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(Chest. 2005;128:1657-1666.)
© 2005 American College of Chest Physicians

Noninvasive Positive Pressure Ventilation in Patients With Acute Exacerbations of COPD and Varying Levels of Consciousness*

Raffaele Scala, MD; Mario Naldi, MD; Ivano Archinucci, MD; Giovanni Coniglio, MD and Stefano Nava, MD

* From the Unità Operativo Pneumologia (Drs. Scala, Naldi, Archinucci, and Coniglio) Ospedale S. Donato, Arezzo, Italy; and the Respiratory Intensive Care Unit (Dr. Nava), Fondazione S. Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Scientifico di Pavia, Pavia, Italy.

Correspondence to: Raffaele Scala, MD, Unità Operativo Pneumologia, Ospedale S. Donato, ASL 8 Arezzo, Via Nenni 20, 52100 Arezzo, Italy; e-mail: raffaele_scala{at}hotmail.com


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: A severely altered level of consciousness (ALC) has been considered a contraindication to noninvasive positive pressure ventilation (NPPV). We compared the clinical outcome of patients with acute respiratory failure (ARF) due to COPD exacerbations and different degrees of ALC.

Design: A 5-year case-control study with a prospective data collection.

Setting: Respiratory Monitoring Unit.

Patients: Eighty of 153 consecutive COPD patients requiring NPPV for ARF were divided into four groups, which were carefully matched for the main physiologic variables, according to the level of consciousness assessed with the Kelly-Matthay Score, in which 1 is normal (control subjects) and 6 is severely impaired.

Measurement and results: Changes from baseline in arterial blood gas (ABG) levels and Kelly score, the rate and causes of NPPV failure, the rate of nosocomial pneumonia, and the 90-day mortality rate were compared. NPPV significantly improved ABG levels and Kelly score in all groups after 1 to 2 h. NPPV failure (Kelly score 1 = 15%; Kelly score 2 = 25%; Kelly score 3 = 30%; Kelly score > 3 = 45%) and 90-day mortality rate (Kelly score 1 = 20%; Kelly score 2 = 35%; Kelly score 3 = 35%; Kelly score > 3 = 50%) significantly increased with the worsening of the level of consciousness. Using a multivariate analysis, the acute nonrespiratory component of the acute physiology and chronic health evaluation (APACHE) III score, and baseline pH independently predicted baseline Kelly score. After 1 to 2 h of NPPV, changes in the Kelly score were associated with those in pH. No correlation was found with PaCO2.

Conclusions: This study confirms that NPPV may be successfully applied to patients experiencing COPD exacerbations with milder ALCs, whereas the rate of failure in patients with severely ALCs (ie, Kelly score > 3) is higher, even though better than expected, so that an initial and cautious attempt with NPPV may be performed even in this latter group. Changes in the level of consciousness induced by NPPV are not correlated with those in PaCO2.

Key Words: acute respiratory failure • case-control study • coma • COPD • endotracheal intubation • hypercapnic encephalopathy • noninvasive positive pressure ventilation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The International Consensus Conference on Noninvasive Positive Pressure Ventilation (NPPV), several reviews, and the state of the art suggested that an altered level of consciousness (ALC) may be a possible contraindication to NPPV in patients experiencing acute respiratory failure (ARF).12345 These suggestions are based partly on clinical practice and partly on the results of published studies assessing the predictors of failure.

As a matter of fact, confused patients are unlikely to adapt to NPPV because of poor cooperation. ALC may also be considered to be a relative contraindication to NPPV because of the risk of pulmonary aspiration, which may indeed increase due to the lack of upper airway protection and gastric distension induced by NPPV application.1234567

However, despite the fact that some studies6789 have reported a significant correlation between poor outcome and ALC, others have not.101112131415 Moreover, most of the randomized controlled studies have excluded a priori patients with an ALC. Most importantly, under the common umbrella of ALC, a pool of different degrees of encephalopathy have been included. These range from coma to agitation or confusion, which in severely hypercapnic COPD patients seem to be related to the level of PaCO2 (ie, hypercapnic encephalopathy). Among the different scales assessing the level of consciousness, only one has been specifically designed for critically ill patients requiring mechanical ventilation (ie, the Kelly and Matthay scale).16

