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Supplemental Digital Content

Global and Regional Respiratory Mechanics During Robotic-Assisted Laparoscopic

Surgery: A Randomized Study

Julio C. Brandão M.D., Marcos A. Lessa M.D. Ph.D., Gabriel Motta-Ribeiro M.Sc., Soshi

Hashimoto M.D. Ph.D, Luis Felipe Paula M.Sc., Vinicius Torsani M.Sc., Linh Le, Xiaodong Bao

M.D., Matthias Eikermann M.D., Douglas M. Dahl M.D., Hao Deng M.D. Ph.D., Shahin Tabatabaei

M.D., Marcelo M.B. Amato M.D., Marcos F. Vidal Melo M.D. Ph.D.

RESULTS

General Cardiopulmonary Measurements

Mechanical ventilation was performed as planned (VT=7.6±1.0 ml.kg-1 and PEEP=6 [6-7] cmH2O),

with adequate oxygenation (SpO2=99±2%) and average PETCO2=39±5 mmHg throughout the study.

Intra-abdominal pressure was 14.4±1.4 mmHg (19.6±1.9 cmH2O) during pneumoperitoneum and

13.5±2.0 mmHg (18.4±2.7 cmH2O) during the Trendelenburg period. Pneumoperitoneum was

associated with a significant and parallel rise in PMAX, PMEAN, and plateau pressure, further

increased with Trendelenburg and decreased following abdominal deflation (Table 2).

Pneumoperitoneum was also associated with a 26% increase in mean arterial pressure (P<0.001)

that returned to baseline after release. Left ventricular function, assessed by fractional shortening,

and heart rate did not show any significant change during the procedure (Table 2).

Lung and Chest Wall Mechanical Properties

When compared to baseline, the driving pressure increased substantially by 74% with

pneumoperitoneum inflation from 9.1±2.9 to 15.8±4.2 cmH2O and further by 16% to 18.3±4.2

cmH2O after Trendelenburg/docked robot (Figure 2A) and both transpulmonary and chest wall

components of the driving pressure increased. The percent change in each of these pressures was

uneven. The transpulmonary pressure component increased by only 28% of its baseline values

with pneumoperitoneum (Figure 2B). Instead, the chest wall component increased by 143% of its

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baseline values (Figure 2C). Both transpulmonary and chest wall tidal pressure changes were

further increased by 16% after Trendelenburg/docked robot resulting in an increase of chest wall

pressure component from 3.6±1.5 cmH2O at baseline to 10.2±3.0 cmH2O after

Trendelenburg/docked robot (Figure 2B,), while the transpulmonary pressure component increased

from 7.0±3.5 to 10.4±4.5 cmH2O between the same points (Figure 2C). These uneven effects

reduced the average distribution of driving pressure to the lungs from 63±15% at baseline to

49±14% during Trendelenburg and docked robot (P<0.001). Of note, while the change in pressure

required to move the chest wall returned to baseline following pneumoperitoneum deflation, a

residual positive increase in driving pressure was present due to an increased transpulmonary

pressure as compared to baseline (Figures 2A and 2B, P<0.001).

From baseline, respiratory system elastance increased by 84% with pneumoperitoneum inflation

(Figure 3A, P<0.001), and further by 10% after Trendelenburg/docked robot (Figure 3A, P<0.01).

Those increases were predominantly due to a 153% increase in chest wall elastance with

pneumoperitoneum inflation and additional 13% with Trendelenburg/robot docked (Figure 3C,

P<0.05). In contrast, significant (P<0.001) but clearly smaller changes were observed for lung

elastance with 35% increase after pneumoperitoneum inflation and no significant change after

Trendelenburg/docked robot (Figure 3B). Indeed, chest wall elastances were lower than lung

elastances at baseline (ECW=6.8±3.5 cmH2O.L-1 versus EL=9.6±5.9 cmH2O.L-1, Figures 3B and 3C,

point a) yet higher during Trendelenburg/docked robot (ECW=19.5±7.9 cmH2O.L-1 versus

EL=13.7±8.0 cmH2O.L-1, Figures 3B and 3C), with a larger increase in chest wall than lung

elastance (12.7±7.6 versus 4.3±5.0 cmH2O.L-1, P<0.001). Because the distribution of driving

pressures to the lungs occurs according to the ratio of EL/(EL+ECW)1, the distribution of those

pressures to the lungs during Trendelenburg/docked robot were reduced to 41%

(=13.7/(13.7+19.5)) from 59% at baseline (=9.6/(9.6+6.8)). The average increase from baseline to

Trendelenburg/docked robot in the component of driving pressure distributed to the chest wall was

6.6±3.1 cmH2O, higher than that to the lungs (3.4±3.1 cmH2O, P<0.001) (Figures 2B and 2C).

