Caracterización de las potenciales interacciones farmacológicas en pacientes de una unidad de cuidados intensivos en un hospital de tercer nivel de Bogotá / Characterization of potential drug-drug interactions in patients hospitalized in the intensive care unit of a tertiary hospital in Bogotá

Resumen Introducción. Las interacciones farmacológicas ocurren con mayor frecuencia en las unidades de cuidados intensivos que en otros servicios. Sin embargo, en Colombia son pocos los estudios en que se han evaluado en pacientes críticamente enfermos. Objetivos. Caracterizar las potenciales interacciones farmacológicas en las prescripciones de pacientes hospitalizados en una unidad de cuidados intensivos y determinar los factores asociados con su aparición. Materiales y métodos. Se analizó una cohorte retrospectiva de pacientes hospitalizados en una unidad de cuidados intensivos, durante un periodo de siete meses. Las prescripciones diarias se evaluaron en busca de potenciales interacciones farmacológicas mediante el programa Lexicomp™. Se calculó la incidencia de interacciones, se clasificaron según su tipo, gravedad y grado de documentación, y se evaluaron los factores asociados con su aparición mediante regresión logística. Resultados. La proporción de pacientes con por lo menos una interacción fue de 84 %, en tanto que el 87 % presentó más de una interacción; la mediana fue de seis interacciones por paciente. La más frecuente fue entre el fentanilo y el midazolam (23 %). Las interacciones de gravedad y grado de documentación moderados fueron las más frecuentes (77,6 y 52,6 %, respectivamente). El fármaco índice más frecuente fue el midazolam (12 %) y el precipitante más frecuente, el fentanilo (10,6 %). La edad (odds ratio, OR=3,1) y el número de medicamentos (OR=11,8), se asociaron con la aparición de interacciones. Conclusiones. Dada su elevada frecuencia y potencial impacto negativo es importante vigilar sistemáticamente las prescripciones en cuidados intensivos para detectar las interacciones, con el fin de contribuir al uso racional de los medicamentos y a mejorar la calidad de la atención.

Abstract Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services. However, in Colombia, there are few studies on this problem in critically ill patients. Objectives: To characterize potential drug-drug interactions generated from prescriptions during hospitalization in an intensive care unit and to determine factors associated with their onset. Materials and methods: A retrospective cohort was assembled with patients hospitalized in an intensive care unit for a seven-month period. The daily prescription was assessed for potential drugdrug interactions using the Lexicomp® program. We calculated the incidence of interactions, classified them by type, severity, and level of documentation, and evaluated the factors associated with their onset using logistic regression. Results: The proportion of patients with at least one interaction was 84% while 87% had more than one interaction; the median was six interactions per patient. The most frequent was fentanyl and midazolam (23%). Moderate interactions were the most frequent by severity (77.6%) and by documentation (52.6%). The most common index and precipitating drugs were midazolam (12%) and fentanyl (10.6%), respectively. Age (OR=3.1) and the number of drugs (OR=11.8) were associated with the occurrence of interactions. Conclusions: Given their high frequency and potential negative impact, the systematic monitoring of prescriptions in intensive care units to detect interactions is important. Such monitoring contributes to the rational use of medicines and to improve the quality of care.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats

PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats. .

Hematoma retroperitoneal espontáneo asociado al uso de enoxaparina y aspirina / Spontaneous retroperitoneal hematoma associated with enoxaparin and aspirin treatment

Se presenta un caso de hematoma retroperitoneal espontáneo asociado al uso de enoxaparina y aspirina a dosis terapéuticas, en una mujer de 75 años de edad que ingresa a la Unidad de Cuidados Intensivos con el diagnóstico de choque cardiogénico por infarto de miocardio son ST no elevado.

A spontaneous retroperitoneal hematoma case associated with use of enoxaparin and aspirin at therapeutic doses in a 75 year old-age woman who was admitted to the ICU with a diagnosis of cardiogenic shock due to non-ST elevated myocardial infarction.

Segurança e efetividade da enoxaparina versus heparina não-fracionada no tratamento de pacientes submetidos a implante eletivo de stents não-farmacológicos: resultados imediatos e tardios / Safety and efficacy of enoxaparin versus unfractionated heparin in patients undergoing elective percutaneous coronary intervention with bare-metal stent implantation: immediate and long-term clinical outcomes

