ORIGINAL ARTICLE

Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax H. Reinius1*, J. B. Borges1,2*, F. Fredén1, L. Jideus3, E. D. L. B. Camargo4, M. B. P. Amato2, G. Hedenstierna5, A. Larsson1 and F. Lennmyr6 1

Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil 3 Department of Surgical Sciences, Section of Cardiothoracic Surgery, Uppsala University, Uppsala, Sweden 4 Department of Mechanical Engineer, Polytechnic School, University of São Paulo, São Paulo, Brazil 5 Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden 6 Department of Surgical Sciences, Section of Cardiothoracic Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden 2

Correspondence J. B. Borges, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Hospital, 751 85 Uppsala, Sweden E-mail: [email protected] Conflicts of interest The authors confirm that there are no conflicts of interest. Funding The Swedish Heart and Lung Foundation and research funds of Uppsala University Hospital supported this study. *Henrik Reinius and João Batista Borges have contributed similarly to the study and share the position as first author. Both are ex aequo first authors. Location where the work was carried out: Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden Submitted 29 October 2014; accepted 17 November 2014; submission 21 March 2014. Citation Reinius H, Borges JB, Fredén F, Jideus L, Camargo EDLB, Amato MBP, Hedenstierna G, Larsson A, Lennmyr F. Real-time assessment of ventilation and perfusion distributions by electrical impedance tomography in a piglet model of one-lung ventilation with capnothorax. Acta Anaesthesiologica Scandinavica 2015

Background: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting. Methods: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19 cm H2O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10 cm H2O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured. Results: During right-sided capnothorax, mixed venous oxygen saturation (P = 0.018), as well as a tissue oxygenation index (P = 0.038) decreased. There was also an increase in central venous pressure (P = 0.006), and a decrease in mean arterial pressure (P = 0.045) and cardiac output (P = 0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/ capnothorax, no or very minor ventilation on the right side could be seen (3 ± 3% vs. 97 ± 3%, right vs. left, P = 0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 ± 2% vs. 82 ± 2%, right vs. left, P = 0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 ± 4% vs. 16 ± 4%, right vs. left). Conclusion: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

doi: 10.1111/aas.12455 Acta Anaesthesiologica Scandinavica 59 (2015) 354–368

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Editorial comment: what this article tells us Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation may entail respiratory and hemodynamic impairments. This paper presents an experimental model setup which together with functional electrical impedance tomography may be valuable to enable future studies addressing optimal perioperative management during the challenging situation of sequential one-lung ventilation with capnothorax. One-lung ventilation (OLV) is an important method to facilitate thoracic surgery.1,2 Thoracoscopic surgery requires further optimized exposure, and this can be achieved by insufflation of carbon dioxide into the pleural cavity, capnothorax.3,4 One indication for sequential OLV/capnothorax is atrial fibrillation surgery, a common disorder, for which the panel of possible interventions includes thoracoscopic surgery.5,6 The physiology of the OLV/capnothorax during this procedure remains to be better understood, characterized and monitored, since previous information of OLV without capnothorax may not be entirely applicable.7 For a better and well-timed decision-making process in the perioperative management, there is a need to promptly detect and appropriately assess any physiologic disturbances that can occur, as well as to promptly evaluate the realtime effects of the interventions decided by the anesthesiologist. Hemodynamic and respiratory perturbations as well as carbon dioxide (CO2) retention are common during this surgery and high-risk patients may be disqualified from surgery due to marked cardiopulmonary dysfunction or physical limitations such as morbid obesity. A method with the ability to track the frequent changes in the lung structure and function that can occur during OLV/capnothorax, allowing for continuous monitoring, and capable of repeated data acquisition and interpretation in real time is desirable. Electrical impedance tomography (EIT) has emerged as a new functional imaging method potentially meeting many clinical needs.8–11 Subjecting the chest to minute electrical currents, this radiation-free, noninvasive technique measures the electric potentials at the chest wall surface to produce two-dimensional (2-D) images that reflect the impedance distribution within the thorax. Cyclic variations in pulmonary air and blood content are the major determinants for the

