Alf Kozian

The Pulmonary Immune Effects of Mechanical Ventilation in Patients Undergoing Thoracic Surgery

Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Paco2 during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-&agr;, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-&agr; (8.4 versus 5.0 &mgr;g/mL) and sICAM-1 (52.7 versus 27.5 &mgr;g/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-&agr; and of sICAM-1.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

Background:Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end–expiratory pressure (PEEP) level and occurrence of PPC. Methods:Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. Results:Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose–response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). Conclusions:These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients.

Background:One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery. Methods:Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg−1 · h−1 propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 &mgr;g · kg−1 · min−1). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg−1 ideal body weight, a peak airway pressure lower than 30 cm H2O, a respiratory rate adjusted to a Paco2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays. Results:Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-&agr;, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml−1). Interleukin-1&bgr; was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible. Conclusions:OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING None.

One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study

BACKGROUND One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique [single-photon emission computed tomography (SPECT)] and relates these findings to lung histopathology after OLV. METHODS Eleven anaesthetized and ventilated pigs (V(T)=10 ml kg(-1), Fio2=0.40, PEEP=5 cm H2O) were studied. After lung separation, OLV and thoracotomy were performed in seven pigs (OLV group). During OLV and in a two-lung ventilation (TLV), control group (n=4) ventilation settings remained unchanged. SPECT with (81m)Kr (ventilation) and (99m)Tc-labelled macro-aggregated albumin (perfusion) was performed before, during, and 90 min after OLV/TLV. Finally, lung tissue samples were harvested and examined for alveolar damage. RESULTS OLV affected ventilation and haemodynamic variables, but there were no differences between the OLV group and the control group before and after OLV/TLV. SPECT revealed an increase of perfusion in the dependent lung compared with baseline (49-56%), and a corresponding reduction of perfusion (51-44%) in non-dependent lungs after OLV. No perfusion changes were observed in the control group. This resulted in increased low V/Q regions and a shift of V/Q areas to 0.3-0.5 (10(-0.5)-10(-0.3)) in dependent lungs of OLV pigs and was associated with an increased diffuse alveolar damage score. CONCLUSIONS OLV in pigs results in a substantial V/Q mismatch, hyperperfusion, and alveolar damage in the dependent lung and may thus contribute to gas exchange impairment after thoracic surgery.

Non-analgetic effects of thoracic epidural anaesthesia.

Purpose of review This review presents a brief overview of the non-analgetic effects of thoracic epidural anaesthesia. It covers the cardiac, pulmonary and gastrointestinal effects of thoracic epidural anaesthesia. The results of newer studies are of particular importance regarding mortality and major morbidity after thoracic epidural anaesthesia. Recent findings The clinical effects of thoracic epidural anaesthesia are mainly attributed to a transient thoracic sympathetic block affecting different organs. Furthermore, local anaesthetic itself reabsorbed from the epidural space may contribute to the non-analgetic effects of thoracic epidural anaesthesia. Experimental studies have suggested that thoracic epidural anaesthesia may attenuate the perioperative stress response after major surgery. The possible beneficial mechanisms of action include an improvement of left ventricular function by direct anti-ischaemic effects, a reduction in cardiovascular complications, an advance on gastrointestinal function, and a reduction in pulmonary complications, as well as a positive impact on the coagulation system and the postoperative inflammatory response. However, it is questionable whether these effects of thoracic epidural anaesthesia may lead to an improved perioperative outcome after major surgery. Recent studies have suggested that, despite the superior quality of pain relief and better quality of life, thoracic epidural anaesthesia does not reduce mortality and major morbidity, especially after major abdominal and cardiac surgery. Summary Despite this controversy, the numerous positive effects and advantages of thoracic epidural anaesthesia are the reasons for its increasing popularity. However, the advantages of thoracic epidural anaesthesia must be incorporated into a multimodal treatment management aimed at improving outcomes after surgery. Abbreviations CABG: coronary artery bypass grafting; HPV: hypoxic pulmonary vasoconstriction; TEA: thoracic epidural anaesthesia.

Ventilatory Protective Strategies during Thoracic Surgery Effects of Alveolar Recruitment Maneuver and Low-tidal Volume Ventilation on Lung Density Distribution

BACKGROUND The increased tidal volume (V(T)) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced V(T) may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different V(T) on pulmonary gas/tissue distribution are examined. METHODS Eight anesthetized piglets were mechanically ventilated (V(T) = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H(2)O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a V(T) of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. RESULTS The dependent lung contained atelectatic (56 ± 10 ml), poorly aerated (183 ± 10 ml), and normally aerated (187 ± 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 ± 35 vs. 526 ± 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased (95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 ± 2 ml; poorly aerated, 94 ± 24 ml; normally aerated, 580 ± 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean ± SD.) CONCLUSIONS The ARM improves aeration and respiratory mechanics. In contrast to OLV with high V(T), OLV with reduced V(T) does not reinforce tidal recruitment, indicating decreased mechanical stress.

