Skip to content

Advertisement

Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Effect of desflurane-remifentanil vs. Propofol-remifentanil anesthesia on arterial oxygenation during one-lung ventilation for thoracoscopic surgery: a prospective randomized trial

BMC AnesthesiologyBMC series – open, inclusive and trusted201717:9

https://doi.org/10.1186/s12871-017-0302-x

Received: 30 November 2016

Accepted: 5 January 2017

Published: 18 January 2017

Abstract

Background

One-lung ventilation during thoracic surgery frequently disturbs normal systemic oxygenation. However, the effect of anesthetics on arterial oxygenation during one-lung ventilation has not been well established in human study. In this clinical trial, we investigated whether a difference between desflurane-remifentanil and propofol-remifentanil anesthesia can be observed with regard to oxygenation during one-lung ventilation for thoracoscopic surgery.

Methods

Adult patients with lung cancer, scheduled for video-assisted thoracoscopic lobectomy without preoperative oxygen support, were screened and randomized to receive desflurane or propofol, with remifentanil continuous infusion in both groups. Mechanical ventilation was performed with tidal volume of 8 ml/kg and FIO2 0.5 during two-lung ventilation, and 6 ml/kg and 1.0 during one-lung ventilation, both with positive end-expiratory pressure of 5 cmH2O. Arterial blood gas analysis was performed preoperatively, during two-lung ventilation, and after 15, 30, 45, and 60 min of one-lung ventilation. The primary endpoint was PaO2 at 30 min after initiating one-lung ventilation. Statistical analyses included the independent t-test for the primary endpoint and a mixed model with a post-hoc analysis to evaluate the serial changes in values.

Results

Patients were recruited between July 9 and December 2, 2014. In total, 103 patients were analyzed (n = 52 in desflurane group and n = 51 in propofol group). The primary endpoint, PaO2 at 30 min of one-lung ventilation was lower in the desflurane group than the propofol group (170 ± 72 vs. 202 ± 82 mmHg; p = 0.039). Serial changes in PaO2 during one-lung ventilation showed lower levels during desflurane anesthesia compared with propofol anesthesia (mean difference, 45 mmHg; 95% confidence interval, 16–75 mmHg; p = 0.003).

Conclusions

In conclusion, desflurane-remifentanil anesthesia resulted in decreased arterial oxygenation compared with that of propofol-remifentanil anesthesia during one-lung ventilation for thoracoscopic surgery in patients with lung cancer.

Trial registration

ClinicalTrials.gov identifier: NCT02191371, registered on July 7, 2014

Keywords

DesfluranePropofolOne-lung ventilationOxygenation

Background

One-lung ventilation (OLV) during thoracic surgery can rapidly result in impaired systemic oxygenation. The grade of hypoxemia during OLV is mainly influenced by an increase in shunt and dead space. Hypoxic pulmonary vasoconstriction (HPV) is a physiological protective mechanism that diverts pulmonary perfusion from the non-ventilated to the ventilated area of the lung, thereby decreasing the shunt of unsaturated blood and ameliorating the degree of hypoxemia. This physiologic modulation is influenced by numerous factors such as various drugs, temperature, acid–base status, airway pressure, patient position, and cardiac output [1]. In numerous animal studies and in studies of isolated lungs, HPV has been shown to be modulated by volatile anesthetics [15]. However, human studies have yielded inconsistent results regarding the effects of different anesthetics on systemic oxygenation during OLV [610]. Moreover, the effects of desflurane-remifentanil balanced anesthesia have not been evaluated in a clinical study.

Most halogenated inhaled anesthetics are characterized by its dose-dependent systemic vasodilatory effect [1114]. We hypothesized that the vasodilatory effect of desflurane may affect any protective role of HPV, thus impair oxygenation during OLV, even when it is used as a balanced anesthesia, compared with total intravenous anesthesia (TIVA). To evaluate this hypothesis, we compared the effects of two commonly used modern anesthetics, desflurane and propofol, with concomitant remifentanil continuous infusion in both arms, on systemic oxygenation during OLV for video-assisted thoracoscopic surgery.

Methods

The Institutional Review Board of Seoul National University Hospital approved this study (reference # 1406-052-587; approval date, July 7, 2014). All patients provided written informed consent, and the study was performed according to Good Clinical Practice guidelines and the principles of the Declaration of Helsinki (ClinicalTrials.gov identifier: NCT02191371; principal investigator, Yunseok Jeon; registered on July 7, 2014).

Patient inclusion and randomization

Patients with lung cancer scheduled for elective video-assisted thoracoscopic lobectomy requiring OLV at Seoul National University Hospital were screened for eligibility. Exclusion criteria were age < 20 years, ASA class > III, BMI > 30 kg/m2, symptomatic or severe obstructive or restrictive lung disease, requirement for preoperative oxygen supply, preoperative intubated state or under mechanical ventilatory support, baseline arterial partial pressure of oxygen (PaO2) < 70 mmHg, symptomatic coronary or peripheral arterial disease, renal failure, preoperative continuous infusion of inotropes or vasopressor, refuse to participate in the study, and pregnancy. The interpretation of the pulmonary function test results was based on the American Thoracic Society/European Respiratory Society guidelines [15]. Obstructive disease was defined when forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was < 0.7, and severity was determined by % predicted FEV1 value; severe disease was diagnosed when FEV1 < 50% predicted value.