changes in thoracic impedance, the former usually of much larger magnitude. Because cyclic changes in local impedance mainly correspond to changes in lung aeration, clinical and experimental studies11–15 have shown that EIT can reliably assess imbalances in the distribution of regional ventilation. Besides other features like portability and the possibility of around-the-clock monitoring, the high temporal resolution is an important aspect of bedside imaging that allows for the study not only of ventilation but also of faster physiological phenomena, such as estimation of regional lung perfusion at the bedside. Indeed, it was recently exhibited that, in both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by single-photonemission computerized tomography.16 The EIT distribution of pulmonary blood flow has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions. We therefore sought to investigate in detail the online physiological effects of OLV/capnothorax by EIT. To that end, we developed a porcine model to mimic the clinical setting during OLV/ capnothorax and to scrutinize the real-time behavior of the physiology of the OLV/ capnothorax procedure. Methods The study was conducted as a prospective animal experiment. The Animal Ethics Committee approved the study protocol. The National Institute of Health guidelines for animal research were followed. Animals Five piglets (weighing 25 to 30 kg) of the Hampshire, Yorkshire, and Swedish country breeds were used.

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Anesthetic management The piglets were pre-medicated by an intramuscular injection of xylazine (2.2 mg/kg, Rompun, Bayer, Leverkusen, Germany), tiletamine/ zolazepam (6 mg/kg, Zoletil, Virbac, Carros, France), and atropine (0.04 mg/kg, NMPharma, Stockholm, Sweden). Anesthesia was then induced with propofol, starting with 5 mg/kg (Diprivan, Astra, Södertälje, Sweden), and with fentanyl (5 μg/kg, Leptanal, Janssen-Cilag AB, Sweden), both administered via an ear vein. After adequate depth of anesthesia was achieved, tested by absence of responses (signs of awakening or withdrawal reactions) to painful stimulation between the back toes, anesthesia was maintained by continuous infusions of propofol (10 mg/kg/h), fentanyl (5 μg/kg/h) and pancuronium (0.3 mg/ kg/h, Pavulon, Organon, Oss, the Netherlands). Depth of anesthesia was intermittently tested with blood pressure and heart rate response to pain stimulation. A bolus dose of fentanyl 0.2 mg was given intravenously if the anesthesia was considered insufficient. An infusion of Ringer’s acetate, 10 ml/kg/h, was administered during the first 2 h of the protocol. The infusion rate was then lowered to 5 ml/kg/h for the rest of the experiment. All piglets received fluid boluses of Ringers acetate 5 ml/kg followed by intravenous bolus of 0.1 mg phenylephrine if signs of hemodynamic instability occurred. Indications for hemodynamic optimization were mean arterial pressure less than 50 mmHg. Body temperature was monitored and kept at 37–39°C by thermal convection. Airway and ventilation Five to 10 min after pre-medication and immediately after deepening of anesthesia, the trachea was intubated with an ID 7.0 mm cuffed endotracheal tube (Mallinckrodt, Athlone, Ireland). During baseline settings and the two-lung ventilation (TLV) periods, the animals were mechanically ventilated with pressure regulated volume controlled ventilation (PRVC) (Servo i, Maquet, Solna, Sweden). Inspired oxygen fraction (FIO2) was 0.5, positive end-expiratory pressure (PEEP) 5 cm H2O, tidal volume (VT) 10 ml/kg and I : E ratio of 1:2. A median tracheotomy was performed, and the orotracheal tube was replaced by a size 35 right-

sided, double-lumen tube (Mallinckrodt), positioned with the tip in the left main bronchus under fiber-bronchoscopy control (EF-B 14L, Xion medical, Berlin, Germany). Respiratory rate (RR) was adjusted to keep an arterial PaCO2 of 4.7–6 kPa throughout the protocol. However, in order to avoid the occurrence of dynamic hyperinflation, a maximum respiratory rate of 35/min was defined. When this limit for the respiratory rate was reached, an increased PaCO2 was accepted. Gas flow and airway pressures were measured at the proximal end of the endotracheal tube (CO2SMO Veterinary CO2 Monitor and Pulse Oximeter, Respironics, Pittsburgh, PA, USA). For oxygen saturation, end-tidal CO2 and hemodynamic measurements, a standard monitor was used (SC 9000 XL, Siemens, Erlangen, Germany). During capnothorax the contralateral lung was ventilated with VT of 7 ml/kg, PEEP 5–10 cm H2O, I : E ratio 1 : 2 and RR 12 to 35/min. During the protocol, lung recruitment maneuvers (RMs) were performed as follows: ventilator mode was switched to pressure control; I : E ratio was changed to 1:1; respiratory rate was decreased to eight breaths per minute and inspiratory pressure level was increased to achieve a peak pressure of 40 cm H2O with a PEEP of 15 cm H2O. These settings were kept for 2 min. Monitoring and measurements Electrical impedance tomography EIT data were acquired using the Enlight impedance tomography monitor, developed by the Experimental Pulmonology Laboratory and Polytechnic Institute of the University of São Paulo, in a partnership with Dixtal Biomédica Ltd, São Paulo, Brazil.16–19 The prototype is capable of producing 50 cross-sectional, real-time images of the lungs per second with 32 electrodes equidistantly placed around the circumference of the thorax just below the level of the axilla. The following functional images were generated by EIT: 1. Ventilation maps derived from the concept introduced by Frerichs and Hahn,20,21 where relative impedance changes reliably track local changes in the content of air within the lung, pixel by pixel.11,22 Acta Anaesthesiologica Scandinavica 59 (2015) 354–368

