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1.  The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study 
Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients. Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.
In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg) for 6 months. We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes.
In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg). PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS). Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients. Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion. There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO2. Improved ventilation–perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases.
We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation–perfusion match and hence better blood gases and lung function. Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation. These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do. Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment. To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population.
PMCID: PMC3224655  PMID: 22135493
noninvasive ventilation; COPD; imaging
2.  Determinants of Noninvasive Ventilation Success or Failure in Morbidly Obese Patients in Acute Respiratory Failure 
PLoS ONE  2014;9(5):e97563.
Acute respiratory failure (ARF) is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS). We aimed to identify the determinants of noninvasive ventilation (NIV) success or failure for this indication.
We prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital.
NIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p<0.0001), high SOFA (10 vs 5; p<0.0001) and SAPS2 score (63 vs 39; p<0.0001) at admission. These patients often experienced poor outcome despite early resort to endotracheal intubation (in-hospital mortality, 92.3% vs 17.5%; p<0.001). The only factor significantly associated with successful response to NIV was idiopathic decompensation of OHS (n = 30, 48% vs n = 0, 0%; p = 0.001). In the NIV success group (n = 63), 33 patients (53%) experienced a delayed response to NIV (with persistent hypercapnic acidosis during the first 6 hours).
Multiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.
PMCID: PMC4018299  PMID: 24819141
3.  Non invasive ventilation after extubation in paediatric patients: a preliminary study 
BMC Pediatrics  2010;10:29.
Non-invasive ventilation (NIV) may be useful after extubation in children. Our objective was to determine postextubation NIV characteristics and to identify risk factors of postextubation NIV failure.
A prospective observational study was conducted in an 8-bed pediatric intensive care unit (PICU). Following PICU protocol, NIV was applied to patients who had been mechanically ventilated for over 12 hours considered at high-risk of extubation failure -elective NIV (eNIV), immediately after extubation- or those who developed respiratory failure within 48 hours after extubation -rescue NIV (rNIV)-. Patients were categorized in subgroups according to their main underlying conditions. NIV was deemed successful when reintubation was avoided. Logistic regression analysis was performed in order to identify predictors of NIV failure.
There were 41 episodes (rNIV in 20 episodes). Success rate was 50% in rNIV and 81% in eNIV (p = 0.037). We found significant differences in univariate analysis between success and failure groups in respiratory rate (RR) decrease at 6 hours, FiO2 at 1 hour and PO2/FiO2 ratio at 6 hours. Neurologic condition was found to be associated with NIV failure. Multiple logistic regression analysis identified no variable as independent NIV outcome predictor.
Our data suggest that postextubation NIV seems to be useful in avoiding reintubation in high-risk children when applied immediately after extubation. NIV was more likely to fail when ARF has already developed (rNIV), when RR at 6 hours did not decrease and if oxygen requirements increased. Neurologic patients seem to be at higher risk of reintubation despite NIV use.
PMCID: PMC2876146  PMID: 20444256
4.  Role of sedation for agitated patients undergoing noninvasive ventilation: clinical practice in a tertiary referral hospital 
Although sedation is often required for agitated patients undergoing noninvasive ventilation (NIV), reports on its practical use have been few. This study aimed to evaluate the efficacy and safety of sedation for agitated patients undergoing NIV in clinical practice in a single hospital.
We retrospectively reviewed sedated patients who received NIV due to acute respiratory failure from May 2007 to May 2012. Sedation level was controlled according to the Richmond Agitation Sedation Scale (RASS). Clinical background, sedatives, failure rate of sedation, and complications were evaluated by 1) sedative methods (intermittent only, switched to continuous, or initially continuous) and 2) code status (do-not-intubate [DNI] or non-DNI).
