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Weaning failure in critical illness 

Weaning failure in critical illness
Weaning failure in critical illness

Annalisa Carlucci

and Paolo Navalesi

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date: 03 December 2020

Key points

  • Weaning failure is defined as either unsuccessfull mechanical ventilation discontinuation or extubation failure.

  • Both are associated with increased morbidity and mortality.

  • An impaired balance between respiratory muscles force and respiratory system impedance (load) is the main cause of weaning failure. Weak cough and increased upper airway resistances are also implicated in the aetiology of extubation failure.

  • A systematic approach to assess readiness by means of a spontaneous breathing trial is crucial to reduce the risk of extubation failure.

  • In selected cases, non-invasive ventilation and intensive physiotherapy may facilitate discontinuation of mechanical ventilation and avert extubation failure.

Definition and outcome

Weaning failure has been defined as either failure to discontinue mechanical ventilation or a need for re-intubation within 48–72 hours after extubation (extubation failure) [1]‌.

The former is generally assessed as an inability to breath spontaneously through an endotracheal tube for a relatively short period of time, commonly 30–120 minutes, the so-called spontaneous breathing trial (SBT) [1]‌. SBT failure is predominantly consequent to an excessive load for the capacity of the respiratory muscles [1].

Extubation failure encompasses a more complex phenomenon. On the one hand, it can be consequent to the incapacity to maintain the spontaneous unassisted breathing after removal of the endotracheal tube, suggesting an increase of the load imposed on the respiratory muscles after extubation. On the other hand, it can be due to the inability to maintain patent the upper airway without necessarily requiring mechanical ventilation or to incapacity to adequately clear secretions [1]‌.

Both discontinuation and extubation failure constitute major clinical and economic burdens. Failure to discontinue mechanical ventilation is associated with increased morbidity and mortality. In particular, patients who require more than 7 days of mechanical ventilation after the first attempt of withdrawal are characterized by a high rate of death [2]‌. Extubation failure is also associated with an increased risk of death, ranging between 40 and 50% [3], which is correlated with the aetiology of extubation failure and the delay in re-intubation [4]. A high incidence of pneumonia and clinical deterioration before re-intubation are considered to play a predominant role in worsening outcome [1,2,3]. Table 103.1 summarizes the major causes of weaning failure.

Table 103.1 Causes of weaning failure

Weaning failure

MV discontinuation failure

Extubation failure


  • Increased load (respiratory system impedance):

    • Increased airway resistance

    • Reduced respiratory system compliance

    • PEEPi

  • Decreased respiratory muscle force:

    • Neuromuscular disease

    • ICU-acquired CINM

    • Prolonged controlled MV

    • Hyperinflation

    • Poor nutritional status

  • Cardiac dysfunction

  • Cerebral dysfunction:

    • Altered consciousness

    • Psychological and psychiatric disorders (delirium, depression)

    • Sedation

  • Deteriorated force/load balance

  • Increased upper airway resistance:

    • Laryngeal inflammation

    • Laryngeal oedema

    • Tracheal obstruction (stenosis, granuloma)

  • Inability to clear secretions

MV, mechanical ventilation; PEEPi, auto- or intrinsic positive end-expiratory pressure; ICU, intensive care unit; CINM, critical illness neuro-myopathy.


The time for weaning accounts for 40–50% of the total duration of mechanical ventilation, depending on the reason for initiating mechanical ventilation [1]‌. In a recent observational multicentre study including 2714 intubated patients who met criteria for weaning readiness, 45% failed at least one attempt. Of these patients, 39% were extubated within 7 days (difficult weaning) and 6% after 7 days (prolonged weaning) after the first attempt [2].

Extubation failure is reported to be as high as 15–18% of planned extubations; about one-third of extubation failures occurs within the first 12 hours and approximately two-thirds within the first 24 hours [1,4].

Causes of failure of mechanical ventilation discontinuation

Readiness for discontinuation of mechanical ventilation is commonly assessed, when overall clinical stability is achieved, which implies that all the acute problems are overcome, the patient is haemodynamically stable, a high FiO2 is not required, positive end-expiratory pressure (PEEP) values not exceeding 5 cmH2O are used, and comfortable breathing and adequate gas exchange are obtained with no or minimal (7–8 cmH2O) inspiratory support [1]‌.

Discontinuation failure may depend on a multiplicity of factors and is often consequent to more than one single cause. Irrespective of the underlying disorder leading to the need for mechanical ventilation, the most common mechanism is an unfavourable balance between the force generating capacity of the respiratory muscles and the load they must face [1,5]. Any treatment able to reduce the load and/or to augment muscle force may favour discontinuation success [5]‌. A highly unfavourable unbalance between force and load represents the most common cause of early SBT failure, which is sometimes unpredictable when the patient receives even a minimal assistance. Indeed, an inspiratory support as low as 5 cmH2O can reduce the respiratory work by nearly 40% [6].

