Informe diário de evidências COVID-19: busca referente aos dias 11, 12 e 13 de julho de 2020 / COVID-19 daily evidence report: search for July 11, 12 and 13, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos.

Effects of hyperbaric oxygen and iloprost on intestinal ischemia-reperfusion induced acute lung injury

PURPOSE: To research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration. METHODS: Forty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination. RESULTS: Compared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group. CONCLUSION: Both HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.

Is There a Role of Pharmacological Treatments in the Prevention or Treatment of Osteonecrosis of the Femoral Head?: A Systematic Review

BACKGROUND: Various pharmacological treatments have been suggested to treat osteonecrosis of the femoral head. However, their practicability remains a controversial issue. METHODS: We systemically reviewed articles published during last 20 years to assess the efficacy and safety of the pharmacological treatments. RESULTS: To date, enoxaparin, statins, bisphosphonates, iloprost and acetylsalicylic acid have been practiced for the treatment of osteonecrosis. However, none of them were proven to be effective by high level studies, and most of them have adverse reactions. CONCLUSIONS: No pharmacological prevention or treatment of osteonecrosis is recommendable at this moment.

Inhaled Iloprost as a First-Line Therapy for Persistent Pulmonary Hypertension of the Newborn

PURPOSE: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience.METHODS: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO₂), respiratory severity score (RSS), heart rate, and mean blood pressure.RESULTS: The inhalation dose was 1 to 2 µg/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO₂, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed.CONCLUSION: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.

Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.</p><p><b>METHODS</b>We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.</p><p><b>RESULTS</b>The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).</p><p><b>CONCLUSIONS</b>The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.</p>

Pulmonary Arterial Hypertension is Normalized Following Six Years of Inhaled Iloprost Treatment in a Patient with Systemic Sclerosis

Pulmonary arterial hypertension is a critical manifestation of systemic sclerosis (SSc) and is a main cause of death. Several treatment modalities for SSc have been identified, with effects that improve quality of life and mortality rates. However, whether these drugs can also normalize pulmonary arterial pressure, remains unclear. Here, we report the case of a woman with diffuse SSc with pulmonary arterial hypertension, who had a functional status equivalent to the New York Heart Association class III. The patient was treated with inhaled iloprost. After six years of inhaled iloprost therapy, echocardiography showed that pulmonary arterial pressure normalized, accompanied by improvement in functional capacity. Inhaled iloprost might not only normalize pulmonary arterial pressure, but also improve the functional status of patients with SSc with pulmonary arterial hypertension.

Iloprost Una alternativa en la prueba de vasorreactividad pulmonar / Iloprost An alternative in pulmonary vasodilator testing

La realización de la prueba de vasorreactividad pulmonar con un vasodilatador arterial inhalado (iloprost), en la evaluación de pacientes con hipertensión arterial pulmonar es recomendación clase IIb, nivel C, según la European Society of Cardiology/European Respiratory Society (ESC/ERS) (1). Su recomendación está dada por la opinión de expertos y pequeños estudios epidemiológicos, siendo este uno de los motivos que debe estimular la realización de estudios que aporten información sobre este tema. El artículo de Sénior JM y cols, es uno de los primeros en nuestro medio que evalúa la utilización de iloprost como un medicamento alternativo para la realización de la prueba de vasorreactividad pulmonar con buenos resultados iniciales (2). La realización de la prueba de vasorreactividad se recomienda para detectar pacientes con hipertensión pulmonar a quienes se les podría administrar como parte de su terapia calcio antagonistas orales, su realización está indicada en hipertensión pulmonar idiopática, hereditaria y asociada con el uso de drogas (anorexígenos) (1, 3). La positividad de la prueba está alrededor de 10% (1, 3), aunque Sénior JM y cols reportan una positividad en su serie de 16.7%, un poco más elevada a la esperada, posiblemente debido a una mayor proporción de mujeres en el estudio y pacientes con clase funcional NYHA II (2). Los criterios de positividad de la prueba fueron adecuadamente evaluados según las guías internacionales .

