Journal of Clinical Anesthesia (2014) xx, xxx–xxx
Original Contribution
Intermittent reinflation is safe to maintain oxygenation without alteration of extravascular lung water during one-lung ventilation☆ Masakazu Yasuuji MD (Assistant Professor)a,⁎, Shinji Kusunoki MD (Assistant Professor)a , Hiroshi Hamada MD (Associate Professor)b , Masashi Kawamoto MD (Professor and Chair)b a
Department of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, Japan Department of Anesthesiology and Critical Care, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan b
Received 3 December 2012; revised 9 October 2013; accepted 11 October 2013
Keywords: Extravascular lung water; Intermittent reinflation; Lung injury; One-lung ventilation; Oxygenation, Maintenance of
Abstract Study Objective: To investigate whether a maneuver for repeated cycles of collapse and reexpansion of the operative lung, termed “intermittent reinflation” (IR), to counter hypoxemia during one-lung ventilation (OLV), results in a time-dependent alteration of extravascular lung water. Design: Prospective, randomized clinical study. Setting: Operating room and postsurgical intensive care unit of a university hospital. Patients: 36 ASA physical status 1 and 2 patients undergoing elective, video-assisted thoracic surgery for lung tumors. Interventions: Patients were randomly assigned to two groups. Group C consisted of 18 patients whose nondependent lung was kept collapsed during OLV, while Group IR included 18 patients with IR that consisted of 4 separate, 10-second manual inflations and 5-second openings within one minute at intervals of 20 minutes during OLV. Measurements: Perioperative parameters included transcutaneous oxygen saturation (SpO2), hemodynamic data, extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) as determined by the single-indicator transpulmonary thermodilution technique, and partial pressure of arterial oxygen/inspired oxygen fraction (PaO2/FIO2) ratio. Main Results: Group IR had significantly higher SpO2 at 20 minutes after commencement of OLV (98.9% vs 96.3%, P = 0.029) and average SpO2 throughout OLV (98.7% vs 97.0%, P = 0.020). Hemodynamic data, EVLWI, PVPI, and PaO2/FIO2 ratio did not differ between the groups, and there were no differences between groups in postoperative morbidity or hospital stay. Conclusions: Intermittent reinflation had a beneficial effect on oxygenation during OLV, without any significant effects on EVLW or postoperative outcomes. © 2014 Elsevier Inc. All rights reserved.
☆ Supported by a Grant-in-Aid for Young Scientists (B; No. 19791066) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Tokyo, Japan. ⁎ Correspondence: Masakazu Yasuuji, MD, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel.: + 81 82 257 5267; fax: + 81 82 257 5269. E-mail address: [email protected] (M. Yasuuji).
http://dx.doi.org/10.1016/j.jclinane.2013.10.006 0952-8180/© 2014 Elsevier Inc. All rights reserved.
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M. Yasuuji et al.
1. Introduction One-lung ventilation (OLV) is an established procedure performed during lung resection to prevent blood vessel injury and facilitate surgical procedures. Hypoxemia is the most important problem encountered during OLV [1,2]. To counter this major concern, a maneuver to expand the collapsed lung, known as “intermittent reinflation” (IR), performed to improve oxygenation at regular intervals of 10-15 minutes, has been recommended [3-5]. Lung injury after lung resection is associated with significant morbidity and mortality [6]. This type of injury generally follows a clinically and histopathologically indistinguishable course from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) [7], and is related to mechanical forces exerted during OLV [8]. Similar to ALI and ARDS, a recent experiment has demonstrated a potential reduction of lung injury due to OLV using a protective ventilatory strategy with low tidal volume (VT) in perioperative patients with normal lungs [9]. Shear forces secondary to repeated collapse and reopening of alveolar units can result in lung injury, known as atelectrauma [10]. However, there are no reports of repeated IR during OLV or the relationship of IR to lung injury after lung resection. Lung injury induced by IR repeatedly applied during surgical resection was investigated. Extravascular lung water (EVLW) is not only an indicator of prognosis and severity of ALI and ARDS [11-13], it is
Table 1
also a useful parameter to assess perioperative respiratory conditions in patients with no preexisting lung injury [9,14]. Thus, it may be useful to quantify the inflammatory process of lung injury, which may increase vascular permeability, resulting in accumulation of fluid and development of pulmonary edema [7]. A continuous cardiac output monitor (PiCCO; Pulsion Medical Systems, Munich, Germany) was recently introduced to measure EVLW using a singleindicator thermodilution method [15]. In this prospective clinical study, a time-dependent alteration of EVLW was evaluated with the PiCCO monitor.
2. Materials and methods 2.1. Study population The study protocol was approved by the Ethics Committee of Hiroshima University (IRB No. 266), and all patients provided written, informed consent before enrollment. This study was registered at www.umin.ac.jp/ctr/ index.htm (UMIN000008759). Eligible patients met the following criteria: 1) 80 years of age or under, 2) ASA physical status 1 or 2, and 3) scheduled for elective, videoassisted thoracic surgery for lung tumors requiring OLV lasting more than 120 minutes (Table 1). Exclusion criteria included decompensated cardiac (New York Heart Association N class II) or pulmonary disease [vital capacity (VC) b
Patient characteristics and intraoperative values
Demographic variables
Group IR (n = 18)
Group C (n = 18)
Age (yrs) Gender (m/f) Weight (kg) Height (cm) ASA physical status (1 / 2) (n) Preop VC (% predicted) Preop FEV1/FVC ratio (%) Right-sided thoracotomy (n) Left-sided thoracotomy (n) Bilateral thoracotomy (n) Segments resected (n) Surgery duration (min) OLV duration (min) Intraop blood loss (mL) Intraop urine output (mL) Intraop fluid administration (mL) Hydroxyethyl starch (0 mL/500 mL/1000 mL) (n) Intraop transfusion (n) Sequential intermittent reinflation (n)
63 ± 9 15 / 3 64 ± 8 165 ± 7 0 / 18 108 ± 13 73 ± 9 7 9 2 3±1 310 ± 107 253 ± 88 193 ± 172 756 ± 373 3456 ± 756 16 / 1 / 1
65 ± 8 11 / 7 63 ± 12 161 ± 8 1 / 17 109 ± 13 74 ± 9 9 8 1 4±1 317 ± 102 269 ± 90 236 ± 206 940 ± 662 3411 ± 1092 15 / 3 / 0
0 12 ± 4
0 3±1
P -value 0.57 0.14 0.85 0.22 0.32 0.85 0.61 0.45 0.09 0.85 0.60 0.50 0.31 0.89 0.69 1.00 b 0.001
Values are means ± SD, unless otherwise noted. Group IR patients underwent intermittent reinflation, Group C patients served as controls. Preop = preoperative, VC = vital capacity, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, OLV = one-lung ventilation, intraop = intraoperative.
