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Biomedical subjects

A Jubran

Publications and source records attributed to A Jubran.

At least 19 recordsLinked to original sources

Effect of endotoxin on ventilation and breath variability: role of cyclooxygenase pathway.

To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also received ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration of endotoxin produced fever, increased respiratory frequency, decreased inspiratory time, and widened alveolar-arterial oxygen tension gradient (all p < or = 0.001); these responses were blocked by ibuprofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increased fractional inspiratory time, minute ventilation, and mean inspiratory flow (all p < or = 0.025). Endotoxin altered the autocorrelative behavior of respiratory frequency by increasing its autocorrelation coefficient at a lag of one breath, the number of breath lags with significant serial correlations, and its correlated fraction (all p < 0.05); these responses were blocked by ibuprofen. Changes in correlated behavior of respiratory frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and dyspnea independent of fever and symptoms, and it curtailed the freedom to vary respiratory timing-a response that appears to be mediated by the cyclooxygenase pathway.

Adult↗

Hypercapnic respiratory failure during weaning: neuromuscular capacity versus muscle loads.

Patients who fail a weaning trial develop hypercapnia as a result of alveolar hypoventilation, which, in turn, is caused by an imbalance between the respiratory muscle load and capacity. In some patients, especially those with obstructive lung diseases, respiratory muscle performance is impaired as a result of dynamic hyperinflation and paradoxical motion of the rib cage and abdomen. Worsening of pulmonary mechanics causes further embarrassment of the respiratory muscles and can lead to marked alterations of oxygen use by the peripheral tissues. The development of rapid shallow breathing together with worsening of pulmonary mechanics results in inefficient clearance of COcf152cf1 during a failed weaning attempt.

Humans↗

Assessment of neural inspiratory time in ventilator-supported patients.

Neural inspiratory time (TI) is a measurement of fundamental importance in studies of patient-ventilator interaction. The measurement is usually based on recordings of flow, esophageal pressure (Pes), and transdiaphragmatic pressure (Pdi), but the concordance of such estimates of neural TI with a more direct measurement of neural activity has not been systematically evaluated. To address this issue, we studied nine ventilator-supported patients in whom we employed esophageal electrode recordings of the diaphragmatic electromyogram (EMG) as the reference measurement of neural TI. Comparison of the indirect estimates of neural TI duration, based on flow, Pes, and Pdi against the reference measurement, revealed a mean difference (bias) ranging from -54 to 612 ms during spontaneous breathing and from -52 to 714 ms during mechanical ventilation; the respective precisions (standard deviations of the differences) ranged from 79 to 175 ms and from 74 to 221 ms. Because an indirect estimate of neural TI duration could be identical to that of the reference measurement and yet be displaced in time, this lag or lead was quantified as the phase angle of neural TI onset. Flow-based estimates of the onset of neural TI displayed a systematic lag, which may be explained at least in part by concurrent intrinsic positive end-expiratory pressure. In conclusion, the indirect estimates of the onset and duration of neural TI in ventilator-dependent patients displayed poor agreement with the diaphragmatic EMG measurement of neural TI.

Aged↗

Effect of isocapnic hypoxia on variational activity of breathing.

In the presence of either hypocapnia or sleep, hypoxia has been shown to induce periodic breathing and increase the total variational activity of breath components. It is not known whether hypoxia induces alterations in breathing variability during wakefulness and in the absence of hypocapnia. To address this issue, we studied nonobtrusively 14 healthy awake subjects before and during the delivery of a hypoxic gas mixture via a plastic hood; the subjects' oxygen saturation decreased from 98 to 79% and end-tidal carbon dioxide tension was kept constant. Compared with air, isocapnic hypoxia increased the gross variability of minute ventilation (V I), tidal volume (VT), inspiratory time (TI), and expiratory time (TE) (all p < 0.004). Isocapnic hypoxia decreased the autocorrelation coefficient at a lag of one breath for TE (p < 0. 008) and V I (p = 0.07), the number of consecutive breath lags having significant autocorrelation coefficients for TE (p = 0.03), and the cycle time of oscillations in V I (p = 0.03). When partitioned, the increase in total variational activity during isocapnic hypoxia was found to result from increases in the random fractions of V I, VT, TI, and TE (all p < 0.05), and the oscillatory fractions of V I, VT, and TE (all p < 0.03). In conclusion, hypoxia induced hidden oscillations in V I, VT, and TE despite wakefulness and an isocapnic state, suggesting that neural responses may have a more important role in the genesis of hypoxia-induced oscillations than previously reported.