Failure can occur later in the course of the trial. Sometimes an inspiratory load that is tolerable at the beginning of the trial increases throughout the SBT. In a series of chronic obstructive pulmonary disease (COPD) patients undergoing SBT, Jubran et al. found that that airway resistance significantly increased throughout the trial (from 9 ± 2 cmH2O to 15 ± 2 cmH2O) within 45 minutes in the patients who failed, while it did not vary in those who succeeded [7]‌. The increase in pulmonary resistance in the course of the SBT may suggest a mechanism related to the cardio-pulmonary interaction [7]. In fact, a remarkable increase of the inspiratory negative intrathoracic pressure swings leads to a rise in both cardiac preload (i.e. venous return) and afterload (i.e. left ventricular transmural pressure), which may cause pulmonary congestion and oedema of the bronchial wall, and consequently worsens pulmonary mechanics and increases the magnitude of the load imposed on the respiratory muscles. Thus, an unrecognized or latent cardiac dysfunction can become evident when interrupting the ventilator support to resume spontaneous breathing [1].

A critical reduction of the force-generating capacity of the respiratory muscles may also lead to a failure to discontinue mechanical ventilation. This is quite common in mechanically-ventilated patients with neuromuscular diseases. Besides, the respiratory muscles can be weakened because of ICU-acquired critical illness neuromyopathy (CINM), which may occur as a complication of sepsis and multiple organ failure, hyperglycaemia and in patients receiving neuromuscular blocking agents for days, aminoglycosides, and/or steroids [8]‌. Also, diaphragm disuse atrophy complicates the clinical course of patients undergoing controlled mechanical ventilation. After 5–6 days of controlled mechanical ventilation the force-generating capacity of the diaphragm was found to be reduced by two-third [9]. This was associated with histobiochemical signs of diaphragmatic injury and atrophy, with a significant correlation between duration of mechanical ventilation and magnitude of diaphragmatic injury [9]. A physiological study performed on patients who had received prolonged mechanical ventilation showed that the recovery from inspiratory muscle weakness is a major determinant of ‘late’ weaning success [10]. A poor nutritional status may also play a role in decreasing muscle force [1]. Finally, in patients with lung hyperinflation because of diseases causing prolonged expiratory time constant and/or expiratory flow limitation, such as asthma and COPD, the force-generating capacity of the diaphragm is reduced because the muscle fibres, though well-functioning, are already shortened at end expiration [11].

Cerebral dysfunctions affecting the level of consciousness [12] or determining psychological or psychiatric disorders, such as ICU-acquired delirium and depression may contribute to discontinuation failure [1]‌.

Causes of extubation failure

Any of the causes of discontinuation failure may also be implicated in the pathogenesis of extubation failure. This holds especially true whenever readiness for discontinuation of mechanical ventilation is not systematically tested with a SBT [6,12].

In some cases, after removal of the endotracheal tube, the inspiratory load may rise up consequent to an increase in upper airway resistance due to laryngeal inflammation and oedema. However, a physiological study showed that the work of breathing necessary to overcome supraglottic airway resistance soon after extubation is on average rather close to that formerly imposed by the endotracheal tube [13]. In patients with prolonged intubation complications leading to tracheal obstruction, such as tracheal stenosis, granuloma, and tracheomalacia may also cause extubation failure [14].

In patients successfully completing SBT, weak cough and the inability to clear secretions may afterwards cause extubation failure not predicted by the conventional parameters used to assess readiness for discontinuation of mechanical ventilation [1]‌. In a prospective study on 115 patients who passed the SBT and were ready to be extubated, a peak expiratory flow during glotic-free cough ≤60 L/min was associated with a five-fold increase in extubation failures [15].

Preventing strategies

Although conventionally considered as a specific period of the time spent on mechanical ventilation, the process of weaning should start as soon as mechanical ventilation is instituted and include any intervention aimed at facilitating resumption of spontaneous breathing through the native airway. If, on the one hand, discontinuation of mechanical ventilation and extubation should be considered as soon as possible to avoid the consequences of unnecessary prolonged intubation, on the other hand, because of their detrimental consequences, both discontinuation and extubation failures must be prevented.

The methodology used to assess readiness for withdrawal of mechanical ventilation and extubation is crucial. A systematic approach to determine readiness utilizing standardized meaningful physiological and clinical criteria may improve weaning and extubation outcome [12]. Assessing readiness by means of the SBT represents a cornerstone of this process. Anyhow, the wide variability of the methods used to perform the SBT, i.e. T-piece trial, minimal levels of CPAP and low values of inspiratory support, may affect the SBT outcome [2]‌.

Based on the aforementioned experimental data, although never proved by clinical studies, a rapid switch from controlled to assisted modes of mechanical ventilation should in principle reduce the risk of diaphragm atrophy and injury. The ventilator settings are also important. Unnecessarily high levels of mechanical support may result in excessively low patient’s respiratory drive and effort, which is associated with poor patient-ventilator interaction and increased risk of prolonged mechanical ventilation [16]. Avoiding excessive sedation can also improve the outcome of weaning [17].