Intermittent reinflation in OLV 50% of predicted values and/or forced expiratory volume in 1 second (FEV1) b 50% of forced vital capacity (FVC)], chronic renal failure (serum creatinine N 1.5 mg/dL), altered liver function (N class B in Child-Pugh), preoperative treatment with an immune modulator (cytostatic drugs, corticosteroids, nonsteroidal antiinflammatory drugs, vaccination, blood products) within one month before surgery, preexisting coagulation disorders, and symptoms of an acute inflammatory process (clinically defined or abnormal data for C-reactive protein, leukocyte count, or body temperature). Arteriosclerosis obliterans and/or iliac artery stenosis and/or aneurysms with or without bypass surgery, which would be associated with an increased risk of complications following femoral arterial cannulation for the PiCCO procedure, also were excluded.
2.2. Patient treatment Anesthetic and surgical management was standardized for each patient. The same experienced surgeons conducted each operation. Surgical procedures were adapted for established or suspected malignancies, and the lung resections were performed using a standard video-assisted thoracic surgery method. None of the patients was premedicated. On arrival at the operating room, a thoracic epidural catheter was placed at the level of thoracic segments Th4-Th5 to Th6-Th7. General anesthesia was induced with intravenous administration of 1.0 - 1.5 mg/kg of propofol or 3.0 - 5.0 mg/kg of thiamylal, 1.5 - 2.5 μg/kg of fentanyl, and 0.1 mg/kg of vecuronium. After induction of anesthesia, an appropriate size left-sided double-lumen tube (Broncho-Cath; Covidien, Dublin, Ireland) was placed and confirmed using a fiberoptic bronchoscope before and after turning the patient to the lateral decubitus position. Anesthesia was maintained with 2.0% 2.5% of sevoflurane and epidural anesthesia with continuous infusions of ropivacaine 0.375% at a rate of 4.0 - 6.0 mL/hr. Appropriate incremental doses of fentanyl and vecuronium were given. The lungs were mechanically ventilated (Fabius GS; Dräger, Lübeck, Germany) using volume-controlled ventilation during two-lung ventilation (TLV) and pressurecontrolled ventilation during OLV, respectively. Volumecontrolled ventilation was initiated with 10 mL/kg of VT at a respiratory rate (RR) of 12 breaths per minute (breaths/min), using 2 cmH2O of positive end-expiratory pressure (PEEP) and an inspiratory:expiratory ratio (I:E) of 1:1.5. When OLV was started, the nondependent lung was completely collapsed and opened to air with suction if necessary, while the dependent lung was initially ventilated at 20 - 25 cmH2O of peak inspiratory pressure providing approximately 300 400 mL of VT with 35 L/min of inspiratory flow at a RR of 20 breaths/min, with 2 cmH2O of PEEP and I:E of 1:1.5. During both TLV and OLV, RR was adjusted to achieve a partial arterial carbon dioxide pressure of 40-45 mmHg. The
3 fraction of inspired oxygen (FIO2) was adjusted to 0.6 in air during TLV and to 1.0 during OLV. Bladder temperature was monitored in all patients and a forced-air warming blanket system was used to prevent hypothermia during surgery. Intraoperative fluid replacement consisted of 10 mL/kg/hr of Ringer's acetate solution. If systolic arterial pressure (BP) was lower than 80 mmHg for more than 30 minutes or urine output was less than 0.5 mL/kg/hr for more than two hours, additional fluid was given of 500 mL of hydroxyethyl starch, repeated up to two times. As a general rule, catecholamines were not administered. After surgery, extubation was performed when patients met the following criteria: 1) temperature higher than 36° C; 2) partial pressure of arterial oxygen (PaO2)/FIO2 ratio greater than 150 mmHg with hemoglobin greater than 7 g/dL; 3) RR less than 25 breaths/min and VT greater than 5 mL/kg during spontaneous breathing; and 4) adequate cough during suctioning. All patients were transferred to the intensive care unit (ICU) after surgery and cared for by attending physicians using a standard postoperative protocol.
2.3. Study protocol Prior to anesthetic induction, patients were randomly assigned to two groups by the concealed allocation approach using opaque sealed envelopes containing the randomization schedule. Randomization was done by computergenerated codes maintained in sequentially numbered opaque envelopes that were opened just prior to induction of general anesthesia. Group C was comprised of control patients, whose nondependent lung was kept collapsed completely during OLV; Group IR patients received IR with 100% oxygen in the two lungs during OLV. In the latter group, IR was performed by manually inflating the nondependent and dependent lungs to 20 cmH2O, which was then held for 10 seconds and opened to the atmosphere for 5 seconds. This action was repeated 4 times per minute at 20-minute intervals during OLV. The maneuvers were visually monitored to confirm that the operative lung was inflated from complete collapse to maximal expansion in the operative hemithorax. In Group C, nondependent lung collapse was maintained as long as transcutaneous oxygen saturation (SpO2) was greater than 90% or until the surgeon's request for reinflation due to confirmation of interlobar surfaces or air leakage from the lung. If SpO2 was less persistent than 90% or the surgeon requested inflation, reinflation was conducted in the same manner as with the IR procedure. In both groups, the remaining ventilator settings were the same except during IR.
2.4. PiCCO monitoring In all patients, a 4-French thermistor-tipped catheter (Pulsiocath PV2014L16; Pulsion Medical System, Munich,
4 Germany) was placed in the descending aorta via the femoral artery using the Seldinger technique. The fiberoptic thermistor was connected to an IntelliVue MP70 monitor equipped with PiCCO-technology module M1012A#C10 (Philips Medical Systems, Amsterdam, the Netherlands) and an accessory lumen of the catheter was connected to a pressure transducer attached to the monitor for continuous recording of BP. A standard central venous catheter was inserted through the right internal jugular vein. PiCCO measurements were obtained by injecting 15 mL of iced 5% dextrose solution (b 8° C) into the central venous catheter for cardiac output (CO) and other volumetric variables. Cardiac output was calculated using the transpulmonary thermodilution curve through a thermistor embedded in the femoral arterial catheter. Intrathoracic blood volume (ITBV), global end-diastolic volume (GEDV), and EVLW were calculated using the mean transit time method, as previously described [16]. PiCCO measurements were obtained by duplicate injections at random moments during the respiratory cycle and recorded as the mean of the two results. If the difference in a subsequent EVLW measurement was greater than 30%, additional injections were performed to obtain two more measurements for the purpose of rejecting the lowest and highest. To avoid variation between operators, the injections were always performed by the same physician.
