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
Corresponding author
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" => "xack348609" "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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 13 | 25 |
| 2024 October | 80 | 51 | 131 |
| 2024 September | 104 | 43 | 147 |
| 2024 August | 86 | 46 | 132 |
| 2024 July | 87 | 30 | 117 |
| 2024 June | 76 | 60 | 136 |
| 2024 May | 80 | 41 | 121 |
| 2024 April | 93 | 51 | 144 |
| 2024 March | 81 | 28 | 109 |
| 2024 February | 93 | 35 | 128 |
| 2024 January | 83 | 33 | 116 |
| 2023 December | 94 | 46 | 140 |
| 2023 November | 97 | 25 | 122 |
| 2023 October | 97 | 25 | 122 |
| 2023 September | 64 | 48 | 112 |
| 2023 August | 60 | 17 | 77 |
| 2023 July | 62 | 23 | 85 |
| 2023 June | 57 | 14 | 71 |
| 2023 May | 73 | 31 | 104 |
| 2023 April | 70 | 17 | 87 |
| 2023 March | 80 | 40 | 120 |
| 2023 February | 87 | 34 | 121 |
| 2023 January | 116 | 20 | 136 |
| 2022 December | 96 | 54 | 150 |
| 2022 November | 128 | 31 | 159 |
| 2022 October | 116 | 31 | 147 |
| 2022 September | 86 | 44 | 130 |
| 2022 August | 76 | 45 | 121 |
| 2022 July | 50 | 24 | 74 |
| 2022 June | 49 | 28 | 77 |
| 2022 May | 72 | 33 | 105 |
| 2022 April | 68 | 39 | 107 |
| 2022 March | 87 | 39 | 126 |
| 2022 February | 90 | 28 | 118 |
| 2022 January | 98 | 34 | 132 |
| 2021 December | 83 | 46 | 129 |
| 2021 November | 88 | 35 | 123 |
| 2021 October | 94 | 63 | 157 |
| 2021 September | 64 | 39 | 103 |
| 2021 August | 56 | 51 | 107 |
| 2021 July | 39 | 28 | 67 |
| 2021 June | 40 | 29 | 69 |
| 2021 May | 63 | 57 | 120 |
| 2021 April | 157 | 98 | 255 |
| 2021 March | 84 | 28 | 112 |
| 2021 February | 85 | 24 | 109 |
| 2021 January | 73 | 14 | 87 |
| 2020 December | 63 | 14 | 77 |
| 2020 November | 51 | 22 | 73 |
| 2020 October | 52 | 31 | 83 |
| 2020 September | 58 | 29 | 87 |
| 2020 August | 36 | 20 | 56 |
| 2020 July | 24 | 20 | 44 |
| 2020 June | 42 | 16 | 58 |
| 2020 May | 40 | 18 | 58 |
| 2020 April | 45 | 14 | 59 |
| 2020 March | 12 | 16 | 28 |
| 2020 February | 63 | 21 | 84 |
| 2020 January | 35 | 26 | 61 |
| 2019 December | 26 | 23 | 49 |
| 2019 November | 27 | 31 | 58 |
| 2019 October | 31 | 23 | 54 |
| 2019 September | 32 | 23 | 55 |
| 2019 August | 56 | 22 | 78 |
| 2019 July | 42 | 27 | 69 |
| 2019 June | 18 | 21 | 39 |
| 2019 May | 35 | 34 | 69 |
| 2019 April | 18 | 25 | 43 |
| 2019 March | 21 | 25 | 46 |
| 2019 February | 25 | 35 | 60 |
| 2019 January | 23 | 42 | 65 |
| 2018 December | 20 | 18 | 38 |
| 2018 November | 28 | 33 | 61 |
| 2018 October | 13 | 12 | 25 |
| 2018 July | 2 | 0 | 2 |
| 2018 June | 0 | 1 | 1 |
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