In some patients with underlying chronic respiratory disorders intubated for treatment of severe hypercapnic acute on chronic respiratory failure, an early extubation followed by immediate application of non-invasive ventilation (NIV) may help to speed up the process of discontinuation, while reducing the risk of developing ventilator associated pneumonia [18].

NIV can be also successfully used to decrease the re-intubation rate in patients at increased risk of extubation failure, such as those with underlying chronic or cardiac disorders, prior weaning failure, and numerous comorbidities [19]. In particular, in patients who develop hypercapnia during the SBT, prophylactic application of NIV at extubation reduces the rate of re-intubation and mortality [20].

In patients at risk of developing extubation failure because of ineffective clearing of secretions, intensive physiotherapy may be helpful. The use of mechanical cough assistance may prevent extubation failure consequent to sputum retention, especially in patients with weak cough [1]‌.


1. Boles JM, Bion J, Connors A, et al. (2007). Weaning from mechanical ventilation. European Respiratory Journal, 29, 1033–56.Find this resource:

2. Peñuelas O, Frutos-Vivar F, Fernández C, et al. (2011). Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. American Journal of Respiratory and Critical Care Medicine, 184, 430–7.Find this resource:

3. Thille AW, Harrois A, Schortgen F, Brun-Buisson C, and Brochard L. (2011). Outcomes of extubation failure in medical intensive care unit patients. Critical Care Medicine, 39, 2612–18.Find this resource:

4. Epstein SK and Ciubotaru RL. (1998). Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. American Journal of Respiratory and Critical Care Medicine, 158, 489–93.Find this resource:

5. Vassilakopoulos T, Zakynthinos S, and Roussos C. (1998). The tension-time index and the frequency/tidal volume ratio are the major pathophysiologic determinants of weaning failure and success. American Journal of Respiratory and Critical Care Medicine, 158, 378–85.Find this resource:

6. Tobin MJ. (2012). Extubation and the myth of ‘minimal ventilator settings’. American Journal of Respiratory and Critical Care Medicine, 185, 349–50.Find this resource:

7. Jubran A and Tobin MJ. (1997). Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. American Journal of Respiratory and Critical Care Medicine, 155, 906–15.Find this resource:

8. de Jonghe B, Lacherade JC, Sharshar T, and Outin H. (2009). Intensive care unit-acquired weakness: risk factors and prevention. Critical Care Medicine, 37, S309–15.Find this resource:

9. Jaber S, Petrof BJ, Jung B, et al. (2011). Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. American Journal of Respiratory and Critical Care Medicine, 183, 364–71.Find this resource:

10. Carlucci A, Ceriana P, Prinianakis G, Fanfulla F, Colombo R, and Nava S. (2009). Determinants of weaning success in patients with prolonged mechanical ventilation. Critical Care, 13, R97.Find this resource:

11. Similowski T, Yan S, Gauthier AP, Macklem PT, and Bellemare F. (1991). Contractile properties of the human diaphragm during chronic hyperinflation. New England Journal of Medicine, 325, 917–23.Find this resource:

12. Navalesi P, Frigerio P, Moretti MP, et al. (2008). Rate of reintubation in mechanically ventilated neurosurgical and neurologic patients: evaluation of a systematic approach to weaning and extubation. Critical Care Medicine, 36, 2986–92.Find this resource:

13. Straus C, Louis B, Isabey D, Lemaire F, Harf A, and Brochard L. (1998). Contribution of the endotracheal tube and the upper airway to breathing workload. American Journal of Respiratory and Critical Care Medicine, 157, 23–30.Find this resource:

14. Rumbak MJ, Walsh FW, and Anderson WM. (1999). Significant tracheal obstruction causing failure to wean in patients requiring prolonged mechanical ventilation: a forgotten complication of long-term mechanical ventilation. Chest, 115, 1092–5.Find this resource:

15. Smina M, Salam A, Khamiees M, Gada P, Amoateng-Adjepong Y, and Manthous CA. (2003). Cough peak flows and extubation outcomes. Chest, 124, 262–8.Find this resource:

16. Thille AW, Cabello B, Galia F, Lyazidi A, and Brochard L. (2008). Reduction of patient-ventilator asynchrony by reducing tidal volume during pressure-support ventilation. Intensive Care Medicine, 34, 1477–86.Find this resource:

17. Strøm T, Martinussen T, and Toft P. (2010). A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet, 375, 475–80.Find this resource:

18. Burns KE, Adhikari NK, Keenan SP, and Meade MO. (2010). Noninvasive positive pressure ventilation as a weaning strategy for intubated adults with respiratory failure. Cochrane Database Systematic Reviews, 8, CD004127.Find this resource:

19. Nava S, Gregoretti C, Fanfulla F, et al. (2005). Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Critical Care Medicine, 33, 2465–70.Find this resource:

20. Ferrer M, Sellarés J, Valencia M, et al. (2009). Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial. Lancet, 374, 1082–8.Find this resource: