Effect of Pressure Support Ventilation on Carboxyhemoglobin Toxicokinetic after Acute Carbon Monoxide Intoxication: a Swine Model.
ABSTRACT: In an experimental study on carbon monoxide (CO) exposure in swine, we aimed to compare the influence of oxygen therapy using a non-rebreathing mask (NRM) to continuous positive airway pressure (CPAP) and two pressure support ventilation (PSV) devices on the decrease of the terminal elimination half-life of carboxyhemoglobin (COHb t1/2). This was the primary outcome.Eight spontaneously breathing pigs were sedated by propofol and exposed to 940 ppm CO several times (n = 25) to obtain COHb levels of 30%. CPAPb (high flow open system, CPAP Boussignac® [7.5 cmH2O]), PSV-Vy (open system, Vylife Boussignac®), and PSV-Leg (closed system, Legendair® [inspiratory/expiratory airway pressure 12/4 cmH2O]) devices were used in a randomized order and compared to NRM (O2 at 15 l min-1) and atmospheric air (AA). The primary outcome was COHb t1/2. Multiple comparisons were performed using Dunn's tests.Median FiO2 and minute ventilation were significantly higher in the PSV-Leg group than the NRM group (p < 0.05). Median COHb t1/2 was 251, 85, 82, 93, and 58 min for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg, respectively. All the interventions were superior to AA in terms of CO elimination (p < 0.001), but there was no statistically significant difference between CPAP or PSV and NRM. There was only a trend between PSV-Leg and NRM (p = 0.18). The median AUCs for ln (COHb) × time (h) were 170, 79, 83, 100, and 64 for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg respectively, with a statistically significant difference only between AA and PSV-Leg (p = 0.002).In conclusion, in our study on CO intoxication in swine, the use of the closed PSV-Leg system led to the shortest COHb t1/2. These results suggest that PSV-Leg can be more efficient than NRM in eliminating CO and support the design of a clinical study to assess this hypothesis.
Project description:Introduction:Continuous positive airway pressure (CPAP) may induce nasal inflammation because of mucosal compression or dryness. This study examined the impact of humidified versus nonhumidified CPAP on nasal inflammation and upper airway symptoms. Methods:Seventeen healthy male subjects with no previous or current history of nasal symptoms were recruited. All subjects underwent 3 hours of nonhumidified CPAP at 12.5 cmH2O via nasal mask. Among the 17 studied subjects, seven returned to receive a humidified CPAP at 12.5 cmH2O via nasal mask. The nasal wash leukocyte count was assessed at baseline and after each CPAP setting. The white blood cell (WBC) count and levels of WBCs that are mononuclear cells (including lymphocytes and monocytes) were monitored. A six-point nasal score was also assessed before and after the CPAP intervention. Results:The nasal wash WBC count (103/µL) and mononuclear cell level (103/µL) at baseline, on 12.5 cmH2O humidified CPAP, and on 12.5 cmH2O nonhumidified CPAP were significantly different (p = 0.016; p = 0.003). Changes in nasopharyngeal symptoms occurred in 12 of 17 subjects (70.5%) in the nonhumidified group. Participants experienced at least one nasal symptom after application of nonhumidified CPAP at 12.5 cmH2O. Conclusion:The present investigation suggests that humidified CPAP was not associated with early nasal inflammation and there were fewer nasopharyngeal symptoms. Further study is required to confirm the results and evaluate the impact of adding heat to the humidified CPAP system.
Project description:Background:Continuous positive airway pressure (CPAP) is a major treatment strategy for severe chronic obstructive pulmonary disease (COPD), especially with respiratory failure. However, it remains inconclusive whether CPAP affects respiratory mechanics and neural drive in stable COPD patients without respiratory failure. Methods:Twenty-two COPD patients without respiratory failure received CPAP starting from 4 to 10 cmH2O in 1 cmH2O increments. Respiratory pattern, end expiatory lung volume (EELV), dynamic PEEPi (PEEPidyn), airway resistance (Raw), pressure-time product of diaphragmatic pressure (PTPdi) and esophageal pressure (PTPeso), root mean square (RMS) of diaphragm electromyogram (EMGdi) and ratio of ventilation (Ve) to EMGdi (i.e., Ve/RMS) were measured before and at each level of continue positive airway pressure (CPAP). A subgroup analysis was performed between patients with and without inspiratory muscle weakness. Results:Nineteen patients completed the treatment. The respiratory pattern improved significantly after CPAP. Raw, PTPdi, and Pdi decreased significantly. ?EELV decreased at 4 cmH2O (P<0.05), but increased significantly at >8 cmH2O. PEEPidyn decreased from 2.18±0.98 to 1.37±0.55 cmH2O. RMS increased while Ve/RMS improved significantly after CPAP (P<0.05). Besides, CPAP could significantly improve respiratory mechanics in patients with inspiratory muscle weakness. Conclusions:CPAP improves respiratory pattern, PEEPi, Raw, work of breathing and efficiency of neural drive in COPD patients without respiratory failure, but easily increases dynamic pulmonary hyperinflation. These effects on respiratory mechanics are significant in patients with inspiratory muscle weakness.
