Claudia Crimi, MD*
Science Institute of Pavia
Fondazione S.Maugeri, IRCCS
Pavia, Italy

Endotracheal intubation and invasive mechanical ventilation, though lifesaving in critical care settings, are related to complications that may prolong hospital stay and increase the risk of death. For example, invasive ventilatory support increases the risk of nosocomial pneumonia by 1% per day.1 Continuous intravenous sedation is associated with prolonged mechanical ventilation and the possible need for heavy sedation or chemical paralysis or relaxation may be responsible for generalized myopathy.1,2

All these complications, directly or indirectly, relate to invasive mechanical ventilation and may per se explain the poor prognosis of mechanically ventilated patients. A physician’s goal must be to minimize the duration of invasive mechanical support. Standardized weaning protocols may improve outcomes and reduce costs compared with traditional physician-directed weaning.3,4 The most popular weaning methods involve getting the patient to breathe through the endotracheal tube while supplemental oxygen is administered (a T-piece trial) or giving the patient only modest assistance from the ventilator (pressure support or continuous positive airway pressure [CPAP]). Both are effective as weaning strategies; confidence with the adopted technique is likely more important than the chosen method.

Weaning With Noninvasive Ventilation
Nearly 41% of the time spent on mechanical ventilation is devoted to weaning.5 For patients affected by chronic obstructive pulmonary disease (COPD), cardiac failure or neurological problems, the number reaches closer to 50%. A weaning failure is associated with an increased risk of death, prolonged intensive care unit (ICU) stay, and transfer to long-term facilities.6

Physiologically, noninvasive ventilation (NIV) may counteract the mechanisms associated with weaning failure by reducing the work of breathing, decreasing the negative deflections of intrathoracic pressure,7 and improving hypoxemia and hypercapnia, even if no effects on ventilation/perfusion mismatch have been demonstrated.8 Invasive and noninvasive pressure supports are equally effective in reducing diaphragm efforts and improving arterial blood gases in COPD patients. Therefore, NIV may be used as a “full alternative” for invasive ventilation as an attempt to shorten the duration of intubation.9

A few anecdotal preliminary studies suggest that the use of NIV may facilitate the weaning process in “difficult-to-wean patients.” A randomized controlled study performed in severe COPD patients showed that the likelihood of weaning success increases, while the duration of mechanical ventilation and ICU stay decreases when using NIV as a weaning technique.10 A French study conducted on patients intubated for acute respiratory failure due to COPD or restrictive diseases confirmed this theory. It showed a shorter duration of invasive mechanical ventilation using NIV versus traditional weaning.11 However, no differences in terms of ICU and hospital length of stay or in three-month survival were found between the two techniques.

In a randomized controlled trial,12 Ferrer compared NIV with conventional weaning in patients with “persistent” weaning failure, showing that using NIV produced a significant reduction in duration of mechanical ventilation as well as ICU and hospital length of stay. However, no difference in the incidence of reintubation between the two techniques was reported. Patients treated with NIV had a minor incidence of serious complications and better ICU and 90-day survival rates.
 

Some small and not randomized trials have been performed using NIV for weaning trauma patients with hypoxemic respiratory failure13 and non-COPD patients with persistent acute respiratory failure after early extubation.14 However, based on these studies, NIV is not recommended as a weaning strategy in severely hypoxic patients.

NIV and Post-Extubation Failure
Prevention. Post-extubation failure is a major clinical problem in the ICU.15 Extubation attempts may fail in as many as 23.5% of patients, and the in-hospital mortality of these patients may reach 30% to 40%.16 The cause of extubation failure and the time elapsed before reintubation are independent predictors of outcome.17

A few studies have evaluated the use of NIV as a means to prevent, rather than to treat, post-extubation respiratory failure. Jiang et al conducted a prospective study on 93 patients randomized to receive NIV or oxygen therapy after planned or unplanned extubation.18 Researchers found no difference in the reintubation rate between the two groups. Epstein et al showed that there is a certain subset of patients whose clinical characteristics at the time of extubation may predict reintubation. Based on this information, two randomized trials were performed to assess whether NIV is effective in preventing the occurrence of post-extubation failure in patients at risk.19 Both studies adopted similar criteria to define patients at risk and had comparable study designs. Both showed that the groups treated with NIV had a lower rate of reintubation than the groups treated with standard therapy. In one of the two studies,20 ICU mortality was also reduced in hypercapnic patients treated with NIV.

Treatment. NIV has been suggested in an attempt to avoid re-intubation in patients that show signs of “incipient” or even overt respiratory failure following extubation. Hilbert et al demonstrated that, when compared to conventional treatment of matched subjects, NIV improved the outcome of patients with COPD and post-extubation hypercapnic respiratory failure by reducing the need for endotracheal intubation, by reducing the mean duration of ventilatory assistance, and by reducing the duration of ICU stay.21

In a more recent randomized controlled trial, patients who developed acute respiratory failure within 48 hours after extubation were randomized to receive standard medical therapy alone or NIV.22 The authors did not find any difference in the reintubation rate, in the hospital mortality rate, or in the ICU and hospital stay, despite a trend that showed a shorter duration of hospital stay in the NIV group.

