Alexander G. Duarte

Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience.

BACKGROUND Pulmonary arterial hypertension (PAH) is a rare disease with a predilection for young women that is associated with right ventricular failure and premature death. PAH can complicate pregnancy with hemodynamic instability or sudden death during parturition and postpartum. Our aim was to examine the impact of PAH on pregnancy outcomes in the modern era. METHODS We conducted a retrospective evaluation of pregnant patients with PAH managed between 1999 and 2009 at five US medical centers. Patient demographics, medical therapies, hemodynamic measurements, manner of delivery, anesthetic administration, and outcomes were assessed. RESULTS Among 18 patients with PAH, 12 continued pregnancy and six underwent pregnancy termination. Right ventricular systolic pressure in patients managed to parturition was 82 ± 5 mm Hg and in patients with pregnancy termination was 90 ± 16 mm Hg. Six patients underwent pregnancy termination at mean gestational age of 13 ± 1.0 weeks with no maternal deaths or complications. Twelve patients elected to continue their pregnancy and were hospitalized at 29 ± 1.4 weeks. PAH-specific therapy was administered to nine (75%) at time of delivery consisting of sildenafil, IV prostanoids, or combination therapy. All parturients underwent Cesarean section at 34 weeks with one in-hospital death and one additional death 2 months postpartum for maternal mortality of 16.7%. CONCLUSIONS Compared with earlier reports, maternal morbidity and mortality among pregnant women with PAH was reduced, yet maternal complications remain significant and patients should continue to be counseled to avoid pregnancy.

Pulmonary and cardiovascular complications of obesity: An autopsy study of 76 obese subjects

CONTEXT Obesity is associated with sleep disordered breathing and cardiovascular morbidity, but the relationship between pulmonary hypertension, heart disease, and obesity is unknown. OBJECTIVE To determine the prevalence of pulmonary and cardiovascular disease in obese subjects undergoing autopsy at a large medical center. DESIGN A search through autopsy records from an 11-year period identified 76 subjects with a body mass index greater than 30 kg/m(2) and 46 age-matched, nonobese controls. Clinical data were collected from medical charts and autopsy records. Formalin-fixed, paraffin-embedded sections of lungs and heart were reviewed for each subject. The presence of pulmonary edema, hemorrhage, diffuse alveolar damage, thrombi, and pulmonary hypertensive changes, including intimal fibrosis, medial hypertrophy, muscularization of arterioles, alveolar capillary hemangiomatosis, hemosiderosis, and iron encrustation were documented. Hearts were examined for the presence of cardiomegaly, ventricular hypertrophy, coronary artery atherosclerosis, acute infarction, fibrosis, and inflammation. Differences between the obese and control groups were compared using a statistical software program. RESULTS The obese group demonstrated a greater occurrence of diabetes mellitus, systemic hypertension, pulmonary edema, hemorrhage, and pulmonary hypertensive changes compared with the control group. Alveolar capillary hemangiomatosis was exclusively observed in the obese subjects. Cardiomegaly and left ventricular hypertrophy were present in all obese subjects; approximately one third of the obese subjects had no coronary atherosclerosis. CONCLUSIONS Pulmonary hypertensive changes, including venous hypertension and capillary hemangiomatosis, were observed in 72% of obese subjects. Cardiomegaly with biventricular hypertrophy was present in all obese subjects and was suggestive of obesity cardiomyopathy.

Original ResearchPulmonary Vascular DiseasesManagement of Pulmonary Arterial Hypertension During Pregnancy: A Retrospective, Multicenter Experience

