Optimal Respiratory Rate for Low-Tidal Volume and Two-Lung Ventilation in Thoracoscopic Bleb Resection

Optimal Respiratory Rate for Low-Tidal Volume and Two-Lung Ventilation in Thoracoscopic Bleb Resection Dong Kyu Lee, MD, PhD,* Hyun Koo Kim, MD, PhD,† Kanghoon Lee, MD,‡ Young Ho Choi, MD, PhD,† Sang Ho Lim, MD, PhD,* and Heezoo Kim, MD, PhD* Objectives: One-lung ventilation is considered to be mandatory in video-assisted thoracoscopic surgery. However, the authors showed in a previous report that two-lung ventilation with low tidal volume is feasible in thoracoscopic bleb resection (TBR). In this study, they evaluated optimal respiratory rate during TBR under two-lung ventilation with low-tidal volume anesthesia. Design: A prospective, randomized, single-blinded intervention study. Setting: An operating room in a teaching hospital. Participants: Forty-eight patients who underwent scheduled TBR under general anesthesia. Interventions: TBR was performed under low-tidal-volume (5 mL/kg), two-lung ventilation. Respiratory rate (RR) varied according to the protocol: 15 (group I), 18 (group II), and 22 cycles/min (group III). Using block randomization method, 16 patients were assigned to each of 3 groups.

Measurements and Main Results: Minute ventilation of group I was lowered significantly compared with the other groups (p o 0.001). The results of arterial blood gas analysis were in the physiologic range in all patients. Surgery and anesthetic times and number of endostaples used were not significantly different among the 3 groups. Conclusions: The RR of 15 cycles/min with low-tidal volume (5 mL/kg) and two-lung ventilation did not produce abnormal physiologic changes including arterial pH, partial arterial oxygen pressure, and partial pressure of carbon dioxide and guaranteed an optimal surgical field. Therefore, these setting are considered acceptable for two-lung ventilation during TBR. & 2015 Elsevier Inc. All rights reserved.

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a single-lumen endotracheal tube [SLT]), is technically difficult (requires bronchoscopy, is difficult to establish adequate OLV in patients with difficult airways, requires more time, etc),7 and has complications, including airway injury, when compared with two-lung ventilation using an SLT.6,8–10 VATS under two-lung ventilation is possible in patients with malignant pleural effusion or effusion of unknown cause, and can provide an excellent operative view.11 The authors have used two-lung ventilation with low tidal volume for thoracoscopic bleb resection (TBR) using an SLT and examined its acceptability in two clinical studies.12,13 However, a respiratory rate (RR) exceeding 20 cycles/min was necessary for pulmonary ventilation (minute ventilation). In this situation, the high RR produced a fast-moving surgical field. To minimize difficulties in surgery with VATS, a slow-moving surgical field has an advantage. Thus far, no report has been published on the acceptable RR for low-tidal-volume, two-lung ventilation during VATS. As an extension of the authors’ previous studies,12,13 a clinical trial was planned to determine the optimal ventilator setting in TBR under two-lung ventilation with respect to gas exchange, RR, and minute ventilation.

RIMARY SPONTANEOUS pneumothorax (PSP) is a common pleural disease, and its annual incidence is reportedly 18 to 28 per 100,000 in men and 1.2 to 6 per 100,000 in women.1 The exact cause of PSP is debatable, but its management is well established among physicians. Because PSP frequently recurs, it often is treated with surgery. Guidelines from the British Thoracic Society recommend bleb resection via open thoracotomy as the gold standard for the prevention of recurrence.1 However, video-assisted thoracoscopic surgery (VATS) has become a popular surgical method for bleb resection. It is less invasive, less painful, produces good cosmetic results, and can be cost-effective due to shorter hospitalization times.2–4 The most widely accepted anesthesia strategy during VATS is one-lung ventilation (OLV) using a double-lumen endotracheal tube (DLT) or variable devices for lung separation.5,6 Although OLV provides a proper surgical field, it is expensive (in Korea, US $283 for one-lung anesthesia management with a DLT, versus US $191 for general anesthesia management with

From the Departments of *Anesthesiolafogy and Pain Medicine; and †Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; and the ‡Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea. Dr. Lee and Dr. Kim were first authors for this paper. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No: 2012012166) and the Korea University Grant (K1326928). Address reprint requests to Heezoo Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, Korea University College of Medicine, 97 Guro-donggil, Guro-gu, Seoul 152-703, Republic of Korea. E-mail: [email protected] © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.06.029 972

