Sound transmission in human thorax through airway insonification: an experimental and computational study with diagnostic applications.

Pulmonary diseases and injury lead to structural and functional changes in the lung parenchyma and airways, often resulting in measurable sound transmission changes on the chest wall surface. Additionally, noninvasive imaging of externally driven mechanical wave motion in the chest (e.g., using magnetic resonance elastography) can provide information about lung stiffness and other structural property changes which may be of diagnostic value. In the present study, a comprehensive computational simulation (in silico) model was developed to simulate sound wave propagation in the airways, parenchyma, and chest wall under normal and pathological conditions that create distributed structural (e.g., pneumothoraces) and diffuse material (e.g., fibrosis) changes, as well as a localized structural and material changes as may be seen with a neoplasm. Experiments were carried out in normal subjects to validate the baseline model. Sound waves with frequency content from 50 to 600 Hz were introduced into the airways of three healthy human subjects through the mouth, and transthoracic transmitted waves were measured by scanning laser Doppler vibrometry at the chest wall surface. The computational model predictions of a frequency-dependent decreased sound transmission due to pneumothorax were consistent with experimental measurements reported in previous work. Predictions for the case of fibrosis show that while shear wave motion is altered, changes to compression wave propagation are negligible, and thus, insonification, which primarily drives compression waves, is not ideal to detect the presence of fibrosis. Results from the numerical simulation of a tumor show an increase in the wavelength of propagating waves in the immediate vicinity of the tumor region. Graphical abstract.

Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock.

OBJECTIVE: To assess the safety and efficacy of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene (PHP), in patients with distributive shock. DESIGN: Phase II multicenter, randomized (1:1), placebo-controlled study. SETTING: Fifteen intensive care units in North America. PATIENTS: Sixty-two patients with distributive shock, > or = 2 systemic inflammatory response syndrome criteria, and persistent catecholamine dependence despite adequate fluid resuscitation (pulmonary capillary wedge pressure > or = 12). INTERVENTIONS: Patients were randomized to PHP at 0.25 mL/kg/hr (20 mg/kg/hr), or an equal volume of placebo, infused for up to 100 hrs, in addition to conventional vasopressor therapy. Because treatment could not be blinded, vasopressors and ventilatory support were weaned by protocol. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients were randomized to PHP (n = 33) or placebo (n = 29). Age, sex, etiology of shock (sepsis in 94%), and Acute Physiology and Chronic Health Evaluation II scores (33.1 +/- 8.3 vs. 30 +/- 7) were similar in PHP and placebo patients, respectively. Baseline plasma nitrite and nitrate levels were markedly elevated in both groups. PHP infusion increased systemic blood pressure within minutes. Overall 28-day mortality was similar (58% PHP vs. 59% placebo), but PHP survivors were weaned off vasopressors faster (13.7 +/- 8.2 vs. 26.3 +/- 21.4 hrs; p = .07) and spent less time on mechanical ventilation (10.4 +/- 10.2 vs. 17.4 +/- 9.9 days; p = .21). The risk ratio (PHP/placebo) for mortality was .79 (95% confidence interval, .39-1.59) when adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II score, and etiology of sepsis. No excess medical interventions were noted with PHP use. PHP survivors left the intensive care unit earlier (13.6 +/- 8.6 vs. 17.9 +/- 8.2 days; p = .21) and more were discharged by day 28 (57.1 vs. 41.7%). CONCLUSIONS: PHP is a hemodynamically active nitric oxide scavenger. The role of PHP in distributive shock remains to be determined.