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PubMed1998

Partial liquid ventilation with perfluorocarbon in the treatment of rats with lethal pneumococcal pneumonia.

BACKGROUND: Partial liquid ventilation with perfluorocarbon is a new therapeutic strategy to treat various lung disorders. The current study was undertaken to determine the efficacy of partial liquid ventilation with a perfluorocarbon (FC-77) in the treatment of pneumococcal pneumonia in rats. METHODS: Male Wistar rats (weight, 275-300 g; n, 75) were infected via direct intratracheal inoculation with ca 10(9) colony-forming units of viable Streptococcus pneumoniae, serotype 3, and 24 h after infection were placed into one of five groups, each containing 15 rats. The groups were (1) no treatment, (2) one intramuscular injection of penicillin G benzathine (200,000 U), (3) partial liquid ventilation with FC-77, (4) partial liquid ventilation with FC-77 and a single intramuscular dose of penicillin G benzathine (200,000 U), and (5) gas ventilation. Animals were observed every 24 h for survival. RESULTS: All untreated or gas-ventilated animals or animals that received only partial liquid ventilation were dead by 7 days. Those receiving only partial liquid ventilation survived longer than untreated controls, but ultimately all succumbed by day 7. Survival was 40% for penicillin-treated rats compared with controls (P < 0.05) and 80% for animals treated with both partial liquid ventilation and penicillin versus antibiotic alone (P < 0.05). CONCLUSIONS: These observations suggest that partial liquid ventilation with perfluorocarbon in combination with antibiotic administration may be an effective therapeutic modality in pneumococcal pneumonia.

Animals↗
PubMed2000

Risk factors for early-onset, ventilator-associated pneumonia in critical care patients: selected multiresistant versus nonresistant bacteria.

BACKGROUND: Ventilator-associated pneumonia is the leading nosocomial infection in critically ill patients. The frequency of ventilator-associated pneumonia caused by multidrug-resistant bacteria has increased in recent years, and these pathogens cause most of the deaths attributable to pneumonia. The authors, therefore, evaluated factors associated with selected multidrug-resistant ventilator-associated pneumonia in critical care patients. METHODS: The authors prospectively recorded potential risk factors at the time of intensive care unit admission. An endotracheal aspirate was obtained in all patients who met clinical criteria for pneumonia. Patients were considered to have ventilator-associated pneumonia only when they met the clinical criteria and aspirate culture was positive for bacteria 48 h or more after initiation of mechanical ventilation. Pediatric patients were excluded. Adult patients with ventilator-associated pneumonia were first grouped as "early-onset" (< 5 days) and "late-onset," determined by episodes of ventilator-associated pneumonia, and then, assigned to four groups based on the bacteria cultured from their tracheal aspirates: Pseudomonas aeruginosa, Acinetobacter baumanii, methicillin-resistant staphylococci, and all others. The first three bacteria were considered to be multidrug resistant, whereas the others were considered to be antibiotic susceptible. Potential risk factors were evaluated with use of univariate statistics and multivariate regression. RESULTS: Among 486 consecutive patients admitted during the study, 260 adults underwent mechanical ventilation for more than 48 h. Eighty-one patients (31%) experienced 99 episodes of ventilator-associated pneumonia, including Pseudomonas(33 episodes), methicillin-resistant staphylococci (17 episodes), Acinetobacter(9 episodes), and nonresistant bacteria (40 episodes). Sixty-six of these episodes were early onset and 33 episodes were late onset. Logistic regression analysis identified three factors significantly associated with early-onset ventilator-associated pneumonia caused by any one of the multidrug-resistant bacterial strains: emergency intubation (odds ratio, 6.4; 95% confidence interval, 2.0-20.2), aspiration (odds ratio, 12.7; 95% confidence interval, 2.4-64.6), and Glasgow coma score of 9 or less (odds ratio, 3.9; 95% confidence interval, 1.3-11.3). A. baumanii-related pneumonia cases were found to be significantly associated with two of these factors: aspiration (odds ratio, 14.2; 95% confidence interval, 1.5-133.8) and Glasgow coma score (odds ratio, 6.0; 95% confidence interval, 1.1-32.6). CONCLUSIONS: The authors recommend that patients undergoing emergency intubation or aspiration or who have a Glasgow coma score of 9 or less be monitored especially closely for early-onset multidrug-resistant pneumonia. The occurrence of aspiration and a Glasgow coma score of 9 or less are especially associated with pneumonia caused by A. baumanii.

Adult↗
PubMed1991

Reduction of duration and cost of mechanical ventilation in an intensive care unit by use of a ventilatory management team.

OBJECTIVE: To test the hypothesis that a formal interdisciplinary team approach to managing ICU patients requiring mechanical ventilation enhances ICU efficiency. DESIGN: Retrospective review with cost-effectiveness analysis. SETTING: A 20-bed medical-surgical ICU in a 450-bed community referral teaching hospital with a critical care fellowship training program. PATIENTS: All patients requiring mechanical ventilation in the ICU were included, comparing patients admitted 1 yr before the inception of the ventilatory management team (group 1) with those patients admitted for 1 yr after the inception of the team (group 2). Group 1 included 198 patients with 206 episodes of mechanical ventilation and group 2 included 165 patients with 183 episodes of mechanical ventilation. INTERVENTION: A team consisting of an ICU attending physician, nurse, and respiratory therapist was formed to conduct rounds regularly and supervise the ventilatory management of ICU patients who were referred to the critical care service. MEASUREMENTS AND MAIN RESULTS: The two study groups were demographically comparable. However, there were significant reductions in resource use in group 2. The number of days on mechanical ventilation decreased (3.9 days per episode of mechanical ventilation [95% confidence interval 0.3 to 7.5 days]), as did days in the ICU (3.3 days per episode of mechanical ventilation [90% confidence interval 0.3 to 6.3 days]), numbers of arterial blood gases (23.2 per episode of mechanical ventilation; p less than .001), and number of indwelling arterial catheters (1 per episode of mechanical ventilation; p less than .001). The estimated cost savings from these reductions was $1,303 per episode of mechanical ventilation. CONCLUSION: We conclude that a ventilatory management team, or some component thereof, can significantly and safely expedite the process of "weaning" patients from mechanical ventilatory support in the ICU.

Aged↗
PubMed1992

Aggressive hydration during continuous positive-pressure ventilation restores atrial transmural pressure, plasma atrial natriuretic peptide concentrations, and renal function.

BACKGROUND AND METHODS: The correlations between continuous positive-pressure ventilation-induced antidiuresis/antinatriuresis, atrial transmural pressure, and atrial natriuretic peptide concentrations have not been clarified. The purpose of the present study was to use aggressive hydration to restore atrial transmural pressure during continuous positive-pressure ventilation and to test for correlations of atrial transmural pressure, atrial natriuretic peptide concentration, diuresis, and natriuresis during this intervention. An intrapleural catheter was used to measure atrial transmural pressure in three ways: a) right atrial pressure minus intrapleural pressure, b) left ventricular end-diastolic pressure minus intrapleural pressure, and c) pulmonary artery occlusion pressure minus intrapleural pressure. Hemodynamic, atrial natriuretic peptide concentrations, and renal measurements were made in 12 anesthetized closed-chest dogs during baseline (intermittent positive-pressure ventilation), during continuous positive-pressure ventilation), during continuous positive-pressure ventilation with 10 cm H2O end-expiratory pressure, and during continuous positive-pressure ventilation plus aggressive hydration (approximately 60 mL/kg lactated Ringer's solution). Pearson's correlation matrix was used to generate all possible correlation coefficients between the three atrial transmural pressures, atrial natriuretic peptide concentrations, urine output, and urine sodium excretion. RESULTS: Application of continuous positive-pressure ventilation resulted in a 60% decrease in right atrial transmural pressure (p less than .05), a 51% decrease in left ventricular end-diastolic transmural pressure (p less than .05), and a 26% decrease in pulmonary artery occlusion transmural pressure (p less than .05) from baseline. Plasma atrial natriuretic peptide concentration decreased from 80 +/- 12 (SEM) pg/mL at baseline to 49 +/- 8 pg/mL during continuous positive-pressure ventilation (p less than .05). Both urine output and sodium excretion decreased by 81% (p less than .05). After aggressive hydration with lactated Ringer's solution during continuous positive-pressure ventilation, to restore atrial transmural pressure to baseline, plasma atrial natriuretic peptide concentration returned to baseline values (81 +/- 12 pg/mL) as did urine output and sodium excretion. Correlation indices (r2 values) between transmural pressure, atrial natriuretic peptide concentration, urine output, and sodium excretion ranged from .835 to .994. Multivariate analysis of covariance demonstrated significant (p less than .05) temporal dependence between the three transmural pressures, atrial natriuretic peptide concentration, urine output, and sodium excretion. CONCLUSIONS: The results demonstrate that aggressive hydration during continuous positive-pressure ventilation will restore diuresis and natriuresis and that this response correlates significantly with atrial transmural filling pressure and plasma atrial natriuretic peptide concentration.

Animals↗
PubMed1993

Decreasing imposed work of the breathing apparatus to zero using pressure-support ventilation.

OBJECTIVES: To apply pressure-support ventilation with the goal of decreasing the imposed work of the breathing apparatus (endotracheal tube, breathing circuit tubing, and the ventilator's demand-flow system) to zero and to evaluate a clinical method of measuring the imposed work of breathing. DESIGN: A prospective evaluation of adult and pediatric patients receiving mechanical ventilatory support. SETTING: A surgical and a pediatric intensive care unit in a university hospital. PATIENTS: Fifteen patients (11 adult and four pediatric), who were diagnosed with acute respiratory failure from various etiologies, and who were intubated and spontaneously breathing, received continuous positive airway pressure and pressure-support ventilation. MEASUREMENTS AND MAIN RESULTS: Imposed work of the breathing apparatus was calculated by integrating pressure measured at the tracheal end of the endotracheal tube from a narrow air-filled catheter and the change in volume from a miniature pneumotachograph (flow sensor) positioned between the "Y" piece of the breathing circuit and the endotracheal tube. Pressure and volume signals were directed to a computerized, portable respiratory monitor (Bicore Monitoring Systems) that provides real-time display of the pressure-volume (work) loops and calculation of the imposed work. Imposed work was measured at 0 cm H2O pressure-support ventilation, and then incremental levels of pressure-support ventilation were applied until the imposed work decreased to zero. Imposed work decreased in a quadratic fashion after incremental levels of pressure-support ventilation (r = -.83 [r2 = .69]; p < .001). At pressure-support ventilation level of 0 cm H2O, the imposed work was 0.60 +/- 0.17 joule/L. At mean pressure-support ventilation levels of 13.5 +/- 4.8 cm H2O, imposed work decreased to 0 joule/L. CONCLUSIONS: Ideally, the imposed work of the breathing apparatus should be zero to decrease the afterload on the ventilatory muscles and, thus, the patient's work of breathing. Eliminating the imposed work is achieved using appropriate levels of pressure-support ventilation. We describe an easily applied, practical method of measuring imposed work using a commercially available, portable, bedside respiratory monitor. We recommend that all patients diagnosed with respiratory failure and compromised pulmonary mechanics and who are intubated and breathing spontaneously, receive at least a minimal level of pressure-support ventilation that results in zero breathing apparatus-imposed work of breathing.

Acute Disease↗
PubMed1999

Regional pulmonary blood flow during partial liquid ventilation in normal and acute oleic acid-induced lung-injured piglets.

OBJECTIVE: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. DESIGN: Prospective randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Regional pulmonary blood flow was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OA-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). CONCLUSIONS: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.

Animals↗
PubMed1997

Indications for mechanical ventilation.

Indications for mechanical ventilation have evolved substantially since widespread use of ventilatory support began in the early 1960s. While the metabolic and blood-gas alterations that mandate institution of ventilatory support have remained unaltered, new noninvasive modes of ventilation have widened the therapeutic options available to patients in acute respiratory failure. An understanding of the effect of mechanical ventilation on other organ systems has clarified the role of mechanical ventilation in the treatment of conditions other than respiratory failure such as stroke or head injury. Studies in patients recovering from major surgery have better defined the benefits and risks of postoperative mechanical ventilation. Finally, a better understanding of disease processes has led to more prognostic information that can help physicians, patients, and families decide on limits to compassionate care. The proper use of mechanical ventilation in disease states that do not involve respiratory failure as their primary manifestation is also important in light of the risks of respiratory support. In patients with CNS injury, the role of hyperventilation is limited to acute control of dangerous elevations of intracranial pressure. Although hypocarbia has been proposed to improve regional cerebral blood flow, studies have not demonstrated an improvement in outcome, suggesting that the risks of intubation, tracheal stimulation, sedation, and inability to examine the mental status outweigh any benefit. Some evidence suggests a detrimental effect from prolonged hyperventilation. The use of mechanical ventilation in postoperative care is another area that requires scrutiny. Numerous studies have shown that with coordination of care between surgeons, anesthesiologists, and nurses, many patients can be extubated significantly sooner than in the past. As techniques for administering anesthesia, performing surgery, and managing pain and mild respiratory insufficiency improve, knowledge in this area will continue to develop. Finally, the relation between mechanical ventilation, quality of life, and patient autonomy has come to play a greater role as the population ages. In many situations, respiratory failure represents the end stage of an irreversible disease. Whereas respiratory failure secondary to pulmonary contusion in young patients does not indicate a poor outcome, progressive respiratory failure in cystic fibrosis or following bone marrow transplantation usually represents a preterminal event. Understanding the epidemiology of respiratory failure in different disease categories is important to physicians, patients, and families in making informed decisions about their care. Mechanical ventilation represents a vital, fundamental form of life support. As the diseases, tools, and treatments change in anesthesia and critical care, careful definition of the role of mechanical ventilation in specific diseases, the route by which it is delivered, and the ability of such a form of life support to affect outcome will continue to be necessary.

Anesthesia, General↗
PubMedDate not supplied

End of life in the NICU. A study of ventilator withdrawal.

PURPOSE: Withdrawal of ventilator support occurs commonly in the neonatal intensive care unit (NICU), but few studies have examined the process surrounding this event. This study reviewed the charts of 18 infants who died after ventilator withdrawal. Documentation of process of ventilator withdrawal, medication administration, parental participation in the decision making, and support of the family were examined. DESIGN AND METHODS: Retrospective chart review of all neonatal deaths during the years 1997 to 1998 in two urban hospitals with Level II and Level III NICUs. Seventy-two neonates died during that time period; 18 had died after ventilator withdrawal. Descriptive statistics were used for analysis. RESULTS: We found a lack of clarity and consistency in the documentation in charts of infants who died after ventilator removal. Twenty-two percent of the charts had no written orders for ventilator removal; only two-thirds of the infants were receiving pain medication in conjunction with ventilator removal; 83% of the charts had a notation about parental participation in the ventilator removal. Regarding support, most charts documented support from family or clergy; however, no charts documented the emotional or social support given by nurses to the families. CLINICAL IMPLICATIONS: Improved provision of and documentation of pain and symptom management upon ventilator withdrawal are needed. More clearly written orders for ventilator termination are suggested. Improved documentation of the support provided by nurses to parents of dying infants is recommended.

Death↗
PubMed2000

Synchronized independent lung ventilation in palliated congenital heart disease with variable sources of pulmonary blood flow.

OBJECTIVE: Presentation of two patient studies demonstrating the use of synchronized independent lung ventilation in the management of acute respiratory failure in patients with complex palliated congenital heart disease and variable sources of pulmonary blood flow. DESIGN: Clinical course of two patients. SETTING: Cardiac intensive care unit in a tertiary care, university-affiliated pediatric teaching hospital. PATIENTS: Patient 1 was a 22-yr-old woman with a single ventricle and right lung blood flow supplied by a classic Glenn shunt and left lung blood flow through a systemic-to-pulmonary artery shunt. Patient 2 was a 12-yr-old boy with tetralogy of Fallot and complete common atrioventricular canal defect with right lung blood flow supplied by a classic Glenn shunt and left lung blood flow supplied by the right ventricle. Both patients presented with acute, left-sided lung disease and hypoxemia. INTERVENTIONS: We used selective bronchial intubation via a double-lumen tracheal tube with a bronchial extension for synchronized independent lung ventilation to permit high-pressure ventilation of the abnormal left lung low-pressure ventilation of the normal right lung supplied by a Glenn shunt. Inhaled nitric oxide was administered to both patients and continued in one when improved oxygenation was observed. MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gas measurements, mechanical indices of pulmonary function, and chest radiographs were closely followed. Synchronized independent lung ventilation contributed to improvements in systemic arterial blood oxygenation and alveolar ventilation allowing resumption of conventional ventilation in both patients. No adverse effects related to bronchial tube placement or maintenance occurred. CONCLUSION: Independent lung ventilation is an effective means of isolating the two lungs for differential ventilation, as well as the selective delivery of inhaled medications. In patients with unilateral lung disease and a Glenn shunt supplying the unaffected lung, selective lung ventilation allows aggressive treatment of the abnormal lung while optimizing flow through the Glenn shunt to maximize effective pulmonary blood flow, systemic oxygenation, and hemodynamics.

Journal Article↗
PubMed2005

Projected incidence of mechanical ventilation in Ontario to 2026: Preparing for the aging baby boomers.

OBJECTIVE: The aging baby boomers are expected to have a significant impact on the healthcare system. Mechanical ventilation is an age-dependent, costly, and relatively nondiscretionary medical service that may be particularly affected by the aging population. We forecast the future incidence of mechanical ventilation to the year 2026 to understand the impact of aging baby boomers on critical care resources. DESIGN: Population-based, sex-specific, and age-specific mechanical ventilation incidences for adults for the year 2000 were directly standardized to population projections to estimate the incidence of mechanical ventilation, in 5-yr intervals, from 2006 to 2026. Sensitivity analyses were performed by varying population projections and mechanical ventilation incidence for the elderly. SETTING: Province of Ontario, Canada. PATIENTS: Noncardiac surgery, mechanically ventilated adults. INTERVENTIONS: None. MAIN RESULTS: The projected number of ventilated patients in 2026 was 34,478, representing an 80% increase from 2000. The crude incidence increased 31%, from 222 to 291 per 100,000 adults. The annually compounded projected growth rate during this 26-yr period was 2.3%, similar to the actual growth rate experienced in the 1990s. The projected incidence was relatively insensitive to changes in assumptions, with estimates for 2026 ranging from 31,473 to 36,313 ventilated adults. CONCLUSIONS: The incidence of mechanical ventilation projected to the year 2026 will steadily increase and outpace population growth as occurred in the 1990s. In the current environment in which intensive care unit resources are limited and ventilated patients already use a significant proportion of acute care resources, planning for this continued growth is necessary. Existing evidence-based strategies that improve both the efficiency and efficacy of critical care services should be carefully evaluated for widespread implementation.

Adult↗
PubMed2006

Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats.

OBJECTIVE: Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin- proteasome pathway. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 wks old. INTERVENTIONS: Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium. MEASUREMENTS AND MAIN RESULTS: In vitro diaphragm force was decreased more significantly after 24 hrs of mechanical ventilation combined with rocuronium infusion than after mechanical ventilation alone (e.g., tetanic force, -27%; p < .001 vs. mechanical ventilation). Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (-38% and -29%, respectively; p < .001 vs. control). Diaphragm hydroperoxide levels increased similarly in both mechanically ventilated groups. Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin-proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control). Significant correlations were found between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber dimensions. CONCLUSIONS: Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin-proteasome pathway. These findings could be important with regard to weaning failure in patients receiving this drug for prolonged periods in the intensive care unit setting.

Androstanols↗
PubMed1970

Passage of macromolecules between alveolar and interstitial spaces in foetal and newly ventilated lungs of the lamb.

1. Experiments were performed on exteriorized foetal lambs to measure transfer of macromolecules (proteins and [(125)I]PVP) between lung alveolar liquid (A(l)) and lung interstitial liquid as represented by lung lymph (L(ly)). Transfer was measured in the foetus and during a 2 hr period of positive pressure ventilation.2. In thirteen experiments [(125)I]PVP was introduced into A(l) and, after a control period, the lungs were ventilated for 2 hr. In six other experiments the [(125)I]PVP was injected intravenously; and in two of these the lungs were ventilated for 2 hr. Measurements were made of protein and of [(125)I]PVP concentration in plasma and L(ly) collected at intervals throughout the experiment, as well as in A(l) obtained before ventilation and at the end of ventilation after degassing the lung. [(125)I]PVP in the samples was separated into fractions of different Stokes-Einstein radius by gel filtration using Sephadex G-200.3. Before ventilation there was evidence of a negligible transfer of protein from L(ly) to A(l) (mean protein A(l)/L(ly) = 0.014) or of [(125)I]PVP from A(l) to L(ly) (mean [(125)I]PVP L(ly)/A(l) = 0.00017). The effect of ventilation for 2 hr was to produce an increase in both ratios, but by a variable amount (after 2 hr ventilation mean protein A(l)/L(ly) = 0.70 +/- 0.08 (S.E. of mean) and mean [(125)I]PVP L(ly)/A(l) = 0.48 +/- 0.09). By calculating L(ly)/A(l) ratios for [(125)I]PVP fractions obtained by gel filtration it was shown that in transfer from A(l) to L(ly) during ventilation molecular sieving could be detected, the degree of which was expressed by means of a Relative Sieving Index (RSI). Significant correlations were found between the minimum surface tension of lung extracts, and two other indicators of lung maturity on the one hand, and the protein and [(125)I]PVP ratios and RSI on the other; so that the more mature the lamb the less the transfer of macromolecules during ventilation and the greater the degree of molecular sieving.4. By comparing concentrations of [(125)I]PVP gel filtration fractions in lymph and plasma, when the [(125)I]PVP had been placed in A(l), we demonstrated some sieving of molecules (in the range 34-15 A) in their absorption from interstitial space to plasma.5. It was concluded that in the lungs of the foetal lamb there is an almost complete barrier to the transfer of macromolecules between alveolar and interstitial spaces; that positive pressure ventilation for 2 hr causes a very variable degree of break-down in this barrier, and that the degree of break-down is usually greater in immature than in mature lungs.

Age Factors↗
PubMed1992

Negative extrathoracic pressure ventilation for phrenic nerve palsy after paediatric cardiac surgery.

OBJECTIVE: To investigate the feasibility of negative extrathoracic pressure ventilation as a respiratory support following phrenic nerve palsy after cardiac surgery. DESIGN: An uncontrolled pilot study. PATIENTS: 14 patients aged one week to 30 months (median 5.3 months) with phrenic nerve palsy diagnosed by phrenic nerve conduction tests and diaphragmatic electromyograms. Four had bilateral and 10 unilateral palsy. Before treatment all required oxygen and 10 were receiving positive pressure ventilation. One of the patients with bilateral and four of the patients with unilateral palsies had undergone a plication before negative pressure ventilation was started. INTERVENTION: Treatment was started 6-65 days (median 23) after operation with a newly designed system which included a Perspex chamber, which gave easy access to the child, and an elastic latex neck seal. Continuous negative pressure was used in conjunction with intermittent positive pressure ventilation while continuous or intermittent negative pressure ventilation was used in extubated infants. RESULTS: All four patients with bilateral palsy survived with long-term intermittent negative pressure ventilation and did not require further surgery. Of the 10 with unilateral lesions, seven required no further surgery, two underwent plication, and one had a re-plication. Three patients with unilateral palsy died of non-respiratory causes. The duration of positive pressure ventilation after starting negative pressure ranged from 0 to 23 days (median 6). Treatment with negative pressure lasted for 3-241 days (median 32) and was predominantly administered off the intensive care unit, including at home. CONCLUSIONS: Negative pressure ventilation may be an alternative to positive airway pressure ventilation in the management of phrenic nerve palsy. A multicentre randomised controlled trial is now required to assess further the role of negative pressure ventilation in phrenic nerve palsy.