2.5. Measurements Transcutaneous oxygen saturation was continuously recorded in both groups. EVLW is extensively used as a marker of lung injury in perioperative patients even without preexisting lung injury [9,14], and the primary outcome in the present study was change in EVLW/body weight (EVLWI). In addition, EVLW/(ITBV-GEDV), as an indicator of pulmonary vascular permeability index (PVPI), as well as PaO2/FIO2 ratio, ITBV/body surface area (ITBVI), cardiac index (CI), systemic BP, central venous pressure (CVP), and heart rate (HR) were recorded. PiCCO measurements were successively obtained during TLV: at baseline after induction of anesthesia (T1); at the end of the surgical procedure and before extubation (T2); just after admission to the ICU (T3); and 12 hours after admission to the ICU (T4). Secondary outcomes included pneumonia within 14 days, atelectasis within 14 days (defined as the need for suctioning of secretions with a fiberoptic bronchoscope), respiratory failure within 14 days (defined as the need for controlled ventilation), duration of postoperative hospitalization, admission to the ICU within 14 days (apart from postoperative care), and thoracic reoperation for any reason within 14 days.
2.6. Power and statistical analysis All collected data were analyzed using a StatView statistical program (StatView; Abacus Concepts, Berkeley, CA). A sample size of 36 patients was used for the calculations,
M. Yasuuji et al. based on previous studies [9,14]. We speculated that a difference of mean 2.4 mL/kg EVLWI (according to a 30% increase) would exist between the two groups with a standard deviation of ± 2.5 mL/kg, allowing for a type I error of 5% and type II error of 20%. Data are means ± SD for quantitative variables and numbers of patients. An unpaired t-test or Mann-Whitney U test was used for variables between the groups. Repeated-measures analysis of variance followed by a Tukey-Kramer test for multiple comparisons were used to evaluate the effects of time within a group. Statistical significance was assumed at a P-value b 0.05.
3. Results We analyzed 36 patients in the present study (Table 1). Even in Group C, IR was conducted at least once in every patient, of whom only one patient was given IR for hypoxemia. Except for frequency of IR strategy (12 ± 4 vs 3 ± 1; P b 0.001), demographic and intraoperative characteristics (including duration of surgery and OLV) did not differ between the groups. Oxygen saturation at 20 minutes after commencement of OLV (98.9 ± 1.0 vs 96.3 ± 4.7%; P = 0.029; Fig. 1A) and average SpO2 values throughout OLV (98.7 ± 1.2 vs 97.0 ± 2.7%; P = 0.020; Fig. 1B) were significantly higher in Group IR than Group C. Differences for EVLWI and PVPI between the groups were not significant at any time point. Within the groups, EVLWI in Group C and PVPI in both groups decreased over time from T2 to T4. EVLWI in Group IR remained unchanged over time (Fig. 2A, 2B), while the PaO2/FIO2 ratio also did not differ between groups (Fig. 3). Furthermore, differences for ITBVI, CI, mean arterial pressure, CVP, and HR were not significant between the groups (Table 2). All patients were discharged from the ICU on the first postoperative day, as their postoperative courses were uneventful. No differences were noted between groups with regard to postoperative morbidity, average duration of postoperative hospitalization, frequency of readmission to the ICU, or thoracic reoperation within 14 days (Table 3).
4. Discussion Use of IR significantly improved oxygenation during OLV as compared with normal ventilation. In addition, repeated IR did not increase EVLW, and there were no differences in complications observed with and without IR. Although hypoxemia is a serious problem encountered during OLV, hypoxic incidents have declined from 10% 40% in the 1980s [1] to 9% in 1993 [17] and 1% in 2003 [18], as a result of recent advances in technology and equipment used for anesthetic management. Nevertheless, it still occurs in cases with difficult to maintain oxygenation during OLV and is a challenge for anesthesiologists. Russell
Intermittent reinflation in OLV
Fig. 1 (A) Serial changes in transcutaneous oxygen saturation via pulse oximetry (SpO2) within the initial 20 minutes after commencement of one-lung ventilation (OLV). (B) Average SpO2 throughout OLV in the intermittent reinflation group (Group IR; solid circles) and the control group (Group C; open circles). Values are means ± SD. ⁎P b 0.05 vs just after the start of OLV (OLVO), a statistically significant difference within a group; †P b 0.05 vs 10 minutes after the start of OLV (OLV10), a statistically significant difference. Group C patients serve as controls; Group IR patients received intermittent reinflation. OLV20 = 20 minutes after the start of OLV.
proposed providing intermittent positive airway pressure to the nonventilated lung by means of slow oxygen inflation of 2 L/min for two seconds repeated every 10 seconds for 5 minutes for patients who are desaturated during OLV [19]. Similarly, the present method of intermittent administration of oxygen to the nonventilated lung significantly increased SpO2 at 20 minutes after commencement of OLV as well as average SpO2 throughout OLV in Group IR versus Group C, though the SpO2 values in both groups were within clinically normal ranges. Common hypoxemia during OLV may suddenly occur for a variety of reasons, such as dislodgment of the double-lumen tube, or occlusion of the respiratory tract with secretions or blood due to manipulation of the lung and bronchi. It requires some time to find treatable causes of hypoxemia and/or bronchoaspiration by fiberoptic bronchoscopy [20]. Additional increase in SpO2 by IR, even if not clinically relevant, may delay the onset of desaturation. In addition, improvement in oxygenation by IR during OLV may lead to reduced FIO2, which can prevent absorption atelectasis [21]. On the other hand, IR was not conducted without the surgeon's cooperation and understanding. The
5
Fig. 2 (A) Serial changes in extravascular lung water indexed to body weight (EVLWI). (B) Extravascular lung water/(intrathoracic blood volume - global end-diastolic volume) ratio as a pulmonary vascular permeability index (PVPI) in the intermittent reinflation group (Group IR; gray bars) and the control group (Group C; white bars) at the baseline time point after induction of anesthesia (T1), at the end of the surgical procedure and before extubation (T2), just after admission to the intensive care unit (ICU; T3), and 12 hours after admission to the ICU (T4). Values are means ± SD. ⁎P b 0.05 vs T1; †P b 0.05 vs T2; ‡P b 0.05 vs T3.
operative lung was completely collapsed during the non-IR period in our study, which may have facilitated the surgical procedures as compared with application of continuous positive airway pressure to the nondependent lung. The only
Fig. 3 Serial changes in partial pressure of arterial oxygen/ inspired oxygen fraction (PaO2/FIO2) ratio in the intermittent reinflation group (Group IR; gray bars) and the control group (Group C; white bars) at the baseline time point after induction of anesthesia (T1), at the end of the surgical procedure and before extubation (T2), just after admission to the intensive care unit (ICU; T3), and 12 hours after admission to the ICU (T4). Values are means ± SD. †P b 0.05 vs T2.