The percentage of volume dependent respiratory system elastance (%E2) became significantly

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more negative during pneumoperitoneum inflation and Trendelenburg/docked robot (Table 2),

consistent with lungs operating in the initial (partially derecruited) portion of the pulmonary

pressure-volume curve. Importantly, pneumoperitoneum deflation did not change the %E2, which

was significantly reduced as compared to baseline (Table 2).

Regional Lung Aeration and Ventilation

Aeration within the whole region-of-interest sampled with EIT was significantly reduced from

baseline to pneumoperitoneum deflation (Figure 4A), as well as along measurements performed

during pneumoperitoneum and Trendelenburg/docked robot stages (Figure 4A). These changes

were present in both ventral and dorsal regions-of-interest, with larger reduction of aeration in

dorsal regions (Fig. 4B and 4C).

Ventilation within the whole region-of-interest was lower at pneumoperitoneum deflation than

baseline due to a significant and predominant reduction in ventilation of the ventral lung regions

(Figures 4D, 4E, and Supplemental Figure 4). No changes in ventilation either within the whole

region of interest or in ventral or dorsal regions were observed between the pneumoperitoneum

and Trendelenburg/docked robot stages (Figures 4D, 4E and 4F). Dorsal ventilation after

pneumoperitoneum deflation returned to baseline values (Figure 4F), suggesting an increase in the

ventilation/aeration ratio in dorsal regions.

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Supplemental Table 1: Least-square means of measured variables at each of the four comparison points for hypotheses 1: Differences at surgical stages.

LS Means

Baseline(T0)

PNP inflation(T1)

Trendelenburg (T2, T3 and T4)

PNP deflation(T5)

Chest Wall Elastance 6.8 17.4 19.8 6.5Chest Wall Resistance 1.6 2.5 2.5 1.2

Driving Pressure 9.1 15.9 18.4 11.1Lung Elastance 9.6 12.8 13.9 10.5

Respiratory System Elastance 16.3 30.2 33.7 17.0Lung Resistance 8.3 9.9 10.0 8.1

Respiratory System Resistance 9.9 12.4 12.5 9.2Mean Oesophageal Pressure 11.8 15.6 16.2 13.1

Heart Rate 64.8 65.6 64.8 70.0Mean Arterial Pressure 77.1 97.7 83.6 78.5

PetCO2 34.4 37.4 41.2 42.7Peak Airway Pressure 19.0 26.3 29.5 23.2

Plateau Pressure 16.1 23.4 26.3 19.3Mean Airway Pressure 10.4 12.6 13.9 12.7

% E2 -4.9 -15.1 -13.9 -12.8Delta Oesophageal Pressure 3.6 8.9 10.3 3.9

Delta Transpulmonary Pressure 7.0 8.9 10.3 9.4Global Aeration -8.4 18.1 -22.6 -49.9

Anterior Aeration -6.6 10.8 -14.9 -20.3Posterior Aeration -2.2 4.8 -10.2 -28.7Global Ventilation 25.3 17.2 17.4 21.1

Anterior Ventilation 17.0 11.4 11.6 12.9Posterior Ventilation 8.3 5.8 5.8 8.2

FiO2 59.6 55.4 53.6 47.2Tidal Volume/PBW 7.4 7.5 7.7 7.7Respiratory Rate 13.2 13.6 15.3 16.3

Tidal Volume 500.4 505.4 515.4 511.7

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Supplemental Table 2: Multiple comparisons between time points. P-values were adjusted by Bonferoni method, with each variable as an independent family.

