Abstract

Background

Prolonged postoperative decrease in lung function is common after major upper abdominal surgery. Evidence suggests that ventilation with low tidal volumes may limit the damage during mechanical ventilation. We compared postoperative lung function of patients undergoing upper abdominal surgery, mechanically ventilated with high or low tidal volumes.

Methods

This was a double-blind, prospective, randomized controlled clinical trial. One hundred and one patients (age ≥50 yr, ASA ≥II, duration of surgery ≥3 h) were ventilated with: (i) high [12 ml kg−1 predicted body weight (PBW)] or (ii) low (6 ml kg−1 PBW) tidal volumes intraoperatively. The positive end-expiratory pressure was 5 cm H2O in both groups and breathing frequency adjusted to normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) until 120 h after operation were compared (P<0.025 considered statistically significant). Secondary outcomes were oxygenation, respiratory and non-respiratory complications, length of stay and mortality.

Results

The mean (sd) values of TWAs of FVC and FEV1 were similar in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre (P=0.12); FEV1: 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre (P=0.15). FVC and FEV1 at any single time point and secondary outcomes did not differ significantly between groups.

Conclusions

Prolonged impaired lung function after major abdominal surgery is not ameliorated by low tidal volume ventilation.

Editor's key points

  • In the intensive care unit, low tidal volume ventilation has been shown to preserve lung function.

  • The authors aimed to study whether low intraoperative tidal volume ventilation would preserve postoperative lung function.

  • Postoperative lung function was similar, irrespective of whether the patients received high or low tidal volume ventilation.

Patients who are mechanically ventilated during surgery experience varying degrees of postoperative lung function impairment, including decreased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1).1 Risk factors for severe postoperative lung function impairment include the duration, site, and technique of surgery.2,3 In contrast, the type of anaesthesia4 and the choice of anaesthetics1 can help to minimize postoperative lung function impairment. Whether intraoperative tidal volume (VT) influences postoperative lung function is unknown. Previous trials found that high VT during abdominal surgery maintained better intraoperative lung mechanics and gas exchange than low VT.5 Relatively high VT is thus routinely used for intraoperative mechanical ventilation. However, high airway pressures, lung overdistention, or both may aggravate or even induce lung injury.6 Based on results from acute respiratory distress syndrome (ARDS) and critically ill patients, there is a growing trend to favour low VT for patients without lung injury who require intraoperative ventilation.7 Of note, there are no robust data on the proper application of PEEP in this context. Low VT is nonetheless increasingly used for intraoperative ventilation without an adjustment of PEEP. It thus remains unclear whether a reduction in VTper se is beneficial compared with traditional high VT with similar PEEP for patients undergoing intraoperative ventilation.

If low intraoperative VT combined with moderate PEEP is protective, patients at high risk for postoperative pulmonary complications might benefit from improved postoperative lung function including earlier recovery of FVC and FEV1. We therefore tested the hypothesis that intraoperative ventilation with low VT improves postoperative time-weighted average (TWA) FVC and FEV1 in patients undergoing elective upper abdominal surgery.

Methods

Our study was approved by the local ethics committee (Ethics committee of the Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany, study number 2974 and registered at ClinicalTrials.gov number 00795964). We studied 101 patients (age ≥50 yr, ASA ≥II) undergoing elective upper abdominal surgery lasting at least 3 h with combined general and epidural anaesthesia. Exclusion criteria were impaired mental state, increased intracranial pressure, or neuromuscular disease.

Patients were premedicated with midazolam 0.1 mg kg−1 orally up to a maximal total dose of 7.5 mg. Before general anaesthesia, arterial and epidural catheters were inserted [epidural catheter level T7–T12; loading dose: 10–15 ml ropivacaine 0.75%, continuous infusion: ropivacaine 0.375% (6–8 ml h−1)]. General anaesthesia was induced with sufentanil 0.4 µg kg−1, thiopental 4–5 mg kg−1, or propofol 1–2 mg kg−1. It was maintained with sevoflurane in oxygen/air and sufentanil. Tracheal intubation was facilitated by succinylcholine (1 mg kg−1), cis-atracurium (0.2 mg kg−1), or rocuronium (0.6 mg kg−1). High-volume, low-pressure cuffs with an internal diameter of 7.5 mm for women and 8.0 mm for men (Mallinckrodt™ Hi-Contour tube) were inflated with air and cuff pressure maintained below 20 mbar. A central venous catheter and a nasogastric tube were inserted. An additional non-depolarizing neuromuscular blocking agent and vasopressors were given as deemed necessary by the attending anaesthesiologist.

Anaesthetic administration was adjusted to maintain arterial pressure and heart rate within 20% of preoperative values. We aimed to maintain normothermia. The primary fluid was Ringer's lactate solution. Up to 500 ml was given with induction of anesthesia and subsequently at a rate of 2–4 ml kg−1 h−1. Blood loss was replaced with Ringer's solution at a 3:1 ratio, with colloids at a 2:1 ratio, or with red blood cells at a 1:1 ratio.

