Authors: Deligianni M.1a, Fyntanidou B.2b*, Foroulis Ch.3c, Kioumis I.3d , Tsagkaropoulos S.3c, Alexiou I.4c, Kotzampassi K.3a, Grosomanidis V.3e
2MD, MSc, PhD
aDepartment of Surgery, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
bEmergency Department AHEPA Hospital, Thessaloniki, Greece
cDepartment of Cardiothoracic Surgery, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
dProfessor, Pulmonologist, Intensivist, Aristotle University of Thessaloniki
eClinic of Anesthesiology and Intensive Care, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
*Corresondence: Kautatzoglou 14A, 54639, Thessaloniki, Greece, Tel: 0030 6977427336, e-mail:
Introduction: Anesthesia for thoracic surgery presents specific challenges since anesthesiologists have to manage patients with several comorbidities, apply One Lung Ventilation (OLV) to facilitate surgery and at the same time they should try to maintain adequate safe oxygen levels. Hypoxemia is a common consequence of OLV. The aim of the present retrospective study was to investigate the impact of intraoperative hypoxia on the early outcome of patients. Material and Methods: In this study120 patients were included, who underwent thoracic surgical procedures with OLV and were assigned into two groups of 60 patients in each group. Group A consisted of patients who experienced severe hypoxia (PiO2/FiO2<100) during OLV, whereas Group B consisted of those who did not suffer from hypoxia. ABG samples were collected intraoperatively at four different phases: Ph1: spontaneous breathing without any oxygen supply before intubation, Ph2: after initiation of mechanical ventilation, Ph3: during OLV and Ph4: immediately before being transferred from the operating theatre. Venous blood samples were collected at three phases: Ph1: after initiation of mechanical ventilation, Ph2: at the time of hypoxia occurrence and Ph3: immediately before being transferred from the operating theatre. During ICU stay, ABG samples were taken at four phases: Ph1: immediately after ICU admission, Ph2: before extubation, Ph3: after extubation and Ph4: before ICU discharge. Results: Intraoperatively, patients in Group B had better oxygenation compared to Group A at all phases. Moreover, during OLV patients in Group A experienced severe hypoxemia. Intraoperative PO2/FiO2 ratio in Group A was 369,8±69,9 / 279,4 ±91,5 / 68,3±11,8 / 324,7± 82,9 and at the corresponding phases the relevant values in Group B were 420,8±68,2 / 373,8±87,5/ 242,9±79,6 / 406,7±64,4. Partial pressure of oxygen in the central venous blood (PcvO2) and Central venous oxygen saturation (ScvO2) differed in a statistically significant manner between the study groups. However, ScvO2 remained at acceptable levels even at the time of hypoxemia in Group A. ScvO2 values in Group A were 78,7±9,1 / 66,8±79,7 / 73,3±5,82 and at the corresponding phases the relevant values in Group B were 87,1±7,2 / 79,8±7,8 / 81,8±7,5. Duration of mechanical ventilation in ICU was longer in Group A compared to Group B (5,34±5,1hrs vs 3,6±2,5hrs), whereas ICU and total hospital stay did not differ between study groups. Conclusion: Hypoxemia during OLV in Group A did not have a negative impact on early outcome of patients.
The majority of patients scheduled for thoracosurgical procedures are heavy smokers with respiratory and cardiovascular comorbidities. During the operation, patients remain in lateral decubitus position for a prolonged period and one of the lungs becomes atelectatic. After surgery these patients, who underwent either lobectomy or pneumonectomy, have excess thick mucus and experience difficulties in clearing it from their lungs1-6.
Respiratory (atelectasis, pneumonia, respiratory failure) and cardiovascular (arrhythmias, myocardial ischaemia) complications are the main causes of perioperative morbidity and mortality associated with cardiothoracic surgery.
One lung ventilation
One lung ventilation (OLV) is a standard approach applied in several operations such as thoracic, oesophagus, aortic and mediastinal surgery. OLV requires double lumen endotracheal tubes (DLT), endobrochial blockers, endobrochial intubation or endotracheal tube7,8. During OLV lungs are isolated and the independed upper lung is not ventilated but is perfused. The opening of the chest results in loss of negative intrapleural pressure, which causes the collapse of the upper independed lung9.
In most of the cases volume control mode of ventilation (VCV) is used. Pressure Control Ventilation (PCP) has been also used in several studies. However, it has not been proven to be superior when compared to VCV10-12.