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2. Perfusion maps obtained by injecting a bolus of 5 ml of a hypertonic solution (NaCl 20%) into a central venous catheter during an expiratory breath hold for 20 s. Due to its high conductivity, NaCl 20% acts as an EIT contrast agent,23–25 which after injection into the right atrium during apnea, passes through the pulmonary circulation, thereby producing a dilution curve that follows typical first-pass kinetics. The resulting regional time-impedance curves are then analyzed to quantitatively assess regional perfusion.16,26,27 For the quantitative analysis of the ventilation and perfusion distributions by EIT, the lungs were subsegmented in two different ways: (1) right and left lung; (2) four quadrants. Circulation and oxygenation A flow-directed pulmonary artery catheter (PAC, 7.0 French, Swan-Ganz thermo-dilution catheter, Baxter, Irvine, CA, USA) and a single lumen central venous catheter (4.0 French, BectonDickinson Critical Care Systems, Franklin Lakes, NJ, USA) were inserted into the right external jugular vein. A triple lumen fiber optic catheter for continuous venous saturation measuring and rapid injection of NaCl contrast boluses was placed in the left external jugular vein (Edwards Lifesciences Corporation, Irvine, CA, USA). An arterial catheter for continuous arterial pressure measurements and arterial blood sampling (20 G; BectonDickinson Critical Care Systems) was inserted into the left femoral artery. For measurement of cerebral Tissue Oxygenation Index (TOI), Near Infrared Light SpectrosSampling: x Preparation

x

Baseline TLV 30 min

copy (NIRS) probes (NIRO-200, Hamamatsu Photonics, Hamamatsu City, Japan) were placed over the parietal skull on the right and left side and shielded from ambient light.

Protocol Time points for data sampling are presented in Fig. 1. After initial preparation and a 30-min stabilization period, an intra-pleural chest tube was inserted into the right pleural space. This was done after clamping of the tracheal lumen side of double-lumen tube. The positions of the doublelumen tube and the chest tube as well as lung collapse were radiographically verified with a Mobile C-arm x-ray device (OEC 7700, GE Healthcare, Salt Lake City, UT, USA). Right-sided capnothorax was then established with a CO2 insufflator (7060-Insufflator, PelviPneu, Semm Systems, Wisap, Munich, Germany) connected to a Verres needle inserted through an airtight membrane into the chest tube. Automatically adjusted insufflation pressure was set to 19 cm H2O. Real-time monitoring and visualization of capnothorax was enabled by EIT. During OLV with capnothorax, RMs to the ventilated lung were performed at 20 min and 40 min. After the RMs, ventilator settings were changed to previous settings except for PEEP: 5 cm H2O at OLV 20 min and 10 cm H2O at OLV 40 min. Following the RM and measurements at 40 min, pleural CO2 exsufflation and suctioning in the chest tube with 15 cm H2O were performed.

x x

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CO2

x TLV 1 30 min

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x x

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Fig. 1. Timeline. Data collection was made after each intervention affecting ventilation or changes in ventilatory settings. The following cardiopulmonary and respiratory variables were recorded at baseline, capnothorax dx 20 min, capnothorax dx 40 min, two-lung ventilation (TLV) (1) 0 min, TLV (1) 30 min, capnothorax sin 20 min, capnothorax sin 40 min, TLV (2) 0 min and TLV (2) 30 min: cardiac output, heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), arterial and mixed venous blood gases. CO2, carbon dioxide, Dx, dexter; OLV, one-lung ventilation; RM, recruitment maneuver; Sin, sinister; TLV, two-lung ventilation; x, data collection points. Acta Anaesthesiologica Scandinavica 59 (2015) 354–368 © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

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30

Compliance ( mL / cm H2O )

TLV was reestablished, and an RM was performed using the same settings as above. Lungexpansion was verified radiographically and by EIT. TLV with baseline ventilator settings was maintained for 30 min. This was followed by 40 min of left-sided capnothorax with right-sided OLV, performed and monitored as on the left side. After the second capnothorax period, TLV was again established and performed as the first TLV period and maintained for 30 min.