Recently, Esteban et al conducted a large multicenter, randomized trial to evaluate the effect of NIV on mortality in this clinical setting.23 Patients who had respiratory failure within the subsequent 48 hours were assigned randomly to either NIV or standard medical therapy. There was no difference between the two groups in the need for reintubation, while ICU mortality was higher in the NIV group (25% vs.14%; relative risk=1.78). The median time from respiratory failure to reintubation was longer in the NIV group, raising the doubt that delayed reintubation may have influenced the negative results. The authors concluded that NIV does not prevent the need for reintubation or reduce mortality in unselected patients with respiratory failure after extubation. It is noteworthy that NIV was used as a “rescue” therapy in patients who failed standard therapy, and the rate of success was much higher than in the NIV group.

Future Use of NIV
Solid evidence suggests that NIV may be used in the weaning process of a selected population of stable hypercapnic patients to shorten the length of invasive mechanical ventilation. The role of NIV in all the other populations (e.g., hypoxic patients and post-surgical patients) remains unclear. Randomized controlled studies have demonstrated that
NIV may even be harmful to treat an overt episode of postextubation respiratory failure, while promising results were obtained in using NIV to prevent reintubation in the subset of patients considered at risk.

References

1. Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D and Sherman G.  The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest 1998;114:541.
2. Berek K, Margreiter J, Willeit J, Berek A, Schmutzard E, Mutz NJ.  Polyneuropathies in critically ill patients: a prospective evaluation.  Intensive Care Med. 1996;22:849.
3. Kollef MH, Shapiro SD, Silver P, St.John RE, Prentice D, Sauer S, Ahrens TS, Shannon W, Baker-Clinkscale D.  A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit.Care Med. 1997;25:567.
4. Ely EW.  Challenges encountered in changing physicians’ practice styles: the ventilator weaning experience.  Intensive Care Med. 1998;24:539.
5. Esteban A., Alia I., Ibanez J., Bonito S., Tobin MJ. Modes of mechanical ventilation and weaning: a national survey of Spanish hospitals. Chest 1994; 106: 1188.
6. Epstein SK, Ciubataru RL and Wong JB.  Effect of failed extubation on the outcome of mechanical ventilation.  Chest 1997;112:186.
7. Diaz O, Iglesia R, Ferrer M, et al. Effects of noninvasive ventilation on pulmonary gas exchange and emodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:1840.
8. Vitacca M, Ambrosino N, Clini E, Porta R, Rampulla C, Lanini B, Nava S.  Physiological response to pressure support ventilation delivered before and after extubation in patients not capable of totally spontaneous autonomous breathing. Am J Respir Crit Care Med. 2001 Aug 15;164(4):638.
9. Udwadia ZF, Santis GK, Steven MH, Simonds AK.  Nasal ventilation to facilitate weaning in patients with chronic respiratory insufficiency. Thorax 1992;47:715.
10. Girault C, Daudenthun I, Chevron V, Tamion F, Leroy J, Bonmarchand G. Noninvasive ventilation as a systematic extubation and weaning technique in acute-on-chronic respiratory failure. A prospective, randomized controlled study. Am J Respir Crit Care Med 1999; 160:86.
11. Ferrer M, Esqinas A, Arancibia F et al. Noninvasive ventilation during persistent weaning failure. Am J Respir Crit Care Med 2003; 168:70.
12. Gregoretti C, Beltrame F, Lucangelo U, Burbi L, Conti G, Turello M, Gregori D.  Physiologic evaluation of non-invasive pressure support ventilation in trauma patients with acute respiratory failure. Intensive Care Med. 1998;24:785.
13. Kilger E, Briegel J, Haller M, Frey L, Schelling G, Stoll C, Pichler B, Peter K. Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficienzy after early extubation. Intensive Care Med. 1999; 25:1374.
14. Torres A, Gatell JM, Aznar E, el-Ebiary M, Puig de la Bellacasa J, Gonzales J, Ferrer M, Rodriguez-Roisisn R.  Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.  Am J Respir Crit Care Med.  1995;152:137.
15. Torres A, Gatell JM, Aznar E, el-Ebiary M, Puig de la Bellacasa J, Gonzales J, Ferrer M, Rodriguez-Roisisn R.  Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.  Am J Respir Crit Care Med.  1995;152:137.
16. Epstein SK, Ciubataru RL and Wong JB.  Effect of failed extubation on the outcome of mechanical ventilation.  Chest 1997;112:186.
17. Espstein SK and Ciubotaru RL.  Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation.  Am J Respir Crit Care Med.  1998;158:489.
18. Jiang JS, Kao SJ and Wang SN. Effect of early application of biphasic positive airway pressure on the outcome of extubation in ventilator weaning. Respirology 1999; 4: 161.
19. Nava S, Gregoretti C, Fanfulla F, Squadrone E, Grassi M, Carlucci A, Beltrame F, Navalesi P: Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Crit Care Med. 2005;33:2465.
20. Ferrer M, Valencia M, Nicolas JM, Bernadich O , Badia JR, Alarcon A, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:164.
21. Hilbert G, Gruson D, Gbikpi-Benissan G, Cardinaud JP.  Sequential use of noninvasive pressure support ventilation for acute exacerbations of COPD.  Intensive Care Med.  1997;23:955.
22. Keenan SP, Powers C, McCormack DG, Block G. Noninvasive Positive-Pressure Ventilation for postextubation Respiratory Distress. JAMA 2002; 287:3238.
23. Esteban A, et al. Non-invasive positive pressure ventilation foe respiratory failure after extubation. New Eng J Med 2004. 10;350(24):2452.

Disclosures
*Author has no disclosures to report.