After receiving informed consent, eligible patients were randomized to receive either inhalational anesthesia with desflurane (Suprane®, Baxter Healthcare, Deerfield, IL) or intravenous anesthesia with propofol (Fresofol®2 MCT 2%, Fresenius Kabi, Graz, Austria) as a main anesthetic, in the morning of the day of surgery. Block randomization (blocks of 4 or 6) was performed before assigning the groups using a computer-generated randomization program operated by a clinician not involved in the study. Baseline pulmonary function, blood pressure and heart rate were recorded one day before surgery.

Study protocol

Standardized pre-surgical and surgical procedures were described previously [16]. Three-lead electrocardiography, pulse oximetry (SpO2), and non-invasive blood pressure monitoring were performed in all patients. Without premedication, general anesthesia was induced with target-controlled infusion of propofol (starting with a target effect site concentration, Ce of 4 μg/ml) in the propofol group. In the desflurane group, we avoided the use of propofol even during the induction period. Therefore, we used etomidate (Etomidate® Lipuro, 0.25 mg/kg; B. Braun, Melsungen, Germany) to induce anesthesia to exclude any potential effects of propofol in the desflurane group. Anesthesia was maintained with either desflurane (5–7 vol%) or propofol (Ce of 3–4 μg/ml), and all patients were continuously infused with remifentanil (Ce of 1.5–3.5 ng/ml, Ultiva™; GlaxoSmithKline, San Polo di-Torrile, Italy) during anesthesia induction and throughout the surgery. Administration of anesthetics (desflurane or propofol) was titrated to maintain appropriate anesthetic depth [bispectral index (BIS), 30–50] using electroencephalogram-based hypnotic monitor (BIS VISTA™ monitor, Aspect Medical Systems, Norwood, MA). In both groups, infusion of remifentanil was adjusted according to hemodynamic changes. A commercial infusion pump (Orchestra®; Fresenius Vial, Brezins, France) was used for target-controlled infusion of propofol and remifentanil according to the patients’ demographic data (sex, age, height and weight). The techniques for anesthesia maintenance in our study were based on those described in previous studies and textbooks [1720]. Infusion of propofol was monitored with the Marsh pharmacokinetic model and remifentanil with the Minto model.

After establishing neuromuscular blockade with administration of rocuronium (0.6–0.8 mg/kg), the patient’s trachea was intubated with a left or right double-lumen endotracheal tube (Mallinckrodt™ endobronchial tube, size 32–39 Fr; Covidien, Mansfield, MA). The size of the tube was chosen based on the patient’s height and mainstem bronchial diameter, and the correct position of the tube was confirmed with a flexible fiber-optic bronchoscope. The lungs were mechanically ventilated with volume-controlled ventilation with a tidal volume of 8 ml/kg (predicted body weight, PBW) during two-lung ventilation (TLV) and 6 ml/kg (PBW) during OLV. The inspired oxygen fraction (FIO2) was set to 0.5 during TLV and 1.0 during OLV. After the patients were positioned in the lateral decubitus position, the endotracheal tube position was rechecked using a fiber-optic bronchoscope before initiation of OLV. Respiratory rate was started at 12/min and adjusted to maintain a carbon dioxide arterial partial pressure of between 35 and 45 mmHg. Positive end-expiratory pressure was maintained at 5 cmH2O.

The right or left radial artery was cannulated with a 20-G Angiocath™ (Becton Dickinson Medical Ltd., Tuas, Singapore) and connected to a FloTrac™ transducer with an EV1000™ monitor (Edwards Lifesciences LLC, Irvine, CA). Arterial blood pressure and cardiac index by pulse-contour analysis were monitored continuously, and arterial blood sampling for gas analysis was conducted through the arterial cannula. A central venous catheter (Multi-Med; Edwards Lifesciences) was placed at either the right or left internal jugular vein under ultrasonographic guidance. Crystalloid or colloid was administered to maintain adequate hemodynamics by the attending anesthesiologist. A paravertebral and/or intercostal nerve block was performed at the surgeon’s discretion before the surgery was completed. Intravenous patient-controlled analgesia with morphine and fentanyl was provided to all patients postoperatively according to their demographic data and the extent of the surgery.

Data collection

Hemodynamic recording and arterial blood gas analysis were conducted at the following time points: (1) preoperatively, (2) TLV before OLV, (3) 15, (4) 30, (5) 45, and (6) 60 min after initiation of OLV. Preoperative data were obtained on room air one day prior to surgery. To minimize the effect of the patient’s position, data during TLV were obtained in the lateral decubitus position. Arterial blood gas analysis was performed using a GEM® Premier 3000 (Model 5700; Instrumentation Laboratory, Lexington, MA) within 3 min after obtaining the blood sample. We restricted recruitment maneuvers to the ventilated lung during OLV, unless there was unacceptable desaturation (defined as SpO2 < 90% or PaO2 < 70 mmHg at FIO2 1.0) or difficulty in maintaining OLV without additional manipulation. If additional manipulation was required, subsequent data were excluded from the analysis to avoid any confounding effects.