Increased Alveolar Damage After Mechanical Ventilation in a Porcine Model of Thoracic Surgery

OBJECTIVE Mechanical stress during one-lung ventilation (OLV) results in lung injury. This study compared the effects of mechanical ventilation, OLV, and surgical manipulation on diffuse alveolar damage (DAD) after application of different anesthetic regimens. DESIGN Prospective, randomized, controlled, blinded animal experiment. SETTING University hospital. OBJECTS Twenty-one piglets. INTERVENTIONS Animals (27.5 kg) were randomized into 4 groups: spontaneous breathing (SB, n = 3), two-lung ventilation (TLV, n = 6), OLV during desflurane (n = 6), and propofol anesthesia (n = 6). SB pigs were killed after the induction of anesthesia. Lung tissue samples were analyzed to obtain reference values for alveolar damage. TLV pigs underwent standard TLV (tidal volumes [V(T)] = 10 mL/kg, F(I)O(2) = 0.40, positive end-expiratory pressure = 5 cmH(2)O). In OLV pigs, after lung separation by a bronchial blocker, OLV (V(T) = 10 mL/kg) and thoracic surgery were performed. After the procedure, the pigs were killed. Lung tissue samples were harvested for histologic examination. Lung injury was quantified by DAD score; sequestration of leukocytes was assessed by the recruitment of CD45(+) cells into the lungs. MAIN RESULTS TLV resulted in increased DAD scores in both lungs (TLV v SB: 6.9 v 2.7, p < 0.05); the number of CD45(+) cells was not increased (TLV v SB: 8.7 v 5.0 cells per view). OLV and surgical manipulation increased DAD and leukocyte sequestration without differences between the ventilated and manipulated lungs. Leukocyte recruitment was not differently affected by the anesthetic regimen (propofol v desflurane: CD45(+) cells per view: 13.5 v 11.3). CONCLUSIONS TLV resulted in increased DAD scores in the lungs as compared with SB. OLV and thoracic surgery further increased lung injury and leukocyte recruitment independently of the administration of propofol or desflurane anesthesia.

Lung computed tomography density distribution in a porcine model of one-lung ventilation

BACKGROUND One-lung ventilation (OLV) exposes the dependent lung to increased mechanical stress which may affect the postoperative course. This study evaluates regional pulmonary gas/tissue distribution in a porcine model of OLV. METHODS Nine anaesthetized and mechanically ventilated (V(T)=10 ml kg(-1), FI(O(2))=0.40, PEEP=5 cm H(2)O) pigs were studied. After lung separation by an endobronchial blocker, lateral thoracotomy and OLV were performed in six pigs. Three animals served as controls. Static end-expiratory and end-inspiratory spiral computed tomography (CT) scans were done before, during, and after OLV and at corresponding times in controls. CT images were analysed by defined regions of interest and summarized voxels were classified by defined lung X-ray density intervals (atelectasis, poorly aerated, normally aerated, and overaerated). RESULTS Dependent lungs contained poorly aerated regions and atelectasis with a significant tidal recruitment during conventional two-lung ventilation (TLV) before OLV (expiration vs inspiration: atelectasis 29% vs 14%; poorly aerated 66% vs 44%; normally aerated 4% vs 41% of the dependent lung volume, P<0.05). During OLV (V(T)=10 ml kg(-1)), cyclic recruitment was increased. The density spectrum of the ventilated lung changed from consolidation to aeration (expiration vs inspiration: atelectasis 10% vs 2%; poorly aerated 71% vs 18%; normally aerated 19% vs 79%, P<0.05). After OLV, increased aeration remained with less atelectasis and poorly aerated regions. Lung density distribution in the non-dependent lung of OLV pigs was unaltered after the period of complete lung collapse. CONCLUSIONS Cyclic tidal recruitment during OLV in pigs was associated with a persistent increase of aeration in the dependent lung.

Anesthetic considerations in patients with previous thoracic surgery.

Purpose of the review This review presents an overview of the different problems and challenges after thoracic surgery. It covers the pathophysiological changes that may occur regularly in the early and late period following surgery. In addition, surgical complications with anesthesiological implications for diagnosis, treatment and prevention are discussed, and consequences for anesthesia in further major and thoracic surgical procedures are shown. Recent findings During the last decade, complications in the early period following surgery after thoracotomy have increasingly moved into the focus caused by their high morbidity and mortality. These problems, such as hemorrhagia and bronchopleural fistulas, are important because they call for a prompt revision or even an emergency operation. The therapy of acute bleeding follows general anesthesiological guidelines whereas the bronchopleural fistula demands methods to prevent aspiration pneumonia as a first priority. In the late period following surgery, typical cardiac and pulmonary modifications can be described that persist and have anesthesiological implications in the case of further surgery. Recent literature, however, lacks clear recommendations regarding anesthesiological management and practice for these cases. Summary Current literature presents no general recommendations on how to manage patients after recent thoracic surgery. Therefore it is necessary to find an individual strategy to handle possible complications and well known pathophysiological changes. Knowledge and understanding of the etiology, the pathophysiology and the risk factors of the perioperative period, allows prevention and target intervention aimed at reducing morbidity and mortality following surgery.