We conducted a case-control study in which patients with severe COPD exacerbations were matched for several physiologic variables, except for pH and PaCO2, first, to assess the effectiveness of NPPV in subjects with different degrees of sensorium impairment, and second, to verify whether changes in acidosis and hypercapnia were correlated with changes in level of consciousness trying to identify the pathogenesis of neurologic impairment.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This was an observational matched case-control study with prospectively collected data that was performed in patients who received NPPV for treatment of ARF due to COPD exacerbation, in our Respiratory Monitoring Unit,17 which is located within the Respiratory Ward of Arezzo "S. Donato" Hospital, between January 1998 and January 2003. The study protocol was approved by the local ethics committee of our hospital, and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Informed written consent was obtained in all cases from either the patient or their proxy.

Case Patients (ALC Groups)
All patients with acute decompensation of COPD who were admitted to our unit over the observed period were considered eligible for the study. The diagnosis of COPD was established according to the European Respiratory Society statement.18

Case patients were divided into the following three groups according to the Kelly-Matthay scale,16 which is based on a score ranging from 1 to 6 (grade 1, alert, follows complex 3-step command; grade 2, alert, follows simple commands; grade 3, lethargic, but arousable and follows simple commands; grade 4, stuporous, that is, patient only intermittently follows simple commands even with vigorous attempts at arousal; grade 5, comatose, brainstem intact; grade 6, comatose with brainstem dysfunction): ALC1 group (Kelly-Matthay score, 2); ALC2 group (Kelly-Matthay score, 3); and ALC3 group (Kelly-Matthay score, > 3).

Case patients were enrolled in the study on the condition that, despite receiving the appropriate medical treatment (ie, controlled oxygen therapy; salbutamol and ipratropium bromide via aerosol every 4 h; and IV aminophylline, corticosteroids, antibiotics; cardiovascular drugs, and therapy for comorbidities if necessary), they fulfilled all of the following criteria: (1) pH < 7.33 and PaCO2 >55 mm Hg; (2) PaO2/fraction of inspired oxygen (FIO2) ratio of <250; (3) dyspnea at rest with a respiratory rate (RR) of >25 or < 12 breaths/min; (4) use of accessory respiratory muscles or paradoxical abdominal breathing; and (5) ALC with Kelly score of > 1.

The exclusion criteria were as follows: (1) refusal of NPPV; (2) facial deformity sufficient to affect mask fitting; (3) preexisting psychiatric and neurologic disorders; (4) overt GI bleeding; (5) upper airway obstruction; (6) acute ischemic heart disease; (7) hemodynamic instability (systolic BP of < 90 mm Hg or need for vasoactive agents); (8) acute hepatic failure (twofold increase in glutamic pyruvic transaminase or alkaline phosphatase concentrations or the development of jaundice); and (9) the need for urgent endotracheal intubation (ETI) due to cardiac or respiratory arrest or prolonged respiratory pauses or psychomotor agitation requiring sedation.919

Control Subjects (Normal Level of Consciousness Group)
Control subjects were selected from among all patients who were recruited during the study period according to the same criteria adopted for the case patients except that they had a normal level of consciousness (NLC) [Kelly score, 1]. In the selection process, the variables used for matching control subjects with case patients in each ALC group were as follows: (1) age (± 5 years); (2) gender; (3) causes triggering ARF (eg, community-acquired pneumonia, cardiogenic pulmonary edema, or COPD exacerbation)19; (4) serum bicarbonate level (±0.3 mEq/L); (5) acute respiratory impairment expressed as the respiratory component of the acute physiology and chronic health evaluation (APACHE) III score20 (±5 points); and (6) the number of comorbidities, calculated as previously described.21 When more than one potential control subject was present, the subject with data closest to the case patient was selected.

The overall effectiveness of matching regarding the six selected variables reached 98% for ALC1 group and ALC3 group, and 99% for ALC2 group. Compared to the control group, the following single levels of matching were achieved: for gender and age: ALC1 group, 95%; ALC2 group, 100%; and ALC3 group, 95%; for comorbidities, serum bicarbonate level, and causes of ARF: all ALC groups, 100%; and for the respiratory component of the APACHE III score: ALC1 group, 100%; ALC2 group, 95%; and ALC3 group, 100%.

