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Biomedical subjects

N R MacIntyre

Publications and source records attributed to N R MacIntyre.

At least 19 recordsLinked to original sources

Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome.

OBJECTIVES: To investigate physiologic and outcome data in patients switched from volume-cycled conventional ratio ventilation to pressure-controlled inverse ratio ventilation that did not produce air trapping and intrinsic positive end-expiratory pressure (PEEP). SETTING: Medical intensive care unit. DESIGN: Retrospective analysis of crossover data and outcome. PATIENTS: Fourteen patients with the adult respiratory distress syndrome who were receiving mechanical ventilation with volume-cycled, conventional ratio ventilation followed by pressure-controlled, inverse ratio ventilation. INTERVENTIONS: Our approach to pressure-controlled, inverse ratio ventilation was to use tidal volumes and applied PEEP values comparable to those volumes and values used on volume-cycled, conventional ratio ventilation, use inspiratory times to increase mean airway pressure instead of additional applied PEEP, and avoid air trapping (intrinsic PEEP). MEASUREMENTS AND MAIN RESULTS: With this approach, there was a reduction in peak airway pressure from 53 +/- 8.5 (SD) to 40 +/- 5.9 cm H2O (p < .01), and an increase in mean airway pressure from 20 +/- 3.9 to 30 +/- 5.2 cm H2O (p < .01). Tidal volume, mean inflation pressure, and compliance did not change. Oxygenation (PaO2) improved from 57 +/- 11.3 torr (7.6 +/- 1.5 kPa) to 94 +/- 40.2 torr (12.5 +/- 5.4 kPa) (p = .01) but the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) did not change significantly (25.9 +/- 10.3 to 27.2 +/- 12.2). There was no significant change in PaCO2 or pH even though delivered minute ventilation decreased from 17.4 +/- 4.3 to 14.8 +/- 5.8 L/min (p = .02). Cardiac index slightly decreased, but hemodynamic values were otherwise stable. Only three of the 14 study patients survived. CONCLUSIONS: These data demonstrate that oxygenation is primarily a function of mean airway pressure, and that longer inspiratory times can be used as an alternative to applied PEEP to increase this oxygenation. If no air trapping develops, lung inflation pressures and delivered volumes remain constant with this approach. Because the technique was used only in patients refractory to conventional techniques, the poor outcome is not surprising.

Adult

Combining pressure-limiting and volume-cycling features in a patient-interactive mechanical breath.

OBJECTIVES: To combine the patient synchrony effects of pressure-limited breath delivery strategies with the volume guarantee of volume-cycled breath delivery strategies, we designed a positive-pressure breath that incorporates both features. This breath is patient triggered and can be pressure limited. Breath termination (i.e., cycling) can either be flow- or volume-cycled, depending on whether a target volume has been attained. The pressure-limiting features are further enhanced by the capability to adjust demand-valve responsiveness at breath initiation. DESIGN: Prospective, mechanical simulation studies. SETTING: Engineering laboratory. INTERVENTIONS: A mechanical lung model that could simulate patient ventilatory efforts was used. Vigorous and weak patient efforts were studied in conjunction with use of volume assist, pressure support, and a combination pressure-limited and volume-cycled breath. MEASUREMENTS AND MAIN RESULTS: Two clinical situations were simulated by the model: a) a patient requiring total mechanical ventilatory support who had a very active ventilatory drive; and b) a patient receiving only partial ventilatory support who had an unstable ventilatory drive. A range of pressure-limiting and volume-cycling settings were given. Volume, pressure, and flow delivery were measured. Synchrony with patient effort was assessed by visual inspection of airway pressure graphics as well as by calculations of patient work during these support strategies. CONCLUSIONS: Flow dyssynchrony during fixed-flow, volume-cycled assisted breaths in patients with active ventilatory drives can be improved with this breath design while a guaranteed tidal volume is maintained. In addition, this combination breath can provide a volume "safety net" for patients in whom partial support with pressure-support ventilation is desired.

Humans

Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise.

Previous approaches to the measurements of pulmonary diffusing capacity (DL) and pulmonary capillary blood flow (QC) utilized either the rebreathing or the single inhalation technique in conjunction with radioisotope gas and mass spectrometry. In the present study, we utilized a newly developed rapid infrared analyzer in conjunction with the slow single exhalation technique on 100 healthy volunteers to establish normal values for DL and QC under sitting, supine, and exercise conditions. The exercise level was determined by a target heart rate: HRex = ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age, sex, height, or weight were then computed for sitting, supine, and exercise values. We found that mean DL and QC increased by approximately 12 percent and 8 percent, respectively, from sitting to supine posture, and by approximately 30 percent and 100 percent, respectively, from sitting (rest) to mild exercise. These results provided a database for further studies in the single exhalation method in various clinical settings.

Acetylene

Epidemiology, pathophysiology and clinical presentation of gram-negative sepsis.

OBJECTIVE: To review the epidemiology and pathophysiology of gram-negative sepsis and the new consensus terminology describing the clinical signs of sepsis. DATA SOURCES: Review of the medical literature and compiled data from animal and clinical trials. PARTICIPANTS: Members of the Society of Critical Care Medicine, American College of Chest Physicians and American Association of Critical-Care Nurses with expertise on the subject of sepsis and its complications. RESULTS: Preconference and general sessions were offered at the National Teaching Institutes of the American Association of Critical-Care Nurses, with the goal of clarifying the epidemiology, risk factors and pathophysiology of gram-negative sepsis. In addition, current terminology and new (1992) consensus terminology describing the clinical signs of sepsis were presented. Special emphasis was placed on the role of the healthcare provider in the prevention and recognition of sepsis and the role of the septic mediators in the septic cascade. CONCLUSIONS: If the incidence of sepsis is to be reduced, the healthcare provider must be aware of the risk factors for sepsis and methods of reducing nosocomial infections. A thorough understanding of the role of mediators and consensus terminology used to describe sepsis, severe sepsis, septic shock and multiple organ dysfunction syndrome is necessary to recognize early or progressive signs of sepsis and to initiate state-of-the-art therapy.