Prueba de vasorreactividad con iloprost en hipertensión arterial pulmonar / Proof of vasoreactivity with iloprost in pulmonary arterial hypertension

Resumen Introducción: la detección de vasorreactividad pulmonar en hipertensión pulmonar es importante para determinar el beneficio del tratamiento con calcioantagonistas a largo plazo. En los últimos años se ha utilizado el iloprost como alternativa para la realización de la prueba con buenos resultados, por lo que es importante evaluar su respuesta en pacientes con esta enfermedad. Métodos: estudio cuasiexperimental no controlado con diseño de antes y después para evaluar la respuesta a un vasodilatador inhalado en pacientes remitidos al laboratorio de hemodinamia para pruebas de reactividad pulmonar. Se analizó una muestra no probabilística por conveniencia con la cohorte descrita. Se les realizó cateterismo derecho con medición de parámetros hemodinámicos y se evaluó la respuesta a la administración de 10 mcg de iloprost inhalado. Se consideró positiva la prueba si la presión arterial pulmonar media disminuía > 10 mmHg hasta < 40 mmHg, con aumento del gasto cardiaco o sin cambios en éste. Resultados: se incluyeron 30 pacientes; el promedio de edad fue de 55.5 ± 12 años, el 76.7% fueron mujeres y la fracción de eyección del ventrículo izquierdo fue de 52 ± 10%. La prueba se consideró positiva en 16.7% de los casos, sin complicaciones relacionadas al uso del medicamento. Se observó aumento no significativo del gasto cardiaco, con descenso importante en la resistencia vascular sistémica (1279 ± 438 vs 1110± 379, p=0.000004), resistencia vascular pulmonar (483 ± 210 vs 383 ± 185, p=0.000002), presión arterial pulmonar (47 ± 6 vs 39 ± 7, p=0.000002) y presión en cuña de la arteria pulmonar (16 ± 5 vs 15 ± 4, p<0.00009). Conclusión: el uso de iloprost inhalado en dosis de 10 mcg, en pacientes con hipertensión pulmonar llevados a cateterismo cardiaco derecho es una alternativa para identificar vasorreactividad, con baja tasa de eventos adversos. (Acta Med Colomb 2016; 40: 229-234).

Abstract Introduction: the detection of pulmonary vasoreactivity in pulmonary hypertension is important to determine the benefit of treatment with long-term calcium antagonists. In recent years, iloprost has been used as an alternative to perform the test with good results, so it is important to evaluate its response in patients with this disease. Methods: a quasi-experimental, uncontrolled study with before and after design to evaluate the response to an inhaled vasodilator in patients referred to the hemodynamic laboratory for pulmonary reactivity tests. A non-probabilistic sample was analyzed for convenience with the described cohort. Right catheterization was performed with measurements of hemodynamic parameters and the response to administration of 10 mcg of inhaled iloprost was performed in these patients. The test was considered positive if mean pulmonary artery pressure decreased >10 mmHg to <40 mmHg, with or without cardiac output increase. Results: 30 patients were included; mean age was 55.5 ± 12 years, 76.7% were women and the left ventricular ejection fraction was 52 ± 10%. The test was considered positive in 16.7% of cases, without complications related to the use of the drug. There was significant increase in cardiac output with an important decrease in systemic vascular resistance (1279 ± 438 vs 1110 ± 379, p = 0.000004), pulmonary vascular resistance (483 ± 210 vs 383 ± 185, p = 0.000002), blood pressure (47 ± 6 vs 39 ± 7, p = 0.000002), and wedge pressure of the pulmonary artery (16 ± 5 vs. 15 ± 4, p <0.00009). Conclusion: The use of inhaled iloprost in doses of 10 mcg in patients with pulmonary hypertension taken to right cardiac catheterization is an alternative to identify vasoreactivity with low rate of adverse events. (Acta Med Colomb 2016; 40: 229-234).

Análisis de impacto presupuestal de las terapias combinadas bosentan + sildenafil, ambrisentan + tadalafil e iloprost + bosentan en pacientes diagnosticados con hipertensión pulmonar grupo 1 (HAPG1 idiopática-HAPI y asociada-HAPA) de clase funcional II, I / Budget impact analysis of the combination therapies bosentan + sildenafil, ambrisentan + tadalafil and iloprost + bosentan in patients diagnosed with pulmonary hypertension group 1 (idiopathic HAPG1-HAPI and associated-HAPA) functional class II, I

