Bennett P. deBoisblanc

Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbations of chronic obstructive pulmonary disease

ObjectiveTo determine whether the bronchodilator effects of albuterol and ipratropium bromide are greater if updraft nebulization is driven by 80% helium and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the treatment of an acute exacerbations of chronic obstructive pulmonary disease (COPD). SettingThe emergency department of a 750-bed inner-city community hospital. MethodsOver a 12-month period, a convenience sample of 50 normoxic patients presenting with signs and symptoms of an acute exacerbation of COPD were prospectively randomized to receive either HELIOX or AIR as the driving gas for updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5 mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and 120 mins after randomization using the assigned gas. Spirometry was obtained while breathing room air before the first treatment (baseline) and at 1 hr and 2 hrs after the initiation of treatment. The primary measure of efficacy was the change in percent of predicted forced expiratory volume in 1 sec (Fev1) over the treatment period. A secondary measure of efficacy was the change in percentage of predicted forced expiratory flow after 25% to 75% of vital capacity had been expelled (Fef25–75). ResultsTwenty-five patients were randomized to each treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the study. The baseline Fev1was 44% (95% confidence interval, 35% to 52%) of predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group. There were no adverse outcomes observed in either the HELIOX group or the AIR group. There were no significant differences in the change of Fev1 between the two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%], AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The improvement in Fef25–75 was significantly greater in the HELIOX group than in the AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3% to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR + 7% [4% to 11%], p = .05). ConclusionUse of HELIOX as a driving gas for the updraft nebulization of bronchodilators during the first 2 hrs of treatment of an acute COPD exacerbation failed to improve Fev1 faster than the use of AIR. The faster improvement in Fef25–75 during the first 2 hrs of treatment was small and of uncertain clinical significance.

Pulmonary Stress Injury Within Physiological Ranges of Airway and Vascular Pressures

PURPOSEnThe aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model.nnnMATERIALS AND METHODSnFour groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability.nnnRESULTSnBALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P < .002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P < .0001).nnnCONCLUSIONSnWe can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

Hemodynamic Consequences of Mechanical Ventilation

Positive pressure ventilation (PPV) is often required in critically ill patients with unstable cardiovascular status. Mechanical ventilation can result in further alterations of cardiac output (CO) and arterial blood pressure. The evidence supporting a variety of potential pathophysiologic mechanisms for hemodynamic instability related to PPV is examined. The predominant determinant of hypotension during mechanical ventilation appears to be a reduction in preload. The impaired preload is due to the smaller gradient for venous return caused by the increased intrathoracic pressure. Additional potential pathophysiologic effects of PPV include increased pulmonary vascular resistance, ventricular interdependence, changes in contractility, and altered humoral and autonomic responses. A number of clinical scenarios such as acute respiratory distress syndrome, obstructive airway disease, and heart failure, which commonly require mechanical ventilation, are examined in further detail.

Ghrelin in Critical Illness

Ghrelin, a recently described peptide, has attracted significant attention in recent years, primarily in the context of its endocrine- and appetite-regulating effects. The versatility of this peptide is manifested in a rapidly expanding body of literature highlighting its nonendocrine functions. This review summarizes the available data on the immunomodulatory as well as the non-immune-mediated effects of ghrelin that form the scientific basis of its role in critical illness.

α-melanocyte stimulating hormone in sepsis: Is your patient's brain smarter than your patient's doctor?

Imagine this scenario: Its 1990. New biotech companies filled with bright energetic scientists are springing up everywhere. Each company is working on an innovative strategy for the immune modulation of sepsis. The stock market is beginning a decade-long bullish run. Could this be a once in a lifetime chance to make millions or a one-way ticket to the poor house? History has revealed that, despite loads of positive preclinical data, beneficial immunomodulation of human sepsis has proved elusive.

Over easy: an updated recipe for acute respiratory distress syndrome.

1318 www.ccmjournal.org May 2014 • Volume 42 • Number 5 acknowledged the limitations of their study: most notably, the lack of outcomes (development of VTE) and inaccuracies in measuring pTP or mTP use as patients may have used these on days other than the predefined study dates. So where does the field of thromboprophylaxis in critically ill children go from here? As suggested by the authors, the low frequency and highly variable use of thromboprophylaxis in critically ill children provide us an opportunity to address the practice. Given the infrequent use of thromboprophylaxis, welldesigned longitudinal observational studies are needed to define the extent and clinical significance of the VTE problem. If a clinically significant VTE problem is found, then the onus would be to risk stratify patients and implement thromboprophylaxis accordingly. To apply thromboprophylaxis across the board without risk stratification would be naive. It would also be helpful to be cognizant of the challenges faced by prior trials in the field (12). Nonetheless, we believe that these challenges are worth taking on. In conclusion, while the PROTRACT study informs the current landscape of thromboprophylaxis utilization in the PICU, the question—should a critically ill child receive pTP or mTP to prevent VTE?—is far from being answered.

