There are two lungs in the human chest; the right lung is composed of three incomplete divisions called lobes, and the left lung has two, leaving room for the heart. The right lung accounts for 55% of total gas volume and the left lung for 45%. Lung tissue is spongy due to very small (200 to 300 ¿½ 10¿½6 m diameter in normal lungs at rest) gas-filled cavities called alveoli, which are the ultimate structures for gas exchange. There are 250 million to 350 million alveoli in the adult lung, with a total alveolar surface area of 50 to 100 m2 depending on the degree of lung inflation (2).
Air is transported from the atmosphere to the alveoli beginning with the oral and nasal cavities, through the pharynx (in the throat), past the glottal opening, and into the trachea or windpipe. Conduction of air begins at the larynx, or voice box, at the entrance to the trachea, which is a fibromuscular tube 10 to 12 cm in length and 1.4 to 2.0 cm in diameter. At a location called the carina, the trachea terminates and divides into the left and right bronchi. Each bronchus has a discontinuous cartilaginous support in its wall. Muscle fibers capable of controlling airway diameter are incorporated into the walls of the bronchi, as well as in those of air passages closer to the alveoli. Smooth muscle is present throughout the respiratory bronchiolus and alveolar ducts but is absent in the last alveolar duct, which terminates in one to several alveoli. The alveolar walls are shared by other alveoli and are composed of highly pliable and collapsible squamous epithelium cells.
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The bronchi subdivide into subbronchi, which further subdivide into bronchioli, which further subdivide, and so on, until finally reaching the alveolar level. Each airway is considered to branch into two subairways. In the adult human there are considered to be 23 such branchings, or generations, beginning at the trachea and ending in the alveoli. Movement of gases in the respiratory airways occurs mainly by bulk flow (convection) throughout the region from the mouth to the nose to the fifteenth generation. Beyond the fifteenth generation, gas diffusion is relatively more important. With the low gas velocities that occur in diffusion, dimensions of the space over which diffusion occurs (alveolar space) must be small for adequate oxygen delivery into the walls; smaller alveoli are more efficient in the transfer of gas than are larger ones (2).
Alveoli are the structures through which gases diffuse to and from the body. To ensure gas exchange occurs efficiently, alveolar walls are extremely thin. For example, the total tissue thickness between the inside of the alveolus to pulmonary capillary blood plasma is only about 0.4 ¿½ 10¿½6 m. Consequently, the principal barrier to diffusion occurs at the plasma and red blood cell level, not at the alveolar membrane (2).
Movement of Air In and Out of the Lungs and the Pressures That Cause the Movement
Is the pressure of the fluid in the thin space between the lung pleura and the chest wall pleura.
Is the pressure of the air inside the lung alveoli. To cause inward flow of air into the alveoli during inspiration, the pressure in the alveoli must fall to a value slightly below atmospheric pressure.
It is the pressure difference between that in the alveoli and that on the outer surfaces of the lungs, and it is a measure of the elastic forces in the lungs that tend to collapse the lungs at each instant of espiration, called the recoil pressure.
Compliance of the Lungs
The extent to which the lungs will expand for each unit increase in transpulmonary pressure (if enough time is allowed to reach equilibrium) is called the lung compliance. The total compliance of both lungs together in the normal adult human being averages about 200 milliliters of air per centimeter of water transpulmonary pressure (3).
Figure 2. Compliance diagram of lungs in a healthy person (3).
Pathophysiology of Weaning Failure
Reversible aetiologies for weaning failure can be categorized in: Respiratory load, cardiac load, neuromuscular competence, critical illness neuromuscular abnormalities (CIMMA), neuropsychological factors, and metabolic and endocrine disorders.
The decision to attempt discontinuation of mechanical ventilation has largely been based on the clinician¿½s assessment that the patient is haemodynamically stable, awake, the disease process has been treated adequately and that indices of minimal ventilator dependency are present. The success of weaning will be dependent on the ability of the respiratory muscle pump to tolerate the load placed upon it. This respiratory load is a function of the resistance and compliance of the ventilator pump.
Excess work of breathing (WOB) may be imposed by inappropriate ventilator settings resulting in ventilator dysynchrony (4).
Reduced pulmonary compliance may be secondary to pneumonia, cardiogenic or noncardiogenic pulmonary oedema, pulmonary fibrosis, pulmonary haemorrhage or other diseases causing diffuse pulmonary infiltrates (5).
Many patients have identified ischaemic heart disease, valvular heart disease, systolic or diastolic dysfunction prior to, or identified during, their critical illness. More subtle and less easily recognized are those patients with myocardial dysfunction, which is only apparent when exposed to the workload of weaning (5).
Liberation from mechanical ventilation requires the resumption of neuromuscular activity to overcome the impedance of the respiratory system, to meet metabolic demands and to maintain carbon dioxide homeostasis. This requires an adequate signal generation in the central nervous system, intact transmission to spinal respiratory motor neurons, respiratory muscles and neuromuscular junctions. Disruption of any portion of this transmission may contribute to weaning failure (5).
Critical illness neuromuscular abnormalities
CINMA are the most common peripheral neuromuscular disorders encountered in the ICU setting and usually involve both muscle and nerve (6).
Delirium, or acute brain dysfunction: Is a disturbance of the level of cognition and arousal and, in ICU patients, has been associated with many modifiable risk factors, including: use of psychoactive drugs; untreated pain; prolonged immobilisation; hypoxaemia; anaemia; sepsis; and sleep deprivation (7).
Anxiety and depression: Many patients suffer significant anxiety during their ICU stay and the process of weaning from mechanical ventilation. These memories of distress may remain for years (8).
Hypophosphataemia, hypomagnesaemia and hypokalaemia all cause muscle weakness. Hypothyroidism and hypoadrenalism may also contribute to difficulty weaning (5).
Overweight: The mechanical effects of obesity with decreased respiratory compliance, high closing volume/functional residual capacity ratio and elevated WOB might be expected to impact on the duration of mechanical ventilation (5).
Ventilator-induced diaphragm dysfunction and critical illness oxidative stress
Ventilator-induced diaphragm dysfunction and critical illness oxidative stress is defined as loss of diaphragm force-generating capacity that is specifically related to use of controlled mechanical ventilation (9).
Clinical Presentation of Patients
Patients can be classified into three groups according to the difficulty and length of the weaning process.
The simple weaning, group 1, includes patients who successfully pass the initial spontaneous breathing trial (SBT) and are successfully extubated on the first attempt. Group 2, difficult weaning, includes patients who require up to three SBT or as long as 7 days from the first SBT to achieve successful weaning. Group 3, prolonged weaning, includes patients who require more than three SBT or more than 7 days of weaning after the first SBT (5).
Clinical Outcomes and Epidemiology
There is much evidence that weaning tends to be delayed, exposing the patient to unnecessary discomfort and increased risk of complications (5). Time spent in the weaning process represents 40¿½50% of the total duration of mechanical ventilation (10) (11). ESTEBAN et al. (10) demonstrated that mortality increases with increasing duration of mechanical ventilation, in part because of complications of prolonged mechanical ventilation, especially ventilator-associated pneumonia and airway trauma (12).
The incidence of unplanned extubation ranges 0.3¿½16%. In most cases (83%), the unplanned extubation is initiated by the patient, while 17% are accidental. Almost half of patients with self-extubation during the weaning period do not require reintubation, suggesting that many patients are maintained on mechanical ventilation longer than is necessary (5). Increase in the extubation delay between readiness day and effective extubation significantly increases mortality. In the study by COPLIN et al. (13), mortality was 12% if there was no delay in extubation and 27% when extubation was delayed.
Failure of extubation is associated with high mortality rate, either by selecting for high-risk patients or by inducing deleterious effects such as aspiration, atelectasis and pneumonia (5). Rate of weaning failure after a single SBT is reported to be 26¿½ 42%. Variation in the rate of weaning failure among studies is due to differences in the definition of weaning failure. VALLVERDU et al. (14) reported that weaning failure occurred in as many as 61% of COPD patients, in 41% of neurological patients and in 38% of hypoxaemic patients. Contradictory results exist regarding the rate of weaning success among neurological patients. The study by COPLIN et al. (13) demonstrated that 80% of patients with a Glasgow coma score of more than 8 and 91% of patients with a Glasgow coma score less than 4 were successfully extubated. In 2,486 patients from six studies, 524 patients failed SBT and 252 failed extubation after passing SBT, leading to a total weaning failure rate of 31.2% (5). The vast majority of patients who fail a SBT do so because of an imbalance between respiratory muscle capacity and the load placed on the respiratory system. High airway resistance and low respiratory system compliance contribute to the increased work of breathing necessary to breathe and can lead to unsuccessful liberation from mechanical ventilation (15).
Mechanical ventilation is mostly used in the intensive care units (ICU) of hospitals. ICUs typically consume more than 20% of the financial resources of a hospital (16). A study that analyzed the incidence, cost, and payment of the Medicare intensive care unit use in the United States (US) reveled that mechanical ventilation costs a sum close to US$2,200 per day (17). One study shows that patients in the ICUs receiving prolonged mechanical ventilation represents 6% of all ventilated patients but consume 37% of intensive care unit (ICU) resources (18). Another study corroborates this numbers also showing that 5% to 10% of ICU patients require prolonged mechanical ventilation, and this patient group consumes more than or as much as 50% of ICU patient days and ICU resources. Prolonged ventilatory support and chronic ventilator dependency, both in the ICU and non-ICU settings, have a significant and growing impact on healthcare economics (19).
The process of initial weaning from the ventilator begins with an assessment regarding readiness for weaning. It is then followed by SBT as a diagnostic test to determine the possibility of a successful extubation. For the majority of patients, the entire weaning process involves confirmation that the patient is ready for extubation. Patients who meet the criteria in table 2 should be considered as being ready to wean from mechanical ventilation. These criteria are fundamental to estimate the likelihood of a successful SBT in order to avoid trials in patients with a high probability of failure (5).
Criteria for Assessing Readiness to Wean
Clinical Assessment Adequate cough
Absence of excessive tracheobronchial secretion
Resolution of disease acute phase for which the patient was intubated
Objective measurements Clinical stability
Stable cardiovascular status (i.e. fC =140 beats*min-1, systolic BP 90¿½160 mmHg, no or minimal vasopressors)
Stable metabolic status
Sa,O2 >90% on =FI,O2 0.4 (or Pa,O2/FI,O2 =150 mmHg)
PEEP =8 cmH2O
Adequate pulmonary function
f =35 breaths*min-1
PImax =-20¿½ -25 cmH2O
Ve < 10 l*min-1
P0.1/PImax < 0.3
VT >5 mL*kg-1
VC >10 mL*kg-1
f/VT <105 breaths*min-1*L-1
CROP > 13 ml*breaths-1*min-1
No significant respiratory acidosis
No sedation or adequate mentation on sedation (or stable neurologic patient)
Taken from (5) and (15). fC: cardiac frequency; BP: blood pressure; Sa,O2: arterial oxygen saturation; FI,O2: inspiratory oxygen fraction; Pa,O2: arterial oxygen tension; PEEP: positive end-expiratory pressure; f: respiratory frequency; PImax: maximal inspiratory pressure; VT: tidal volume; VC: vital capacity; CROP: integrative index of compliance. 1 mmHg=0.133 kPa.
According to an expert panel, among these criteria only seven variables have some predictive potential: minute ventilation (VE), maximum inspiratory pressure (PImax), tidal volume (VT), breathing frequency (f), the ratio of breathing frequency to tidal volume (f/VT), P0.1/PImax (ratio of airway occlusion pressure 0.1 s after the onset of inspiratory effort to maximal inspiratory pressure), and CROP (integrative index of compliance, rate, oxygenation, and pressure) (20) .
Minute ventilation is the total lung ventilation per minute, the product of tidal volume and respiration rate (21). It is measure by assessing the amount of gas expired by the patients lungs. Mathematicly, minute ventilation can be calculated after this formula: V_E=V_T¿½f
It is reported that a VE less than 10 litres/minute is associated with weaning success (22). Other studies found that VE values more than 15-20 litres/minute are helpful in identifying if a patient is unlikely to be liberated from mechanical ventilation but lower values were not helpful in predicting successful liberation (15). A more recent study concluded that short VE recovery times (3-4 minutes) after a 2-hour SBT can help in determining respiratory reserve and predict the success of extubation (23).
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When mechanical ventilation takes place, this parameter is calculated monitoring flow and pressure by the ventilator in use itself or by an independent device attached to the airway circulation system such as the Respironics NM3¿½ by Phillips Medical. Other ways to determine minute ventilation are by measuring the impedance across the thoracic cavity (24). This method though, is invasive and requires implanted electrodes.
