Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.

Airway pressure release ventilation: theory and practice.

Airway pressure release ventilation (APRV) is a relatively new mode of ventilation, that only became commercially available in the United States in the mid-1990s. Airway pressure release ventilation produces tidal ventilation using a method that differs from any other mode. It uses a release of airway pressure from an elevated baseline to simulate expiration. The elevated baseline facilitates oxygenation, and the timed releases aid in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, decreased sedation use, and near elimination of neuromuscular blockade. Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. Future research will probably support the use of APRV as the primary mode of choice for patients with acute lung injury.

Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion.

OBJECTIVE: To review effects of the vehicle of lorazepam, propylene glycol, in regard to lactate, osmolarity, and renal dysfunction. DESIGN: Case report. SETTING: Intensive care unit of a Level I trauma center. Patient A 36-yr-old Hispanic man who developed severe respiratory failure and required high-dose lorazepam for sedation. The patient was ventilated with low tidal volumes in a lung-protective fashion, with resultant "permissive hypercapnia." Lactates and osmolalities rose on initiation and fell, as expected, on discontinuation of the lorazepam infusion. However, there was no renal compensation for the hypercapnia except while the patient was not receiving lorazepam. MEASUREMENTS AND MAIN RESULT: Serial osmolalities, lactates, serum bicarbonate, PaCO2, and pH were measured during lorazepam infusion. Rise and fall of serum lactate and osmolality closely correlated with lorazepam. Serum bicarbonate rose significantly while the patient was not receiving lorazepam in response to hypercarbia and failed to rise while the patient was receiving lorazepam. CONCLUSION: The vehicle of lorazepam, propylene glycol, can cause hyperlactatemia and elevated osmolar gaps. However, propylene glycol may also interfere with renal tubular function and may blunt renal compensation for respiratory acidosis.

Extracorporeal support in an adult with severe carbon monoxide poisoning and shock following smoke inhalation: a case report.

The objective of this study was to discuss the case of a patient with severe smoke inhalation-related respiratory failure treated with extracorporeal support. The study was set in a 12-bed multi-trauma intensive care unit at a level one trauma center and hyperbaric medicine center. The patient under investigation had carbon monoxide poisoning, and developed acute respiratory distress syndrome and cardiovascular collapse following smoke inhalation. Rapid initiation of extracorporeal support, extreme inverse-ratio ventilation and intermittent prone positioning therapy were carried out. Admission and serial carboxyhemoglobin levels, blood gases, and computerized tomography of the chest were obtained. The patient developed severe hypoxia and progressed to cardiovascular collapse resistant to resuscitation and vasoactive infusions. Veno-venous extracorporeal support was initiated. Cardiovascular parameters of blood pressure, cardiac output, and oxygen delivery were maximized; oxygenation and ventilation were supported via the extracorporeal circuit. Airway pressure release ventilation and intermittent prone positioning therapy were instituted. Following 7 days of extracorporeal support, the patient was decannulated and subsequently discharged to a transitional care facility,neurologically intact. Smoke inhalation and carbon monoxide poisoning may lead to life-threatening hypoxemia associated with resultant cardiovascular instability. When oxygenation and ventilation cannot be achieved via maximal ventilatory management, extracorporeal support may prevent death if initiated rapidly.

Interhospital transport of the extremely ill patient: the mobile intensive care unit.

BACKGROUND: Critically ill patients may require specialized care that is offered only at tertiary referral centers. As regionalization and specialization of critical care become more common, transportation of critically ill patients must be refined. Transportation of critically ill patients within a hospital, much less outside the hospital, is often deemed unsafe because of medical instability. We report, here, our results from 2 yrs' experience of transporting extremely ill patients with respiratory failure via a ground critical care transport service. METHODS: A mobile intensive care unit was equipped and staffed to nearly recreate the intensive care environment. Staffing included a physician, nurse, respiratory therapist, and driver--all with extensive critical care experience. The mobile intensive care unit was equipped with a full pharmacy, advanced ventilatory equipment, and capability for full invasive hemodynamic monitoring. Data were analyzed by retrospective review. The predicted mortality rate, based on Pao2/Fio2 ratios, was compared with the actual mortality rate. RESULTS: During a 2-yr period, 39 critically ill patients were transported. Thirty-six of the 39 were candidates for extracorporeal lung assist, with a mean positive end-expiratory pressure requirement of 15.9, a mean Fio2 requirement of .93, and a mean Pao2/Fio2 ratio of 59.8. Pulmonary arterial catheters and peripheral arterial catheters were in place in 66.6% and 72% of patients, respectively. Vasoactive medications were being infused in 56%, and 74% were receiving medical paralytics. One patient died during movement from the bed to the transport gurney. Other than one episode of transient hypotension, there were no complications or untoward outcomes related to transport. Unique therapeutic interventions were performed at the receiving facility on 34 of 39 patients. The predicted mortality rate, based on indicators of lung dysfunction, was 68% to 100%; the actual subsequent hospital mortality rate was 43%. CONCLUSIONS: When a mobile intensive care unit is properly staffed and equipped and patient stabilization is performed before transfer, severely ill patients with respiratory failure can be transferred safely. For patients with respiratory failure, there may be a survival advantage in transfer to regional centers of expertise.

Life-threatening acute systemic lupus erythematosus: survival after multiple extracorporeal modalities: a place for the multipotential extracorporeal service.

Diffuse alveolar hemorrhage secondary to systemic lupus erythematosus (SLE) may cause life-threatening respiratory failure and may be associated with multiple organ failure. Extensive support may be necessary to sustain life while systemic therapy becomes effective. We report here a patient with profound respiratory failure secondary to SLE associated with multiorgan failure, who was supported with veno-arterial extracorporeal lung assist (ECLA), veno-venous ECLA, and multiple continuous renal replacement therapies during plasmapheresis. The full spectrum of extracorporeal life support and treatment modalities was performed seamlessly by a single service within the critical care department.

Veno-venous extracorporeal lung assist with concurrent distal aortic perfusion: repair of ruptured aorta in a patient with dense ARDS.

Extracorporeal lung assist (ECLA) allowed surgical repair of a ruptured descending thoracic aorta to be performed in a patient with profound respiratory failure. Dense acute respiratory distress syndrome (ARDS) developed during his 15-day hospitalization at a regional trauma center. After transfer to a Level I facility, an additional injury was diagnosed: traumatic rupture of the aorta, contained within a pseudoaneurysm. ECLA by the veno-venous route was required immediately preoperatively and distal aortic perfusion was performed during the aortic repair. Despite deflation of the left lung, the patient was oxygenated and ventilated adequately during surgery. Cross-clamp time was 48 minutes. The patient was weaned from ECLA by the fifth postoperative day. To our knowledge, this is the first report of concurrent veno-venous pulmonary support with distal aortic perfusion.

Low blood flow extracorporeal carbon dioxide removal (ECCO2R): a review of the concept and a case report.

Despite advances in respiratory and critical care medicine, the mortality from ARDS remains unchanged. Recent research suggests current ventilatory therapy may produce additional lung injury, retarding the recovery process of the lung. Alternative supportive therapies, such as ECMO and ECCO2R, ultimately may result in less ventilator induced lung injury. Due to the invasiveness of ECMO/ECCO2R, these modalities are initiated reluctantly and commonly not until patients suffer from terminal or near-terminal respiratory failure. Low flow ECCO2R may offer advantages of less invasiveness and be suitable for early institution before ARDS becomes irreversible. We describe a patient with ARDS and severe macroscopic barotrauma supported with low flow ECCO2R resulting in significant CO2 clearance, reduction of peak, mean airway pressures and minute ventilation.

Extracorporeal lung assist in the adult trauma patient.

Acute respiratory distress syndrome (ARDS) is a common complication of trauma and critical illness. Despite medical advances, the mortality associated with this disease process remains consistently around 50%. Extracorporeal lung assist (ECLA) is a therapeutic alternative to conventional mechanical ventilation. This therapy removes all or a substantial percentage of total body carbon dioxide production, allowing for much lower ventilator support and facilitating "lung rest". Although the use of ECLA is controversial, it represents a viable option for patients with severe respiratory failure.

An in vitro physiologic model for cardiopulmonary simulation: a system for ECMO training.

Extracorporeal life support (ELS) systems may be run by certified perfusionists, specially trained nurses or respiratory therapy staff. Guidelines for the training, certification and retraining of ELS operators have been established by the Extracorporeal Life Support Organization. Recommendations include "... a well defined program for staff training, certification, and retraining". Some clinicians have suggested that ELS operators be certified and recertified in an animal laboratory. But such practice involves veterinary expenses, animal use issues and considerable clean-up and disposal. We describe an alternative method of training, using an in vitro physiologic model designed to simulate various pathophysiologic states. In addition, the in vitro physiologic model may be used to evaluate membrane lung characteristics. This model's ease of construction, maintenance and use for training compared with live animal techniques are discussed. Research capabilities may be more flexible than with the use of the live animal technique. The in vitro physiologic model can be a useful and convenient asset to an extracorporeal membrane oxygenation/extracorporeal carbon dioxide removal (ECMO/ECCO2R) program.