The patients were randomly assigned to (i) the high VT (12 ml kg−1 predicted body weight (PBW)] group or (ii) the low VT (6 ml kg−1 PBW) group. Computer-generated randomization codes (permuted blocks of 10, allocation ratio 1:1) were kept in sequentially numbered sealed opaque envelopes until shortly before induction of general anaesthesia. PBW was calculated as follows: 

formula

After intubation, VT was set to the designated values. The initial breathing rate of 14 (low VT) or 7 (high VT) min−1 was subsequently adjusted to maintain end-tidal Pco2 of 4.6–5.4 kPa (35–40 mm Hg). Other ventilator settings were identical in both groups, including an initial fresh gas flow of 10 litre min−1 with an inspired oxygen fraction forumla of 1.0, PEEP 5 cm H2O, and inspiratory-to-expiratory ratio 1:2. forumla was reduced to 0.5 shortly after intubation, and fresh gas was provided by a ZEUS anaesthesia machine in the autoflow mode (Dräger, Lübeck, Germany).

If deemed necessary by the attending physician, forumla or PEEP was increased to maintain forumla within 20% of preoperative values or forumla≥95%.

Before weaning, forumla was increased to 1.0 for 15 min. The neuromuscular blocking agent was antagonized if necessary at the discretion of the attending anaesthesiologist. When spontaneous breathing began, support was achieved with a continuous positive airway pressure of 5 cm H2O and assisted spontaneous breathing adjusted so as to maintain end-tidal Pco2 4.6–5.4 kPa (35–40 mm Hg) with pressure support levels of 3–10 cm H2O. All patients received a lung expansion manoeuvre consisting of three manual bag ventilations with a maximum pressure of 40 cm H2O shortly before extubation. Mechanical ventilation of patients who were transferred intubated to the intensive care unit (ICU) was continued according to group assignment under the discretion of the intensivist in charge. After operation, all patients received standard institutional care, including regular visits and treatment by our pain service and personal physiotherapy with respiratory exercises, mobilization, and incentive spirometry.

Measurements

Patients and postoperative investigators were blinded to intraoperative group assignment; thus, all postoperative data were collected in a double-blinded fashion.

Blood loss and fluid administration including allogenic blood, vital signs, core temperature, ventilator settings, forumla, end-tidal CO2, and airway pressures were recorded at 15 min intervals throughout surgery, and blood gas analyses were performed hourly or more often as clinically indicated.

Spirometry

Preoperative spirometry was performed after the patient had received a detailed instruction. Measurements were performed in accordance with the American Thoracic Society's standards8 using a single pneumotachograph (SpiroPro, Jaeger, Würzburg, Germany). We made all measurements in the supine position with 30° upper body elevation. After operation, measurements were taken at 1–2, 24, 72, and 120 h after extubation. We aimed to measure FEV1 and FVC three times at each time point with the highest values selected for analysis. Patients were requested to rate their pain at rest in the supine position with 30° upper body elevation on a numeric rating scale of 0–10 (0, no pain; 10, maximum pain). Spirometric testing was only performed if pain scores at rest were ≤3. Otherwise, pain therapy was optimized before spirometric measurements.

Blood gas analysis

Before and after operation, blood was sampled for gas analysis just after each spirometric measurement. If an arterial catheter was in place, blood was withdrawn from it; otherwise, arterialized blood gases [pre-treatment of the ear lobe with a nonivamid- and nicoboxil-containing cream (finalgon®)] were sampled from the patient's ear lobe. Supplemental oxygen, if being used, was withdrawn 15 min before each postoperative spirometry and blood gas analysis.

Chest radiographs

Immediate postoperative chest radiographs were performed as part of the clinical routine after central line placement and prolonged surgery. Anteroposterior X-rays were taken with the patients in the supine position using a portable X-ray machine. Results were scored by a radiologist unaware of group assignment using a Radiological Atelectasis Score: 0, clear lung field; 1, plate like atelectasis or slight infiltration; 2, partial atelectasis; 3, lobar atelectasis; 4, bilateral lobar atelectasis.9

Others

The Sequential Organ Failure Assessment score was calculated on the fifth postoperative day.10 The duration of hospitalization, ICU stay, and mortality were recorded from the patients' charts and the hospital data management system. Severe postoperative complications (acute heart failure, myocardial infarction, ARDS, renal insufficiency, venous embolism, and wound infections) were assessed using a checklist during the daily visits until postoperative day 5. Information until hospital discharge was obtained from the hospital data management system.

The incidence of postoperative pulmonary complications was defined as: (i) respiratory failure: forumla≤6.7 kPa while breathing ambient air or forumla≥6.7 kPa while breathing spontaneously;11 (ii) reintubation for respiratory distress during hospital stay; (iii) pneumonia; (iv) unplanned mechanical ventilation >24 h for pulmonary reasons; or (v) pneumothorax. Impaired oxygenation was defined by a forumla ratio of <40 kPa.

Statistical analysis

Our primary outcome variables were TWAs of postoperative FVC and FEV1.

The sample-size estimate indicated that a minimum of 48 patients per group would provide an 80% chance of detecting a 20% relative increase in FVC from a presumed postoperative FVC of 2.0 (0.7) litre with a corresponding FEV1 of 1.5 (0.5) litre.

Data are presented as absolute values, mean (sd), or percentages on an intention-to-treat basis. Two-tailed Fishers' exact test, Student’s t-test, or Wilcoxon rank-sum tests were used as appropriate. Because there were two primary outcomes, time-weighted FVC and FEV1, a P-value of <0.025 was considered statistically significant. For secondary outcomes, which were exploratory, a P–value of <0.05 was accepted. We used ‘R’ software (R Foundation for Statistical Computing, Vienna, Austria, http:www.R-project.org).

Results

Over a 2 yr period, 101 patients were enrolled (Fig. 1) and randomized to high or low VT. The two groups had similar preoperative and intraoperative characteristics, except for the randomly assigned ventilatory parameters (Table 1). Chronic medications and doses of anaesthetics, including neuromuscular blocking agents, did not differ significantly between the groups (data not shown).