A heparina não fracionada (HNF) é terapia anticoagulante clássica na intervenção percutânea, prevenindo complicações trombóticas agudas. Estudos sugerem que as heparinas de baixo peso molecular podem ser uma alternativa segura e eficaz. Objetivos: Avaliar a segurança e a efetividade da enoxaparina (ENO) versus HNF em pacientes tratado por intervenção percutânea eletiva nas fases hospitalar (FH) e tardia (FT). Método: No período de outubro a novembro de 2004, incluímos 57 pacientes consecutivos tratados com ENO 0,75 mg/kg (G2) versus grupo controle de 143 pacientes tratados com UI/kg (G1) nos três meses prévios. Todos receberam stents não-farmacológicos e foram pré-tratados com aspirina mais ticlopidina. Analisamos as complicações vasculares (CV) e hemorrágicas (CH) e os eventos combinados (EC) morte, infarto agudo do miocárdio (IAM), acidente vascular encefálico (AVE) e revascularização de urgência (RU) na FH e EC morte, IAM, AVE e nova revascularização na FT. No G2-ENO, mensuramos o fator anti-Xa 10 minutos após bolus EV e no fim da intervenção percutânea. Resultados: A média de idade foi de 59,8 mais ou menos 9,8 anos, 30 por cento eram diabéticos...

Background: Unfractionated heparin (UFH) is the classic anticoagulant therapy used during percutaneous intervention (PCI) to prevent acute thrombotic events. Preliminary studies with low molecular weight heparin have demonstrated the safety and efficacy of this alternative regimen during PCI. Our objective was to evaluate in-hospital and long-term safety and efficacy of enoxaparin (ENO) compared to UFH in patients (P) undergoing elective PCI. Methods: From 10/2004-11/2004, 57 P treated with ENO 0.75 mg/kg IV (G2) were enrolled and compared to a control group of 143 consecutive P treated with UFH 100 IU/kg IV (G1) during the preceding 3 months. All P received a baremetal stent and were pre-treated with ASA + ticlopidine. We analyzed the in-hospital vascular and bleeding complications as well as in-hospital and long-term composite clinical outcome of death, myocardial infarction (MI), stroke or target-vessel revascularization (TVR). Anti-Xa levels were measured in G2-ENO at the beginning (10 minutes after IV bolus) and at the end of PCI. Results: The mean age was 59.8 ± 9.8 years, 30% were diabetics, and clinical and angiographic characteristics were similar in both groups. Procedure success ocurred in 100% without in-hospital major bleedings nor vascular complications in both groups; a non-significant increase in minor bleedings in G2-ENO (p = 0.15) was observed and CKMB > 3x occurred in 2...

Massive pontine hemorrhagic transformation associated with an anticoagulant for basilar artery occlusion.

Symptomatic hemorrhagic transformation is common in supratentorial and cerebellar infarction, but is rare in brainstem infarction. It is seldom reported in basilar artery occlusion. Although early arterial recanalization by thrombolytic agent has became the new trend of treatment, for some neurologists anticoagulant is still a conventional alternative treatment of basilar artery occlusion, especially in longer-existing ischemic deficits. We report a case of massive pontine hemorrhage associated with enoxaparin (low-molecular-weight heparin) treatment for basilar artery occlusion. On the basis of the clinical information and neuroimaging, an embolism was the most likely cause of stroke. The case presented herein adds massive pontine hemorrhagic transformation to the list of possible complications of anticoagulants for basilar artery occlusion. Apart from no evidence-based benefit in treatment of basilar artery occlusion, anticoagulant may contribute to devastating hemorrhagic transformation.

Projeto para a implantação de um programa de investigação de efeitos adversos à enoxaparina sódica em hospital da rede privada no município do Rio de Janeiro / Project for the implementation of an adverse effects inquiry program to the use of sodium enoxaparin in a hospital of the private net in the town of the Rio de Janeiro

O desenvolvimento de um programa de farmacovigilância pode representar a melhoria da qualidade assistencial, também através de ações continuadas que monitorem parâmetros clínico/laboratoriais e forneçam retro-alimentação sobre a terapêuticamedicamentosa. De modo a estimular a implantação da farmacovigilância em umhospital da rede privada do Rio de Janeiro identificou-se o medicamento, enoxaparina sódica, e formulou-se um projeto de investigação de efeitos adversos nas unidades Emergência/Hemodinâmica e Coronariana do hospital. Revisou-se a literatura, por meio de busca nas bases Medline e Lilacs, para identificar indicações de uso, efeitos adversosmais freqüentes e fatores de risco para o aparecimento de reações adversas (RAM) à enoxaparina sódica. A seguir, elaborou-se um instrumento para a coleta dos dados e propôs-se o fluxo de encaminhamento das notificações, seguidos da análise e classificação das reações segundo a WHO-ART. O projeto incluiu também planejamento para cursos de capacitação em farmacovigilância e estruturação doprograma. Aplicou-se o pré-teste do instrumento durante 30 dias nas unidades. Coletaram-se dados referentes a variáveis demográficas, indicação para uso do medicamento, dose e medicamentos associados, existência de co-morbidades e fatoresde risco relacionados ao estilo de vida. Os dados clínicos foram obtidos a partir dos prontuários e exames laboratoriais e informações do serviço de hemoterapia. As informações consideradas relevantes foram avaliadas juntamente com outrosprofissionais de saúde. Foram coletados dados de 39 pacientes dos quais 24 da unidade coronariana e 15 da Emergência/Hemodinâmica. O instrumento mostrou-se de fácilaplicabilidade. A coleta mostrou que as variáveis eram passíveis de resgate nas fontes e que situações específicas poderiam ser descritas com base no relato, o que possibilitaria, no futuro, a análise de causalidade...