Adult↗

Pulse oximetry.

Pulse oximetry is one of the most commonly employed monitoring modalities in the critical care setting. This review describes the latest technological advances in the field of pulse oximetry. Accuracy of pulse oximeters and their limitations are critically examined. Finally, the existing data regarding the clinical applications and cost-effectiveness of pulse oximeters are discussed.

Journal Article↗

Monitoring patient mechanics during mechanical ventilation.

This article provides a review of respiratory mechanics that can be monitored in ventilator-dependent patients during passive and spontaneous breathing. Special focus is placed on resistance, compliance, and work of breathing. A description of methods and techniques, and a summary of clinical observations and applications in critically-ill patients are also included.

Humans↗

Respiratory muscle dysfunction in mechanically-ventilated patients.

The interaction between a patient and a ventilator is the major determinant of the amount of respiratory muscle rest achieved by the machine. We are beginning to acquire a better understanding of the mechanisms that underlie this complex interaction, but this information has yet to be integrated into the routine clinical management of ventilator-supported patients. To achieve that goal, we need better techniques of detecting and monitoring patient-ventilation asynchrony, and the development of simple algorithms that can minimize its occurrence. Finally, research is needed to determine the occurrence and importance of respiratory muscle fatigue during failed weaning attempts so as to better guide the timing and pace of the weaning process in problematic patients.

Humans↗

Effect of lung volume reduction surgery on neuromechanical coupling of the diaphragm.

The mechanisms for symptomatic improvement following lung volume reduction surgery for emphysema are poorly understood. We hypothesized that enhanced neuromechanical coupling of the diaphragm is an important factor in this improvement. We studied seven patients with diffuse emphysema before and 3 mo after surgery. Patients showed improvements in 6-min walking distance (p = 0.002) and dyspnea (p = 0.04). The pressure output of the respiratory muscles, quantified as pressure-time product per minute (PTP/min), decreased after surgery (p = 0.03), as did PaCO2 (p = 0.02). Maximal transdiaphragmatic pressures (Pdi(max)) increased from 80.3 +/- 9.5 (SE) to 110.8 +/- 9.3 cm H2O after surgery (p = 0.03), and the twitch transdiaphragmatic pressure response to phrenic nerve stimulation (Pdi(tw)) increased from 17.2 +/- 2.4 to 25.9 +/- 3.0 cm H2O (p = 0.02); these increases were greater than could be accounted for by a decrease in lung volume. The contribution of the diaphragm to tidal breathing, assessed by relative changes in gastric and transdiaphragmatic pressures, increased after surgery (p = 0.008). Net diaphragmatic neuromechanical coupling, quantified as the quotient of tidal volume (normalized to total lung capacity) to tidal change in Pdi (normalized to Pdi(max)), improved after surgery (p = 0.03) and was related to the increase in 6-min walking distance (r = 0.86, p = 0.03) and decrease in dyspnea (r = 0.76, p = 0.08). In conclusion, lung volume reduction surgery effects an improvement in diaphragmatic function, greater than can be accounted for by a decrease in operating lung volume, and enhances diaphragmatic neuromechanical coupling.

Aged↗

Effect of resistive loading on variational activity of breathing.

To examine the effect of resistive loading on variational activity of breathing, we studied 18 healthy subjects breathing at rest and with inspiratory resistive loads of 3 and 6 cm H2O/L/s, applied randomly for 1 h each. Compared with resting breathing, a resistive load of 3 cm H2O/L/s decreased the total variational activity of expiratory time (TE) and minute ventilation (V I), whereas a load of 6 cm H2O/L/s increased the total variational activity of inspiratory time (TI). Compared with the load of 3 cm H2O/L/s, the load of 6 cm H2O/L/s increased total variational activity of tidal volume (VT), TI, TE, and V I. Partitioning of the total variational activity revealed that these alterations were due to changes in the random uncorrelated fraction. Compared with rest, both the resistive loads of 3 and 6 cm H2O/L/s increased the number of breath lags displaying significant serial correlations ("short-term memory") of TI. Compared with rest, the load of 3 cm H2O/L/s increased the autocorrelation coefficient at a lag of one breath for VT and the load of 6 cm H2O/L/s increased the correlated fraction of variational activity of VT. Thus, three measures of correlated behavior-autocorrelation coefficient at a lag of 1 breath, "short-term memory," and the correlated fraction of total variational activity- increased with loading. In conclusion, resistive loading changed total variational activity according to the size of the load: the random fraction decreased with the smaller load but increased with the larger load; in contrast, correlated behavior increased with both loads. The different behaviors of random and correlated variability with loading may reflect different physiologic influences on respiratory control.

