Bradycardia in a pediatric population after sugammadex administration: case series

Abstract Sugammadex is a distinctive neuromuscular reversal drug that acts by encapsulating the neuromuscular relaxant molecule and dislodging it from its site of action. Sugammadex has been approved for pediatric patients over 2 years of age. Although arrhythmias have been reported, there is no report of adverse effects in healthy children, such as severe bradycardia requiring intervention. We report two cases of severe bradycardia immediately after the administration of sugammadex in healthy children. Our aim is to alert to the occurrence of one of the most severe adverse effects of sugammadex, in the healthy pediatric population as well.

Changes in gap junction proteins Connexin30. 2 and Connexin40 expression in the sinoatrial node of rats with dexmedetomidine-induced sinus bradycardia

Abstract Background Dexmedetomidine (Dex) is widely used, and its most common side effect is bradycardia. The complete mechanism through which Dex induces bradycardia has not been elucidated. This research investigates the expression of gap junction proteins Connexin30.2 (Cx30.2) and Connexin40 (Cx40) within the sinoatrial node of rats with Dex-induced sinus bradycardia. Methods Eighty rats were randomly assigned to five groups. Saline was administered to rats in Group C. In the other four groups, the rats were administered Dex to induce bradycardia. In groups D1and D2, the rats were administered Dex at a loading dose of 30 μg.kg−1 and 100 μg.kg−1 for 10 min, then at 15 μg.kg−1.h−1 and 50 μg.kg−1.h−1 for 120 min separately. The rats in group D1A and D2A were administered Dex in the same way as in group D1and D2; however, immediately after the administration of the loading dose, 0.5 mg atropine was administered intravenously, and then at 0.5 mg.kg−1.h−1 for 120 min. The sinoatrial node was acquired after intravenous infusion was completed. Quantitative real-time polymerase chain reaction and western blot analyses were performed to measure mRNA and protein expression of Cx30.2 and Cx40, respectively. Results The expression of Cx30.2 increased, whereas the expression of Cx40 decreased within the sinoatrial node of rats with Dex-induced sinus bradycardia. Atropine reversed the effects of Dex on the expression of gap junction proteins. Conclusion Dex possibly altered the expression of gap junction proteins to slow down cardiac conduction velocity in the sinoatrial node.

Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia / Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

Severe bradycardia and asystole associated with sugammadex: case report / Bradicardia grave e assistolia associadas ao sugamadex: relato de caso

Abstract Background and objectives: Sugamadex is a modified gamma-cyclodextrin, the first selective agent for reversal of neuromuscular blockade induced by steroidal non-depolarizing muscle relaxants, with greater affinity for rocuronium. In this article we present a case of severe bradycardia and asystole following sugammadex administration. Case report: A 54-year-old male patient, ASA II, with a history of hypertension, dyslipidemia and obesity, who underwent an emergency umbilical herniorrhaphy under balanced general anesthesia. Intraoperative muscle relaxation was maintained with rocuronium. At the end of the surgery, the patient maintained a neuromuscular block with two TOF responses, and sugammadex (200 mg) was administered. About thirty seconds after its administration, the patient developed marked bradycardia (HR 30 bpm) followed by asystole. Conclusions: Documented bradycardia and asystole were attributed to the administration of sugammadex. This case shows that, although rare, cardiac arrest is a possible adverse effect of this drug, and that the knowledge of this situation can be determinant for the patient's evolution.

Resumo Justificativa e objetivos: O sugamadex é uma gama ciclodextrina modificada, o primeiro agente seletivo para reversão do bloqueio neuromuscular induzido pelos relaxantes musculares não despolarizantes do tipo esteroide, com maior afinidade para o rocurônio. Neste artigo apresentamos um caso de bradicardia grave e assistolia após administração de sugamadex. Relato do caso: Doente do sexo masculino, 54 anos, ASA II, com antecedentes pessoais de hipertensão, dislipidemia e obesidade, submetido à herniorrafia umbilical em regime de urgência sob anestesia geral balanceada. O relaxamento muscular intraoperatório foi mantido com rocurônio. No fim da cirurgia o doente mantinha bloqueio neuromuscular com duas respostas no TOF, pelo que foi administrado sugamadex 200 mg. Cerca de trinta segundos após a sua administração, o doente desenvolveu bradicardia acentuada (FC 30 bpm) seguida de período de assistolia. Conclusões: A bradicardia e a assistolia documentadas foram atribuídas à administração do sugamadex. Este caso evidencia que, apesar de rara, a parada cardíaca é um efeito adverso possível desse fármaco e que o conhecimento dessa situação pode ser determinante para a evolução do doente.

The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis / A experiência da vida real com complicações cardiovasculares na primeira dose de fingolimode

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Fingolimode é um tratamento novo e eficaz para esclerose múltipla (EM). A administração desta droga requer atenção especial para a primeira dose, uma vez que eventos adversos cardiovasculares podem ser observados nas seis horas iniciais da ingestão de fingolimode. O presente estudo consistiu de uma revisão de dados cardiovasculares de 180 pacientes com EM ao receberem a primeira dose de fingolimode. A taxa de bradicardia nestes pacientes foi maior do que aquele observada em estudos clínicos que tem critérios de inclusão muito rigorosos para seleção de pacientes. Menos de 10% dos casos necessitou de atenção especial, mas não houve casos fatais. Todos os pacientes exceto por um continuaram o tratamento após esta dose inicial. Este é o primeiro relato de dados de administração de fingolimode na vida real de pacientes brasileiros com EM, e um dos poucos trabalhos com estas características no mundo.

The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice

BACKGROUND/AIMS: Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. METHODS: Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response. RESULTS: The mean daily dose of amiodarone was 227 +/- 126 mg, and the mean duration was 490 +/- 812 days. During the mean follow-up duration of 982 +/- 1,137 days, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year). CONCLUSIONS: Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.

Progress on suxamethonium chloride analysis / 法医学杂志

Abstract: Suxamethonium chloride is a depolarizing muscle relaxant used in general anesthesia. In overdose, it causes adverse reactions such as bradycardia, arrhythmia, cardiac arrest, and death. The article reviews the progress on testing methods of suxamethonium chloride such as infrared spectroscopy, chemical color reaction, chemical titration, enzyme electrode, chromatography and mass spectrometry.

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Symptomatic sinus bradycardia: a rare adverse effect of intravenous ondansetron

Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind

Case report and review of literature: temporary asymptomatic sinus bradycardia with carboplatin, paclitaxel and bevacizumab: under-reported in clinical trials and under-disclosed in practice

Paclitaxel, Carboplatin, and Bevacizumab [PCB] is one of the standard chemotherapy regimens for the treatment of non-small cell lung cancer. Temporary asymptomatic bradycardia is recognized toxicity of paclitaxel. However, it is under-disclosed to patients during consent for treatment and is under-reported in clinical phase III trials. Here, were report a case of severe but temporary asymptomatic sinus bradycardia [heart rate 39 bpm] in a patient immediately after receiving PCB. The patient was not informed of this risk during consent to therapy leading to non-compliance with future plan of management. Literature search showed that bradycardia is documented. However, it is not reported adequately in land mark phase III trials' reports. The cause of bradycardia in this patient is probably paclitaxel. Oncologists should disclose this potential risk to patients during consent to chemotherapy. Investigators should monitor and report it when conducting land mark trials

Bloqueio atrioventricular total experimental em cães: observação por tempo prolongado / Experimental complete heart block in dogs: long-term folow-up

Fundamento: O bloqueio atrioventricular (BAVT) induzido experimentalmente é um método de indução de bradicardia estável e permanente em estudos nos quais situações de baixa frequência cardíaca são exigidas. Objetivos: Apresentar os resultados da técnica de indução e acompanhamento de BAVT experimental em cães, por tempo prolongado. Casuística e Método: O BAVT foi induzido cirurgicamente em 64 cães de raça mestiça, com peso médio de 12,84 + - 4 kg, sob anestesia geral com thionembutal sódico (25 mg/kg) e analgesia com fentanil e droperidol. A técnica consistiu de injeção de formol a 40 por cento na região do nó atrioventricular, no feixe de Hiss ou em seus ramos, sem atriotomia. O eletrocardiograma foi usado durante o procedimento e mensalmente para controle. Doze animais foram seguidos por tempo prolongado. Os cães foram sacrificados por meio de aprofumdamento anestésico. Após a morte, o coração dos animais foi retirado, fixado...