Primary endpoint and power analysis

The primary endpoint was PaO2 at 30 min of OLV. In a previous study that investigated oxygenation during OLV in patients receiving propofol, mean ± SD PaO2 at 30 min of OLV was 28 ± 9 kPa (209 ± 68 mmHg) [21]. We calculated that 52 patients would be required per group to detect a PaO2 difference of 20% after 30 min of OLV between the groups, as compared using an independent t-test, including a 20% dropout rate, using a two-sided design at a significance level of 5% and 80% power (G*Power ver. 3.1.9.2; Franz Faul, Universitat Kiel, Germany).

Statistical analyses

Data are presented as the means ± SD, numbers (%), or median (95% confidence interval). Normality of the data was checked using the Kolmogorov–Smirnov and Shapiro–Wilk tests. Residuals vs. fitted values plots were used for repeated-measured variables to check that the error terms (residuals) had a mean of zero and constant variance. The plots showed a pattern consistent with equal variances. The normality assumption for the model residuals was checked with histograms and normal quantile-quantile (Q-Q) plots of the residuals, and the data were determined to be normally distributed. Comparisons were conducted using the independent t-test or Mann–Whitney U-test for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test for non-continuous variables. Sequential changes of variables were analysed using linear mixed models with Bonferroni’s correction. In the mixed model, the treatment group, time, and the interaction between group and time were regarded as fixed effects, and subject was regarded as a random effect. Analysis was performed using SPSS software (ver. 21.0.0.0 for Windows; IBM, Armonk, NY). In all analysis, p <0.05 was taken to indicate statistical significance.

Results

Patient recruitment and data collection was performed between July and December 2014. Among the 183 patients with lung cancer screened for eligibility, 104 patients were randomized to either desflurane (n = 52) or propofol group (n = 52; Fig. 1). After completion of protocol, 103 patients (52 in the desflurane and 51 in the propofol group) were analyzed. One patient in the propofol group was excluded from the primary analysis, as her baseline PaO2 was lower than the exclusion criteria (70 mmHg). The characteristics of the patients included in this study were well balanced between the groups (Table 1). There was no difference in underlying diseases and current medications between groups. We included patients scheduled for a lobectomy at enrolment, but several patients required procedures other than pre-planned lobectomy during surgery (Table 1). The distribution of operation types was comparable between the groups (p = 0.428). The right lung was ventilated during OLV in 32/52 and 34/51 patients in the desflurane and propofol groups, respectively (p = 0.682).
Figure 1
Fig. 1

CONSORT diagram of study flow

Table 1

Characteristics of patients receiving desflurane-remifentanil or propofol-remifentanil during one-lung ventilation for thoracoscopic surgery

 

Desflurane group (n = 52)

Propofol group (n = 51)

p value

Female

18 (35%)

23 (45%)

0.277

Age (year)

63 ± 8

62 ± 10

0.841

Body mass index (kg/m2)

24.0 ± 2.8

22.9 ± 2.8

0.050

ASA class

  

0.914

 I

24 (46%)

23 (45%)

 

 II

28 (54%)

28 (55%)

 

Smoking history

  

0.257

 Never smoker

28 (54%)

28 (55%)

 

 Current smoker

11 (21%)

16 (31%)

 

 Former smoker

13 (25%)

7 (14%)

 

Preoperative hemoglobin (g/dl)

13.2 ± 1.3

13.2 ± 1.3

0.820

Preoperative FEV1 (% predicted)

100.6 ± 16.3

103.8 ± 19.0

0.356

Preoperative FVC (% predicted)

98.0 ± 12.6

100.2 ± 13.7

0.391

Preoperative PaO2 (mmHg)

92 ± 14

93 ± 11

0.798

Preoperative medications

 Aspirin

7 (14%)

8 (16%)

0.749

 COX inhibitor other than aspirin

2 (4%)

4 (8%)

0.437

 Calcium antagonist

12 (23%)

11 (22%)

0.854

 ACE inhibitor

0 (0%)

1 (2%)

0.495

 ARB

10 (20%)

13 (26%)

0.446

 Beta blocker

2 (4%)

3 (6%)

0.678

 Diuretics

2 (4%)

6 (12%)

0.160

 OHA

7 (14%)

9 (18%)

0.558

 Clopidogrel

0 (0%)

2 (4%)

0.243

 Statin

8 (15%)

14 (28%)

0.135

 Steroid

0 (0%)

2 (4%)

0.243

 Prostacyclin

0 (0%)

1 (2%)

0.495

Anesthesia time (min)

222 ± 47

211 ± 46

0.243

Infused crystalloid (ml)

940 ± 505

784 ± 378

0.079

Infused colloid (ml)

117 ± 192

99 ± 167

0.600

Urinary output (ml)

192 ± 159

201 ± 152

0.769

Estimated blood loss (ml)

160 ± 89

143 ± 75

0.299

Extent of operation

  

0.428

 Lobectomy

41 (79%)

44 (86%)

 

 Segmentectomy

7 (13%)

3 (6%)

 

 Wedge resection

4 (8%)

4 (8%)

 

Mainly resected lobe

  

0.747

 Right upper lobe

16 (31%)

15 (29%)

 

 Right middle lobe

3 (6%)

7 (14%)

 

 Right lower lobe

13 (25%)

12 (23%)

 

 Left upper lobe

10 (19%)

8 (16%)

 

 Left lower lobe

10 (19%)

9 (18%)

 