KEY WORDS: pulmonary ventilation, video-assisted thoracoscopic surgery, anesthesia, pneumothorax

METHODS

This study was conducted at Korea University Guro Hospital from May 2010 to December 2012. Fifty-eight PSP patients who were scheduled to undergo TBR were considered for inclusion in the study. Written informed consent was obtained from all patients after the study was approved by the hospital’s institutional review board (KUGH14105-001). The patients were managed according to the guidelines of the hospital’s thoracic surgery department before surgical treatment. Indications for TBR were complicated pneumothorax, visible blebs on computed tomography (CT), or ipsilateral recurrent episodes. Complicated pneumothorax was defined as a persistent air leak, hemothorax, failure of lung re-expansion, bilateral pneumothorax, and tension pneumothorax. Exclusion

Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 4 (August), 2015: pp 972–976

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criteria included first episode without any complications, radiologic finding of significant pleural adhesion, and blebs not visible on chest CT. Cases in which surgery was set for open thoracotomy, patients with an American Society of Anesthesiologists (ASA) physical status classification of 3 or 4, and those who refused to participate, also were excluded. General anesthesia and surgery were performed using similar techniques and anesthetic agents as in previous trials.12,13 Standard patient monitoring (electrocardiogram, oxygen saturation, noninvasive blood pressure, and end-tidal carbon dioxide) were applied to all patients during anesthesia. After tracheal intubation with an SLT (Sheridan/CF Tracheal Tubes, ID 7.0 for women and ID 8.0 for men; Hudson RCI, Durham, NC), mechanical ventilation was established with full tidal volume settings (10 mL/kg tidal volume, 12 cycles/min RR, 0.5 fraction of inspired oxygen FIO2, 1:2 inspiratory-toexpiratory ratio, and 1.5 L/min flow rate each of O2 and N2O, without positive end-expiratory pressure). During anesthesia induction, a catheter was placed in the radial artery for intermittent arterial blood gas analysis. After stable vital signs were confirmed, the patient was assigned to 1 of 3 groups described below. Randomized allocation was achieved using the block randomization method. The patients were placed in the lateral decubitus position, and tidal volume was reduced to 5 mL/kg (low tidal volume) just before surgery began. The RR was increased to 15 cycles/min (group I), 18 cycles/min (group II), or 22 cycles/min (group III). During low-tidal-volume ventilation, CO2 retention and intrinsic positive end-expiratory pressure were monitored using end-tidal carbon dioxide, a flow curve, and a manometer integrated with an anesthetic ventilator (S/5 Avance with monitor; Datex-Ohmeda, Madison, WI), and any signs of associated hypercapnia and hypoxemia carefully were monitored. All surgeries were performed by one surgeon. The chest tube was removed and a 5-mm thoracoscope with a 30-degree lens was introduced through the former thoracostomy site. Lung inspection was performed to identify blebs on the lung parenchyma. Two-lung ventilation was abandoned when there was moderate-to-severe pleural adhesion, or when apical bullae exposure was not sufficient for VATS. In cases in which more extensive surgery was required, the authors prepared an endobronchial blocker (Coopdech Endobronchial Blocker Tube; Daiken Medical., Osaka, Japan) that enabled rapid establishment of OLV without a position change. After the identification of blebs, two 2-mm thoracoscopic ports were made for the minisite endograsp (Auto Suture; Covidien, Norwalk, CT) and the 2-mm thoracoscope at the fifth and sixth intercostal spaces along the midaxillary and posterior axillary lines. To secure the pulmonary margins, endostaplers were used for bleb resection. The test for air leakage was performed with a positive pressure of 20 cm H2O. The stapler line was covered by fibrin sealant (Beriplast P Combi-set; CSL Behring GmbH, Marburg, Germany), and mechanical and chemical pleurodesis with minocycline were performed at the apical area of the pleura. A 28-French chest tube was placed in the pleura through the previous thoracostomy site just before the surgery was completed. Demographic data, including age, gender, height, and weight, were recorded. Airway pressures, oxygen saturation,

