Case report
Anaphylactic shock versus Kounis syndrome in cardiac surgery: Differential diagnosis
Shock anafiláctico versus síndrome de Kounis durante el intraoperatorio de cirugía cardiaca: diagnóstico diferencial
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"apellidos" => "Fernández García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología y Reanimación, Complejo Asistencial Universitario de León, León, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cirugía Cardiaca, Complejo Asistencial Universitario de León, León, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Shock anafiláctico versus síndrome de Kounis durante el intraoperatorio de cirugía cardiaca: diagnóstico diferencial" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Kounis syndrome (KS) is defined as the appearance of an acute coronary event during an allergic reaction. In KS, the release of inflammatory mediators triggers coronary artery spasms and weakens the force of muscular contractions, which in turn reduces myocardial contractility. The incidence of KS is unknown and probably underdiagnosed. The information available on this entity comes from case reports and small case series,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> most of them related to beta-lactam antibiotics and non-steroidal anti-inflammatory agents.</p><p id="par0010" class="elsevierStylePara elsevierViewall">KS presenting as cardiogenic shock is rare, and hardly any cases have been published in the context of cardiac surgery.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 69-year-old patient scheduled for replacement of a prosthetic mitral valve due to paravalvular regurgitation. His medical history was significant for high blood pressure, chronic obstructive pulmonary disease, hypothyroidism, dyslipidaemia, hyperuricaemia, and possible Paget's disease. He had been evaluated by an allergist in 2011 due to adverse drug reactions, after which allergy to cefuroxime, paracetamol and omeprazole was ruled out. His surgical history included hydrocelectomy, transurethral resection of prostatic adenoma and mitral valve replacement in 1993, with replacement of the valve in 2000 due to endocarditis. During his latest hospital stay, and after several days of treatment with vancomycin, gentamicin, rifampicin and fluconazole, he presented urticaria with pruritus and alteration of hepatic enzymes, which was diagnosed as a toxic reaction.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the current preoperative work-up, he presented a positive indirect Coombs test identifying anti-E and anti-Jkb antibodies, which is why transfusion of red blood cells negative for Jkb was recommended. He was under treatment with furosemide, losartan, atorvastatin, allopurinol, alprazolam, inhaled beclomethasone plus formoterol, and intravenous sodium heparin.</p><p id="par0025" class="elsevierStylePara elsevierViewall">On arrival at the operating room, a peripheral line was inserted to deliver prophylaxis with 2<span class="elsevierStyleHsp" style=""></span>g intravenous cefazolin. The radial artery was cannulated for delivery of 2<span class="elsevierStyleHsp" style=""></span>ml lidocaine, and then anaesthetic induction and tracheal intubation was performed with midazolam 0.03<span class="elsevierStyleHsp" style=""></span>mg/kg, fentanyl 4<span class="elsevierStyleHsp" style=""></span>mcg/kg, etomidate 0.3<span class="elsevierStyleHsp" style=""></span>mg/kg and cisatracurium 0.2<span class="elsevierStyleHsp" style=""></span>mg/kg, after which the internal jugular vein was cannulated. The arterial and venous puncture sites and the surgical field were swabbed with povidone-iodine. Before proceeding with median sternotomy, the transesophageal echocardiography probe was put in place, 1<span class="elsevierStyleHsp" style=""></span>g of tranexamic acid was delivered over 20<span class="elsevierStyleHsp" style=""></span>min, following by continuous perfusion at a rate of 2<span class="elsevierStyleHsp" style=""></span>mg/kg/h. Anaesthesia was maintained with O<span class="elsevierStyleInf">2</span>-air (FiO<span class="elsevierStyleInf">2</span> 0.5–0.8), continuous perfusion of remifentanil, and inhalational sevoflurane to achieve BIS values between 40 and 60, and cisatracurium 0.03<span class="elsevierStyleHsp" style=""></span>mg/kg/h. After systemic heparinisation, and following ascending aorta and double vena cava cannulation, extracorporeal circulation (ECC) was started without incident. The mitral valve prosthesis showed extensive, inflammatory dehiscence in P2-P3 and A1, suggestive of endocarditis, so antibiotic therapy was immediately started with daptomycin 1<span class="elsevierStyleHsp" style=""></span>mg and gentamycin 280<span class="elsevierStyleHsp" style=""></span>g. Once the prosthesis had been replaced, and after monitoring with transesophageal echocardiography, we proceeded to disconnect the bypass pump. While doing so, the patient presented several episodes of supraventricular tachycardia with haemodynamic instability, which were treated with electrical cardioversion and amiodarone. During amiodarone infusion, and coinciding with the start of protamine infusion, we observed an increase in peak airway pressure and a capnography curve suggestive of obstruction, abrupt decrease in EtCO<span class="elsevierStyleInf">2</span>, and profound arterial hypotension refractory to aggressive volume expansion with crystalloids, intravenous 0.2<span class="elsevierStyleHsp" style=""></span>mg phenylephrine boluses, and ultimately 0.1<span class="elsevierStyleHsp" style=""></span>mg