Adult

A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.

OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

Aged

Psychological outcomes of a pulmonary rehabilitation program.

This study assessed physiologic, psychological, and cognitive functioning in outpatients with COPD. Sixty-four subjects, 53 to 82 years of age, participated in the 30-day exercise rehabilitation program. The program consisted of exercise, education and psychosocial counselling. Participants were assessed prior to beginning the program and at the end of 30 days. Assessments at both times included physiologic functioning (bicycle ergometry testing, pulmonary function tests, 12-min walk), psychological well-being (anxiety, depression, psychiatric symptoms, perceived well-being) and an abbreviated neuropsychological test battery. Results indicate significant improvement in physical endurance and pulmonary function, significant reductions in symptoms of depression and anxiety, and improvement in measures of general well-being and neuropsychological functioning. The study suggests that exercise rehabilitation of older adults with COPD contributes not only to improvements in physical functioning and endurance, but also to enhanced cognitive functioning and psychological well-being.

Aged

Effects of initial flow rate and breath termination criteria on pressure support ventilation.

To assess whether adjustments in the initial flow rate or breath termination criteria affected patient-ventilator synchrony, we studied the ventilatory pattern response to PS in 33 patients under two sets of circumstances: during seven different levels of delivered initial PS flow and during PS termination at 50 percent and at 25 percent of peak flow. In the study on initial PS flow, we found the following: (a) an optimal initial PS flow could be defined for a given level of PS that resulted in the patient obtaining maximal pressure and volume from the ventilator; (b) initial PS flows above and below this optimal flow were associated with faster breathing frequencies, shorter inspiratory times, smaller tidal volumes and a tendency for airway pressure to not reach the selected PS level; and (c) optimal initial PS flow was fastest in patients with the lowest compliances and the most active ventilatory drives. Changing PS termination criteria from 50 to 25 percent of peak flow had minimal effects on the ventilatory pattern or synchrony. We conclude that the initial PS flow to achieve the selected PS level is important in patient-ventilator synchrony but that termination criteria set between 25 and 50 percent of peak flow is not.

Humans

Ventilatory muscle loads and the frequency-tidal volume pattern during inspiratory pressure-assisted (pressure-supported) ventilation.

Pressure support ventilation (PSV) is a new form of mechanical ventilatory support that assists a patient's spontaneous ventilatory effort with a clinician-selected amount of inspiratory pressure. In order to assess the muscle unloading effect and the ventilatory pattern response to increasing levels of this inspiratory pressure assist, we first utilized a computer respiratory system model with variable alveolar ventilation demands and impedances. From this model, we calculated ventilatory muscle loads (expressed either as the work/min or as the pressure time index) during simulated, unassisted breathing and during simulated breathing with levels of inspiratory pressure assist up to that which resulted in a VT of 800 ml and no work being performed by the muscles (defined as PSVmax for the model conditions being studied). The optimal ventilatory pattern (i.e., frequency-tidal volume) under each ventilation and impedance condition was defined as that which resulted in minimal muscle load. Under these model conditions, we found that PSVmax ranged from 5 to 41 cm H2O and that as the level of inspiratory pressure assist was increased from zero to PSVmax, there was a biphasic response of both the ventilatory muscle loading and the ventilatory pattern. Specifically, at low levels of inspiratory pressure assist, the model predicted that the applied pressure would only partially unload the ventilatory muscles. Continued muscle energy expenditure would thus still be required, whereas the ventilatory pattern would change little. Conversely, at higher levels of inspiratory pressure assist, the model predicted that the applied pressure would be sufficient to completely unload the ventilatory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests.

The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (n = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.

Airway Obstruction

Mechanical loads on the ventilatory muscles. A theoretical analysis.

Two indices of the total mechanical load on the ventilatory muscles, i.e., the work per minute (W.min-1) and the inflation pressure time index (PTI), have been developed to better assess muscle energy demands and fatigue potential. However, the relationship of these two indices to the various individual determinants of load and to muscle energy demands and fatigue potential are not well understood. To investigate these relationships in a theoretical fashion, we first constructed a computer model to quantitate the magnitude and relative effects of changes in the ventilation component of load, i.e., alveolar ventilation demands (VA) and dead space volume (VD), and changes in the respiratory system impedance component of load, i.e., compliance (Crs) and resistance (Raw), on W.min-1 and PTI over a wide, clinically relevant, range of ventilatory conditions. From this analysis, we demonstrated that: (1) high mechanical loads could be developed over a wide range of circumstances (i.e., W.min-1 ranged from 0.29 kg.m.min-1 to 30.55 kg.m.min-1 and PTI ranged from 1.22 to 28.8 cm H2O as ventilation increased from 7 to 39 L.min-1 and impedances worsened from normal to a combined restricted and obstructed pattern); (2) each load determinant (i.e., VA, VD, Crs, and Raw) contributed substantially to these two indices of total mechanical load; (3) although impedance changes had comparable effects on W.min-1 and PTI, ventilation changes, as would be expected, had a greater effect on W.min-1 than on PTI.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation