Case report
Kounis syndrome after rocuronium administration
Síndrome de Kounis tras administración de rocuronio
B. del Val Villanueva
, S. Telletxea Benguria, I. González-Larrabe, J.M. Suárez Romay
Corresponding author
Servicio de Anestesiología y Reanimación, Hospital de Galdakao-Usánsolo, Galdakao, Vizcaya, Spain
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Telletxea Benguria, I. González-Larrabe, J.M. Suárez Romay" "autores" => array:4 [ 0 => array:4 [ "nombre" => "B." "apellidos" => "del Val Villanueva" "email" => array:1 [ 0 => "Beatriz.delvalvillanueva@osakidetza.eus" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Telletxea Benguria" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "González-Larrabe" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Suárez Romay" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital de Galdakao-Usánsolo, Galdakao, Vizcaya, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Kounis tras administración de rocuronio" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Allergic angina syndrome and allergic myocardial infarction, now known as Kounis syndrome, was first described by Kounis and Zavras in 1991.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Kounis syndrome is the concurrence of an acute coronary syndrome with hypersensitivity to an antigen. This leads to the activation and degranulation of mast cells and basophils and the subsequent release of inflammatory mediators, which cause coronary vasospasm and/or rupture of atheromatous plaque</p><p id="par0015" class="elsevierStylePara elsevierViewall">Three subtypes of Kounis syndrome have so far been described in the literature: type <span class="elsevierStyleSmallCaps">i</span>, no coronary artery disease; type <span class="elsevierStyleSmallCaps">II</span>, coronary disease; and type <span class="elsevierStyleSmallCaps">iii,</span> in patients with drug-eluting stent thrombosis.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It is important to understand this disease and take it into consideration in patients presenting with an acute coronary syndrome in the context of anaphylaxis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0025" class="elsevierStylePara elsevierViewall">We present the case of a 65-year-old man with no known drug allergies, ex-smoker, with high blood pressure, chronic kidney failure, ischaemic heart disease that had begun with unstable angina in 1996, and single vessel coronary artery disease (anterior descending artery). His condition had been stabilised with medical treatment, and his last echocardiogram, in 2012, was normal. He was under treatment with acetylsalicylic acid, bisoprolol, valsartan and nitro-glycerine, and had been scheduled for ultralow anterior resection due to colorectal cancer.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A peripheral line was placed on arrival in the operating room, and non-invasive blood pressure, pulse oximetry and 12-lead electrocardiogram monitoring was started after confirming that the patient haemodynamically stable. Following this, he was preoxygenated.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After anaesthetic induction with propofol 120<span class="elsevierStyleHsp" style=""></span>mg, fentanyl 150 mcg and rocuronium 50<span class="elsevierStyleHsp" style=""></span>mg, direct laryngoscopy was performed, during which sinus tachycardia of up to 150<span class="elsevierStyleHsp" style=""></span>bpm with ST depression in all leads, hypotension of 70/40<span class="elsevierStyleHsp" style=""></span>mmHg and signs of tissue hypoperfusion were observed. The patient was given 90<span class="elsevierStyleHsp" style=""></span>mcg phenylephrine and fluids (crystalloid 1500<span class="elsevierStyleHsp" style=""></span>ml), which improved blood pressure, decreased tachycardia, and normalised the electrocardiogram. In light of the situation, the surgical intervention was suspended and the patient was extubated without incident and transferred to the post anaesthesia care unit (PACU).</p><p id="par0040" class="elsevierStylePara elsevierViewall">Cardiac catheterisation was performed in the PACU, showing severe anterior descending artery stenosis. Angioplasty was performed to insert a drug-eluting stent and dual antiplatelet therapy with clopidogrel 75<span class="elsevierStyleHsp" style=""></span>mg and acetylsalicylic acid 100<span class="elsevierStyleHsp" style=""></span>mg was started.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patient was admitted to the Cardiology Ward, where he remained hemodynamically stable with no further cardiac events.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Three months after the episode described above, the patient was rescheduled for surgery. He was admitted 6 days before surgery to start bridging therapy, but given the high risk of bleeding (3 months after drug-eluting stent placement), the cardiologist recommended discontinuing clopidogrel and ruling out bridging therapy.</p><p id="par0055" class="elsevierStylePara elsevierViewall">On the day of the new intervention, the patient was haemodynamically stable on transfer to the anaesthetic room, where he was given antibiotic prophylaxis with metronidazole 500<span class="elsevierStyleHsp" style=""></span>mg and premedicated with midazolam 1<span class="elsevierStyleHsp" style=""></span>mg. Anaesthesia was induced with etomidate 18<span class="elsevierStyleHsp" style=""></span>mg and fentanyl 100<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mcg. At the start of rocuronium administration (50<span class="elsevierStyleHsp" style=""></span>mg), we observed onset on tachyarrhythmia of 145<span class="elsevierStyleHsp" style=""></span>bpm, severe hypotension and a skin rash on trunk and extremities.