis.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Many factors may be involved in the activation of mast cells and the release of their contents, such as histamine, tryptase and leukotrienes. The most common triggers for the release of these substances include: alcohol, physical exertion, high or low temperatures, ultraviolet radiation, stress and anxiety, infections, allergens, and various drugs, including morphine and its derivatives, some muscle relaxants such as succinylcholine and atracurium, NSAIDs, induction agents used in general anaesthesia, local aesthetics, colloids or iodinated contrasts.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,4</span></a> This means that medical procedures that include sedation, analgesia or general anaesthesia may pose a risk in patients with mastocytosis.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">There is scant information on the perioperative management of patients with mastocytosis undergoing on-pump cardiac surgery, and the few data available come mainly from isolated case reports.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">We present the case of a 71-year-old patient with indolent systemic mastocytosis presenting with episodes of histaminergic crisis, followed up by cardiology with a diagnosis of ischaemic heart disease since 2003 and aortic valvular stenosis. On his last visit, he reported dyspnoea on moderate exertion that had increased in recent months, and stable angina on moderate to strenuous exertion. He was therefore scheduled for on-pump heart surgery involving aortic valve replacement and anterior descending coronary artery bypass graft.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient's history was significant for several cardiovascular risk factors, such as hypertension, diabetes mellitus type 2, dyslipidaemia, overweight, and ischaemic heart disease, treated with the placement of various stents during different episodes of angina in the last 15 years. He also had hepatic steatosis, and presented incipient pulmonary fibrosis which was being followed up by pulmonology and treated with inhalers and continuous positive airway pressure.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Systemic mastocytosis is a chronic disease that presents with urticaria pigmentosa and several histaminergic crises, and requires close follow-up. A skin biopsy taken from the patient was positive for mastocytosis with a D816V mutation in c-kit and a bone marrow biopsy with 2% mast cells.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The day before surgery, a peripheral line was inserted and the patient was given 1 tablet of 10<span class="elsevierStyleHsp" style=""></span>mg montelukast 24<span class="elsevierStyleHsp" style=""></span>h before surgery, and a further tablet 1<span class="elsevierStyleHsp" style=""></span>h before surgery; 80<span class="elsevierStyleHsp" style=""></span>mg IV methylprednisolone the night before surgery and a further infusion 1<span class="elsevierStyleHsp" style=""></span>h before surgery; and 5<span class="elsevierStyleHsp" style=""></span>mg IV dexchlorpheniramine and 100<span class="elsevierStyleHsp" style=""></span>mg IV ranitidine 1<span class="elsevierStyleHsp" style=""></span>h before surgery. Because of his lung disease, he was also given 3 puffs of ipratropium bromide and 2 of formoterol/beclomethasone prior to the intervention. Finally, he was given 1 sublingual tablet of 1<span class="elsevierStyleHsp" style=""></span>mg lorazepam the night before surgery and a further tablet 1<span class="elsevierStyleHsp" style=""></span>h before surgery.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Once in the operating room, he was monitored with electrocardiogram, non-invasive cerebral oximetry, bispectral index, and pulse oximetry; he was sedated with 2<span class="elsevierStyleHsp" style=""></span>mg IV midazolam and the left radial artery was cannulated. Antibiotic prophylaxis with 2<span class="elsevierStyleHsp" style=""></span>g IV cefazolin was administered, together with 1<span class="elsevierStyleHsp" style=""></span>g IV tranexamic acid. Following this, anaesthesia was induced with IV remifentanil (0.1<span class="elsevierStyleHsp" style=""></span>mcg/kg/min), 8% sevoflurane and rocuronium (100<span class="elsevierStyleHsp" style=""></span>mg IV). Anaesthesia was maintained with 1%–2% sevoflurane, 0.05–0.2<span class="elsevierStyleHsp" style=""></span>mcg/kg/min remifentanil and rocuronium. The patient had undergone laparoscopic cholecystectomy in our hospital 8 years previously, and during that intervention sevoflurane, fentanyl and rocuronium were used without incident, so we were confident that the same drugs would be safe this time. Following induction, cardiac function was monitored with continuous transoesophageal echocardiography.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patient underwent a single left internal mammary artery-left anterior descending coronary artery bypass graft and replacement of the aortic valve with a biological prosthesis. Perfusion time was 59<span class="elsevierStyleHsp" style=""></span>min, aortic clamping time was 49<span class="elsevierStyleHsp" style=""></span>min, and nasopharyngeal and rectal temperature was between 35.3 and 36.5<span class="elsevierStyleHsp" style=""></span>°C during cardiopulmonary bypass (CPB). Spontaneous sinus rhythm was obtained after aortic declamping, and the surgery was uneventful. The patient remained haemodynamically stable, with no need for amines for vasoactive support, with the exception of 0.2<span class="elsevierStyleHsp" style=""></span>mg phenylephrine during pump weaning, and no need for blood transfusion. A total of 318<span class="elsevierStyleHsp" style=""></span>ml blood was transfused from the cell saver.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Serum tryptase was measured before anaesthesia induction and during CPB, being 58.1<span class="elsevierStyleHsp" style=""></span>mcg/l and 61.4<span class="elsevierStyleHsp" style=""></span>mcg/l, respectively.</p><p id="par0055" class="elsevierStylePara elsevierViewall">After surgery, with the patient haemodynamically and respiratorily stable, he was transferred to the intensive care unit and connected to mechanical ventilation. His clinical evolution was favourable, and he was extubated after 5<span class="elsevierStyleHsp" style=""></span>h and discharged to the cardiac surgery ward the day after surgery. He was discharged home 5 days later, with no complications. The only analgesia given during his hospital stay was paracetamol and metamizole, which had been previously well tolerated by the patient. He reported good pain, and did not required NSAIDs.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The patient has understood and signed a form consenting to the publication of this case report.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Mastocytosis is a rare clinical condition, with an estimated incidence of 1:150,000 inhabitants. Indolent systemic mastocytosis is the most common form of systemic mastocytosis, and accounts for approximately two thirds of all cases.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In most patients with systemic indolent mastocytosis, the disease remains dormant for many years, while in others, symptoms progress and can even be life-threatening. The cumulative incidence of anaphylaxis in adult patients with mastocytosis is as high as 49%.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,5</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Surgery can trigger mast cell degranulation in these patients, either due to the procedure itself or to the drugs administered. Many drugs commonly used in the surgical setting can cause a histaminergic reaction. The mediators released act on the heart, vessels, skin, and lung, among others, and can lead to cardiac, haemodynamic and metabolic disorders similar to those observed in anaphylactic reactions or severe clotting disorders.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,4,6</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The capacity of some of these drugs to trigger mastocyte degranulation has been demonstrated <span class="elsevierStyleItalic">in vitro</span>, and several cases of severe reactions during anaesthesia have been described. According to data collected by the Spanish Mastocytosis Network, around 4% of adults with systemic mastocytosis present severe reactions during general anaesthesia.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> This is why it is essential to carefully plan and organise the anaesthesia strategy in these patients, starting with the preoperative anaesthesia evaluation and continuing throughout the intraoperative and postoperative period. However, given the rarity of systemic mastocytosis, along with the scant probability of patients with this disease requiring cardiac surgery, there are no clear guidelines for safe surgery, and the few recommendations published are based on an analysis of the clinical cases published to date.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,5</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Cardiac surgery carries a greater risk of systemic mastocytosis degranulation than general surgical procedures, given the artificial surface of the bypass pump, aortic clamping, ischaemia-reperfusion injury, endotoxaemia, surgical trauma and hypothermia induced for cardiopulmonary bypass.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Our patient presented a chronic form of indolent systemic mastocytosis, and although he had previously presented skin and histaminergic syndromes, at the time of surgery he was stable with decreasing serum tryptase levels, and had not presented a crisis in recent years.</p><p id="par0090" class="elsevierStylePara elsevierViewall">He was admitted 36<span class="elsevierStyleHsp" style=""></span>h before the intervention in order to receive montelukast, methylprednisolone, dexchlorpheniramine and ranitidine for premedication. As anxiety can also trigger mast cells degranulation, he was sedated with oral lorazepam and intravenous midazolam upon arrival at the operating room. We were careful to avoid preoperative administration of intramuscular morphine, which is usually included in the premedication protocol of patients undergoing cardiac surgery. We also avoided administering colloids during the patient's hospital stay, since both morphine and colloids are known to cause anaphylactic reaction in mastocytosis.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">For anaesthesia induction and maintenance, we chose drugs with minimum histamine-releasing action that had been used uneventfully in the patient's previous surgeries. For example, we considered the possibility of using etomidate, since it has no histamine-releasing effect; however we opted for induction with sevoflurane, since fluorinated inhalational anaesthetics have a similar safety profile with respect to histamine release, and sevoflurane had previously been used safely in the patient. Furthermore, single-breath vital capacity inhalation induction with 8% sevoflurane in patients undergoing cardiac surgery procedures gives rapid onset of anaesthesia, good airway management, and a good haemodynamic profile. All these factors are beneficial in an individual who also had lung disease.