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PubMed1995

Significant reduction in methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia associated with the institution of a prevention protocol.

OBJECTIVE: To determine whether the institution of a methicillin-resistant Staphylococcus aureus prevention protocol was associated with a decrease in methicillin-resistant S. aureus ventilator-associated pneumonia in long-term, acute care ventilator patients. DESIGN: A retrospective chart review comparing the number of episodes of clinical pneumonia per patient ventilator day in the 12 months preceding and 24 months following the introduction of the protocol. SETTING: University affiliated, long-term, acute care ventilator hospital. PATIENTS: Long-term, acute care ventilated patients who presented with clinical pneumonia. INTERVENTIONS: Addition of a methicillin-resistant S. aureus prevention protocol. In addition to universal precautions, the protocol consisted of mupirocin 2% ointment applied to the anterior nares, and whole body washing with chlorhexidine. All patients were given mupirocin and chlorhexidine twice weekly. Patients were cohorted in the same room if they were, or had been, infected or colonized with methicillin-resistant S. aureus in any anatomical location or at any time. This procedure replaced strict isolation of methicillin-resistant S. aureus-infected or colonized individuals. MEASUREMENTS AND MAIN RESULTS: Clinical pneumonia was diagnosed when a patient developed fever, bronchorrhea, increased white blood cell count, methicillin-resistant S. aureus isolated from the tracheal aspirate, and new or increasing infiltrate on chest roentgenograph. During the 12 months preceding the protocol, there were 0.2% episodes of methicillin-resistant S. aureus ventilator-associated pneumonia per ventilated patient day compared with 0.026% in the 24 months after the protocol (p < .001). The relative and absolute risk reductions associated with the introduction of the protocol were 87% and 6, respectively. CONCLUSIONS: The period following the institution of the protocol showed a significant reduction in episodes of clinical pneumonia compared with the 12-month period preceding the use of the protocol (p < .001). Thus, we conclude that the introduction of this protocol is associated with a significant decrease in methicillin-resistant S. aureus ventilator-associated pneumonia.

Adult↗
PubMed1995

Association of myocardial ischemia with failure to wean from mechanical ventilation.

OBJECTIVE: To determine if myocardial ischemia, as detected by continuous electrocardiographic monitoring, is correlated with continued ventilator dependence in patients who have had difficulties weaning from mechanical ventilation. DESIGN: A prospective, observational study. SETTING: A university, tertiary care hospital. PATIENTS: Seventeen medical and postsurgical patients (age 70 +/- 9 yrs; range 54 to 84) who had received mechanical ventilation for 5 to 67 days at the time of entry into the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients wore a calibrated, frequency-modulated, two-channel electrocardiographic recorder with two bipolar chest leads attached to exploring electrodes for 24 hrs. We recorded the following data: a) electrocardiographic evidence of myocardial ischemia; b) eventual separation from mechanical ventilation; c) whether the patient survived to be discharged from the hospital; d) duration of tracheal intubation and mechanical ventilation; and e) length of hospital stay. The key outcome variable tested was successful weaning, which was defined as breathing without mechanical ventilatory assistance on discharge from the hospital. Six (35%) of 17 patients had electrocardiographic evidence of myocardial ischemia at the time of entry into the study. The presence of ischemia was associated with failure to wean from mechanical ventilation (p < .05; relative risk 3.05). CONCLUSIONS: Myocardial ischemia (as detected by a 24-hr, continuous Holter monitor) occurs frequently in ventilator-dependent patients. The occurrence of ischemia was associated with failure to wean from mechanical ventilation in this patient population.

Aged↗
PubMed1995

Influence of the quality of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the influence of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease. DESIGN: Data were collected prospectively over a 1-yr period (study year) and compared with previously collected prospective data recorded in our chronic obstructive pulmonary disease database during a 5-yr period. SETTING: The medical intensive care unit (ICU) of a university hospital. PATIENTS: Eighty-seven patients with chronic obstructive pulmonary disease. Fifteen patients had chronic obstructive pulmonary disease that required mechanical ventilation for acute exacerbation of their disease (study year), and 72 were patients with chronic obstructive pulmonary disease from the previously collected data. INTERVENTIONS: The ICU course (duration of mechanical ventilation, mortality) was recorded, as well as several respiratory parameters (pulmonary function tests and arterial blood gases in stable conditions, and nutritional status), and they were compared with an "index of nursing." MEASUREMENTS AND MAIN RESULTS: We developed an "index of nursing", comparing the effective workforce of the nurses (number and qualifications) with the ideal workforce required by the number of patients and the severity of their diseases. A value of 1.0 represented a perfect match between the needed and the effectively present nurses, whereas a lesser value signified a diminished available workforce. This index was compared with the complications and duration of weaning from mechanical ventilation. During the first 5 yrs, the duration of mechanical ventilation increased progressively from 7.3 +/- 8.0 to 38.2 +/- 25.8 days (p = .006). A significant inverse correlation between the duration of mechanical ventilation and the nursing index (p = .025) was found. In the sixth comparative year, the number of nurses increased (nursing index = 1.05) and the duration of mechanical ventilation decreased to 9.9 +/- 13 days (p < .001, yr 5 vs. yr 6). CONCLUSIONS: The quality of nursing appears to be a measurable and critical factor in the weaning from mechanical ventilation of patients with chronic obstructive pulmonary disease. Below a threshold in the available workforce of ICU nurses, the weaning duration of patients with chronic obstructive pulmonary disease increases dramatically. Therefore, very close attention should be given to the education and number of ICU nurses.

Aged↗
PubMed1996

Predictors of extubation success and failure in mechanically ventilated infants and children.

OBJECTIVE: To predict extubation success and failure in mechanically ventilated infants and children using bedside measures of respiratory function. DESIGN: Prospective collection of data. SETTING: A university-affiliated children's hospital with a 51-bed critical care unit. PATIENTS: All infants and children who were mechanically ventilated for at least 24 hrs, except neonates < or = 37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: Bedside measurements of cardiorespiratory function were obtained immediately before extubation. MEASUREMENTS AND MAIN RESULTS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori) of preextubation measures of breathing effort, ventilatory support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxical breathing, inspiratory pressure, maximal negative inspiratory pressure (maximal negative inspiratory pressure), inspiratory pressure/maximal negative inspiratory pressure ratio, and tidal volume indexed to body weight of a spontaneous breath. Ventilatory support was measured by the fraction of inspired oxygen (F10(2)), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics were assessed by determination of peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the compliance, rate, oxygenation, and pressure indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. Thirty-four of the 208 patients who were studied were reintubated for an overall failure rate of 16.3% (95% confidence interval 11.3% to 21.4%). The reasons for reintubation were poor effort (n = 8), excessive effort (n = 14), altered mental status or absent airway reflexes (n = 2), cardiovascular instability (n = 3), inadequate oxygenation (n = 3), respiratory acidosis (n = 3), and undocumented (n = 1). Extubation failure increased significantly with decreasing tidal volume indexed to body weight of a spontaneous breath, increasing F10(2), increasing mean airway pressure, increasing oxygenation index, increasing fraction of total minute ventilation provided by the ventilator, increasing peak ventilatory inspiratory pressure, or decreasing mean inspiratory flow (p < .05). Dynamic compliance showed a trend of increasing failure rate with decreasing dynamic compliance but did not reach statistical significance (p = .116). Respiratory rate standardized to age, inspiratory pressure, maximal negative inspiratory pressure, inspiratory pressure/maximal negative inspiratory pressure ratio, frequency to tidal volume ratio, and compliance, rate, oxygenation, and pressure did not show any trend in failure rate with increasing or decreasing values. Threshold values that defined a low risk (< or = 10%) and a high risk (> or = 25%) of extubation failure could be determined for tidal volume indexed to body weight of a spontaneous breath, F10(2), mean airway pressure, oxygenation index, fraction of total minute ventilation provided by the ventilator, peak ventilatory inspiratory pressure, dynamic compliance, and mean inspiratory flow. Neither a low nor a high risk of failure could be defined for frequency to tidal volume ratio or the compliance, rate, oxygenation, and pressure (CROP) index. CONCLUSIONS: Bedside measurements of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in

Child↗
PubMed1997

Tracheal gas insufflation during pressure-control ventilation: effect of using a pressure relief valve.

OBJECTIVES: Pressure-control ventilation minimizes alveolar overdistention by limiting peak airway pressure, but a consequence of this pressure limitation may be a reduction in tidal volume with subsequent hypercarbia. Tracheal gas insufflation (TGI) can be used in combination with pressure-control ventilation to augment CO2 elimination. During pressure-control ventilation with continuous TGI, we observed that peak airway pressure increased above the set inspiratory pressure. Based on this observation, we investigated the ability of the pressure-control ventilator circuit to compensate for continuous TGI and the effect of insertion of a pressure relief valve to eliminate over-pressurization. SETTING: University research laboratory. DESIGN: Using an artificial lung model, we studied the effects of continuous TGI with varying catheter flows (0, 2, 6, and 10 L/ min); ventilator frequencies (10 and 20 breaths/min); inspiratory duty cycles (0.33, 0.50, and 0.67); lung compliance (0.01, 0.02, and 0.04 L/cm H2O); and airway resistance (5, 20, and 50 cm H2O/L/sec) on: a) peak airway pressure; b) total inspiratory tidal volume; c) ventilator-derived tidal volume; and d) intrapulmonary pressure at end-exhalation (auto-PEEP). Tests were performed with and without a pressure relief valve whose threshold "pop-off" pressure was adjusted to match the set inspiratory pressure (35 cm H2O) for a total of 432 experimental conditions. MEASUREMENTS AND MAIN RESULTS: Our data demonstrate that pressure-control ventilation augmented with continuous TGI can increase peak airway pressure above set inspiratory pressure due to delivery of a higher than intended tidal volume. Predisposing conditions include catheter flow rates of 6 and 10 L/min, long inspiratory time, low compliance, and low resistance. With the pressure relief valve, peak airway pressure was maintained at the set inspiratory pressure and total inspiratory tidal volume remained constant. CONCLUSION: A pressure relief valve is a necessary adjunct to maintain peak airway pressure at set inspiratory pressure and keep total inspiratory tidal volume constant when continuous TGI is administered in conjunction with pressure-control ventilation.

Airway Resistance↗
PubMed1997

A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation.

OBJECTIVE: To compare a practice of protocol-directed weaning from mechanical ventilation implemented by nurses and respiratory therapists with traditional physician-directed weaning. DESIGN: Randomized, controlled trial. SETTING: Medical and surgical intensive care units in two university-affiliated teaching hospitals. PATIENTS: Patients requiring mechanical ventilation (n = 357). INTERVENTIONS: Patients were randomly assigned to receive either protocol-directed (n = 179) or physician-directed (n = 178) weaning from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the duration of mechanical ventilation from tracheal intubation until discontinuation of mechanical ventilation. Other outcome measures included need for reintubation, length of hospital stay, hospital mortality rate, and hospital costs. The median duration of mechanical ventilation was 35 hrs for the protocol-directed group (first quartile 15 hrs; third quartile 114 hrs) compared with 44 hrs for the physician-directed group (first quartile 21 hrs; third quartile 209 hrs). Kaplan-Meier analysis demonstrated that patients randomized to protocol-directed weaning had significantly shorter durations of mechanical ventilation compared with patients randomized to physician-directed weaning (chi 2 = 3.62, p = .057, log-rank test; chi 2 = 5.12, p = .024, Wilcoxon test). Cox proportional-hazards regression analysis, adjusting for other covariates, showed that the rate of successful weaning was significantly greater for patients receiving protocol-directed weaning compared with patients receiving physician-directed weaning (risk ratio 1.31; 95% confidence interval 1.15 to 1.50; p = .039). The hospital mortality rates for the two treatment groups were similar (protocol-directed 22.3% vs. physician-directed 23.6%; p = .779). Hospital cost savings for patients in the protocol-directed group were $42,960 compared with hospital costs for patients in the physician-directed group. CONCLUSION: Protocol-guided weaning of mechanical ventilation, as performed by nurses and respiratory therapists, is safe and led to extubation more rapidly than physician-directed weaning.

Adult↗
PubMed2000

Validation of predictors of extubation success and failure in mechanically ventilated infants and children.

OBJECTIVE: To validate predictors of extubation success and failure in mechanically ventilated infants and children by using bedside measures of respiratory function. DESIGN: Prospective, descriptive study. SETTING: A university-affiliated children's hospital with a 51-bed critical care area. PATIENTS: All infants and children who were mechanically ventilated for > or =24 hrs except neonates < or =37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: None. MEASUREMENTS AND METHODS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori of preextubation measures of breathing effort, ventilator support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxic breathing, inspiratory pressure, maximal negative inspiratory pressure, ratio of inspiratory pressure to maximal negative inspiratory pressure, and tidal volume indexed to body weight of a spontaneous breath. Ventilator support was measured by F(IO2), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics was assessed by peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the CROP (compliance, rate, oxygenation, and pressure) indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. A regression test for a linear trend in proportions was performed with preselected ranges and the corresponding failure rates. The failure rates from this study (validation group) were compared to those published previously (prediction group) by the chi-square test for proportions. The distribution of categorical variables between groups was analyzed by using the chi-square test or the Fisher's exact test, and p < .05 was considered significant. MAIN RESULTS: The study involved 312 patients. There were no differences in any of the clinical characteristics between the prediction and validation groups. The reasons for reintubation were similar in both groups. Preextubation data were also similar between the two groups. There were no differences between the prediction and the validation groups in failure rates with different ranges. There were no differences in the failure rates for any of the cutoff values for peak ventilatory inspiratory pressure, mean airway pressure, F(IO2), oxygenation index, dynamic compliance, tidal volume indexed to body weight of a spontaneous breath, fraction of total minute ventilation provided by the ventilator, and mean inspiratory flow. CONCLUSIONS: Bedside measures of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined by using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in infants and children. Our study validates our previously published study.

Child, Preschool↗
PubMed1986

A ventilator for magnetic resonance imaging.

Breathing motion severely degrades the quality of magnetic resonance images (MRI) of the thorax and upper abdomen and interferes with the acquisition of quantitative data. To minimize these motion effects, we built an MRI compatible ventilator for use in animal studies. Solid state circuitry is used for controlling ventilation parameters. The ventilator can be triggered internally at frequencies of 0.1 to 30 Hz or it can be triggered externally such as by the MRI pulse sequence. When triggered by the scanner, ventilation is synchronized to occur between image data acquisitions. Thus, image data are obtained when there is no breathing motion and at a minimum lung volume when hydrogen density is maximum. Since the ventilator can be adjusted to operate at virtually any frequency from conventional to high frequency, ventilation can be synchronized to all commonly used repetition times (100 ms to 2000 ms or more; 600 to 30 breaths/min). Scan synchronous ventilation eliminates breathing motion artifacts from most imaging sequences (single and multiple spin echo and inversion recovery). Best image quality is obtained when scan synchronous ventilation is combined with cardiac gating. These methods are also useful for quantitative research studies of thoracic and abdominal organs.

Abdomen↗
PubMedDate not supplied

Early clinical experience with high-frequency oscillatory ventilation for ARDS in adult burn patients.

Lung protective ventilation strategies are recommended in acute respiratory distress syndrome to avoid ventilator associated lung injury, a recently characterized complication of mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is an unconventional ventilation strategy which may achieve this goal. We reviewed our experience with HFOV in six severely burned patients with acute respiratory distress syndrome. The mean age (+/- SD) of the patients was 34 +/- 13 years, and the mean TBSA burn was 52 +/- 10%, with a mean full-thickness injury of 49 +/- 12%. HFOV was initiated as "rescue therapy" in three patients with oxygenation failure (mean PaO2/FIO2 ratio of 71 +/- 8 and mean oxygenation index [OI] of 42 +/- 3) that was unresponsive to conventional ventilation (mean FIO2, 1.0 +/- 0; mean positive end expiratory pressure, 14.8 +/- 2.8 cm H2O; and mean inhaled nitric oxide, 20 +/- 0 ppm). In the other three cases, HFOV was initiated "prophylactically" as a lung protective ventilation strategy in an attempt to prevent further respiratory deterioration. All six patients showed a rapid and substantial improvement in oxygenation after initiation of HFOV, with significant improvements in the PaO2/FIO2 and OI by 12 hours (P = 0.02). In four patients HFOV was also used during anesthesia and surgery, where a total of 10 procedures involving a mean excision and closure of 15 +/- 7% TBSA burns was performed. Five of the six patients died, but none died because of oxygenation failure. In three patients death resulted from sepsis and multiple organ dysfunction syndrome; their mean PaO2/FIO2 was 107 +/- 31 and their mean OI was 30 +/- 11 immediately before death. Two patients with multiple organ dysfunction syndrome died after withdrawal of life support; their mean PaO2/FIO2 and OI were 178 +/- 31 and 18 +/- 2 respectively, at the time of this decision. Although HFOV had no impact on mortality, it played a useful role in the supportive management of burn patients with severe oxygenation failure unresponsive to conventional ventilation. Importantly, HFOV allowed surgery to proceed in patients who may have otherwise been too unstable to go to the operating room. As far as we are aware, this is the first report of the use of intraoperative HFOV in burn patients.

Adult↗
PubMed1992

Use of theophylline in neonates as an aid to ventilator weaning.

Respiratory diseases are major causes of morbidity and mortality in premature neonates. Theophylline has been utilized as an adjunct in facilitating ventilator weaning and in the management of apnea with or without bradycardia. Patient characteristics associated with improved outcome from theophylline have not been determined. The purpose of this study was to evaluate parameters associated with improved outcome in neonates with respiratory diseases receiving theophylline. The study population consisted of premature neonates that were studied retrospectively. Criteria for entry into the study were (1) less than 40 weeks gestation, (2) a diagnosis of respiratory distress syndrome (RDS), apnea of prematurity, hyaline membrane disease (HMD), or bronchopulmonary dysplasia (BPD), (3) dependence on intermittent mandatory ventilation, (4) failure to wean from the ventilator 24 h or more before the study, or (5) receiving theophylline. In this study, we found no correlations between time to wean from the ventilator and postnatal age at the time theophylline was initiated, 5-min APGAR score, and final theophylline serum concentration before complete weaning from the ventilator. However, there were significant negative correlations between birthweight and gestational age with respect to time to wean from the ventilator. The average theophylline serum concentration before weaning from the ventilator for this population of neonates was approximately 5-10 micrograms/ml, indicating that theophylline is not beneficial as an aid to ventilator weaning at serum concentrations < 10 micrograms/ml.

Apgar Score↗
PubMed2005

Noninvasive ventilation for acute respiratory failure.

PURPOSE OF REVIEW: This review critically examines recent literature related to applications of noninvasive ventilation in the acute setting. RECENT FINDINGS: Recent articles have strengthened the evidence supporting the use of noninvasive ventilation for patients with cardiogenic pulmonary edema and exacerbation of severe chronic pulmonary obstructive disease. In the former, however, it remains unclear whether noninvasive ventilation offers any significant advantages over continuous positive airway pressure. The rate of myocardial infarction seems to be no higher when patients with cardiogenic pulmonary edema are treated with noninvasive ventilation rather than continuous positive airway pressure, although caution is still advised in patients with acute coronary syndromes. Noninvasive ventilation also does not seem to increase the risk of dissemination of severe acute respiratory syndrome to health care workers as long as strict isolation procedures are used. Noninvasive ventilation facilitates weaning in patients with chronic obstructive pulmonary disease but should not be used routinely to treat extubation failure, and necessary intubation should not be delayed. Guidelines for the use of noninvasive ventilation can alter caregivers' behavior but have not been clearly shown to improve outcomes. Outcomes do seem to improve, however, as caregivers acquire experience with the technique. SUMMARY: The recent literature has refined some of the current indications for noninvasive ventilation in the acute-care setting, including chronic pulmonary obstructive disease and cardiogenic pulmonary edema. Guidelines for use are now being developed, and outcomes seem to be improving, partly as a consequence of greater caregiver experience and possibly related to technologic advances.

Acute Disease↗
PubMed2003

Heliox does not affect gas exchange during high-frequency oscillatory ventilation if tidal volume is held constant.

OBJECTIVE: To compare gas exchange with heliox and oxygen-enriched air during high-frequency oscillatory ventilation, while controlling for tidal volume, in a pediatric swine model of acute lung injury. We hypothesized that when tidal volume delivery is held constant, heliox does not alter gas exchange. DESIGN: Randomized, crossover trial. SETTING: University animal research laboratory. SUBJECTS: Ten swine (4.4-5.4 kg). INTERVENTIONS: Acute lung injury (A-a gradient of >300 mm Hg) was created using repeated saline lavage during conventional mechanical ventilation. The animals were then administered high-frequency oscillatory ventilation and ventilated with 60% oxygen/40% helium and 60% oxygen/40% nitrogen in a randomized, crossover trial. When changing gas mixtures within each animal, mean airway pressure (Paw = 16.8 +/- 0.3 cm H(2)O) and frequency (10 Hz) were held constant. Oscillation amplitude (DeltaP) was adjusted to maintain constant tidal volume delivery as measured by respiratory inductive plethysmography. Next, the animals were ventilated with 40% oxygen/60% helium and 40% oxygen/60% nitrogen in a randomized crossover trial, again controlling for tidal volume. MEASUREMENTS AND MAIN RESULTS: Gas exchange was assessed by arterial blood gas analysis after ventilation with each gas mixture. We demonstrated no significant difference in Paco(2) or Pao(2) between the heliox and oxygen-enriched air with either the 40% or 60% oxygen mixtures. The oscillation amplitude required to achieve the same tidal volume delivery was significantly less with heliox. CONCLUSIONS: We conclude that if tidal volume delivery is maintained constant, heliox does not alter gas exchange when compared with oxygen-enriched air. However, to achieve the same tidal volume delivery, a lower oscillation amplitude is required with heliox. The clinical benefit of heliox administration during high-frequency oscillatory ventilation has yet to be determined. Possible advantages of heliox include improved ventilation of larger patients when approaching the power limitations of the Sensormedics 3100A oscillator and a potential reduction in the oscillation amplitude delivered to the more proximal gas exchange units.

Animals↗
PubMed2004

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level.

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.

Analysis of Variance↗
PubMed2004

Clinical relevance of angiotensin-converting enzyme gene polymorphisms to predict risk of mechanical ventilation after coronary artery bypass graft surgery.

OBJECTIVE: Prolonged mechanical ventilation is a significant complication after coronary artery bypass graft surgery. Angiotensin-converting enzyme mediates ischemia-reperfusion injury, which is an important mechanism of postcoronary artery bypass graft complications. An insertion/deletion polymorphism within the angiotensin-converting enzyme gene is associated with variable concentrations of angiotensin-converting enzyme. Whether this polymorphism is associated with prolonged mechanical ventilation is not known. The primary objective was to determine whether the insertion/deletion angiotensin-converting enzyme gene polymorphism is associated with prolonged mechanical ventilation. The release of inflammatory mediators and risk of prolonged mechanical ventilation are higher after conventional coronary artery bypass graft compared with off-pump coronary artery bypass graft. Therefore, we examined the risk of prolonged mechanical ventilation for angiotensin-converting enzyme genotypes in patients undergoing conventional coronary artery bypass graft and off-pump coronary artery bypass graft separately. Tumor necrosis factor down-regulates angiotensin-converting enzyme concentrations, and functional polymorphisms within the tumor necrosis factor gene have been associated previously with prolonged mechanical ventilation. Therefore, we examined interactions between these polymorphisms. DESIGN: Prospective observational cohort study. SETTING: Tertiary care center. SUBJECTS: Patients who underwent coronary artery bypass graft (with or without valve replacement surgery). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured angiotensin-converting enzyme genotype and time to extubate. Patients with the DD and DI genotypes were at higher risk of prolonged mechanical ventilation compared with those with the II genotypes (hazard ratio = 2.2 and 1.6, respectively, p =.0005). Interactions were seen between the angiotensin-converting enzyme genotypes with surgical technique and with tumor necrosis factor-308/lymphotoxin + 250 GG haplotype for prolonged mechanical ventilation (p =.078 and.0003, respectively). The association was stronger for those undergoing conventional coronary artery bypass graft, whereas neither angiotensin-converting enzyme genotype conferred higher risk to those undergoing off-pump coronary artery bypass graft. CONCLUSIONS: Angiotensin-converting enzyme gene polymorphisms are associated with respiratory complications postcardiopulmonary bypass. The increased risk associated with genotype may be amenable to alternative surgical technique or pharmacologic manipulation.

Aged↗
PubMed2005

High-frequency percussive ventilation.

OBJECTIVE: To review the technique and clinical application of high-frequency percussive ventilation in critically ill patients. DESIGN: Literature search and descriptive review. RESULTS: High-frequency percussive ventilation is a time-cycled, pressure-limited mode of ventilation that delivers subphysiologic tidal volumes at rates that can exceed 500 breaths/min. It offers the potential advantage over conventional ventilation of providing equal or improved oxygenation and ventilation at lower peak and end-expiratory pressures. This modality has been used to manage severe lung disease in the neonatal and pediatric population, treat inhalation injury in pediatric and adult patients, and as salvage therapy in adult patients with acute respiratory distress syndrome. CONCLUSIONS: High-frequency percussive ventilation has been shown to provide favorable gas exchange in several well-defined patient populations. It reliably improves oxygenation and provides adequate ventilation at lower peak pressures than conventional ventilation. Adequately powered, randomized, prospective studies demonstrating significant mortality benefit have not yet been performed.

Adult↗
PubMed2006

A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients.

OBJECTIVE: To compare duration of mechanical ventilation for patients randomized to receive lorazepam by intermittent bolus administration vs. continuous infusions of propofol using protocols that include scheduled daily interruption of sedation. DESIGN: A randomized open-label trial enrolling patients from October 2001 to March 2004. SETTING: Medical intensive care units of two tertiary care medical centers. PATIENTS: Adult patients expected to require mechanical ventilation for >48 hrs and who required > or =10 mg of lorazepam or a continuous infusion of a sedative to achieve adequate sedation. INTERVENTIONS: Patients were randomized to receive lorazepam by intermittent bolus administration or propofol by continuous infusion to maintain a Ramsay score of 2-3. Sedation was interrupted on a daily basis for both groups. MEASUREMENTS AND MAIN RESULTS: The primary outcome was median ventilator days. Secondary outcomes included 28-day ventilator-free survival, intensive care unit and hospital length of stay, and hospital mortality. Median ventilator days were significantly lower in the daily interruption propofol group compared with the intermittent bolus lorazepam group (5.8 vs. 8.4, p = .04). The difference was largest for hospital survivors (4.4 vs. 9.0, p = .006). There was a trend toward greater ventilator-free survival for patients in the daily interruption propofol group (median 18.5 days for propofol vs. 10.2 for lorazepam, p = .06). Hospital mortality was not different. CONCLUSIONS: For medical patients requiring >48 hrs of mechanical ventilation, sedation with propofol results in significantly fewer ventilator days compared with intermittent lorazepam when sedatives are interrupted daily.

Drug Administration Schedule↗
PubMed2007

Perflubron dosing affects ventilator-induced lung injury in rats with previous lung injury.

OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing 300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha-naphtylthiourea to produce mild permeability pulmonary edema. They were then given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity) perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was used to assess lung microvascular permeability. Quasi-static respiratory system pressure-volume curves were analyzed. Administration of low and moderate perflubron doses significantly improved respiratory mechanics and reduced the ventilator-induced permeability alterations to the level observed in rats that were not ventilated. By contrast, a perflubron dose that was near functional residual capacity increased end-inspiratory plateau pressure and aggravated the permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near functional residual capacity but not low perflubron dose worsens ventilation-induced lung injury of preinjured lungs. This may provide some explanation for the negative results of the recent clinical trials, and it stresses the importance of the amount of perflubron used for partial liquid ventilation.

Animals↗
PubMed2007

Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse.

OBJECTIVE: To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia. DESIGN: Prospective observational study during a 36-month period. SETTING: Medical-surgical intensive care unit of a university hospital. PATIENTS: One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p=.04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria. CONCLUSIONS: A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.

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