Intraoperative low tidal volume ventilation in peritonitis patients undergoing emergency laparotomy: A randomized controlled trial

Postoperative pulmonary complication is a major cause of morbidity in patients undergoing major abdominal surgery, adversely affecting clinical outcomes and healthcare utilization¹. Lung protective ventilation with low tidal volume and positive end expiratory pressures has been shown to reduce mortality in mechanically ventilated patients with ARDS² and has became a “gold standard” in these patients. 

Use of high tidal volumes (10 to 15 ml/kg predicted body weight) and no PEEP is still common in the operative setup. However, the benefit of lung protective ventilation has been demonstrated in a number of clinical settings in patients without ALI/ARDS. Low tidal volume ventilation has been associated with a reduction in plasma and bronchoalveolar lavage fluid levels of inflammatory cytokines³ and lower risk of prolonged mechanical ventilation, prolonged ICU stay and hemodynamic instability. Also the IMPROVE trial⁴ has demonstrated fewer postoperative complications with lung protective ventilation with 6 to 8 ml/kg Vt, 6 to 8 cm PEEP and recruitment maneuvers every 30 min after tracheal intubation in patients undergoing elective major abdominal surgery. On the contrary another randomized trial found that intraoperative low tidal volume ventilations does not prevent postoperative pulmonary complications after elective upper abdominal surgeries⁵.

Treatment of complicated intraabdominal infection which encompass a wide variety of pathological conditions ranging from uncomplicated appendicitis to fecal peritonitis requires both surgical and antibiotic therapy⁶ and the level of urgency of treatment is determined by the affected organ(s), the relative speed at which clinical symptoms progress and worsen, and the underlying physiological stability of the patient⁷. Abdominal sepsis often results in acute lung injury⁸. Patients suffering from abdominal sepsis often undergo emergency laparotomy and these surgeries are usually of long duration and complex.  However, the effect of low volume ventilation has not been addressed in patients with intraabdominal sepsis undergoing emergency laparotomy.

Aims and objectives

We therefore propose to conduct this study to determine the effect of lung protective ventilation in reducing postoperative pulmonary complication in patients with intraabdominal sepsis undergoing emergency laparotomy.

Material Methods

After obtaining permission from institutional ethics committee and written informed consent from the participants, 60 will be randomized to two groups. Randomization will be done with a computer generated random number table and each patient will be allotted a random number in a sealed envelope.

Group A receiving protective lung ventilation with tidal volume 6 to 8ml/kg and PEEP 6 to 8cm H2O, along with recruitment maneuvers (30 cm H2O for 30 seconds) every half hourly from the time of intubation.

Group B receiving conventional mechanical ventilation with tidal volume 10 to 12 ml/kg, no PEEP and no recruitment maneuvers.

A plateau pressure of not more than 30 cmH2O will be targeted in each group. All other ventilation parameters are identical in both the groups.

The predicted body weight will be calculated based on previously defined formula².

In the event of desaturation, use of FiO2 1.0, use of nonprotective ventilation, recruitment maneuver PEEP will be allowed. Use of anesthetic agents, intraoperative and postoperative pain management, perioperative fluid management will be done according to the norms of standard clinical practice and protocol of our institution.

Inclusion criteria

Age > 18 yrs, <70 years

Emergency laparotomy expected duration >2hrs

Suspected or identified abdominal source of infection

Preoperative risk index for pulmonary complications⁹ >2

Exclusion Criteria

Mechanical ventilation within 2 weeks preceeding surgery

BMI ≥ 35

History of respiratory failure or sepsis within the 2 weeks preceding surgery

Requirement for intrathoracic surgery, history of lung surgery

History of severe COPD, with (non-invasive) ventilation and/or oxygen therapy at home and/or repeated systemic corticosteroid therapy for acute exacerbations of COPD

Progressive neuromuscular illness

ALI or acute respiratory distress syndrome expected to require prolonged post-operative

mechanical ventilation,

Persistent hemodynamic instability or intractable shock

Primary outcome

Pulmonary complications occurring by day 7 after surgery

         1.         Acute respiratory failure

Mild respiratory failure responding to supplemental oxygen

Severe respiratory failure requiring invasive or noninvasive mechanichal ventilation

         2.         Pneumonia

         3.         ARDS

         4.         Pneumothorax

Major extra pulmonary complications were defined as

         1.         Development of severe sepsis, septic shock, organ dysfunction (hepatic, renal, cardiac)

         2.         Hemodynamic instability and requirement of inotropes/vasopressors

         3.         Death

Secondary outcome during the follow up period till patient discharge

         1.         Pulmonary complications graded on a scale 0 to 4¹⁰

         2.         Ventilation related adverse events during surgery

         3.         Severe sepsis, septic shock, organ dysfunction

         4.         Number of days of ICU admission and duration of hospital stay

         5.         Surgical complications like development of intraabdominal abscess, anastomotic leakage, unplanned re-exploration

Statistical analysis

SPSS software version 21.0 (SPSS Inc, Chicago, Illinois, USA) will be used for statistical analysis.

Since there are no previous studies of patients with abdominal sepsis undergoing emergency laparotomy, we propose to take 30 patients in each group (n=30), the total sample size being sixty (N=60). Whether the outcome variables will follow a normal distribution in population, can be found out by considering a minimum sample size of 30 patients in each group.

Review of literature

Mechanical ventilation causing excessive end-inspiratory stretch and/or collapse/recruitment of lung units can lead to lung injury and perhaps lead to the development of multiple system organ failure¹¹.  Traditional use of tidal volumes of 10 to 15 ml/kg body weight may cause stretch induced lung injury and lead to acute respiratory distress syndrome².

The ARDS net trial² demonstrated that  ventilation with low Vt 4 to 6 ml/kg predicted body weight (PBW) targeting a plateau pressure ≤ 30 cm H2O as compared to ventilation with a Vt 12 ml/kg PBW and a plateau pressure ≤ 50 cm H2O was associated with lower mortality (P<0.007, 95% confidence interval 2.4 to 15.3% ), increased number of ventilator free days, increased number of days free from nonpulmonary organ dysfunction and greater decrease in plasma interleukin 6 concentration (P<0.001).  

The surviving sepsis campaign 2012¹² has recommended the use of target tidal volume of 6 ml/kg predicted body weight, use of strategies based on higher PEEP and the initial upper limit goal for plateau pressures in a passively inflated lung be ≤ 30 cm H2O in patients with sepsis induced ARDS. Also they have suggested the use of recruitment maneuver in severe refractory hypoxemia due to ARDS.

The IMPROVE trial⁴ has demonstrated fewer pulmonary and extrapulmonary complications in the first 7 days(21/200 vs 55/200; P=0.001) in patients receiving lung protective ventilation. Over the 7 day postoperative period, fewer patients required noninvasive ventilation or intubation due to acute respiratory failure(10/200 vs 34/200; P=0.001) and a reduced duration of hospital stay(P=0.006) in the lung protective ventilation group.

The beneficial effect of lung protective ventilation has also been demonstrated in other clinical settings like cardiac surgery¹³ and in short-term mechanical ventilation in patients without preexisting lung injury¹⁴.

However specific recommendation about the strategy of mechanical ventilation is lacking in patients with sepsis without ARDS¹².

We therefore propose to conduct this study in order to investigate the effect of protective lung ventilation in major abdominal surgery in patients with abdominal sepsis in the emergency setting.

References

         1.         Rock P, Rich PB. Postoperative pulmonary complications. Curr Opin

Anaesthesiol. 2003;16:123-31.

         2.         The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8.

         3.         E. Zupancich, D. Paparella, F. Turani et al. Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial. Journal of Thoracic and Cardiovascular Surgery 2005;130(2):378–83.

         4.         Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A,

Marret E, Beaussier M, Gutton C, Lefrant JY, Allaouchiche B, Verzilli D, Leone M,

De Jong A, Bazin JE, Pereira B, Jaber S; IMPROVE Study Group. A trial of

intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med.

2013;369(5):428-37.

         5.         Treschan TA, Kaisers W, Schaefer MS, Bastin B, Schmalz U, Wania V, Eisenberger CF, Saleh A, Weiss M, Schmitz A, Kienbaum P, Sessler DI, Pannen B, Beiderlinden M. Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function. Br J Anaesth. 2012;109:263-71.

         6.         Pieracci FM, Barie PS: Management of severe sepsis of abdominal origin.

Scand J Surg 2007,96:184-96.

         7.         Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.

         8.         Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR,

Voelkel NF, Fowler AA 3rd, Natarajan R. Mechanisms of attenuation of abdominal

sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol

Physiol. 2012;303:L20-32.

         9.         Arozullah AM, Khuri SF, Henderson WG, Daley J. Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery. Ann Intern Med 2001;135:847-57

       10.       Hulzebos EH, Helders PJ, Favié NJ, et al. Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: a randomized clinical trial. JAMA 2006;296:1851-7.

       11.       Slutsky AS. Lung injury caused by mechanical ventilation. Chest. 1999

Jul;116(1 Suppl):9S-15S.

       12.       Vassalos A, Rooney K. Surviving sepsis guidelines 2012. Crit Care Med. 2013

Dec;41:e485-6.

       13.       Schultz MJ: Lung-protective mechanical ventilation with lower tidal volumes in patients not suffering from acute lung injury: A review of clinical studies. Med Sci Monit 2008; 14: RA22–26.

       14.       Wolthuis EK, Choi G, Dessing MC, Bresser P, Lutter R, Dzoljic M, van der Poll T, Vroom MB, Hollmann M, Schultz MJ: 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.