FEV 1 forced expiratory volume in 1 s, FVC forced vital capacity, PaO 2 arterial partial pressure of oxygen, COX cyclooxygenase, ACE angiotensin converting enzyme, ARB angiotensin receptor blocker, OHA oral hypoglycemic agent. Preoperative FEV1 and FVC are expressed as percentages of the predicted value. Values are numbers (%) or means (SD)

Intraoperative blood gas and anesthetic variables at each time point in each group are shown in Table 2. Preoperative and pre-OLV (during TLV before initiation of OLV) PaO2 were comparable between the groups (92 ± 14 vs. 93 ± 11 mmHg and 217 ± 35 vs. 231 ± 60 mmHg in the desflurane vs. propofol group, respectively). Three pre-OLV PaO2 data (2 in the propofol group and 1 in the desflurane group) were excluded from analysis, as FIO2 (0.5) was not maintained during the period. The primary endpoint, PaO2 at 30 min of OLV was lower in the desflurane group than the propofol group (170 ± 72 vs. 202 ± 82 mmHg in desflurane vs. propofol group, respectively; p = 0.039). For other time points during OLV, PaO2 was lower in the desflurane group compared to the propofol group [180 ± 75 vs. 226 ± 84 mmHg (p = 0.004), 179 ± 85 vs. 214 ± 82 mmHg (p = 0.043), and 198 ± 90 vs. 258 ± 122 mmHg (p = 0.009) in desflurane vs. propofol group at 15, 45, and 60 min of OLV, respectively; Fig. 2]. The lowest PaO2 during the OLV period was lower in the desflurane group than the propofol group (133 ± 50 vs. 162 ± 63 mmHg, respectively; p = 0.010). The serial changes in PaO2 during 60 min of OLV revealed a lower PaO2 in the desflurane group compared to that in the propofol group (mean difference, 45 [95% CI, 16–75] mmHg; p = 0.003). The interaction between group and time was not significant during OLV (p = 0.098). Compared to the pre-OLV state, PaO2 at 15, 30, and 45 min of OLV were significantly lower in the desflurane group (217 ± 35 vs. 180 ± 75, 170 ± 72, and 179 ± 85 mmHg; adjusted p = 0.003, p < 0.001, and p = 0.002, respectively), but not in the propofol group at any time point (Fig. 2).
Table 2

Intraoperative blood gas and anesthetic variables in patients receiving desflurane-remifentanil or propofol-remifentanil during one-lung ventilation

 

TLV

15 min of OLV

30 min of OLV

45 min of OLV

60 min of OLV

Desflurane group (n = 52)

 End-tidal desflurane (vol%)

5.4 ± 1.0

6.2 ± 0.8

6.2 ± 0.8

6.2 ± 0.8

6.2 ± 0.8

 Minimum alveolar concentration

1.0 ± 0.2

1.1 ± 0.2

1.1 ± 0.2

1.1 ± 0.1

1.1 ± 0.2

 Ce, remifentanil (ng/ml)

2.3 ± 1.1

2.4 ± 0.9*

2.1 ± 1.1*

1.9 ± 1.0*

1.8 ± 1.0*

 MAP (mmHg)

84 ± 13

85 ± 15

78 ± 12*

75 ± 12*

78 ± 9*

 HR (beats/min)

68 ± 13

67 ± 11

70 ± 11

68 ± 10

69 ± 12

 BT (°C)

36.1 ± 0.4

36.1 ± 0.4

36.0 ± 0.4

35.9 ± 0.4

35.8 ± 0.5

 CVP (mmHg)

7 ± 3

8 ± 3

7 ± 3

7 ± 3

7 ± 3

 CI (l/min/m2)

2.7 ± 0.6

2.6 ± 0.6

2.9 ± 0.7

2.9 ± 0.7

2.9 ± 0.7

 Ppeak (cmH2O)

19 ± 2

22 ± 3

23 ± 4

23 ± 3

23 ± 3

 PaCO2 (mmHg)

41 ± 4

45 ± 5

45 ± 4

45 ± 4

45 ± 5

 Arterial blood pH

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

 Base excess (mmol/l)

2.1 ± 2.2

1.9 ± 2.1

1.5 ± 2.2

1.6 ± 2.0

1.5 ± 2.1

Propofol group (n = 51)

 Ce, propofol (μg/ml)

3.6 ± 0.6

3.6 ± 0.6

3.5 ± 0.5

3.5 ± 0.5

3.6 ± 0.5

 Ce, remifentanil (ng/ml)

2.5 ± 1.2

3.0 ± 1.3*

3.1 ± 1.3*

3.2 ± 1.1*

3.3 ± 1.1*

 MAP (mmHg)

82 ± 13

85 ± 13

84 ± 10*

81 ± 10*

83 ± 10*

 HR (beats/min)

64 ± 11

65 ± 12

68 ± 12

65 ± 11

65 ± 11

 BT (°C)

36.0 ± 0.4

35.9 ± 0.4

35.9 ± 0.4

35.8 ± 0.4

35.8 ± 0.4

 CVP (mmHg)

6 ± 3

7 ± 3

7 ± 3

7 ± 4

7 ± 3

 CI (l/min/m)

2.6 ± 0.7

2.7 ± 0.7

2.8 ± 0.9

2.8 ± 0.8

2.9 ± 0.8

 Ppeak (cmH2O)

19 ± 2

21 ± 3

23 ± 3

23 ± 3

23 ± 3

 PaCO2 (mmHg)