The comparison between the NLC group and the ALC groups was further evaluated on the basis of the following data: (1) FEV1 in stable patients (ie, within 6 months before hospitalization); (2) body mass index; (3) chronic cor pulmonale22; (4) functional limitation evaluated with activities of daily living (ADL) score23; and (5) need for long-term oxygen therapy (LTOT) and home mechanical ventilation (HMV).

Noninvasive Ventilation
Case patients and all potential control subjects received NPPV in our three-bed Respiratory Monitoring Unit by nurses and physicians who had been adequately trained in this technique. The mean nurse/patient ratio was 1:9. During the earliest phase of NPPV, one pulmonologist was continuously present at the patient’s bedside; later, the patient was supervised by one nurse with one pulmonologist on call.21 ECG, pulse oximetric saturation (SpO2), and noninvasive BP were monitored continuously. Arterial blood gases (ABGs) were sampled before NPPV, after the first trial of 1 to 2 h of NPPV, and then at regular intervals depending on the physician’s judgment. Patient tolerance to NPPV was assessed by a simplified score (1, low; 2, medium; 3, good).19 All patients received ventilation in a semirecumbent position with the head raised at 45°. To minimize the risk of pulmonary aspiration, a nasogastric tube was inserted for a short time in case of gastrodistension, and a seal connector was applied in the dome of the mask to reduce the amount of air leakage. ETI and transfer to the ICU were promptly available if NPPV failed.

NPPV (Bi-PAP Vision; Respironics Inc; Murrysville, PA) was delivered in spontaneous timed mode via a well-fitting full-face mask. A plateau exhalation valve was applied to the circuit in order to minimize CO2 rebreathing24; the inspiratory positive airway pressure (IPAP) was initially set at 10 cm H2O and then gradually increased to a maximum of 25 cm H2O depending on the clinical and blood gas response as well as on the patient tolerance. IPAP was not titrated according to the expiratory tidal volume because the NPPV device, like all single-tube ventilators, fails to give an accurate monitoring of the exhaled volumes. Positive end-expiratory pressure was always set at 5 cm H2O, which is usually able to offset at least the major portion of the inspiratory threshold induced by intrinsic positive end-expiratory pressure.25 Back-up RR was set at 16 breaths/min. The FIO2 was adjusted in order to keep the SpO2 at ≥ 90% with the aim of achieving a satisfactory level of PaO2 without increasing the degree of hypercapnia, especially in ALC patients.79101519212627282930

Psychoactive drugs were not administered to all patients. NPPV was applied intermittently with sessions lasting 2 to 6 h tid. The duration of each session was determined by the improvement in ABG levels, the level of consciousness, patient compliance, and the patient’s degree of ventilatory autonomy at the end of the session. NPPV was discontinued when all the following criteria had been achieved for > 24 h while breathing oxygen: pH > 7.33; PaO2/FIO2 ratio, 250; RR, 25 breaths/min; Kelly score, 1.21

Criteria for ETI
NPPV was considered to have failed if at least one of the following criteria for ETI9 occurred: (1) cardiac arrest or severe hemodynamic instability (systolic BP < 90 mm Hg or the need for vasoactive agents); (2) respiratory arrest, gasping, or prolonged respiratory pauses; (3) mask intolerance with psychomotor agitation requiring sedation; (4) severe difficulty clearing bronchial secretions; (5) worsening of gas exchange during NPPV (at least two of the following: decrease or increase of < 0.02 from the baseline value in pH; decrease or increase of < 20 points from the baseline in PaO2/FIO2 ratio; increase or decrease of < 10% from the baseline in PaCO2); and (6) no change or worsening of the level of consciousness during NPPV (Kelly score, > 1 with respect to baseline). In cases in which the patient and/or proxy refused invasive ventilation, NPPV was considered to have failed when the a priori criteria for ETI were met.

End Points and Statistical Analysis
The effects of 1 to 2 h of NPPV on ABG levels and Kelly score, the rate and causes of NPPV failure, the rate of nosocomial pneumonia (diagnosis based on clinical, radiographic, and biological criteria),8 and the 90-day mortality rate were compared between the ALC groups and NLC group. The Kolmogorov-Smirnov test was used to verify whether all recorded variables were normally distributed (p > 0.05). Continuous data were expressed as the mean (SD) or the median (interquartile range [IQR]) if distributed normally or not, respectively. Categoric data are presented as frequencies.

