Utility of bedside lung ultrasound for assessment of lung recruitment in a case of acute respiratory distress syndrome.

Lung recruitment maneuvers are rescue measures commonly used to improve oxygenation in severely hypoxemic patients with acute respiratory distress syndrome (ARDS), who fail to improve on standard treatment. After recruitment, appropriate level of positive end-expiratory pressure (PEEP) is applied to prevent alveolar de-recruitment during expiration. Computed tomography scan of thorax and quasi-static pressure-volume curves have played a pivotal role are important in the assessment of recruitment, but they have several limitations. Lung ultrasound (LUS), which is now easily available in nearly every Intensive Care Unit, could be an attractive alternative method for assessing lung recruitment. It is noninvasive, easily repeatable and is devoid of radiation hazards. We are presenting a case of 24-year-old female patient with moderate ARDS in whom bedside LUS was successfully used into assessing lung recruitment as well as into determining the appropriate level of PEEP.

INTRODUCTION

Mechanical ventilation (MV) with low tidal volume (TV) and high-positive end-expiratory pressure (PEEP) is conventional strategy for improving oxygenation in patients with acute respiratory distress syndrome (ARDS).[1] However, patients who fail to show improvement in oxygenation with standard therapy require frequent recruitment maneuvers with high pressures to achieve satisfactory opening of the collapsed alveoli.[2] Imaging has played a key role in the evaluation of lung recruitment since last three decades. The computed tomography (CT) scan thorax and quasi-static pressure-volume (PV) curve have played a pivotal role in the assessment of recruitment but have several disadvantages. CT cannot be performed routinely and repeated easily.[3] It also requires the patient to be transported outside the Intensive Care Units (ICUs) and is associated with significant radiation exposure. PV curve requires deep sedation, muscle paralysis, and expensive software on the ventilator.[4] The arterial oxygenation method has also been validated to detect the efficacy of recruitment. It is available in all ICUs and is easy to measure by performing arterial blood gas (ABG) analysis frequently with arterial catheter. However, it is an invasive procedure associated with complications such as hematoma, arterial thrombosis, and catheter-related infections. Repeated sampling also adds a significant cost burden to patients. Lung ultrasound (LUS) is now available in almost every ICU and is used routinely for the evaluation of pleural fluid, pulmonary edema, pneumothorax, and also for the diagnosis of pneumonia by measuring lung aeration score.[56] With the same principle, it has also recently been used to assess the lung recruitment with the application of PEEP.[7] LUS has the advantage of being noninvasive, safe with no radiation exposure, and easily repeatable. We are reporting a case of young female with severe ARDS, in whom bedside LUS was used successfully for assessing lung recruitment and for selecting an appropriate level of PEEP to prevent derecruitment during expiration.

CASE REPORT

A 24-year-old previously healthy woman was admitted to the hospital with chief complaints of high-grade fever, generalized body ache, and decreased appetite for 5 days followed by breathlessness for 1 day. Her vital parameters on examination were as follows: pulse 140/min, blood pressure 110/70 mm Hg, respiratory rate (RR) 60/min, temperature 38.4°C (101°F), and pulse showing oxygen saturation of 60% on room air. Respiratory system examination revealed bilateral air entry with no adventitious sounds. Other systemic examination revealed no significant abnormality. She was found to have thrombocytopenia (50,000/cm3). The serology of dengue and malaria showed negative results. Scrub typhus serology (IgM Elisa >1.5) was positive (normal cutoff value <0.5). Rest all laboratory investigations were within normal limit. Her chest radiography on the 1st day of admission showed bilateral infiltrates involving all zones suggestive of ARDS. The ABG showed pH of 7.51, PaO2 of 23.1 mm Hg (3.1 kPa), PaCO2 of 26.9 mm Hg (3.6 kPa), and alveolar–arterial gradient of 55 mm Hg (7.3 kPa) on room air. The diagnosis of moderate ARDS secondary to scrub typhus infection was confirmed as per Berlin criteria.[8] She was initially placed on Venturi mask with FiO2 (fraction of inspired oxygen) 60%, but oxygenation could not be improved and her condition further worsened. Intubation and MV were initiated immediately to correct hypoxemia and reduce work of breathing. A radial arterial catheter was inserted for ABG sampling and arterial blood pressure monitoring. ABG analysis parameters were recorded after optimum calibration. She was placed on initial ventilator settings: FiO21.00, volume control mode, constant-flow inflation, TV 300 mL (6 mL/kg of predicted body weight, baseline PEEP of 5 cm H2O, and RR 35/min to keep PaCO2 within normal limit). Repeat ABG revealed pH 7.49, PaO2102 mm Hg (13.6 kPa), PaCO228.3 mm Hg (3.8 kPa), and PaO2/FIO2 ratio 102. Lung mechanics parameters recorded at baseline were as follows: peak inspiratory pressure (Pinsp) 36 cm H2O and plateau pressure (Pplat) 28 cm H2O. Ultrasound examination was also performed simultaneously to assess baseline lung aeration, which was C pattern (consolidation = 3) at same ventilator setting. This severity of loss of aeration has been adopted from LUS scoring patterns as defined by Bouhemad et al.:[7] Normal aeration (N) = 0: the presence of lung sliding with A lines (horizontal repetitive artifacts originating from the pleural line) or fewer than two isolated B lines (vertical, comet-tail artifacts originating from the pleural line, long, hyperechoic, well-defined, dynamic, erasing A lines); moderate loss of lung aeration (B1) = 1: Multiple well-defined B lines 7 mm apart caused by thickened interlobular septa (interstitial edema); severe loss of lung aeration (B2) = 2: Multiple coalescent B lines <3 mm apart caused by ground-glass areas (alveolar edema) and lung consolidation (C) = 3: The presence of a tissue pattern characterized by dynamic air bronchograms. These patterns are represented pictorially in Figure 1. The patient was examined in the semi-recumbent position with 4 MHz frequency probe of bedside portable LUS (LOGIQe ULTRASOUND, BT 12; GE-Health Care, Philips, USA). The probe was positioned parallel to the rib on the dependent region at the left side of chest perpendicular to the skin and without angulation at the posterior axillary line in sixth ICS. PEEP was then increased to 12 cm H2O for improving oxygenation; however, no significant response was observed as PaO2 remained low (117 mm Hg-15.6 kPa) as well as LUS aeration pattern remained unchanged (C pattern) and FiO2 could not be reduced to <60%. Fluid resuscitation was started along with hemodynamic monitoring. Two-dimensional echocardiography revealed normal ejection fraction and normal heart chambers. The recruitment maneuver was then performed with pressure control ventilation using stepwise increase in sustained inflation pressure starting from 30 cm H2O and successively rising to 40 and 50 cm H2O, applied for 50 s till PaO2+ PaCO2 is increased to 406.5 mm Hg (54.2 kPa). The recruitment maneuver was stopped at 50 cm H2O as target of maximal recruitment strategy (PaO2+ PaCO2≥400 mm Hg-53.3 kPa) was achieved based on previous validated study.[9] The ABG analysis and ultrasound examination were performed simultaneously at different settings to estimate trends in change of oxygenation and LUS aeration patterns. The LUS aeration pattern at this point was N (normal = 0). It was followed by PEEP titration starting from highest set PEEP of 24 cm H2O where other ventilator settings were adjusted to maintain Pplat below 30 cm H2O. The PEEP was then lowered stepwise by 2 cm H2O after every 10 min. The ABG analysis was performed at each level of PEEP with simultaneous LUS examination. The PEEP titration was continued till 14 cm H2O, where decrease by >10% of maximally achieved PaO2+ PaCO2 was observed, i.e., 357.3 mm Hg (47.6 kPa). The LUS also revealed some derecruitment or loss of aeration at this point and B1 = 1 pattern was recorded. These changes are demonstrated in Table 1 as well as pictorially in Figure 2a–j. The patient again underwent re-recruitment to maintain oxygenation; however, this time LUS was used primarily to guide recruitment maneuver as well as titration of appropriate level of PEEP and simultaneous oxygenation parameters were also noted by the ABG analysis at each level of set PEEP. The findings of the ABG analysis were blinded to the operator performing LUS. A similar trend was observed with improvement in LUS aeration score during recruitment maneuver, i.e., conversion from C pattern at baseline PEEP (5 cm H2O) to N pattern at continuous positive airway pressure (CPAP) of 50 cm H2O. The LUS also detected derecruitment at PEEP of 14 cm H2O during appropriate level of PEEP titration as conversion to B1 pattern from N pattern was observed. The corresponding changes in oxygenation (PaO2+ PaCO2) values were 172.9 (23.1 kPa), 411.8 (54.9 kPa), and 352.2 mm Hg (47 kPa) at baseline PEEP, recruitment maneuver with CPAP 50 cm H2O, and PEEP of 14 cm H2O, respectively. These findings, including pictorial illustrations, are summarized in Table 2 and Figure 3a–l. The probe was placed in the same position for the assessment of aeration pattern at all settings. Similar changes were also detected in the same position in the contralateral right lung. The patient was again re-recruited, and PEEP was finally set at appropriate level of 16 cm H2O, i.e., 2 cm higher than the level of derecruitment PEEP to maintain quality of care. The LUS at this point of time revealed N pattern. These findings show significant agreement as well as good correlation between oxygenation parameters and LUS aeration patterns during recruitment maneuver as well as appropriate level of PEEP titration, as shown in Figures 4a and b (r = 0.732, P = 0.02). There was further improvement in oxygenation parameters during course of illness as the patient got extubated after 4 days of admission. She was discharged after 1 week of extubation in a stable general condition.

Figure 1

(a) N pattern (normal aeration): The presence of lung sliding with horizontal A lines; (b) B1 pattern (moderate loss of aeration): The presence of multiple well-defined B lines >7 mm apart-marked with dots; (c) B2 pattern (severe loss of aeration): The presence of multiple coalescent B lines <3 mm apart-marked with dots; (d) C pattern (consolidation): The presence of tissue pattern characterized by punctate lesions and dynamic air bronchograms

Table 1

Serial oxygenation parameters and corresponding lung ultrasound scores in our patient with acute respiratory distress syndrome undergoing recruitment as well as appropriate level of positive end-expiratory pressure titration

PEEP setting (cm H2O)	FiO2 (%)	PaO2 in mm Hg (kPa)	PaCO2 in mm Hg (kPa)	PaO2 + PaCO2 in mm Hg (kPa)	LUS pattern	LUS score
Baseline PEEP (5)	100	114 (15.2)	41.9 (5.6)	155.9 (20.8)	C	3
RM with CPAP (30)	100	140 (18.7)	42.9 (5.7)	182.9 (24.4)	C	3
RM with CPAP (40)	100	286 (38.1)	47 (6.3)	333 (44.4)	B2	2
RM with CPAP (50)	100	340 (45.3)	66.5 (8.9)	406.5 (54.2)	N	0
PEEP (24)	100	349 (46.5)	62.2 (8.3)	411.2 (54.8)	N	0
PEEP (22)	100	342 (45.6)	60.4 (8.1)	402.4 (53.7)	N	0
PEEP (20)	100	343 (45.7)	59.9 (8)	402.9 (53.7)	N	0
PEEP (18)	100	339 (45.2)	55.2 (7.4)	394.2 (52.6)	N	0
PEEP (16)	100	335 (44.7)	52.8 (7.1)	387.8 (51.8)	N	0
PEEP (14)	100	311 (41.5)	46.3 (6.2)	357.3 (47.7) - fall by >10% from that of CPAP 50 cm H2O	B1 (loss of aeration)	1

PEEP: Positive end-expiratory pressure, LUS: Lung ultrasound, RM: Recruitment maneuver, CPAP: Continuous positive airway pressure, kPa- Kilopascal (The level of PEEP and corresponding LUS score and oxygenation is marked in bold)

Figure 2

(a-j) Arterial oxygenation parameters with corresponding lung ultrasound aeration patterns (pictorial view) in our patient with ARDS undergoing recruitment as well as appropriate level of positive end-expiratory pressure titration at different positive end-expiratory pressure settings

Table 2

Serial lung ultrasound scores and corresponding oxygenation parameters in the same patient with acute respiratory distress syndrome undergoing recruitment as well as appropriate level of positive end-expiratory pressure titration

PEEP setting (cm H2O)	FiO2 (%)	LUS pattern	LUS score	PaO2 in mm Hg (kPa)	PaCO2 in mm Hg (kPa)	PaO2 + PaCO2 in mm Hg (kPa)
Baseline PEEP (5)	100	C	3	131 (17.5)	41.9 (5.6)	172.9 (23.1)
RM with CPAP (30)	100	C	3	144 (19.2)	42.9 (5.7)	186.9 (24.9)
RM with CPAP (40)	100	B2	2	293.2 (39.1)	47 (6.3)	340.2 (45.4)
RM with CPAP (50)	100	N	0	345 (46)	66.8 (8.9)	411.8 (54.9)
RM with CPAP (60)	100	N	0	364.7 (48.7)	68.5 (9.1)	433.2 (57.8)
PEEP (24)	100	N	0	356 (47.5)	64.5 (8.6)	420.5 (56.1)
PEEP (22)	100	N	0	351 (46.8)	65.2 (8.7)	416.2 (55.5)
PEEP (20)	100	N	0	343 (45.7)	61.9 (8.3)	404.9 (54)
PEEP (18)	100	N	0	339.4 (45.2)	62.2 (8.3)	401.6 (53.5)
PEEP (16)	100	N	0	338 (45.1)	61.8 (8.2)	399.8 (53.3)
PEEP (14)	100	B1 (loss of aeration)	1	293.9 (39.2)	58.3 (7.8)	352.2 (47) - fall by >10% from that of CPAP 50 cm H2O
PEEP (12)	100	B2	2	290.6 (38.7)	47.2 (6.3)	337.8 (45)

PEEP: Positive end-expiratory pressure, LUS: Lung ultrasound, RM: Recruitment maneuver, CPAP: Continuous positive airway pressure, kPa- Kilopascal (The level of PEEP and corresponding LUS score and oxygenation are marked in bold)

Figure 3

(a-l) Lung ultrasound aeration patterns in our patient with acute respiratory distress syndrome undergoing recruitment as well as appropriate level of positive end-expiratory pressure titration with corresponding arterial oxygenation parameters at different positive end-expiratory pressure settings

Figure 4

(a) Bland and altman plot for difference in PaO2 + PaCO2 calculated at two different times from Tables 1 and 2, with the representation of the limits of agreement (dotted line), from 1.96 s to + 1.96 s. (b) Prediction of differences of PaO2 + PaCO2 by lung ultrasound aeration patterns with significant correlation (r = 0.732, P = 0.02) with all values lying between upper and lower confidence limit

DISCUSSION

This case report demonstrated the utility of bedside LUS in assessing lung recruitment as well as in determining the appropriate level of PEEP required to prevent derecruitment in patients with severe ARDS. The LUS has been used for similar indications previously also by various authors in different case reports and observational studies but with a heterogeneity in methodological approach as well as investigation used for comparison.[6710111213141516171819202122] Few studies have been described in Online supplementary material. ARDS is a condition characterized by diffuse alveolar as well as lung capillary damage, interstitial edema, and alveolar flooding leading to increased lung water. This can cause alveolar collapse and consolidation, especially of dependent lung; and decreased lung aeration, leading to poor compliance accompanied by ventilation-perfusion mismatch.[1] The LUS can detect increased interstitial and alveolar fluids in patients with ARDS by examination of artifacts known as B lines.[23] It is characterized by the presence of three or more discrete laser-like vertical hyperechoic reverberation artifacts that arise from the pleural line (previously described as 'comet tails'), extend to the bottom of the screen without fading, and move synchronously with lung sliding. These B lines correlate well with the ultrasound interstitial syndrome. A scoring system has been proposed to assess lung recruitment by LUS in ARDS.[7] Most cases of ARDS occur because of various systemic etiologies resulting in the production of inflammatory exudate, which lead to the collapse of lungs because of distal airways closure, especially in basal or dependent areas. These areas are subjected to a superimposed hydrostatic pressure of overlying upper or nondependent lung under the influence of gravity and the effect increases from sternal to vertebral regions in supine position. This sternovertebral gradient results in heterogeneous collapse of dependent regions of lung even though the lung is uniformly involved in ARDS. Recruitment of these collapsed areas is essential to improve oxygenation by early positive pressure through application of either PEEP or recruitment maneuver. The gold standard CT scan has significantly contributed in understanding the pathophysiology of ARDS and the regional distribution of lung aeration with recruitment maneuver.[3] Bedside LUS can directly evaluate effectiveness of recruitment. This was shown by Bouhemad et al.[6] as they observed a highly significant correlation between CT and LUS reaeration score before and after antibiotic therapy in 30 patients with ventilator-associated pneumonia. Subsequently, they observed a change in LUS score before and after recruitment maneuver that was quantified on the basis of reaeration scoring system: 1 point, from multiple B lines to normal, from coalescent B lines to multiple B lines, and from consolidation to coalescent B lines; 3 points, from coalescent B lines to normal or from consolidation to multiple B lines; and 5 points, from consolidation to normal.[7] Thereafter, other studies also assessed recruitment maneuver under direct guidance with bedside LUS with successful outcome.[11121314] Few studies used alternative approach to assess recruitment by LUS.[1516] Stefanidis et al.[15] observed that reduction in the nonaerated areas of dependent lung regions in 10 patients with ARDS as estimated by the LUS was associated with significant improvement in oxygenation during incremental PEEP titration trial. Tusman et al.[24] has proposed an algorithm for assessing recruitment maneuver as well as appropriate level of PEEP titration by the LUS to conduct and personalize recruitment maneuver in a real-time way at the bedside. There is requirement of uniform approach by framing systematic LUS-guided lung recruitment protocol available for daily clinical practice.

The strength of our case report is that we have compared arterial oxygenation parameters with the LUS scores and found strong correlation in their values when both modalities were used independently. However, the LUS cannot detect hyperinflation of nondependent areas of the lung due to overtitration resulting in barotrauma. The selection of the appropriate PEEP level should not only consider optimizing lung recruitment but also focus on limiting hyperinflation.[25] A new method such as electrical impedance tomography can fulfill these requirements but is expensive, not commonly used and evidence regarding its utility is not well defined. In conclusion, this case highlights the usefulness of bedside LUS in the assessment of RM as well as appropriate level of PEEP titration. However, properly designed studies involving a large number of patients are required before it can be recommended for routine use in clinical practice. The LUS may become the primary means for diagnostic evaluation of patients with ARDS in the future.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table S1

Various observational studies investigating the utility of bedside lung ultrasound in the assessment of lung recruitment in patients of acute respiratory distress syndrome

Author/year	Number of ARDS cases included in the study	Primary diagnostic modality	Diagnostic modality used for comparison	Methodology	Result
Lichtenstein et al., 2004[10]	32	Lung auscultation Bedside chest radiography LUS	Thoracic CT	Diagnostic accuracy of auscultation, bedside chest radiography, and LUS was compared with that of thoracic CT Evaluation of three pathologic entities in 384 lung regions (12 per patient)  1. Pleural effusion  2. Alveolar consolidation  3. Alveolar-interstitial syndrome	Diagnostic accuracy of auscultation  1. Pleural effusion - 61%  2. Alveolar consolidation-36%  3. Alveolar-interstitial syndrome-55% Diagnostic accuracy of bedside chest radiography  1. Pleural effusion - 47%  2. Alveolar consolidation - 75%  3. Alveolar - interstitial syndrome - 72% Diagnostic accuracy of LUS  1. Pleural effusion - 93%  2. Alveolar consolidation - 97%  3. Alveolar-interstitial syndrome - 95%
Bouhemad et al., 2010[6]	VAP - 30	LUS Chest radiography	Thoracic CT	CT, chest radiography, and LUS performed at baseline and 7 days following initiation of antibiotics CT reaeration was measured as the additional volume of gas present within both lungs following 7 days of antimicrobial therapy LUS of the entire chest wall was performed Four entities were defined  1. Consolidation  2. Multiple irregularly spaced B-lines  3. Multiple abutting ultrasound lung “comets” issued from the pleural line or a small subpleural consolidation  4. Normal aeration LUS changes were measured between day 0 and 7 for each of 12 regions LUS reaeration score was calculated	LUS score >5: CT reaeration >400 mL and a successful antimicrobial therapy LUS score <−10: Loss of CT aeration >400 mL and a failure of antibiotics Highly significant correlation between CT and LUS reaeration (Rho=0.85, P<0.0001) Chest radiography was inaccurate in predicting lung reaeration
Bouhemad et al., 2011[7]	ARDS-30 ALI - 10	LUS	PV curve analysis	PV curves and LUS were performed in PEEP 0 and PEEP 15 cm H2O PEEP-induced lung recruitment was measured using the PV curve method. Four LUS entities were defined  1. Consolidation-C;  2. Multiple, irregularly spaced B lines-B2;  3. Multiple coalescent B lines-B1;  4. Normal aeration-N PEEP-induced LUS changes were measured for each of the 12 lung regions, and an LUS reaeration score was calculated	Highly significant correlation between PEEP-induced lung recruitment measured by PV curves and LUS reaeration score (Rho=0.88; P<0.0001) LUS reaeration score of ≥ + 8: PEEP-induced lung recruitment >600 ml LUS reaeration score of ≤ + 4: PEEP-induced lung recruitment 75 to 450 ml Statistically significant correlation between LUS reaeration score and PEEP-induced increase in PaO2 (Rho=0.63; P<0.05)
Stefanidis et al., 2011[15]	10	LUS	Arterial oxygenation	LUS was performed in all patients to depict the nonaerated area in the dependent lung regions Incremental PEEP settings of 5, 10 and 15 cm H2O LUS assessment of the nonaerated lung area and ABG analysis performed simultaneously at different levels of PEEP	-Significant reduction in nonaerated areas in the dependent lung regions (P<0.01) PEEP 5 cm H2O - 27±31 cm2 PEEP 10 cm H2O - 20±24 cm2 PEEP 15 cm H2O - 11±12 cm2 - A significant increase in PaO2 (P<0.01) PEEP 5 cm H2O - 74±15 mmHg PEEP 10 cm H2O - 90±19 mmHg PEEP 15 cm H2O - 102±26 mmHg
Rode et al., 2012[16]	17	LUS	PV curve analysis	Two methods one inspiratory LIP on the ventilator PV curve and another LUS probe were compared for setting the ventilators PEEP The LIP that helps in estimating the required PEEP for recruitment of alveolar consolidation was measured with continuous low-flow method, as pressure in cmH2O Expiratory leveling between the lower border of subpleural consolidation and adjacent pleural line, which means lung recruitment, was followed with linear ultrasound probe	LIP pressure never exceeded the PEEP for recruitment of subpleural consolidations followed with LUS and a significant correlation (r=0.839; P<0.05) was found between two methods LUS method could be the guide for PEEP lung recruitment
