Abstract
Rationale: Patients who fail noninvasive ventilation are generally intubated and are then subjected to complications of invasive mechanical ventilation. With transtracheal open ventilation, ventilator support is delivered through an uncuffed small bore minitracheostomy tube, which eliminates pooling of secretions above the cuff and thus reduces the risk of tracheobronchial microbial colonization.
Objective: To compare transtracheal open ventilation (treatment group) with conventional invasive ventilation (control group) in patients with exacerbation of chronic obstructive pulmonary disease who initially failed noninvasive ventilation.
Methods: Patients were randomized to receive trans-tracheal open ventilation (n = 19) or conventional invasive ventilation (n = 20).
Measurements and Main Results: There was no difference in arterial blood gases after 1 and 30 h between the two groups. Two patients receiving transtracheal open ventilation and 13 undergoing conventional ventilation had complications (p < 0.0001). Compared with conventional ventilation, transtracheal open ventilation significantly decreased both the duration of mechanical ventilation (7.6 ± 4.7 vs. 18.6 ± 10.6 d, p < 0.0001) and length of stay in the intensive care unit (10.2 ± 4.5 vs. 21.3 ± 9.7 d, p < 0.0001).
Conclusions: Transtracheal open ventilation was as effective as conventional ventilation in maintaining adequate gas exchange and reducing complications, duration of mechanical ventilation, and intensive care unit length of stay.
In hypercapnic acute respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive ventilation (NIV) improves gas exchange, relieves respiratory distress, and reduces the need for endotracheal intubation (1–6). The rate of NIV failure, however, remains high both in case series and randomized controlled trials (1–9) and may exceed 50% in the most severe patients (8, 9). Frequent causes of NIV failure are ineffective ventilatory support, difficult management of secretions, air leaks, and mask intolerance, leading to patient discomfort (7–9). Because patients who fail NIV are commonly intubated and mechanically ventilated, they are exposed to complications and side effects of invasive mechanical ventilation, including ventilator-associated pneumonia.
The use of a cuffless small-bore tracheotomy tube was initially introduced to treat postoperative sputum retention (10). More recently, the use of pressure-controlled ventilation through a minitracheotomy tube has been reported as an alternative method to provide mechanical ventilatory assistance (11–14), a technique referred to as transtracheal open ventilation (13). As opposed to NIV, transtracheal open ventilation is free of mask-related side effects and may facilitate clearance of secretions. As opposed to endotracheal invasive ventilation, where secretions are pooled above the cuff, transtracheal open ventilation might reduce the risk of tracheal microbial colonization (15, 16). In addition, by preserving glottic function, transtracheal open ventilation may allow spontaneous expectoration.
We hypothesized that in patients with COPD with hypercapnic acute respiratory failure who fail NIV, transtracheal open ventilation might be used to provide effective ventilatory assistance, while avoiding the risks of invasive mechanical ventilation. We therefore designed a randomized controlled trial aimed at comparing transtracheal open ventilation and conventional endotracheal ventilation in patients with COPD with hypercapnic acute respiratory failure who had previously failed NIV.
Some of the results of this study have been previously reported in the form of an abstract (17).
All patients who received NIV for acute respiratory failure from COPD exacerbation at the intensive care unit (ICU) of S. Luigi Gonzaga University Hospital (Orbassano) between October 1997 and January 1999 and failed were considered eligible. (More details are presented in the online supplement.)
The criteria for NIV failure and exclusion criteria were predefined.
The study protocol was approved by the hospital's ethics committee. All patients gave written, informed consent at the time they started noninvasive ventilation; moreover, patients who failed noninvasive ventilation and did not meet exclusion criteria were requested to verbally confirm their consent before being randomized to one group.
Patients who satisfied the predefined criteria and gave informed consent were randomly assigned to receive conventional ventilation or transtracheal open ventilation.
The enrolled patients were randomly allocated using a computer-generated sequence to the following groups:
Conventional ventilation group (control group): patients were orally intubated and mechanically ventilated in volume-controlled mode. Sedation was maintained for 12 h. When spontaneous breathing resumed, patients were switched to pressure support ventilation. All patients were weaned off the ventilator and eventually extubated according to predefined criteria (18, 19).
Transtracheal open ventilation (treatment group): patients underwent percutaneous minitracheotomy and a 4-mm internal diameter, 10-cm length (Mini-Trach II; Portex Limited, Hythe, England) was left in place. Patients were ventilated using high levels of assisted pressure-controlled ventilation (11–14). Criteria for transtracheal open-ventilation weaning had been predefined (13).
The primary endpoints were improvement in gas exchange and rate of serious complications. Arterial blood gases were determined at the time of NIV failure (baseline), 1 h, and 30 h after the onset of conventional and transtracheal open ventilation and at least once daily thereafter or whenever clinically warranted. Improvement in arterial blood gases was defined by an increase of 0.1 or more in arterial pH, a reduction of 10% or more in PaCO2 and a rise of 20% or more in PaO2/FiO2, with respect to baseline. Patients were monitored for the development of infections and other complications, including those related to the insertion and the maintenance of the minitracheotomy tube (20–24). Secondary endpoints were the duration of mechanical ventilation, the length of ICU stay, rate of patients who underwent tracheostomy, ICU mortality, and mortality at 60 d after ICU discharge, regardless of patient location.
Based on previously published studies (3) and on retrospective observations from a database of patients treated in the same ICU, the study was powered to ascertain a reduction in the rate of serious complications from 60 to 20%, with a 5% risk of type I error and a power of 80%, which required recruiting 19 patients in each group.
Results are reported as mean ± SD. The statistical analysis was performed with the SAS software (SAS Institute, Cary, NC). Data were compared between the two groups using the two-tailed unpaired t test for continuous data and the Fisher's exact test, as indicated. A p value < 0.05 was considered significant.
One hundred seventy-eight patients were admitted to the ICU during the 28-mo study. Ninety-eight patients (55.5%) met the exclusion criteria for NIV, whereas 80 patients (45.5%) underwent NIV. All patients accepted to participate in the study. Twenty-five patients (31.3%) improved, whereas 55 patients (68.7%) failed NIV. Sixteen patients were excluded from the study. The exclusion criteria were lack of cooperation, including agitation and mild to moderate altered mental status (n = 10) and need for immediate intubation (n = 6). All remaining 39 patients confirmed their intention to participate in the study. Nineteen patients were randomized to the transtracheal open-ventilation group (treatment group) and 20 in the conventional ventilation group (control group).
There were no significant differences in patients' characteristics between intervention and control group at study entry. Figure 1 shows a patient on transtracheal open ventilation.
As shown in Figure 2, the patients from both groups had similar changes in their blood gases after 1 h. When arterial blood gases were analyzed for the predefined criteria of improvement after 1 h versus baseline, there was no significant difference in the number of patients who entered the predefined criteria (19 patients [100%] in the transtracheal open-ventilation group and 17 [85%] in the control group, p = 0.23). Eighteen and nineteen patients in the transtracheal open-ventilation and control groups, respectively, were able to trigger the ventilator after 30 h. Of these, the rate of patients who improved arterial blood gases at the 30th hour versus baseline was not significantly different between the two groups (100 and 89% in the transtracheal open-ventilation and control groups, respectively; p = 0.63).
Figure 2. Arterial blood gas (PaO2, PaCO2, and pH) at baseline and after 1 h, for the treatment (transtracheal open ventilation, TOV) and control (endotracheal invasive ventilation, EIV) group.
[More] [Minimize]Group mean values for ventilator settings, arterial blood gases and respiratory rate after 30 h are presented in Table 1.