Continuous variables for the NLC group and for each of the ALC groups were compared with the two-tailed unpaired t test (parametric data) and the Mann-Whitney U test (nonparametric data). A comparison of continuous variables within each group before and after the first trial of NPPV was performed with the two-tailed paired t test (parametric data) and the Wilcoxon signed rank test (nonparametric data).

Categoric data were compared using the {chi}2 test or, when appropriate, the Fisher exact test. A p value of < 0.05 was considered to be statistically significant.

Independent predictors of Kelly score at baseline were searched in all patients by means of multivariate analysis. The collected quantitative variables that were significantly correlated with Kelly score at baseline as a result of the Spearman test (p < 0.01) were entered into a stepwise linear regression.

Survival time after hospital discharge was compared between case patients and control subjects by means of the Kaplan-Meier method. Differences between survival curves were evaluated by applying the log-rank test. Analyses were performed using a statistical software package (SPSS, version 10.0; SPSS, Inc; Chicago IL).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
During the study period, 685 patients with acute decompensation of COPD were admitted to our unit; most of them improved quickly with medical therapy (485 of 685 patients; 70.8%). Among the remaining 200 eligible patients with ARF, 32 (16%) were excluded from the study because of the need for urgent ETI, and 15 (7.5%) were excluded because of their refusal of NPPV. The remaining 153 patients received NPPV a median time of 9.0 h (IQR, 1.50 to 69.75 h) after admission into our unit; 60 of them fulfilled the criteria for ALC according to the three different case groups (ALC1 group, 20 patients; ALC2 group, 20 patients; ALC3 group, 20 patients). From the remaining 93 NLC patients of a total of 153, 20 control subjects were then selected as a result of a careful matching with each ALC group (Table 1 ). As expected, according to the guidelines of the Global Initiative for Chronic Obstructive Pulmonary Disease31 and as pointed out by an epidemiologic study conducted in a Mediterranean population,32 men were more prevalent in each group, representing 76.3% of the entire population.


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  		Table 1. Comparison of Variables Used for Matching Between NLC Group and ALC Groups*

 
Among the variables not used for the matching process, no significant differences emerged between the NLC group and the ALC groups regarding FEV1, ADL score, body mass index, presence of cor pulmonale, need for LTOT and HMV, while, on the contrary, APACHE III score and its acute nonrespiratory component were significantly higher as the ALC worsened (Table 2 ).


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  		Table 2. Comparison of Variables Not Used for Matching Between NLC Group and ALC Groups*

 
NPPV was delivered for a median duration of 40.75 h (IQR, 21.63 to 73 h) (mean duration for the first day, 12.3 h [SD, 6.7 h]) for a median duration of 5.0 days (IQR, 3 to 9 days). The number of hours of NPPV in the first day were higher, worsening the ALC, and were significantly different in the NLC group vs the ALC2 group (p = 0.017) and the ALC3 group (p < 0.0001). NPPV was well-tolerated with a compliance score ≥ 2 in 71.2% of patients. The mean IPAP applied was 19.5 cm H2O (SD, 4.2 cm H2O). No significant differences in NPPV compliance and level of IPAP applied occurred among the groups (Table 2).

ABG levels at baseline differed only for pH and PaCO2, which respectively dropped and rose as the ALC worsened. Within the first 2 h, NPPV significantly improved ABG levels in both the control subject and case patient groups; the percentage of improvement in pH and PaCO2 was significantly greater in the ALC2 group vs the NLC group. Kelly score was significantly decreased in all ALC groups, in which the percentage of changes was significantly greater with respect to the control subjects, among whom neurologic score increased (Table 3 ). Similar behavior was observed when the Glasgow coma score (GCS)33 was used to assess the level of consciousness. At hospital discharge, ABG level and Kelly score had significantly improved compared to the baseline value, with a statistically significant difference between the ALC3 group and the NLC group only in PaO2/FIO2 ratio and SpO2.


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  		Table 3. ABG and Level of Consciousness at Baseline (While Breathing Oxygen), after 1 to 2 h of NPPV, and at Hospital Discharge (While Breathing Oxygen) in the NLC Group and ALC Groups*

 
NPPV failed in 23 of 80 patients (28.8%) a median time of 4 days (IQR, 2 to 8 days) after study enrollment due to the following: worsening of ABG levels, 11 patients (47.8%); worsening of level of consciousness, 11 patients (47.8%); mask intolerance, 4 patients (17.4%); retention of secretions, 2 patients (8.7%); cardiac arrest or hemodynamic instability, 7 patients (30.4%); and respiratory arrest, 1 patient (4.4%). More than one condition caused NPPV failure in 11 patients (Table 4 ).


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  		Table 4. Intubation Need, Intubation Rate, Causes of NPPV Failure, and Hospital and 90-Day Mortality Rate in NLC group and ALC groups*

 
Although a nasogastric tube was more frequently needed as consciousness impairment increased (NLC group, 1 patient; ALC1 group, 3 patients; ALC2 group, 4 patients; ALC3 group, 7 patients; p = 0.018 [ALC3 group vs NLC group]), gastrodistension was fully reversible in all subjects. Nosocomial pneumonia, including pulmonary aspiration, was never observed.

NPPV failure and the 90-day mortality rate increased with worsening ALC, even though they were both significantly higher only in ALC3 group vs NLC group. The causes of NPPV failure were similar among all groups except for cardiovascular events, which developed more frequently in the ALC3 group vs the NLC group (p = 0.017) [Table 4]. The timing of NPPV failure among all groups is represented in Figure 1 ; NPPV failed within the first 24 h in 10 of 23 patients (43.4%). According to a Kaplan-Meier analysis, survival time after hospital discharge was significantly shorter only in the ALC3 group vs NLC group (Fig 2 ).



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  		Figure 1. Curves of NPPV failure according to the time of NPPV in case patients, control subjects, and the overall groups.

 


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  		Figure 2. Survival curves in the NLC group (74 days; 95% confidence interval, 59 to 88 days) vs the ALC1 group (63 days; 95% confidence interval, 46 to 80 days; log-rank, 1.07; p = 0.300), the ALC2 group (70 days; 95% confidence interval, 55 to 86 days; log-rank, 0.99; p = 0.320), and the ALC3 group (47 days; 95% confidence interval, 27 to 66 days; log-rank, 3.95; p = 0.046).

 
Six of 23 subjects were intubated as the others refused ETI and died. Four intubated patients died after a mean duration of 37.3 days (SD, 17.7 days) of ICU stay due to septic shock (two case patients), multiple organ dysfunction syndrome (one case patient), and cardiac arrest (one case patient). Only two intubated patients were discharged from the hospital alive. Seven patients died within 90 days after hospital discharge due to a further episode of ARF (two case patients), multiple organ dysfunction syndrome (one case patient), stroke (one case patient), pulmonary embolism (one case patient), acute myocardial infarction (one case patient), and complications after pneumonectomy for lung cancer (one case patient). The overall in-hospital and 90-day mortality rates of the enrolled population were 26.3% (21 of 80 patients) and 35% (28 of 80 patients), respectively. In the majority of case patients (19 of 28; 68%), the 90-day mortality rate was primarily due to the advanced stage of the chronic lung disease.

As a result of the multivariate analysis, the acute nonrespiratory component of the APACHE III and baseline pH independently predicted the baseline Kelly score in the studied population. Changes in Kelly score after 1 to 2 h of NPPV were significantly correlated with pH (Spearman {rho} = –0.241; p = 0.031), but not with PaCO2 changes (Spearman {rho} = 0.217; p = 0.053).

The median length of stay in the hospital was 15.5 days (IQR, 11.25 to 21 days). At hospital discharge, LTOT and HMV were prescribed for 16 and 6 patients, respectively.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This is the first case-control study performed in patients experiencing acute exacerbations of COPD that was aimed at evaluating the efficacy of NPPV in patients with increasing degrees of ALC compared to fully alert subjects. The application of NPPV was able to quickly improve gas exchange and neurologic status in the large majority of patients, irrespective of the severity of the ALC. However, while in patients with mild-to-moderate ALC (Kelly score, ≤ 3) NPPV was highly successful in terms of clinical outcomes, those patients with a severely ALC had an increased but not a dramatically high rate of NPPV failure and 90-day mortality rate. In this subset of patients, cardiovascular events were more frequently the cause of NPPV failure. Pulmonary aspiration was not observed in any of the subjects. Changes in the ALC after NPPV application were not strictly correlated with those in PaCO2.