Shen et al., 2014[12]	18	LUS	Pressure-Volume curve analysis	PV curves and LUS were performed at PEEP 12, 8, 4 and 0 cm H2O For each of the 12 lung regions examined, PEEP-induced ultrasound changes were measured, and an LUS was calculated	Highly significant correlation between PEEP-induced lung volume change measured by PV curves and LUS change (r=0.82, P<0.01) Statistically significant correlation between LUS change and PEEP-induced increase in PaO2 (r=0.66, P<0.01)
Algieri et al., 2014[11]	7	LUS	CT scan	LUS was performed considering six areas for each lung to assign reaeration score Aeration score used: 0 - Normal lung; 1-?≥3 noncoalescent B-lines; 2-≥3 coalescent B-lines; 3 - consolidation Cumulative LUS score (0-36) for the two lungs was obtained as sum of all areas’ individual scores, each area’s score being the average of all pertaining LUS findings LUS recruiters upon PEEP increase from 5 to 15 cm H2O were defined by the switch of at least three areas to well aerated (area score 0) LUS-based assessment of lung aeration and lung recruitability was compared with qCT findings	14 conditions were evaluated Median LUS score was 19 (IQR 14-23) LUS score≥19 (n=8): 34±13% of nonaerated tissue at qCT LUS score>20 (n=6): 48±18% (P<0.05) Reduction at LUS of consolidated areas (area score 3) versus reduction of qCT nonaerated volume (R2=0.66, significant correlation) Reduction at LUS of poorly aerated areas (area score 1 to 2) versus reduction of qCT poorly aerated volume (R2=0.74, significant correlation) Change at LUS of at least three areas to well aerated (LUS recruiters, n=4) corresponded to a qCT increase in well-aerated lung volume of 788±262 g versus 431±35 g in the LUS nonrecruiter group (n=3) (P<0.05)
Du et al., 2015[14]	1	LUS	Arterial oxygenation	LUS assessment of the lung status and ABG analysis were performed simultaneously at different levels of incremental PEEP applied during RM	Area of consolidation observed with LUS at baseline PEEP 5 cm H2O (corresponding PaO2-89 mm Hg, FiO2-0.75 and PaO2/FiO2-119 mm Hg) Recruitment (consolidation→lung tissue) observed with LUS at PEEP 40 cm H2O for >40 s during incremental PEEP titration The PEEP was decreased and maintained at 20 cm H2O. (corresponding PaO2-100 mm Hg and PaO2/FiO2-167 mm Hg with a FiO2 of 0.60) After 12 h, PaO2/FiO2-261 mm Hg with recruitment of lung tissue under direct LUS guidance
Li et al., 2015[13]	12 rabbits	LUS	Arterial oxygenation	Random allocation of 12 rabbits with saline lavage-induced lung injury in two groups Group 1  Recruitment guided by LUS Method: The estimated LUS reaeration score was compared with the previous score at each PEEP level  Adequacy of recruitment was achieved if the reaeration score stopped further increasing. Group 2  Recruitment guided by maximal oxygenation Method: RM were applied according to a stepwise incremental PEEP pressure strategy (2 cm H2O) PaO2+PaCO2 ≥400 mm Hg was used to define adequate recruitment	Opening pressure significantly higher in the LUS group than the oxygenation group (23.4±3.4 cm H2O versus 18.7±2.1 cm H2O; P<0.05). Arterial oxygenation significantly higher in the LUS group than the oxygenation group (552±77 mm Hg versus 465±57 mm Hg; P<0.05). The reaeration score in the LUS group significantly increased during alveolar recruitment (6.5±1.6 points at baseline versus 13.8±3.0 points after completion; P<0.05) LUS-guided recruitment improved aeration in all regions and substantially improving lung heterogeneity compared to maximal oxygenation method
Lu et al., 2017[21]	18/50	LUS	Arterial oxygenation	Patients with paraquat intoxication assessed by LUS at day 1, day 3 and day 7 after the treatment Lung aeration represented by the LUS score Relationship of LUS score with the development of ARDS (PaO2/FiO2) was evaluated 12 lung areas were examined on right and left lung in each patient delineated by parasternal line, anterior axillary line, posterior axillary line, and paravertebral line: anterosuperior, anteroinferior, laterosuperior; lateroinferior, posterosuperior, and posteroinferior lung region Number assigned to each area according to the most severe LUS pattern  0. Normal aeration: presence of lung sliding with horizontal A lines or fewer than two isolated vertical B lines  1. Moderate loss of lung aeration: either multiple well defined and spaced B1 lines, issued from the pleural line or from small juxtapleural consolidations and corresponding to interstitial edema; or coalescent B1 lines, issued from the pleural line or from small juxtapleural consolidations, present in a limited portion of the intercostal space and corresponding to localized alveolar edema  2. Severe loss of lung aeration: multiple coalescent vertical B2 lines issued either from the pleural line or from juxtapleural consolidations, detected in the whole area of one or several intercostal spaces and corresponding to diffuse alveolar edema  3. Lung consolidation: the presence of tissue pattern containing either hyperechoic punctiform images representative of static air bronchograms, or hyperechoic tubular images, representative of dynamic air bronchograms, corresponding to complete loss of aeration LUS score was calculated as the sum of points ranging from 0 to 36	18 ARDS and 32 non-ARDS patientsTotal LUS score significantly different (P<0.001) on Day 1 (7.8±3.1 vs. 5.6±2.4) Day 3 (12.0±3.4 vs. 8.3±2.2) Day 7 (14.8±4.4 vs. 8.5±3.9) PaO2/FiO2 ratio significantly different (P<0.001) Day 1 (230.2±50.3 vs. 185.4±51.8) Day 3 (228.8±52.4 vs. 139.0±43.7) Day 7 (244.3±69.3 vs. 82.1±26.7) A significant difference between the two groups (P<0.001) on day 3 and day 7 for median LUS score and PaO2/FiO2 ratio Decrease in PaO2/FiO2 was significantly correlated (R=0.013; P=0.035) with the increase in LUS between day 1 and day 7
Tang et al.[22]	40	LUS	Arterial oxygenation	40 ARDS patients randomly divided into two groups: LUS group (n=20) and oxygenation group (n=20) The PEEP incremental method was used to perform recruitment maneuvers Ultrasound scoring based on the scoring pattern as adopted by Bouhemad and the oxygenation method were used to evaluate the pulmonary recruitment end-point LUS group  Recruitment guided by LUS Method: The estimated LUS reaeration score was compared with the previous score at each PEEP level  Adequacy of recruitment was achieved if the reaeration score stopped further increasing Oxygenation group Recruitment guided by maximal oxygenation  Method: RM were applied according to a stepwise incremental PEEP pressure strategy for 15 min each time PaO2 + PaCO2 ≥400 mm Hg was used to define adequate recruitment  PEEP incremental method was used to select the best PEEP to reduce the PEEP for 2 cm H2O every 5 min  LUS group - 2 consecutive scores suddenly increased by >30%, then the last level was the best PEEP Oxygenation group - PaO2/FiO2 reduced by more than 10%, then the last level was the best PEEP	The oxygenation index, PEEP, peak airway pressure (Ppeak), mean airway pressure (Pmean), and dynamic compliance (Cdyn) in the oxygenation group were significantly lower than those in the LUS group (P<0.05) at the pulmonary recruitment end-point Best PEEPs in the oxygenation and LUS groups - 13.1±3.1 versus 15.7±4.2 cm H2O, respectively, with a significant difference (t=2.227, P=0.016) Compared with the basal state, the Cdyn, oxygenation index, Pmean, and Ppeak in both groups significantly increased after pulmonary recruitment (P<0.05) Cdyn and oxygenation index in the LUS group were significantly higher than those in the oxygenation group after pulmonary recruitment (P<0.05)

ABG: Arterial blood gas, ARDS: Acute respiratory distress syndrome, CT: Computed tomography, LUS: Lung Ultrasound, PEEP: Positive end-expiratory pressure, PV: Pressure-volume, LIP: Lower inflection point, FiO2: Fraction of inspired oxygen, qCT: Quantitative CT, RM: Recruitment maneuver, VAP: Ventilator associated pneumonia, ALI: Acute lung injury