Child, Preschool↗
PubMed2005

Predictors of mortality in mechanically ventilated patients.

OBJECTIVES: There are scarce data from India validating scoring systems used to predict outcome in patients requiring mechanical ventilation. This study prospectively compared the organ system failure (OSF), the acute physiology and chronic health evaluation (APACHE) II, and the APACHE III, scores on patients requiring mechanical ventilation in the medical intensive care unit, to predict outcome. METHODS: 200 consecutive patients requiring mechanical ventilation in a medical intensive care unit were recruited. OSF, APACHE II, and APCHE III scores were calculated at admission and daily for one week or until discharge in all patients. Other variables recorded include age, sex, diagnosis, oxygen therapy before ventilation, complications on ventilation, duration in hospital before ventilation, duration of ventilation, type of respiratory failure, alveolar arterial oxygen gradient, P/F ratio, use of tracheostomy, time on ventilator before tracheostomy, muscle relaxant used, fluid balance, inotrope support. Logistic regression analysis and area under the curve were computed to determine which variables independently predict outcome. RESULTS: Of the 200 patients, at discharge 143 patients (71.5%) had died. The factors that independently predicted outcome among these patients on mechanical ventilation were the type of respiratory failure (type I) OR = 2.7 (p = 0.02), the use of inotropes OR 2.4 (p = 0.04), and the APACHE II score OR = 1.8 (p = 0.008) for every five point increase in APACHE II score. CONCLUSIONS: Type 1 respiratory failure, the use of inotropes, and the APACHE II score measured at admission are significant independent predictors of mortality in the patients on mechanical ventilation.

APACHE↗
PubMed2005

Randomised crossover study of pressure and volume non-invasive ventilation in chest wall deformity.

BACKGROUND: Non-invasive ventilation is an established treatment for chronic respiratory failure due to chest wall deformity. There are few data available to inform the choice between volume and pressure ventilators. The aim of this study was to compare pressure and volume targeted ventilation in terms of diurnal arterial blood gas tensions, lung volumes, hypercapnic ventilatory responses, sleep quality, and effect on daytime function and health status when ventilators were carefully set to provide the same minute ventilation. METHODS: Thirteen patients with chest wall deformity underwent a 4 week single blind randomised crossover study using the Breas PV403 ventilator in either pressure or volume mode with assessments made at the end of each 4 week period. RESULTS: Minute ventilation at night was less than that set during the day with greater leakage for both modes of ventilation. There was more leakage with pressure than volume ventilation (13.8 (1.9) v 5.9 (1.0) l/min, p = 0.01). There were no significant differences in sleep quality, daytime arterial blood gas tensions, lung mechanics, ventilatory drive, health status or daytime functioning. CONCLUSIONS: These data suggest that pressure and volume ventilation are equivalent in terms of the effect on nocturnal and daytime physiology, and resulting daytime function and health status.

Cross-Over Studies↗
PubMed1994

Effect of detergent on alveolar particle clearance due to large tidal ventilation.