Case patients with different ALCs were similar to the control subjects not only in terms of the variables defined in the matching process but also in terms of further historical clinical-physiologic data and of pH and PaCO2 at hospital discharge, indicating that the severity of acute illness, mental status aside, and of the underlying disease were comparable between patients with ALCs and those without sensorium impairment. The absolute serum bicarbonate level, which was included in the matching criteria, may be unreliable in patients with chronic hypercapnic respiratory failure. However, since we did not find any statistical difference between the changes in serum bicarbonate level and those in base excess, we decided to simply apply the former as a matching criterion. As acute hypercapnia may play a role in mental status perturbations,34 it is not surprising that patients with ALC and control subjects significantly differed in baseline pH and PaCO2. Most reports in the literature on NPPV refer to "hypercapnic encephalopathy," the altered sensorium observed in some critically ill COPD patients, even though no study has so far systematically looked at the possible correlation between improvement in ABG levels and level of consciousness.

ALC is reported as a classic contraindication for NPPV in patients with COPD exacerbations because this noninvasive support is believed to be less effective in uncooperative patients and unsafe, considering the risk of pulmonary aspiration and the difficulty in the management of bronchial secretions.1234567 However, it has been demonstrated that ETI in patients with severely ALCs does not add further benefits compared to NPPV.2635 Moreover, the effects of NPPV on gas exchange, the need for ETI, and mortality in patients with different degrees of ALC have not been deeply studied as they were mostly excluded by randomized controlled trials.

The only study that has systematically enrolled patients with very severely ALCs (ie, GCS, ≤ 8),27 demonstrated that a consistent portion of patients could be successfully ventilated noninvasively using the iron lung. The authors27 clearly showed therefore that a noninvasive ventilation technique could be sometimes applied "beyond" the boundaries proposed by the international recommendation. In contrast to the iron lung, the application of a nasal or facial interface, which requires greater patient collaboration, has been considered a major limitation to the success of NPPV.1234512 As has been reported in other series of patients,10131415 we found that mask compliance was as good in case patients as in control subjects and that mask intolerance caused NPPV failure as often in the former groups as in the latter.

The main safety concern about the use of NPPV in patients with altered mental status is the possibility of aspiration pneumonia due to the lack of upper airways protection in patients with depressed cough reflex and copious secretions.12345 The above-mentioned risk was minimized by the insertion of a nasogastric tube in a large portion of patients with a Kelly score of > 3 and by the rather rapid improvement in neurologic status after 1 to 2 h of NPPV. In our study, as previously described,101112131415 a short trial of NPPV was followed by a significant improvement in respiratory acidosis and neurologic status. This should have sensibly reduced the risk of pulmonary aspiration and secretion retention. In fact, nosocomial pneumonia never developed in our study and the number of NPPV failures for difficult secretion clearing was not significantly different in case patients than in control subjects. This is in accordance with the results of previous studies89123637 showing that nosocomial pneumonia rarely complicated NPPV in ARF patients, mainly because of ETI prevention. However, as most of our patients were not intubated after NPPV failure, it could not be excluded that the postintubation pneumonia rate could have been different among the various groups. In a series of 30 patients with ARF, Benhamou et al11 reported only three cases (2 of 24 patients with ALCs) of NPPV failure for pulmonary atelectasis due to bronchial hypersecretion.

In our study, only those patients with the most severely impaired mental status (ie, the ALC3 group) had a significantly higher failure rate for NPPV and a higher 90-day mortality rate compared to control subjects; those with milder alterations in cognitive function did not significantly differ from control subjects in either regard. It may not be excluded that the substantial rate of ETI refusal after NPPV failures (17 of 23 patients; 74%) could have had some influence on the hospital and 90-day mortality rates among the groups. However, as the highest percentage of treatment failures not followed by intubation was found in the ALC3 group, this possible bias concerning mortality might have overestimated the worst prognosis in patients with the greatest degree of hypercapnic encephalopathy. We may also not exclude the fact that the higher rate of refusal was influenced by the "paternalistic" approach of the physician with the patient and their relatives. In Europe, and in southern Europe in particular, the family and the patient are usually marginally involved in this decision.38 The physician takes most of the responsibility in deciding whether to intubate or not. This holds particularly true when the emergency department physician meets the patient and their relatives, who have not received any information relevant to this decision, for the first time.

Benhamou et al11 found that NPPV using a nasal mask was successful in 60% of ARF patients (mean pH, 7.29), most of them (24 of 30 patients) showing clinical signs of hypercapnic encephalopathy. In a prospective study performed in a respiratory ward, Dueñas-Pareja et al15 reported a hospital survival rate of 69% after treatment with NPPV using a facial mask in 13 ARF patients (mean pH, 7.17) who were in hypercapnic coma (GCS, ≤ 7) and were not candidates for ICU admission.

These data are difficult to compare with our experience because of differences in setting, mode of ventilation, interface, severity of ARF, criteria of inclusion, and failure (Table 5 ). Furthermore, the degree of consciousness was not uniformly assessed in the different studies. The major problem is due to the fact that not one of the available scoring systems (ie, encephalopathy score, GCS, and Kelly score)91633 has been validated specifically for measuring hypercapnia-induced changes in mental status both during spontaneous breathing and during mechanical ventilation. Like other authors assessing the level of consciousness in mechanically ventilated patients,192135 we employed the Kelly score,16 which is easily and quickly administered as well as being the only scale sensitive to minor changes in mental status in mechanically ventilated patients, even though it has not been calibrated in noninvasively ventilated patients. Therefore, there is an urgent need to develop and/or validate a neurologic score specifically designed for assessing changes in mental status induced by decompensated hypercapnia both during spontaneous breathing and during invasive and noninvasive ventilation.


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  		Table 5. ABGs, Level of Consciousness and Clinical Outcomes of NPPV in Patients With Hypercapnic Encephalopathy According to Different Studies in the Literature in Comparison With the Present Study*

 
Concerning the possible correlations between sensorium and ABG level changes after NPPV, we found that the degree of respiratory acidosis did not fully explain the changes in Kelly score and that other factors, like nonpulmonary acute organ dysfunction, seemed to play an important role. This justifies, at least in part, why the rate of NPPV failure was not as dramatically high in patients with milder degrees of ALC as it could have been expected by only considering the severity of the respiratory acidosis.

Interestingly, the highest rate of cardiovascular complications in the case patients with greater ALCs is in agreement with the known physiopathologic effects of acidosis on myocardial inotropism and excitability, which lead to as high a risk of cardiac pump failure and life-threatening arrhythmias as when pH is low.39

In conclusion, we have shown that during an episode of COPD exacerbation NPPV could be successfully applied to a large majority of patients with mild-to-moderate sensorium impairment. Patients with severely ALCs may still benefit from NPPV application. However, close monitoring is needed with the latter, and prompt intubation should be available in case of the lack of a rapid response. The changes in mental status after a brief trial of NPPV seem not to be exclusively associated with variations in ABG level, but rather with acute nonrespiratory organ impairment. Further controlled and randomized studies comparing NPPV to the usual medical treatment (including ETI) among the different strata of levels of consciousness are needed to confirm our results.


   Acknowledgements
 
The authors thank Professor Maria Attard for her help with the American English language and in editing the manuscript.


   Footnotes
 
Abbreviations: ABG = arterial blood gas; ADL = activities of daily living; ALC = altered level of consciousness; APACHE = acute physiology and chronic health evaluation; ARF = acute respiratory failure; ETI = endotracheal intubation; FIO2 = fraction of inspired oxygen; GCS = Glasgow coma score; HMV = home mechanical ventilation; IPAP = inspiratory positive airway pressure; IQR = interquartile range; LTOT = long-term oxygen therapy; NPPV = noninvasive positive pressure ventilation; NLC = normal level of consciousness; RR = respiratory rate; SpO2 = pulse oximetric saturation

Received for publication September 20, 2004. Accepted for publication February 14, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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E. Garpestad, J. Brennan, and N. S. Hill
Noninvasive Ventilation for Critical Care
Chest, August 1, 2007; 132(2): 711 - 720.
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