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The rising in placenta accreta spectrum (PAS) incidence, highlights the need for critical care allotment for these patients. Due to risk for hemorrhage and possible hemorrhagic shock requiring blood product transfusion, hemodynamic instability and risk of end-organ damage, having an intensive care unit (ICU) with surgical expertise (surgical ICU or equivalent based on institutional resources) is highly recommended. Intensive care units physicians and nurses should be familiarized with intraoperative anesthetic and surgical techniques as well as obstetrics physiologic changes to provide postpartum management of PAS. Validated tools such of bedside point of care ultrasound and viscoelastic tests such as thromboelastogram/rotational thromboelastometry (TEG/ROTEM) are clinically useful in the assessment of hemodynamic status (shock diagnosis, assessment of both fluid responsiveness and tolerance) and transfusion guidance (in patients requiring massive transfusion as opposed to tranditional hemostatic resuscitation) respectively. The future of PAS management lies in the collaborative and multidisciplinary environment. We recommend that women with high suspicion or a confirmed PAS should have a preoperative plan in place and be managed in a tertiary center who is experienced in managing surgically complex cases. KEY POINTS: · The rising in placenta accreta spectrum incidence highlights the need for critical care expertise.. · Emerging tools such as point-of-care ultrasound and thromboelastography/rotational thromboelastometry represent new avenues for real time optimization of hemodynamic and hematological care of patients with PAS.. · Patients with PAS should be referred to a tertiary center having an intensive care unit (ICU) with surgical expertise (or equivalent based on institutional resources)..
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Obstetricia , Placenta Accreta , Placenta Previa , Embarazo , Femenino , Humanos , Placenta Accreta/diagnóstico , Placenta Accreta/terapia , Placenta Accreta/epidemiología , Cesárea , Transfusión Sanguínea , Cuidados Críticos , Estudios Retrospectivos , Histerectomía , Placenta , Placenta Previa/epidemiologíaRESUMEN
We present images of Venus from the Wide-Field Imager for Parker Solar Probe (WISPR) telescope on board the Parker Solar Probe (PSP) spacecraft, obtained during PSP's third and fourth flybys of Venus on 2020 July 11 and 2021 February 20, respectively. Thermal emission from the surface is observed on the night side, representing the shortest wavelength observations of this emission ever, the first detection of the Venusian surface by an optical telescope observing below 0.8 µm. Consistent with previous observations at 1 µm, the cooler highland areas are fainter than the surrounding lowlands. The irradiances measured by WISPR are consistent with model predictions assuming a surface temperature of T = 735 K. In addition to the thermal emission, the WISPR images also show bright nightglow emission at the limb, and we compare the WISPR intensities with previous spectroscopic measurements of the molecular oxygen nightglow lines from Venus Express.
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BACKGROUND AND AIM: Septic emboli (SE) associated with infectious endocarditis (IE) can result in splenic abscesses and infectious intracranial aneurysms (IIA). We investigated the impact of SE on patient outcomes following surgery for IE. METHOD: From January-2000 to October-2015, all patients with surgical IE (n = 437) were evaluated for incidence and management of SE. RESULTS: Overall SE was found in 46/437 (10.52%) patients (n = 17 spleen, 13 brain, and 16 both). No mortality was seen in the brain emboli groups, but in the splenic abscess group the in-hospital mortality was 8.69% (n = 4); and was associated with Age >35 (OR = 2.63, 1.65-4.20) and congestive heart failure (OR = 14.40, 1.23-168.50). Patients with splenic emboli had excellent mid-term outcome following discharge (100% survival at 4-years). Splenic emboli requiring splenectomy was predicted by a >20 mm valve vegetation (OR = 1.37, 1.056-1.77) and WBC >12000 cells/mm (OR = 5.58, 1.2-26.3). No patient with streptococcus-viridians infection had a nonviable spleen (OR = 0.67, 0.53-0.85). Postoperative acute-kidney-injury was higher in the splenectomy group (45.45% vs 9%) (p = 0.027). There were 6 patients with symptomatic IIAs that required coiling/clipping which was associated with age <30 years, (OR = 6.09, 1.10-33.55). Survival in patients with cerebral emboli decreased to 78% at 3-4 years. Patients with both splenic and brain emboli had a 92% survival rate at 1-year and 77% at 2-4 years. CONCLUSION: Septic emboli is common in endocarditis patients. Patients with high preoperative WBC level and large valve vegetations require CT imaging of the spleen. Both spleen and brain interventions in the setting of IE can be performed safely with excellent early and mid-term outcomes.