Of 3506 patients who received NIV, 120 (3.4 %) consecutive patients were analyzed. Sedation was performed only intermittently in 72 (60 %) patients, was switched to continuously in 37 (31 %) and was applied only continuously in 11 (9 %). Underlying diseases in 48 % were acute respiratory distress syndrome/acute lung injury/severe pneumonia or acute exacerbation of interstitial pneumonia. In non-DNI patients (n = 39), no patient required intubation due to agitation with continuous sedation, and in DNI patients (n = 81), 96 % of patients could continue NIV treatment. PaCO2 level changes (6.7 ± 15.1 mmHg vs. -2.0 ± 7.7 mmHg, P = 0.028) and mortality in DNI patients (81 % vs. 57 %, P = 0.020) were significantly greater in the continuous use group than in the intermittent use group.
According to RASS scores, sedation during NIV in proficient hospitals may be favorably used to potentially avoid NIV failure in agitated patients, even in those having diseases with poor evidence of the usefulness of NIV. However, with continuous use, we must be aware of an increased hypercapnic state and the possibility of increased mortality. Larger controlled studies are needed to better clarify the role of sedation in improving NIV outcomes in intolerant patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-015-0072-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4499444  PMID: 26164393
Continuous sedation; Intermittent sedation; Noninvasive ventilation; Agitation; Richmond Agitation Sedation Scale
5.  End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate to monitor capnia during non-invasive ventilation 
In acute respiratory failure, arterial blood gas analysis (ABG) is used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated, ABG should at least be repeated within 1 h to assess PaCO2 response to treatment in order to help detect NIV failure. The main aim of this study was to assess whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The additional aim was to assess whether active or passive prolonged expiratory maneuvers could improve the agreement between expiratory CO2 and PaCO2.
This is a prospective study in adult patients suffering from acute hypercapnic respiratory failure (PaCO2 ≥ 45 mmHg) treated with NIV. EtCO2 and expiratory CO2 values during active and passive expiratory maneuvers were measured using a dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The agreement between two consecutive values of EtCO2 (delta EtCO2) and two consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant expiratory CO2 values was assessed using the Bland and Altman method adjusted for the effects of repeated measurements.
Fifty-four datasets from a population of 11 patients (8 COPD and 3 non-COPD patients), were included in the analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg. In the observed agreement between delta EtCO2 and deltaPaCO2, bias was −0.3 mmHg, and limits of agreement were −17.8 and 17.2 mmHg. In agreement between PaCO2 and EtCO2, bias was 14.7 mmHg, and limits of agreement were −6.6 and 36.1 mmHg. Adding active and passive expiration maneuvers did not improve PaCO2 prediction.
During NIV delivered for acute hypercapnic respiratory failure, measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict both PaCO2 and PaCO2 variations over time. Active and passive expiration maneuvers did not improve PaCO2 prediction.
Trial registration NCT01489150.
PMCID: PMC4385013  PMID: 25852962
Respiratory monitoring; Non-invasive ventilation; End-tidal CO2; Hypercapnic respiratory failure
6.  Noninvasive ventilation: Are we overdoing it? 
Use of noninvasive ventilation (NIV) outside guideline recommendations is common. We audited use of NIV in our tertiary care critical care unit (CCU) to evaluate appropriateness of use and patient outcomes when used outside level I recommendations.
Materials and Methods:
Prospective observational study of all patients requiring NIV. Clinical parameters and arterial blood gases were recorded at initiation of NIV and 2 h later (or earlier if clinically warranted). NIV titration and decision to intubate were left to the discretion of treating intensivist. Patients were categorized into two groups: Group 1: Those with level I indications for use of NIV and group 2: All other levels of indications. Patients were followed until hospital discharge.
From January 2010 to June 2010, 1120 patients were admitted to the CCU. Of these 106 patients required NIV support with 40.6% (n = 43/106) being in group 1 and 59.4% (n = 63/106) in group 2. Of these 35.8% patients (38/106) failed NIV and required endotracheal intubation. NIV failure rates (41.27% vs. 27.91%; P = 0.02) and mortality (30.6% vs. 18.6%; P = 0.03) were significantly higher in group 2 patients. In a logistic regression analysis Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.02), time on NIV before intubation (P = 0.001) and baseline PaCO2 levels (P = 0.01) were strongly associated with mortality.
