A pulmonary hypertension model induced by continuous pulmonary air embolization.

BACKGROUND: Our goal was to create a clinically relevant large animal model of pulmonary hypertension to serve as a platform allowing preclinical risk/benefit assessment of innovative therapies including artificial lung prototypes. METHODS: Small amounts of filtered air were continuously infused into the pulmonary circulation of sheep (n = 4) for 8 wk. Hemodynamics and blood gases were measured daily. After termination of air embolization, the sheep were observed for 1 additional wk to assess the constancy of the pulmonary artery pressure changes. At the end of wk 9, all sheep were sacrificed and necropsy was performed. RESULTS: All animals survived the study and developed pulmonary hypertension by wk 5. Mean pulmonary artery pressures were elevated from 14 ± 1 at baseline to 35 ± 1 mmHg at wk 8 (P < 0.01) and remained unchanged throughout wk 9. A similar increase in pulmonary vascular resistance was observed. Systemic arterial pressure and PaO(2) dropped slightly compared with baselines but remained in safe ranges. Histologic evidence of severe pulmonary arterial remodeling and significant right ventricle hypertrophy was observed. CONCLUSIONS: We conclude that our 8-wk model of continuous air embolization produces reliable, chronic pulmonary hypertension in sheep with sustained hemodynamic changes, significant pulmonary vascular remodeling, and right ventricle hypertrophy.

Mechanical ventilation and acute respiratory distress syndrome.

Acute respiratory distress syndrome continues to be a high-mortality condition. The role of mechanical ventilation remains primarily a supportive modality. Recent research has elucidated the adverse impact of traditional ventilation strategies on development of the disease and, ultimately, mortality. The institution of low tidal volume ventilation has been the only intervention that has resulted in definitive improvement in survival. Animal and human investigations that culminated in the Acute Respiratory Distress Syndrome Network low tidal volume study are reviewed. Current controversies in the application of mechanical ventilation including the use of positive end-expiratory pressure, recruitment maneuvers, and high frequency oscillatory ventilation are also addressed.

Adjuncts to mechanical ventilation in ARDS.

Since its first description, acute respiratory distress syndrome has been characterized by abnormal physiologic and gas exchange properties of the lungs. Many adjunctive therapies have been developed to reduce the stresses of mechanical ventilation on already damaged lungs. We examined the mechanism of action and the latest clinical trial information of several adjunctive therapies including prone positioning, nitric oxide, extracorporeal membrane oxygenation, arterial venous carbon dioxide removal, and liquid ventilation. While all of these therapies have demonstrated short-term improvements in arterial blood gases and in the limitation of lung injury, none have shown an evidence-based survival benefit.

Percutaneous venovenous CO2 removal with regional anticoagulation in an ovine model.

Extracorporeal CO2 removal may reduce minute ventilation requirements and allow for better tolerance of low tidal volume ventilating strategies in patients with severe respiratory insufficiency. Conventional extracorporeal gas exchange is labor-intensive, expensive, and usually requires systemic anticoagulation. In this study, a simplified venovenous circuit was developed by using regional citrate anticoagulation to avoid potential complications associated with systemic heparin. Five healthy adult sheep underwent percutaneous placement of a double-lumen 18F catheter into the internal jugular vein. The extracorporeal circuit consisted of a hollow fiber oxygenator and a variable speed roller pump. Regional anticoagulation consisted of a continuous citrate infusion to the inflow limb of the circuit. Systemic calcium levels were maintained by calcium chloride infusion through a central line. CO2 transfer was measured at varying levels of blood and gas flow. CO2 transfer ranged from 31 ml/min (500 ml/min blood flow; 2 l/min gas flow) to 150 ml/min (1000 ml/min blood flow; 15 l/min gas flow) and was directly proportional to blood flow and gas flow (p < 0.05). Normocapnia was maintained despite a 75% reduction in minute ventilation. At 24 hours, there was no significant clot formation in the circuit.

Posttraumatic versus Mycotic Dorsalis Pedis Pseudoaneurysm.

Reports of dorsalis pedis aneurysms are rare, and there are currently no reports of mycotic dorsalis pedis aneurysms in the literature. Most dorsalis pedis pseudoaneurysms are diagnosed by physical exam and color flow duplex. Surgical treatment includes aneurysm resection with or without reconstruction of the dorsalis pedis artery. We report a dorsalis pedis pseudoaneurysm diagnosed clinically and via duplex ultrasound, treated by excision and ligation of the aneurysm.

Complete respiratory support with AVCO2R and CPAP-mimic ventilation for total gas exchange in sheep.