Project description:Neurally adjusted ventilatory assist (NAVA) could improve patient-ventilator interaction; its effects on ventilation distribution and dead space are still unknown. The aim of this study was to evaluate the effects of varying levels of assist during NAVA and pressure support ventilation (PSV) on ventilation distribution and dead space in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Fifteen mechanically ventilated patients with AECOPD were included in the study. The initial PSV levels were set to 10 cmH2O for 10 min. Thereafter, the ventilator mode was changed to NAVA for another 10 min with the same electrical activity of the diaphragm as during PSV. Furthermore, the ventilation mode was switched between PSV and NAVA every 10 min in the following order: PSV 5 cmH2O; NAVA 50%; PSV 15 cmH2O; and NAVA 150% (relative to the initial NAVA support level). Ventilation distribution in the lung was evaluated in percentages in regions of interest (ROI) of four anteroposterior segments of equal height (ROI1 to ROI4 represents ventral, mid-ventral, mid-dorsal, and dorsal, respectively). Blood gases, ventilation distribution (electrical impedance tomography), diaphragm activity (B-mode ultrasonography), and dead space fraction (PeCO2 and PaCO2) were measured.The trigger and cycle delays were lower during NAVA than during PSV. The work of trigger was significantly lower during NAVA compared to PSV. The diaphragm activities based on ultrasonography were higher during NAVA compared to the same support level during PSV. The ventilation distribution in ROI4 increased significantly (P?<?0.05) during NAVA compared to PSV (except for a support level of 50%). Similar results were found in ROI3?+?4. NAVA reduced dead space fraction compared to the corresponding support level of PSV.NAVA was superior to PSV in AECOPD for increasing ventilation distribution in ROI4 and reducing dead space.Clinicaltrials.gov, NCT02289573 . Registered on 12 November 2014.
Project description:Predicting whether an obese critically ill patient can be successfully extubated may be specially challenging. Several weaning tests have been described but no physiological study has evaluated the weaning test that would best reflect the post-extubation inspiratory effort.This was a physiological randomized crossover study in a medical and surgical single-center Intensive Care Unit, in patients with body mass index (BMI) >35 kg/m2 who were mechanically ventilated for more than 24 h and underwent a weaning test. After randomization, 17 patients were explored using five settings : pressure support ventilation (PSV) 7 and positive end-expiratory pressure (PEEP) 7 cmH2O; PSV 0 and PEEP 7cmH2O; PSV 7 and PEEP 0 cmH2O; PSV 0 and PEEP 0 cmH2O; and a T piece, and after extubation. To further minimize interaction between each setting, a period of baseline ventilation was performed between each step of the study. We hypothesized that the post-extubation work of breathing (WOB) would be similar to the T-tube WOB.Respiratory variables and esophageal and gastric pressure were recorded. Inspiratory muscle effort was calculated as the esophageal and trans-diaphragmatic pressure time products and WOB. Sixteen obese patients (BMI 44 kg/m2?±?8) were included and successfully extubated. Post-extubation inspiratory effort, calculated by WOB, was 1.56 J/L?±?0.50, not statistically different from the T piece (1.57 J/L?±?0.56) or PSV 0 and PEEP 0 cmH2O (1.58 J/L?±?0.57), whatever the index of inspiratory effort. The three tests that maintained pressure support statistically underestimated post-extubation inspiratory effort (WOB 0.69 J/L?±?0.31, 1.15 J/L?±?0.39 and 1.09 J/L?±?0.49, respectively, p?<?0.001). Respiratory mechanics and arterial blood gases did not differ between the five tests and the post-extubation condition.In obese patients, inspiratory effort measured during weaning tests with either a T-piece or a PSV 0 and PEEP 0 was not different to post-extubation inspiratory effort. In contrast, weaning tests with positive pressure overestimated post-extubation inspiratory effort.Clinical trial.gov (reference NCT01616901 ), 2012, June 4th.
