Invasive Mechanical Ventilation in ARDS Patients: Role of Tidal Volume
It is well documented that lower tidal volumes (6 mL/kg of predicted body weight) compared to higher tidal volumes (12 mL/kg of predicted body weight) associated with PEEP levels titrated by a PEEP/FiO2 table reduced mortality in a randomized, clinical trial that analyzed 861 ARDS patients (ARMA trial) . In the ARMA trial, lower tidal volumes led to lower levels of plasma IL-6, IL-8 ,and TNFR1 over the subsequent 1-3 days .
So, low tidal ventilation (<6 mL/kg of predicted body weight) must be initiated as soon as the ARDS patient is intubated and mechanically ventilated. The predicted body weight (PBW) can be calculated as follows: for women, PBW= 45.5 + 0.91 (height in centimeters - 152.4) and, for men, PBW = 50.0 + 0.91 (height in centimeters -152.4). It is important to adjust tidal volume to lung size that depends on the height and sex but, more importantly, to adjust the tidal volume to functional lung size that depends on the ARDS severity (lung compliance), sex, height, and chest wall compliance. It also depends where in the pressure-volume curve of the respiratory system the tidal ventilation takes place, even more, the interaction between the FRC (functional residual capacity) and tidal ventilation inside the thoracic cage during controlled ventilation. During assisted ventilation other two factors must be added to the interaction between the FRC and above tidal ventilation inside the thoracic cage: the patient’s negative inspiratory efforts, and the pressures that resulted from the desynchronization between the patient and the mechanical ventilator. Recent evidences showed that in severe ARDS, patients’ inspiratory efforts during assisted ventilation could worsen ventilator lung injury induced by the mechanical ventilation during the ventilatory support of the ARDS patients . This associated and added injury could explain the results of a phase IV randomized controlled trial in moderate/severe ARDS patients (PaO2/FiO2 < 150); comparing cisatracurium to placebo for 48 h showed an improved adjusted 90-day survival rate and increased ventilator-free in the cisatracurium group without a significant increase in muscle weakness. Short-term paralysis may facilitate patient-ventilator synchrony in the setting of lung-protective ventilation. Short-term paralysis would eliminate patient triggering and expiratory muscle activity. In combination, these effects may serve to limit regional overdistention and cyclic alveolar collapse. Paralysis may also act to lower metabolism and overall ventilatory demand .
At the same time that a low tidal volume is set, an adequate respiratory rate must be concurrently set in order to keep a minute ventilation around 7-8 L/min and a PaCO2 around 40-60 mmHg and a pH above 7.2. In the more severe ARDS patients, sometimes after the adjustment of a minute ventilation around 8 L/min with tidal volumes lesser than 6 mL/kg of predicted body weight, the PaCO2 levels stay above 80 mmHg and pH less than 7.2 (specially patients with septic shock and metabolic acidosis). In these cases, the VCO2 must be assessed and be kept as least as possible (fever control, low carbohydrate intake), and hemodialysis can be initiated (specially in ARDS patients with concomitant acute renal failure ) in order to help control the metabolic acidosis. Efforts must be taken to decrease the pulmonary death space by means of recruitment maneuvers and PEEP titration, tidal volume and respiratory rate adjustments, or even the initiation of prone ventilation. In the most difficult cases, tracheal gas insufflation or extracorporeal CO2 removal or extracorporeal oxygenation should be started in order to keep the protective low tidal volume ventilation .
Potentially harmful consequences of permissive hypercapnia include pulmonary vasoconstriction and pulmonary hypertension, proarrythmic effects of increased discharge of catecholamines, and cerebral vasodilation yielding increased intracranial pressure. Special attention should be given to patients with pulmonary hypertension and right ventricular dysfunction secondary to ARDS that could not tolerate high PaCO2 and low pH levels .
Nonetheless, permissive hypercapnia should probably be used with caution in patients with heart disease and is relatively contraindicated in those with elevated intracranial pressure. In ARDS cases with pulmonary hypertension and right ventricular dysfunction, prone position ventilation should be preferred .
Recent evidence showed that prolonged prone position ventilation (16 h) must be used in early ARDS with PaO2/FiO2 <150 with PEEP levels of or more than 5 cmH2O in order to significantly improve 90-day mortality compared to supine ventilation . Recent meta-analysis also showed that in the era of low tidal ventilation, the prone position use improved mortality of moderate/severe ARDS patients that needed invasive mechanical ventilatory support . If PEEP titration during prone position ventilation should improve survival of ARDS patients is still a matter of debate .
Another recent approach for application of extracorporeal carbon dioxide removal new devices (ECMO-R) in ARDS patients is the demonstration that in severe ARDS, even the low tidal volume ventilation with 6 mL/kg of predicted body weight can cause tidal hyperdistension in the nondependent regions of the lungs accompanied by plateau airway pressures greater than 28 cmH2O and elevated plasma markers of inflammation. In this group application of ECMO-R could allow the authors to decrease the tidal volume to less than 6 mL/kg with a consequent plateau pressure less than 25 cmH2O that was associated with a lower radiographic index of lung injury and lower levels of lung-derived inflammatory cytokines . However, prognostic implication of this new ECMO-R devices application in clinical practice is still under investigation .
Pumpless interventional lung assist (iLA) is also used in patients with ARDS and is aimed at improving extracorporeal gas exchange with a membrane integrated in a passive arteriovenous shunt. iLA serves as an extracorporeal assist to support mechanical ventilation by enabling low tidal volume and a reduced inspiratory plateau pressure in extremely severe ARDS patients. Zimmermann and colleagues used iLA in 51 severe ARDS patients and observed a decrease in PaCO2 allowing the decrease in tidal volume and plateau pressure (ultraprotective ventilation) with a hospital mortality rate of 49% . Recently, Fanelli and colleagues described the feasibility and safety of use of an ultraprotective strategy using 4 mL/kg of predicted body weight associated with low-flow extracorporeal carbon removal in 15 moderate ARDS patients .