Values are means ± SD. T1 = baseline time, after induction of anesthesia, T2 = end of surgical procedure but before extubation, T3 = just after admission to intensive care unit (ICU), T4 = 12 hours after admission to ICU. Group IR underwent intermittent reinflation, Group C served as controls. ITBVI = intrathoracic blood volume/body surface area, CI = cardiac index, MAP = mean arterial pressure, CVP = central venous pressure, HR = heart rate. ⁎ P b 0.05 vs T1. † P b 0.05 vs T2. ‡ P b 0.05 vs T3.
b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 221 ⁎,†,‡ 0.6 ⁎ 10 ⁎,† 2.5 † 12 ⁎ 1054 ± 3.8 ± 84 ± 1.8 ± 79 ± 1052 ± 137 ⁎,†,‡ 3.7 ± 0.5 ⁎ 86 ± 15 ⁎,† 1.7 ± 2.0 ⁎,† 79 ± 11 ⁎ 957 ± 143 4.1 ± 0.7 ⁎,† 88 ± 12 ⁎,† 2.2 ± 2.3 † 84 ± 10 ⁎ 956 ± 100 4.0 ± 0.7 ⁎,† 90 ± 14 ⁎,† 2.4 ± 3.0 † 83 ± 11 ⁎,† ± 196 ± 0.8 ⁎ ±8 ± 4.3 ± 11 ⁎ 926 3.8 67 4.7 80 885 ± 128 3.4 ± 0.4 ⁎ 62 ± 6 4.1 ± 2.1 77 ± 8 ⁎ ± 136 ± 0.3 ±9 ± 2.6 ±8 934 2.2 69 3.8 58
Time Group C Group IR Group C Group IR Group C Group IR Group C Group IR
914 ± 108 2.0 ± 0.3 63 ± 7 3.6 ± 1.8 53 ± 5 ITBVI (mL/m ) CI (L/min/m2) MAP (mmHg) CVP (mmHg) HR (bpm)
2
Statistical comparison T4 T3 T2 T1
Serial changes in hemodynamic variables Table 2
NS NS NS NS NS
M. Yasuuji et al. Groups
6 Table 3
Postoperative pulmonary complications Group IR Group C P-value (n = 18) (n = 18)
Pneumonia within 14 days (n) Atelectasis within 14 days (n) Respiratory failure within 14 days (n) Postop hospitalization (days) Admission to ICU within 14 days (n) Reoperation within 14 days (n)
0 0 0
0 0 0
1.00 1.00 1.00
8.7 ± 4.4 9.9 ± 4.1 0.39 0 0 1.00 0
0
1.00
Values are means ± SD. Group IR underwent intermittent reinflation, Group C served as controls. Postop = postoperative, ICU = intensive care unit.
disadvantage of IR is the time required. However, there were no differences between groups in duration of surgery or total OLV time. In this study, we performed IR an average of 12 times during OLV in Group IR. However, IR is not needed as frequently in clinical practice, as long as oxygenation is maintained within an acceptable range. In the present study, we examined whether preservation of oxygenation by IR would also provide safety in terms of lung injury caused by repeated mechanical forces. To test the relationship between IR and lung injury, we compared EVLW values using a PiCCO system. Lung injury due to OLV is related to mechanical forces exerted during OLV [8], and was reduced in a previous study with the use of a protective ventilatory strategy in perioperative patients with normal lungs similar to ALI and ARDS [9]. In addition, EVLW has been though to play a role not only as an indicator of prognosis and severity of ALI and ARDS [11-13], but also as a parameter to assess perioperative respiratory condition in patients with no preexisting lung injury [9,14]. Furthermore, the PiCCO device accurately detects small (10% - 20%) increases in EVLV in normal lungs [22]. In another study, Suh et al provided the theoretical basis for derecruitmentassociated lung injury [10], from which we speculated that IR might induce lung injury because of the repeated cycle of collapse and reopening of the operative lung. In the present cases, we expanded the lung to a pressure of 20 cmH2O and held it for 10 seconds for each IR procedure. The inflammatory process of lung injury is assumed to be associated with an increase in vascular permeability; thus we speculated that repeated IR might cause an increase in EVLW. However, no significant effect of IR occurred on EVLW. An important question to consider is why EVLW was decreased in the present subjects. Patients with lung cancer have a higher production of oxygen free radicals than normal individuals and tumor resection removes a large oxidative burden [23]; thus, EVLW might have been decreased by resection of the lesion where vascular permeability was increased. Another possible reason for the decreased EVLW was that the accuracy of transpulmonary thermodilution was affected by lung resection, which is a serious concern.
Intermittent reinflation in OLV Indeed, estimation of EVLW by thermodilution is based on the equation: ITBV = 1.25 × GEDV. Since the difference between ITBV and GEDV is pulmonary blood volume, any decrease in that volume (eg, due to lung resection) would affect the GEDV/ITBV ratio and hence the estimation of EVLW. ITBV is overestimated by approximately 10% after a pneumonectomy, because the 50% surgical reduction in pulmonary blood volume is not taken into account by the preceding equation [24]. Since EVLW is calculated as the difference between intrathoracic thermal volume and overestimated ITBV, transpulmonary thermodilution underestimates EVLW after lung resection [24]; thus, the value of EVLWI after T2 would be underestimated as compared with T1. However, we considered it appropriate to compare the groups who were treated in the same manner in the same conditions except for IR [25]. Potential limitations of this study include the small number of patients treated at a single institution, limiting our ability to generalize the findings. Moreover, because we targeted patients with relatively low ASA physical status, further studies should be performed using patients with concomitant illnesses or without respiratory reserve, eg, those with repeated pneumonia due to lung tumor, irradiation pneumonitis, carcinomatous lymphangiitis, or severe malnutrition. In fact, such patients are in need of IR against possible hypoxemia during OLV. Another limitation was that lung injury may have occurred due to inhalation of a high concentration of oxygen during IR. However, there was consequently no influence of FIO2, because we used 100% oxygen during OLV in both groups. In conclusion, IR had a beneficial effect on maintenance of oxygenation during OLV without any significant effects on EVLW or postoperative complications. Intermittent reinflation is a safe maneuver for maintenance of oxygenation in similar cases.
Acknowledgments We gratefully acknowledge Ryuji Nakamura, MD, Toshimichi Yasuda, MD, and Noboru Saeki, MD, for their helpful support with data analysis and manuscript preparation.