IV Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention

The rapid progress in the field of interventional cardiology in the last few years necessitates a continuous search for the most safe and effective methods to gain an optimum results, either equipments or drugs. to examine the use of enoxaparin as an anticoagulant in elective PCI, and compare it with unfractionated heparin regarding the acute procedural complications and the immediate 24-hour post-PCI events. The study was conducted on 84 patients who were classified independently into 2 groups. 50 patients represent group [A], received IV single bolus of enoxaparin in a dose of 0.5mg/kg at the start of the procedure and 34 patients represent group [B], received the usual traditional dose of unfractionated heparin [10000-15000 units].All patients were prepared by clopidogrel or ticlopidin before PCI in addition to aspirin 150 mg daily.Follow up was done for all patients during the immediate 24 hours after PCI for death, myocardial infarction, myocardial ischemia requiring urget coronary intervention and cerobrovascular stroke. There was no statistical significant difference between the two groups regarding the type of vessels treated or number of stents placed. None of the patients of both groups experienced any of the following complications during the procedure or 24 hours after: major bleeding, myocardial infarction, myocardial ischemia requiring urgent surgical or repeat percutaneous coronary revascularization or death. The major difference between the two groups was the immediate sheath removal in the enoxaparin group, without sheath site complication [minor haematoma] which was observed in 9% of the UFH group. Angiographic complications were coronary artery dissection [in one patient in group A [2%] and 3 patients in group B [9%]] and acute closure of the culprit vessel [occurred in one patient in group A [2%] and none in group B. The results were quite encouraging, with no statistical differences between the two arms of the study regarding the acute complications and the clinical outcome. The use of enoxaparin in this reduced dose is feasible in elective PCI with adequate level of anticoagulation without need for monitoring its anticoagulant effect. The early sheath removal in group A necessitates further studies to assess its impact on the duration of hospital stay and the possibility of early discharge of the patients

De la FDA (FOOD AND DRUG ADMINISTRATION) Estados Unidos: Informes sobre hematomas epidurales o espinales con el uso simultáneo de heparina de bajo peso molecular y anestesia espinal/epidural o punción espinal / From the FDA (FOOD AND DRUG ADMINISTRATION) USA: Reports about epidural or spinal hematomas with the simultaneous use of heparin of low molecular weight and spinal/epidural anesthesia or spinal punction

Hasta el mes de noviembre de 1997 se recibieron más de 30 informes voluntarios describiendo pacientes que desarrollaron hematomas epidurales o espinales con el uso simultáneo de enoxaparina sódica y anestesia espinal/epidural o punción dural. La mayoría de los hematomas epidurales o espinales causaron lesión neurológica, incluyendo parálisis prolongada o permanente. Apróximadamente el 75 por ciento de los pacientes fueron mujeres de edad avanzada que se sometieron a cirugía ortopédica. En este momento la FDA considera que los médicos deben tener presentes las siguientes consideraciones si utilizan estos productos: Cuando se emplea anestesia neuraxial (anestesia epidural/espinal) o punción espinal, los pacientes tratados o que van a ser tratados con anticoagulantes del tipo heparina de bajo peso molecular o heparoinoides para prevenir complicaciones tromboembólicas, tienen riesgo de desarrollar hematoma epidural o espinal que puede producir parálisis prolongada o permanente. El riesgo de estos episodios se incrementa con el uso de catéteres epidurales continuos para administrar analgesia o por el uso concomitante de drogas que afectan la hemostasis como las drogas antiinflamatorias no esteroides (DAINES), los inhibidores de las plaquetas u otros anticoagulantes. El riesgo también parece incrementarse con la punción espinal o epidural traumática o repetida. Se debe monitorear con frecuencia a los pacientes por signos y síntomas de deficiencia neurológica. Si se observa compromiso neurológico, es necesario un tratamiento urgente. Los médicos deben considerar en su totalidad el beneficio potencial versus el riesgo antes de la intervención neuraxial en los pacientes que recibieron o recibirán anticoagulantes para la tromboprofilaxis.