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Embolia/etiología , Endocarditis/complicaciones , Endocarditis/cirugía , Embolia Intracraneal/etiología , Bazo/irrigación sanguínea , Absceso/epidemiología , Absceso/etiología , Absceso/mortalidad , Absceso/cirugía , Adulto , Factores de Edad , Anciano , Embolia/epidemiología , Embolia/mortalidad , Embolia/cirugía , Femenino , Insuficiencia Cardíaca , Válvulas Cardíacas/cirugía , Humanos , Incidencia , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/etiología , Aneurisma Intracraneal/mortalidad , Aneurisma Intracraneal/cirugía , Embolia Intracraneal/epidemiología , Embolia Intracraneal/mortalidad , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Pronóstico , Esplenectomía , Enfermedades del Bazo/epidemiología , Enfermedades del Bazo/etiología , Enfermedades del Bazo/mortalidad , Enfermedades del Bazo/cirugía , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Mechanical ventilation (MV) during a cardio-thoracic surgery contributes to diaphragm muscle dysfunction that impairs weaning and can lead to the ventilator- induced diaphragm dysfunction. Especially, it is critical in older adults who have lower muscle reparative capacity following MV. Reports have shown that the intraoperative intermittent hemidiaphragm electrical stimulation can maintain and/or improve post-surgery diaphragm function. In particular, from a molecular point of view, intermittent ES may reduce oxidative stress and increase regulatory autophagy levels, and therefore improve diaphragm function in animal studies. We have recently shown in humans that intraoperative ES attenuates mitochondrial dysfunction and force decline in single diaphragm muscle fibers. The aim of this study was to investigate an effect of ES on oxidative stress, antioxidant status and autophagy biomarker levels in the human diaphragm during surgery. METHODS: One phrenic nerve was simulated with an external cardiac pacer in operated older subjects (62.4 ± 12.9 years) (n = 8) during the surgery. The patients received 30 pulses per min every 30 min. The muscle biopsy was collected from both hemidiaphragms and frozen for further analyses. 4-hydroxynonenal (4-HNE), an oxidative stress marker, and autophagy marker levels (Beclin-1 and the ratio of microtubule-associated protein light chain 3, I and II-LC3 II/I) protein concentrations were detected by the western blot technique. Antioxidant enzymatic activity copper-zinc (CuZnSOD) and manganese (MnSOD) superoxide dismutase were analyzed. RESULTS: Levels of lipid peroxidation (4-HNE) were significantly lower in the stimulated side (p < 0.05). The antioxidant enzyme activities (CuZnSOD and MnSOD) in the stimulated side of the diaphragm were not different than in the unstimulated side (p > 0.05). Additionally, the protein concentrations of Beclin-1 and the LC3 II/I ratio were higher in the stimulated side (p < 0.05). CONCLUSION: These results suggest that the intraoperative electrical stimulation decreases oxidative stress levels and upregulates autophagy levels in the stimulated hemidiaphragm. These results may contribute future studies and clinical applications on reducing post-operative diaphragm dysfunction.
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Autofagia , Diafragma/patología , Diafragma/cirugía , Cuidados Intraoperatorios , Estrés Oxidativo , Respiración Artificial , Regulación hacia Arriba , Anciano , Proteínas Relacionadas con la Autofagia/metabolismo , Biopsia , Demografía , Estimulación Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate whether a transesophageal echocardiography (TEE) simulator with motion analysis can be used to impart proficiency in TEE in an integrated curriculum-based model. DESIGN: A prospective cohort study. SETTING: A tertiary-care university hospital. PARTICIPANTS: TEE-naïve cardiology fellows. INTERVENTIONS: Participants underwent an 8-session multimodal TEE training program. Manual skills were assessed at the end of sessions 2 and 8 using motion analysis of the TEE simulator's probe. At the end of the course, participants performed an intraoperative TEE; their examinations were video captured, and a blinded investigator evaluated the total time and image transitions needed for each view. Results are reported as mean±standard deviation, or median (interquartile range) where appropriate. MEASUREMENTS AND MAIN RESULTS: Eleven fellows completed the knowledge and kinematic portions of the study. Five participants were excluded from the evaluation in the clinical setting because of interim exposure to TEE or having participated in a TEE rotation after the training course. An increase of 12.95% in post-test knowledge scores was observed. From the start to the end of the course, there was a significant reduction (p<0.001 for all) in the number of probe. During clinical performance evaluation, trainees were able to obtain all the required echocardiographic views unassisted but required a longer time and had more probe transitions when compared with an expert. CONCLUSION: A curriculum-based approach to TEE training for cardiology fellows can be complemented with kinematic analyses to objectify acquisition of manual skills during simulator-based training.
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Cardiología/educación , Cardiología/normas , Competencia Clínica/normas , Simulación por Computador/normas , Ecocardiografía Transesofágica/normas , Internado y Residencia/normas , Fenómenos Biomecánicos , Cardiología/instrumentación , Estudios de Cohortes , Ecocardiografía Transesofágica/instrumentación , Estudios de Factibilidad , Femenino , Humanos , Internado y Residencia/métodos , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To compare the determination of stroke volume (SV) and cardiac output (CO) using 2-dimensional (2D) versus 3-dimensional (3D) transesophageal echocardiography (TEE). DESIGN: Prospective observational study. SETTING: Tertiary care university hospital. PARTICIPANTS: 35 patients without structural valve abnormalities undergoing isolated coronary artery bypass grafting. INTERVENTIONS: Left ventricular outflow tract (LVOT) diameter determined with 2D TEE was used to estimate LVOT cross-sectional area (CSALVOT). LVOT area was measured directly with 3D TEE by planimetry on an en face view. SV and CO were calculated for both methods using the continuity equation. MEASUREMENTS AND MAIN RESULTS: The area of the LVOT differed significantly between methods, being significantly larger in the 3D method (3.57±0.70 cm(2)v 3.98±0.93 cm(2)) . This resulted in a 10% lower CO with the 2D method of LVOT area estimation. CONCLUSIONS: LVOT area is underestimated with the single- axis 2D method when compared with 3D planimetered area. This results in a CO that is approximately 10% lower with the 2D method.
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Gasto Cardíaco/fisiología , Ecocardiografía Tridimensional/métodos , Anciano , Anatomía Transversal , Puente de Arteria Coronaria , Ecocardiografía , Ecocardiografía Transesofágica , Femenino , Ventrículos Cardíacos/anatomía & histología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Current approaches to stratify the risk for disease progression in thoracic aortic aneurysm (TAA) lack precision, which hinders clinical decision making. Connective tissue phenotyping of children with TAA previously identified the association between skin striae and increased rate of aortic dilation. The objective of this study was to analyze associations between connective tissue abnormalities and clinical endpoints in adults with aortopathy. Participants with TAA or aortic dissection (TAD) and trileaflet aortic valve were enrolled from 2016 to 2019 in the setting of cardiothoracic surgical care. Data were ascertained by structured interviews with participants. The mean age among 241 cases was 61 ± 13 years. Eighty (33%) had history of TAD. While most participants lacked a formal syndromic diagnosis clinically, connective tissue abnormalities were identified in 113 (47%). This included 20% with abdominal hernia and 13% with skin striae in atypical location. In multivariate analysis, striae and hypertension were significantly associated with TAD. Striae were associated with younger age of TAD or prophylactic aortic surgery. Striae were more frequent in TAD cases than age- and sex-matched controls. Thus, systemic features of connective tissue dysfunction were prevalent in adults with aortopathy. The emerging nexus between striae and aortopathy severity creates opportunities for clinical stratification and basic research.
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Aorta/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Válvula Aórtica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The treatment of patients with symptomatic tandem lesions of their carotid artery is challenging. One solution is carotid endarterectomy with retrograde ipsilateral proximal endovascular intervention, but it is associated with a higher postoperative risk of stroke. Unfortunately, symptomatic patients with tandem lesions often present with stenotic, calcified supra-aortic arch vessels and require multiple modalities to adequately revascularize including staged approaches or hybrid procedures. Herein, we report the successful treatment of a symptomatic 76-year-old female with a calcific severe stenosis of her innominate artery treated by a prosthetic bypass graft from her ascending aorta to proximal common carotid artery, interval ligation, and use of TransCarotid artery revascularization with reverse-flow to treat her proximal internal carotid artery stenosis via this bypass graft.
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Aorta/cirugía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Arteria Carótida Interna/cirugía , Estenosis Carotídea/cirugía , Procedimientos Endovasculares/instrumentación , Stents , Calcificación Vascular/cirugía , Anciano , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/fisiopatología , Velocidad del Flujo Sanguíneo , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/fisiopatología , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/fisiopatología , Femenino , Humanos , Flujo Sanguíneo Regional , Resultado del Tratamiento , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/fisiopatologíaRESUMEN
BACKGROUND: Fluid retention following "maze" and mitral valve surgery has been associated with diminished levels of atrial natriuretic peptide (ANP). We hypothesized prophylactic administration of nesiritide (human recombinant brain natriuretic peptide, NES, Natrecor, Scios, Fremont, CA, USA), which has similar physiologic properties to ANP and would promote diuresis in maze and mitral patients postoperatively. METHODS: Randomized, blinded, prospective pilot study comparing patients undergoing maze and mitral surgery including excision of the left atrial appendage. Three hours after cardiopulmonary bypass, patients received either a 72-hour infusion of NES at 0.01 mcg/kg/min (n = 9) or placebo (n = 10). Diuresis, diuretics, time to extubation, oxygenation, ANP, and serum Endothelin-1 levels were measured. Nonparametric analysis with Mann-Whitney test was performed with SPSS (SPSS Inc., Chicago, IL, USA). RESULTS: In both groups, postoperative ANP levels fell from baseline (NES 330 to 280 ng/mL and control 220 to 150 ng/mL). There were no significant differences in patients receiving NES compared to controls in diuresis (1.33 mL/kg/hour urine output NES vs. 1.68 mL/kg/hour controls, p = 0.14); furosemide dosage (0.04 mg/kg/hour NES vs. 0.04 mg/kg/hour controls, p = 0.08); time to extubation (17.5 hours NES vs. 19.5 control, p = 0.42) or PaO2/FiO2 ratio at 48 hours (NES 200 vs. 273 control, p > 0.05). Endothelin-1 levels were higher at baseline with NES but not at 1 and 72 hours after cardiopulmonary bypass (NES 3.1, 3.8, 2.9 pg/mL vs. control 1.85, 4.05, 2.75 pg/mL; p = 0.01, 0.77, 0.47). CONCLUSIONS: This pilot study did not demonstrate additional diuresis with nesiritide in postoperative mitral/maze patients already following a loop diuretic protocol.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Edema Cardíaco/tratamiento farmacológico , Edema Cardíaco/etiología , Válvula Mitral/cirugía , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Factor Natriurético Atrial/sangre , Biomarcadores/sangre , Método Doble Ciego , Edema Cardíaco/sangre , Endotelina-1/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/patología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: There is an absence of widely accepted guidelines for the management of infectious intracranial aneurysms (IIAs) owing to a dearth of high-quality evidence in the literature. OBJECTIVE: To better define the incidence of IIAs, treatment practices, and patient outcomes by performing a Nationwide Inpatient Sample (NIS) database query. METHODS: We queried the NIS database from 2002 to 2011 for all patients with the primary diagnosis of infectious endocarditis (IE), subarachnoid hemorrhage (SAH), or unruptured cerebral aneurysm by ICD-9-CM codes. ICD-9 procedure codes were used to identify patients undergoing neurosurgical or cardiothoracic procedures. RESULTS: The query identified 393 patients with primary diagnosis of IE, SAH or unruptured cerebral aneurysm treated during 2002-2011. The mean age of the patients was 53.5â years; 244 (62%) were male. The majority of patients presented with SAH (361; 91.9%). Only 73 (18.6%) patients underwent neurosurgical coiling or clipping for IIA. Of patients undergoing a neurosurgical procedure, 65 had SAH (constituting only 18% of patients with SAH) and 8 had unruptured aneurysms (constituting only 25% patients with unruptured aneurysms). Cardiac procedures were performed in only 72/393 patients (18.3%) patients. Only 67 (18.6%) of the patients with SAH and 5 (15.6%) with unruptured aneurysms underwent a cardiac corrective surgical procedure. Mortality was significantly higher in those patients managed conservatively (26.7%) than in those who underwent clipping or embolization (15.1%; p<0.001). CONCLUSIONS: In this NIS database study, the majority of patients with IIAs were managed non-operatively, regardless of rupture status. Further investigation is warranted to standardize the management of these lesions.
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Aneurisma Infectado/terapia , Manejo de la Enfermedad , Endocarditis/terapia , Aneurisma Intracraneal/terapia , Adulto , Anciano , Aneurisma Infectado/epidemiología , Embolización Terapéutica/métodos , Embolización Terapéutica/tendencias , Endocarditis/epidemiología , Femenino , Hospitalización/tendencias , Humanos , Aneurisma Intracraneal/epidemiología , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/tendencias , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effects of preemptive ultrasound-guided thoracic paravertebral block versus intercostal block on postoperative respiratory function and pain control in patients undergoing video-assisted thoracoscopic surgery. SUBJECTS: 50 consecutive patients undergoing video-assisted thoracoscopic surgery. METHOD: A prospective cohort of patients who received either ultrasound-guided thoracic paravertebral block immediately before the procedure or intercostal block placed by the surgeon at the end of the procedure were studied. Pulmonary function was assessed before surgery and 4 h postoperatively. Pain was assessed with the visual analog scale at 2 and 4 h after surgery both at rest and on coughing. RESULTS: 30 patients on the paravertebral block group and 20 on the intercostal block group were studied. Forced vital capacity (p < 0.001), forced expiratory volume at 1 s (p < 0.001) and forced expiratory flow 25-75% (p = 0.001) were significantly higher at 4 h with paravertebral block compared to the intercostal block group. The visual analog score for pain was significantly improved with paravertebral block at rest (p < 0.05) and with cough (p = 0.00). Perioperative narcotic use was significantly reduced with paravertebral block in comparison to intercostal block (p = 0.04). CONCLUSIONS: When compared to intercostal blocks, ultrasound-guided thoracic paravertebral block appears to preserve lung function and provide better pain control in the immediate postoperative period after video-assisted thoracoscopic surgery.
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Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Complicaciones Posoperatorias , Cirugía Torácica Asistida por Video/métodos , Adulto , Anciano , Analgésicos/uso terapéutico , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Periodo Posoperatorio , Estudios Prospectivos , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: Post-lung transplant reperfusion edema (PLTRE) and its more severe form, primary graft failure (PGF), occur in 10% to 60% of lung transplant recipients. We hypothesized that PLTRE and PGF would be associated with an elevated proinflammatory cascade and that the allograft would be the source of cytokine appearance in the circulation. METHODS: Pulmonary arterial and systemic arterial samples were obtained at baseline and at 4, 8, and 24 hours after reperfusion. Post-lung transplant reperfusion-edema and PGF were defined as PaO2/FiO2 less than 300 with a mild or moderate infiltrate, or less than 200 with a severe infiltrate and ventilator dependence after 72 hours, respectively. Tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-10 concentrations were determined by immunoassay. RESULTS: Fifteen single and 6 bilateral lung recipients were studied. Six (29%) had PLTRE and 4 (19%) had PGF; these patients had an overall elevation in plasma IL-6, IL-8, and IL-10 concentrations (all p < 0.05). Subgroup analysis revealed a significantly greater elevation in IL-6, IL-8, and IL-10 levels in PGF patients (all p < 0.01) versus PLTRE. In the PGF group, TNFalpha and IL-10 concentrations were significantly greater in the systemic versus the pulmonary arterial samples (p < 0.05). CONCLUSIONS: Patients with PLTRE and PGF exhibited graded increases in IL-6, IL-8, and IL-10 concentrations. The PGF patients had higher TNFalpha and IL-10 systemic arterial concentrations overall, consistent with the allograft being a source of this cytokine production.
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Citocinas/sangre , Trasplante de Pulmón/fisiología , Edema Pulmonar/sangre , Daño por Reperfusión/sangre , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Edema Pulmonar/etiología , Daño por Reperfusión/etiología , Factores de Tiempo , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: Treatment of postoperative pulmonary hypertension with intravenous (IV) pulmonary vasodilators is hampered by the lack of selectivity. Inhaled nitric oxide produces selective pulmonary vasodilation; however, it requires a special device, and weaning can cause rebound. Oral sildenafil is a phosphodiesterase type V inhibitor. Sildenafil can produce sustained pulmonary vasodilatation in patients with hypoxic or primary pulmonary hypertension; however, experience with postoperative pulmonary hypertension is limited. We report our initial experience with eight patients who received oral sildenafil as adjunctive therapy for postoperative pulmonary hypertension METHODS: We reviewed the charts of eight adult patients with postoperative pulmonary hypertension who received oral sildenafil (25 to 50 mg) to facilitate weaning of IV (milrinone, nitroglycerine, and sodium nitroprusside) and inhaled (nitric oxide) pulmonary vasodilators. Hemodynamic data were recorded before and 30 and 60 minutes after the initial dose of sildenafil. RESULTS: After the initial dose of sildenafil, mean pulmonary artery pressure was reduced by 20% and 22% at 30 and 60 minutes, respectively (p < 0.05). Pulmonary vascular resistance index decreased by 49% and 44% at 30 and 60 minutes, respectively (p < 0.05). Sildenafil had no clinically significant effects on cardiac index, mean arterial pressure, or systemic vascular resistance. Subsequent doses of sildenafil were administered at regular intervals, allowing successful weaning of concomitant pulmonary vasodilators. CONCLUSIONS: Oral sildenafil is an effective agent for treatment of postoperative pulmonary hypertension and can be used to facilitate weaning of inhaled and IV pulmonary vasodilators.