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Original Contribution
Intermittent reinflation is safe to maintain oxygenation without alteration of extravascular lung water during one-lung ventilation☆ Masakazu Yasuuji MD (Assistant Professor)a,⁎, Shinji Kusunoki MD (Assistant Professor)a , Hiroshi Hamada MD (Associate Professor)b , Masashi Kawamoto MD (Professor and Chair)b a
Department of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, Japan Department of Anesthesiology and Critical Care, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan b
Received 3 December 2012; revised 9 October 2013; accepted 11 October 2013
Keywords: Extravascular lung water; Intermittent reinflation; Lung injury; One-lung ventilation; Oxygenation, Maintenance of
Abstract Study Objective: To investigate whether a maneuver for repeated cycles of collapse and reexpansion of the operative lung, termed “intermittent reinflation” (IR), to counter hypoxemia during one-lung ventilation (OLV), results in a time-dependent alteration of extravascular lung water. Design: Prospective, randomized clinical study. Setting: Operating room and postsurgical intensive care unit of a university hospital. Patients: 36 ASA physical status 1 and 2 patients undergoing elective, video-assisted thoracic surgery for lung tumors. Interventions: Patients were randomly assigned to two groups. Group C consisted of 18 patients whose nondependent lung was kept collapsed during OLV, while Group IR included 18 patients with IR that consisted of 4 separate, 10-second manual inflations and 5-second openings within one minute at intervals of 20 minutes during OLV. Measurements: Perioperative parameters included transcutaneous oxygen saturation (SpO2), hemodynamic data, extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) as determined by the single-indicator transpulmonary thermodilution technique, and partial pressure of arterial oxygen/inspired oxygen fraction (PaO2/FIO2) ratio. Main Results: Group IR had significantly higher SpO2 at 20 minutes after commencement of OLV (98.9% vs 96.3%, P = 0.029) and average SpO2 throughout OLV (98.7% vs 97.0%, P = 0.020). Hemodynamic data, EVLWI, PVPI, and PaO2/FIO2 ratio did not differ between the groups, and there were no differences between groups in postoperative morbidity or hospital stay. Conclusions: Intermittent reinflation had a beneficial effect on oxygenation during OLV, without any significant effects on EVLW or postoperative outcomes. © 2014 Elsevier Inc. All rights reserved.
☆ Supported by a Grant-in-Aid for Young Scientists (B; No. 19791066) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Tokyo, Japan. ⁎ Correspondence: Masakazu Yasuuji, MD, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel.: + 81 82 257 5267; fax: + 81 82 257 5269. E-mail address: [email protected] (M. Yasuuji).
http://dx.doi.org/10.1016/j.jclinane.2013.10.006 0952-8180/© 2014 Elsevier Inc. All rights reserved.
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M. Yasuuji et al.
1. Introduction One-lung ventilation (OLV) is an established procedure performed during lung resection to prevent blood vessel injury and facilitate surgical procedures. Hypoxemia is the most important problem encountered during OLV [1,2]. To counter this major concern, a maneuver to expand the collapsed lung, known as “intermittent reinflation” (IR), performed to improve oxygenation at regular intervals of 10-15 minutes, has been recommended [3-5]. Lung injury after lung resection is associated with significant morbidity and mortality [6]. This type of injury generally follows a clinically and histopathologically indistinguishable course from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) [7], and is related to mechanical forces exerted during OLV [8]. Similar to ALI and ARDS, a recent experiment has demonstrated a potential reduction of lung injury due to OLV using a protective ventilatory strategy with low tidal volume (VT) in perioperative patients with normal lungs [9]. Shear forces secondary to repeated collapse and reopening of alveolar units can result in lung injury, known as atelectrauma [10]. However, there are no reports of repeated IR during OLV or the relationship of IR to lung injury after lung resection. Lung injury induced by IR repeatedly applied during surgical resection was investigated. Extravascular lung water (EVLW) is not only an indicator of prognosis and severity of ALI and ARDS [11-13], it is
Table 1
also a useful parameter to assess perioperative respiratory conditions in patients with no preexisting lung injury [9,14]. Thus, it may be useful to quantify the inflammatory process of lung injury, which may increase vascular permeability, resulting in accumulation of fluid and development of pulmonary edema [7]. A continuous cardiac output monitor (PiCCO; Pulsion Medical Systems, Munich, Germany) was recently introduced to measure EVLW using a singleindicator thermodilution method [15]. In this prospective clinical study, a time-dependent alteration of EVLW was evaluated with the PiCCO monitor.
2. Materials and methods 2.1. Study population The study protocol was approved by the Ethics Committee of Hiroshima University (IRB No. 266), and all patients provided written, informed consent before enrollment. This study was registered at www.umin.ac.jp/ctr/ index.htm (UMIN000008759). Eligible patients met the following criteria: 1) 80 years of age or under, 2) ASA physical status 1 or 2, and 3) scheduled for elective, videoassisted thoracic surgery for lung tumors requiring OLV lasting more than 120 minutes (Table 1). Exclusion criteria included decompensated cardiac (New York Heart Association N class II) or pulmonary disease [vital capacity (VC) b
Patient characteristics and intraoperative values
Demographic variables
Group IR (n = 18)
Group C (n = 18)
Age (yrs) Gender (m/f) Weight (kg) Height (cm) ASA physical status (1 / 2) (n) Preop VC (% predicted) Preop FEV1/FVC ratio (%) Right-sided thoracotomy (n) Left-sided thoracotomy (n) Bilateral thoracotomy (n) Segments resected (n) Surgery duration (min) OLV duration (min) Intraop blood loss (mL) Intraop urine output (mL) Intraop fluid administration (mL) Hydroxyethyl starch (0 mL/500 mL/1000 mL) (n) Intraop transfusion (n) Sequential intermittent reinflation (n)
63 ± 9 15 / 3 64 ± 8 165 ± 7 0 / 18 108 ± 13 73 ± 9 7 9 2 3±1 310 ± 107 253 ± 88 193 ± 172 756 ± 373 3456 ± 756 16 / 1 / 1
65 ± 8 11 / 7 63 ± 12 161 ± 8 1 / 17 109 ± 13 74 ± 9 9 8 1 4±1 317 ± 102 269 ± 90 236 ± 206 940 ± 662 3411 ± 1092 15 / 3 / 0
0 12 ± 4
0 3±1
P -value 0.57 0.14 0.85 0.22 0.32 0.85 0.61 0.45 0.09 0.85 0.60 0.50 0.31 0.89 0.69 1.00 b 0.001
Values are means ± SD, unless otherwise noted. Group IR patients underwent intermittent reinflation, Group C patients served as controls. Preop = preoperative, VC = vital capacity, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, OLV = one-lung ventilation, intraop = intraoperative.