BACKGROUND Pulmonary arterial hypertension (PAH) is a rare disease with a predilection for young women that is associated with right ventricular failure and premature death. PAH can complicate pregnancy with hemodynamic instability or sudden death during parturition and postpartum. Our aim was to examine the impact of PAH on pregnancy outcomes in the modern era. METHODS We conducted a retrospective evaluation of pregnant patients with PAH managed between 1999 and 2009 at five US medical centers. Patient demographics, medical therapies, hemodynamic measurements, manner of delivery, anesthetic administration, and outcomes were assessed. RESULTS Among 18 patients with PAH, 12 continued pregnancy and six underwent pregnancy termination. Right ventricular systolic pressure in patients managed to parturition was 82 ± 5 mm Hg and in patients with pregnancy termination was 90 ± 16 mm Hg. Six patients underwent pregnancy termination at mean gestational age of 13 ± 1.0 weeks with no maternal deaths or complications. Twelve patients elected to continue their pregnancy and were hospitalized at 29 ± 1.4 weeks. PAH-specific therapy was administered to nine (75%) at time of delivery consisting of sildenafil, IV prostanoids, or combination therapy. All parturients underwent Cesarean section at 34 weeks with one in-hospital death and one additional death 2 months postpartum for maternal mortality of 16.7%. CONCLUSIONS Compared with earlier reports, maternal morbidity and mortality among pregnant women with PAH was reduced, yet maternal complications remain significant and patients should continue to be counseled to avoid pregnancy.

Outcomes of morbidly obese patients requiring mechanical ventilation for acute respiratory failure

Objective:To examine the outcomes of morbidly obese patients with acute respiratory failure treated with mechanical ventilation. Design:Retrospective study. Setting:A 14-bed medical intensive care unit in an 800-bed university-based hospital. Patients:A total of 50 morbidly obese subjects with acute respiratory failure requiring ventilatory assistance. Interventions:None. Measurements:Arterial blood gas measurements, intubation rate, days of mechanical ventilation, intensive care unit length of stay, hospital length of stay, and mortality. Results:From January 1997 to December 2004, 50 morbidly obese patients with acute respiratory failure were treated with mechanical ventilation. Invasive mechanical ventilation was implemented in 17 patients with a mean body mass index of 53.2 ± 12.2 kg/m2. A total of 33 patients were treated with noninvasive ventilation (NIV), of which 21 avoided intubation (NIV success) and 12 required intubation (NIV failure). Mean body mass index for the NIV success group was significantly less than for the NIV failure group (46.9 ± 8.9 and 62.5 ± 16.1 kg/m2, respectively, p = .001). Acute Physiology and Chronic Health Evaluation II scores were similar for patients treated with invasive and noninvasive ventilation. Significant improvements in pH and Paco2 were noted for the invasive mechanical ventilation and NIV success groups. No improvements in gas exchange were noted in the NIV failure group. Of patients treated with NIV, 36% required intubation. Hospital mortality for the invasive ventilation and NIV failure groups was increased. Conclusion:The type of ventilatory assistance may influence clinical outcomes in morbidly obese patients with acute respiratory failure.

Inhalation therapy during mechanical ventilation

An increasing number of pharmacologic agents, including bronchodilators, prostaglandin, proteins, surfactant, mucolytics, and antibiotics are administered to mechanically ventilated patients by the inhalation route. To achieve a therapeutic effect, adequate amounts of an inhaled agent must be delivered to the desired site of action. The delivery of inhaled drugs to the lower respiratory tract of mechanically ventilated patients is complicated by deposition of the aerosol particles in the ventilator circuit and endotracheal tube, and the factors governing pulmonary deposition in mechanically ventilated patients are different from those in ambulatory patients. Meticulous adherence to several steps in the technique of aerosol administration is necessary for successful aerosol therapy in mechanically ventilated patients. With a proper technique of administration, an increasing number of inhaled drugs may be administered safely, conveniently, and effectively to mechanically ventilated patients.

Restoration of Cough Reflex in Lung Transplant Recipients

BACKGROUND Lung transplantation involves vagal nerve interruption resulting in sensory airway denervation and impairment of the cough reflex. Following lung transplantation, it is unclear whether functional recovery of the cough reflex occurs over time. Our objective was to evaluate the afferent limb of the cough reflex in lung transplant recipients. METHODS The assessment of cough reflex involved upper airway anesthesia, conscious sedation, and fiberoptic bronchoscopy; the biopsy forceps and a 5% dextrose solution were applied through the bronchoscope to the airway mucosa at the main carina, proximal and distal to the anastomosis. A cross-sectional group of seven subjects underwent a single assessment, while eight subjects in a longitudinal group underwent assessment at 1.5 and 12 months. Cough frequency was determined by counting the number of audible coughs and abdominal muscle contractions measured with a surface electromyogram recorder. The airway anastomosis from deceased subjects in the longitudinal group was examined for nerves. RESULTS All seven subjects from the cross-sectional group demonstrated a similar cough frequency after mechanical and chemical irritation of all airway sites. All subjects in the longitudinal group who were evaluated at 1.5 weeks had a cough response at all sites except distal to the anastomosis. Twelve months after transplantation, cough was present at all sites. Immunohistochemical staining for protein gene product 9.5, low-affinity neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial regions proximal and distal to the airway anastomosis. CONCLUSION In human lung transplant recipients, recovery of the cough reflex was noted 12 months after lung transplantation.