42 ± 5

44 ± 5

45 ± 5

44 ± 5

44 ± 5

 Arterial blood pH

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

7.4 ± 0.0

 Base excess (mmol/l)

2.5 ± 1.9

2.3 ± 2.0

2.2 ± 2.0

2.0 ± 2.0

2.0 ± 1.9

TLV two-lung ventilation, OLV one-lung ventilation, Ce effect-site concentration, MAP mean arterial pressure, HR heart rate, BT body temperature, CVP central venous pressure, CI cardiac index, P peak peak airway pressure, PaCO 2 arterial partial pressure of carbon dioxide. Values are means (SD)

* p <0.05 between the groups

Figure 2
Fig. 2

Arterial oxygenation during desflurane-remifentanil vs. propofol-remifentanil anesthesia for one-lung ventilation. Data points are mean; error bars are SD. PaO2 during OLV was lower in the desflurane group than the propofol group. During desflurane anesthesia, PaO2 was significantly lower at 15, 30, and 45 min of OLV compared to the TLV state. PaO2, arterial partial pressure of oxygen; TLV, two-lung ventilation; OLV, one-lung ventilation; OLV15, 15 min of OLV; OLV30, 30 min of OLV; OLV45, 45 min of OLV; OLV60, 60 min of OLV. * p <0.01 between the two groups during OLV period (linear mixed model). # Adjusted p <0.01 when compared to the TLV state in the desflurane group (linear mixed model with Bonferroni’s correction)

After 30 min of OLV, mean arterial pressure (MAP) was lower in the desflurane group, and accordingly, lesser remifentanil was used in the desflurane group than propofol group (Table 2). The total amounts of remifentanil administered during surgery were 911 ± 337 μg in the desflurane group and 1407 ± 638 μg in the propofol group, respectively (p <0.001). BIS was maintained within the target range (30–50) throughout the surgery in both groups.

Two patients in the desflurane group received continuous infusion of a vasoactive drug (noradrenaline and phenylephrine, respectively) to maintain adequate hemodynamics. None of the patients received transfusion peri-operatively. Three cases in the desflurane group (p = 0.243) required lung recruitment strategies during OLV to maintain an adequate oxygenation profile, and therefore subsequent data were excluded from comparison of PaO2 in these patients after the recruitment maneuvers. The rescue maneuvers were performed after 30 min of OLV in all three cases. After alveolar recruitment, hypoxemia was improved and no changes in the anesthetic protocol were required.

Discussion

In this study, oxygenation under desflurane-remifentanil balanced anesthesia was lower than that under propofol-remifentanil TIVA during OLV for video-assisted thoracoscopic surgery. This is the first reported clinical trial in which desflurane was shown to impair oxygenation during OLV compared to TIVA in lung cancer patients undergoing thoracoscopic lung surgery.

Recently, many surgical procedures have been performed using less-invasive approaches. Large percentages of thoracic operations for lung resection are performed through video-assisted thoracoscopic surgery. Thus, the durations of both the operation and postoperative recovery period have been shortened. Both desflurane and propofol are relatively new anesthetics with short-acting properties characterized by rapid onset and offset due to their low blood gas partition coefficient and low context-sensitive half time, respectively. Therefore, they are highly attractive and offer fast-track anesthesia and earlier recovery for postoperative rehabilitation in minimal invasive thoracic surgery. However, the roles of these modern anesthetics in management of oxygenation during OLV remain unclear in humans.

In animal studies, inhalational anesthetics are known to inhibit the protective role of HPV during alveolar hypoxia combined with OLV both in vitro and in vivo [2]. Halothane, enflurane, isoflurane, sevoflurane, and desflurane depressed HPV in a dose-dependent manner in isolated rat or rabbit lung [4, 22, 23]. Isoflurane or desflurane impaired oxygenation during OLV, while intravenous anesthetics, such as propofol or pentobarbital, had no detrimental impact on HPV in animal studies [3, 5, 24, 25]. However, in clinical investigations, results regarding the effects of anesthetics on oxygenation and HPV during OLV have been inconsistent [610, 26, 27]. Propofol improved oxygenation and shunt fraction during OLV compared to sevoflurane anesthesia in patients undergoing esophagectomy [6] or thoracotomy pulmonary lobectomy [27]. In other studies, propofol anesthesia did not differ in changes in shunt fraction or oxygenation during OLV for thoracic surgery in comparison with sevoflurane or isoflurane [710]. Moreover, arterial oxygenation was not different between propofol-alfentanil vs. isoflurane anesthesia during OLV in patients undergoing thoracoscopic pulmonary surgery or esophageal surgery [26]. Above all, there have been no previous reports comparing the effects of the two commonly used anesthetics, desflurane and propofol, on arterial oxygenation during OLV in thoracic surgical patients.

In accordance with previous reports [21, 28], our data demonstrated a decrease in PaO2 during the first 30 min of OLV and gradual improvement thereafter in both groups (Fig. 2). During desflurane anesthesia, PaO2 decreased significantly after 15 min of OLV compared to the pre-OLV state, and then recovered gradually to pre-OLV levels at 60 min. On the other hand, arterial oxygenation was relatively well maintained during propofol anesthesia throughout the study. None of the time points during OLV indicated a lower PaO2 compared to pre-OLV state in the propofol group.