Intermittent reinflation in OLV 50% of predicted values and/or forced expiratory volume in 1 second (FEV1) b 50% of forced vital capacity (FVC)], chronic renal failure (serum creatinine N 1.5 mg/dL), altered liver function (N class B in Child-Pugh), preoperative treatment with an immune modulator (cytostatic drugs, corticosteroids, nonsteroidal antiinflammatory drugs, vaccination, blood products) within one month before surgery, preexisting coagulation disorders, and symptoms of an acute inflammatory process (clinically defined or abnormal data for C-reactive protein, leukocyte count, or body temperature). Arteriosclerosis obliterans and/or iliac artery stenosis and/or aneurysms with or without bypass surgery, which would be associated with an increased risk of complications following femoral arterial cannulation for the PiCCO procedure, also were excluded.
2.2. Patient treatment Anesthetic and surgical management was standardized for each patient. The same experienced surgeons conducted each operation. Surgical procedures were adapted for established or suspected malignancies, and the lung resections were performed using a standard video-assisted thoracic surgery method. None of the patients was premedicated. On arrival at the operating room, a thoracic epidural catheter was placed at the level of thoracic segments Th4-Th5 to Th6-Th7. General anesthesia was induced with intravenous administration of 1.0 - 1.5 mg/kg of propofol or 3.0 - 5.0 mg/kg of thiamylal, 1.5 - 2.5 μg/kg of fentanyl, and 0.1 mg/kg of vecuronium. After induction of anesthesia, an appropriate size left-sided double-lumen tube (Broncho-Cath; Covidien, Dublin, Ireland) was placed and confirmed using a fiberoptic bronchoscope before and after turning the patient to the lateral decubitus position. Anesthesia was maintained with 2.0% 2.5% of sevoflurane and epidural anesthesia with continuous infusions of ropivacaine 0.375% at a rate of 4.0 - 6.0 mL/hr. Appropriate incremental doses of fentanyl and vecuronium were given. The lungs were mechanically ventilated (Fabius GS; Dräger, Lübeck, Germany) using volume-controlled ventilation during two-lung ventilation (TLV) and pressurecontrolled ventilation during OLV, respectively. Volumecontrolled ventilation was initiated with 10 mL/kg of VT at a respiratory rate (RR) of 12 breaths per minute (breaths/min), using 2 cmH2O of positive end-expiratory pressure (PEEP) and an inspiratory:expiratory ratio (I:E) of 1:1.5. When OLV was started, the nondependent lung was completely collapsed and opened to air with suction if necessary, while the dependent lung was initially ventilated at 20 - 25 cmH2O of peak inspiratory pressure providing approximately 300 400 mL of VT with 35 L/min of inspiratory flow at a RR of 20 breaths/min, with 2 cmH2O of PEEP and I:E of 1:1.5. During both TLV and OLV, RR was adjusted to achieve a partial arterial carbon dioxide pressure of 40-45 mmHg. The
3 fraction of inspired oxygen (FIO2) was adjusted to 0.6 in air during TLV and to 1.0 during OLV. Bladder temperature was monitored in all patients and a forced-air warming blanket system was used to prevent hypothermia during surgery. Intraoperative fluid replacement consisted of 10 mL/kg/hr of Ringer's acetate solution. If systolic arterial pressure (BP) was lower than 80 mmHg for more than 30 minutes or urine output was less than 0.5 mL/kg/hr for more than two hours, additional fluid was given of 500 mL of hydroxyethyl starch, repeated up to two times. As a general rule, catecholamines were not administered. After surgery, extubation was performed when patients met the following criteria: 1) temperature higher than 36° C; 2) partial pressure of arterial oxygen (PaO2)/FIO2 ratio greater than 150 mmHg with hemoglobin greater than 7 g/dL; 3) RR less than 25 breaths/min and VT greater than 5 mL/kg during spontaneous breathing; and 4) adequate cough during suctioning. All patients were transferred to the intensive care unit (ICU) after surgery and cared for by attending physicians using a standard postoperative protocol.
2.3. Study protocol Prior to anesthetic induction, patients were randomly assigned to two groups by the concealed allocation approach using opaque sealed envelopes containing the randomization schedule. Randomization was done by computergenerated codes maintained in sequentially numbered opaque envelopes that were opened just prior to induction of general anesthesia. Group C was comprised of control patients, whose nondependent lung was kept collapsed completely during OLV; Group IR patients received IR with 100% oxygen in the two lungs during OLV. In the latter group, IR was performed by manually inflating the nondependent and dependent lungs to 20 cmH2O, which was then held for 10 seconds and opened to the atmosphere for 5 seconds. This action was repeated 4 times per minute at 20-minute intervals during OLV. The maneuvers were visually monitored to confirm that the operative lung was inflated from complete collapse to maximal expansion in the operative hemithorax. In Group C, nondependent lung collapse was maintained as long as transcutaneous oxygen saturation (SpO2) was greater than 90% or until the surgeon's request for reinflation due to confirmation of interlobar surfaces or air leakage from the lung. If SpO2 was less persistent than 90% or the surgeon requested inflation, reinflation was conducted in the same manner as with the IR procedure. In both groups, the remaining ventilator settings were the same except during IR.
2.4. PiCCO monitoring In all patients, a 4-French thermistor-tipped catheter (Pulsiocath PV2014L16; Pulsion Medical System, Munich,
4 Germany) was placed in the descending aorta via the femoral artery using the Seldinger technique. The fiberoptic thermistor was connected to an IntelliVue MP70 monitor equipped with PiCCO-technology module M1012A#C10 (Philips Medical Systems, Amsterdam, the Netherlands) and an accessory lumen of the catheter was connected to a pressure transducer attached to the monitor for continuous recording of BP. A standard central venous catheter was inserted through the right internal jugular vein. PiCCO measurements were obtained by injecting 15 mL of iced 5% dextrose solution (b 8° C) into the central venous catheter for cardiac output (CO) and other volumetric variables. Cardiac output was calculated using the transpulmonary thermodilution curve through a thermistor embedded in the femoral arterial catheter. Intrathoracic blood volume (ITBV), global end-diastolic volume (GEDV), and EVLW were calculated using the mean transit time method, as previously described [16]. PiCCO measurements were obtained by duplicate injections at random moments during the respiratory cycle and recorded as the mean of the two results. If the difference in a subsequent EVLW measurement was greater than 30%, additional injections were performed to obtain two more measurements for the purpose of rejecting the lowest and highest. To avoid variation between operators, the injections were always performed by the same physician.