and arterial blood gas analysis (pH, partial arterial oxygen pressure [PaO2], and partial pressure of carbon dioxide in arterial blood [PaCO2]) were obtained every 10 minutes at full tidal volume and low-tidal-volume ventilator settings. Surgical and anesthesia time also were recorded. Complications related to hypercapnia were evaluated, including tachycardia, hypertension, arrhythmias during anesthesia, headache, confusion, flushing, hypoventilation, tachycardia, and hypertension, for 24 hours postoperatively). Before initiating this trial, a power analysis was performed to calculate the required sample size. Because hypercapnia is expected with low tidal volume and a low RR, the lowest possible theoretical RR was calculated. It was assumed that minute ventilation of 120 mL/(kg/min) (10 mL/kg tidal volume and 12 cycles/min RR, full tidal volume setting) resulted in 40 mmHg PaCO2.14 As long as the production rate of CO2 is constant and anatomic deadspace is fixed, PaCO2 and minute ventilation are inversely related.15,16 Therefore, RR of 15, 18, and 22 cycles/min with 5 mL/kg low tidal volume produced reduced minute ventilation in groups I, II, and III of 63%, 75%, and 92% (75, 90, and 110 mL/kg/min), respectively, compared with full-tidal-volume settings, and expected PaCO2 of 64, 53, and 44 mmHg, respectively. Under these conditions, the effect size f was 1.139. Thus, the number of patients required was 12, with 0.05 alpha error probability and 0.80 power. The authors performed a pilot test with 12 patients and reevaluated the number of patients required to achieve adequate power, because PaCO2 was not correlated simply with the amount of minute ventilation. After reevaluation, the calculated effect size f was 0.506. Using 0.05 alpha error probability and 0.80 power, the number of patients required was 42. With an assumed patient loss of up to 10% and an equal number of patients in each group, the total required number of patients was 48. Statistical analyses were performed with IBM SPSS Statistics 18.0.1 (PASW Statistics for Windows; SPSS, Chicago, IL). Data were analyzed using the paired t test, one-way analysis of variance following Scheffe’s multiple comparison test, or Kruskal-Wallis one-way analysis of variance on ranks following all pairwise multiple comparisons, according to the characteristics of the data. A p value o0.05 was considered statistically significant. RESULTS

Demographic data are presented in Table 1. The 58 eligible patients received TBR for spontaneous pneumothorax during the study period. Some patients were excluded before randomization, based on the exclusion criteria described above; 3

Table 1. Demographic Data

Gender (male/female) Age (years) Height (cm) Weight (kg)

Group I (15

Group II (18

Group III (22

Breaths/Min)

Breaths/Min)

Breaths/Min)

14/2 29.6 ⫾ 16.2 172.7 ⫾ 7.9 61.4 ⫾ 11.0

15/1 24.2 ⫾ 9.9 172.6 ⫾ 3.6 59.5 ⫾ 8.7

16/0 21.8 ⫾ 5.0 174.7 ⫾ 5.6 59.8 ⫾ 6.8

NOTE. Values are expressed as counts or mean ⫾ standard deviation.

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Table 2. Ventilation Properties During Low-Tidal-Volume Ventilation Low-Tidal-Volume Ventilation