Table 1

Patient characteristics and intraoperative data. Data are presented as absolute values and percentage or mean (sd). A P-value of <0.05 was considered statistically significant; n, number of patients. *Represent values averaged over anaesthesia duration

 6 ml group (n=50) 12 ml group (n=51) P-value 
Male gender (n36 (72%) 39 (76%) 0.654 
Age (yr) (range) 68 (8) (52–87) 68 (9) (51–86) 0.905 
Height (cm) 173 (8) 175 (10) 0.306 
Weight (kg) 79 (16) 77 (22) 0.319 
Current smoker (n15 (30%) 12 (24%) 0.610 
ASA class (II/III/IV) 15/34/1 14/35/2 0.851 
Forced vital capacity (litre) 3.04 (1.0) 3.02 (0.9) 0.464 
Forced expiratory volume in 1 s (litre) 2.30 (0.8) 2.37 (0.6) 0.310 
Haemoglobin (g dl−110.8 (1.9) 10.8 (2.6) 0.220 
Preoperative Po2 (kPa) 10.9 (1.8) 11.1 (1.7) 0.640 
Preoperative Pco2 (kPa) 4.9 (0.5) 4.9 (0.5) 0.588 
Type of operation (n
 Liver resection 18 (36%) 24 (47%) 0.365 
 Gastrectomy 8 (16%) 8 (16%) 
 Whipple 24 (48%) 17 (33%) 
 Others: hemicolectomy, rectum resection 2 (4%) 
Type of anaesthesia (n
 General and epidural anaesthesia 39 (78%) 44 (86%) 0.650 
 General anaesthesia alone 11 (22%) 7 (14%) 
Reasons for missing epidural (n
 Coagulation disturbance 0.407 
 Technical difficulties 
 Discretion of attending 
Duration of surgery (h) 6.1 (2.7) 6.1 (2.1) 0.617 
Duration of mechanical ventilation (h) 8.7 (5.2) 8.7 (5.9) 0.661 
Patients extubated in the operating theatre (n41 (82%) 44 (86%) 0.157 
Ventilatory parameters averaged over anaesthesia duration 
 Absolute tidal volume (ml) 448 (88) 834 (194)* <0.001 
 Relative tidal volume (ml kg−1 PBW) 6.7 (1.1) 12.0 (2.3)* <0.001 
 Minute ventilation (litre) 7.8 (2.1) 6.2 (1.9)* <0.001 
 Breaths per minute 17 (4) 8 (4)* <0.001 
Pmax (cm H2O) 15 (3) 17 (3)* <0.001 
Pmean (cm H2O) 9 (3) 10 (3)* <0.001 
Oxygenation with forumla 0.5, PEEP 5 cm H2   
 Maximum forumla (kPa) 29.7 (5.5) 35.3 (5.7)* <0.001 
 Minimum forumla (kPa) 21.6 (6.4) 26.6 (7.5)* <0.001 
Adjustments of forumla or PEEP, total (n10 0.176 
 Increase in forumla only (n0.234 
 Increase in PEEP only (n0.322 
 Increase in forumla and PEEP (n0.243 
forumla>0.5 throughout surgery (n0.027 
Intraoperative fluids and transfusions    
 Total fluid balance (litre) 4.0 (2.3) 4.2 (2.2) 0.622 
 Crystalloids (litre) 3.4 (1.3) 3.2 (1.4) 0.431 
 Hetastarch (litre) 0.9 (0.4) 0.9 (0.6) 0.809 
 Gelatin (litre) 1.5 (1.0) 1.8 (1.0) 0.098 
 Urine output (litre) 0.9 (0.7) 1.0 (0.7) 0.800 
 Blood loss (litre) 1.7 (2.2) 1.3 (1.1) 0.278 
 Packed red blood cells (units) 4.5 (3.0) 4.4 (3.4) 0.878 
 FFP (litre) 1.7 (0.9) 1.4 (1.2) 0.511 
 Thrombocyte transfusion (units) 0.12 (0.6) 0.17 (0.6) 0.632 
Cumulative catecholamines (mg) 3.4 (2.5) 3.2 (2.4) 0.903 
End of operation core body temperature (°C) 36.9 (0.6) 36.7 (0.6) 0.356 
 6 ml group (n=50) 12 ml group (n=51) P-value 
Male gender (n36 (72%) 39 (76%) 0.654 
Age (yr) (range) 68 (8) (52–87) 68 (9) (51–86) 0.905 
Height (cm) 173 (8) 175 (10) 0.306 
Weight (kg) 79 (16) 77 (22) 0.319 
Current smoker (n15 (30%) 12 (24%) 0.610 
ASA class (II/III/IV) 15/34/1 14/35/2 0.851 
Forced vital capacity (litre) 3.04 (1.0) 3.02 (0.9) 0.464 
Forced expiratory volume in 1 s (litre) 2.30 (0.8) 2.37 (0.6) 0.310 
Haemoglobin (g dl−110.8 (1.9) 10.8 (2.6) 0.220 
Preoperative Po2 (kPa) 10.9 (1.8) 11.1 (1.7) 0.640 
Preoperative Pco2 (kPa) 4.9 (0.5) 4.9 (0.5) 0.588 
Type of operation (n
 Liver resection 18 (36%) 24 (47%) 0.365 
 Gastrectomy 8 (16%) 8 (16%) 
 Whipple 24 (48%) 17 (33%) 
 Others: hemicolectomy, rectum resection 2 (4%) 
Type of anaesthesia (n
 General and epidural anaesthesia 39 (78%) 44 (86%) 0.650 
 General anaesthesia alone 11 (22%) 7 (14%) 
Reasons for missing epidural (n
 Coagulation disturbance 0.407 
 Technical difficulties 
 Discretion of attending 
Duration of surgery (h) 6.1 (2.7) 6.1 (2.1) 0.617 
Duration of mechanical ventilation (h) 8.7 (5.2) 8.7 (5.9) 0.661 
Patients extubated in the operating theatre (n41 (82%) 44 (86%) 0.157 
Ventilatory parameters averaged over anaesthesia duration 
 Absolute tidal volume (ml) 448 (88) 834 (194)* <0.001 
 Relative tidal volume (ml kg−1 PBW) 6.7 (1.1) 12.0 (2.3)* <0.001 
 Minute ventilation (litre) 7.8 (2.1) 6.2 (1.9)* <0.001 
 Breaths per minute 17 (4) 8 (4)* <0.001 
Pmax (cm H2O) 15 (3) 17 (3)* <0.001 
Pmean (cm H2O) 9 (3) 10 (3)* <0.001 
Oxygenation with forumla 0.5, PEEP 5 cm H2   
 Maximum forumla (kPa) 29.7 (5.5) 35.3 (5.7)* <0.001 
 Minimum forumla (kPa) 21.6 (6.4) 26.6 (7.5)* <0.001 
Adjustments of forumla or PEEP, total (n10 0.176 
 Increase in forumla only (n0.234 
 Increase in PEEP only (n0.322 
 Increase in forumla and PEEP (n0.243 
forumla>0.5 throughout surgery (n0.027 
Intraoperative fluids and transfusions    
 Total fluid balance (litre) 4.0 (2.3) 4.2 (2.2) 0.622 
 Crystalloids (litre) 3.4 (1.3) 3.2 (1.4) 0.431 
 Hetastarch (litre) 0.9 (0.4) 0.9 (0.6) 0.809 
 Gelatin (litre) 1.5 (1.0) 1.8 (1.0) 0.098 
 Urine output (litre) 0.9 (0.7) 1.0 (0.7) 0.800 
 Blood loss (litre) 1.7 (2.2) 1.3 (1.1) 0.278 
 Packed red blood cells (units) 4.5 (3.0) 4.4 (3.4) 0.878 
 FFP (litre) 1.7 (0.9) 1.4 (1.2) 0.511 
 Thrombocyte transfusion (units) 0.12 (0.6) 0.17 (0.6) 0.632 
Cumulative catecholamines (mg) 3.4 (2.5) 3.2 (2.4) 0.903 
End of operation core body temperature (°C) 36.9 (0.6) 36.7 (0.6) 0.356 
Fig 1