In the past, mechanical ventilation with high tidal volumes has been used aiming to improve oxygenation since high tidal volumes keep the lungs open independed of whether PEEP was high or low13.
Recently, according to relevant literature, it has become clear that high tidal volumes during OLV may be associated with an increase of postoperative respiratory complications14-16.
Current ventilation strategies suggest low tidal volumes <8ml/kg, PEEP application and recruitment maneuvers for both protecting and keeping the lung open. Whereas there is an unambiguous positive effect of low tidal volume ventilation on the degree of lung injury, its effect on oxygenation still remains unclear17,18.
Respiratory rate is determined to maintain normocapnia. Permissive hypercapnia refers to the ventilation strategy with low tidal volumes applied on ICU ARDS patients aiming to reduce airway pressures and lung injury. This strategy has been also studied in OLV patients with good results19-21.
Since PEEP application reduces atelectatic regions and contributes to keeping the lungs open, it should be a standard routine in mechanical ventilation both in the setting of OLV and two lungs ventilation. A minimum level of 5cmH2O PEEP should be applied on all patients. Thereafter, in case of hypoxia, PEEP levels should be titrated. Moreover, endogenous PEEP should always be taken into consideration22.
OLV has become a standard ventilation practice in daily clinical work. When OLV is applied, anesthesiologists are trying to preserve adequate oxygenation despite the fact that only one lung is ventilated. However, this not always feasible and 40-50% of the patients might experience some degree of hypoxemia. Nevertheless, the rate of severe hypoxemia has declined from 20-25% in the 1970s to 1% today. This is attributed mainly to better education and training of anesthesiologists in DLT placement, to the use of bronchoscope for confirmation of the correct DLT position, to the use of novel inhalational anesthetic agents, which cause a less significant inhibition of the Hypoxic Pulmonary Vasoconstriction (HPV), to better understanding of the relevant pathophysiological mechanisms and immediate application of appropriate management techniques23.
Several predictive risk factors for hypoxemia have been recognized such as operation on the right lung, poor oxygenation during the period of two lungs ventilation, high ventilation (V) or perfusion (Q) ratio in the preoperative V/Q scan of the lung which will be operated, normal preoperative FVC and FEV1 values and obesity.
The most significant predictive risk factor is the partial pressure of oxygen in the arterial blood (PaO2), when patient is in the lateral decubitus position and two lungs ventilation is applied. In addition to that, another important parameter is the rate of PaO2 deterioration after initiation of mechanical ventilation24, 25.
Pulse oximetry is used for hypoxia detection but arterial blood gases (ABGs) are necessary for detailed oxygenation assessment26.
Several strategies are used for hypoxia management such as:
- Confirmation of correct DLT position by the use of bronchoscope
- FiO2 increase in the depended lung
- CPAP application on the independed lung
- Oxygen insufflation in the independed lung
- PEEP optimization in the depended lung
- Intermittent re-expansion of the independed lung
- OLV cessation and initiation of two lungs ventilation
- Pulmonary artery occlusion (in lung resection operations)
For the efficient management of hypoxemia, quite often one intervention is not enough27-33. The combination of recruitment maneuvers, FiO2 increase, PEEP increase and CPAP application on the independed lung seem to have the best results34, 35.
Perioperative lung injury
Since the beginning of thoracosurgery, post-lobectomy or post-pneumonectomy pulmonary edema was recognized as one of the associated postoperative complications. Today this entity is described as perioperative lung injury, is defined as Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS) and is the main cause of death after thoracosurgical procedures36.
Morbidity and mortality rates related to other postoperative complications such as atelectasis and pneumonia have been reduced over the years. However, this is not the case for lung injury37, 38.
Lung injury pathophysiological mechanisms are different in the ventilated and the non ventilated lung39, 40.
High tidal volumes ventilation, low tidal volumes associated atelectasis, hyperperfusion and oxidative stress response have been implicated in the lung injury pathogenesis of the lower ventilated lung41.
Respectively, atelectasis, recruitment maneuvers, hypoperfusion, ischemia-reperfusion and surgical trauma can cause injury in the upper non ventilated lung. OLV duration is another important risk factor for lung injury. Excessive fluid administration has been associated with lung injury without clear evidence about this association. Preventive measures could attribute to lower rates of occurrence42, 43.
The aim of the present retrospective study was to investigate the impact of intraoperative hypoxia on the early outcome of patients.