Difference SE 95% CI LB 95% CI UB P-Value

Adj. P-ValueChest Wall Elastance

Baseline - PNP inflation -10.6 1.1 -12.7 -8.5 0.000 <0.001PNP inflation - Trendelenburg -2.4 0.9 -4.1 -0.6 0.008 0.030

Baseline - PNP deflation 0.2 1.1 -1.9 2.4 0.823 0.999Trendelenburg - PNP deflation 13.2 0.9 11.5 15.0 0.000 <0.001

Chest Wall ResistanceBaseline - PNP inflation -0.9 0.1 -1.2 -0.6 0.000 <0.001

PNP inflation - Trendelenburg 0.0 0.1 -0.2 0.2 0.948 0.999Baseline - PNP deflation 0.4 0.1 0.1 0.7 0.004 0.018

Trendelenburg - PNP deflation 1.4 0.1 1.1 1.6 0.000 <0.001Driving Pressure

Baseline - PNP inflation -6.9 0.5 -7.8 -5.9 0.000 <0.001PNP inflation - Trendelenburg -2.5 0.4 -3.3 -1.7 0.000 <0.001

Baseline - PNP deflation -2.0 0.5 -3.0 -1.1 0.000 <0.001Trendelenburg - PNP deflation 7.3 0.4 6.5 8.1 0.000 <0.001

Lung ElastanceBaseline - PNP inflation -3.3 0.8 -4.8 -1.7 0.000 <0.001

PNP inflation - Trendelenburg -1.1 0.7 -2.4 0.2 0.112 0.449Baseline - PNP deflation -0.9 0.8 -2.5 0.7 0.249 0.994

Trendelenburg - PNP deflation 3.4 0.7 2.1 4.7 0.000 <0.001Respiratory System Elastance

Baseline - PNP inflation -13.9 1.3 -16.4 -11.4 0.000 <0.001PNP inflation - Trendelenburg -3.4 1.0 -5.5 -1.4 0.001 0.005

Baseline - PNP deflation -0.7 1.3 -3.2 1.8 0.596 0.999Trendelenburg - PNP deflation 16.6 1.1 14.5 18.7 0.000 <0.001

Lung ResistanceBaseline - PNP inflation -1.5 0.5 -2.5 -0.6 0.001 0.004

PNP inflation - Trendelenburg -0.2 0.4 -0.9 0.6 0.700 0.999Baseline - PNP deflation 0.3 0.5 -0.7 1.2 0.592 0.999

Trendelenburg - PNP deflation 2.0 0.4 1.2 2.7 0.000 <0.001Respiratory System Resistance

Baseline - PNP inflation -2.5 0.5 -3.5 -1.5 0.000 <0.001PNP inflation - Trendelenburg -0.2 0.4 -1.0 0.7 0.693 0.999

Baseline - PNP deflation 0.7 0.5 -0.3 1.7 0.190 0.762Trendelenburg - PNP deflation 3.3 0.4 2.5 4.1 0.000 <0.001

Mean Oesophageal PressureBaseline - PNP inflation -3.8 0.7 -5.1 -2.4 -3.8 <0.001

PNP inflation - Trendelenburg -0.7 0.6 -1.8 0.5 -0.7 0.995Baseline - PNP deflation -1.3 0.7 -2.7 0.1 -1.3 0.251

Trendelenburg - PNP deflation 3.1 0.6 1.9 4.3 3.1 <0.001Heart Rate

Baseline - PNP inflation -0.8 2.0 -4.7 3.2 0.705 0.999PNP inflation - Trendelenburg 0.8 1.6 -2.4 4.0 0.618 0.999

Baseline - PNP deflation -5.1 2.0 -9.1 -1.2 0.012 0.046

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Trendelenburg - PNP deflation -5.2 1.6 -8.4 -2.0 0.002 0.007Mean Arterial Pressure

Baseline - PNP inflation -20.6 2.9 -26.4 -14.9 0.000 <0.001PNP inflation - Trendelenburg 14.1 2.3 9.5 18.7 0.000 <0.001

Baseline - PNP deflation -1.5 2.9 -7.2 4.3 0.615 0.999Trendelenburg - PNP deflation 5.1 2.3 0.5 9.7 0.032 0.126

PetCO2Baseline - PNP inflation -2.9 0.9 -4.6 -1.2 0.001 0.003

PNP inflation - Trendelenburg -3.8 0.7 -5.2 -2.4 0.000 <0.001Baseline - PNP deflation -8.2 0.9 -10.0 -6.5 0.000 <0.001