Noninvasive ventilation failure and mortality rates were significantly higher when used outside level I recommendations. APACHE II score, baseline PaCO2 and duration on NIV prior to intubation were predictors of increased mortality.
PMCID: PMC4134623  PMID: 25136188
Acute respiratory failure; invasive ventilation; Indian Society of Critical Care Medicine recommendations; noninvasive ventilation; NIV failure
7.  Shrinking the room for invasive ventilation in hypercapnic respiratory failure 
Noninvasive ventilation (NIV) was introduced as an alternative to invasive mechanical ventilation for acute respiratory failure caused from exacerbations of chronic obstructive pulmonary disease in the 1980s, and its use gradually rose worldwide. Seventy-eight patients (57 males, mean age 78.3 ± 9.2 years) undergoing NIV were evaluated. Of them, 48 (62.3%) had acute hypercapnic respiratory failure because of a chronic obstructive pulmonary disease exacerbation, and the remaining 30 had acute hypercapnic respiratory failure from other causes, mainly cardiac failure. All patients were treated by NIV using the bi-level positive airway pressure set up at high pressure/high backup rate. NIV was successful in 67 subjects (85.9%) and the patients were discharged, 57 of whom continued NIV at home and ten had spontaneous breathing. NIV was unsuccessful in eleven patients, ten of whom died and one was successfully treated by invasive mechanical ventilation. Significant differences were detected for a higher basal Glasgow Coma Scale score in successfully treated patients (P = 0.007), a higher basal Acute Physiology and Chronic Health Evaluation score in unsuccessfully treated patients (P = 0.004), and a lower pH after 1 hour in unsuccessfully treated patients (P = 0.015). These findings show a very high rate of success of NIV in patients with acute hypercapnic respiratory failure not only from chronic obstructive pulmonary disease but also from cardiac failure. This suggests that the use of invasive mechanical ventilation may be further reduced, with a decrease in its known complications as well.
PMCID: PMC3600934  PMID: 23516004
invasive ventilation; noninvasive ventilation; acute respiratory failure
8.  Non-invasive ventilation in acute respiratory failure in children 
Pediatric Reports  2012;4(2):e16.
The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO2 at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO2/FiO2 improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42–71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33–111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection.
PMCID: PMC3395974  PMID: 22802994
non-invasive ventilation; acute respiratory failure; child; infant; predictive factors; pediatric intensive care unit.
9.  Mechanisms of improvement of respiratory failure in patients with COPD treated with NIV 
Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure. We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics.
Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5–8 days (D5) and 3 months (3M) after starting NIV.
Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12). Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001). Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035). At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods.
These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV. Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort.
PMCID: PMC2629992  PMID: 18990974
COPD; hypercapnic respiratory failure; NIV; pulmonary mechanics; ventilatory drive
10.  Long-Term Home Noninvasive Mechanical Ventilation Increases Systemic Inflammatory Response in Chronic Obstructive Pulmonary Disease: A Prospective Observational Study 
Mediators of Inflammation  2014;2014:503145.
Background. Long-term home noninvasive mechanical ventilation (NIV) is beneficial in COPD but its impact on inflammation is unknown. We assessed the hypothesis that NIV modulates systemic and pulmonary inflammatory biomarkers in stable COPD. Methods. Among 610 patients referred for NIV, we shortlisted those undergoing NIV versus oxygen therapy alone, excluding subjects with comorbidities or non-COPD conditions. Sputum and blood samples were collected after 3 months of clinical stability and analyzed for levels of human neutrophil peptides (HNP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha). Patients underwent a two-year follow-up. Unadjusted, propensity-matched, and pH-stratified analyses were performed. Results. Ninety-three patients were included (48 NIV, 45 oxygen), with analogous baseline features. Sputum analysis showed similar HNP, IL-6, IL-10, and TNF-alpha levels (P > 0.5). Conversely, NIV group exhibited higher HNP and IL-6 systemic levels (P < 0.001) and lower IL-10 concentrations (P < 0.001). Subjects undergoing NIV had a significant reduction of rehospitalizations during follow-up compared to oxygen group (P = 0.005). These findings were confirmed after propensity matching and pH stratification. Conclusions. These findings challenge prior paradigms based on the assumption that pulmonary inflammation is per se detrimental. NIV beneficial impact on lung mechanics may overcome the potential unfavorable effects of an increased inflammatory state.
PMCID: PMC4058212  PMID: 24976687
11.  Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study 
Critical Care  2013;17(2):R63.
Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU).
In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure.
Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30).
Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting.
Trial registration NCT01268410.
PMCID: PMC3672504  PMID: 23557378
12.  Non-invasive ventilation as a first-line treatment for acute respiratory failure: "real life" experience in the emergency department 
Emergency Medicine Journal : EMJ  2005;22(11):772-777.
Objective: To describe our experience with non-invasive ventilation (NIV) for patients with acute respiratory failure (ARF) in the emergency department (ED).
Methods: A prospective/retrospective, observational study on 190 patients with ARF (mean ±SD age 72.2±12.9 years, mean APACHE II score 18.9±5.9), who received 200 NIV trials in an ED. We analysed the NIV register data (prospectively collected) and medical records (retrospective data abstraction) and evaluated clinical indications for NIV, patient outcomes, and predictive factors for success and death. NIV success was defined as tolerance of the procedure and no need for endotracheal intubation (ETI).
Results: Main indications to NIV were cardiogenic pulmonary oedema (CPE) (70 trials), acute exacerbation of COPD (39), both CPE and acute exacerbation of COPD (11), pneumonia (48), decompensation of obesity/hypoventilation (6), other conditions (26). The procedure was successful in 60.5% of trials. Global mortality was 34.5%, similar to the APACHE II predicted mortality of 32%. ETI rates were 6.5% and tracheostomy rates 1%. The improvement of pH within six hours after NIV initiation was predictive of survival in the hypercapnic group.
Conclusions: Our results confirm the global efficacy of NIV in an ED setting, and show that, in spite of lower success rate in "real practice" in comparison with RCTs, an intermediate care unit can represent an appropriate and less expensive setting to perform this technique. The low rate of ETI seems to be because of the high number of patients for whom NIV was used as "ceiling" treatment.
PMCID: PMC1726611  PMID: 16244332
13.  Role of noninvasive ventilation in weaning from mechanical ventilation in patients of chronic obstructive pulmonary disease: An Indian experience 
Endotracheal intubation and mechanical ventilation (MV) are often needed in patients of chronic obstructive pulmonary disease (COPD) with acute hypercapnic respiratory failure. The rate of weaning failure is high and prolonged MV increases intubation associated complications.
To evaluate the role of Noninvasive ventilation (NIV) in weaning patients of chronic obstructive pulmonary disease (COPD) from MV, after T piece trial failure.
A prospective, randomized, controlled study was conducted in a tertiary care centre. 30 patients of acute exacerbation of COPD with acute on chronic hypercapnic respiratory failure, who were mechanically ventilated, were included in the study A T-piece weaning trial was attempted once the patients achieved satisfactory clinical and biochemical parameters. After T-piece failure, defined as pH < 7.35, PaCO2 >50 mmHg, PaO2 <50 mmHg, HR >100/min, RR >35, patients were randomized to receive either NIV or PSV.
Demography, severity of disease and clinical profiles were similar in both groups. No significant difference between the two groups in duration of MV (6.20 ± 5.20 days vs. 7.47 ± 6.38 days, P > 0.05), duration of weaning (35.17 ± 16.98 and 47.05 ± 20.98 hours, P > 0.05) or duration of ICU stay (8.47 ± 4.79 and 10.80 ± 5.28 days, P > 0.05) in Gp I and Gp II, respectively. Five patients developed VAP in the PSV group, where as only one patient had pneumonia in the NIV group. Lesser number of deaths in the NIV group at discharge from ICU (3 vs. 5 patients, respectively) and at 30 days (5 vs. 9 patients, respectively), it did not achieve statistical significance (P > 0.05).