2.5. Measurements Transcutaneous oxygen saturation was continuously recorded in both groups. EVLW is extensively used as a marker of lung injury in perioperative patients even without preexisting lung injury [9,14], and the primary outcome in the present study was change in EVLW/body weight (EVLWI). In addition, EVLW/(ITBV-GEDV), as an indicator of pulmonary vascular permeability index (PVPI), as well as PaO2/FIO2 ratio, ITBV/body surface area (ITBVI), cardiac index (CI), systemic BP, central venous pressure (CVP), and heart rate (HR) were recorded. PiCCO measurements were successively obtained during TLV: at baseline after induction of anesthesia (T1); at the end of the surgical procedure and before extubation (T2); just after admission to the ICU (T3); and 12 hours after admission to the ICU (T4). Secondary outcomes included pneumonia within 14 days, atelectasis within 14 days (defined as the need for suctioning of secretions with a fiberoptic bronchoscope), respiratory failure within 14 days (defined as the need for controlled ventilation), duration of postoperative hospitalization, admission to the ICU within 14 days (apart from postoperative care), and thoracic reoperation for any reason within 14 days.
2.6. Power and statistical analysis All collected data were analyzed using a StatView statistical program (StatView; Abacus Concepts, Berkeley, CA). A sample size of 36 patients was used for the calculations,
M. Yasuuji et al. based on previous studies [9,14]. We speculated that a difference of mean 2.4 mL/kg EVLWI (according to a 30% increase) would exist between the two groups with a standard deviation of ± 2.5 mL/kg, allowing for a type I error of 5% and type II error of 20%. Data are means ± SD for quantitative variables and numbers of patients. An unpaired t-test or Mann-Whitney U test was used for variables between the groups. Repeated-measures analysis of variance followed by a Tukey-Kramer test for multiple comparisons were used to evaluate the effects of time within a group. Statistical significance was assumed at a P-value b 0.05.
3. Results We analyzed 36 patients in the present study (Table 1). Even in Group C, IR was conducted at least once in every patient, of whom only one patient was given IR for hypoxemia. Except for frequency of IR strategy (12 ± 4 vs 3 ± 1; P b 0.001), demographic and intraoperative characteristics (including duration of surgery and OLV) did not differ between the groups. Oxygen saturation at 20 minutes after commencement of OLV (98.9 ± 1.0 vs 96.3 ± 4.7%; P = 0.029; Fig. 1A) and average SpO2 values throughout OLV (98.7 ± 1.2 vs 97.0 ± 2.7%; P = 0.020; Fig. 1B) were significantly higher in Group IR than Group C. Differences for EVLWI and PVPI between the groups were not significant at any time point. Within the groups, EVLWI in Group C and PVPI in both groups decreased over time from T2 to T4. EVLWI in Group IR remained unchanged over time (Fig. 2A, 2B), while the PaO2/FIO2 ratio also did not differ between groups (Fig. 3). Furthermore, differences for ITBVI, CI, mean arterial pressure, CVP, and HR were not significant between the groups (Table 2). All patients were discharged from the ICU on the first postoperative day, as their postoperative courses were uneventful. No differences were noted between groups with regard to postoperative morbidity, average duration of postoperative hospitalization, frequency of readmission to the ICU, or thoracic reoperation within 14 days (Table 3).
4. Discussion Use of IR significantly improved oxygenation during OLV as compared with normal ventilation. In addition, repeated IR did not increase EVLW, and there were no differences in complications observed with and without IR. Although hypoxemia is a serious problem encountered during OLV, hypoxic incidents have declined from 10% 40% in the 1980s [1] to 9% in 1993 [17] and 1% in 2003 [18], as a result of recent advances in technology and equipment used for anesthetic management. Nevertheless, it still occurs in cases with difficult to maintain oxygenation during OLV and is a challenge for anesthesiologists. Russell
Intermittent reinflation in OLV
Fig. 1 (A) Serial changes in transcutaneous oxygen saturation via pulse oximetry (SpO2) within the initial 20 minutes after commencement of one-lung ventilation (OLV). (B) Average SpO2 throughout OLV in the intermittent reinflation group (Group IR; solid circles) and the control group (Group C; open circles). Values are means ± SD. ⁎P b 0.05 vs just after the start of OLV (OLVO), a statistically significant difference within a group; †P b 0.05 vs 10 minutes after the start of OLV (OLV10), a statistically significant difference. Group C patients serve as controls; Group IR patients received intermittent reinflation. OLV20 = 20 minutes after the start of OLV.
proposed providing intermittent positive airway pressure to the nonventilated lung by means of slow oxygen inflation of 2 L/min for two seconds repeated every 10 seconds for 5 minutes for patients who are desaturated during OLV [19]. Similarly, the present method of intermittent administration of oxygen to the nonventilated lung significantly increased SpO2 at 20 minutes after commencement of OLV as well as average SpO2 throughout OLV in Group IR versus Group C, though the SpO2 values in both groups were within clinically normal ranges. Common hypoxemia during OLV may suddenly occur for a variety of reasons, such as dislodgment of the double-lumen tube, or occlusion of the respiratory tract with secretions or blood due to manipulation of the lung and bronchi. It requires some time to find treatable causes of hypoxemia and/or bronchoaspiration by fiberoptic bronchoscopy [20]. Additional increase in SpO2 by IR, even if not clinically relevant, may delay the onset of desaturation. In addition, improvement in oxygenation by IR during OLV may lead to reduced FIO2, which can prevent absorption atelectasis [21]. On the other hand, IR was not conducted without the surgeon's cooperation and understanding. The
5
Fig. 2 (A) Serial changes in extravascular lung water indexed to body weight (EVLWI). (B) Extravascular lung water/(intrathoracic blood volume - global end-diastolic volume) ratio as a pulmonary vascular permeability index (PVPI) in the intermittent reinflation group (Group IR; gray bars) and the control group (Group C; white bars) at the baseline time point after induction of anesthesia (T1), at the end of the surgical procedure and before extubation (T2), just after admission to the intensive care unit (ICU; T3), and 12 hours after admission to the ICU (T4). Values are means ± SD. ⁎P b 0.05 vs T1; †P b 0.05 vs T2; ‡P b 0.05 vs T3.
operative lung was completely collapsed during the non-IR period in our study, which may have facilitated the surgical procedures as compared with application of continuous positive airway pressure to the nondependent lung. The only
Fig. 3 Serial changes in partial pressure of arterial oxygen/ inspired oxygen fraction (PaO2/FIO2) ratio in the intermittent reinflation group (Group IR; gray bars) and the control group (Group C; white bars) at the baseline time point after induction of anesthesia (T1), at the end of the surgical procedure and before extubation (T2), just after admission to the intensive care unit (ICU; T3), and 12 hours after admission to the ICU (T4). Values are means ± SD. †P b 0.05 vs T2.