Bradycardia induced by Mesobuthus tamulus scorpion venom involves muscarinic receptor-G-protein-coupled cell signaling pathways.

Indian red scorpion (Mesobuthus tamulus; MBT) envenomation produces various cardio-respiratory abnormalities including cardiac dysrhythmias. The underlying cell signaling pathways for the cardiac dysrhythmias produced by MBT venom are not known. The present study was therefore conducted to delineate the second messenger signaling pathways involved in MBT venom-induced atrial rhythm changes. The effects of venom and various antagonists were examined on spontaneously beating rat right atrial preparations in vitro. The MBT-venom produced an increase (35%), a decrease (45%) and again an increase (50%) in rate at 0.03, 0.3 and 3.0 microg/ml of venom, respectively. On the other hand, force of contraction exhibited a concentration-dependent rise (up to 40%) at all concentrations of venom. Pretreatment with atropine (0.3 microM) blocked the decrease in atrial rate at 0.3 microg/ml concentration of venom while no such blockade was seen in force of contraction. Submaximal concentration of ACh (0.1 nM) decreased the atrial rate by 25%. In the presence of MBT venom (0.3 microg/ml), ACh-induced fall in atrial rate was enhanced. The venom-induced fall in atrial rate and augmentation of ACh response were blocked by pertussis toxin (PTx; a Gi-inhibitor) or methylene blue (a G-cyclase inhibitor). The results indicate that the decrease in atrial rate produced by venom is mediated muscarinic by receptors via Gi-guanylyl cyclase mediated cell signaling pathways.

Incidence and risk factors of hypotension and bradycardia after spinal anesthesia for cesarean section.

BACKGROUND: Hypotension or bradycardia after spinal anesthesia for cesarean section remain common and are serious complications. The current study evaluated factors associated to the incidences of hypotension or bradycardia in this context. MATERIAL AND METHOD: A prospective cross sectional study from November 1, 2004 to July 31, 2005 was conducted on 722 parturients undergoing cesarean section under spinal anesthesia. T-test and Chi-square test were used in univariate analysis to compare continuous data and categorical data respectively. Multivariate logistic regression was performed on the variables hypotension (systolic pressure decrease > 30% of baseline value) and bradycardia (heart rate < 60 bpm) p-value < 0.05 was considered significant. RESULTS: Incidence of hypotension and bradycardia were 52.6% and 2.5%. The probability of hypotension increased with estimated blood loss 500-1000 mL (odds ratio [OR] = 1.86; 95% CI 1.30-2.67, p = 0.001), estimated blood loss > 1000 mL (OR = 5.31; 95% CI 1.47-19.19, p = 0.011), and analgesia level > T4 (OR = 1.94; 95% CI 1.18-3.19, p = 0.009). Hypotension occurred despite left uterine displacement (OR = 1.56; 95% CI 1.11-2.19, p = 0.01). Risk factors associated with bradycardia were adding intrathecal morphine 0.2 mg (0.2 mL) (OR = 4.61; 95% CI 1.31-16.19, p = 0.017) to local anesthetics. CONCLUSION: The present results indicated that the incidence of hypotension after spinal anesthesia for cesarean section increased with amount of estimated blood loss > 500 mL and analgesic level > T4. Adding intrathecal morphine 0.2 mg (0.2 mL) to local anesthetics increased incidence of bradycardia.

Comparação da anestesia geral e bloqueio do plexo cervical superficial em tireoidectomias parciais / Comparison between general anesthesia and superficial cervical plexus block in partial thyroidectomies

Tireoidectomia sob efeito de bloqueio do plexo cervical superficial (BPCS) tem sofrido resistência. OBJETIVO: Comparar variáveis cirúrgicas e anestésicas, custos do tratamento e grau de satisfação de pacientes submetidos à hemitireoidectomia sob efeito de anestesia geral e BPCS. CASUÍSTICA E MÉTODOS: Foram 21 pacientes submetidos à anestesia geral (AG) e outro tanto ao BPCS. Após sedação, no grupo com BPCS, usou-se marcaína com vasoconstritor, e quando necessário, lidocaína a 2 por cento com vasoconstritor. Sedação intra-operatória com diazepam endovenoso e metoprolol para controle da PA e FC eram administradas quando necessário. Usou-se anestesia geral (AG) segundo padronização do serviço. RESULTADOS: Foram significantes (p<0,05, teste t de Student) para o tempo de cirurgia (ag111,4:bpcs125,5 min), tempo de anestesia (ag154,1:bpcs488,6 min), tempo de permanência na sala cirúrgica (ag15:bpcs1 min), custos do tratamento (ag203,2:bpcs87,4 R$), presença de bradicardia (ag0:bpcs23,8 por cento) e lesão laringotraqueal (ag51:bpcs0 por cento). Como resultados não significativos tiveram: tempo de internação (ag17,3:bpcs15,1 hora); volume de sangramento (ag41,9:bpcs47,6 gr), tamanho da peça operatória (ag52,1:bpcs93,69 cm3) e grau de satisfação dos pacientes (ag3,8:bpcs3,9). CONCLUSÃO: Embora com incidência maior de bradicardia (23,8 por cento), o bloqueio permitiu ressecar tumorações de até 348 cm3 com menor custo e sem apresentar lesões laringotraqueais, presentes em 51 por cento dos pacientes submetidos à AG.

Thyroidectomy under the effect of superficial cervical plexus block (SCPB) has met resistance. AIM: to compare variables in patients submitted to hemithyroidectomy under the effect of general anesthesia (GA) and SCPB. CASE REPORT AND METHODS: GA was used in 21 patients, and SCPB was used in another 21 patients. Following sedation, marcaine 0.5 percent with vasoconstrictor was used in the SCPB group. Intraoperative sedation with diazepam and metoprolol to control arterial pressure and cardiac frequency was given as needed. GA followed the standard method in the unit. RESULTS: We found significant results (p<0.05, Student’s t-test) for surgery time (GA - 111.4 min; SCPB - 125.5 min), anesthesia time (GA - 154.1 min; SCPB - 488.6 min), time in the surgery room (GA - 15 min; SCPB - 1 min), treatment costs (GA - R$203.2; SCPB - R$87.4), presence of bradycardia (GA - 0; SCPB - 23.8 percent) and laryngotracheal injury (GA - 51; SCPB - 0 percent). We also found the following non-significant results: hospitalization time (GA - 17.3; SCPB - 15.1 hours); bleeding volume (GA - 41,9 g; SCPB - 47.6 g), size of the operative specimen (GA - 52.1 cm3; SCPB - 93.69 cm3) and patient satisfaction level (GA - 3.8; SCPB - 3.9). CONCLUSION: Although the incidence of bradycardia was higher (23.8 percent), SCPB was done for the resection of tumors measuring up to 348 cm3, at a lower cost and with no laryngotracheal injuries; these were present in 51 percent of patients undergoing GA.

Transient asymptomatic bradycardia in patients on infusional 5-fluorouracil.

The incidence of 5-fluorouracil (5-FU)-related cardiotoxicity seems to be dosage and schedule dependent. Although various other cardiac events have been reported in literature, a series of patients having transient asymptomatic bradycardia has not been reported in the literature as yet. We report such a series of patients who had transient asymptomatic bradycardia after being treated with continuous infusion 5-FU. We plan to do a Holter study during the period of bradycardia in subsequent patients and this may throw more light on the issue.