Adult↗

Partitioning of lung and chest-wall mechanics before and after lung-volume-reduction surgery.

In the study reported here, we partitioned the mechanics of the respiratory system into lung and chest-wall components, using the rapid occlusion technique in seven patients with severe emphysema before lung-volume-reduction surgery and 3 mo later. Patients showed improvements in 6-min walk (p < 0.01) and dyspnea (p < 0.05). The resistances of the respiratory system and chest wall were not altered by surgery. Ohmic airway resistance did not change, but the component of lung resistance (DeltaRL) due to viscoelastic behavior (stress relaxation) and time-constant inhomogeneities (pendelluft) decreased in six patients (p < 0.03). Dynamic elastance of the lung (Edyn,L) decreased after surgery (p < 0.02), whereas dynamic elastance of the chest wall did not change. The ratio of dynamic intrinsic positive end-expiratory pressure (PEEPi) to static PEEPi, which also reflects viscoelastic properties and time-constant inhomogeneities, increased after surgery (p < 0.05). The decrease in dyspnea was related to the decrease in Edyn,L (r = 0.81, p = 0.03), and tended to be related to the decrease in DeltaRL (r = 0.71, p = 0. 07). In conclusion, lung-volume-reduction surgery decreased dynamic pressure dissipations caused by stress relaxation and time-constant inhomogeneities within lung tissue, and it had no effect on the static mechanical properties of the chest wall.

Aged↗

Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation.

Research on patient-ventilator interactions has largely focused on inspiratory events, with little attention paid to expiration. We sought to determine the importance of the timing and magnitude of expiratory muscle activity in causing patient-ventilator dyssynchrony. Our study was done with healthy subjects receiving pressure support in whom we induced airflow limitation with a Starling resistor. The timing and magnitude of expiratory muscle activity were obtained by wire electromyographic recording of the activity of the transversus abdominis muscle, and were compared with the cycling of the ventilator and inspiratory muscle activity as determined from a flow tracing and diaphragmatic electromyogram (EMG), respectively. Induction of airflow limitation produced significant phase differences in the cycling of the subjects' expiratory muscle group and that of the machine. Some inspiratory efforts failed to trigger the ventilator, owing in part to an increase in elastic recoil consequent to the commencement of expiratory efforts before the termination of mechanical inflation. A delay in relaxation of the expiratory muscles did not interfere with the success of subsequent inspiratory efforts to trigger the ventilator. We also investigated the accuracy of two approaches for distinguishing between the contributions of expiratory muscle activity and elastic recoil to intrinsic positive end-expiratory pressure (PEEPi): the expiratory increase in gastric pressure (Pga) correlated better with transversus abdominis electromyographic activity (r = 0.7 to 0.95) than did the early inspiratory decrease in Pga (r = 0.04 to 0.53). In conclusion, the continuation of mechanical inflation into neural expiration was associated with failure of the subsequent inspiratory attempt to trigger the ventilator.

Abdominal Muscles↗

Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramifications thereof.

To define the importance of hemodynamic performance and global tissue oxygenation in determining weaning outcome, we recorded mixed venous oxygen saturation (SvO2) continuously in eight ventilator-supported patients who failed a trial of spontaneous breathing and 11 patients who tolerated a trial and were successfully extubated. Immediately before the weaning trial, SvO2 was not statistically different in the two groups (p = 0.28). On discontinuation of the ventilator, SvO2 fell progressively in the failure group (p < 0.01), whereas it did not change in the success group. During the trial of spontaneous breathing, O2 demand was similar in the two groups, but it differed in the manner with which it was met. The success group demonstrated an increase in cardiac index (p < 0.05) and O2 transport (p < 0.02). The failure group did not increase O2 transport, partly because of elevations in right- and left-ventricular afterload, but, instead, increased O2 extraction ratio (p < 0.02) with a consequent fall in SvO2. In turn, the low SvO2 combined with greater venous admixture (p < 0.0006) led to rapid arterial desaturation (p < 0.006) and a relative decrease in O2 being supplied to the tissues. In conclusion, ventilator-supported patients who failed a trial of spontaneous breathing developed a progressive decrease in SvO2 caused by the combination of a relative decrease in convective O2 transport and an increase in O2 extraction by the tissues.