Tecnologías evaluadas: Nueva: ambrisentan (principal) + tadalafil (complementario) Nueva: iloprost (principal) + bosentan (complementario), Actual: bosentan (principal) + sildenafil (complementario). Población: Pacientes diagnosticados con hipertensión pulmonar grupo 1 (HAP idiopática-HAPI y asociada-HAPA) de clase funcional II, III y IV de la NYHA/WHO en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte Temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo promedio ponderado de l mg de a mbrisentán, tadalafil, bosentan y sildenafil y costo promedio del mcg del iloprost en Colombia; Costo de las dosis individuales y en terapia combinada de ambrisentan, tadalafil, bosentan, sildenafil e iloprost para la población objetivo del AIP Colombia. Fuentes de Costos: Precios de ambrisentan, tadalafil, bosentan, sildenafil e iloprost en sus diferentes CUM s reportados por SISMED. Escenarios: Escenario 1: la participación de mercado de iloprost se reduce significativamente mientras que ambrisentan gana un espacio importante y bosentan disminuye ligeramente su participación en el primer año y la conserva \r\nen los dos años siguientes debido a que i) iloprost no es más efectivo que bosentan o ambrisentan, ii) la terapia combinada ambrisentan + tadalafil reduce hospitalizaciones, iii) ambrisentan es más barata que iloprost y iv) el sistema de salud en Colombia viene ganando eficiencia. Además, en la práctica la mayoría \r\nde los pacientes inician con terapia combina da y con seguridad 100% de ellos hace tránsito a terapia combinada si comenzaron con monoterapia; Escenario 2: la participación de mercado de ambrisentan se incrementa de manera pausada y llega a un nivel no superior a la participación de mercado de iloprost, que mantiene un segmento importante del mercado por la fuerte formulación de ese medicamento. En este escenario bosentan conserva su participación de mercado inalterada dada su comprobada efectividad en el tratamiento de HAPG1 y a que es la tecnología más antigua y conocida en el mercado. Resultados:\r\nEl costo de la tecnología actual de la terapia combinada bosentan + sildenafil, es de 98.773 millones COP en el año base. Bajo el escenario 1, el costo de adopción de las terapias combinadas nuevas analizadas, ambrisentan + tadalafil e iloprost + bosentan, implica un esfuerzo financiero adicional de 12.318 millones COP, mientras que bajo el escenario 2 el esfuerzo adicional es de 40.645 millones COP, es decir, 3.3 veces más. Para el segundo año el es fuerzo adicional requerido decrece con relación al año 1 ubicándose en 2.734 y de 3.071 millones COP en los escenarios 1 y 2 respectivamente. En el tercer año el impacto adicional se incrementa en 3.215 y 7.055 millones COP en cada caso.(AU)

Uso de iloprost inhalatorio para el manejo de hipertensión pulmonar en pacientes en riesgo de falla del ventrículo derecho aguda en el periodo perioperatorio de una cirugía cardiaca / Use of inhaled iloprost for the management of pulmonary hypertension in patients at risk of acute right ventricular failure in the perioperative period of cardiac surgery

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación iloprost respecto a su uso en el periodo perioperatorio de pacientes con diagnóstico de Hipertensión Pulmonar (PAPm > 25mmHg), o previo a una cirugia cardiaca o trasplante cardiaco, con el objetivo de prevenir falla aguda de ventrículo derecho (FAVD) y muerte. Aspectos Generales: La Falla Aguda del Ventrículo Derecho (FAVD) es una condición que se puede desencadenar en el periodo perioperatorio de pacientes con diagnóstico establecido de Hipertensión Pulmonar (HTP) que suele suceder por 3 mecanismos fisiopatológicos: a) Incremento de la presión de la aurícula izquierda transmitido a la circulación pulmonar; b) Remodelamiento vascula de la musculatura pulmonar en respuesta a la obstrucción crónica al drenaje venoso pulmonar y c) Vasoconstricción arterial pulmonar. Tecnología Sanitaria de Interés: iloprost: El iloprost es una solución inhalatoria, análogo sintético más estable de prostaciclina (PGI2), cuyo mecanismo de acción es la dilatación de los vasos arteriales predominantemente a nivel pulmonar. Se sabe que también afecta la agregación plaquetaria, pero la relevancia de este efecto en el tratamiento de Hipertensión Pulmonar plaquetaria, pero la relevancia de este efecto en el tratamiento de Hipertensión Pulmonar (HP) es aún desconocida. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura a la eficacia y seguridad de iloprost en pacientes con riesgo de desarrollar o que desarrollasen FAVD en el periodo perioperatorio de cirugía cardiaca. Primero se identificó en colaboración con médicos del INCOR las patologías con más riesgo de desarrollar FAVD, posteriormente se realizó una búsqueda primaria de revisiones sistemáticas y Guias de Práctica Clínica en las bases: National Library of Medicine (Pubmed-Medline), Translating Research into Practive (TRIPDATABASE), Cochrane Library y National Guideline of Clearinghouse. RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de iloprost en los escenarios que puedan desencadenar la Falla Aguda del Ventrículo Derecho en el periodo perioperatorio de una cirugía cardiaca. Por cada uno de los siguientes escenarios clínicos com riesgo de desarrollo de FAVD i.e., Trasplante Cardiaco, Correcición de Valvulopatías Tromboendarterectomía y Cardiomiopatía isquémica con disfunción ventricular izquierda, se presenta la evidencia disponible en Guías de Práctica Clínica, Revisiones sistemáticas y Meta-análisis, Ensayos Clínicos y Estudios observacionales. CONCLUSIONES: El iloprost inhalado es un vasodilatador con acción local pulmonar que ha mostrado tener un efecto beneficioso en la prevención y manejo de la hipertensión pulmonar en el momento perioperatório de la cirugia cardiaca. Sin embargo, la evidencia científica que respalda este benefício del iloprost es limitada al provenir de estudios observacionales y ensayos clínicos con limitaciones metodológicas que no permiten reducir el riesgo de sesgos con potencial impacto en los hallazgos de dichos estudios. Así se aprueba el uso del iloprost para ser utilizado para el maejo de la hipertensión pulmonar aguda en pacientes que desarollan o están riesgo de desarrollar falla del ventrículo derecho aguda en el contexto perioperatorio o post-operatorio inmediato de una cirugía cardiaca. Dado que la evidencia que respalda este uso del iloprost es aún limitada, se recomienda la realización de estudios de epidemiología que sistematice la información clínica que se genere de la experiencia del uso de este medicamento bajo el contexto del presente Dictamen Preliminar en ESSALUD. Esta información será tomada em cuenta en la re-evaluación de este medicamento para efectos de un nuevo dictamen al terminar la vigencia del presente Dictamen Preliminar.

Iloprost inhalado, un vasodilatador pulmonar selectivo. Evidencia clínica de su uso en la hipertensión pulmonar del perioperatorio de cirugía cardiovascular / Inhaled iloprost, a selective pulmonary vasodilator. Clinical evidence from its use in perioperative pulmonary hypertension cardiovascular surgery

El iloprost inhalado es uno de los fármacos más recientes del grupo de prostanoides en el tratamiento de la hipertensión arterial pulmonar. No se ha definido su importancia en la hipertensión pulmonar en el perioperatorio de cirugía cardiovascular. En esta revisión se analizan los grupos con hipertensión pulmonar susceptibles de cirugía cardiaca, la importancia de la hipertensión pulmonar en cirugía cardiaca y, además, la evidencia clínica actual del uso del fármaco en este contexto.

Inhaled iloprost is one of the most recent drugs from prostanoids group's in the treatment of pulmonary arterial hypertension. His place in pulmonary hypertension seen in the perioperative cardiovascular surgery has not been defined. In this review we analyze pulmonary hypertension group's susceptibles of cardiac surgery and its importance, besides the current clinical evidence from drug use in this context.

Cambios agudos en la función auricular derecha post uso de iloprost inhalatorio en pacientes con hipertensión arterial pulmonar: estudio con técnicas de deformación de imagen / Acute changes in right atrial funcion after Iloprost inhalation in patients with pulmonary hypertension: a study using image deformation techniques