Trendelenburg - PNP deflation -1.5 0.7 -2.9 -0.1 0.032 0.127Peak Airway Pressure

Baseline - PNP inflation -7.4 0.6 -8.5 -6.3 0.000 <0.001PNP inflation - Trendelenburg -3.2 0.5 -4.1 -2.3 0.000 <0.001

Baseline - PNP deflation -4.3 0.6 -5.4 -3.1 0.000 <0.001Trendelenburg - PNP deflation 6.3 0.5 5.4 7.2 0.000 <0.001

Plateau PressureBaseline - PNP inflation -7.2 0.5 -8.2 -6.2 0.000 <0.001

PNP inflation - Trendelenburg -2.9 0.4 -3.8 -2.1 0.000 <0.001Baseline - PNP deflation -3.1 0.5 -4.2 -2.1 0.000 <0.001

Trendelenburg - PNP deflation 7.0 0.4 6.2 7.9 0.000 <0.001Mean Airway Pressure

Baseline - PNP inflation -2.2 0.2 -2.7 -1.8 0.000 <0.001PNP inflation - Trendelenburg -1.3 0.2 -1.6 -0.9 0.000 <0.001

Baseline - PNP deflation -2.3 0.2 -2.8 -1.9 0.000 <0.001Trendelenburg - PNP deflation 1.2 0.2 0.8 1.6 0.000 <0.001

% E2Baseline - PNP inflation 10.2 2.1 6.0 14.4 0.000 <0.001

PNP inflation - Trendelenburg -1.1 1.8 -4.6 2.3 0.515 0.999Baseline - PNP deflation 7.9 2.1 3.6 12.1 0.000 0.001

Trendelenburg - PNP deflation -1.2 1.8 -4.7 2.4 0.516 0.999Delta Oesophageal Pressure

Baseline - PNP inflation -5.3 0.5 -6.2 -4.4 0.000 <0.001PNP inflation - Trendelenburg -1.4 0.4 -2.1 -0.6 0.000 0.001

Baseline - PNP deflation -0.2 0.5 -1.1 0.7 0.606 0.999Trendelenburg - PNP deflation 6.4 0.4 5.7 7.2 0.000 <0.001

Delta Transpulmonary PressureBaseline - PNP inflation -2.0 0.5 -2.9 -1.0 0.000 <0.001

PNP inflation - Trendelenburg -1.4 0.4 -2.1 -0.6 0.001 0.002Baseline - PNP deflation -2.4 0.5 -3.4 -1.5 0.000 <0.001

Trendelenburg - PNP deflation 0.9 0.4 0.1 1.7 0.026 0.105Global AerationPNP inflation – Trendelenburg 40.7 4.6 31.6 49.9 0.000 <0.001

Baseline - PNP deflation 41.5 6.0 29.7 53.3 0.000 <0.001Anterior AerationPNP inflation – Trendelenburg 25.7 3.2 19.3 32.1 0.000 <0.001

Baseline - PNP deflation 13.7 4.1 5.5 21.9 0.001 0.002Posterior Aeration

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PNP inflation – Trendelenburg 15.0 2.8 9.4 20.6 0.000 <0.001Baseline - PNP deflation 26.5 3.6 19.3 33.7 0.000 <0.001

Global VentilationPNP inflation – Trendelenburg -0.2 0.7 -1.6 1.3 0.801 0.999

Baseline - PNP deflation 4.2 1.0 2.3 6.1 0.000 <0.001Anterior VentilationPNP inflation – Trendelenburg -0.1 0.6 -1.2 1.0 0.822 0.999

Baseline - PNP deflation 4.1 0.7 2.7 5.5 0.000 <0.001Posterior VentilationPNP inflation – Trendelenburg -0.1 0.4 -0.8 0.6 0.848 0.999

Baseline - PNP deflation 0.0 0.5 -0.9 0.9 0.974 0.999FiO2

Baseline - PNP inflation 4.2 2.0 0.3 8.1 0.037 0.148PNP inflation - Trendelenburg 1.8 1.6 -1.4 5.1 0.259 0.999

Baseline - PNP deflation 12.3 2.0 8.4 16.3 0.000 <0.001Trendelenburg - PNP deflation 6.3 1.6 3.1 9.5 0.000 0.001

Tidal Volume/PBWBaseline - PNP inflation -0.1 0.1 -0.4 0.2 0.497 0.999

PNP inflation - Trendelenburg -0.2 0.1 -0.4 0.1 0.150 0.601Baseline - PNP deflation -0.2 0.1 -0.5 0.0 0.095 0.379