NIV is as useful as PSV in weaning and can be better in weaning failure especially in COPD for earlier weaning, decrease ICU stay, complications and mortality.
PMCID: PMC2856148  PMID: 20436689
Chronic obstructive pulmonary disease; mechanical ventilation; noninvasive ventilation; respiratory failure; weaning
14.  Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies 
Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes. However, very little attention has been paid to the timing of the failure. This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.
The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony. The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation. The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure. However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate. Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.
Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV. Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation.
PMCID: PMC3925956  PMID: 24520952
Noninvasive ventilation; Treatment failure; Respiratory insufficiency
15.  Polysomnography in stable COPD under non-invasive ventilation to reduce patient–ventilator asynchrony and morning breathlessness 
Sleep & Breathing = Schlaf & Atmung  2011;16(4):1081-1090.
Stable severe chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure treated by nocturnal bi-level positive pressure non-invasive ventilation (NIV) may experience severe morning deventilation dyspnea. We hypothesised that in these patients, progressive hyperinflation, resulting from inappropriate ventilator settings, leads to patient–ventilator asynchrony (PVA) with a high rate of unrewarded inspiratory efforts and morning discomfort.
Polysomnography (PSG), diaphragm electromyogram and transcutaneous capnography (PtcCO2) under NIV during two consecutive nights using baseline ventilator settings on the first night, then, during the second night, adjustment of ventilator parameters under PSG with assessment of impact of settings changes on sleep, patient–ventilator synchronisation, morning arterial blood gases and morning dyspnea.
Eight patients (61 ± 8 years, FEV1 30 ± 8% predicted, residual volume 210 ± 30% predicted) were included. In all patients, pressure support was decreased during setting adjustments, as well as tidal volume, while respiratory rate increased without any deleterious effect on nocturnal PtcCO2 or morning PaCO2. PVA index, initially high (40 ± 30%) during the baseline night, decreased significantly after adjusting ventilator settings (p = 0.0009), as well as subjective perception of PVA leaks, and morning dyspnea while quality of sleep improved.
The subgroup of COPD patients treated by home NIV, who present marked deventilation dyspnea and unrewarded efforts may benefit from adjustment of ventilator settings under PSG or polygraphy.
PMCID: PMC3497941  PMID: 22051930
Non-invasive ventilation; COPD; Patient–ventilator asynchrony
16.  Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation 
PLoS ONE  2012;7(4):e35245.
Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.
Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.
Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.
Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.
PMCID: PMC3335154  PMID: 22539963
17.  Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia 
Thorax  2005;60(12):1019-1024.
Background: Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV.
Methods: Forty eight patients with congenital neuromuscular or chest wall disease aged 7–51 years and vital capacity <50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria.
Results: Peak nocturnal transcutaneous carbon dioxide tension (TcCO2) did not differ between the groups, but the mean (SD) percentage of the night during which TcCO2 was >6.5 kPa decreased in the NIV group (–57.7 (26.1)%) but not in controls (–11.75 (46.1)%; p = 0.049, 95% CI –91.5 to –0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (–1.12 (2.02)%; p = 0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months.
Conclusion: Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.
PMCID: PMC1747266  PMID: 16299118
18.  Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial 
Critical Care  2013;17(2):R39.
Noninvasive ventilation (NIV), as a weaning-facilitating strategy in predominantly chronic obstructive pulmonary disease (COPD) mechanically ventilated patients, is associated with reduced ventilator-associated pneumonia, total duration of mechanical ventilation, length of intensive care unit (ICU) and hospital stay, and mortality. However, this benefit after planned extubation in patients with acute respiratory failure of various etiologies remains to be elucidated. The aim of this study was to determine the efficacy of NIV applied immediately after planned extubation in contrast to oxygen mask (OM) in patients with acute respiratory failure (ARF).