One explanation for our results is that more vasodilation induced by desflurane anesthesia would have attenuated any protective effect of HPV during alveolar hypoxemia, thus decreased systemic PaO2 in the desflurane group compared to the propofol group. This is partially supported by significantly lower arterial blood pressure despite the lesser use in remifentanil during desflurane anesthesia compared to propofol anesthesia in the present study (Table 2). Significant drop in MAP during desflurane anesthesia compared to propofol anesthesia also has been reported in previous animal study (66 vs. 103 mmHg), in which the effect of anesthetics (desflurane vs. propofol) on arterial oxygenation during OLV was evaluated [3].

Previously, an attempt to inhibit HPV by infusing the potent vasodilator sodium nitroprusside (SNP) during OLV has failed to show significant changes in pulmonary vascular resistance (PVR), shunt fraction, or arterial oxygenation [29]. However, only seven patients were used to evaluate the effect of administering SNP on HPV, by measuring related parameters only once during OLV, before the surgery commenced. Moreover, there was no time window from drug administration to measurement of the variables, or duration of drug infusion to reach the predefined goal (25% decrease in MAP), as presented by the authors. Although vasodilation induced by SNP decreased PVR (166 ± 23–131 ± 22 dynes/s/cm5) and PaO2 (285 ± 42–225 ± 47 mmHg) in that study, the decreases were not significant. Therefore, further investigations may be needed.

Decreases in PaO2 and use of lung recruitment maneuvers during OLV were observed in three patients that received desflurane, while no cases were observed in the propofol group. During the events, the lowest PaO2 levels under FIO2 of 1.0 were 60, 69, and 87 mmHg, respectively. All episodes occurred after 30 min following initiation of OLV. In the last case, the degree of hypoxemia was not severe; however, the attending anesthesiologist decided to provide rescue treatment and proceed with OLV for the remainder of the surgical procedure. Similar events have been reported in previous animal studies comparing desflurane and propofol during in vivo OLV [3]. In this previous study, 3 of 10 pigs showed oxygen desaturation < 90% during OLV with desflurane anesthesia, while no cases were observed in the group receiving propofol. Although there were no further complications after desaturation in our study, these results suggest that desflurane anesthesia for OLV could result in deterioration of oxygenation especially in subjects with under-reserved pulmonary function.

In the current study, blood pressure was managed using adjustment of remifentanil infusion according to the hemodynamic changes during the surgical procedure. We tried to use anesthetic techniques relevant to real clinical practice. It is clearly reflected in the lower use of remifentanil in the desflurane group mainly due to the sustained lower blood pressure in this group compared to the propofol group. In a previous study investigated the effects of different concentrations of remifentanil during OLV, no differences in PaO2 were observed despite the significantly different blood pressures [30]. Therefore, we considered that the observed difference in PaO2 may not the consequence of the difference in remifentanil use between the two groups in this study.

Although a significant difference in PaO2 was detected between the groups (170 vs. 202 mmHg at 30 min of OLV in the desflurane vs. propofol group, respectively; p = 0.039), the difference may be clinically irrelevant to the anesthesiologist who is managing oxygenation in patients undergoing OLV. In this trial, we used a FIO2 of 1.0 throughout the OLV period with the expectation that it would better distinguish the difference in oxygenation between the groups [31]. A clinically significant difference in PaO2 may have been found between the two groups if a lower FIO2 had been used.

In some studies, desflurane showed relatively conserved vascular resistance compared to sevoflurane [32]. In other studies, desflurane has shown more vasodilatory effect among inhalational anesthetics [1114]. Although no differences were observed in oxygenation between sevoflurane and propofol anesthesia during OLV in several previous studies [810], desflurane, even as balanced anesthesia, showed more impaired oxygenation during OLV compared with propofol anesthesia in the present study. However, we did not compare the two popular inhales, sevoflurane vs. desflurane, in the present trial. Further studies are required for comparison of effects of two commonly used volatile anesthetics.

The following limitations should be considered when interpreting our results. First, we did not measure the pulmonary shunt fraction, perfusion or the extent of pulmonary vasoconstriction in each isolated lung during surgery, which could have explained the effects of the anesthetic on pulmonary circulation, arteriovenous shunt fraction, or the degree of ventilation/perfusion mismatch. Therefore, it is difficult to conclude that there were any effects of the anesthetics on the role of HPV during OLV from these results. Second, we did not fix the dose of desflurane, propofol, or remifentanil during this study. Instead, they were titrated by attending anesthesiologists in charge according to anesthetic depth (BIS) or hemodynamic values. Therefore, our results do not reflect the effect of any specific anesthetic dose. Third, although we fixed FIO2 at 1.0 during OLV in both groups, minimal loss of inspired oxygen in the desflurane group was inevitable due to the volume of inhaled anesthetic. However, the present anesthetic protocol was based on the general practice of the institution. Thus, these results should be interpreted in the context of a thoracic surgery anesthesia practice using inhalational and/or intravenous anesthetics. The FIO2 or concentration of inhalational anesthetics could be adjusted according to the clinical setting. Fourth, the cardiac index used in this study was calculated based on non-externally calibrated pulse contour analysis, which may be less precise than pulmonary or transpulmonary thermodilution methods. Therefore, this may have obscured the interpretation of the effects of cardiac output on HPV. Finally, the dose of desflurane administered during the study was 1.0–1.1 MAC. This dosage may seem rather high for a balanced anesthesia protocol, reflecting the lower MAP and less use of remifentanil in the desflurane group compared to those in the propofol group. However, in real clinical situation, anesthesiologist continuously changes the dose of anesthetics according to the patient’s responses, and we believe that the results of our study may be more useful in the clinical practice.