Introducción: El efecto de prostanoides inhalatorios sobre la función auricular derecha (AD) en hipertensión arterial idiopática (HAP) no ha sido estudiado. Objetivo: Evaluar cambios agudos en la función AD y función diastólica del ventrículo derecho en pacientes con HAP post uso de Iloprost inhalatorio. Métodos: Se incluyeron pacientes con HAP sin uso previo de prostanoides. Se realizó un ecocardiograma transtorácico basal y 30 min posterior a la inhalación de iloprost. Se midió dimensión AD, relación E/e' y strain de la AD por speckle tracking, registrando la onda negativa de contracción auricular (SaAD) y la onda positiva de la fase de reservorio (SsAD). Se midió el tiempo de inicio de la fase de reservorio AD durante el sístole ventricular. Resultados: Se estudiaron 16 pacientes (15 mujeres), con edad promedio 44 ± 7,8 años. Post Iloprost disminuyó el volumen AD (basal: 140ml, post Iloprost: 109 ml; p 0,008) y las presiones de llenado (E/e’ basal: 13, post Iloprost: 9,8; p 0,028). No se registraron diferencias en el SaAD (basal: -8,4%, post Iloprost: -8,5%; p 0,834). El SsAD fue mayor post Iloprost (basal: 8,6%, post Iloprost: 11,7%; p 0,002) iniciándose antes durante el sístole ventricular (basal: 445ms, post Iloprost: 368ms; p 0,001). Conclusión: Con Iloprost inhalatorio en pacientes con HAP se observa una reducción aguda en el tamaño de la AD y en las presiones de llenado del VD. La deformación durante la fase de reservorio de la AD aumenta y se inicia significativamente antes. Esto sugiere que el Iloprost podría mejorar en forma aguda el trabajo mecánico de la AD en paciente con HAP.

Background: The effects of inhaled prostanoids on right atrial (RA) function in patients with Pulmonary Arterial Hypertension (PAH) have not been studied. We evaluated acute changes in RA function and right ventricular diastolic function after inhaled iloprost. Methods: We included PAH patients without prior prostanoid treatment. A surface echocardiogram was performed at baseline and 30 minutes after iloprost inhalation. Measurements included RA dimensions, right E/e’ ratio and RA strain by speckle tracking, registering a RA contraction wave (RASa) and RA reservoir wave (RASs). RA time to peak of deformation during the reservoir phase was also measured. Results: We included 16 patients (15 females, aged 44±7.8 years. Post iloprost there was a reduction in RA volume (baseline: 140ml, post iloprost: 109ml; p 0.008) and right ventricular filling pressure (baseline E/e’: 13, post iloprost: 9.8; p 0.028). There was no difference in the magnitude of the RASa wave (baseline: -8.4%, post iloprost: -8.5%; p 0.834). The RASs wave was larger post iloprost (baseline: 8.6%, post iloprost: 11.7%; p 0.002), and began earlier (baseline RA time to peak of deformation during reservoir phase: 445ms, post iloprost: 368ms; p 0.001). Conclusion: Inhaled iloprost acutely reduces RA size and right ventricular filling pressure in patients with HAP It also significantly increases the magnitude of RA systolic deformation as well as making it occur earlier in RA filling phase. This suggests that iloprost might improve RA mechanical performance.

Efficacy of inhaled iloprost on top of other targeted therapies for patients with pulmonary hypertension and severe right heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of inhaled iloprost on top of other pulmonary hypertension (PH) specific therapies for patients with PH and severe right heart failure.</p><p><b>METHODS</b>We consecutively enrolled WHO functional class IV patients with PH and chronic thromboembolic pulmonary hypertension (CTEPH) in Shanghai Pulmonary Hospital from January 2011 to January 2013. Inhaled iloprost was administrated to all enrolled patients, oral endothelin antagonist receptors (ERAs) and/or type 5 phosphodiasterase inhibitors (PDE5-I) were also used as basis therapies. The in-hospital outcomes and the changes of right heart functional parameters were observed.</p><p><b>RESULTS</b>Twenty-four patients with PH and 5 patients with CTEPH were enrolled. After a mean treatment duration of (23 ± 13) days, 3 patients dead and significant improvement was observed in the remaining 26 patients. Compared with the baseline, heart rate decreased from (99 ± 14) to (91 ± 12) bpm (P = 0.001), plasma NT-proBNP level decreased from 5 823 (3 029-13 248) to 3 220 (1 678-6 720) ng/L (P < 0.001), tricuspid annular plane systolic excursion (TAPSE) increased from (1.3 ± 0.4) to (1.4 ± 0.3) cm (P = 0.018), right ventricular diameter decreased (left-to-right diameter from (57 ± 11) to (53 ± 10) mm, P = 0.040, and superoinferior diameter from (69 ± 11) to (64 ± 16) mm, P = 0.027), Tbil also decreased from (41 ± 34) to (26 ± 17) µmol/L (P < 0.001). No severe side effects were observed.</p><p><b>CONCLUSION</b>The strategy of inhaled iloprost on top of other PAH-specific target therapy medications is effective and safe for PH patients with severe right heart failure.</p>