Project description:Upper airway collapsibility is a key determinant of obstructive sleep apnea (OSA) which can influence the efficacy of certain non-continuous positive airway pressure (CPAP) treatments for OSA. However, there is no simple way to measure this variable clinically. The present study aimed to develop a clinically implementable tool to evaluate the collapsibility of a patient's upper airway.Collapsibility, as characterized by the passive pharyngeal critical closing pressure (Pcrit), was measured in 46 patients with OSA. Associations were investigated between Pcrit and data extracted from patient history and routine polysomnography, including CPAP titration.Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit (r2=0.51, p < .001) of all the variables investigated including apnea-hypopnea index, body mass index, sex, and age. Patients with a mildly collapsible upper airway (Pcrit ≤ -2 cmH2O) had a lower therapeutic CPAP level (6.2 ± 0.6 vs. 10.3 ± 0.4 cmH2O, p < .001) compared to patients with more severe collapsibility (Pcrit > -2 cmH2O). A therapeutic CPAP level ≤8.0 cmH2O was sensitive (89%) and specific (84%) for detecting a mildly collapsible upper airway. When applied to the independent validation data set (n = 74), this threshold maintained high specificity (91%) but reduced sensitivity (75%).Our data demonstrate that a patient's therapeutic CPAP requirement shares a strong predictive relationship with their Pcrit and may be used to accurately differentiate OSA patients with mild airway collapsibility from those with moderate-to-severe collapsibility. Although this relationship needs to be confirmed prospectively, our findings may provide clinicians with better understanding of an individual patient's OSA phenotype, which ultimately could assist in determining which patients are most likely to respond to non-CPAP therapies.
Project description:PURPOSE:Respiratory variations in pulse pressure (dPP) and photoplethysmographic waveform amplitude (dPOP) are used for evaluation of volume status in mechanically ventilated patients. Amplification of intrathoracic pressure changes may enable their use also during spontaneous breathing. We investigated the association between the degree of hypovolemia and dPP and dPOP at different levels of two commonly applied clinical interventions; positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP). METHODS:20 healthy volunteers were exposed to progressive hypovolemia by lower body negative pressure (LBNP). PEP of 0 (baseline), 5 and 10 cmH2O was applied by an expiratory resistor and CPAP of 0 (baseline), 5 and 10 cmH2O by a facemask. dPP was obtained non-invasively with the volume clamp method and dPOP from a pulse oximeter. Central venous pressure was measured in 10 subjects. Associations between changes were examined using linear mixed-effects regression models. RESULTS:dPP increased with progressive LBNP at all levels of PEP and CPAP. The LBNP-induced increase in dPP was amplified by PEP 10 cmH20. dPOP increased with progressive LBNP during PEP 5 and PEP 10, and during all levels of CPAP. There was no additional effect of the level of PEP or CPAP on dPOP. Progressive hypovolemia and increasing levels of PEP were reflected by increasing respiratory variations in CVP. CONCLUSION:dPP and dPOP reflected progressive hypovolemia in spontaneously breathing healthy volunteers during PEP and CPAP. An increase in PEP from baseline to 10 cmH2O augmented the increase in dPP, but not in dPOP.
Project description:BACKGROUND:Continuous positive airway pressure (CPAP) is a mode of non-invasive ventilation used to treat a variety of respiratory conditions in the emergency department and intensive care unit. In low-resource settings where ventilators are not available, the ability to improvise a CPAP system from locally available equipment would provide a previously unavailable means of respiratory support for patients in respiratory distress. This manuscript details the design of such a system and its performance in healthy volunteers. METHODS:An improvised CPAP system was assembled from standard emergency department equipment and tested in 10 healthy volunteers (6 male, 4 female; ages 29-33). The system utilizes a water seal and high-flow air to create airway pressure; it was set to provide a pressure of 5 cmH2O for the purposes of this pilot study. Subjects used the system in a monitored setting for 30 min. Airway pressure, heart rate, oxygen saturation, and end-tidal CO2 were monitored. Comfort with the device was assessed via questionnaire. RESULTS:The system maintained positive airway pressure for the full trial period in all subjects, with a mean expiratory pressure (EP) of 5.1 cmH2O (SD 0.7) and mean inspiratory pressure (IP) of 3.2 cmH2O (SD 0.8). There was a small decrease in average EP (5.28 vs 4.88 cmH2O, p = 0.03) and a trend toward decreasing IP (3.26 vs 3.07 cmH2O, p = 0.22) during the trial. No significant change in heart rate, O2 saturation, respiratory rate, or end-tidal CO2 was observed. The system was well tolerated, ranked an average of 4.0 on a 1-5 scale for comfort (with 5 = very comfortable). CONCLUSIONS:This improvised CPAP system maintained positive airway pressure for 30 min in healthy volunteers. Use did not cause tachycardia, hypoxia, or hypoventilation and was well tolerated. This system may be a useful adjunctive treatment for respiratory distress in low-resource settings. Further research should test this system in settings where other positive pressure modalities are not available.