Trial profile.

Fig 1

Trial profile.

Spirometry

TWA FVC was 1.8 (0.7) litre for the 6 ml group vs 1.6 (0.5) litre for the 12 ml group (P=0.12) and TWA FEV1 1.4 (0.5) litre for the 6 ml group vs 1.2 (0.4) litre for the 12 ml group (P=0.15). FVC and FEV1 also did not differ significantly between groups at any postoperative time point (Fig. 2). Spirometry was performed in 58 patients immediately after surgery and in 54 patients on day 1. The measurement could not be performed as planned in the missing cases due to ventilatory support, reduced consciousness and lack of willingness, or high pain scores. On postoperative days 3 and 5, measurements were possible in 70 and 75 patients, respectively.

Fig 2

Spirometry results in the two groups. Data are expressed as mean (sd). (a) Forced vital capacity. (b) Forced expiratory volume in 1 second. There were no statistically significant differences between groups, or between the groups.

Fig 2

Spirometry results in the two groups. Data are expressed as mean (sd). (a) Forced vital capacity. (b) Forced expiratory volume in 1 second. There were no statistically significant differences between groups, or between the groups.

Intraoperative respiratory parameters

Intraoperative forumla ratios, compliance, resistance, and airway pressures of the 12 ml group were significantly higher (Figs 3 and 4). One patient in the 12 ml group suffered from severe bronchospasm immediately after intubation and received extensive bronchospasmolytic therapy. Two patients received neostigmine to antagonize muscle relaxation; both of them were in the 12 ml group.

Fig 3

Pre- and intraoperative oxygenation in the two groups. The forumla ratio was significantly higher in the 12 ml group during the intraoperative period.

Fig 3

Pre- and intraoperative oxygenation in the two groups. The forumla ratio was significantly higher in the 12 ml group during the intraoperative period.

Fig 4

Intraoperative respiratory mechanics. (a) Dynamic respiratory system compliance. (b) Airway resistance. (c) Maximum airway pressure. (d) Mean airway pressure. Data are expressed as mean (sd). *P<0.05 at individual time points. The P-value at the corner of each panel shows the overall statistical difference between the groups.

Fig 4

Intraoperative respiratory mechanics. (a) Dynamic respiratory system compliance. (b) Airway resistance. (c) Maximum airway pressure. (d) Mean airway pressure. Data are expressed as mean (sd). *P<0.05 at individual time points. The P-value at the corner of each panel shows the overall statistical difference between the groups.