Values are means ± SD. T1 = baseline time, after induction of anesthesia, T2 = end of surgical procedure but before extubation, T3 = just after admission to intensive care unit (ICU), T4 = 12 hours after admission to ICU. Group IR underwent intermittent reinflation, Group C served as controls. ITBVI = intrathoracic blood volume/body surface area, CI = cardiac index, MAP = mean arterial pressure, CVP = central venous pressure, HR = heart rate. ⁎ P b 0.05 vs T1. † P b 0.05 vs T2. ‡ P b 0.05 vs T3.
b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 221 ⁎,†,‡ 0.6 ⁎ 10 ⁎,† 2.5 † 12 ⁎ 1054 ± 3.8 ± 84 ± 1.8 ± 79 ± 1052 ± 137 ⁎,†,‡ 3.7 ± 0.5 ⁎ 86 ± 15 ⁎,† 1.7 ± 2.0 ⁎,† 79 ± 11 ⁎ 957 ± 143 4.1 ± 0.7 ⁎,† 88 ± 12 ⁎,† 2.2 ± 2.3 † 84 ± 10 ⁎ 956 ± 100 4.0 ± 0.7 ⁎,† 90 ± 14 ⁎,† 2.4 ± 3.0 † 83 ± 11 ⁎,† ± 196 ± 0.8 ⁎ ±8 ± 4.3 ± 11 ⁎ 926 3.8 67 4.7 80 885 ± 128 3.4 ± 0.4 ⁎ 62 ± 6 4.1 ± 2.1 77 ± 8 ⁎ ± 136 ± 0.3 ±9 ± 2.6 ±8 934 2.2 69 3.8 58
Time Group C Group IR Group C Group IR Group C Group IR Group C Group IR
914 ± 108 2.0 ± 0.3 63 ± 7 3.6 ± 1.8 53 ± 5 ITBVI (mL/m ) CI (L/min/m2) MAP (mmHg) CVP (mmHg) HR (bpm)
2
Statistical comparison T4 T3 T2 T1
Serial changes in hemodynamic variables Table 2
NS NS NS NS NS
M. Yasuuji et al. Groups
6 Table 3
Postoperative pulmonary complications Group IR Group C P-value (n = 18) (n = 18)
Pneumonia within 14 days (n) Atelectasis within 14 days (n) Respiratory failure within 14 days (n) Postop hospitalization (days) Admission to ICU within 14 days (n) Reoperation within 14 days (n)
0 0 0
0 0 0
1.00 1.00 1.00
8.7 ± 4.4 9.9 ± 4.1 0.39 0 0 1.00 0
0
1.00
Values are means ± SD. Group IR underwent intermittent reinflation, Group C served as controls. Postop = postoperative, ICU = intensive care unit.
disadvantage of IR is the time required. However, there were no differences between groups in duration of surgery or total OLV time. In this study, we performed IR an average of 12 times during OLV in Group IR. However, IR is not needed as frequently in clinical practice, as long as oxygenation is maintained within an acceptable range. In the present study, we examined whether preservation of oxygenation by IR would also provide safety in terms of lung injury caused by repeated mechanical forces. To test the relationship between IR and lung injury, we compared EVLW values using a PiCCO system. Lung injury due to OLV is related to mechanical forces exerted during OLV [8], and was reduced in a previous study with the use of a protective ventilatory strategy in perioperative patients with normal lungs similar to ALI and ARDS [9]. In addition, EVLW has been though to play a role not only as an indicator of prognosis and severity of ALI and ARDS [11-13], but also as a parameter to assess perioperative respiratory condition in patients with no preexisting lung injury [9,14]. Furthermore, the PiCCO device accurately detects small (10% - 20%) increases in EVLV in normal lungs [22]. In another study, Suh et al provided the theoretical basis for derecruitmentassociated lung injury [10], from which we speculated that IR might induce lung injury because of the repeated cycle of collapse and reopening of the operative lung. In the present cases, we expanded the lung to a pressure of 20 cmH2O and held it for 10 seconds for each IR procedure. The inflammatory process of lung injury is assumed to be associated with an increase in vascular permeability; thus we speculated that repeated IR might cause an increase in EVLW. However, no significant effect of IR occurred on EVLW. An important question to consider is why EVLW was decreased in the present subjects. Patients with lung cancer have a higher production of oxygen free radicals than normal individuals and tumor resection removes a large oxidative burden [23]; thus, EVLW might have been decreased by resection of the lesion where vascular permeability was increased. Another possible reason for the decreased EVLW was that the accuracy of transpulmonary thermodilution was affected by lung resection, which is a serious concern.
Intermittent reinflation in OLV Indeed, estimation of EVLW by thermodilution is based on the equation: ITBV = 1.25 × GEDV. Since the difference between ITBV and GEDV is pulmonary blood volume, any decrease in that volume (eg, due to lung resection) would affect the GEDV/ITBV ratio and hence the estimation of EVLW. ITBV is overestimated by approximately 10% after a pneumonectomy, because the 50% surgical reduction in pulmonary blood volume is not taken into account by the preceding equation [24]. Since EVLW is calculated as the difference between intrathoracic thermal volume and overestimated ITBV, transpulmonary thermodilution underestimates EVLW after lung resection [24]; thus, the value of EVLWI after T2 would be underestimated as compared with T1. However, we considered it appropriate to compare the groups who were treated in the same manner in the same conditions except for IR [25]. Potential limitations of this study include the small number of patients treated at a single institution, limiting our ability to generalize the findings. Moreover, because we targeted patients with relatively low ASA physical status, further studies should be performed using patients with concomitant illnesses or without respiratory reserve, eg, those with repeated pneumonia due to lung tumor, irradiation pneumonitis, carcinomatous lymphangiitis, or severe malnutrition. In fact, such patients are in need of IR against possible hypoxemia during OLV. Another limitation was that lung injury may have occurred due to inhalation of a high concentration of oxygen during IR. However, there was consequently no influence of FIO2, because we used 100% oxygen during OLV in both groups. In conclusion, IR had a beneficial effect on maintenance of oxygenation during OLV without any significant effects on EVLW or postoperative complications. Intermittent reinflation is a safe maneuver for maintenance of oxygenation in similar cases.
Acknowledgments We gratefully acknowledge Ryuji Nakamura, MD, Toshimichi Yasuda, MD, and Noboru Saeki, MD, for their helpful support with data analysis and manuscript preparation.
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