25

20

15

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5

0

*

*

*

P = 0.002

Statistics Data are expressed as means ± standard deviation unless otherwise stated. The Shapiro–Wilk test was used to test data for normality. One-way repeated measures analysis of variance (ANOVA) and two-way repeated measures ANOVA were applied, depending on the presence of one or two within-subjects factors, respectively. The Bonferroni adjustment for multiple tests was applied for post hoc comparisons. The statistical analyses were conducted by SPSS (version 20.0.0). Statistical tests were carried out with the significance level set at P value less than 0.05. Results Four piglets survived the entire experiment, and one suffered fatal hemodynamic collapse at the end of the first OLV period. In four cases, there was a complete separation between right and left lung during OLV, and in one case the separation was partial. The respiratory system compliance and gas exchange data are presented in Figs 2 and 3. Hemodynamics During right-sided capnothorax, SvO2 as well as the NIRS tissue oxygenation index (TOI) decreased [SvO2: 61 ± 2% to 18 ± 6% (P = 0.018); TOI dx: 55 ± 2% to 39 ± 6% and TOI sin: 54 ± 5% to 36 ± 4% (P = 0.038)]. There was also an increase in central venous pressure (P = 0.006) and a decrease in mean arterial pressure (P = 0.045) and cardiac output (P = 0.017). During the left-sided capnothorax the hemodynamic impairment was less than during the right side (Fig. 4).

Fig. 2. Compliance. Compliance measurements along the study are presented. Compliance was statistically significantly different along the different steps of the protocol (P value in the Figure, ANOVA). *Represents the significant differences between the steps baseline vs. OLV1 – 20 min, baseline vs. OLV1 – 40 min, and baseline vs. OLV2 – 20 min, P = 0.039, 0.017 and 0.01, respectively. †Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 0 min, and OLV1 – 20 min vs. TLV1 – 30 min, P = 0.049 and 0.048, respectively. ‡Represents the significant difference between the steps OLV1 – 40 min vs. TLV1 – 30 min, P = 0.017. §Represents the significant difference between the steps OLV2 – 40 min vs. TLV2 – 30 min, P = 0.014. *†‡§: Pairwise comparisons with Bonferroni corrections.

Regional pulmonary ventilation by EIT At baseline, the ventilation was slightly unequal between the two lungs (56 ± 8% vs. 44 ± 8%; right vs. left, respectively), and between the upper and lower regions (54 ± 6% vs. 46 ± 6%, respectively). During the first period of OLV/ capnothorax, no or very minor ventilation on the right side could be seen (3 ± 3% vs. 97 ± 3%, right vs. left, respectively, P = 0.007). During the first TLV period, ventilation was completely restored (P = 0.03). The collapse of the left side during the second OLV/capnothorax was almost complete in three (94 ± 4% vs. 6 ± 4%, right vs. left, respectively) and partial in one (67% vs. 33%, right vs. left, respectively) of the four remaining animals (Fig. 5). Representative EIT images are shown in Fig. 6. Regional pulmonary perfusion by EIT Perfusion maps were pixel-wise calculated based on the impedance changes in response to hyperActa Anaesthesiologica Scandinavica 59 (2015) 354–368

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pO2

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Fig. 3. Gas exchange. Gas exchange measurements are presented. Samples were drawn from an arterial line (pO2, pCO2), a pulmonary artery catheter (SvO2) or collected from NIRS (TOI) (mean value of readings from electrodes placed over the right and left parietal lobe of the brain). Each line represents one animal. SvO2 and TOI were statistically significantly different along the different steps of the protocol (P values in the respective figures, ANOVA). SvO2: *Represents the significant differences between the steps baseline vs. OLV1 – 20 min and baseline vs. OLV1 – 40 min, P = 0.018 and 0.043, respectively. †Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 0 min and OLV1 – 20 min vs. TLV1 – 30 min, P = 0.044 and 0.017, respectively. ‡Represents the significant difference between the steps OLV1 – 40 min vs. TLV1 – 30 min, P = 0.047. TOI: *Represents the significant difference between the steps baseline vs. OLV1 – 20 min, P = 0.038. pO2, partial pressure of oxygen in arterial blood; pCO2, partial pressure of carbon dioxide in arterial blood; SvO2, mixed venous oxygen saturation; TOI, tissue oxygenation index. *†‡: Pairwise comparisons with Bonferroni corrections.