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Regarding opiates, which are among the drugs with the greatest histamine-releasing effect, the patient's history showed that fentanyl had been used safely. Fentanyl and remifentanil have also been used safely in patients with mastocytosis; however, like neuromuscular relaxants, it is important to individualise their use, since severe reactions have been described.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The effects of mastocyte degranulation were controlled by monitoring levels of serum tryptase, which is considered the most specific marker in these cases. Values were determined before induction and after the start of CPB, since total serum tryptase levels are an indicator of mast cell burden, so elevated levels of tryptase increase the likelihood of systemic mastocytosis with multiorgan involvement (>20<span class="elsevierStyleHsp" style=""></span>mcg/l).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Although our patient had high baseline tryptase levels (58.1<span class="elsevierStyleHsp" style=""></span>mcg/l), no complications were observed in either the intra- or postoperative periods.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The main aim of these precautions and the premedication strategy used was to prevent an intraoperative histaminergic crisis. Despite this, epinephrine, actocortin and H1 and H2 antihistamines were available in the operating room, in case the patient presented an anaphylactic shock.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> If a reaction had occurred, we would have measured serum tryptase at the time of the event, and again at 6 postoperative hours, following the protocols in place in our centre.</p><p id="par0110" class="elsevierStylePara elsevierViewall">A detailed, carefully planned premedication strategy involving H<span class="elsevierStyleInf">1</span>, H<span class="elsevierStyleInf">2</span> and leukotriene receptor antagonists and corticosteroids, together with appropriate anxiolysis, suitable anaesthetic agents, and other non-histamine-releasing drugs, ensure that surgery can be performed safely and effectively, even in patients with possible multiorgan involvement. This enabled us to treat our patient correctly, despite the lack of guidelines and the paucity of published studies and scientific evidence.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors confirm that they have no known conflict of interest associated with the publication of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1196207" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1114605" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1196206" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1114604" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-11-27" "fechaAceptado" => "2019-01-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1114605" "palabras" => array:5 [ 0 => "Mastocytosis" 1 => "Cardiac surgery" 2 => "Anaphylaxis" 3 => "Prevention" 4 => "Pre-medication" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1114604" "palabras" => array:5 [ 0 => "Mastocitosis" 1 => "Cirugía cardíaca" 2 => "Anafilaxia" 3 => "Prevención" 4 => "Premedicación" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mastocytosis is a disease characterised by an abnormal proliferation of mast cells. The degranulation of mast cells can be triggered by chemical, physical, and psychological factors, and in severe cases may be accompanied by cardiovascular alterations and shock. Tryptase concentrations greater than 20<span class="elsevierStyleHsp" style=""></span>μg/L may be associated with an increased risk of mastocyte degranulation. The case is presented on a 71 year-old man that underwent an aortic valve replacement and aortic-coronary bypass surgery. He had an indolent systemic mastocytosis and a history of histaminergic crises, with a baseline value of tryptase prior to surgery of 58.1<span class="elsevierStyleHsp" style=""></span>μg/L.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La mastocitosis es una enfermedad caracterizada por una proliferación anormal de los mastocitos. La degranulación de los mastocitos puede desencadenarse por factores químicos, físicos y psíquicos, y en casos graves puede cursar con alteraciones cardiovasculares y shock. Concentraciones de triptasa superiores a 20<span class="elsevierStyleHsp" style=""></span>mcg/l se podrían correlacionar con mayor riesgo de degranulación mastocitaria. Presentamos el caso de un varón de 71 años sometido a cirugía de sustitución valvular aórtica y derivación aortocoronaria con mastocitosis sistémica indolente, con antecedentes de crisis histaminérgicas y con valores basales previos a la cirugía de tripatasa de 58,1<span class="elsevierStyleHsp" style=""></span>mcg/l.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín Serrano P, Martín Hernández JG, Martín Celemín R, de Antonio Antón N, Orús García R, Planas Roca A. Riesgo anafiláctico por mastocitosis sistémica: manejo perioperatorio en cirugía cardíaca. Rev Esp Anestesiol Reanim. 2019;66:346–349.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perioperative management of patients with mastocytosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Dewachter" 1 => "M. 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