Project description:BACKGROUND:Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient-ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (VT) at protective levels with NAVA and PSV in patients with ARDS. METHODS:We conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and VT. Asynchrony events detection was based on waveform analysis. RESULTS:We randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain VT below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, VT was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH2O) than in PSV (19 ± 3 cmH2O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0-2.7) in PSV and 0% (0-2.2) in NAVA (p = 0.6835). CONCLUSIONS:It was feasible to keep VT in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar VT, RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation. Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258.
Project description:Acute high level carbon monoxide (CO) exposure can cause immediate cardio-respiratory arrest in anyone, but the effects of lower level exposures in susceptible persons are less well known. The percentage of CO-bound hemoglobin in blood (carboxyhemoglobin; COHb) is a marker of exposure and potential health outcomes. Indoor air quality guidelines developed by the World Health Organization and Health Canada, among others, are set so that CO exposure does not lead to COHb levels above 2.0%, a target based on experimental evidence on toxicodynamic relationships between COHb and cardiac performance among persons with cardiovascular disease (CVD). The guidelines do not consider the role of pathophysiological influences on toxicokinetic relationships. Physiological deficits that contribute to increased CO uptake, decreased CO elimination, and increased COHb formation can alter relationships between CO exposures and resulting COHb levels, and consequently, the severity of outcomes. Following three fatalities attributed to CO in a long-term care facility (LTCF), we queried whether pathologies other than CVD could alter CO-COHb relationships. Our primary objective was to inform susceptibility-specific modeling that accounts for physiological deficits that may alter CO-COHb relationships, ultimately to better inform CO management in LTCFs.We reviewed experimental studies investigating relationships between CO, COHb, and outcomes related to health or physiological outcomes among healthy persons, persons with CVD, and six additional physiologically susceptible groups considered relevant to LTCF residents: persons with chronic obstructive pulmonary disease (COPD), anemia, cerebrovascular disease (CBD), heart failure, multiple co-morbidities, and persons of older age (? 60 years).We identified 54 studies published since 1946. Six studies investigated toxicokinetics among healthy persons, and the remaining investigated toxicodynamics, mainly among healthy persons and persons with CVD. We identified one study each of CO dynamics in persons with COPD, anemia and persons of older age, and no studies of persons with CBD, heart failure, or multiple co-morbidities. Considerable heterogeneity existed for exposure scenarios and outcomes investigated.Limited experimental human evidence on the effects of physiological deficits relevant to CO kinetics exists to support indoor air CO guidelines. Both experimentation and modeling are needed to assess how physiological deficits influence the CO-COHb relationship, particularly at sub-acute exposures relevant to indoor environments. Such evidence would better inform indoor air quality guidelines and CO management in indoor settings where susceptible groups are housed.
Project description:Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs.We conducted a crossover trial in the ICU of a university hospital in Brazil and included mechanically ventilated patients considered ready to undergo an SBT on the day of the study. Patients underwent two SBTs in randomized order: 30 min in PSV of 5 cmH2O or NAVA titrated to generate equivalent peak airway pressure (Paw), with a positive end-expiratory pressure of 5 cmH2O. The ICU team, blinded to ventilatory mode, evaluated whether patients passed each SBT. We captured flow, Paw and electrical activity of the diaphragm (EAdi) from the ventilator and used it to calculate respiratory rate (RR), tidal volume (VT), and EAdi. Detection of asynchrony events used waveform analysis and we calculated the asynchrony index as the number of asynchrony events divided by the number of neural cycles.We included 20 patients in the study. All patients passed the SBT in PSV, and three failed the SBT in NAVA. Five patients were reintubated and the extubation failure rate was 25% (95% CI 9-49%). Respiratory parameters were similar in the two modes: VT = 6.1 (5.5-6.5) mL/Kg in NAVA vs. 5.5 (4.8-6.1) mL/Kg in PSV (p = 0.076) and RR = 27 (17-30) rpm in NAVA vs. 26 (20-30) rpm in PSV, p = 0.55. NAVA reduced AI, with a median of 11.5% (4.2-19.7) compared to 24.3% (6.3-34.3) in PSV (p = 0.033).NAVA reduces patient-ventilator asynchrony index and generates a respiratory pattern similar to PSV during SBTs. Patients considered ready for mechanical ventilation liberation may be submitted to an SBT in NAVA using the same objective criteria used for SBTs in PSV.ClinicalTrials.gov ( NCT01337271 ), registered April 12, 2011.