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Evolving Evidence for Lung Recruitment Maneuvers in ARDS

Updated: Oct 7, 2022



BACKGROUND

The main pathology in ARDS is a decreased functional size of the lung (baby lung) due to poorly aerated lung units as a result of collapse or consolidation. This pathology places patients at risk of ventilator-induced lung injury due to overdistension of normal lung units (volutrauma and barotrauma) and opening and closing of collapsed lung units (atelectrauma).


Lung recruitment maneuver (LRM) employs a transient increase in transpulmonary pressure aiming to open recruitable alveoli (collapsed lung units) and keep them open with the appropriate PEEP application. This will potentially decrease the risk of atelectrauma.


Positive effects of LRMs are demonstrated with new lung unit recruitments and associated with improvement in lung compliance and oxygenation. Negative effects include the heart, the lungs, and the brain. Patients may have a hemodynamic compromise with increased pulmonary resistance and a decreased cardiac output as a result of increased intrathoracic pressure. Lung complications include barotrauma, VILI, and overdistention of aerated areas. Brain complications include increased intracranial pressure (ICP), which makes these maneuvers contra-indicated in patients with increased ICP.

TYPES OF LRMs

Different LRMs have been used, from a sustained inflation pressure with a continuous positive airway pressure, to increasing PEEP with a constant driving pressure or higher driving pressure at a constant PEEP. There is a consensus that a stepwise approach with PEEP titration is the preferred method. However, there is no need to detail these methods unless the evidence shows a favorable outcome, which is not the case yet.

Stepwise PEEP titration consists of a "recruitment phase" that starts at baseline-PEEP (around 10 cmH2O) and goes up to maximum-PEEP (around 45 cmH2O), transiently generating plateau-inspiratory pressures around 60 cmH2O. This is followed by a "PEEP titration phase" in which the PEEP is titrated down at 3 cmH2O increments from 25 cmH2O down to a PEEP level of 10. Oxygenation and lung compliance are monitored and the optimal PEEP is the one associated with the best compliance plus 2 cm H2O.

Sustained Inflation Pressure versus Stepwise PEEP Titration

THE EVIDENCE

Meade et al. randomized patients to receive an "open lung strategy" consisting of target tidal volumes of 6 mL/kg of the predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures compared to low tidal volume strategy. The open lung strategy resulted in no significant difference in all-cause hospital mortality or barotrauma and did not appear to improve secondary endpoints related to hypoxemia and use of rescue therapies [1].


Two randomized controlled trials compared a staircase recruitment as a part of the open lung strategy followed by decremental PEEP titration with a well-established low-PEEP strategy. They suggested beneficial effects on oxygenation, lung compliance, and systemic cytokines, without increasing barotrauma or other adverse events [2-3]. In addition, two meta analyses were published in 2017 and 2018 with conflicting results on mortality outcome. One shows a better mortality outcome [4], while the other shows no mortality benefit [5].


The ART trial looked at mortality outcome in 1010 patients with moderate to severe ARDS at 120 critical care units in 9 countries. Patients were randomized to

lung recruitment associated with PEEP titration according to the best respiratory-system compliance compared with a conventional low-PEEP strategy as per ARDSnet study. 28-day mortality (55.3% vs 49.3%, HR,1.20; 95% CI, 1.01 to 1.42; P = .041) and 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04) were higher in the experimental group compared to the control group. There is an absolute mortality risk increase of 6% [number needed to cause harm is about 17]. The experimental group had a lower number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), a higher rate of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and a higher risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). The length of ICU and hospital stay was not different between the two groups. This study does not support the routine use of recruitment maneuvers in moderate to severe ARDS patients [6]. An exceptional analysis of the trial is available on PulmCCM.


The ART trial has some concerns. As you can see, the mortality rate is relatively higher than the reported mortality rates in previous studies including the ALVEOLI Trial, LOVS, and EXPRESS. In addition, the percentage of patients with pulmonary cause of ARDS is 62%, a subset of ARDS that is known not to respond to recruitment maneuvers. Therefore, it is possible that different results may have been obtained only if extra-pulmonary causes of ARDS were included in the trial.

ART Trial

The PHARLAP trial was terminated early based on the negative results and the worse mortality associated with recruitment maneuvers similar to reported results by the ART trial. They used a protocol that is very similar to the ART trial called the stairway recruitment method. It was used by increasing the PEEP by 10 cmH2O from 20 to 40 every 2 minutes with a constant driving pressure of 15 cmH2O. Then, PEEP was titrated down from 25 cmH2O every 3 minutes until the SpO2 decreased by 2% to a minimum PEEP of 15 cmH2O and the PEEP was returned to 2.5 cmH2O above the desaturation level. The study was negative, with no difference in primary outcome (free-ventilator days at 28 days) or secondary outcome (mortality, barotrauma, or use of hypoxemic adjuvant therapies). Notably, 13% of patients in the intervention group had a clinically significant hypotension during the stairway recruitment. The PHARLAP trial strongly indicates that the cardiovascular consequences and quite likely the overdistension induced by the procedures outweigh the possible benefits of the maximal lung recruitment strategy [7]. A good analysis of the trial is available on PulmCCM.