adrenaline, which was repeated until a total of 5<span class="elsevierStyleHsp" style=""></span>mg had been administered. The ECG showed ST segment elevation in the anterior and inferior leads. Arterial blood gas measured by pulse oximetry fell to 75%. Although no crackles or wheezing were heard on auscultation, 2 puffs of salbutamol were administered via the endotracheal tube and a further 100<span class="elsevierStyleHsp" style=""></span>mcg intravenously. No skin rash was observed in accessible areas. Ultrasound monitoring showed severe biventricular dysfunction. Given the situation, and with a suspicion of anaphylactic shock, we decided to interrupt infusion of both protamine and amiodarone, perform emergency recannulation and re-start ECC, while starting support with norepinephrine 0.8<span class="elsevierStyleHsp" style=""></span>mcg/kg/min and adrenaline 0.1<span class="elsevierStyleHsp" style=""></span>mcg/kg/min, and administration of 200<span class="elsevierStyleHsp" style=""></span>mg of hydrocortisone plus 100<span class="elsevierStyleHsp" style=""></span>mg methylprednisolone. Once ECC had been restarted, a venous sample was obtained and sent for determination of serum tryptase. Arterial hypotension persisted despite vasoconstrictors but gradually improved until vasoactive support could be partially reduced. Transesophageal echocardiography was performed again, and showed normal functioning of the mitral valve prosthesis and severe global biventricular dysfunction without segmental contractility abnormalities, which improved after starting dobutamine 15 mcg/kg/min. Once haemodynamics had stabilised, ECC was disconnected and the venous line was removed. Heparin was reversed with protamine at a very slow infusion rate through the peripheral line. The aortic catheter was only removed when half the dose had been administered, and no further haemodynamic or respiratory alterations were observed. After transfusion of 700<span class="elsevierStyleHsp" style=""></span>ml of frozen fresh plasma and 2 bags of red blood cells, the patient was transferred to the postanaesthesia care unit (PACU) with dobutamine, norepinephrine and adrenaline support, the latter 2 in tapering doses. Blood samples taken after re-start of ECC showed serum tryptase levels of to 38.40 mcg/l (tryptase reference value: 0–13.5<span class="elsevierStyleHsp" style=""></span>mcg/l), which subsequently fell to 23.3 and 15.2<span class="elsevierStyleHsp" style=""></span>mcg/l at 4 and 24<span class="elsevierStyleHsp" style=""></span>h post-shock. Sixteen hours after PACU admission, sedation was withdrawn and neurological integrity was confirmed, allowing us to extubate the patient without incident. The patient developed stage I acute kidney injury, with peak creatinine levels of 1.78<span class="elsevierStyleHsp" style=""></span>mg/dl, which was treated successfully with furosemide 10<span class="elsevierStyleHsp" style=""></span>mg/6<span class="elsevierStyleHsp" style=""></span>h. Maximum levels of ultrasensitive troponin and CK-MB were 1038<span class="elsevierStyleHsp" style=""></span>ng/l and 51<span class="elsevierStyleHsp" style=""></span>U/l, respectively at 8<span class="elsevierStyleHsp" style=""></span>h post-shock (reference values ultrasensitive troponin: 0–13<span class="elsevierStyleHsp" style=""></span>ng/l and CK-MB: 1–25<span class="elsevierStyleHsp" style=""></span>U/l). Vasoactive support was gradually withdrawn, and the patient was transferred to the ward 48<span class="elsevierStyleHsp" style=""></span>h after PACU admission. He was referred to the Allergy Service to undergo skin and epicutaneous tests due to a suspicion of anaphylactic shock. The prick test was positive for amiodarone and negative for protamine and vancomycin. The intradermal and epicutaneous tests were also negative for protamine and vancomycin. The echocardiogram performed at 7 days showed normal biventricular function.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">Diagnosis of KS is primarily clinical, based on the observation of signs and symptoms of acute allergic reaction coinciding with an acute coronary event.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> It can occur in patients without heart disease (KS type <span class="elsevierStyleSmallCaps">I</span>), in patients with pre-existing atherosclerosis (KS type II), or in patients with coronary stents (KS type III).</p><p id="par0035" class="elsevierStylePara elsevierViewall">In our case, diagnosis was complicated by the acute coronary event occurring during heart surgery, since cardiac enzymes are elevated after practically all types of heart surgery and the electrocardiographic changes suggestive of ischaemia that can occur after ECC are nonspecific, at least at that time. However, the severe biventricular dysfunction presented by our patient after disconnection from the heart bypass pump, combined with the need for inotropic support and the presence of ST segment elevation in the anterior and inferior leads, led us to at least take KS into consideration. In addition, the fact that the echocardiogram performed a week later was normal supported our initial diagnosis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">With regard to analytical work-up, increased levels of tryptase over baseline has a sensitivity of 73% and a specificity of 98% for the diagnosis of anaphylaxis, and these parameters increase when serial testing is performed.