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Crystalloids (1000<span class="elsevierStyleHsp" style=""></span>ml), i.v. hydrocortisone 200<span class="elsevierStyleHsp" style=""></span>mg, i.v. dexchlorpheniramine 5<span class="elsevierStyleHsp" style=""></span>mg, phenylephrine 50<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mcg and ranitidine 50<span class="elsevierStyleHsp" style=""></span>mg were administered, which gradually increased blood pressure and slowed heart rate to 120–110<span class="elsevierStyleHsp" style=""></span>bpm.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Surgery was again postponed. When blood pressure had normalised, samples were taken for tryptase and total IgE analysis due to suspicion of anaphylactic shock, and the patient was transferred to the PACU.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Lab results showed tryptase levels of up to 87.3<span class="elsevierStyleHsp" style=""></span>mcg/L at the time of anaesthesia induction, with total IgE levels within normal parameters in each sample collected (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Suspecting anaphylaxis, the patient was referred to the allergy service, where he underwent skin tests. Prick testing was performed with undiluted drugs, and was positive for rocuronium and negative for cisatracurium, succinylcholine, midazolam, etomidate, propofol and fentanyl. Given the positive results of the skin test, intradermal rocuronium was not performed, but intradermal testing for all other study drugs was negative. On the basis of these results, the episode presented by our patient was classified as Kounis type <span class="elsevierStyleSmallCaps">II</span> syndrome, given the presence of atherothrombotic disease, and ultralow anterior resection was re-scheduled.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Succinylcholine, which had tested negative on both skin and intradermal tests, was used for orotracheal intubation together with etomidate and fentanyl. Sevoflurane and epidural infusion of levobupivacaine were used during anaesthesia maintenance to improve muscle relaxation and avoid the need for other neuromuscular blocking agents. The surgery was uneventful, and the patient was transferred to the PACU for postoperative monitoring.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Three types of Kounis syndrome have so far been described.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Type <span class="elsevierStyleSmallCaps">I</span> is seen in patients with coronary artery in whom anaphylaxis induces a coronary spasm; type <span class="elsevierStyleSmallCaps">ii</span> occurs in patients with known or unsuspected pre-existing atherosclerotic disease, in whom acute release of inflammatory mediators can induce erosion or rupture of atheromatous plaque; and finally, type <span class="elsevierStyleSmallCaps">iii</span>, in which drug-eluting stent thrombosis occurs.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In the case described here, the patient was classified as Kounis type <span class="elsevierStyleSmallCaps">II</span>.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Kounis syndrome has been associated with various medical conditions (asthma, hives, food allergies), hymenoptera stings, environmental exposure, and a wide variety of drugs such as beta-lactams, non-steroidal anti-inflammatory drugs, general anaesthetics, corticosteroids and iodinated radio contrast agents.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The wide range of potentially allergenic drugs used during anaesthesia can make it difficult to pinpoint the agent triggering the anaphylactic reaction. However, recent case reports have described onset of Kounis syndrome associated with the administration of rocuronium<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6,7</span></a> and cisatracurium<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> during anaesthesia induction. Although cisatracurium-induced histamine release is milder than atracurium-induced reactions, allergic reactions are mediated by IgE and can therefore be triggered by cisatracurium.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The case reported by Yang et al. shows that cisatracurium can trigger anaphylaxis and Kounis syndrome, and even suggests the existence of a cross-reaction between these neuromuscular blockers.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The aetiology of this syndrome remains unclear, but the release of mast cell mediators such as histamine, serotonin, tryptase and leukotrienes is thought to induce coronary artery spasm in Kounis syndrome type <span class="elsevierStyleSmallCaps">i</span> and erosion of a pre-existing atheromatous plaque in type <span class="elsevierStyleSmallCaps">II</span>Kounis syndrome.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Although diagnosis can be misled by the presence of cardiac events that mask the allergic reaction, it is advisable to carry out laboratory tests to objectify the cardiac damage and reveal a possible allergic reaction. Tryptase is a good marker of anaphylaxis, although it does not differentiate between allergic and nonallergic anaphylaxis.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In our case, elevated levels of tryptase together with a history of coronary heart disease and the appearance of signs and symptoms of anaphylaxis (tachycardia of 145<span class="elsevierStyleHsp" style=""></span>bpm, skin rash and severe hypotension) supported our suspicion that the symptoms had been triggered by a drug reaction.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> This was later confirmed with the positive prick test for rocuronium.