The altered respiratory mechanics in patients with chronic obstructive pulmonary disease (COPD) present unique challenges with regard to treatment during an acute exacerbation that often leads to respiratory support with mechanical ventilation. Alternative therapies are badly needed to reduce morbidity and mortality associated with mechanical ventilator use. We hypothesized that arteriovenous carbon dioxide removal (AVCO(2)R) coupled with continuous positive airway pressure (CPAP) would achieve total gas exchange eliminating the need for intubation/mechanical ventilation, thus reducing baro/volutrauma. This hypothesis was tested in six adult sedated apneic sheep with AVCO(2)R administered through a simple arteriovenous (AV) shunt for CO(2) removal. Because it is impractical to apply a CPAP mask to conscious sheep, the CPAP was mimicked in intubated/sedated sheep by positive end-expiratory pressure (PEEP) of 5-10 mmH(2)O with negligible ventilation. The AVCO(2)R and CPAP-mimic maintained Pa(o)(2) and Pa(co)(2) in the normal physiological ranges. The CO(2) removal was 120-150 ml/min through AVCO(2)R with AV blood flow of 1.1-1.5 L/min. A high fraction of inspired oxygen percentage (Fi(o)(2)) level (89 ± 3%) was required to achieve 40 ± 7% O(2) in the small bronchus. Thus, AVCO(2)R and CPAP-mimic achieved total gas exchange in anesthetized sheep and may be a potential option for acute COPD exacerbation in humans.

Extracorporeal CO(2) removal in ARDS.

Acute respiratory distress syndrome remains one of the most clinically vexing problems in critical care. As technology continues to evolve, it is likely that extracorporeal CO(2) removal devices will become smaller, more efficient, and safer. As the risk of extracorporeal support decreases, devices' role in acute respiratory distress syndrome patients remains to be defined. This article discusses the functional properties and management techniques of CO(2) removal and intracorporeal membrane oxygenation and provides a glimpse into the future of long-term gas-exchange devices.

Aerosolized amphotericin for the treatment of allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus fumigatus that occur frequently in patients with cystic fibrosis (CF). Recurrent episodes of bronchial obstruction, inflammation, and mucoid impaction occur in ABPA and results in bronchiectasis, fibrosis, and respiratory failure. The treatment of ABPA includes corticosteroids to reduce the acute inflammation and intraconazole to reduce the fungal colonization load in order to reduce lung injury. This case discusses the successful use of aerosolized amphotericin B for the treatment of ABPA in a 14-year-old patient with CF listed for lung transplant. The patient required fewer hospitalizations, and both oral corticosteroids and anti-fungal therapy were eventually stopped.

Venovenous carbon dioxide removal in chronic obstructive pulmonary disease: experience in one patient.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Acute exacerbations of COPD account for up to 84% of the total economic cost of this disease. The altered mechanics of the COPD patient represent a unique challenge to the clinician instituting assisted ventilation in this population. We developed an alternative mode of limited extracorporeal support termed Venovenous carbon dioxide removal (VVCO2R). We report our first case using VVCO2R, a 42-year-old white woman with a history of COPD and asthma, who was a heavy smoker at the time of admission. We utilized a compact, low flow pediatric extracorporeal circuit interposed with a low resistance gas exchange device. Venovenous carbon dioxide removal allowed for a reduction in the patient's minute ventilation to 30% of baseline with improved arterial blood gases (ABGs), a reduction in peak airway pressures and improvement in her hyperinflation. Our experience demonstrates that this system can effectively remove CO2 safely in a single cannula venous configuration while maintaining minimal anticoagulation. We believe this system could potentially be utilized in any medical or surgical intensive care unit.

Transthoracic closure of a postpneumonectomy bronchopleural fistula with coils and cyanoacrylate.

Standard treatment for persistent bronchopleural fistulas involves thoracotomy with primary closure and transposition of a vascularized muscle flap to the bronchial leak site. This major operation may be ineffective or medically contraindicated. We successfully treated 2 patients by insertion of coils and cyanoacrylate glue into and adjacent to the fistula of a postpneumonectomy bronchial stump with computed tomographic-guided transthoracic needle. The coils served as scaffolding for cyanoacrylate glue to control the bronchopleural fistula.

A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation.

Routine administration of large amounts of pain and sedative medication is common to critically ill pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) for cardiopulmonary failure. It has been our experience that pediatric patients are the most difficult age group in which to achieve an ideal pain and sedative control due to the narrow margin of safety. The purpose of this study was to determine the general practice guideline used for pain and anxiolytic pharmacotherapy for pediatric patients at ECMO centers. We sent a survey questionnaire to all ECMO centers in the USA that treat pediatric respiratory failure patients. Of the 46 responding centers (including telephone follow-ups), 37 (80%) centers had an active pediatric ECMO programs for patients with severe respiratory failure. Fentanyl was the most commonly used pain medication and continuous infusion, administered directly to the patient, was preferred. Subjective effectiveness of various pharmacological agents was variable without clear consensus; however, midazolam was considered to be the most effective agent used.

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation.

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

Bone wax cast to repair a cannula leakage during prolonged extracorporeal membrane oxygenation.

During prolonged extracorporeal perfusion, thin-walled wire-wound cannulas have become the standard for low resistance cannula access for extrathoracic cannulation. We present an unusual technique of bone wax casting to repair a leak in a cannula to continue long-term extracorporeal membrane oxygenation.