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the causative agent, amiodarone is a class 3 antiarrhythmic drug used for the treatment of both atrial and ventricular arrhythmias. It has been associated with several side effects, most of which are dose-dependent and appear in the context of prolonged oral administration.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> The adverse cardiovascular effects are potentially the most serious, and occur with intravenous administration. The incidence of allergic reaction to amiodarone is extremely low, even in patients with known allergy to iodinated contrast agents<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a>; anaphylaxis to amiodarone is rarely described in the medical literature,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> and has only once been reported in connection with severe haemodynamic collapse that required mechanical ventricular assistance.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> Fortunately, we were able to re-start cardiopulmonary bypass immediately because the event occurred during heart surgery, and despite having implemented adequate measures for the treatment of anaphylaxis, these were not effective, at least initially. Venoarterial extracorporeal membrane oxygenation has been used to resuscitate patients presenting anaphylaxis and cardiogenic shock, and may be an alternative if these events occur during non-cardiac surgery, or when ECC is unavailable.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">To date, 3 other entities have been linked to SK:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Tako-Tsubo cardiomyopathy, which mainly affects the apical area of the left ventricle.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Coronary vascular disease in allogeneic heart transplant.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Hypersensitivity myocarditis, mostly associated with viral infections.</p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">KS management involves treating the acute coronary syndrome and the anaphylaxis, and is aggravated by the fact that the drugs used are indicated for acute coronary syndrome and anaphylaxis separately, but may present contraindications when used in combination. This is particularly true of adrenalin which, though first-line treatment in anaphylaxis, can aggravate ischaemia, prolong the QT interval, and induce coronary vasospasm and arrhythmias. Further studies are needed before it can be fully recommended for the treatment of SK.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> The treatment currently recommended for the syndrome includes antihistamines, corticosteroids and antithrombotic therapy.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> In young, healthy patients, first-line treatment includes vasodilator agents (nitrates and calcium antagonists).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0075" class="elsevierStylePara elsevierViewall">KS is probably under-diagnosed, and should be included in the differential diagnosis of cardiogenic shock, particularly when accompanied by signs of hypersensitivity. It is important to consider KS in patients presenting an anaphylactic reaction, since treatment of this condition may require a multidisciplinary approach.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0080" 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" => "xres1135253" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1067350" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1135252" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1067351" "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" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-24" "fechaAceptado" => "2018-08-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1067350" "palabras" => array:6 [ 0 => "Kounis" 1 => "Anaphylaxis" 2 => "Acute biventricular failure" 3 => "Amiodarone" 4 => "Hypersensitivity" 5 => "Cardiac surgery" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1067351" "palabras" => array:6 [ 0 => "Kounis" 1 => "Anafilaxia" 2 => "Fracaso biventricular agudo" 3 => "Amiodarona" 4 => "Hipersensibilidad" 5 => "Cirugía cardiaca" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Although Kounis syndrome was described almost 3 decades ago, there has been a notable increase in the reports of cases of acute coronary syndromes developed in the context of allergic reactions, also known as Kounis syndrome. This article discusses the diagnostic possibility in the face of an acute biventricular failure in the course of an anaphylactic reaction during the intra-operative period of a cardiac valve surgery.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pese a que fue descrito hace casi 3 décadas, ha sido en los últimos años cuando se ha producido un incremento notable en la comunicación de casos de síndromes coronarios agudos desarrollados en el contexto de reacciones alérgicas, entidad que es conocida como síndrome de Kounis. En este artículo nos planteamos esta posibilidad diagnóstica ante un fracaso biventricular agudo en el transcurso de una reacción anafiláctica durante el intraoperatorio de una cirugía valvular cardiaca.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Merino García M, Castaño Ruiz M, Marcos-Vidal JM, González de Castro R, Marcos Contreras S, Fernández García D. Shock anafiláctico versus síndrome de Kounis durante el intraoperatorio de cirugía cardiaca: diagnóstico diferencial. Rev Esp Anestesiol Reanim. 2019;66:53–56.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Síndrome de Kounis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Rico Cepeda" 1 => "E. Palencia Herrejón" 2 => "M.M. 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