Comparative Study of Effects of Intraoperative Use of Positive End-Expiratory Pressure, Intermittent Recruitment Maneuver, and Conventional Ventilation on Pulmonary Functions during long-Duration Laparotomy.

BACKGROUND: With an increase in the duration of general anesthesia, there is a gradual deterioration in pulmonary functions. Intraoperative atelectasis is the major cause of deterioration in pulmonary functions. This study was performed to compare and determine the best ventilatory strategy among conventional ventilation, application of positive end-expiratory pressure (PEEP), and intermittent recruitment maneuver.
MATERIALS AND METHODS: Seventy-five patients were divided into three groups each of 25 patients. In the first group (zero positive end-expiratory pressure [ZEEP]), we have applied zero PEEP intraoperatively. In the second group (PEEP), we have applied PEEP of 6 cm of H2O. In the third group (intermittent lung recruitment maneuver [IRM]), we have done intermittent recruitment maneuver intraoperatively. Pulmonary functions were analyzed by partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F) and static lung compliance (Cstat).
RESULTS: While comparing the mean P/F ratio between the groups, a significant decrease in P/F ratio of the ZEEP group was found from 90 min after induction up till the end (i. e. 24 h after extubation) of our observations as compared to both the PEEP and IRM groups. However, it did not differ (P > 0.05) between the PEEP and IRM groups at all time points on statistical analysis. On comparing the mean of Cstat between the groups, there was a significant decrease in lung compliance of the ZEEP group as compared to both the PEEP and IRM groups at all time points. However, like P/F ratio, compliance was also found to be statistically insignificant between the PEEP and IRM groups.
CONCLUSIONS: Pulmonary functions are relatively preserved with application of either PEEP or doing intermittent recruitment maneuver. Copyright:

INTRODUCTION

It is a well-established fact that with an increase in the duration of general anesthesia, there is a gradual deterioration in pulmonary functions which has largely been attributed to progressive alveolar collapse and ventilation–perfusion mismatch.[1] After induction of general anesthesia, combined effects of supine position, muscle paralysis, loss of physiological positive end-expiratory pressure (PEEP), and surgical manipulations result in atelectasis, reduced functional residual capacity (FRC), and increased closing volume.

General anesthesia causes impairment in pulmonary gas exchange and respiratory mechanics, even in patients with healthy lungs.[2] Atelectasis has been described both during laparotomy and laparoscopic surgery.[3] It invariably develops within minutes after the induction of general anesthesia[4] and is the major cause of alterations in gas exchange.[5]

Intraoperative changes in pulmonary functions may extend into postoperative period. It may delay discharge from postanesthesia care unit and increase the need for respiratory physiotherapy and the probability of ventilator support. These all lead to increased morbidity as well as cost burden to the patients.

There is a lack of randomized controlled trials to define optimal intraoperative tidal volume, PEEP, and the use of intraoperative lung recruitment.[6]

Anesthetic management, particularly mechanical ventilation settings, can influence the extent and course of deterioration of pulmonary functions. Various intraoperative ventilatory strategies have been studied to improve gas exchange in these patients including large tidal volume, high ventilatory frequency, or both,[7] use of PEEP,[8] and reverse Trendelenburg position.[9] However, the effects of these interventions have been variable.

There had been studies which compared different levels of PEEP and different recruitment maneuvers during laparotomies, but there is no study which compared the efficacy of PEEP and intraoperative intermittent recruitment maneuver with no PEEP in preserving pulmonary functions in perioperative period of laparotomies of prolonged duration. We designed the present study to compare the effects of conventional ventilation with PEEP, conventional ventilation without PEEP, and intermittent lung recruitment maneuver (IRM) on pulmonary functions in patients undergoing prolonged laparotomies under general anesthesia.

MATERIALS AND METHODS

Study design and settings

It was a comparative, prospective, monocentric, interventional study commenced after obtaining approval from Institute's Ethical Committee (no. 17/16). This study was conducted between April 2017 and December 2018 at a tertiary care center.

Inclusion criteria

The American Society of Anesthesiologists (ASA) physical status Class I–II patients of either sex belonging to the age group of 18–65 years, undergoing laparotomy in supine position with an expected duration of 3 h or more, were included in the study.

Exclusion criteria

Patients who were expected to have or were having hemodynamic instability and had any preexisting comorbidity including any pulmonary pathology, body mass index (BMI) ≥30 kg/m2, and preoperative anemia (hemoglobin <10 gm.dl-1) were excluded from the study.

Sample size

It was determined by taking partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio as a primary outcome. On the basis of data available from previous study[7] that tested the effect of ventilatory strategy on perioperative arterial oxygenation, it was determined that for the primary outcome, i.e., PaO2/FiO2 ratio, a sample size of twenty patients per group would provide statistical power (two-tailed, α = 0.05) of >80% to detect a difference of 10 kPa or 75 mmHg. To take care of dropouts, 25 patients were recruited in each group.

After obtaining informed written consent, 84 patients were enrolled for this study, out of which 9 patients were dropped from the study. The rest 75 patients were divided into 3 groups each of 25 by sequential sampling. The first patient was allocated to the first group, the second patient was allocated to the second group, and the third patient in the third group, and then, sampling was continued in the same cyclical order.

Following were the three study groups:

Zero positive end-expiratory pressure (ZEEP) group: Patients were ventilated intraoperatively with zero PEEP

PEEP group: Patients were ventilated intraoperatively with PEEP of 6 cm of water

IRM group: Patients were ventilated intraoperatively with intermittent recruitment maneuver, by sustained inflation using a pressure of 30 cm H2O for 20 s, every 30 min, by shifting the mechanical ventilation to manual mode.

Primary outcome measure – Ratio of PaO2/FiO2, i.e., P/F ratio

Secondary outcome – Static lung compliance (Cstat).

All patients were premedicated with tablet ranitidine 150 mg and alprazolam 0.5 mg, the night before surgery, and at 6:00 a.m. on the day of surgery. All patients fasted for minimum 6 h preoperatively. Patients were allowed to drink water till 2 h before taking to operation suite.

On arrival in the operation theater, intravenous (i.v.) access was established and an i.v. fluid was started. Standard monitors were attached.

Epidural catheter was placed after proper cleaning and draping in appropriate space according to surgery planned. After a test dose of 3 mL of 2% lignocaine with adrenaline (1 in 200,000), a bolus dose of 10 mL of 0.125% bupivacaine was given through epidural catheter in all patients.

Radial artery was cannulated under local anesthesia to measure blood pressure as well as for repeated arterial blood gas (ABG) sampling.

Patients were preoxygenated with 100% oxygen using a Drager Primus anesthesia workstation and then induced with i.v. midazolam (1–2 mg stat), fentanyl (1–2 μg.kg−1), and i.v. 1% propofol (1–2 mg.kg−1). After assessing for mask ventilation, vecuronium (0.08–0.12 mg.kg−1) was administered to achieve muscle relaxation. Bag-and-mask ventilation was continued with 100% oxygen.

Tracheal intubation was performed with appropriate-sized endotracheal tube (ETT), cuff inflated with the help of cuff pressure monitor. Anesthesia was maintained in all cases with 30% oxygen and 70% air along with isoflurane 0.8%–1.2%. Bolus doses of i.v. fentanyl 1 μg.kg−1 and i.v. vecuronium 0.08–0.12 mg.kg−1 were supplemented intermittently.

Patients were ventilated in volume-controlled mode with a tidal volume of 6–8 mL.kg−1, respiratory rate of 10-12 min-1, FiO2 of 0.3, and I:E ratio of 1:2 to maintain end-tidal carbon dioxide in the range of 30–35 mm of Hg.

Five minutes after intubation and ventilation, patients were allocated to one of the three groups – ZEEP, PEEP, and IRM.

All the hemodynamic parameters (mean arterial blood pressure [MAP], heart rate [HR], and oxygen saturation [SpO2]) were noted before intubation, after intubation, every 30 min after intubation intraoperatively and after extubation till 24 h.

ABG sample was taken 5 min after intubation and thereafter every 30 min in intraoperative period. In postoperative period, ABG analysis was done after 30 min, 6 h, 12 h, 18 h, and 24 h of arrival in the postoperative ward.

Cstat was noted in this study after intubation (baseline) and thereafter every 30 min till the end of surgery as displayed on anesthesia workstation.

Cstat is derived from plateau pressure, PEEP, and expiratory tidal volume.

Where Pplat= plateau pressure; VT= tidal volume; PEEP = positive end-expiratory pressure.

All patients received i.v. ondansetron (0.1 mg.kg−1) and i.v. paracetamol (15 mg.kg−1) approximately 30 min before the end of surgery. Isoflurane was tapered at the beginning of skin suturing and stopped after skin closure. Neuromuscular blockade was reversed with i.v. neostigmine 0.05 mg.kg−1 and glycopyrrolate 0.01 mg.kg−1.

Once satisfactory extubation criteria were met as led down in ether.standford.edu., patients were extubated. After extubation, oxygen was supplemented by Hudson mask. Thereafter, assessment of neurological and neuromuscular recovery was done once again, and if found satisfactory, patients were shifted to postoperative ward.

In postoperative ward, patients received oxygen supplementation by Venturi mask ventilation FiO2 of 0.4 for 6 h. After 6 h, oxygen support was withdrawn. If on discontinuation of oxygen support, SpO2 was <95%, then such patients were continued with oxygen therapy. Patients were reassessed every hour, and if able to maintain SpO2 of >95%, without oxygen supplementation, then Venturi mask was removed and a patient was allowed to breathe room air.

Postoperative pain was managed with continuous epidural infusion of a mixture of bupivacaine 0.0625% and fentanyl 2 μg.ml−1 and titrated according to postoperative pain using the Numerical Rating Scale (NRS) till 48 h along with injection paracetamol 1 g 6 hourly. NRS was done in postanesthesia care unit at 3 h, 6 h, 12 h, 18 h, 24 h, 48 h, and at the time of discharge. Target was to maintain NRS ≤3.

RESULTS

The demographic characteristics (age, sex, BMI, and ASA grade) of three groups were found to be comparable [Table 1].

Table 1

Demographic data comparison between zero positive end-expiratory pressure, positive end-expiratory pressure, and intermittent lung recruitment maneuver groups

Variable	Group 1 (ZEEP)	Group 2 (PEEP)	Group 3 (IRM)	P
Age (years)	40.72±2.16	40.12±2.13	41.40±2.03	0.745
Sex
Female	9 (36.0)	9 (36.0)	7 (28.0)	0.78
Male	16 (64.0)	16 (64.0)	18 (72.0)
BMI (kg/m2)	22.38±0.58	21.82±0.45	22.68±0.49	0.48
ASA grade
I	18 (72)	16 (64)	15 (60.0)	0.662
II	7 (28)	9 (36)	10 (40)

ZEEP=Zero positive end-expiratory pressure, PEEP=Positive end-expiratory pressure, IRM=Intermittent lung recruitment maneuver, BMI=Body mass index

Enrollment of patients for the study, their allocation to different groups, follow up and analysis are shown in the CONSORT diagram [Figure 1]. The duration of surgery ranged from 4:30 h to 6 h. As all surgeries included in our study were prolonged for ≥4:30 h, we have compared intraoperative data of each group up to 4:30 h to make the comparison of groups homogeneous. The duration of surgery in each group was statistically comparable.

Figure 1

CONSORT diagram

Hemodynamic parameters such as HR, MAP, and SpO2 among the three groups were found to be comparable across all time periods, i.e., intraoperatively as well as after extubation till 24 h after extubation.

In the ZEEP group, two patients showed SpO2 of 93% after 6 h on withdrawal of oxygen support. In these two patients, supplemental oxygen support had to be continued up to 12 h in postoperative period.

P/F ratio of three groups over the time period is summarized in Table 2 and Figure 2. On comparing the mean P/F ratio among groups, using the Newman–Keuls test showed a significant (P < 0.05) decrease in P/F ratio in the ZEEP group as compared to the other two groups at 30 min after intubation to 24 h postextubation [Table 3]. There was no significant difference in P/F ratio among patients of the PEEP and IRM groups.

Table 2

Comparison (P) of mean partial pressure of oxygen/fraction of inspired oxygen ratio by Newman- Keuls test

Time periods	ZEEP (P)	PEEP (P)	IRM (P)
Before intubation	Reference	Reference	Reference
After intubation	0.099	0.612	0.637
30 min after intubation	0.002	0.005	0.034
1:00 h after intubation	<0.001	<0.001	<0.001
1:30 h after intubation	<0.001	<0.001	<0.001
2:00 h after intubation	<0.001	<0.001	<0.001
2:30 h after intubation	<0.001	<0.001	<0.001
3:00 h after intubation	<0.001	0.002	0.003
3:30 h after intubation	<0.001	0.098	0.112
4:00 h after intubation	<0.001	0.096	0.080
4:30 h after intubation	<0.001	0.090	0.658
30 min postextubation	<0.001	0.007	0.117
6:00 h after extubation	<0.001	0.060	0.223
12:00 h after extubation	<0.001	0.218	0.427
18:00 h after extubation	<0.001	0.602	0.653
24:00 h after extubation	<0.001	0.925	0.759

ZEEP=Zero positive end-expiratory pressure, PEEP=Positive end-expiratory pressure, IRM=Intermittent lung recruitment maneuver

Figure 2

Mean partial pressure of oxygen/fraction of inspired oxygen ratio of three groups over the time periods

Table 3

Intergroup analysis of mean partial pressure of oxygen/fraction of inspired oxygen ratio by Newman- Keuls test

Time periods	ZEEP versus PEEP	ZEEP versus IRM	PEEP versus IRM
Before intubation	0.994	0.960	0.677
After intubation	0.986	0.856	0.991
30 min after intubation	0.969	0.946	0.996
1:00 h after intubation	0.678	0.793	0.985
1:30 h after intubation	0.294	0.562	0.712
2:00 h after intubation	0.007	0.007	0.992
2:30 h after intubation	<0.001	<0.001	0.968
3:00 h after intubation	<0.001	<0.001	0.998
3:30 h after intubation	<0.001	<0.001	0.986
4:00 h after intubation	<0.001	<0.001	0.986
4:30 h after intubation	<0.001	<0.001	0.946
30 min postextubation	<0.001	<0.001	0.987
6:00 h after extubation	<0.001	<0.001	0.998
12:00 h after extubation	<0.001	<0.001	0.995
18:00 h after extubation	0.003	<0.001	0.971
24:00 h after extubation	0.024	0.006	0.929

ZEEP=Zero positive end-expiratory pressure, PEEP=Positive end-expiratory pressure, IRM=Intermittent lung recruitment maneuver

The Cstat of the three groups over the time periods is summarized in Table 4 and Figure 3. In the ZEEP group, the mean of Cstat progressively decreased during the intraoperative period as compared to baseline. The Newman–Keuls test showed a significant (P < 0.01 or P < 0.001) decrease in Cstat at all time periods in this group. In the PEEP and IRM groups, Cstat decreased marginally after intubation till 1:30 h, but after 1:30 h, it started improving. Lung compliance reached near baseline value at 3:00 h after intubation. On intergroup analysis of Cstat using the Newman–Keuls test, it showed a significant (P < 0.001) decrease in lung compliance in the ZEEP group as compared to the PEEP as well as IRM groups [Table 4].

Table 4

Intragroup analysis of static lung compliance by Newman- Keuls test

Time periods	ZEEP (P)	PEEP (P)	IRM (P)
After intubation	Reference	Reference	Reference
30 min intubation	0.002	0.836	0.968
1:00 h after intubation	<0.001	0.545	0.347
1:30 h after intubation	<0.001	0.327	0.309
2:00 h after intubation	<0.001	0.567	0.280
2:30 h after intubation	<0.001	0.747	0.785
3:00 h after intubation	<0.001	0.899	0.714
3:30 h after intubation	<0.001	0.944	0.137
4:00 h after intubation	<0.001	0.788	0.126
4:30 h after intubation	<0.001	0.771	0.101

ZEEP=Zero positive end-expiratory pressure, PEEP=Positive end-expiratory pressure, IRM=Intermittent lung recruitment maneuver

Figure 3

Mean static lung compliance of three groups over the time periods

However, an intergroup comparison of Cstat between the PEEP and IRM groups [Table 5] showed no significant difference in change of Cstat at all time periods.

Table 5

Intergroup analysis of static lung compliance between groups by Newman- Keuls test

Time periods	ZEEP versus PEEP	ZEEP versus IRM	PEEP versus IRM
After intubation	0.763	0.861	0.979
30 min after intubation	<0.001	<0.001	0.852
1:00 h after intubation	<0.001	<0.001	0.902
1:30 h after intubation	<0.001	<0.001	0.387
2:00 h after intubation	<0.001	<0.001	0.948
2:30 h after intubation	<0.001	<0.001	0.983
3:00 h after intubation	<0.001	<0.001	0.938
3:30 h after intubation	<0.001	<0.001	0.674
4:00 h after intubation	<0.001	<0.001	0.511
4:30 h after intubation	<0.001	<0.001	0.650

ZEEP=Zero positive end-expiratory pressure, PEEP=Positive end-expiratory pressure, IRM=Intermittent lung recruitment maneuver

DISCUSSION

This was the first-ever study which involved a head-to-head comparison of the effects of conventional ventilation with or without PEEP and IRM on pulmonary functions in patients undergoing prolonged laparotomies under general anesthesia.

Lung recruitment is a maneuver aimed to revert atelectasis by means of a brief controlled increase in airway pressure.[10] Clinical studies demonstrated that the alveolar recruitment strategy, a cycling recruitment maneuver combined with an adequate level of PEEP also improved lung physiology in thoracic surgery with open-lung ventilation (OLV).[1112] In a recent meta-analysis, it was concluded that the use of IRM reduced the incidence of postoperative pulmonary complication (PPC), especially combined with lung protection ventilation strategy. Combining with PEEP, there was no remarkable reduction in the incidence of PPC.[13] Alveolar recruitment is achieved broadly by two types – sustained inflation of the lungs for 5–30 sec to a predetermined peak inspiratory pressure of 30–40 cm of H2O or incrementally increasing PEEP in a stepwise manner.[14] In the meta-analysis, it was found that sustained inflation technique may be better than stepwise lung recruitment maneuver in preventing PPC.[13] We utilized sustained manual inflations of the lungs to a peak inspiratory pressure of 30 cm H2O.

Partial pressure of oxygen/fraction of inspired oxygen ratio

On comparing the mean P/F ratio among groups, there was a significant decrease in P/F ratio in the ZEEP group as compared to both the PEEP and IRM groups from 2 h after intubation till 24 h after extubation [Table 2]. However, P/F ratio did not differ between the PEEP and IRM groups [Table 3] at all time periods. Application of either PEEP or doing IRM has probably prevented atelectasis during the intraoperative period,[71516] improving pulmonary mechanics and decreasing pulmonary shunt,[2] resulting in improvement of P/F ratio. A previous study reported that during OLV-related hypoxemia in a healthy lung model, increasing PEEP had a beneficial effect on oxygenation, based on its effect on lung inspiratory recruitment and its ability to preserve end-expiratory lung volume (EELV).[17] Tusman et al. reported that an increase in arterial oxygenation after the recruitment maneuver suggests a reversal of anesthesia-induced atelectasis and the ventilation/perfusion inhomogeneity.[11] PEEP can counterbalance the decrease in EELV, thereby preventing atelectasis during the intraoperative period,[71516] improving pulmonary mechanics, and decreasing pulmonary shunt.[2] Further, the application of PEEP minimizes lung collapse and prevents the repeated opening and collapse of lung units.[18] In patients with OLV, it had been reported that the better the underlying lung function, the better the response to PEEP.[1920] In this situation, the improvement of oxygenation by PEEP of 5 cm H2O was shown to be mainly related to an increase in FRC.[20] We have used PEEP of 6 cm of H2O as the BMI of our patients was in the normal range. It was reported that the level of effective PEEP in patients with normal BMI was 6-8 cm of H2O. In obese patients, higher PEEP (10 cm H2O or higher) might be needed. Low PEEP will not be enough to keep the airways open and may therefore not be expected to recruit or even keep all lung open.[21]

Static lung compliance

In the ZEEP group, there is a significant decrease in Cstat at all time periods as compared to baseline [Table 4 and Figure 3]. In the PEEP and IRM groups, Cstat decreased marginally from baseline after intubation till 1:30 h of intubation but later on started improving during intraoperative period. The decrease in Cstat in initial 1:30 h period would be attributed to atelectasis and reduced lung volume which happens at the time of induction. Institution of PEEP probably leads to alveolar recruitment which is a continuum process and probably takes 1:30 h for all alveoli to recruit to approximately to the level of preinduction state.

Lung compliance reached near baseline value at 3:00 h after intubation and above baseline value at 3:30 h and thereafter [Table 4 and Figure 3]. On intergroup analysis, there was a significant decrease in lung compliance of the ZEEP group as compared to both the PEEP and IRM groups at all time periods [Table 5]. Cstat was comparable between the PEEP and IRM groups at all time intervals.

This study is comparable with a previous study,[22] in which three levels of PEEP were applied in random order: (1) zero (ZEEP), (2) PEEP of 5 cm of H2O, and (3) PEEP of 10 cm H2O. It was reported that a more aggressive PEEP level is required to reduce shunt and to maximize compliance in case of laparoscopic surgery.

Our result is also comparable with another study[18] where the authors tested the hypothesis that during laparoscopic surgery, Trendelenburg position and pneumoperitoneum may worsen chest wall elastance, concomitantly decreasing transpulmonary pressure, and that a protective ventilator strategy applied after pneumoperitoneum induction, by increasing transpulmonary pressure, would result in alveolar recruitment and improvement in respiratory mechanics and gas exchange. They concluded that in patients submitted to laparoscopic surgery in Trendelenburg position, an open-lung strategy applied after pneumoperitoneum induction increased transpulmonary pressure and led to alveolar recruitment and improvement of elasticity of chest wall and gas exchange.[16]

Our results are comparable with another study of elderly patients (>65 years), who underwent major open abdominal surgery.[23] In that study, OLV (recruitment maneuvers, tidal volume of 6 ml.kg−1, and PEEP of 12 cm H2O) was compared with conventional ventilation (no recruitment maneuvers, tidal volume 10 ml.kg−1, and zero end-expiratory pressure) with regard to oxygenation, respiratory system mechanics, and hemodynamic stability, and their result was that lung recruitment strategy in elderly patients is well tolerated and improves intraoperative oxygenation as well as lung mechanics during laparotomy.

The above findings of our study show that the use of either PEEP or IRM prevents a decrease in Cstat in long-duration surgery under general anesthesia.

Limitations of the study

We understand that the sample sizes were small and so we suggest that larger, multicentric studies might be conducted to confirm the findings of the present study.

CONCLUSIONS

From the findings of this study, we may conclude that the decline in pulmonary functions (P/F ratio and compliance) that occurs during laparotomies of prolonged duration under general anesthesia can be prevented effectively by application of PEEP, and whenever application of PEEP is not feasible due to patient's hemodynamic compromise or due to nature of surgery (as in neurosurgical patients), intermittent recruitment maneuver may be instituted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.