Conclusions

In conclusion, oxygenation under desflurane-remifentanil balanced anesthesia was lower than that under propofol-remifentanil TIVA during OLV for video-assisted thoracoscopic surgery. In patients who develop hypoxemia during OLV with inhalational anesthetics, change anesthetics to an intravenous agent should be considered.

Abbreviations

BIS: 

Bispectral index

Ce: 

Effect site concentration

FEV1

Forced expiratory volume in 1 s

FIO2

Inspired oxygen fraction

FVC: 

Forced vital capacity

HPV: 

Hypoxic pulmonary vasoconstriction

MAP: 

Mean arterial pressure

OLV: 

One-lung ventilation

PaO2

Arterial partial pressure of oxygen

PBW: 

Predicted body weight

PVR: 

Pulmonary vascular resistance

SNP: 

Sodium nitroprusside

SpO2

Pulse oximetry

TIVA: 

Total intravenous anesthesia

TLV: 

Two-lung ventilation

Declarations

Acknowledgments

We thank to the Medical Research Collaborating Center for their advice concerning the statistical analyses.

Funding

None.

Availability of data and materials

The dataset supporting the conclusions of this article is included within the article.

Authors’ contributions

YJ, J-HS and YJC designed and coordinated the study. YJC conducted the study, analyzed the data and drafted the manuscript. TKK and J-HS collected and analyzed the data. TKK, DMH and J-HB have made substantial contributions to data acquisition and have been involved in drafting the manuscript. YJC, TKK, DMH, J-HB, and YJ contributed the data interpretation and revision of the manuscript. YJ was the principal investigator. All authors read and approved the final version of the manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

The Institutional Review Board of Seoul National University Hospital approved this study (reference # 1406-052-587; approval date, July 7, 2014). All patients provided written informed consent, and the study was performed according to Good Clinical Practice guidelines and the principles of the Declaration of Helsinki (ClinicalTrials.gov identifier: NCT02191371; principal investigator, Yunseok Jeon; registered on July 7, 2014).