A Letter From New Orleans Five Years Later

It has already been 5 years since Hurricane Katrina, the most costly natural disaster in American history, drowned New Orleans and the surrounding Gulf Coast. Moment by moment as levees softened and failed and flood waters poured in, scores of television cameras beamed indelible images of horrific human suffering into every living room across America. Over 1,800 people died as a direct result of Katrina, most of them homebound elderly in New Orleans. In addition, over 250,000 persons were rendered homeless and over half of those have been permanently displaced. No other event in American history, including the great flood of 1926, has displaced so many people. A full year after Hurricane Katrina, New Orleans’ population was less than 50% of what it had been before the storm. In one year New Orleans went from America’s 33rd largest city to its 89th. Although the events that unfolded in the late summer of 2005 had been predicted for over 50 years, the healthcare system of New Orleans, the State of Louisiana, and the U.S. Federal Government were each ill-prepared to deal with the magnitude of humanitarian need that resulted. Critical resources were either inadequate or poorly positioned to care for the 100,000 persons who either chose not to leave or could not leave in the days preceding the storm. The result was that thousands of mostly poor New Orleanians were stranded for days without food, water, shelter, or medical care. Even those trapped inside of New Orleans’ dark and silent hospitals, many with life-threatening medical problems, remained invisible to the outside world, including the incident command. Without any hope of outside help, patient survival had been squarely placed on the shoulders of tired, frightened, and often inexperienced healthcare workers. Somewhat surprisingly, it seemed that these same healthcare workers, who themselves suffered tremendous losses, turned out to be better suited for the task of nurturing and rescuing patients than the armed militias dispatched by the federal government. Such a struggle of an ICU team to save its critically ill patients inside of Charity Hospital was shared with this same readership 5 years ago (1). In the weeks following Katrina we received countless letters from well wishers expressing their condolences for what we had experienced. Our simple response at that time was to reassure them that the singular emotion that so many of us felt was gratitude for having had the opportunity to serve. For all of those trapped inside hospitals without the technological distractions of modern medicine, there were frequent unanticipated discoveries about the goodness of human beings. Amid all of the chaos, time seemed to slow down and acts of kindness by young resident physicians, nurses, and allied health professionals became commonplace. In the early months after the water was pumped out and the television cameras had been turned off, the realities of rebuilding began to set in. With three quarters of New Orleans housing uninhabitable, there was a mass exodus of anyone who could afford to leave and who had a place to go. The poor, who seem to wear homing beacons for disasters, found themselves left behind, housed in toxic mobile trailers in neighborhoods that lacked public transportation, schools, grocery stores, recreation facilities, places of worship, and importantly mental health facilities. At a time when outpatient clinics were nonexistent, only 3 of New Orleans’ 16 acute care hospitals were able to re-open, and 70% of physician practices were dislocated. Predictably, rates of crime, depression, and suicide doubled. If New Orleans had been on life support before Katrina, in the first year following Katrina, she had become ‘‘a DNR.’’ But the old and wise will remind us that disruptions on any scale, whether they affect whole communities or individuals, can offer us a gift: the opportunity to change. And change we did. Many institutions that had been crumbling before Katrina have been built anew. New Orleans’ public schools, which had been on a path to extinguish the light of learning for generations to come, have attracted the attention and service of educators and advocates of social justice from all over the world. And for many of us, it has turned out to be a blessing to be offered the opportunity to resurrect from the destruction the things we treasured, and to rebuild them from fragments, to choose all over again our work, our homes, our partners, our friends. Through evolution rather than revolution, day-to-day life has slowly become richer. Men and women of conscience from all over the country have descended on New Orleans with fresh ideas and boundless energy. Families have been reunited, new charter schools have opened, businesses have returned, and an NFL franchise has inspired a nation with the idea that with the right work ethic and perseverance, all things are possible. One brick at a time, the healthcare infrastructure in New Orleans is also being rebuilt, but now with a different focus. Community clinics and medical homes have replaced hospitals as the focal points for the delivery of services, and disease management programs have reduced hospitalizations for chronic medical conditions. Charity Hospital, one of the oldest hospitals in continuous operation in the United States and the major teaching hospital for Tulane and LSU Schools of Medicine, the place where ‘‘the unusual occurs and miracles happen’’ (Figure 1), remains closed and will likely never reopen again as a hospital. In its place a new

Effect of granulocyte colony-stimulating factor on acute lung injury in the rat.

2.4 billion state-of-the-art healthcare complex is being planned, with anticipated ground breaking just around the corner. This medical corridor will become the home of a new regional VA hospital and a new state-funded academic medical center scheduled to open in 2014. There is no doubt that the world is plagued with problems more devastating than Katrina. Poverty, hunger, disease, natural and human-caused disasters, and violence occur close to home and far away. The legacy of Hurricane Katrina will not be the blown down trees and the flooded homes; rather, it will be how this natural disaster yanked at a nation’s heart strings and