Maximal Inspiratory Pressure
Maximal inspiration pressure is the maximum pressure within the alveoli of the lungs that occurs during a full inspiration (21). Is it commonly used to test respiratory muscle strength. On patients in the ICU or those not capable to cooperate, the PImax is measured by occluding the end of the endotracheal tube for a period of time close to 22 seconds with a one-way valve that only allows the patient to exhale. This configuration leads to increasing inspiratory effort measuring PImax towards the end of the occlusion period. However PImax is not enough to predict reliably the likeliness of successful weaning due to low specifity (15). The measurement of PImax can be performed by devices equipped with pressure sensors.
Tidal volume is the amount of air inhaled and exhaled during normal ventilation (21). Spontaneous tidal volumes greater than 5 ml/kg can predict weaning outcome (25). More recent studies found that a technique that measures the amount of regularity in a series analyzing approximate entropy of tidal volume and breathing frequency patterns is a useful indicator of reversibility of respiratory failure. A low approximate entropy that reflects regular tidal volume and respiratory frequency patterns is a good indicator of weaning success (26). Tidal volume can be measured using a pneumotachographic device.
The degree of regularity in the pattern of the breathing frequency shown by approximate entropy rather than the absolute value of the breathing frequency is been proven to be useful in discriminating between weaning success and failure (26). The breathing rate or frequency is measured by counting the breathing cycles per a defined period of time.
The Ratio of Breathing Frequency to Tidal Volume
Yang and Tobin  then performed a prospective study of 100 medical patients receiving mechanical ventilation in the ICU in which they demonstrated that the ratio of frequency to tidal volume (rapid shallow breathing index (RSBI)) obtained during the first 1 minute of a T-piece trial and at a threshold value of =105 breaths/minute/l was a significantly better predictor of weaning outcomes However, there remains a principle shortcoming in the RSBI: it can produce excessive false positive predictions (that is, patients fail weaning outcome even when RSBI is =105 breaths/minute/l) [35-36] Also, the RSBI has less predictive power in the care of patients who need ventilatory support for more than 8 days and may be less useful in chronic obstructive pulmonary disease (COPD) and elderly patients [37-39].
The Ratio of Airway Occlusion Pressure to Maximal Inspiratory Pressure
The airway occlusion pressure (P0.1) is the pressure measured at the airway opening 0.1 s after inspiring against an occluded airway . The P0.1 is effort independent and correlates well with central respiratory drive. When combined with PImax, the P0.1/PImax ratio at a value of <0.3 has been found to be a good early predictor of weaning success [11,43] and may be more useful than either P0.1 or PImax alone. Previously, the clinical use of P0.1/PImax has been limited by the requirement of special instrumentation at the bedside; however, new and modern ventilators are incorporating respiratory mechanics modules that provide numerical and graphical displays of P0.1 and PImax.
Air way Resistance
The CROP index is an integrative index that incorporates several measures of readiness for liberation from mechanical ventilation, such as dynamic respiratory system compliance (Crs), spontaneous breathing frequency (f), arterial to alveolar oxygenation (partial pressure of arterial oxygen (PaO2)/partial pressure of alveolar oxygen (PAO2)), and PImax in the following relationship:
CROP = [Crs ¿½ PImax ¿½ (PaO2/PAO2)]/f
PAO2 = (PB-47) ¿½ FiO2 – PaCO2/0.85
and PB is barometric pressure. The CROP index assesses the relationship between the demands placed on the respiratory system and the ability of the respiratory muscles to handle them . Yang and Tobin  reported that a CROP value >13 ml/breaths/minute offers a reasonably accurate predictor of weaning mechanical ventilation outcome. In 81 COPD patients, Alvisi and colleagues  showed that a CROP index at a threshold value of >16 ml/breaths/minute is a good predictor of weaning outcome. However, one disadvantage of the CROP index is that it is somewhat cumbersome to use in the clinical setting as it requires measurements of many variables with the potential risk of errors in the measurement techniques or the measuring device, which can significantly affect the value of the CROP index.
Clinical Treatment Profiles
CONCLUSIONS AND RECOMMENDATIONS
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