Scientific Letter
Near fatal bronchospasm and bradycardia after carbetocin administration
Broncoespasmo y bradicardia grave posterior a la administración de carbetocina
O.R. Pérez-Nieto, J.A. Castañón-González
, I.M. Lima-Lucero, L.A. Gorordo Delsol
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Unidad de Cuidados Intensivos y Medicina Crítica, Hospital Juárez de México, México City, Mexico
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Pérez-Nieto, J.A. Castañón-González, I.M. Lima-Lucero, L.A. Gorordo Delsol" "autores" => array:4 [ 0 => array:2 [ "nombre" => "O.R." "apellidos" => "Pérez-Nieto" ] 1 => array:4 [ "nombre" => "J.A." "apellidos" => "Castañón-González" "email" => array:1 [ 0 => "jorge.castanong@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:2 [ "nombre" => "I.M." "apellidos" => "Lima-Lucero" ] 3 => array:2 [ "nombre" => "L.A. Gorordo" "apellidos" => "Delsol" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Cuidados Intensivos y Medicina Crítica, Hospital Juárez de México, México City, Mexico" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Broncoespasmo y bradicardia grave posterior a la administración de carbetocina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1649 "Ancho" => 2504 "Tamanyo" => 140815 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pulmonary mechanics.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Uterotonics are widely used as prophylactic and therapeutic drugs for uterine atony, the major cause of direct maternal mortality due to postpartum hemorrhage.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1,2</span></a> Carbetocin [1-deamino-1-carba-2-tyrosine-(0-methyl)-oxytocin], a synthetic oxytocin analogue effective for treating and preventing post-partum hemorrhage, increases intracellular calcium, stimulates myosin phosphorylation and contraction in uterine smooth muscle cells; has an onset of action of 2<span class="elsevierStyleHsp" style=""></span>min and a plasma half-life six to seven times longer than oxytocin. It can be administered by intravenous (IV) and intramuscular route. Despite its safety profile, chest tightness, palpitations and breathing discomfort are frequently reported after its administration,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3,4,5</span></a> therefore prescription information and some reviews recommend caution when it is administered to patients with asthma or cardiovascular disease. Herein we report a case of near fatal bronchospasm and bradycardia after carbetocin administration.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 22 years-old pregnant female, with a past history of a ruptured ectopic tubal pregnancy two years earlier and asthma diagnosed during the first trimester of her current pregnancy, was admitted with at 39-week pregnancy to the obstetric ward for an elective Cesarean-section, current medication were two puffs of dose metered inhaled albuterol on a per needed basis. Surgery was performed under regional anesthesia. Due to uterine hemorrhage after birth, a bolus of 100<span class="elsevierStyleHsp" style=""></span>mcg of intravenous carbetocine was administered by intravenous infusion over 60<span class="elsevierStyleHsp" style=""></span>s, 2<span class="elsevierStyleHsp" style=""></span>min later, she presented sudden onset of dyspnea, wheezing, disseminated rash, hypotension and severe bradycardia – irresponsive to 1<span class="elsevierStyleHsp" style=""></span>mg of intravenous atropine – that progressed to a complete cardiac arrest; four minutes of advanced cardiopulmonary resuscitation which included 1<span class="elsevierStyleHsp" style=""></span>mg epinephrine was needed to restore pulse. After tracheal intubation severe wheezing and hypotension persisted, a single dose of 1.5<span class="elsevierStyleHsp" style=""></span>mg/kg IV methylprednisolone and a norepinephrine drip were initiated. Bleeding stopped, so surgery was finished and the patient was transferred to the Intensive Care Unit (ICU).</p><p id="par0015" class="elsevierStylePara elsevierViewall">She was admitted to the ICU on mechanical ventilation, pulmonary mechanics reported high intrathoracic pressures with an auto-PEEP of 12<span class="elsevierStyleHsp" style=""></span>cm H<span class="elsevierStyleInf">2</span>O and a peak inspiratory pressure of 35<span class="elsevierStyleHsp" style=""></span>cm H<span class="elsevierStyleInf">2</span>O. Arterial blood gases reported: PCO<span class="elsevierStyleInf">2</span> 91<span class="elsevierStyleHsp" style=""></span>mmHg, PaO<span class="elsevierStyleInf">2</span> 224<span class="elsevierStyleHsp" style=""></span>mm Hg, pH 6.99, HCO<span class="elsevierStyleInf">3</span> 19<span class="elsevierStyleHsp" style=""></span>meq/L, SaO<span class="elsevierStyleInf">2</span> 93. An ECG was obtained in sinus rhythm, with a heart rate of 95<span class="elsevierStyleHsp" style=""></span>min without conduction abnormalities. The chest X-ray ruled out pneumothorax or hyperinflation. After analgesia, sedation, and paralysis with vecuronium, under controlled mechanical ventilation, ventilator settings were modified to reduce respiratory rate and increase expiratory time, which gradually lowered intrathoracic pressures and allowed us to stop vasopressors. Albuterol 2.5<span class="elsevierStyleHsp" style=""></span>mg and ipratropium bromide 500 mcg were nebulized every 20<span class="elsevierStyleHsp" style=""></span>min, hydrocortisone and a single dose of 2<span class="elsevierStyleHsp" style=""></span>g of intravenous magnesium sulphate were also needed to finally totally overcome bronchospasm 3<span class="elsevierStyleHsp" style=""></span>h after ICU admission. Sedation was stopped, the patient regained consciousness, and 20<span class="elsevierStyleHsp" style=""></span>h after admission she was extubated and then discharged from the ICU (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Asthma is estimated to occur in approximately 4% of pregnancies, frequently as a pre-existing disease, although sometimes – like in this case –, asthma may initially present during pregnancy. Prospective studies show that about 28% of pregnant asthmatics improve, 33% remain unchanged and nearly 35% deteriorate usually between 24 and 36 weeks of gestation. During labor and delivery only 10% of asthmatics report symptoms and less than 5% require treatment.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6-8</span></a> Arrhythmias are an infrequent adverse event; however, alterations such as QT interval prolongation have been reported. These electrocardiographic alterations appear to be time and dose dependent.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Pulmonary mechanics at admission to the ICU and without neuromuscular blockade did not correlate with the severity of the clinical presentation, which could be related to the way we perform clinical measurements of gas trapping, which rely in the assumption that through all expiration, all of the airways remain in communication with the proximal airway; but frequently in severe bronchoconstriction, all of them may not be in communication with the proximal airway due to heterogeneous distribution of bronchial edema, secretions and mucus plugging; therefore, flow, pressure or gas volume cannot be accurately measured from a noncommunicating airway. In addition, expiratory muscle contraction can elevate auto-PEEP without adding to dynamic hyperinflation, therefore for accurate measurements of auto-PEEP the patient should be relaxed.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although we did not find severe bronchospasm reported after carbotecin administration in our medical literature search; profound reversible intraoperative bradycardia during cesarean section has been reported recently as a novel occurrence associated with the use of carbetocin.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Carbetocin prescription should have a clear indication and should be carefully individualized, based on individual medical and obstetric risk factors like prolonged labor, previous oxytocin administration, multiparity, multiple pregnancies, macrosomy, general anesthesia, and any condition that overdistends the uterus or interfere with effective uterine contraction.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical medicine is full of uncertainties, ambiguous data, unusual presentations, and atypical therapeutic responses as this case, until we gather more data, and based on the approximately 4% prevalence of asthma during pregnancy, it seems wise to avoid carbetocin in asthmatic pregnant women, as well as in those with a past medical history that suggest bronchial hyperreactivity.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financing</span><p id="par0045" class="elsevierStylePara elsevierViewall">No funding was received for this paper.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">No conflict of interest for disclosure.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financing" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:2 [ "identificador" => "xack348373" "titulo" => "Acknowledgments" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1649 "Ancho" => 2504 "Tamanyo" => 140815 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pulmonary mechanics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 12 | 16 | 28 |
| 2024 Octubre | 73 | 61 | 134 |
| 2024 Septiembre | 89 | 39 | 128 |
| 2024 Agosto | 83 | 56 | 139 |
| 2024 Julio | 70 | 29 | 99 |
| 2024 Junio | 107 | 67 | 174 |
| 2024 Mayo | 69 | 38 | 107 |
| 2024 Abril | 72 | 43 | 115 |
| 2024 Marzo | 69 | 37 | 106 |
| 2024 Febrero | 56 | 43 | 99 |
| 2024 Enero | 50 | 35 | 85 |
| 2023 Diciembre | 42 | 34 | 76 |
| 2023 Noviembre | 47 | 42 | 89 |
| 2023 Octubre | 71 | 33 | 104 |
| 2023 Septiembre | 57 | 45 | 102 |
| 2023 Agosto | 40 | 16 | 56 |
| 2023 Julio | 56 | 23 | 79 |
| 2023 Junio | 39 | 47 | 86 |
| 2023 Mayo | 60 | 43 | 103 |
| 2023 Abril | 55 | 36 | 91 |
| 2023 Marzo | 85 | 65 | 150 |
| 2023 Febrero | 52 | 40 | 92 |
| 2023 Enero | 35 | 32 | 67 |
| 2022 Diciembre | 80 | 58 | 138 |
| 2022 Noviembre | 69 | 54 | 123 |
| 2022 Octubre | 74 | 41 | 115 |
| 2022 Septiembre | 53 | 37 | 90 |
| 2022 Agosto | 74 | 44 | 118 |
| 2022 Julio | 69 | 47 | 116 |
| 2022 Junio | 73 | 37 | 110 |
| 2022 Mayo | 70 | 55 | 125 |
| 2022 Abril | 94 | 52 | 146 |
| 2022 Marzo | 59 | 54 | 113 |
| 2022 Febrero | 70 | 35 | 105 |
| 2022 Enero | 60 | 54 | 114 |
| 2021 Diciembre | 74 | 47 | 121 |
| 2021 Noviembre | 92 | 53 | 145 |
| 2021 Octubre | 122 | 81 | 203 |
| 2021 Septiembre | 50 | 52 | 102 |
| 2021 Agosto | 45 | 53 | 98 |
| 2021 Julio | 36 | 44 | 80 |
| 2021 Junio | 51 | 39 | 90 |
| 2021 Mayo | 61 | 70 | 131 |
| 2021 Abril | 167 | 106 | 273 |
| 2021 Marzo | 78 | 39 | 117 |
| 2021 Febrero | 89 | 33 | 122 |
| 2021 Enero | 75 | 42 | 117 |
| 2020 Diciembre | 76 | 32 | 108 |
| 2020 Noviembre | 31 | 26 | 57 |
| 2020 Octubre | 45 | 37 | 82 |
| 2020 Septiembre | 97 | 47 | 144 |
| 2020 Agosto | 33 | 34 | 67 |
| 2020 Julio | 38 | 30 | 68 |
| 2020 Junio | 40 | 30 | 70 |
| 2020 Mayo | 37 | 23 | 60 |
| 2020 Abril | 45 | 26 | 71 |
| 2020 Marzo | 33 | 26 | 59 |
| 2020 Febrero | 118 | 54 | 172 |
| 2020 Enero | 52 | 44 | 96 |
| 2019 Diciembre | 134 | 17 | 151 |
| 2019 Noviembre | 160 | 39 | 199 |
| 2019 Octubre | 192 | 32 | 224 |
| 2019 Septiembre | 47 | 35 | 82 |
| 2019 Agosto | 51 | 33 | 84 |
| 2019 Julio | 51 | 35 | 86 |
| 2019 Junio | 69 | 17 | 86 |
| 2019 Mayo | 48 | 56 | 104 |
| 2019 Abril | 26 | 33 | 59 |
| 2019 Marzo | 33 | 41 | 74 |
| 2019 Febrero | 43 | 46 | 89 |
| 2019 Enero | 34 | 65 | 99 |
| 2018 Diciembre | 60 | 41 | 101 |
| 2018 Noviembre | 148 | 117 | 265 |
| 2018 Octubre | 126 | 36 | 162 |
| 2018 Septiembre | 12 | 10 | 22 |
| 2018 Agosto | 2 | 1 | 3 |
| 2018 Julio | 6 | 1 | 7 |
| 2018 Junio | 2 | 1 | 3 |
| 2018 Mayo | 1 | 0 | 1 |
| 2017 Septiembre | 0 | 1 | 1 |
| 2017 Julio | 0 | 3 | 3 |
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