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Management of Kounis syndrome can be challenging. Although both the acute coronary syndrome and allergic reaction need to be addressed, the drugs used during treatment may in fact aggravate the anaphylaxis or worsen cardiac function.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Anaphylaxis needs to be treated promptly, without waiting for laboratory confirmation. The treatment of choice in these cases is usually vasopressors, corticosteroids, antihistamines and antithrombotic agents. In our patient, intravascular volume was normalised with the administration of phenylephrine and fluids, and the symptoms were controlled with the administration of corticosteroids and antihistamines.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The use of adrenaline is controversial, since it can aggravate ischaemia, prolong the QT interval, and induce coronary vasospasm and arrhythmias; however, it should be administered in the presence of severe hypotension or cardiac arrest.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> Although adrenaline is the drug of choice for the treatment of anaphylaxis, it was not deemed necessary in our patient and was therefore not administered.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Administration of acetylsalicylic acid can aggravate the allergic reaction by increasing circulating leukotriene levels. It should only be used when the benefit outweighs the risk, and should be administered under continuous monitoring. Nitro-glycerine, which can cause hypotension and tachycardia, should be used with caution, but is beneficial in haemodynamically stable patients. Fluid replacement therapy can cause acute pulmonary oedema in patients with Kounis syndrome. If administered, blood pressure and left ventricular function should be monitored. Coronary vasospasm generally responds to calcium channel blockers, and these are therefore the anti-ischaemic drugs of choice in Kounis syndrome.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Opioids should be used with caution, because morphine, meperidine and codeine can cause nonspecific degranulation of mast cells and aggravate the allergic reaction. In haemodynamically stable patients, allergic symptoms can sometimes be treated with H1 and H2 blockers and corticosteroids alone.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The number of case reports involving Kounis syndrome is growing steadily, and it is important to understand the diagnosis and management of this syndrome in order to differentiate it from a classic allergic reaction.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have received no funding for the publication of this manuscript.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1042056" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec994814" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1042055" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec994813" "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" => "Funding" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-04-10" "fechaAceptado" => "2017-12-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec994814" "palabras" => array:6 [ 0 => "Kounis" 1 => "Allergic myocardial infarction" 2 => "Allergic angina" 3 => "Rocuronium" 4 => "Hypersensitivity" 5 => "Anaphylaxis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec994813" "palabras" => array:6 [ 0 => "Kounis" 1 => "Infarto de miocardio alérgico" 2 => "Angina alérgica" 3 => "Rocuronio" 4 => "Hipersensibilidad" 5 => "Anafilaxia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kounis syndrome encompasses concepts including angina and allergic infarction described in relation to exposure to different allergens. The aim of this article is to describe a case of Kounis Syndrome type <span class="elsevierStyleSmallCaps">II</span> after exposure to rocuronium as well as the patholophysiology and the treatment of this syndrome.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El síndrome de Kounis engloba conceptos entre los que se incluyen la angina e infarto alérgico descritos en relación con la exposición a diferentes alérgenos. El objetivo de este artículo es describir un caso de síndrome de Kounis tipo <span class="elsevierStyleSmallCaps">ii</span> tras la exposición a rocuronio así como la fisiopatología y tratamiento de este síndrome.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: del Val Villanueva B, Telletxea Benguria S, González-Larrabe I, Suárez Romay JM. Síndrome de Kounis tras administración de rocuronio. Rev Esp Anestesiol Reanim. 2018;65:343–346.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Tryptase reference values: 0–13.5<span class="elsevierStyleHsp" style=""></span>mcg/L.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Serum tryptase \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After anaesthesia induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87.3<span class="elsevierStyleHsp" style=""></span>mcg/L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>h after induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.9<span class="elsevierStyleHsp" style=""></span>mcg/L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">20 days after induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>mcg/L \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1770384.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Serum levels of tryptase after induction, at 2<span class="elsevierStyleHsp" style=""></span>h and at 20-days.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histamine-induced coronary artery spasm: the concept of allergic angina" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N.G. 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