p Value*

6.43 ⫾ 1.18 6.06 ⫾ 1.51 5.81 ⫾ 0.93 0.349

4.14 ⫾ 0.78 5.13 ⫾ 1.01 5.46 ⫾ 0.86 o0.001

o0.001 0.001 0.005

16.00 ⫾ 3.90 15.38 ⫾ 3.85 11.31 ⫾ 1.49‡ o0.001

10.44 ⫾ 2.92 10.94 ⫾ 3.09 6.50 ⫾ 2.00‡ o0.001

o0.001 o0.001 o0.001

32.13 ⫾ 3.32 31.06 ⫾ 3.02 33.56 ⫾ 4.26 0.151

36.69 ⫾ 3.93 34.25 ⫾ 4.09 34.75 ⫾ 3.86 0.196

o0.001 o0.001 0.068

7.49 ⫾ 0.04 7.47 ⫾ 0.04 7.43 ⫾ 0.04 o0.001

7.43 ⫾ 0.04 7.44 ⫾ 0.04 7.39 ⫾ 0.04 0.004

o0.001 o0.001 0.003

37.13 ⫾ 7.46 38.38 ⫾ 5.52 38.94 ⫾ 8.18 0.765

42.50 ⫾ 4.44 39.50 ⫾ 3.18 42.25 ⫾ 4.20 0.072

0.001 0.357 0.108

295.13 ⫾ 63.07 314.38 ⫾ 92.12 294.00 ⫾ 25.08 0.621

260.38 ⫾ 50.77 301.25 ⫾ 102.78 250.13 ⫾ 31.01 0.094

Full-Tidal-Volume Ventilation

Minute ventilation (L/min) Group I (15) Group II (18) Group III (22) p† Peak pressure (mmHg) Group I (15) Group II (18) Group III (22) p† ETCO2 (mmHg) Group I (15) Group II (18) Group III (22) p† pH Group I (15) Group II (18) Group III (22) p† PaCO2 (mmHg) Group I (15) Group II (18) Group III (22) p† PaO2 (mmHg) Group I (15) Group II (18) Group III (22) p†

0.001 0.693 o0.001

NOTE. Values are expressed as mean ⫾ standard deviation. Numbers in parenthesis (column 1) represent assigned respiration rate in each study group (cycles/min). Abbreviations: ETCO2, end-tidal carbon dioxide. *p values for comparison between variables during full- and low-tidal-volume ventilation. †p values for comparison between variables of 3 groups at each full- and small-tidal-volume ventilation. ‡p o 0.05 in multiple comparison test followed analysis of variance among 3 groups at each full- and small-tidal-volume ventilation.

patients were excluded due to planned open thoracotomy, 2 were ASA physical status classification 3, and 5 refused to participate. Because block randomization was used for the 3 groups, patient enrollment was continued until the number of included patients reached 48. Once randomized, no patients were excluded. All patients underwent surgery with VATS. No case was converted to an open thoracotomy, and in no case was two-lung ventilation converted to OLV. Forty-five men (93.75%) and 3 women (6.25%) were enrolled, with a mean age of 25.35 ⫾ 11.46 years (Table 1). The most common indications for VATS were a visible bleb on chest CT (60.42%), ipsilateral recurrent episode (22.92%), and complicated pneumothorax (18.75%). The results for variables related to ventilation and the surgery are presented in Table 2. The amount of minute ventilation during low tidal volume differed significantly among the 3 groups. Group I had the smallest minute ventilation (p o 0.001). Peak airway pressure (peak inspiratory pressure) during low tidal volume differed significantly among the 3 groups (p o 0.001). PaCO2 values during low tidal volume were in the normal physiologic range in

all 3 groups, and no significant differences were detected among the 3 groups. PaO2 during low tidal volume remained within the normal range in all 3 groups. There were statistically significant differences in measured pH during low tidal volume between some groups; however, all values were within the normal physiologic range. No patient presented any sign associated with hypoxemia or hypercapnia.

Table 3. Surgical and Anesthetic Times, and Number of Endostaplers Used Group I (15

Group II (18

Group III (22

p

Breaths/Min)

Breaths/Min)

Breaths/Min)

Value

Operation time 24.29 ⫾ 6.96 31.19 ⫾ 12.72 26.00 ⫾ 7.38 0.123 (min) Anesthesia 68.57 ⫾ 16.58 71.56 ⫾ 13.51 62.813 ⫾ 7.952 0.166 time (min) Number of 2 (1-2) 2 (2-3) 2 (2-2.75) 0.171 endostaplers NOTE. Values are expressed as mean ⫾ standard deviation or median (25%-75%).

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A thoracoscope was introduced, the surgical field was assessed, and a decision was made to proceed with the remaining surgical procedures. There was no case in which the low-tidal-volume setting was abandoned. Surgery times (from introduction of thoracoscope to skin closure) and anesthesia times (from induction of general anesthesia to emergence) did not differ significantly among the 3 groups (Table 3), and there was no significant difference in the numbers of endostaples used. DISCUSSION