A randomized, prospective, controlled, unblinded clinical study in a single center of a 24-bed adult general ICU in a university hospital was carried out in a 12-month period. Included patients met extubation criteria with at least 72 hours of mechanical ventilation due to acute respiratory failure, after following the ICU weaning protocol. Patients were randomized immediately before elective extubation, being randomly allocated to one of the study groups: NIV or OM. We compared both groups regarding gas exchange 15 minutes, 2 hours, and 24 hours after extubation, reintubation rate after 48 hours, duration of mechanical ventilation, ICU length of stay, and hospital mortality.
Forty patients were randomized to receive NIV (20 patients) or OM (20 patients) after the following extubation criteria were met: pressure support (PSV) of 7 cm H2O, positive end-expiratory pressure (PEEP) of 5 cm H2O, oxygen inspiratory fraction (FiO2) ≤ 40%, arterial oxygen saturation (SaO2) ≥ 90%, and ratio of respiratory rate and tidal volume in liters (f/TV) < 105. Comparing the 20 patients (NIV) with the 18 patients (OM) that finished the study 48 hours after extubation, the rate of reintubation in NIV group was 5% and 39% in OM group (P = 0.016). Relative risk for reintubation was 0.13 (CI = 0.017 to 0.946). Absolute risk reduction for reintubation showed a decrease of 33.9%, and analysis of the number needed to treat was three. No difference was found in the length of ICU stay (P = 0.681). Hospital mortality was zero in NIV group and 22.2% in OM group (P = 0.041).
In this study population, NIV prevented 48 hours reintubation if applied immediately after elective extubation in patients with more than 3 days of ARF when compared with the OM group.
Trial Registration number
ISRCTN: 41524441.
PMCID: PMC3672522  PMID: 23497557
19.  Nutritional Risk Screening 2002 as a Predictor of Outcome During General Ward-Based Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease with Respiratory Failure 
Noninvasive ventilation (NIV) may reduce the need for intubation and mortality associated with chronic obstructive pulmonary disease (COPD) with type II respiratory failure. Early and simple predictors of NIV outcome could improve clinical management. This study aimed to assess whether nutritional risk screening 2002 (NRS2002) is a useful outcome predictor in COPD patients with type II respiratory failure treated by noninvasive positive pressure ventilation (NIPPV).
This prospective observational study enrolled COPD patients with type II respiratory failure who accepted NIPPV. Patients were submitted to NRS2002 evaluation upon admission. Biochemical tests were performed the next day and blood gas analysis was carried out prior to NIPPV treatment and 4 hours thereafter. Patients were divided into NRS2002 score ≥3 and NRS2002 score <3 groups and NIV failure rates were compared between both groups.
Of the 233 patients, 71 (30.5%) were not successfully treated by NIPPV. The failure rate was significantly higher in the NRS2002 score ≥3 group (35.23%) in comparison with patients with NRS2002 score <3 (15.79%) (p<0.05). Multivariate analysis indicated that PaCO2 (OR 1.25, 95%CI 1.172–1.671, p<0.05) prior to NIPPV treatment and NRS2002 score ≥3 (OR 1.76, 95%CI 1.303–2.374, p<0.05) were independent predictive factors for NIPPV treatment failure.
NRS2002 score ≥3 and PaCO2 values at admission may predict unsuccessful NIPPV treatment of COPD patients with type II respiratory failure and help to adjust therapeutic strategies. NRS2002 is a noninvasive and simple method for predicting NIPPV treatment outcome.
PMCID: PMC4581684  PMID: 26386778
Biological Markers; Lung Diseases, Obstructive; Noninvasive Ventilation; Nutritional Status; Respiratory Insufficiency
20.  Aggressive treatment with noninvasive ventilation for mild acute hypoxemic respiratory failure after cardiovascular surgery: Retrospective observational study 
Acute hypoxemic respiratory failure (AHRF) is one of the most serious complications after cardiovascular surgery. It remains unclear whether noninvasive ventilation (NIV) has potential as an effective therapy for AHRF after cardiovascular surgery, although many reports have described the use of NIV for AHRF after extubation. The aim of this study was to investigate the effectiveness of NIV in the early stage of mild AHRF after cardiovascular surgery.