BACKGROUND: It has recently been shown that large tidal volume ventilation accelerates the alveolar clearance of insoluble particles and this may be related to accelerated surfactant evacuation from the alveolus into the airway. The aim of this study was to investigate if the effect of large tidal volume ventilation is modified in an experimental model of surfactant dysfunction. METHODS: Fluorescent latex particles of 0.63 microns diameter were administered in aerosol form to 30 rabbits during anaesthesia with thiopentone and mechanical ventilation. Six animals were killed immediately after aerosol administration in order to show the initial deposition of particles. Twenty four animals were divided into two groups and ventilated for three hours with either large tidal volume (mean tidal volume 30 ml/kg) or conventional ventilation (mean tidal volume 12.5 ml/kg). Six rabbits in each of the two groups were administered either the synthetic detergent dioctyl sodium sulphosuccinate in aerosol form or aerosolised vehicle. After the period of experimental ventilation the lungs were removed and dried in the expanded state. Particles in the alveolar region were counted with fluorescent microscopy in sections of the lung. RESULTS: Compared with the baseline group (mean (SD) 24.8 (9.9)) the count of residual alveolar particles was lower after large tidal volume ventilation in the absence of detergent aerosol (13.2 (6.5)). Particle count after large tidal volume ventilation and detergent treatment (23.3 (6.4)) was similar to that in the baseline group and to that in the groups exposed to conventional ventilation. CONCLUSIONS: The increase in alveolar clearance of insoluble particles caused by large tidal volume ventilation is inhibited by detergent aerosol. This might be due to reduced stability of the surfactant film after detergent aerosol.

Aerosols↗
PubMed2003

Variable ventilation induces endogenous surfactant release in normal guinea pigs.

Variable or noisy ventilation, which includes random breath-to-breath variations in tidal volume (Vt) and frequency, has been shown to consistently improve blood oxygenation during mechanical ventilation in various models of acute lung injury. To further understand the effects of variable ventilation on lung physiology and biology, we mechanically ventilated 11 normal guinea pigs for 3 h using constant-Vt ventilation (n = 6) or variable ventilation (n = 5). After 3 h of ventilation, each animal underwent whole lung lavage for determination of alveolar surfactant content and composition, while protein content was assayed as a possible marker of injury. Another group of animals underwent whole lung lavage in the absence of mechanical ventilation to serve as an unventilated control group (n = 5). Although lung mechanics did not vary significantly between groups, we found that variable ventilation improved oxygenation, increased surfactant levels nearly twofold, and attenuated alveolar protein content compared with animals ventilated with constant Vt. These data demonstrate that random variations in Vt promote endogenous release of biochemically intact surfactant, which improves alveolar stability, apparently reducing lung injury.

Animals↗
PubMed2004

Mechanisms of early pulmonary neutrophil sequestration in ventilator-induced lung injury in mice.

Polymorphonuclear leukocytes (PMN) play an important role in ventilator-induced lung injury (VILI), but the mechanisms of pulmonary PMN recruitment, particularly early intravascular PMN sequestration during VILI, have not been elucidated. We investigated the physiological and molecular mechanisms of pulmonary PMN sequestration in an in vivo mouse model of VILI. Anesthetized C57/BL6 mice were ventilated for 1 h with high tidal volume (injurious ventilation), low tidal volume and high positive end-expiratory pressure (protective ventilation), or normal tidal volume (control ventilation). Pulmonary PMN sequestration analyzed by flow cytometry of lung cell suspensions was substantially enhanced in injurious ventilation compared with protective and control ventilation, preceding development of physiological signs of lung injury. Anesthetized, spontaneously breathing mice with continuous positive airway pressure demonstrated that raised alveolar pressure alone does not induce PMN entrapment. In vitro leukocyte deformability assay indicated stiffening of circulating leukocytes in injurious ventilation compared with control ventilation. PMN sequestration in injurious ventilation was markedly inhibited by administration of anti-L-selectin antibody, but not by anti-CD18 antibody. These results suggest that mechanical ventilatory stress initiates pulmonary PMN sequestration early in the course of VILI, and this phenomenon is associated with stretch-induced inflammatory events leading to PMN stiffening and mediated by L-selectin-dependent but CD18-independent mechanisms.

Animals↗