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, South Korea

References

  1. Lumb AB, Slinger P. Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications. Anesthesiology. 2015;122:932–46.View ArticlePubMedGoogle Scholar
  2. Eisenkraft JB. Effects of anaesthetics on the pulmonary circulation. Br J Anaesth. 1990;65:63–78.View ArticlePubMedGoogle Scholar
  3. Karzai W, Haberstroh J, Priebe HJ. Effects of desflurane and propofol on arterial oxygenation during one-lung ventilation in the pig. Acta Anaesthesiol Scand. 1998;42:648–52.View ArticlePubMedGoogle Scholar
  4. Loer SA, Scheeren TW, Tarnow J. Desflurane inhibits hypoxic pulmonary vasoconstriction in isolated rabbit lungs. Anesthesiology. 1995;83:552–6.View ArticlePubMedGoogle Scholar
  5. Schwarzkopf K, Schreiber T, Preussler NP, Gaser E, Huter L, Bauer R, et al. Lung perfusion, shunt fraction, and oxygenation during one-lung ventilation in pigs: the effects of desflurane, isoflurane, and propofol. J Cardiothorac Vasc Anesth. 2003;17:73–5.View ArticlePubMedGoogle Scholar
  6. Xu WY, Wang N, Xu HT, Yuan HB, Sun HJ, Dun CL, et al. Effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients undergone esophagectomy. Int J Clin Exp Pathol. 2014;7:272–9.PubMedGoogle Scholar
  7. Sharifian Attar A, Tabari M, Rahnamazadeh M, Salehi M. A comparison of effects of propofol and isoflurane on arterial oxygenation pressure, mean arterial pressure and heart rate variations following one-lung ventilation in thoracic surgeries. Iran Red Crescent Med J. 2014;16:e15809.View ArticlePubMedPubMed CentralGoogle Scholar
  8. Pruszkowski O, Dalibon N, Moutafis M, Jugan E, Law-Koune JD, Laloe PA, et al. Effects of propofol vs sevoflurane on arterial oxygenation during one-lung ventilation. Br J Anaesth. 2007;98:539–44.View ArticlePubMedGoogle Scholar
  9. Schwarzkopf K, Hueter L, Schreiber T, Preussler NP, Loeb V, Karzai W. Oxygenation during one-lung ventilation with propofol or sevoflurane. Middle East J Anaesthesiol. 2009;20:397–400.PubMedGoogle Scholar
  10. Beck DH, Doepfmer UR, Sinemus C, Bloch A, Schenk MR, Kox WJ. Effects of sevoflurane and propofol on pulmonary shunt fraction during one-lung ventilation for thoracic surgery. Br J Anaesth. 2001;86:38–43.View ArticlePubMedGoogle Scholar
  11. Sundeman H, Biber B, Martner J, Raner C, Winso O. Vasodilator effects of desflurane and isoflurane in the feline small intestine. Acta Anaesthesiol Scand. 1995;39:1105–10.View ArticlePubMedGoogle Scholar
  12. Weiskopf RB, Holmes MA, Eger 2nd EI, Johnson BH, Rampil IJ, Brown JG. Cardiovascular effects of I653 in swine. Anesthesiology. 1988;69:303–9.View ArticlePubMedGoogle Scholar
  13. Pagel PS, Farber NE. Inhaled anesthetics: cardiovascular pharmacology. In: Miller RD, editor. Miller’s anesthesia. 8th ed. Philadelphia, USA: Saunders Elsevier; 2015. p. 706–51.Google Scholar
  14. Inhaled anesthetics. In: Butterworth JF, Mackey DC, Wasnick JD. Morgan and Mikhail’s clinical anesthesiology. 5th Edn. New York, USA: Lange Medical Books/McGraw Hill; 2013. p.153-73.Google Scholar
  15. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948–68.View ArticlePubMedGoogle Scholar
  16. Cho YJ, Ryu H, Lee J, Park IK, Kim YT, Lee YH, et al. A randomised controlled trial comparing incentive spirometry with the acapella(R) device for physiotherapy after thoracoscopic lung resection surgery. Anaesthesia. 2014;69:891–8.View ArticlePubMedGoogle Scholar
  17. Camu F, Lauwers M, Vanlersberghe C. Total intravenous anesthesia. In: White PF, editor. Textbook of intravenous anesthesia. 1st ed. Baltimore, USA: Williams & Wilkins; 1997. p. 375–92.Google Scholar
  18. Leslie K, Clavisi O, Hargrove J. Target-controlled infusion versus manually-controlled infusion of propofol for general anaesthesia or sedation in adults. Cochrane Database Syst Rev. 2008;3:CD006059.Google Scholar
  19. Eikaas H, Raeder J. Total intravenous anaesthesia techniques for ambulatory surgery. Curr Opin Anaesthesiol. 2009;22:725–9.View ArticlePubMedGoogle Scholar
  20. Gritti P, Carrara B, Khotcholava M, Bortolotti G, Giardini D, Lanterna LA, et al. The use of desflurane or propofol in combination with remifentanil in myasthenic patients undergoing a video-assisted thoracoscopic-extended thymectomy. Acta Anaesthesiol Scand. 2009;53:380–9.View ArticlePubMedGoogle Scholar
  21. Kim SH, Choi YS, Lee JG, Park IH, Oh YJ. Effects of a 1:1 inspiratory to expiratory ratio on respiratory mechanics and oxygenation during one-lung ventilation in the lateral decubitus position. Anaesth Intensive Care. 2012;40:1016–22.PubMedGoogle Scholar
  22. Marshall C, Lindgren L, Marshall BE. Effects of halothane, enflurane, and isoflurane on hypoxic pulmonary vasoconstriction in rat lungs in vitro. Anesthesiology. 1984;60:304–8.View ArticlePubMedGoogle Scholar
  23. Ishibe Y, Gui X, Uno H, Shiokawa Y, Umeda T, Suekane K. Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused rabbit lung. Anesthesiology. 1993;79:1348–53.View ArticlePubMedGoogle Scholar
  24. Domino KB, Borowec L, Alexander CM, Williams JJ, Chen L, Marshall C, et al. Influence of isoflurane on hypoxic pulmonary vasoconstriction in dogs. Anesthesiology. 1986;64:423–9.View ArticlePubMedGoogle Scholar
  25. Benumof JL, Wahrenbrock EA. Local effects of anesthetics on regional hypoxic pulmonary vasoconstriction. Anesthesiology. 1975;43:525–32.View ArticlePubMedGoogle Scholar
  26. Reid CW, Slinger PD, Lenis S. A comparison of the effects of propofol-alfentanil versus isoflurane anesthesia on arterial oxygenation during one-lung ventilation. J Cardiothorac Vasc Anesth. 1996;10:860–3.View ArticlePubMedGoogle Scholar
  27. Jin Y, Zhao X, Li H, Wang Z, Wang D. Effects of sevoflurane and propofol on the inflammatory response and pulmonary function of perioperative patients with one-lung ventilation. Exp Ther Med. 2013;6:781–5.PubMedPubMed CentralGoogle Scholar
  28. Ishikawa S. Oxygenation may improve with time during one-lung ventilation. Anesth Analg. 1999;89:258–9.View ArticlePubMedGoogle Scholar
  29. Friedlander M, Sandler A, Kavanagh B, Winton T, Benumof J. Is hypoxic pulmonary vasoconstriction important during single lung ventilation in the lateral decubitus position? Can J Anaesth. 1994;41:26–30.View ArticlePubMedGoogle Scholar
  30. Ryu CG, Min SW, Kim J, Han SH, Do SH, Kim CS. Effect of remifentanil on arterial oxygenation during one-lung ventilation. J Int Med Res. 2010;38:1749–58.View ArticlePubMedGoogle Scholar
  31. Karzai W, Klein U. FIO2 and studies on oxygenation during one-lung ventilation. Br J Anaesth. 2012;109:644–5.View ArticlePubMedGoogle Scholar
  32. Blaudszun G, Morel DR. Superiority of desflurane over sevoflurane and isoflurane in the presence of pressure-overload right ventricle hypertrophy in rats. Anesthesiology. 2012;117:1051–61.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s). 2017

Advertisement