Material and Methods
In this study 120 patients were included, who underwent thoracic surgical procedures in the Cardiothoracic Department of AHEPA University Hospital, Thessaloniki, Greece. Patients received either open surgery by thoracotomy or Video Assisted Thoracoscopic Surgery (VATS), underwent lobectomy, pneumonectomy or decortication for lung diseases (cancer, pneumothorax, empyema). Anesthesia induction and maintenance was performed by the same anesthetic agents in all patients. OLV by use of DLT was applied in all patients during the operation. Patients were assigned into two groups with 60 patients in each group, Group A & B. Group A consisted of patients who experienced severe hypoxia (PiO2/FiO2<100) during OLV, whereas Group B consisted of those who did not suffer from hypoxia.
ABG samples were collected intraoperatively at four different phases: Ph1: spontaneous breathing without any oxygen supply before intubation, Ph2: after initiation of mechanical ventilation, Ph3: during OLV and Ph4: immediately before being transferred from the operating theatre. Venous blood samples were collected at three phases: Ph1: after initiation of mechanical ventilation, Ph2: at the time of hypoxia occurrence and Ph3: immediately before being transferred from the operating theatre.
After the end of the surgery, all patients were transferred to ICU, where they were extubated after a short time period.
During ICU stay, ABG samples were taken at four phases: Ph1: immediately after ICU admission, Ph2: before extubation, Ph3: after extubation and Ph4: before ICU discharge.
Other recorded parameters included, hemodynamic variables, fluid balance, need of any vasoactive support, surgery duration, OLV duration, ICU mechanical ventilation duration, ICU and total hospital stay.
SPSS 25 was used for the statistical analysis. Analysis of variance (ANOVA) was used as a statistical method to evaluate the alterations of recorded quantitative parameters over time. Mean values and standard deviation (SD) were calculated and diagrams depicting the alterations of the parameters over time were created. Statistical significance was set at 0.05 or 5%. Thereafter, values lower than 0.05 were considered statistically significant. In addition to this, 95% confidence intervals which did not overlap were considered to be correlated with mean values that show statistically significant difference. All statistical tests were performed two sided. Chi-square test (x2) was used for the statistical analysis of quality parameters.
OLV by the use of DLT was applied to all patients. Group A consisted of patients who experienced severe hypoxia, whereas Group B consisted of those who did not suffer from hypoxia. Demographic data and variables related to the surgical procedure, anesthesia management, ICU and total hospital stay are depicted on Tables 1-3.
As far as preoperative variables are concerned, there were statistically significant differences between the study groups on the incidence of diabetes mellitus, on the specific indication for surgery and on the side of surgery (Table 1). With regard to the side of surgery, more patients in Group A were operated on the right lung compared to Group B (Table 2).
Table 1. Patient characteristics and preoperative variables.
|Variable||Total||Group A||Group B||P value|
|Number of patients||120||60||60|
|FVC preop||80,1± 17,4||77,7±15,3||81,9±18,9||0,31|
Coronary artery disease
M: male, F: female, BMI: body mass index, ASA/PS: American society of Anesthesiology/physical status, FVC: forced vital capacity, FEV1: forced expiratory volume in one second, preop: preoperatively, p<0,05: statistical significance.
Table 2. Intraoperative Variables.
|Variable||Total||Group A||Group B||p value|
|Number of patients||120||60||60|
|Site of operation:
Right lung/Left lung
|Duration of OLV (min)||160±88,4||144,8±87,3||175,7±87,9||0,59|
|Duration of operation (min)||264,2±110||244,5±102||284,2±116||0,53|
|Fluids intraoperative (ml)||5676±1717||5449±1547||5908±1860||0,14|
|Urine output intraoperatively (ml)||1488±1077||1468±1205||1508±940||0,84|
OLV: One lung ventilation, pRBC: packed red blood cells, p<0,05: statistical significance.
Duration of mechanical ventilation was longer in Group A, whereas ICU stay did not differ statistically significant between study groups. Three patients in Group A died, one of which suffered massive pulmonary embolism. None of the patients in Group B died (Table 3).
Table 3. Postoperative variables.
|Variable||Total||Group A||Group B||p Value|
|Number of patients||120||60||60||0,08|
|Mechanical Ventilation (hr)||4,5±4,1||5,34±5,1||3,6±2,5||0,03|
|ICU stay (hr)||14,1±10,9||13,5±9,4||14,5±12,5||0,62|
|Hospital stay (day)||8,2±4,2||8,9±4,8||7,5±3,3||0,08|
ICU: intensive care unit, p<0,05: statistical significance.
