Continuous Positive Airway Pressure

CPAP delivers a constant pressure throughout spontaneous inspiration and exhalation without assisting inspiration. Because spontaneous breathing is not assisted, this technique requires an intact respiratory drive and adequate alveolar ventilation. CPAP increases functional residual capacity and opens underventilated alveoli, thus decreasing right-to-left intrapulmonary shunt and improving oxygenation and lung mechanics (34). Moreover, CPAP may reduce the work of breathing and dyspnea in COPD patients by counterbalancing the inspiratory threshold load imposed by intrinsic PEEP (35). Effects on hemodynamics during CPAP have been widely described. By lowering left ventricular transmural pressure in patients with left congestive heart failure, CPAP may reduce left ventricular afterload without compromising cardiac index (36,37). For several years, it was hypothesized that positive airway pressure, by increasing right atrial pressure (38), reduced venous return by decreasing the pressure gradient between mean systemic filling pressure and right atrial pressure (39). However, as demonstrated in experimental (40,41) and human (42) studies, positive airway pressure does not affect the gradient for venous return, because pleural pressure is transmitted to the same extent to both the mean systemic and right atrial pressures. CPAP can be applied by various devices including low-flow generators with an inspiratory reservoir, high-flow jet venturi circuits (Fig. 103.7)—both of them with an expiratory mechanical or water valve—and bilevel and critical care ventilators. Continuous positive pressure may be administered using the demand flow (DF) or the gold standard continuous flow (CF) system. With DF CPAP, the patient has to trigger a preset pressure to open the demand valve, whereas with CF CPAP, no valves are present. The work of breathing is significantly greater with the DF system than with the CF system (43–45). It is crucial to provide an adequate airflow rate for maintaining a continuous positive pressure, especially in dyspneic patients who breathe at high-flow rates. A low CPAP level may be obtained by delivering oxygenation through high-flow nasal cannula (HFNC). During HFNC at a flow rate of 35 L/min in patients with the mouth closed, a mean nasopharyngeal airway pressure of 2.7 cm H₂O has been measured (46).

Pressure Support Ventilation

Pressure support ventilation (PSV) is a pressure-triggered, pressure-targeted, flow-cycled mode of ventilation. It delivers a preset inspiratory pressure to assist spontaneous breathing, augmenting spontaneous breaths and offsetting the work imposed by the breathing apparatus. A sensitive patient-initiated trigger causes the delivery of inspiratory pressure support that is maintained throughout inspiration, and a reduction in inspiratory flow drives the ventilator to cycle into expiration. Therefore, the patient can control either inspiratory duration or breathing rate.

Bilevel Positive Airway Ventilation

In bilevel positive airway pressure (BiPAP), a valve sets two pressure levels, the expiratory positive airway pressure (EPAP) level, and the inspiratory positive airway pressure (IPAP) level, even in the presence of rapidly changing flows. With this technique, ventilation is produced by the cyclic delta pressure between the IPAP and EPAP. EPAP also recruits underventilated lung and offsets eventual intrinsic PEEP.

Controlled Mechanical Ventilation

In the mandatory controlled mechanical ventilation (CMV) mode, no patient effort is required, as full ventilatory support is provided. In this mode, ventilator settings include inflation pressure or tidal volume, frequency, and the timing of each breath. Pressure control ventilation (PCV) delivers time-cycled preset inspiratory and expiratory pressures with adjustable inspiratory-to-expiratory ratios at a controlled rate. The resulting tidal volume is determined by the compliance of the lungs and chest wall, and the resistance to flow of ventilator tubing. In volume control ventilation (VCV), tidal volume is set and the resulting pressure depends on the thoracic and circuit compliance.

Assist/Control Ventilation

In assist/control (A/C) ventilation, the ventilator delivers a breath either when triggered by the patient’s inspiratory effort (assist) or independently, if such an effort does not occur within a preselected time period (control). When triggering occurs, the ventilator delivers an identical breath to mandatory breaths; volume-cycled and pressure-limited or pressure-targeted modes are available.

Proportional Assist Ventilation

Proportional assist ventilation (PAV) is an alternative technique in which both flow and volume are independently adjusted. In this technique, the ventilator generates volume and pressure in proportion to the patient’s effort, increasing comfort and so improving success and compliance with NIV (47). Despite the promising concept, there is a substantial lack of large clinical studies (48).

Techniques to Assist Cough

The cough mechanism may be severely impaired in neuromuscular diseases when weak expiratory muscles are combined with a markedly reduced vital capacity. An effective cough depends on the ability to generate adequate expiratory airflow, estimated at more than 160 L/min (49), which is determined by lung and chest wall elasticity, airway conductance, and expiratory muscle force. Additionally, intact glottic function is needed for yielding high peak expiratory cough flows. Manually assisted coughing consists of quick thrusts applied to the abdomen using the palms of the hands, timed to coincide with the patient’s cough effort. The maneuver should be applied cautiously after meals and with the patient positioned semi-upright to reduce the risk of aspiration of gastric contents.

Manually assisted coughing may enhance expiratory force, but it does not increase inspired volume, so that patients with severely restricted volumes may still achieve insufficient cough flows. Such a limitation may be overcome by using the mechanical insufflator–exsufflator (MI-E) (Fig. 103.8), which delivers a positive inspiratory pressure of 30 to 40 cm H₂O via a face mask and then rapidly switches to an equal negative pressure (50). The positive pressure produces an adequate tidal volume, whereas the negative pressure stimulates the high peak expiratory cough flows. An MI-E may be combined with manually assisted coughing to further augment cough effectiveness. In a randomized trial, patients who were extubated and allocated to three daily sessions of MI-E experienced a lower rate of reintubations and postextubation ICU length of stay (51). In any event, all the techniques used to assist cough can be performed effectively and frequently by skilled caregivers, with minimal discomfort to the patient.

TABLE 103.1 Criteria for Noninvasive Ventilation Discontinuation and Endotracheal Intubation

Patient Selection

The criteria for selecting appropriate patients to receive NIV for ARF include clinical indicators of acute respiratory distress, such as moderate-to-severe dyspnea, tachypnea, accessory muscle use and paradoxical abdominal breathing, and gas exchange deterioration. Blood gas parameters aid in identifying patients with acute or acute superimposed on chronic CO₂ retention. A conscious and cooperative patient is crucial for initiating NIV (Table 103.2), although hypercapnic patients with narcosis who are otherwise good candidates for NIV may be an exception (52,53).

TABLE 103.2 Contraindications to Noninvasive Ventilation

During NIV, patients can achieve a level of control and independence totally different from when intubated, and sedation is infrequently required. If benzodiazepines or opiates are administered, caution is advised to prevent undue hypoventilation. NIV should be avoided in patients with hemodynamic instability and in those who are unable to protect the airways (i.e., coma, impaired swallowing) (see Table 103.2). Patients with severe hypoxemia (PaO₂/FiO₂ <100) or morbid obesity (>200% of ideal body weight) should be closely managed only by experienced personnel and with a low threshold for endotracheal intubation (20,21,54). In the presence of a pneumothorax, NIV can be initiated provided an intercostal drain is inserted. Criteria for NIV discontinuation and endotracheal intubation must be thoroughly considered to avoid dangerous delays (see Table 103.1).

Identification of predictors of success or failure may help in recognizing patients who are appropriate candidates for NIV and those in whom NIV is not likely to be effective, thereby avoiding its application and unnecessary delays before invasive ventilation is given.

Predictors of NIV failure observed in COPD patients with ARF are the following:

• Lower arterial pH at baseline (55,56)
  
• Greater severity of illness, as indicated by Acute Physiology and Chronic Health Evaluation (APACHE) II score (57)
  
• Inability to coordinate with the ventilator (57)
  
• Inability to minimize the amount of mouth leak with nasal mask ventilation (57)
  
• Less efficient or less rapid correction of hypercapnia, pH, or tachypnea in the early hours (57)
  
• Functional limitations caused by COPD before ICU admission, evaluated using a score correlated to home activities of daily living (ADL) (56)

Predictors of NIV failure observed in hypoxemic patients with ARF are the following:

• Higher severity score (Simplified Acute Physiology Score [SAPS] II ≥35 (58), SAPS II >34 (59), higher SAPS II (60))
  
• Older age (>40 years) (58)
  
• Presence of acute respiratory distress syndrome (ARDS) or community-acquired pneumonia (58,60,61)
  
• Failure to improve oxygenation after 1 hour of treatment (PaO₂/FiO₂ ≥146 (58), PaO₂/FiO₂ ≥175 (59))
  
• Higher respiratory rate under NIV (61)
  
• Need for vasopressors (61)
  
• Need for renal replacement therapy (61)

Ventilation Mode Selection

The choice of the correct ventilatory mode is crucial for achieving physiologic and clinical benefit during NIV. However, each ventilation mode has theoretical advantages and limitations.

Work of breathing during ARF may be significantly reduced if the selection is made properly. In a physiologic study (62) performed in hypoxemic patients with ARF, noninvasive PSV combined with PEEP improved dyspnea and gas exchange, and lowered neuromuscular drive and inspiratory muscle effort; in these patients, CPAP used alone improved oxygenation but failed to unload the respiratory muscles.

The application of external PEEP is a valid strategy to counterbalance the effects of dynamic hyperinflation in patients with acute hypercapnic exacerbations of COPD. In this setting, NIV delivered through different ventilator modes can provide respiratory muscle rest and improve respiratory physiologic parameters. No difference in clinical outcome or arterial blood gases between patients ventilated in ACV and PSV modes has been found, even though PSV is in general better accepted by the patients and associated with fewer side effects in comparison with ACV mode (63). However, in patients with severe chest wall deformity or obesity, who typically need higher inflation pressures, VCV may be preferred.

Triggering systems are critical to the success of NIV in both assist and control modes. During assisted ventilation, flow triggering reduces breathing effort more effectively as compared with pressure triggering, obtaining a better patient–ventilator interaction (64). Similarly, in COPD patients, the increase of expiratory trigger (10% to 70% of peak expiratory flow) may reduce the magnitude of delayed cycling, intrinsic PEEP and nontriggering breaths (65).

There are no clear recommendations or specific requirements from bench studies on the performance of NIV ventilators and interfaces (66). Personal experience, clinical setting, etiology, and severity of the pathologic process responsible for ARF should lead physicians’ decisions; however assisted modes, particularly PSV, are more often used. As regards pressure-targeted ventilation, it is thought that starting at low pressures to facilitate patient tolerance (appropriate initial pressures are a CPAP of 3 to 5 cm H₂O and an inspiratory pressure of 8 to 12 cm H₂O above CPAP) is appropriate and then, if necessary, to gradually increase pressures, as tolerated, to obtain alleviation of dyspnea, decreased respiratory rate, adequate exhaled tidal volume, and good patient–ventilator interaction (Table 103.3). Pressures commonly used to administer CPAP in patients with ARF range from 5 to 12 cm H₂O. In patients with hypoxemic ARF and bilateral pulmonary infiltrates, undergoing 10 cm H₂O CPAP delivered via a helmet, adding a 25 cm H₂O sigh for 8 seconds, once a minute, improved oxygenation (67). Oxygen supplementation should be targeted to achieve an oxygen saturation above 92% or between 85% and 90% in patients at risk of worsening hypercapnia. A modality that provides a backup rate is necessary for patients with inadequate ventilatory drive.

Patient–Ventilator interaction and Carbon Dioxide Rebreathing

NIV tolerance is strictly correlated with an optimal synchrony between the patient’s breathing activity and ventilator parameters. When an optimal patient–ventilator interaction is lacking, increase in the work of breathing and patient discomfort may be remarkable (68). Patient–ventilator asynchrony may be determined by a number of events including ineffective triggering, double-triggering, auto-triggering, premature cycling, and delayed cycling.

TABLE 103.3 Proposed Ventilator Settings for Pressure Support Ventilation Mode

During NIV in PS modality, several forms of patient–ventilator asynchrony may occur, causing breathing discomfort. In a multicenter French study, the level of pressure support and the magnitude of leaks were identified as independent predictors of increased patient–ventilator asynchrony (number of ineffective breaths and delayed cycling) (69). In addition, ineffective triggering due to excessive levels of PS (17.5 cm H₂O vs. 15 cm H₂O) and less sensitive inspiratory triggers has been shown contributing to longer duration of mechanical ventilation (17.5 vs. 7.5 days) (70). Eventual air leaks during noninvasive PSV may impede the inspiratory flow decay required to open the expiratory valve, thereby prolonging inspiratory flow. In these circumstances, air leaks should be minimized by optimizing the fitting or size of the interface, or even switching to another type of interface. To reduce leaks, it may also be helpful to decrease ventilator pressure settings as much as allowed by clinical parameters. In older machines, when an air leak occurs, an option to obtain a better patient–ventilator interaction is to select pressure-limited, time-cycled ventilation modes, or even PSV mode with a maximal inspiratory time. With ventilators that allow changing the cycling off criteria (expiratory trigger), raising the cycling off airflow threshold (i.e., the percentage of peak inspiratory flow at which transition from inspiration to expiration occurs) can activate an earlier switchover to expiration, thus avoiding prolonged insufflations and patient–ventilator asynchrony.

Pressurization rate is another parameter that can be modified during PS NIV in order to reduce patient–ventilator asynchrony. In COPD patients, faster values are able to reduce the diaphragmatic metabolic consumption (expressed as pressure time product) but may determine significant air leaks and poor tolerance (71). Similarly, in hypoxemic subjects, a “fast” pressure ramp significantly decreased the work of breathing even though either the lowest or the highest pressurization rates were associated with patient discomfort (72). In the presence of significant air leaks, pressure-targeted modes are preferred to deliver NIV as they can maintain delivered tidal volume better than volume-targeted modes (73). In new ventilators, an NIV algorithm, usually referred to as “NIV mode,” measures and compensates leaks in order to minimize their detrimental impact on patient–machine synchrony (74,75). Neurally adjusted ventilatory assist (NAVA) seems to a very promising mode to help improve adaptation during NIV (76–78).

An optimal ventilator setting should also take into account the type of interface used to deliver NIV. It has been advised that the highest PEEP and PS levels clinically indicated and tolerated by the patient should be applied when NIV is administered with the helmet, in order to increase the elastance of the system, enhancing the trigger sensitivity (79). Vargas et al. (80) suggested that increasing both PEEP and PS levels and using the highest pressurization rate may be suitable when providing NIV through this interface. In their study, the helmet with the same settings as the face mask was associated with less inspiratory-muscle unloading and with worse patient–ventilator asynchrony. In contrast, specific settings with a fast ramp and higher pressures provided results similar to the mask, ameliorating the inspiratory trigger delay, without discomfort. In addition, as observed in a helmet NIV bench study, a double tube circuit (with one inspiratory and one expiratory line) seems to improve patient–ventilator interaction and reduce the rate of wasted efforts, compared with a standard circuit (a Y-piece connected only to one port of the helmet) (81).

Humidification

Prolonged exposure of tracheobronchial epithelium to cool and dry gases may be a clinical issue during NIV. So, both humidification and warming may be required to prevent upper airways irritation. Two humidifying devices are commonly used with ICU ventilators: heated humidifiers (HHs), and heat and moisture exchangers (HMEs). The latter are the most commonly used due to their simplicity and cost-effectiveness. However, because the HMEs are placed between the Y-piece and the patient, they add a substantial amount of dead space, compared to an HH, which is placed in the inspiratory circuit. In addition, compared to HHs, HMEs may increase resistance to flow (82).

Heated humidification during NIV in patients with ARF can minimize work of breathing and improve CO₂ clearance. In a physiologic study on nine COPD patients with hypercapnic ARF requiring NIV, Lellouche et al. (83) showed that the use of HMEs, compared with HHs, greatly increased work of breathing. Nonetheless, despite significantly higher minute ventilation during the HME study phase, arterial partial pressure of CO₂ (PaCO₂) was not different. By way of contrast, in another study on 24 patients with ARF undergoing face mask NIV with HME or HH, Jaber et al. (84) found that HME was associated with a significantly higher PaCO₂.

Given the above-mentioned physiologic implications, in a recent randomized clinical trial, a multicenter French study group tested the hypothesis that HH use during NIV, compared with HME, could reduce the rate of intubation in patients with ARF (both hypoxemic and hypercapnic). Surprisingly, no differences in terms of intubation rate, ICU or hospital length of stay and ICU mortality were observed between the two groups, even in the subgroup of hypercapnic patients (85). In addition, no difference in the patients’ mucosal dryness was reported with HH in comparison with HME. The authors concluded that HHs during NIV cannot be recommended as a first-line treatment in all patients with ARF but they may be considered in the presence of persistent high PaCO₂ levels associated with threatening encephalopathy. Additionally, in COPD patients under long-term NIV, no firm conclusion can be drawn on the type of humidification system to be used. A randomized crossover 1-year study on 16 COPD patients receiving long-term NIV with either HH or HME, showed that compliance with treatment and occurrence of infections were similar with HH and HME, albeit patients with HH showed less dryness of the throat (86). Of note, at the end of this study, a higher number of patients decided to continue NIV with HH.

Monitoring

In the acute setting, patients can initiate NIV anywhere, at the onset of the acute respiratory distress, but after initiation, they should be transferred to an ICU or a step-down unit for continuous monitoring until they are sufficiently stable to be moved to a medical ward. During transfers, NIV and monitoring should not be discontinued. The early use of NIV for less acutely ill patients with COPD on a medical ward seems to be effective, but if pH is lower than 7.30, admission to an environment with intensive care monitoring is highly recommended (87).

TABLE 103.4 Monitoring of Patients Receiving Noninvasive Ventilation in the Acute Care Setting

Monitoring of patients undergoing NIV is aimed at determining whether the initial goals are being achieved, including relief of symptoms, reduced work of breathing, improved or stable gas exchange, good patient–ventilator synchrony, and patient comfort (Table 103.4). Gas exchange is monitored by continuous oximetry and arterial blood gases at baseline, after 30 to 60 minutes, and as clinically indicated; physiologic responses are evaluated by continuous electrocardiography, respiratory rate, blood pressure, and heart rates. Finally, dyspnea, as well as tolerance of the technique, symptoms of impaired sleep, patient–ventilator asynchrony, and air leaking can be easily assessed through patient queries, bedside observation, and flow, volume, and pressure waveform analysis. If a poor response to NIV occurs and the specific measures used to correct the situation fail to address an adequate improvement, NIV should be considered a failure, and invasive ventilation should be promptly considered.

Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD-E)

In patients with ARF resulting from acute COPD-E, the use of NIV has been proven to be effective in ameliorating dyspnea, improving vital signs and gas exchange (87–91), preventing endotracheal intubation (88–91), and improving hospital survival (87,88,90). Consequently, there is a general agreement concerning the early use of NIV in such patients (92,93). In a 10 years (from 1998 to 2008) prevalence study on more than 7 million patients with acute COPD-E, a 462% increase in NIV use and a 42% decline in invasive mechanical ventilation use were observed. Surprisingly, the study documented a rising mortality rate in the subgroup of patients who needed endotracheal intubation after failing NIV (94). Such findings were explained by patients’ severity, the time before NIV failure and possible difficulties with the interface tolerance (95).

In COPD patients with acute respiratory decompensations, the increased flow resistance and the impossibility to complete the expiration before inspiration determine high levels of dynamic hyperinflation, and substantial shortening of the diaphragm and the inspiratory intercostals and accessory muscles, thereby reducing their mechanical efficiency and endurance. The need to overcome the inspiratory threshold load due to auto-PEEP and to drive the tidal volume against airway resistances increases the respiratory muscle fatigue. During NIV, the combination of external PEEP and PSV offsets the auto-PEEP level and reduces the work of breathing that the inspiratory muscles must generate to produce the tidal volume (96).

In an early study on the use of face mask NIV in patients with ARF, Meduri et al. (13) obtained improvements of gas exchanges and avoided endotracheal intubation in a group of COPD patients. Soon thereafter, Brochard et al. (14) described the short-term (45 minutes) physiologic effects of inspiratory assistance with a face mask on gas exchange and respiratory-muscle work in 11 patients with COPD and evaluated the therapeutic use of the technique in 13 patients with COPD-E, comparing the results in the latter group with the results of conventional treatment in 13 matched historical-control patients. In the physiologic study, arterial pH rose from 7.31 to 7.38 (p < 0.01), PaCO₂ fell from 68 to 55 mmHg (p < 0.01), PaO₂ rose from 52 to 69 mmHg (p < 0.05), and respiratory rate reduced from 31 to 21 breaths per minute (p < 0.01) (14). Only 1 of 13 patients treated with NIV needed intubation, as compared with 11 of the 13 historical controls (p < 0.001). In addition, the NIV-treated patients were weaned from the ventilator faster and spent less time in the ICU than did the control subjects (14). Subsequently, numerous randomized controlled trials using NIV in ARF caused by COPD have been published (Table 103.5).

In the first randomized, prospective study on 60 COPD patients, Bott et al. (89) compared NIV delivered through nasal mask with conventional therapy as a treatment of ARF. Patients receiving NIV had a significant reduction of PaCO₂, dyspnea score, and 30-day mortality (10% vs. 30%). A multicenter European trial (88) on the efficacy of NIV in acute COPD-E randomized 85 COPD patients to receive face mask PSV or conventional treatment (oxygen therapy plus drugs). After 1 hour of NIV, respiratory rate, but not PaCO₂, showed a significant decrease. The group of patients treated with NIV had a significantly lower intubation rate, a lower complication rate (14% vs. 45%), length of hospital stay, and mortality rate. In another randomized study on 23 COPD patients that compared NIV with conventional treatment, the investigators reported a reduction of intubation rate, with a significant improvement in PaO₂, heart rate, and respiratory rate in the NIV group, even though PaCO₂ did not significantly decrease (90). A randomized study on 30 COPD patients with ARF (91) confirmed that early application of NIV facilitates gas exchange improvement, reduces the need for invasive mechanical ventilation, and decreases the duration of hospitalization. In a randomized trial on 50 acute COPD-E patients, NIV reduced weaning time, shortened the length of stay in the ICU, decreased the incidence of nosocomial pneumonia, and improved 60-day survival rates (99). Other and more recent prospective randomized controlled studies on patients with ARF due to COPD-E (103,104) have confirmed the benefit of applying NIV in improving clinical status and blood gases.

A randomized prospective study by Conti et al. (102) compared the short- and long-term response to face mask NIV versus invasive conventional ventilation in COPD patients with ARF failing to sustain the initial improvement with conventional medical therapy in the emergency department and needing ventilatory assistance. In this study, the intubation rate of 52% in the NIV group was higher than in other randomized controlled trials, which is not surprising given the higher severity of illness of these patients, as evidenced by the mean pH of 7.2, compared with 7.27 in the study of Brochard et al. (88) and 7.32 in the study of Plant et al. (87). Although the patients who received NIV were sicker than those reported in previous studies, they showed a trend toward a lower incidence of nosocomial pneumonia during the ICU stay and a better outcome at a 1-year follow-up, as well as no significant differences in ICU and hospital mortality, overall complications, duration of mechanical ventilation and ICU. These findings support early use of NIV during the course of acute exacerbation of COPD patients. However, if NIV is started later, after the failure of medical treatment, it is comparable to invasive mechanical ventilation in terms of survival.

TABLE 103.5 Main Randomized Controlled Studies Using Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease

In a matched case-control study conducted in ICU, 64 COPD patients with advanced ARF (pH ≤7.25, PaCO₂ ≥70 torr, and respiratory rate ≥35 breaths/min) prospectively received NIV, and their outcomes were compared with those of a control group of 64 COPD patients (105). NIV had a high rate of failure (40/64), although mortality rate, duration of mechanical ventilation, and lengths of ICU and post-ICU stay were not different between the two groups, and the NIV group had fewer complications. In this study, patients who failed NIV were not harmed by the delayed institution of invasive ventilation, and those who avoided endotracheal intubation had a clear-cut benefit. Based on these results, the authors suggested that in COPD patients with advanced ARF, it might be worthwhile to attempt a trial of NIV prior to a shift to invasive ventilation with endotracheal intubation.

In summary, NIV should be considered the first-line therapeutic option to prevent endotracheal intubation and improve outcome in patients with exacerbations of COPD who have no contraindication to NIV (see Table 103.3).

Asthma

NIV is considered an option in asthmatic patients at risk for endotracheal intubation. However, mechanical ventilation may be dangerous in patients with asthma, first, by worsening lung hyperinflation with the risk of causing barotrauma, and second, by inducing hemodynamic deterioration by increased intrathoracic pressure. To date, guidelines for NIV in severe asthma are not supported by strong data. In one study (106), only 2 of 17 severe asthmatic patients (average initial pH of 7.25 and PaCO₂ of 65 mmHg) required intubation after starting therapy with face mask PSV, and the use of NIV was associated with a rapid correction of gas exchange abnormalities and improvement in dyspnea. A retrospective analysis of 33 asthmatic patients treated with NIV or invasive mechanical ventilation (107) found that, although the NIV patients were less hypercapnic than the other group, gas exchange and vital signs improved rapidly in the NIV group, and only three patients eventually required endotracheal intubation. A prospective, randomized, placebo-controlled study compared 15 patients with acute asthma who received NIV plus conventional therapy versus conventional therapy alone, and found an improvement in lung function and decreased hospital admission rate in the NIV group (108). In contrast, another randomized trial found no significant advantages of NIV in patients with acute asthma (109), and medical therapy alone can be highly effective in the management of asthmatic patients (110). Therefore, in the absence of clear evidence, no conclusions can be drawn regarding the relative effectiveness of NIV versus conventional therapy in acute exacerbations of asthma.

Hypoxemic Respiratory Failure

Trials of NIV in patients with hypoxemic respiratory failure, defined as those with ARF not related to COPD, have yielded conflicting results. In hypoxemic ARF patients, NIV has been adopted to decrease the amount of work of breathing, correct the rapid shallow breathing, and prevent respiratory muscle fatigue and endotracheal intubation. The studies reviewed in these sections have been conducted on heterogeneous groups of patients with hypoxemic respiratory failure, whereas the analyses of homogeneous patient populations are discussed under each specific topic. Randomized controlled trials using NIV in hypoxemic ARF patients are shown in Table 103.6.

Meduri et al. (13) in 1989 reported one of the first clinical applications of NIV in patients with hypoxemic respiratory failure. Subsequently, Pennock et al. (116) reported a 50% success in a large group of patients with ARF of different causes, and similar good results were achieved using NIV with nasal mask in a second study (117). Wysocki et al. (111) randomized 41 non-COPD patients with ARF to NIV delivered by face mask versus conventional medical therapy. NIV reduced the need of endotracheal intubation, the duration of ICU stay, and mortality rate only in those patients with hypercapnia (PaCO₂ >45 mmHg), while having no significant advantages in the hypoxemic group without concomitant hypercarbia. On the basis of these results, the investigators concluded that NIV may not be beneficial in all forms of ARF not related to COPD. In a study conducted by Meduri et al. (118) on the use of NIV to treat respiratory failure of varied origins, 41 of 158 patients were hypoxemic. These patients required endotracheal intubation in only 34% of cases and showed a mortality rate of 22% compared with a predicted mortality (using the APACHE II score) of 40%. In a pilot study on patients with hematologic malignancies complicated by ARF (119), 15 of 16 individuals showed a significant improvement in blood gases and respiratory rate within the first 24 hours of nasal mask NIV treatment.

Antonelli et al. (20) conducted a prospective, randomized study comparing NIV via a face mask to endotracheal intubation with conventional mechanical ventilation in 64 patients with hypoxemic ARF who required ventilatory assistance after failure to improve with aggressive medical therapy. After 1 hour of mechanical ventilation, both groups had a significant improvement in oxygenation. Ten (31%) patients treated with NIV required endotracheal intubation. Patients randomized to conventional ventilation developed significantly more frequent septic complications such as pneumonia or sinusitis (31% vs. 3%). Among survivors, NIV patients had a lower duration of mechanical ventilation (p = 0.006) and a shorter ICU stay (p = 0.002). On the basis of these results, this trial suggested that NIV may lead to more favorable outcomes than conventional ventilation in the management of patients with hypoxemic respiratory failure. Conversely, Wood et al. (112) had a substantially negative evaluation of the use of NIV when applied to patients with hypoxemic ARF. These investigators randomized 27 patients in the emergency department to receive conventional medical therapy or NIV for the treatment of hypoxemic respiratory failure. The 16 patients who were randomized to the NIV group had an intubation rate and duration of ICU stay similar to the 11 patients who received medical treatment alone, but there was a trend toward a greater rate of hospital mortality among the patients in the NIV group compared to patients in the conventional medical therapy group. Several factors may have influenced these negative results of this study. Among patients requiring endotracheal intubation, those of the NIV group had a longer delay to intubation (26 vs. 4.8 hours, p = 0.055). In addition, it cannot be excluded that a sicker patient population was randomized to NIV. Indeed, the NIV population had a lower PaO₂ (60 vs. 71), fewer patients with COPD (12% vs. 36%), and more patients with pneumonia (44% vs. 18%), ARDS, and interstitial lung disease (1 vs. 0). Furthermore, the NIV group had a higher APACHE II score (18 vs. 16), and more required admission to an ICU (81% vs. 64%).

TABLE 103.6 Main Randomized Controlled Studies Using Noninvasive Ventilation I\In Nonchronic Obstructive Pulmonary Disease

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