tonic saline injection as described.16 At baseline, the perfusion distribution was equal between the right and left lung (51 ± 4% vs. 49 ± 4%, respectively). During the first OLV/capnothorax, perfusion decreased in the non-ventilated and increased in the ventilated lung (18 ± 2% vs. 82 ± 2%, right vs. left, P = 0.03, Fig. 7). TLV restored the perfusion (P = 0.015). During the second OLV/ capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 ± 4% vs. 16 ± 4%, right vs. left). Representative EIT images are shown in Fig. 8. The case with incomplete collapse of the left side showed a perfusion of 43%, which decreased

to 24% across the second OLV/capnothorax period. Discussion In this experimental model of OLV with capnothorax, whose setup and timeline was very close to the clinical situation, real-time EIT promptly detected, quantified and tracked any changes in pulmonary ventilation and perfusion distributions that occurred during OLV/capnothorax. Our findings also highlighted that OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed

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Cardiac Output

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8

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L/min

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50 P = 0.045

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Fig. 4. Hemodynamics. Hemodynamic measurements are presented. CO was measured with thermo-dilution, and lactate was measured in arterial blood drawn from the left femoral artery. Each line represents one animal. MAP, CO and CVP were statistically significantly different along the different steps of the protocol (P values in the respective figures, ANOVA). CO: *Represents the significant difference between the steps OLV1 – 20 min vs. TLV1 – 30 min, P = 0.012. CVP: *Represents the significant differences between the steps OLV1 – 20min vs. TLV1 – 30 min and OLV1 – 20 min vs. TLV2 – 30 min, P = 0.011 and 0.021, respectively. †Represents the significant differences between the steps OLV1 – 40 min vs. TLV1 – 30 min and OLV1 – 40 min vs. TLV2 – 30 min, P = 0.009 and 0.041, respectively. CVP, central venous pressure; CO, cardiac output; MAP, mean arterial pressure; OLV, one-lung ventilation; TLV, two-lung ventilation. *†: Pairwise comparisons with Bonferroni corrections.

venous saturation, in contrast with the contralateral OLV that presented less hemodynamic impairment. Specifically, the OLV with capnothorax procedure comprises the use of the supine position, the sequential collapse of the lungs, and increased intrathoracic pressure with risk of prolonged hemodynamic impairment and CO2 accumulation due to the capnothorax. In the lateral decubitus position, the perfusion distribution during OLV tends to match the ventilation distribution of the dependent lung.28 However, in the supine position, as in our case, the diversion of blood flow from the

non-ventilated lung may be less effective. Hypoxic pulmonary vasoconstriction may still be stimulated but without the synergistic effect of gravitational influence.29 The sequential bilateral OLV and insufflation of CO2 means that both lungs, at different times, will suffer almost complete atelectasis. During the second closure, the previously atelectatic lung has to provide the entire gas exchange. This may lead to increased mechanical stress to this lung and impair gas exchange.30 To avoid excessive hypercapnia and respiratory acidosis, mechanical ventilation settings different from standard protocols may be required. Acta Anaesthesiologica Scandinavica 59 (2015) 354–368

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1.0

1.0

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

0.8 0.6 0.4

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

0.8 0.6 0.4 0.2

0.0

0.0

*

*

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

0.2

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Fraction

EIT ventilation right

EIT ventilation left

Fraction

A

P < 0.0005

B Upper right

Upper left

P = 0.003

0.6 0.4

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P = 0.005

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Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

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Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