Trendelenburg - PNP deflation 0.0 0.1 -0.2 0.3 0.819 0.999Respiratory Rate

Baseline - PNP inflation -0.4 0.4 -1.1 0.3 0.289 0.999PNP inflation - Trendelenburg -1.7 0.3 -2.3 -1.1 0.000 <0.001

Baseline - PNP deflation -3.1 0.4 -3.9 -2.4 0.000 <0.001Trendelenburg - PNP deflation -1.0 0.3 -1.6 -0.4 0.001 0.005

Tidal VolumeBaseline - PNP inflation -5.0 9.0 -22.8 12.8 0.578 0.999

PNP inflation - Trendelenburg -9.9 7.4 -24.6 4.7 0.182 0.728Baseline - PNP deflation -11.3 9.0 -29.1 6.5 0.212 0.849

Trendelenburg - PNP deflation 3.7 7.4 -11.0 18.3 0.620 0.999Trendelenburg represents the mean over the time. PNP, pneumoperitoneum.

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Supplemental Table 3: Least-square means of the deep and moderate relaxation (TOF) states during the crossover period for hypothesis 2: Deep vs. Moderate Group differences at T2-T4 .

LS Group Means Difference 95% CI

LB95% CI

LBP-

Value

Deep

Moderate

(Deep-Moderate)

Chest Wall Elastance 19.6 19.2 0.3 -0.9 1.5 0.601Driving Pressure 18.4 18.3 0.1 -0.5 0.7 0.687Lung Elastance 13.8 13.6 0.2 -0.8 1.2 0.690

Respiratory System Elastance 33.4 33.0 0.4 -1.0 1.8 0.568

Lung Resistance 10.1 10.0 0.1 -0.5 0.7 0.701Mean Arterial Pressure 82.8 84.5 -1.6 -5.1 1.8 0.349

Delta Oesophageal Pressure 10.3 10.1 0.1 -0.5 0.7 0.664

Delta Transpulmonary Pressure 10.4 10.4 0.0 -0.5 0.6 0.976

Global Aeration -22.7 -26.8 4.0 -1.0 9.0 0.111Anterior Aeration -15.2 -17.6 2.4 -1.8 6.6 0.256Posterior Aeration -10.3 -11.7 1.4 -1.4 4.2 0.310Global Ventilation 17.0 17.9 -1.0 -2.3 0.4 0.167

Anterior Ventilation 11.3 12.0 -0.7 -1.7 0.3 0.160Posterior Ventilation 5.7 5.9 -0.3 -0.8 0.3 0.374

(All models are looking at T2-T4 while adjusting for baseline as well as time). The P-values are raw P-values and Linear Mixed Effects model was used.

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Figure legends

Supplemental Figure 1: Tracings representative of the different patterns of eletrical

stimulatiom and evoked muscule response according with the level of neuromuscular

blockade (NMB). TOF, train-of-four; TS, tetanic stimulation; PTS, post-tetanic stimulation;

PTC, post-tetanic count.

Supplemental Figure 2: Flow diagram for determination of time point corresponding to 1

twitch in the train-of-four (TOF) in anesthetized patients undergoing robotic laparoscopic

surgery. Two equal TOF responses were required for acceptance of target.

Supplemental Figure 3: Flow diagram for determination of time point corresponding to 1-

2 twitches in the post-tetanic count (PTC) in anesthetized patients undergoing robotic

laparoscopic surgery. TOF = train-of-four.

Supplemental Figure 4: Ventral (V) and (D) dorsal distribution of regional lung ventilation

as assessed by electrical impedance tomography in a supine anesthetized patient

undergoing robotic surgery at baseline (immediately after intubation) and at the end of the

surgery, following deflation of the pneumoperitoneum. There is a reduction in ventral

ventilation at the end of the surgery. Ventilation is shown in a dark blue (no ventilation) to

white (maximal ventilation in the image) scale.

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Supplemental Figure 1

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Supplemental Figure 2

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Supplemental Figure 3

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Supplemental Figure 4

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References

1. Polese G, Rossi A, Appendini L, Brandi G, Bates JH, Brandolese R. Partitioning of respiratory mechanics in mechanically ventilated patients. J Appl Physiol 1991; 71(6): 2425-2433