Aged↗

Sparfloxacin vs ofloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis: a multicenter, double-blind, randomized, comparative study. Sparfloxacin Multicenter ABECB Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin vs ofloxacin for treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). DESIGN: Multicenter, double-blind, randomized study. SETTING: Sixty-eight private offices and outpatient clinics in the United States and Canada. PATIENTS: Seven hundred ninety-eight adults with ABECB, as confirmed by the acute onset of new (or worsened from the immediate premorbid state) cough and sputum production. INTERVENTIONS: Randomization 1:1 to sparfloxacin, 400 mg on day 1, then 200 mg once daily, or ofloxacin, 400 mg twice daily, with matching comparator placebos, given concurrently for 10 consecutive days. RESULTS: The primary efficacy parameter was overall response in the bacteriologically evaluable population. Overall success rates in this population were 85.3% and 89.3% for sparfloxacin and ofloxacin, respectively. The two-sided 95% confidence interval was -9.9, 1.9, indicating that sparfloxacin was statistically equivalent to ofloxacin. The all-treated population analysis was similar to that in the evaluable population. Bacterial eradication rates were similar in both treatment groups for Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Enterobacter cloacae, and Staphylococcus aureus. The frequency of adverse events overall was comparable in the two treatment groups. The sparfloxacin group had a lower frequency of digestive and nervous system adverse events, but a higher frequency of photosensitivity reactions than the ofloxacin group. CONCLUSIONS: Once-daily oral treatment with 200 mg sparfloxacin (after initial 400 mg dose) is as effective as twice-daily treatment with 400 mg ofloxacin in patients with ABECB.

Acute Disease↗

Effects of aerosolized surfactant in patients with stable chronic bronchitis: a prospective randomized controlled trial.

CONTEXT: Chronic bronchitis, estimated to affect more than 13 million adults in the United States, is characterized in part by retention of airway secretions, but no approved or effective therapy for airway mucus retention in patients with chronic bronchitis has been established. Surfactant reduces sputum adhesiveness, which contributes to difficulty in clearing secretions, but surfactant has not been tested in patients with chronic bronchitis. OBJECTIVE: To examine the effects of exogenous surfactant on sputum clearance and pulmonary function in patients with stable chronic bronchitis. DESIGN: A prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled comparison of the effects of 2 weeks of treatment with 3 doses of aerosolized surfactant (palmitoylphosphadidylcholine [DPPC]) or saline (placebo). SETTING: Four US teaching hospitals. PARTICIPANTS: A total of 87 adult patients with the diagnosis of stable chronic bronchitis. MAIN OUTCOME MEASURES: Pulmonary function, respiratory symptoms, and sputum properties before treatment (day 0), after 2 weeks of treatment (day 14), and 7 days after stopping treatment (day 21). RESULTS: A total of 66 patients were randomized to surfactant treatment and 21 to saline treatment. Patient demographic characteristics between groups were similar at baseline. In patients who received a DPPC dose of 607.5 mg/d for 2 weeks, prebronchodilator forced expiratory volume in 1 second (FEV1) increased from 1.22 L (SEM, 0.08 L) at day 0 to 1.33 L (SEM, 0.09 L) at day 21 (P=.05), an improvement of 11.4%; postbronchodilator FEV1 improved 10.4% by days 14 and 21 (P=.02); and the ratio of residual volume to total lung capacity, a measure of thoracic gas trapping, decreased 6.2% by day 21 (P=.009). In the surfactant groups, there was a dose-dependent increase in the ability of sputum to be transported by cilia in vitro. CONCLUSION: Aerosolized surfactant improved pulmonary function and resulted in a dose-related improvement in sputum transport by cilia in patients with stable chronic bronchitis.

Administration, Intranasal↗