What do we take consideration in the patient who has an unpredicted severe portopulmonary hypertension in liver transplantation?: a case report / 대한마취과학회지

Severe portopulmonary hypertension (PPHT) is considered a contraindication for liver transplantation (LT) because of the associated high mortality and poor prognosis. We report the case of a 57-year-old cirrhotic woman with severe PPHT (mean pulmonary artery pressure [mPAP] > 65 mmHg), who underwent a successful living donor LT. Intra-operative use of inhaled iloprost, milrinone, dobutamine, and postoperative use of inhaled nitric oxide and oral sildenafil failed to lower the pulmonary artery pressure (PAP). The patient responded only to nitroglycerin and drainage of massive ascites. Meticulous intra-operative volume control, which included minimizing blood loss and subsequent transfusion, was carried out. The use of vasopressors, which may have elevated the PAP, was strictly restricted. Intra-operative PAP did not show an increase, and the hemodynamics was maintained within relatively normal range, compared to the preoperative state. The patient was discharged without any complications or related symptoms.

Utilidad clínica del iloprost inhalado en la hipertensión arterial pulmonar / Clinical utility of inhaled iloprost in pulmonary arterial hypertension

El iloprost inhalado es un fármaco del grupo de las prostaciclinas utilizado en el tratamiento de la hipertensión arterial pulmonar. La eficacia y seguridad de su administración han permitido su uso como monoterapia y en terapia combinada. En esta revisión se describen las características del medicamento, los grupos susceptibles de tratamiento y la evidencia clínica actualizada del uso del fármaco.

Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

Complete resolution of chronic pericardial effusion with an intensive course of inhaled iloprost in an adult patient with unrepaired ventricular septal defect, and life-threatening severe pulmonary arterial hypertension

A 38-year-old male was diagnosed with unrepaired ventricular septal defect associated with severe pulmonary arterial hypertension, cyanosis, and significant exercise intolerance. His echocardiogram showed right ventricular dysfunction and moderate pericardial effusion with no signs of cardiac tamponade. He was treated with an intensive course of inhaled iloprost and sildenafil. He showed a dramatic clinical response; his saturation went up from 60% on admission to 90% on minimal oxygen with significant improvement in his symptoms and signs of heart failure and total resolution of pericardial effusion. On follow up 3 and 6 weeks later, he was stable and could walk 360 meters in a 6 minutes walk test with disappearance of pericardial effusion. With unavailability of intravenous prostacyclin, we have shown in this case that intensive administration of inhaled iloprost could be used intensively as a rescue therapy in severe cases of pulmonary arterial hypertension with excellent results

Challenges in the management of concomitant TB arthritis and AVN in a lupus patient with adverse drug reaction to anti-Koch's medications

BACKGROUND: Non traumatic osteonecrosis also known as  avascular necrosis (AVN),and tuberculous arthritis (TB    arthritis)most commonly present as chronic monoarticular conditions. Corticosteroid intake is known to predispose individuals to the development of these two conditions.                       In AVN, corticosteroid remains to be the most common cause that leads to a final  common pathway of disrupting    blood supply to segments of bone causing cell death. In TB arthritis, corticosteroid renders  a patient relatively immunocompromised predisposing to this extrapulmonary infection.                                                                                                                                                          The incidence of tubercular osteonecrosis in a patient with systemic lupus erythematosus is rare. A review of literature only showed one case report of tubercular osteonecrosis diagnosed by aspiration cytology. Since tuberculosis (TB) is a destructive but curable disease, early diagnosis  and  treatment  are essential.OBJECTIVE: To present a case of tubercular osteonecrosis in a patient with systemic lupus erythematosus treated with anti-Koch's regimen and iloprost infusion.CASE: A 27-year old Filipino female who was diagnosed with lupus nephritis and underwent three days  methylprednisolone pulse therapy. Lupus nephritis improved  and  was clinically inactive for two years. She  developed insidious onset of intermittent pain on her left knee, associated with swelling for four months with  subsequent right hip pain of one week duration. MRI of the left knee showed osteonecrosis and arthritis. Radiograph of the right hip showed osteonecrosis. She underwent arthrocentesis of the left knee and the synovial  fluid tested positive for tuberculosis by PCR. We started the patient on quadruple anti-Koch's regimen together with iloprost infusion which afforded clinical improvement.  CONCLUSION: To our knowledge, this is the first reported case of a lupus patient with concomitant polyarticular osteonecrosis complicated by monoarticular tuberculous arthritis. Medical treatment, while it may be complicated by adverse drug events, is effective in symptomatic treatment, but a multidisciplinary approach is suggested for optimal outcome.