Treatment Group (n = 18) | Control Group (n = 19) | p Value | |
|---|---|---|---|
| pH | 7.45 ± 0.05 | 7.40 ± 0.06 | 0.009 |
| PaCO2, mm Hg | 47.8 ± 6.3 | 50.3 ± 8.5 | 0.31 |
| PaO2, mm Hg | 89.8 ± 18.4 | 92.5 ± 16.9 | 0.64 |
| FIO2 | 0.44 ± 0.05 | 0.5 ± 0.06 | 0.002 |
| PaO2:FIO2 | 205.3 ± 48.2 | 186.5 ± 42.9 | 0.21 |
| HCO3−, mmol/L | 34.7 ± 6 | 33.6 ± 5.1 | 0.55 |
The respiratory rate was not comparable after 1 h because the patients in the control group were still receiving controlled mechanical ventilation at that time. After 30 h, the spontaneous breathing frequency was 20.6 ± 3.3 in the control group versus 22.2 ± 2.9 in the transtracheal open-ventilation group (p = 0.12).
As outlined in Table 2, the proportion of patients presenting with one or more complications was significantly lower with transtracheal open ventilation, compared with conventional ventilation (p < 0.0001). In particular, 13 of 20 patients in the control group, as opposed to none in the treatment group, developed ventilator-associated pneumonia (p < 0.0001). No complication specifically related to the minitracheotomy was observed.
Treatment Group (n = 19) | Control Group (n = 20) | |
|---|---|---|
| Patients with complications, no. (%) | 2 (10.5) | 13 (65) |
| Patients with complications leading to death in ICU, no. | 1 | 5 |
| Complications, total no*/no. causing death in ICU | 2/1 | 25/5 |
| Myocardial infarction or cardiogenic shock | 1/1 | 2/2 |
| Pleural effusion | 1/0 | 5/0 |
| Sepsis | 0/0 | 1/1 |
| Ventilator-associated pneumonia | 0/0 | 13/0* |
| Pulmonary embolism | 0/0 | 2/2 |
| Renal failure | 0/0 | 2/0 |
One patient in the transtracheal open-ventilation group required conventional ventilation after 9 h because of the lack of improvement in arterial blood gases.
Duration of mechanical ventilation (7.6 ± 4.7 vs. 18.6 ± 10.6 d, for transtracheal open-ventilation and control groups, respectively; p < 0.0001) and length of ICU stay (10.2 ± 4.5 vs. 21.3 ± 9.7 d for transtracheal open-ventilation and control groups, respectively; p < 0.0001) were significantly reduced in the transtracheal open-ventilation group. Of interest, the patients in the control group who developed pneumonia spent significantly more days on mechanical ventilation (p < 0.0001) and in ICU (p < 0.0001) than those who did not.
Of the 18 patients who succeeded in transtracheal open ventilation, 15 patients had the minitracheotomy tube removed in the ICU and three patients 1 wk after ICU discharge. No patients underwent tracheostomy in the transtracheal open-ventilation group, whereas 10 patients were tracheostomized in the control group (p = 0.0004).
One (5%) and five (25%) patients in the transtracheal open ventilation and in the control group died in the ICU (p = 0.18). The patient who died in the treatment group was the same who failed transtracheal open ventilation and required endotracheal intubation. He died of myocardial infarction without developing pneumonia. All patients who died in the control group had early or late ventilator-associated pneumonia. Patients who developed pneumonia had a significantly higher mortality rate (p = 0.018) than those who did not. In both groups, all the patients who survived were successfully weaned off mechanical ventilation. At 60 d after ICU discharge, one patient in the transtracheal open-ventilation group and three in the control group died (p = 0.31).
The main findings of the present study were that transtracheal open ventilation was as effective as conventional ventilation in improving gas exchange both after 1 and 30 h and that the proportion of patients presenting one or more complications was significantly lower with transtracheal open ventilation compared with conventional mechanical ventilation. Furthermore, the patients who received transtracheal open ventilation spent significantly fewer days on mechanical ventilation and in the ICU than those who underwent conventional ventilation. Although several observational and physiologic studies have demonstrated the feasibility and the potential advantages of open ventilation (11–14), this is, to our knowledge, the first randomized controlled trial showing the clinical benefits of delivering mechanical ventilation through an uncuffed tube, compared with the conventional approach based on the use of a cuffed tube.
Because of the high resistance of the small-bore tube and of the air leaks through the upper airway, the pressure distending the lung during transtracheal open ventilation is actually much less than the pressure applied to the airway opening (11–14, 25–27). Uchyiama and colleagues found that a preset inspiratory pressure of 50 cm H2O resulted in an actual tracheal pressure of 4–5 cm H2O (13). In addition, because glottis aperture (and leaks) may vary between breaths, tracheal pressure also varies breath by breath (14). With transtracheal open ventilation, exhalation predominantly occurs through the native upper airways, which decreases the amount of hyperinflation and intrinsic positive end-expiratory pressure secondary to the increase in expiratory resistance caused by the cuffed endotracheal tube (28, 29).
PaCO2 and respiratory rate were not significantly different between the control group and the transtracheal open-ventilation group, suggesting that alveolar ventilation was also not different. As with NIV, glottis function is preserved with transtracheal open ventilation and the patient is allowed to cough, speak, and eat without risk of aspiration (30). However, for these actions to take place with transtracheal open ventilation, the ventilatory support does not need to be withdrawn and may be continuously provided. This is in contrast to NIV in which the mask discomfort may also limit the number of hours of assistance. Moreover, transtracheal open ventilation is preferable to NIV because the patients who are not able to clear secretions can be promptly suctioned through the tube.
Transtracheal open ventilation, however, cannot be considered a noninvasive form of mechanical ventilation because it requires a percutaneous minitracheotomy that, although relatively free of complications, still requires an invasive procedure to be performed by qualified personnel (31).
Endotracheal intubation is considered the single most important predisposing factor for ventilator-associated pneumonia (15, 32). Compared with other studies (6, 8), the incidence of ventilator-associated pneumonia in our study was quite elevated. However, the definitions and diagnostic criteria for ventilator-associated pneumonia are still debated and may vary from one study to the other (32). In the control group, ventilator-associated pneumonia occurred on Day 4 in three patients; on Day 8 in two patients; and on Days 5, 6, 7, 9, 10, 11, 12, and 13 in individual patients. Pneumonia was caused by Pseudomonas aeruginosa in seven patients, methicillin-resistant Staphylococcus aureus in three patients, and Acinetobacter spp. in the remaining three patients. Similarly to NIV, which, compared with control group, has been demonstrated to avert ventilator-associated pneumonia (6–8), none of the patients in our study who received transtracheal open ventilation developed ventilator-associated pneumonia. Indeed, there is increasing recognition that the inflated cuff, rather than the endotracheal tube itself, represents the major source of risk for ventilator-associated pneumonia (33). In fact, pooling of secretions above the inflated balloon represents a source of colonization of bacteria, which may be aspirated in the lungs through the incompletely occluding seal of the cuff, determining soiling of the lower airway (33). Furthermore, during transtracheal open ventilation, the patient whose glottis function is entirely preserved can spontaneously clear the airway.
The number of invasive medical devices is also an important determinant for the pathogenesis and development of ventilator-associated pneumonia (34). There was no significant difference in the number of medical devices used between the two groups.
The patients in the transtracheal open-ventilation group had shorter duration of mechanical ventilation and spent fewer days in the ICU. Indeed, the reduced rate of pneumonia allowed an overall shorter period of mechanical ventilation and concomitantly decreased the need for ICU stay.
Although a limitation for a randomized controlled trial, we preferred to limit this study to a single center because transtracheal open ventilation is a novel method of ventilation with unusual specific features, requiring an experienced and well-trained staff. Caution is also advisable in extrapolating our results to patient populations other than those with COPD with acute exacerbation and in particular to patients with low respiratory system elastance who require high inspiratory airway pressure.
In conclusion, in patients with hypercapnic acute respiratory failure from COPD exacerbation who had initially failed NIV, compared with conventional invasive ventilation, transtracheal open ventilation was equally effective in maintaining adequate gas exchange, but significantly reduced the rate of serious complications and decreased duration of mechanical ventilation and ICU length of stay. Although not free of invasiveness, transtracheal open ventilation may offer a unique opportunity to avoid conventional ventilation in patients with COPD failing NIV. Further multicenter randomized controlled trials are necessary to confirm these results.
The authors thank Jennifer Beck who carefully revised the manuscript.
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