It was confirmed that the RR could be reduced to 15 cycles/ min with low-tidal-volume (5 mL/kg) and two-lung ventilation. With this ventilator setting, minute ventilation was reduced significantly compared with a conventional mechanical ventilation setting, and no physiologic problems related to hypoventilation were encountered. Introduction of VATS to the management of PSP has brought great changes because of its minimal invasiveness. Compared with conventional open thoracotomy, VATS entails less pain and yields better cosmetic results and more favorable postoperative pulmonary function outcomes. Moreover, it is associated with a lower number of hospital days and an earlier return to work, thus providing economic advantages.2,17 For these reasons, TBR under VATS is recommended as a first-line choice instead of open thoracotomy.3,18 The most broadly accepted anesthetic strategy for VATS is OLV. OLV has provided several advantages since its introduction to thoracic anesthesia.1,19 However, the establishment and management of OLV during thoracic surgery require a skillful anesthesiologist and time for bronchoscopic examination, and an additional cost is associated with use of a DLT or endobronchial blocker.20 Moreover, the large size of a DLT compared with an SLT can result in complications, including vocal cord and tracheal injuries.21,22 Sometimes, a dislodged endobronchial cuff from the DLT results in a poor surgical field or interferes with contralateral lung ventilation.23 Cerfolio et al20 reported the successful use of VATS under two-lung ventilation with low tidal volume to provide an adequate working field for pleural biopsy and talc pleurodesis. In previous studies,12,13 low tidal volume with two-lung ventilation did not result in technical problems during TBR. When VATS for TBR was performed with low tidal volume and two-lung ventilation, the time from intubation to incision was significantly reduced, it was cost-effective, and patients experienced significantly less pain and fewer airway complications than with OLV. The present study focused on the RR in ventilation. Under two-lung ventilation, periodic movement of the targeted lesions for bleb resection is inevitable, which differs from OLV. Because reduced movement of the target lesion during the surgery is more convenient for the surgeon, the optimal RR for TBR with low-tidal-volume anesthesia was ascertained. In determining the lowest acceptable RR, minute ventilation was a crucial factor. During low tidal volume, minute ventilation was significantly smaller in group I than in the other groups. However, hypercapnia and hypoxemia did not develop in any of the groups. Some variables differed

significantly between some of the groups, including the pH in arterial blood, but all values were within normal physiologic ranges. An RR of 15 cycles/min with low tidal volume was tolerated in all cases, and no clinical problems were encountered. Using low tidal volume to prevent ventilator-induced lung injury is an emerging concept aimed at promoting patient safety.24,25 Even in a patient without acute lung injury, mechanical ventilation with a tidal volume of approximately 6 mL/kg with positive end-expiratory pressure has potential benefits compared with a conventional larger tidal volume.25 Unfortunately, there currently is a lack of evidence to guide optimal tidal volume during general anesthesia.26 However, it seems clear that a mechanical ventilation strategy incorporating low tidal volumes has beneficial effects compared with conventional large tidal volumes.26 In addition, low-tidal-volume ventilation itself guarantees an adequate surgical field without CO2 gas insufflation.12 Low tidal volume with moderate FIO2 may have several benefits. In this study, airway pressure during low-tidal-volume ventilation remained comparatively low. Moreover, with a relatively low FIO2 of 0.5, PaO2 remained at an adequate level. In this situation, a protective effect on the lung with this ventilator setting in a patient with mild lung injury from the pneumothorax itself, chest tube insertion, and negative pressure drainage could be expected. Regrettably, it could not be proven that an RR of 15 cycles/ min made the surgery easier with respect to surgery time or the number of endostaples used. TBR under VATS is a standardized surgery method, entailing a short surgery time. Because the surgeries in the present study were not complicated, they were not ideal for investigating whether relatively lower RR would shorten the surgery time or reduce the number of endostaples used. However, the surgeon reported that an RR of 15 cycles/min resulted in a more feasible surgery field for manipulating endoscopic devices than an RR of 22 cycles/min. A limitation of this study was that the patients included were young and without comorbidities. Only patients having an ASA physical status classification of 1 or 2 were included. Most patients who suffer from PSP are tall, thin boys and men.27 The characteristics of the patients in this study were similar, whereas in clinical practice, mechanical ventilation strategies should be individualized according to the particular characteristics and comorbidities of the patient (eg, morbid obesity, old age, and other conditions). CONCLUSIONS

The present study confirmed that in otherwise healthy, young, nonobese adults undergoing TBR surgery under VATS due to PSP, two-lung ventilation with a low tidal volume of 5 mL/kg and an RR of 15 cycles/min met most patients’ O2 requirements and facilitated adequate CO2 excretion. It is possible that a high RR will have negative implications for the feasibility of some surgeries. Further study is required to investigate whether the RR can be reduced safely below 15 cycles/min if permissive hypercapnia is allowed.

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