Iloprost inhibits fracture repair in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone. However, the effect of prostaglandin I2 (PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a study on fracture healing process in closed tibia fractures was designed.</p><p><b>METHODS</b>Thirty-six Sprague-Dawley male rats were randomized into two groups. On the first day, their right tibias were fractured by three-point bending technique. The study group (n = 18) received a single injection of 10 µg/kg iloprost for 5 days, while the control group (n = 18) received saline solution in the same way. On the 7th, 14th and 28th days following the fracture, six rats were sacrificed and their right legs were harvested in each group. The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al).</p><p><b>RESULTS</b>On the 7th day, the radiographic and histologic scores were equal. On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group, whereas radiographic total score was 11 and histologic total score was 33 in the control group. On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P < 0.05). On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group, whereas radiographic total score was 15 and histologic total score was 40 in the control group. On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group, it was not statistically significant (P > 0.05).</p><p><b>CONCLUSION</b>Iloprost delays fracture healing in early stage in rats.</p>

Effects of iloprost combined with low dose tadalafil in adult congenital heart disease patients with severe pulmonary arterial hypertension: a single-center, open-label controlled study / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).</p><p><b>METHODS</b>Adult CHD patients with severe PAH were included and divided into the sequential combination therapy group [iloprost: 10 µg/inhalation, 6 times per day for 6 months, and then add oral tadalafil (5 mg/d) till 12 months, n = 32] and upfront combination therapy group [iloprost: 10 µg/inhalation, 6 times per day combined with oral tadalafil (5 mg) for 12 months, n = 36]. Data on 6 min walking test (6MWT), Borg dyspnea score, oxygen saturation measurement, WHO classification, and cardiac catheterization were obtained at baseline, 6 and 12 months.</p><p><b>RESULTS</b>Seventy-two patients were enrolled in the study and 68 patients completed the study. Pulmonary vascular resistance (PVR) was significantly reduced in the sequential combination therapy group[ (12.96 ± 6.48 ) Wood U vs. (16.94 ± 8.11) Wood U, P < 0.05] and in the upfront combination therapy group [(12.45 ± 7.32) Wood U vs. (16.73 ± 9.28) Wood U, P < 0.05] while pulmonary blood flow [(6.77 ± 3.17) L/min vs. (5.08 ± 2.36) L/min, P < 0.05; (6.95 ± 3.32) L/min vs. (5.03 ± 2.32) L/min, P < 0.05], the 6 MWD were significantly increased [(458 ± 59) m vs. (427 ± 65) m, P < 0.05; (494 ± 59) m vs. (436 ± 62) m, P < 0.01], the Borg dyspnea score (2.04 ± 0.72 vs. 2.52 ± 0.79, P < 0.05; 1.72 ± 0.73 vs. 2.51 ± 0.77, P < 0.01) was significantly improved in both groups at 6 months compared to baseline levels. In the upfront combination therapy group, venous oxygen saturation [(68.4 ± 9.3)% vs. (62.9 ± 9.5)%, P < 0.05] and systemic oxygen saturation during exercise[ (87.2 ± 9.7)% vs. (83.1 ± 15.6)%, P < 0.05]at 6 months were also significantly improved compared to baseline. At month 12, significantly lowered pulmonary artery pressure, PVR, Rp/Rs and increased pulmonary blood flow and cardiac index were evidenced in both groups compared to baseline.</p><p><b>CONCLUSION</b>Iloprost combined with low dose tadalafil regimen can effectively reduce PVR, increase 6MWD, and improve cardiopulmonary function in adults CHD patients with severe PAH. Compared with the sequential therapy regimen, the upfront combination therapy regimen can more rapidly improve the clinical symptoms of patients.</p>