PaO2/FiO2 ratio showed statistically significant differences both in the way it changed over time and when compared between Groups (Figure 1 & Table 4).
Table 4: Intraoperative descriptive statistics of PO2/FiO2 ratio
|Phase||Group||Mean||SD||SE||Median||95 Confidence Interval|
|p value||A vs B||p<0,001|
|p value||A vs B||p<0,001|
|p value||A vs B||p<0,001|
|p value||A vs B||p<0,001|
At each phase following comparisons were made: (i) Comparison to corresponding baseline value for each group, (ii) Comparison between study groups. Asterisks indicate statistically significant difference against baseline (*** p<0,001).
Arterial oxygen saturation (SaO2) changed in a different way over time. However, hypoxia (<90%) occurred only in Group A at Phase 2 (Figure 2).
Partial pressure of carbon dioxide in the arterial blood (PaCO2) showed statistically significant alterations over time. Nevertheless, the difference between study groups was not statistically significant (Figure 3).
Alterations of partial pressure of oxygen in the central venous blood (PcvO2) and Central venous oxygen saturation (ScvO2) are depicted on Figures 4 and 5 respectively.
PO2/FiO2 ratio during ICU stay changed over time compared to baseline in both groups and there were statistically significant differences at most of the study phases between groups (Table 5). Similarly, PaCO2 and SaO2 values changed over time compared to baseline in both groups but there were no statistically significant differences at any study phases between groups.
Table 5. Descriptive Statistics of postoperative PaO2/FiO2 ratio.
|Phase||Group||Mean||SD||SE||Median||95 Confidence Interval|
|p value||A vs B||p=0,05|
|p value||A vs B||p=0,15|
|p value||A vs B||p=0,002|
|p value||A vs B||p=0,55|
At each study phase following comparisons were made: (i) Comparison to corresponding baseline value for each group, (ii) Comparison between study groups. Asterisks indicate statistically significant difference against baseline (** p<0,01).
OLV is an approach which on the one hand facilitates surgery but on the other hand causes oxygenation impairment. It results in collapse of the independed lung and in an increase of the atelectatic regions of the depended lung, which unavoidably lead to intrapulmonary shunt increase and subsequent oxygen impairment35,44.
OLV has an impact on ventilation and on perfusion of both lungs45. OLV diverts ventilation from the upper (independed) lung to the lower (depended) lung), while the independed lung continues to receive perfusion. Nervertheless, due to gravity and to the HPV reflex, the depended lung receives most of the perfusion. In the best case scenario shunt magnitude is 20-25% of the cardiac output26,46, 47.
Occurrence of hypoxia is common during OLV and is ranging from 5 to 10%. It should be mentioned that to some degree the incidence of hypoxia is influenced by its definition33,48,49. Immediately after OLV initiation, oxygenation is impaired but gradually it gets improved by the activation of HPV reflex47,50,51.
Usually, intraoperative hypoxia is well tolerated by patients on the precondition that there is no hypoperfusion52. However, intraoperative hypoxia has been incriminated as a cause for postoperative complications53.
A hundred and twenty patients were included in this study, which were assigned into two groups of 60. Patients in Group A experienced intraoperative hypoxia, whereas patients in Group B did not. Patients underwent thoracosurgical procedures for lung diseases under general anesthesia and mechanical ventilation. During the operation OLV was applied by the use of DLT48,54.
In both groups lung protective mechanical ventilation with the same settings was applied throughout the whole surgery and in the ICU. VCV was selected and ventilation settings entailed a VT of 8ml/kg during two lungs ventilation and 5ml/kg during OLV with the PEEP level set at 5cmH2O. Protective lung ventilation with low tidal volumes and addition of PEEP is a standard of care for mechanical ventilation during thoracosurgical procedures since it reduces lung injury55. Different ventilation modes have been applied in thoracosurgery without any of those having been proven to be superior10,56.
Hypoxia was defined as PaO2/FiO2 ratio<100 (Normal PaO2/FiO2 ratio is approximately 400-500mmHg). PaO2/FiO2 ratio is used in ARDS for the definition of hypoxia as well as in several severity scoring systems (SOFA, SAPS-II and SAPS-III57. The advantage of using PaO2/FiO2 ratio is that it is relatively easy to calculate. However, its usefulness is questioned mainly because PaO2/FiO2 ratio is not involved in any biological procedure and no human organ is able to detect it58.
Based on the fact that during OLV oxygenation is impaired, most of the researches define hypoxia as the state of arterial oxygen saturation (SaO2) below 90% or PaO2 below 60mmHg on FiO2=133,35.
In the clinical setting, when patients are under general anesthesia it is not possible to determine the exact level of accepted hypoxia for each patient35,52,59.
As far as demographic data, laboratory tests and spirometry results, there were statistically significant differences between the study groups only on the surgical site, on indication for surgery and on comorbidities. Namely, more patients in Group A were operated on the right lung compared to Group B.
Right sided thoracotomy is one of the three most important factors affecting occurrence of hypoxia during OLV25,33.
Since the right lung is larger than the left one, oxygenation is expected to be better in left sided thoracotomies, during which the lower (ventilated) lung is the right one24,25.
Most of the patients in both groups were smokers (either active or former). FVC, FEV1 and preoperative laboratory values did not differ statistically significant between groups.
Similarly, OLV and surgery duration and data related to diuresis and fluid administration did not show any statistically significant difference between the study groups.
Intraoperative PaO2/FiO2 ratio showed a statistically significant change over time against baseline values and moreover differed statistically significant between groups at all study phases. Patients in Group B had better oxygenation both during spontaneous ventilation and during two lungs ventilation. Impaired oxygenation during two lungs ventilation is another risk factor for the occurrence of hypoxia during OLV25,61. Application of recruitment maneuvers before OLV could improve oxygenation13,55,62.
There were statistically significant differences on SaO2 between the study groups. However, this significance became clinically relevant only during OLV, when SaO2 was less than 90% in Group A.
PaCO2 showed a statistically significant increase over time during OLV but without any statistically significant differences between groups. Lung protective mechanical ventilation with low VT during OLV causes a PaCO2 increase, which is well tolerated by patients who do not suffer from severe health conditions20,63. Special attention should be given to patients with pulmonary hypertension or intracranial pathology.
PcvO2 alterations over time were similar to those of PO2/FiO2 ratio.ScvO2 values were kept at acceptable levels in both groups despite the fact that there were statistically significant differences between the study groups. ScvO2 is used instead of SvO2 and reflects the balance between oxygen delivery (DO2) and oxygen consumption (VO2) 64-66. Actually, it is a global oxygenation indicator.
Oxygenation of patients in ICU differed between study groups only at the time point of ICU admission. Oxygenation was the only indicator of the recorded ABG parameters in ICU which differed statistically significant. At Phase 1 the increase of PiO2/FiO2 in Group B was statistically significant but marginal. This difference became really important at Phase 3. Recruitment maneuvers and lung re-expansion at the end of OLV seemed to improve oxygenation in Group A. However, this improvement was not maintained after extubation.
In thoracosurgery, intraoperative recruitment maneuvers are widely used in clinical practice to improve oxygenation. Nevertheless, their positive effect is not maintained after the release of positive pressure67-69.
Mechanical ventilation duration was longer in Group A, but ICU and total hospital length of stay did not differ between study groups. None of the patients developed ARDS postoperatively.
Postoperative respiratory failure after thoracosurgical procedures is considered to be the most severe complication since it is associated with increased mortality rates, which have not declined over the years38,39.
Three patients in Group A died, one suffered massive pulmonary embolism, a second patient was operated for empyema and the third one for lung abscess. Based on the medical history of those patients, deaths cannot be related to perioperative hypoxemia.
Limitations of the study
Group A included 12 patients, who were operated for empyema (one of those had lung abscess). Their oxygenation was impaired due to the underlying pathology. PO2/FiO2 ratio calculation is not reliable, when oxygen is being administered via a face mask since it is difficult to determine FiO2.Oxygen needs, duration of additional oxygen therapy (in case that additional oxygen was supplied) and blood oxygen levels were not recorded after ICU discharge during hospitalization in wards.
According to the results of the present study, hypoxia during OLV does not have a negative impact on early outcome of patients undergoing thoracic surgical procedures, on the precondition that there is no underlying pathology.
Addittional materials: No
DM drafted the paper and is the lead author. FB contributed to planning and the critical revision of the paper. FCh contributed to planning and the critical revision of the paper. KI contributed to planning and the critical revision of the paper. TS contributed to planning and the critical revision of the paper. AI contributed to planning and the critical revision of the paper. KK contributed to planning and the critical revision of the paper. GV contributed to planning and the critical revision of the paper.
Funding: Not applicable.
Availability of supporting data:
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ethical approval and consent to participate:
No IRB approval required, patients consent obtained.
The authors declare that they have no competing interests.
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