PHARLAP Trial

The LIVE study highlights the need for assessing the lung morphology to determine a personalized approach with alveolar lung maneuvers, high PEEP, or prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment maneuvers and high PEEP. There was no difference in 90-day mortality between the group treated with personalized ventilation and the control group. Unfortunately, the trial had a high rate of 21% of misclassification and the 90-day mortality of those patients was higher in the personalized group compared to the control group. Further studies are required to assess ARDS phenotypes [8].

A meta-analysis in 2019 included 14 RCTs and revealed that LRMs are not associated with a reduced 28-day mortality compared to no-LRM. However, LRM use is associated with positive effects such as oxygenation improvement and a less frequent use of rescue therapy. In addition, LRM use is associated with negative effects such as hemodynamic impairment [9].


CONCLUSION

The current available evidence does not support the routine use of recruitment maneuvers in ARDS patients. However, there may be a subset of patients who benefit from maximal alveolar recruitment and could be useful in determining such patients. Unfortunately, there is no practical or reliable way to make such an assessment. CT scan imaging is not feasible, pressure-volume curve assessment is not practical, and measurement of compliance is not always reliable. New techniques such as lung ultrasound and electrical impedance tomography may prove to be helpful in making such an assessment.



REFERENCES

1. Meade MO, Cook DJ, Guyatt GH, et al. Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial. JAMA. 2008;299(6):637–645. doi:10.1001/jama.299.6.637


2. Hodgson CL, Tuxen DV, Davies AR, et al. A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome. Crit Care. 2011;15(3):R133. doi:10.1186/cc10249


3. Kacmarek RM, Villar J, Sulemanji D, et al.; Open Lung Approach Network . Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial. Crit Care Med. 2016;44(1):32-42.


4. Goligher EC, Hodgson CL, Adhikari NKJ, Meade MO, Wunsch H, Uleryk E, Gajic O, Amato MPB, Ferguson ND, Rubenfeld GD, Fan E. Lung Recruitment Maneuvers for Adult Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2017 Oct;14(Supplement_4):S304-S311. doi: 10.1513/AnnalsATS.201704-340OT. PMID: 29043837.


5. Bhattacharjee S, Soni KD, Maitra S. Recruitment maneuver does not provide any mortality benefit over lung protective strategy ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis and systematic review of the randomized controlled trials. J Intensive Care. 2018 Jun 26;6:35. doi: 10.1186/s40560-018-0305-9. PMID: 29983985; PMCID: PMC6019312.


6. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators, Cavalcanti AB, Suzumura ÉA, Laranjeira LN, Paisani DM, Damiani LP, Guimarães HP, Romano ER, Regenga MM, Taniguchi LNT, Teixeira C, Pinheiro de Oliveira R, Machado FR, Diaz-Quijano FA, Filho MSA, Maia IS, Caser EB, Filho WO, Borges MC, Martins PA, Matsui M, Ospina-Tascón GA, Giancursi TS, Giraldo-Ramirez ND, Vieira SRR, Assef MDGPL, Hasan MS, Szczeklik W, Rios F, Amato MBP, Berwanger O, Ribeiro de Carvalho CR. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1335-1345. doi: 10.1001/jama.2017.14171. PMID: 28973363; PMCID: PMC5710484.


7. Hodgson CL, Cooper DJ, Arabi Y, King V, Bersten A, Bihari S, Brickell K, Davies A, Fahey C, Fraser J, McGuinness S, Murray L, Parke R, Paul E, Tuxen D, Vallance S, Young M, Nichol A. Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP). A Phase II, Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1363-1372. doi: 10.1164/rccm.201901-0109OC. PMID: 31356105.


8. Constantin JM, Jabaudon M, Lefrant JY, Jaber S, Quenot JP, Langeron O, Ferrandière M, Grelon F, Seguin P, Ichai C, Veber B, Souweine B, Uberti T, Lasocki S, Legay F, Leone M, Eisenmann N, Dahyot-Fizelier C, Dupont H, Asehnoune K, Sossou A, Chanques G, Muller L, Bazin JE, Monsel A, Borao L, Garcier JM, Rouby JJ, Pereira B, Futier E; AZUREA Network. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial. Lancet Respir Med. 2019 Oct;7(10):870-880. doi: 10.1016/S2213-2600(19)30138-9. Epub 2019 Aug 6. PMID: 31399381.


9. Pensier J, de Jong A, Hajjej Z, Molinari N, Carr J, Belafia F, Chanques G, Futier E, Azoulay E, Jaber S. Effect of lung recruitment maneuver on oxygenation, physiological parameters and mortality in acute respiratory distress syndrome patients: a systematic review and meta-analysis. Intensive Care Med. 2019 Dec;45(12):1691-1702. doi: 10.1007/s00134-019-05821-9. Epub 2019 Nov 7. PMID: 31701204.




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