Fatal reactive hemophagocytosis related to disseminated histoplasmosis with endocarditis: an unusual case diagnosed at autopsy.

Reactive hemophagocytic syndrome (RHS) is an uncommon life-threatening disorder. It is believed to be caused by widespread non-neoplastic proliferation and inappropriate activation of mature macrophages, resulting in excessive cytokine activation which leads to hematophagocytosis by cells of the macrophage-monocyte lineage and multiorgan dysfunction. RHS may be associated with infections caused by bacterial, viral and fungal organisms as well as lymphoproliferative disorders, nonhematopoietic malignancies, autoimmune diseases and some therapeutic drugs. Immunosuppression is a frequent underlying condition in RHS. The following case presentation describes a patient with a history of chronic hepatitis C, cryoglobulinemia, renal failure and Staphylococcus aureus perinephric abscess and bacteremia, who, at autopsy, was found to have disseminated histoplasmosis with fungal endocarditis and RHS.

Toward ambulatory arteriovenous CO2 removal: Initial studies and prototype development

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100–150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500–900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 ± 0.8 mm Hg, and mean CO2 removal was 104.8 ± 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.

ARDS in pregnancy.

Acute respiratory distress syndrome (ARDS) is an uncommon condition in pregnant patients. The causes of ARDS are associated with obstetric causes such as amniotic fluid embolism, preeclampsia, septic abortion, and retained products of conception or nonobstetric causes that include sepsis, aspiration pneumonitis, influenza pneumonia, blood transfusions, and trauma. An essential component in management of ARDS involves good communication between the obstetrics team and critical care specialist and a fundamental understanding of mechanical ventilatory support. Medical therapies such as nitric oxide and corticosteroids play a complimentary role. Extracorporeal life support is beneficial in the management of the parturient with severe ARDS.

Incidence of right heart catheterization in patients initiated on pulmonary arterial hypertension therapies: A population-based study

BACKGROUND Pulmonary hypertension represents a heterogeneous collection of conditions classified into 5 groups according to pathology, pathophysiology and response to treatment. Right heart catheterization is required to classify patients and before initiation of specific therapy for treatment of pulmonary arterial hypertension. The aim of this study was to determine performance of right heart catheterization in patients prescribed pulmonary arterial hypertension (PAH)-specific medications. METHODS A retrospective review of administrative claims was performed using the Clinformatics Data Mart database. Individuals with an encounter diagnosis of pulmonary hypertension were identified by ICD-9 codes. An initial encounter diagnosis was defined as continuous enrollment for 12 months without a previous ICD-9 diagnosis of pulmonary hypertension. These individuals were followed for 15 months after initial encounter diagnosis. Individuals prescribed PAH-specific medications were assessed for characteristics, comorbidities and performance of echocardiography and right heart catheterization. RESULTS From 2002 to 2011, 15,772 patients had an outpatient visit with a diagnosis of pulmonary hypertension. From the initial group, 969 (6.1%) patients were prescribed PAH-specific medications within 1 year of encounter diagnosis. Oral PAH-specific medications were prescribed to 94.2% of patients. In patients prescribed PAH-specific medications, 91% had an echocardiogram within 1 year of encounter diagnosis. Cardiac catheterization was performed in 407 patients (42%) within 3 months of initial prescription and in 583 patients (60.2%) during the entire study period. CONCLUSION Performance of right heart catheterization was low in this population-based study of patients with an ICD-9 diagnosis code of pulmonary hypertension and taking PAH-specific medications.