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Previous issue date: 2017-05-31 / Introdu??o: A s?ndrome do QT longo (SQTL) induzida por medicamentos pode levar ao Torsade de Pointes (TdP), uma taquicardia ventricular polim?rfica rara que pode ser fatal. Objetivos: Investigar o prolongamento do intervalo QTc em pacientes admitidos em Unidade de Terapia Intensiva (UTI) geral quanto a preval?ncia, grau de associa??o com os medicamentos administrados e intera??es medicamentosas, evolu??o no tempo e rela??o com desfechos cl?nicos. M?todos: Aprovado pelo Comit? de ?tica em Pesquisa de acordo com o parecer n? 666.969. Estudo observacional, prospectivo e transversal, realizado entre maio de 2014 a julho de 2016 na UTI do Hospital Universit?rio Onofre Lopes. Os pacientes admitidos foram investigados quanto a presen?a de prolongamento QT na admiss?o atrav?s do eletrocardiograma em um estudo de casos-controle. A corre??o do intervalo QT pela frequ?ncia card?aca (QTc) foi realizada pela f?rmula de Bazzet. Todos os pacientes foram observados at? a alta da UTI (fase de coorte anal?tico prospectivo) para os eventos de parada card?aca ou ?bito, e aqueles com SQTL foram observados por 48 horas e no momento da alta para nova avalia??o do intervalo QTc. A compara??o da diferen?a do QTc para o valor inicial foi analisada por covari?ncia. Para a determina??o do risco de prolongamento do QTc associado a cada medicamento foi utilizada a regress?o log?stica. A compara??o entre pacientes com e sem SQTL do tempo at? parada card?aca ou morte foi analisado com o teste do logrank e por regress?o log?stica. O risco desses eventos foi estimado por Kaplan-Meier. Resultados: Foi identificado uma preval?ncia de 34% (249/734) de SQTL em que 13,3% (33/249) possu?am QTc maior que 500 ms. Amiodarona (OR 2.434, p=0.02) e haloperidol (OR 3.333, p=0.02) foram associados ao SQTL, assim como medicamentos ainda n?o descritos em literatura: sufentanil (OR 3.667, p<0.01), clopidogrel (1.894, p=0.02), midazolam (OR 1.575, p= 0.04), noradrenalina (OR 1.701, p=0.01), nitroglicerina (OR 1.904, p=0.01), cefazolina (OR 1.897, p<0.01), cefepime (OR 0.417, p=0.01) e protamina (OR 5.952, p<0.01). A presen?a de intera??o medicamentosa aumentou o intervalo QTc em 16,8 ms (IC 95% 4.6 a 29.0 ms, p <0.01), sendo que as do tipo farmacodin?micas foram associadas a um aumento de 27.6 ms (IC 95% 2.1 a 53.2 ms, p = 0.03). Nos pacientes em que foram prescritos medicamentos associados ao SQTL, a diferen?a do QTc em 48h para o valor inicial foi de 15,8 ms (IC 95% -9,9 a 41,4 ms) maior do que no grupo que n?o utilizou medicamentos (p=0,22). Dos pacientes com SQTL na admiss?o, 39% o apresentaram ap?s 48 horas e 40% na alta. Foi identificado um risco 3 vezes maior de parada card?aca nos pacientes com SQTL (OR 3,030, p=0,02), enquanto que n?o se observou diferen?a significativa no risco de ?bito (rank p=0,87). Conclus?es: Observou-se preval?ncia elevada de SQTL em pacientes cr?ticos. Medicamentos ainda n?o descritos foram identificados como poss?veis indutores de SQTL. Observou-se que o uso de medicamentos n?o impactou significativamente o intervalo QTc, mas que as intera??es medicamentosas aumentaram o intervalo QTc, destacando-se apenas as do tipo farmacodin?mica. Verificou-se aumento do risco de parada card?aca entre o grupo QTc longo, mas sem diferen?a para a mortalidade. / Introduction: Medication-induced long QT syndrome (LQTS) can lead to Torsade de Pointes (TdP), a rare polymorphic ventricular tachycardia that can be fatal. Objectives: To investigate the QTc interval prolongation in patients admitted to the General Intensive Care Unit (ICU) in terms of prevalence, degree of association with medications administered and drug interactions, time evolution and relation to clinical outcomes. Methods: Approved by the Research Ethics Committee in accordance with opinion No. 666,969. Observational, prospective and cross-sectional study, conducted between May 2014 and July 2016 at the ICU of the University Hospital Onofre Lopes. The admitted patients were investigated for the presence of QT prolongation at admission via the electrocardiogram in a case-control study. Correction of the QT interval by heart rate (QTc) was performed using the Bazzet formula. All patients were observed until discharge from the ICU (prospective analytical cohort phase) for cardiac arrest or death events, and those with LQTS were observed for 48 hours and at discharge for reassessment of the QTc interval. Difference from the QTc to the initial value was analyzed by covariance. For the determination of the risk of QTc prolongation associated with each medication, logistic regression was used. The comparison between patients with and without LQTS from time to cardiac arrest or death was analyzed with the logrank test and logistic regression. The risk of these events was estimated by Kaplan-Meier. Results: A prevalence of 34% (249/734) of LQTS was identified in which 13.3% (33/249) had QTc greater than 500 ms. Amiodarone (OR 2.434, p = 0.02) and haloperidol (OR 3.333, p = 0.02) were associated with LQTS, as well as medicines not yet described in the literature: sufentanil (OR 3.667, p <0.01), clopidogrel (1,894, p = (OR 1.174, p = 0.01), or cephalosporin (OR 1.575, p = 0.04), noradrenaline (OR 1,701, p = 0.01), nitroglycerin (OR 1,904, p = 0.01), cefazolin ) And protamine (OR 5,952, p <0.01). The presence of drug interaction increased the QTc interval by 16.8 ms (95% CI 4.6 to 29.0 ms, p <0.01), and the pharmacodynamic type was associated with an increase of 27.6 ms (95% CI 2.1 to 53.2 ms , P = 0.03). In patients who were prescribed drugs associated with LQTS, the difference in QTc in 48 hours for the initial value was 15.8 ms (95% CI -9.9 to 41.4 ms) higher than in the non-medication group (P = 0.22). Of the patients with LQTS at admission, 39% presented it after 48 hours and 40% at discharge. A 3-fold higher risk of cardiac arrest was observed in patients with LQTS (OR 3.030, p = 0.02), whereas no significant difference in risk of death was observed (rank p = 0.87). Conclusions: There was a high prevalence of LQTS in critically ill patients. Drugs not yet described were identified as possible inducers of LQTS. It was observed that the use of drugs did not significantly affect the QTc interval, but that the drug interactions increased the QTc interval, with only those of the pharmacodynamic type being highlighted. There was an increased risk of cardiac arrest between the long QTc group, but no difference in mortality.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/23841 |
| Date | 31 May 2017 |
| Creators | Fernandes, Fl?via Evelyn Medeiros |
| Contributors | 70573918465, http://lattes.cnpq.br/0119633997550691, Ara?jo, Aurigena Antunes de, 83806059420, http://lattes.cnpq.br/3531154240424211, Fonteles, Marta Maria de Fran?a, 28529839315, http://lattes.cnpq.br/0574180390413250, Oliveira, Antonio Manuel Gouveia de |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMAC?UTICAS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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