0.4

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Fraction

0.8

Lower right

Fraction

1.0

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

0.2

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Fraction

0.8

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

Fraction

1.0

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Fig. 5. Regional pulmonary ventilation distribution by electrical impedance tomography. Regional pulmonary ventilation distributions by EIT from the following steps are presented: baseline, OLV with capnothorax on the right side at PEEP levels of 5 and 10 cm H2O (OLV 1 20 min, 40 min), two-lung ventilation (TLV 1 30 min), OLV with left capnothorax at the same PEEP levels (OLV2 20 min, 40 min) and final bilateral ventilation (TLV2 30 min). Each line represents one animal. The y axes depict the regional pulmonary ventilation distributed in two kinds of regions-of-interest (ROI): right and left lungs (Figure 5A) and four quadrants (Figure 5B). It is shown the proportion (fraction, in %) of the total pulmonary ventilation for each ROI in each step. Figure 5A: regional pulmonary ventilation distributed in right and left lungs was statistically significantly different along the different steps of the protocol (P value in the Figure 5A, ANOVA). *Represents the significant differences between the steps baseline vs. OLV1 – 20min and baseline vs. OLV1 – 40 min, P = 0.012 and 0.007, respectively. †Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 30 min, OLV1 – 20 min vs. OLV2 – 20 min and OLV1 – 20 min vs. OLV2 – 40 min, P = 0.03, 0.014 and 0.028, respectively. ‡Represents the significant differences between the steps OLV1 – 40 min vs. TLV1 – 30 min, OLV1 – 40 min vs. OLV2 – 20 min and OLV1 – 40 min vs. OLV2 – 40 min, P = 0.018, 0.013 and 0.026, respectively. Figure 5B: in the regional pulmonary ventilation distributed in four quadrants there was a statistically significant interaction between quadrant and protocol-step, P = 0.001. Regional pulmonary ventilation distribution in all four quadrants was statistically significantly different along the different steps of the protocol (P values in the respective figures, ANOVA). Upper right quadrant: *Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 30 min and OLV1 – 20 min vs. TLV2 – 30 min, P = 0.02 and 0.036, respectively. †Represents the significant differences between the steps OLV1 – 40 min vs. TLV1 – 30 min and OLV1 – 40 min vs. TLV2 – 30 min, P = 0.007 and 0.021, respectively. Lower right quadrant: *Represents the significant difference between the steps baseline vs. OLV2 – 20 min, P = 0.041. †Represents the significant difference between the steps OLV1 – 20 min vs. OLV2 – 40 min, P = 0.019. ‡Represents the significant difference between the steps OLV1 – 40 min vs. OLV2 – 40 min, P = 0.018. § Represents the significant difference between the steps OLV2 – 20 min vs. TLV2 – 30 min, P = 0.019. EIT, electrical impedance tomography; OLV, one-lung ventilation; PEEP, positive end-expiratory pressure; TLV, two-lung ventilation. *†‡§: Pairwise comparisons with Bonferroni corrections.



Fig. 6. Representative images of regional pulmonary ventilation distribution by electrical impedance tomography. 1. At baseline with bilateral ventilation. 2. OLV 1, left-sided one-lung ventilation with right-sided capnothorax, PEEP 5 cm H2O. 3. OLV 1, left-sided one-lung ventilation with right-sided capnothorax, PEEP 10 cm H2O. 4. Two-lung ventilation after the first capnothorax period. 5. OLV 2, right-sided one-lung ventilation with left-sided capnothorax, PEEP 5 cm H2O. 6. OLV 2, right-sided one-lung ventilation with left-sided capnothorax, PEEP 10 cm H2O. 7. Two-lung ventilation after the second capnothorax period. EIT, electrical impedance tomography; OLV, one-lung ventilation; PEEP, positive end-expiratory pressure.

The hemodynamic effects of capnothorax resemble those of tension pneumothorax, where the circulatory effects are related to the intrathoracic pressure.31–33 However, while the latter may be promptly relieved upon detection, the former is maintained for hours with consequent physiological alterations,3 including pulmonary artery pressure changes with consequences for hemodynamics and oxygenation.34,35 Additionally, although increased cardiac output have been

reported after moderate hypercapnia,4 the effects of applying ‘permissive hypercapnia’ in this setting were unknown. It is likely also that there is an uptake of carbon dioxide from the pleural surfaces during the capnothorax, similar to what is seen in laparoscopic surgery.36,37 In the non-complete OLV, the circulatory changes were much less. In a clinical situation, where there may be no need for a total abolishing Acta Anaesthesiologica Scandinavica 59 (2015) 354–368

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EIT perfusion left

1.0

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

0.8 0.6 0.4

1.0

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

0.8 0.6 0.4

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0.0

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*

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Fraction

EIT perfusion right

Fraction

A

P = 0.001 Upper left

1.0

P = 0.008 0.6 0.4

*

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1.0

0.6 0.4 0.2

0.0

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Lower left

0.6

1.0

P = 0.002

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Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