We retrospectively analyzed all patients admitted to the intensive care unit after cardiovascular surgery, whose oxygenation transfer (PaO2/FIO2) deteriorated mildly after extubation, and in whom NIV was initiated. A two-way analysis of variance and the Bonferroni multiple comparisons procedure, the Mann–Whitney test, Fisher’s exact test or the χ2test was performed.
A total of 94 patients with AHRF received NIV, of whom 89 patients (94%) successfully avoided endotracheal intubation (successful group) and five patients required reintubation (reintubation group). All patients, including the reintubated patients, were successfully weaned from mechanical ventilation and discharged from the intensive care unit. In the successful group, PaO2/FIO2 improved and the respiratory rate decreased significantly within 1 h after the start of NIV, and the improvement in PaO2/FIO2 remained during the whole NIV period.
We conclude that NIV is beneficial for mild AHRF after cardiovascular surgery when it is started within 3 h after mild deterioration of PaO2/FIO2. We also think that it is important not to hesitate before performing reintubation when NIV is judged to be ineffective.
PMCID: PMC3434065  PMID: 22554005
Acute hypoxemic respiratory failure; Cardiovascular surgery; Post-extubation; Noninvasive ventilation; PaO2/FIO2
21.  Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome 
Thorax  2001;56(9):708-712.
BACKGROUND—Non-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation. The second aim was to determine the long term survival of patients treated with and without NIV.
METHODS—In this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998. Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic factors were identified using logistic regression analysis. All patients were followed until death or 1 January 1999.
RESULTS—At enrolment the H+ concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and PaCO2 (OR 1.14 per kPa, 95% CI 1.14to 1.81, p<0.01) were associated with treatment failure. Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80). After 4hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to 0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84 to 0.99, p=0.04) were associated with success. Median length of survival was 16.8 months in those treated with NIV and 13.4 months in those receiving standard treatment (p=0.12). The trend in improved survival was attributable to prevention of death during the index admission.
CONCLUSION—Initial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation. NIV reduces this risk and progress should be monitored using change in respiratory rate and pH. The long term survival after NIV is sufficiently good to render treatment appropriate.

PMCID: PMC1746126  PMID: 11514692
22.  Epidemiology of noninvasive mechanical ventilation in acute respiratory failure - a retrospective population-based study 
Noninvasive mechanical ventilation (NIV) is a front-line therapy for the management of acute respiratory failure (ARF) in the intensive care units. However, the data on factors and outcomes associated with the use of NIV in ARF patients is lacking. Therefore, we aimed to determine the utilization of NIV for ARF in a population-based study.
We conducted a populated-based retrospective cohort study, where in all consecutively admitted adults (≥18 years) with ARF from Olmsted County, Rochester, MN, at the Mayo Clinic medical and surgical ICUs, during 2006 were included. Patients without research authorization or on chronic NIV use for sleep apnea were excluded.
Out of 1461 Olmsted County adult residents admitted to the ICUs in 2006, 364 patients developed ARF, of which 146 patients were initiated on NIV. The median age in years was 75 (interquartile range, 60–84), 48% females and 88.7% Caucasians. Eighteen patients (12%) were on Continuous Positive Airway Pressure (CPAP) mode and 128 (88%) were on noninvasive intermittent positive-pressure ventilation (NIPPV) mode. Forty-six (10%) ARF patients were put on NIV for palliative strategy to alleviate dyspnea. Seventy-six ARF patients without treatment limitation were given a trial of NIV and 49 patients succeeded, while 27 had to be intubated. Mortality was similar between the patients initially supported with NIV versus invasive mechanical ventilation (33% vs 22%, P=0.289). In the multivariate analysis, the development of acute respiratory distress syndrome (ARDS) and higher APACHE III scores were associated with the failure of initial NIV treatment.
Our results have important implications for a future planning of NIV in a suburban US community with high access to critical care services. The higher APACHE III scores and the development of ARDS are associated with the failure of initial NIV treatment.