Other postoperative parameters

The majority of the patients was extubated immediately after surgery (6 ml group, n=41; 12 ml group, n=44; P=0.556). Postoperative disposition (post-anaesthetic care unit, ICU, or normal ward), the need for mechanical ventilation, requirement for supplemental oxygen via a mask, and pain scores did not differ significantly between the groups at any postoperative time point. Immediate postoperative chest X-ray examinations revealed significantly more patients with atelectasis in the 6 ml group (88% vs 68%, P=0.017). However, the severity of radiological atelectasis did not differ significantly between groups.

The postoperative forumla values for patients' breathing room air were comparable between groups until day 3. On day 5, oxygenation was significantly higher in the 12 ml group [forumla 10.4 (1.7) vs 9.2 (1.3) kPa, P=0.005].

Other secondary outcomes did not differ between groups (Table 2). There was one unplanned postoperative mechanical ventilation of more than 24 h: a patient in the 12 ml group had myocardial infarction at the end of surgery. Per definition, this was not counted as a pulmonary complication. Another patient from the 12 ml group was reintubated on day 3 due to respiratory distress. His X-ray showed significant atelectasis and mediastinal shift. In the 6 ml group, three patients were admitted to the critical care unit after 5, 8, and 11 days—one after a planned second surgical intervention and two due to sepsis.

Table 2

Postoperative pulmonary complications and other clinical outcomes. Data are presented as absolute values or mean (sd). There were no statistically significant differences between groups. SOFA, sequential organ failure assessment; n, number of patients. *One patient in the 6 ml group fulfilled two criteria for postoperative pulmonary complications

 6 ml group (n=50) 12 ml group (n=51) P-value 
Postoperative pulmonary complications    
 Total number of patients 13* 11 0.966 
 Respiratory failure within first 5 days (n0.200 
 Unplanned MV >24 h (n1.0 
 Reintubation due to respiratory distress within first 5 days (n1.0 
 Pneumonia (n0.776 
 Pneumothorax (n0.617 
Incidence of forumla <40 kPa (%) 20 19 0.839 
Primary postoperative ICU admission (n31 30 0.744 
Duration of primary ICU stay (days) 4 (10) 3 (4) 0.218 
Readmission to ICU (n1.0 
Secondary ICU admission only (n0.118 
Total duration of ICU stay (days) 9 (17) 5 (8) 0.313 
Duration of hospitalization (days) 30 (15) 25 (15) 0.259 
SOFA Score on day 5 2.8 (2.1) 2.4 (2.1) 0.826 
Acute heart failure (n1.0 
Myocardial infarction (n0.492 
Acute respiratory distress syndrome (n0.495 
Renal insufficiency (n0.487 
Venous embolism (n0.205 
Delayed wound healing/wound infections (n12 17 0.380 
In-hospital deaths (n) due to 0.715 
 Septic multiorgan failure 0.362 
 Cardiac decompensation 0.495 
 Bleeding 1.0 
 Progression of malignancy 1.0 
 6 ml group (n=50) 12 ml group (n=51) P-value 
Postoperative pulmonary complications    
 Total number of patients 13* 11 0.966 
 Respiratory failure within first 5 days (n0.200 
 Unplanned MV >24 h (n1.0 
 Reintubation due to respiratory distress within first 5 days (n1.0 
 Pneumonia (n0.776 
 Pneumothorax (n0.617 
Incidence of forumla <40 kPa (%) 20 19 0.839 
Primary postoperative ICU admission (n31 30 0.744 
Duration of primary ICU stay (days) 4 (10) 3 (4) 0.218 
Readmission to ICU (n1.0 
Secondary ICU admission only (n0.118 
Total duration of ICU stay (days) 9 (17) 5 (8) 0.313 
Duration of hospitalization (days) 30 (15) 25 (15) 0.259 
SOFA Score on day 5 2.8 (2.1) 2.4 (2.1) 0.826 
Acute heart failure (n1.0 
Myocardial infarction (n0.492 
Acute respiratory distress syndrome (n0.495 
Renal insufficiency (n0.487 
Venous embolism (n0.205 
Delayed wound healing/wound infections (n12 17 0.380 
In-hospital deaths (n) due to 0.715 
 Septic multiorgan failure 0.362 
 Cardiac decompensation 0.495 
 Bleeding 1.0 
 Progression of malignancy 1.0 

Discussion

Intraoperative mechanical ventilation with low VT of 6 ml kg−1 PBW when compared with high VT of 12 ml kg−1 PBW—with a PEEP of 5 cm H2O in both groups—did not significantly improve postoperative lung function in patients undergoing major upper abdominal surgery. There was no significant difference in FVC or FEV1 values between groups over the first 5 postoperative days.

Postoperative pulmonary dysfunction after upper abdominal surgery results from reduced ventilatory muscle activity, diaphragmatic dysfunction, and decreased lung compliance.12 As might therefore be expected, lung function was significantly impaired for 5 days, regardless of intraoperative VT. Thus, despite a manual recruitment manoeuvre before extubation, the reductions in FVC and FEV1 in our patients were higher than expected13 and in fact comparable with values reported from patients after cardiac surgery.14 This is in line with findings from a recent large prospective multicentre study, which found upper abdominal and intrathoracic surgeries to have equal impact on lung function and introduced them into a new individual risk score to predict postoperative pulmonary complications.15 Pulmonary dysfunction after major surgery thus remains an important clinical problem, and one that is not ameliorated by intraoperative ventilation with low tidal volumes. In contrast, prophylactic chest physiotherapy13 and optimal pain control16 have been shown to significantly improve postoperative pulmonary function and to reduce the incidence of postoperative pulmonary complications.

Our trial was designed to show a difference in spirometric lung function of 20% between groups, a difference we defined as clinically relevant, because comparable effects on lung function have been shown after modifications of surgical and anaesthesiological techniques.4,17 With the observed variance, we had 80% power to detect a 25% difference. We thus cannot rule out smaller differences between the groups. Our lung function measurements ended on postoperative day 5 and differences between the groups could have potentially occurred afterwards. We collected clinical outcome parameters until hospital discharge, but our trial was not powered to detect significant differences for secondary outcomes.

As in previous trials,5 intraoperative lung mechanics and gas exchange were better and atelectasis less with high VT. Using a higher PEEP in the low VT group could have influenced the results in favour of lower VT. We did not do so for several reasons. First, differences between groups, if any, could then not be attributed to low VT alone, and our trial was specifically designed to study effects of intraoperative low VT. Secondly, the ideal PEEP is just high enough to keep the lungs open at end-expiration. Individual patients' ‘ideal-PEEP’ can be identified by PEEP trials. However, they are time-consuming and difficult to implement into the intraoperative setting. Thirdly, the use of high PEEP (≥10 cm H2O) may be limited in the surgical setting. To address the latter issue, a large multicentre trial is currently underway.18

Even low VT without PEEP induces significant pulmonary inflammation.19 Previous trials of intraoperative mechanical ventilation which reported higher levels of proinflammatory cytokines or more pulmonary coagulation activation with high VT nonetheless compared high VT without PEEP to low VT plus PEEP.20–22 We used a minimum PEEP of 5 cm H2O in both groups in order to counterbalance this component of cyclic airway opening and closing. However, cyclic airway opening and closing also depends on the VT and respiratory rate. Using a lower VT inevitably increases dead space fraction. Per protocol, we kept our patients normocapnic. Therefore, a significantly higher minute ventilation and a two-fold higher respiration rate were used in the low VT group, which may contribute to ventilator-induced lung injury.23 Additionally, there were more atelectases in the low VT group and more venous admixture which resulted in significantly lower intraoperative forumla ratios. Thus, potential benefits from mechanical ventilation with low tidal volumes could have been out-weighed by the higher minute ventilation and frequency and the lower intraoperative forumla ratio in those patients. Alternatively, to achieve similar minute ventilation in both groups, we would have had to accept permissive hypercapnia in our low VT patients, a practice that is uncommon in patients with healthy lungs. However, protective effects of hypercapnia on pulmonary function have been suggested.24 Whether these apply to the setting of intraoperative ventilation in patients with healthy lungs was beyond the scope of our trial. Furthermore, to minimize atelectasis and venous admixture and to optimize forumla ratios with low VT, a PEEP higher than 5 cm H2O is needed.

Although few data exist, it seems that in clinical routine, VT rarely exceeds 10 ml kg−1. For ventilation of healthy lungs in the surgical setting, the rationale behind this common practice is not quite obvious. Positive effects of VT as high as 15 ml kg−1 on intraoperative gas exchange are well documented.5 In this trial, we looked at the so far unreported consequences of different VT at a similar PEEP on postoperative lung function and used 12 ml kg−1 as the higher volume for comparison. Based on available data, we did not see a reason to consider this VTper se as harmful for healthy lungs. Gattinoni and colleagues6 estimated that VT must exceed 17 ml kg−1 to induce injury in otherwise healthy lungs.

We found no substantive difference in postoperative pulmonary function. It is thus quite unlikely that a comparison of 10 vs 6 ml kg−1 would have revealed differences.

We present a single-centre trial with a small sample size on a specific group of patients undergoing a selected type of surgery. Thus, our data cannot be generalized to other groups of patients or types of surgery. We did not titrate PEEP levels individually. The duration of mechanical ventilation was substantial (i.e. an average of 8.5 h), but it remains possible that differences in lung function as a function of tidal volume only develop after longer periods. In summary, intraoperative mechanical ventilation with low VT when compared with high VT applied over a mean of 8.5 h in patients with healthy lungs did not result in spirometric or other lung function differences during the first 5 days after major abdominal surgery. However, intraoperative parameters suggest poorer pulmonary mechanics and gas exchange with low VT at a PEEP of 5 cm H2O. Thus, further evaluation of potential outcome benefits of low VT and the adequate PEEP setting for intraoperative ventilation of healthy lungs are needed.

Declaration of interest

T.A.T. had received a postgraduate stipend from Novartis-Stiftung für therapeutische Forschung.

Funding

This work was supported by institutional support, Department of Anaesthesiology, Düsseldorf University Hospital.

Acknowledgements

We thank Renate Babian and Claudia Dohle for their qualified assistance.

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Comments

3 Comments
What is an adequate measure of Lung Function?
19 August 2012
Gordon B Drummond

Treschan and co-workers1 set out to determine if setting low tidal volumes for intraoperative mechanical ventilation could affect lung function after surgery. Their hypothesis was that excess stress to lung tissue causes damage. As they state in their introduction, this is not a new concept.2 Small tidal volumes have often been used in patients with acute lung injury, as a generally accepted means of reducing lung damage. However the range of stress within the lungs of patients with different conditions, and in normal lungs, can vary considerably.3 Studies similar to the study of Treschan have shown previously that smaller tidal volumes are associated with less inflammation, even in patients with normal lungs.4 5 However Treschan and co-workers1 conclude that low volumes "do not improve postoperative lung function", although they have used a crude measure of "lung function" unlikely to indicate damage to lung parenchyma.

Their conclusion misrepresents "lung function" tests. Forced vital capacity is one of the most widely employed "lung function" tests in medicine. Measurements from a forced vital capacity manoeuvre, such as expired volume in one second, or mid-expiratory flow, are used to assess a variety of conditions that affect the chest wall, lung airways and parenchyma, the most common being asthma and emphysema. In many subjects, these values often co-vary strongly: the FEV1 depends on the preceding inspiration, essentially because the flow out of the airways is limited by the elastic properties of the lung and airways. Indeed the "effort independence" of the test, if done properly, is the prime reason why, in standardised circumstances, it is a good test of "lung function". The factors that affect the value of FVC can be sensibly divided into those that impair chest wall movement, including the ribs and the respiratory muscles, and those affecting the lung airways and parenchyma. Conditions such as respiratory muscle weakness can reduce vital capacity, and may have secondary pulmonary effects. For example chest wall restriction, as occurs after abdominal surgery, affects lung function as a result of changes in chest wall position and movement.6

A vital capacity manoeuvre requires full patient co-operation and maximal effort. Indeed, a classic textbook on lung function tests includes a cartoon of the technician shouting at the patient!7 For many years, abdominal surgery has been known to have substantial effects on vital capacity,8 because both inspiratory and expiratory muscle force are reduced.9 Beecher9 used the powerful expression "crippling of the respiratory mechanics indicated by decrease of vital capacity" and wrote: "A consideration of how vital capacity is obtained should make this evident. The patient is required to take the deepest possible breath and then to expire as completely as possible. This procedure requires great cooperation on the part of normal persons while in the sick it demands more than can always be obtained." The substantial effect of upper abdominal surgery in reducing vital capacity, by up to 70% or so, is mediated by reduced ability or willingness to undertake the large muscle effort, and by reduced chest wall movement, both of which are needed to perform the test. Impairment of deep breathing and coughing has been related frequently to the development of pulmonary complications.

Because restriction of chest wall movement can be related to pain, Bromage suggested that the ability to perform the vital capacity manoeuvre could be used to measure of analgesia after surgery.10 Thus a "lung function" test became a measure of pain, and perhaps even personality.11 Even after obtaining satisfactory analgesia, vital capacity remains substantially reduced after abdominal surgery.12-14 The possibility that this test could provide a suitable measure of possible subtle pulmonary damage is remote, when one compares the relative muscle forces needed to expand lung tissue with those required to perform a forced vital capacity manoeuvre.15

What was the reason to choose such an outcome for the purpose of this study? As evidence that mechanical ventilation can reduce "lung function" the authors cite a recent study of patients having back surgery, where vital capacity was reduced by about 5%, and suggest that the choice of anaesthetic agent can alter such vital capacity changes. They cite a further study of patients having vaginal surgery, using either general or regional anaesthesia, where again the changes in vital capacity were only about 10%.16 Such effects are not comparable to the large changes in vital capacity that occur after upper abdominal surgery. In discussion, the authors suggest that lung function is reduced after abdominal surgery by "reduced ventilatory muscle activity, diaphragmatic dysfunction, and decreased lung compliance", citing a study by Dureil and co-workers.17 However, this paper did not report values of lung compliance, and the index of "dysfunction" of the diaphragm used in this paper is controversial.18 Thus the choice of primary outcome measure in this study is ill-suited to detecting evidence of lung damage. The authors have chosen a measure of chest wall movement that is substantially affected by the presence of an upper abdominal wound. For decades, an upper abdominal incision has been known to have a substantial effect on the capacity to take in a large breath in, and force it out. Any effect on lung mechanics caused by mechanical ventilation will pale into insignificance.

The authors suggest that their study was of sufficient size to detect a difference of 200 ml, relative to a forced vital capacity after surgery of 2 litre. This value was chosen on the basis of data from studies of patients after vaginal surgery 16 and patients who had open or laparoscopic cholecystectomy. 19 Neither of these patient groups resemble the patients studied, where the vital capacity was reduced from 3 litre to about 1.7 litre. Epidural analgesia was planned for the patients they studied, and achieved in 83 of the 101 patients. Forced vital capacity could be measured in 58 patients after surgery and in 54 patients at 24 hours. From these values, a "time weighted" average was calculated although the exact procedure used for this calculation is not given. None of the secondary measures, many of which were not postoperative, were powered to show a difference, and several were inappropriately tested for significance since they were outcomes of the planned intervention. The evidence in this paper is insufficient to support the conclusion of the title. A better conclusion would be that no difference is not the same as the same.

References

1. Treschan TA, Kaisers W, Schaefer MS, et al. Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function. Br J Anaesth 2012; 109: 263-71

2. Mead J, Takishima T, Leith D. Stress distribution in lungs - a model of pulmonary elasticity. J Appl Physiol 1970; 28: 596 - 608.

3. Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med 2008; 178: 346-55

4. Hong CM, Xu DZ, Lu Q, et al. Low tidal volume and high positive end- expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs. Anesth Analg 2010; 110: 1652-60

5. Wolthuis EK, Choi G, Dessing MC, et al. Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury. Anesthesiology 2008; 108: 46-54

6. Klineberg PL, Rehder K, Hyatt RE. Pulmonary mechanics and gas exchange in seated men with chest restriction. J Appl Physiol 1981; 51: 26-32

7. Cotes JE. Lung function : assessment and application in medicine, 5 edn. Oxford: Blackwell Scientific, 1993

8. Head JR. The Effect of Operation upon the Vital Capacity. Boston Med Surg J 1927; 197: 83-7

9. Beecher HK. The measured effect of laparotomy on the respiration. J Clin Invest 1933; 12: 639-50

10. Bromage PR. Spirometry in assessment of analgesia after abdominal surgery. Br Med J 1955; ii: 589-93

11. Parbrook GD, Steel DF, Dalrymple DG. Factors predisposing to postoperative pain and pulmonary complications. A study of male patients undergoing elective gastric surgery. Br J Anaesth 1973; 45: 21-33

12. Miller L, Gertel M, Fox GS, MacLean LD. Comparison of effect of narcotic and epidural analgesia on postoperative respiratory function. Am J Surg 1976; 131: 291-4

13. Kimball WR, Carwood CM, Chang Y, McKenna JM, Peters LE, Ballantyne JC. Effect of effort pain after upper abdominal surgery on two independent measures of respiratory function. J Clin Anesth 2008; 20: 200-5

14. Spence AA, Smith G. Postoperative analgesia and lung function: a comparison of morphine with extradural block. Br J Anaesth 1971; 43: 144-8

15. Agostoni E. Action of respiratory muscles. In: Fenn WO, Rahn H, eds. Handbook of physiology: American Physiological Society, 1997; 377-86

16. von Ungern-Sternberg BS, Regli A, Reber A, Schneider MC. Effect of obesity and thoracic epidural analgesia on perioperative spirometry. Br J Anaesth 2005; 94: 121-7

17. Dureuil B, Cantineau JP, Desmonts JM. Effects of upper or lower abdominal surgery on diaphragmatic function. Br J Anaesth 1987; 59: 1230-5

18. Drummond GB. Diaphragmatic dysfunction: an outmoded concept. Br J Anaesth 1998; 80: 277-80

19. Putensen-Himmer G, Petensen C, Lammer H, Lignau W, Aigner F, Benzer H. Comparison of postoperative respiratory function after laparoscopy or open laparotomy for cholecystectomy. Anesthesiology 1992; 77: 675-80

Conflict of Interest:

None declared

Submitted on 19/08/2012 8:00 PM GMT
Indeed, what is an adequate measure of lung function?
3 September 2012
Tanja A. Treschan

Postoperative pulmonary complications are serious clinical problems and patients after upper-abdominal surgery are at especially great risk (1). Drummond clearly explains of the impact of postoperative pulmonary impairment, measured spirometrically as reduced FVC and FEV1, and clinically as reduced deep breathing and coughing. Drummond points out that deep breathing, coughing, and spirometric lung function testing are all influenced by factors ranging from surgical pain to diaphragmatic dysfunction to patients' personality. He concludes that "Any effect on lung mechanics caused by mechanical ventilation will pale into insignificance". But if this were true, why should we use low tidal volumes in our surgical patients with healthy lungs for intraoperative ventilation?

Intraoperative oxygenation is worse with lower tidal volumes. Lower tidal volumes increase atelectasis and it remains unclear how much PEEP is necessary to counterbalance this effect. In contrast to Drummond's suggestion, there is no clear evidence for less inflammation with lower tidal volumes in healthy lungs, especially not when low and high tidal volumes are compared using the same level of PEEP (2,3). Specifically, the study by Hong et al.(4), cited by Drummond as evidence that small tidal volumes are associated with less inflammation, demonstrates that there is no difference in cytokines when low and high tidal volumes are used with the same low level of PEEP in healthy lungs. What that study does show is less histological lung injury with high tidal volumes and low PEEP than with low tidal volumes and low PEEP.

Spirometric lung function testing does not measure subtle pulmonary damage. But we were not especially interested in subtle pulmonary damage. "We tested the hypothesis that intraoperative ventilation with low tidal volume improves postoperative time-weighted average FVC and FEV1 in patients undergoing upper abdominal surgery" -- a clinically relevant and important outcome (5). The results of our trial indicate that the potential effects on lung mechanics, if any, caused by mechanical ventilation "have paled into insignificance". Low tidal volumes during upper-abdominal surgery did not improve postoperative lung function. That is the clinically important outcome.

(1) Canet, J. et al. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology 113, 1338-1350 (2010). (2) Koner, O. et al. Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass. Intensive Care Med 30, 620-626(2004).

(3) Wrigge, H. et al. Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial. Intensive Care Med 31,1379-1387(2005).

(4) Hong, C. M. et al. Low tidal volume and high positive end- expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs. Anesth. Analg 110, 1652-1660 (2010).

(5) Treschan, T. A. et al. Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function. British Journal of Anaesthesia (2012).doi:10.1093/bja/aes140

Conflict of Interest:

None declared

Submitted on 03/09/2012 8:00 PM GMT
Re:Indeed, what is an adequate measure of lung function?
2 October 2012
Gordon B Drummond

This answer evades the correct conclusion to be drawn from this study. The study asks "does a low tidal volume during surgery improve lung function?". To test this possibility, a test was used that does not indicate lung damage, but rather impaired chest wall movement. The study, and the correspondence, provide no plausible biological evidence that this test would provide evidence of the effect sought. What was measured may well be clinically relevant: but is very unlikely to provide any indication of the effect that was being sought. An obvious analogy would be to claim that mental function, or recovery of bowel function after surgery (clinically relevant) are affected by the mode of mechanical ventilation. If the link between the hypothesis and the measure used is poor and implausible, then the result of the study will be incredible.

Conflict of Interest:

None declared

Submitted on 02/10/2012 8:00 PM GMT