0.4

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Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Fraction

0.8

Lower right

Fraction

P = 0.009

*

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

0.2

1.0

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

P = 0.033 0.8

Ba se O lin LV e 1 20 O m LV in 1 40 m TL in V1 30 O m LV in 2 20 O m LV in 2 40 TL m in V2 30 m in

Fraction

0.8

Upper right

Fraction

B

Pig 1 Pig 2 Pig 3 Pig 4 Pig 5

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Fig. 7. Regional pulmonary blood flow distribution by electrical impedance tomography. Regional pulmonary blood flow distributions by EIT from the following steps are presented: baseline, OLV with capnothorax on the right side at PEEP levels of 5 and 10 cm H2O (OLV 1 20 min, 40 min), two-lung ventilation (TLV 1 30 min), OLV with left capnothorax at the same PEEP levels (OLV 2 20 min, 40 min), and final bilateral ventilation (TLV 2 30 min). Each line represents one animal. The y axes depict the regional pulmonary blood flow distributed in two kinds of regions-of-interest (ROI): right and left lungs (Figure 7A), and four quadrants (Fig. 7B). It is shown the proportion (fraction, in %) of the total pulmonary blood flow for each ROI in each step. Figure 7A: regional pulmonary blood flow distributed in right and left lungs was statistically significantly different along the different steps of the protocol (P value in the Figure 7A, ANOVA). *Represents the significant differences between the steps baseline vs. OLV1 – 20 min and baseline vs. OLV1 – 40 min, P = 0.031 and 0.036, respectively. †Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 30 min, OLV1 – 20 min vs. OLV2 – 40 min and OLV1 – 20 min vs. TLV2 – 30 min, P = 0.015, 0.004 and 0.002, respectively. ‡Represents the significant differences between the steps OLV1 – 40 min vs. OLV2 – 40min and OLV1 – 40 min vs. TLV2 – 30min, P = 0.002 and 0.006, respectively. Figure 7B: in the regional pulmonary blood flow distributed in four quadrants there was a statistically significant interaction between quadrant and protocol-step, P = 0.003. Regional pulmonary blood flow distribution in all four quadrants was statistically significantly different along the different steps of the protocol (P values in the respective figures, ANOVA). Upper left quadrant: *Represents the significant difference between the steps TLV1 – 30 min vs. OLV2 – 40 min, P = 0.019. †Represents the significant difference between the steps OLV2 – 40 min vs. TLV2 – 30 min, P = 0.001. Upper right quadrant: *Represents the significant difference between the steps OLV1 – 20 min vs. TLV2 – 30 min, P = 0.011. Lower right quadrant: *Represents the significant differences between the steps OLV1 – 20 min vs. TLV1 – 30 min and OLV1 – 20 min vs. TLV2 – 30 min, P = 0.025 and 0.011, respectively. †Represents the significant difference between the steps TLV1 – 30 min vs. TLV2 – 30 min, P = 0.02. EIT, electrical impedance tomography; OLV, one-lung ventilation; PEEP, positive end-expiratory pressure. *†‡: Pairwise comparisons with Bonferroni corrections.



Fig. 8. Representative images of regional blood flow distribution by electrical impedance tomography. (1) At baseline with bilateral ventilation; (2) OLV 1, left-sided one-lung ventilation with right-sided capnothorax, PEEP 5 cm H2O; (3) OLV 1, left-sided one-lung ventilation with right-sided capnothorax, PEEP 10 cm H2O; (4) Two-lung ventilation after the first capnothorax period; (5) OLV 2, right-sided one-lung ventilation with left-sided capnothorax, PEEP 5 cm H2O; (6) OLV 2, right-sided one-lung ventilation with left-sided capnothorax, PEEP 10 cm H2O; (7) Two-lung ventilation after the second capnothorax period. OLV, one-lung ventilation; PEEP, positive end-expiratory pressure

of ventilation for surgery to be successful, it may be useful to apply a not absolute OLV. This may also be valuable in cases where the patient for any reason has a compromised circulation already before OLV. Functional EIT enables real-time monitoring with a high temporal resolution that allows not only regional measurements of the ventilation distribution but also of faster physiological phenomena.23,24 We recently presented an EIT-based method to estimate regional lung perfusion based on the first-pass kinetics of a bolus of hypertonic contrast.16 The novel indicator dilution method