PMCID: PMC3637539  PMID: 23570601
Noninvasive mechanical ventilation; Acute respiratory failure; Epidemiology; Olmsted county; Health care delivery
23.  Predictive Factors for Reintubation following Noninvasive Ventilation in Patients with Respiratory Complications after Living Donor Liver Transplantation 
PLoS ONE  2013;8(12):e81417.
Postoperative respiratory complications are a major cause of mortality following liver transplantation (LT). Noninvasive ventilation (NIV) appears to be effective for respiratory complications in patients undergoing solid organ transplantation; however, mortality has been high in patients who experienced reintubation in spite of NIV therapy. The predictors of reintubation following NIV therapy after LT are not exactly known.
Of 511 adult patients who received living-donor LT, data on the 179 who were treated by NIV were retrospectively examined.
Forty-three (24%) of the 179 patients who received NIV treatment required reintubation. Independent factors associated with reintubation by multivariate logistic regression analysis were controlled preoperative infections (odds ratio [OR] 8.88; 95% confidence interval (CI) 1.64 to 48.11; p = 0.01), ABO-incompatibility (OR 4.49; 95% CI, 1.50 to 13.38; p = 0.007), and presence of postoperative pneumonia at the time of starting NIV (OR 3.28; 95% CI, 1.02 to 11.01; p = 0.04). The reintubated patients had a significant higher rate of postoperative infectious complications and a significantly longer intensive care unit stay than those in whom NIV was successful (p<0.0001). Of the 43 reintubated patients, 22 (51.2%) died during hospitalization following LT vs. 8 (5.9%) of the 136 patients in whom NIV was successful (p<0.0001).
Because controlled preoperative infection, ABO-incompatibility or pneumonia prior to the start of NIV were independent risk factors for reintubation following NIV, caution should be used in applying NIV in patients with these conditions considering the high rate of mortality in patients requiring reintubation following NIV.
PMCID: PMC3855274  PMID: 24339926
24.  Twenty-four hour noninvasive ventilation in Duchenne muscular dystrophy: A safe alternative to tracheostomy 
Almost all patients with Duchenne muscular dystrophy (DMD) eventually develop respiratory failure. Once 24 h ventilation is required, either due to incomplete effectiveness of nocturnal noninvasive ventilation (NIV) or bulbar weakness, it is common practice to recommend invasive tracheostomy ventilation; however, noninvasive daytime mouthpiece ventilation (MPV) as an addition to nocturnal mask ventilation is also an alternative.
The authors’ experience with 12 DMD patients who used 24 h NIV with mask NIV at night and MPV during daytime hours is reported.
The mean (± SD) age and vital capacity (VC) at initiation of nocturnal (only) NIV subjects were 17.8±3.5 years and 0.90±0.40 L (21% predicted), respectively; and, at the time of MPV, 19.8±3.4 years and 0.57 L (13.2% predicted), respectively. In clinical practice, carbon dioxide (CO2) levels were measured using different methods: arterial blood gas analysis, transcutaneous partial pressure of CO2 and, predominantly, by end-tidal CO2. While the results suggested improved CO2 levels, these were not frequently confirmed by arterial blood gas measurement. The mean survival on 24 h NIV has been 5.7 years (range 0.17 to 12 years). Of the 12 patients, two deaths occurred after 3.75 and four years, respectively, on MPV; the remaining patients continue on 24 h NIV (range two months to 12 years; mean 5.3 years; median 3.5 years).
Twenty-four hour NIV should be considered a safe alternative for patients with DMD because its use may obviate the need for tracheostomy in patients with chronic respiratory failure requiring more than nocturnal ventilation alone.
PMCID: PMC3628652  PMID: 23457679
Duchenne; Lung volume recruitment; Neuromuscular; Noninvasive ventilation; Ventilation
25.  Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors 
Critical Care  2013;17(6):R269.
We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).
This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.
Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO2/FiO2 >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.
With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO2/FiO2 > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.
PMCID: PMC4057073  PMID: 24215648

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