outperformed lung pulsatility as a surrogate for regional lung perfusion, and we therefore used this method in this study. The capnothorax elicits two important and opposing hemodynamic consequences, hyperdynamic effects with increased cardiac output due to hypercapnia38,39 and hemodynamic impairment due to intrathoracic tension. Despite efforts to avoid dynamic hyperinflation with air trapping, gradually increased PaCO2 levels and a mixed respiratory and lactic acidosis were observed during the capnothorax periods. In our experiment, the hemodynamic impairment prevailed, Acta Anaesthesiologica Scandinavica 59 (2015) 354–368

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especially during the initial, right-sided capnothorax, where resuscitation with intravenous fluids and vasoactive drugs was required. The recovery upon TLV was prompt, with measured values of hemodynamic parameters exceeding the baseline recordings, possibly due to the presence of vasopressors, adequate pre-load and the endogenous stress response. Less hemodynamic effects were found during the second leftsided capnothorax. This is in line with previous data, showing a milder response to left-sided compared with right-sided capnothorax.40 This could be explained by the venous anatomy, where the right-sided central veins are likely to be more susceptible to pressure changes than the arterial structures on the right side. Different PEEP levels may also alter hemodynamics in specific lung and cardiocirculatory conditions. In our data, no hemodynamic differences were found between the PEEP levels of 5 and 10 cm H2O. In addition, when isolation of ventilation was incomplete, the hemodynamic effects were consistently lower. The mechanisms underlying the decreased blood flow to the non-ventilated lung may be hypoxic pulmonary vasoconstriction, mechanical compression or a combination of both. Induced selective lower left lobe hypoxia in healthy pigs caused approximately 75% reduction of blood flow to the lower left lobe.41 The same model but with atelectasis in the left lower lobe showed the same level of results.42 This is in agreement with evidence that in atelectatic lung the main determinant of the blood flow is hypoxic pulmonary vasoconstriction, being more important than mechanical compression of the lung.43,44 In our model, we found a similar degree of reduction of perfusion to the non-ventilated lung. Since hypoxic pulmonary vasoconstriction is expected to be weaker in a larger hypoxic region, a mechanical component due to the elevated pressure in the thoracic cavity on the vessels in the non-ventilated lung may explain our results. Our data revealed that the perfusion of the right lung is decreased to very low levels during rightlung capnothorax, whereas PaO2 is decreased markedly and shunt fraction is modestly increased. The most likely explanation for such findings is the pattern of overperfusion (hyperflow) observed in the left lung during right-lung capnothorax. Our perfusion analysis that dis-

criminated quadrants exhibited that there is an enormous increase in the perfusion to the lower left quadrant (a mean increment of 160%, from 0.16 to 0.42), whereas the incremental perfusion in the upper left quadrant was just 11%, from 0.37 to 0.4. Thus, the blockage of perfusion in the right lung (hypoxic pulmonary vasoconstriction plus increased mechanical resistance caused by atelectasis) caused hyper-perfusion of the left lung, which increased disproportionally in the dependent left lung. This probably caused an increased shunt in the left lung. This effect would be similar to the one we previously observed during intravenous infusion of nitroprusside16 or norepinephrine, when such drugs caused an increased cardiac output and, consequently, an increased shunt because of a preferential increase in perfusion in the most dependent lung regions (at the same time that ventilation was kept constant in those zones). A limitation of the study design is that all experiments followed the same right-to-left sequence. Thus, carry-on effects such as fluid optimization may confound the observations, a bias possible to reduce by randomization of the sides’ sequence. Also the lateralized perfusion seen at the end of the last TLV may be due to incomplete recruitment of collapsed tissue, which is compatible with the simultaneous decrease in ventilation. Finally, although a previous study described the use of OLV/capnothorax in piglets,45 they did not track in real time the frequent and dynamic changes in the lung structure and function with a functional imaging method as the EIT. In conclusion, in this experimental model of sequential OLV with capnothorax, EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation. Our findings suggest that key factors that need to be online and closely monitored during the perioperative period include a complete lung separation, ventilation and perfusion distributions and hemodynamic responses. We believe that this experimental model setup and functional EIT are valuable tools to enable future studies addressing optimal perioperative management during the challenging situation of sequential OLV with capnothorax.

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Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax.

Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. ...
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