ABSTRACT
Background:
Evaluation of the efficacy and safety of mechanical ventilation settings is a cornerstone of the early phase of the management of acute respiratory distress syndrome (ARDS). This study aimed to evaluate the adherence to currently recommended lung-protective ventilator strategies (tidal volume, plateau pressure, driving pressure, prone positioning, and positive end-expiratory pressure [PEEP]) for adults with moderate-to-severe ARDS in a tertiary care setup, thereby evaluating if lung-protective ventilation is associated with improved outcomes.
Methods:
This was an observational study over 1 year in ventilated moderate-to-severe ARDS participants. All participants were mechanically ventilated when required using the protocol followed by the ARDS Network low-tidal volume lung-protective ventilation strategy and monitored.
Results:
The total number of participants in the study was 32. Septic shock was the most common cause of ARDS. The mean duration of intensive care unit (ICU) stay was 6.13 (±5.4) days, mean ventilator days were 3.66 (±3.75) days and mortality rate of 71.8%.Adherence to low-tidal volume was 78.12% with an improvement of 36% in the adherent group (P = 0.06). Adherence to high PEEP was 34.38% with a survival of 73% in the adherent group (P = 0.0004). Adherence to prone ventilation was 18.75% with a survival of 33% in the adherent group (P = 0.7).
Conclusion:
Intensivists should take an extra effort to focus on evidence-based ventilator strategies and increase adherence to these recommendations in their ICUs to improve patient survival.
Key Words: Acute respiratory distress syndrome, intensive care units, mechanical ventilation
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is a type of lung injury associated with an elevated overall incidence and with a high attributable mortality ranging from 40% to 60%.[1] Providing safe mechanical ventilation is the cornerstone of the management of patients with ARDS.[2] There is a large potential for improvement in the management of this patient group, as this syndrome appears to be underrecognized, undertreated, and associated with a high mortality rate.[3] Lung-protective ventilation with lower tidal volumes and airway pressures reduces mortality in moderate-to-severe ARDS.[4-6] The effects of prone positioning, optimal levels of positive end-expiratory pressure (PEEP), and neuromuscular blockade have shown variable results in clinical trials.[7]
The lung-protective ventilator strategies suggest the use of the following parameters: (1) low-tidal volume <6 ml/kg of predicted body weight (PBW),[2,5] (2) high PEEP >5 cm of water,[2] (3) plateau pressure (Pplat) <30 cm of water,[2,5] (4) driving pressure <15 cm of water,[8] (5) ARDS net protocol of either low FIO2 with high PEEP or high FIO2 with low PEEP,[5] and (6) prone position ventilation for a 12–24-h stabilization period.[2,9]
Lung-protective strategies traditionally use low-tidal volume (<6 ml/kg of PBW) and low Pplat (<30 cm of water) with or without high PEEP to achieve this goal.[5] Such lung-protective ventilation strategies are associated with limited driving pressure. Among all ventilator variables, driving pressure best predicted survival in patients with ARDS.[8] There is growing evidence that if lung-protective ventilation is applied, even to healthy lungs at the onset of mechanical ventilation, before the recognized development of lung injury, it is associated with improved patient outcomes. This leads to reduced incidence of pulmonary complications and shorter period of mechanical ventilation, in addition to decreased duration of plasma cytokine production.[10,11] A multicenter audit done in the UK stated that the overall adherence with low-tidal volume ventilation was reported to be in only 34% of the ventilated participants.[12]
Our study aimed to evaluate the degree of adherence with currently recommended lung-protective ventilator strategies (tidal volume, Pplat, driving pressure, prone positioning, and PEEP) in adult patients with moderate-to-severe ARDS admitted to a tertiary care setup in India over 1 year. Thereby evaluating the impact of the adherence and if lung-protective ventilation is associated with improved outcomes in patients with ARDS.
METHODS
Study method and ethical clearance
This study was a prospective, observational study conducted in the adult intensive care unit of P. D. Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, India, between July 1, 2017, and June 30, 2018. The study was carried out after obtaining approval from the institutional ethics committee and written consent from either the participants or their legally accepted representatives. Details and purpose of the study were disclosed. The manuscript adheres to the STROBE guideline. Participants with a confirmed diagnosis of moderate-to-severe ARDS were identified and enrolled. The diagnosis of ARDS was established according to Berlin’s definition of ARDS.[13]
The etiology and severity of ARDS were decided based on medical history, physical examination, cardiac evaluation (electrocardiography and two-dimensional [2D] echocardiography), routine radiology, biochemical, microbiological investigations, and arterial blood gas analysis. Causes of ARDS were categorized as community-acquired pneumonia, septic shock (other than pneumonia), and other causes, as lung infections form a significant proportion of the ARDS etiology. The other causes encompassed tropical infection, trauma, pancreatitis, and aspiration pneumonia. From the available variables, Simplified Acute Physiology Score II (SAPS II) was calculated to assess the severity of illness within 24 h of admission. All participants were mechanically ventilated when required using the protocol followed by the ARDS Network lung-protective ventilation strategy.[5]
All the variables were recorded on intensive care unit (ICU) admission and thereafter every 8 h. Day 0 was defined as the start of mechanical ventilation. This included tidal volume (ml/kg), respiratory rate, minute ventilation (l/min), peak pressure (Ppeak), Pplat, PEEP and any complication associated with ventilation were recorded. P: F ratio (also called PaO2:FIO2 ratio) – which is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FIO2 expressed as a fraction) and I: E ratio (ratio of the duration of inspiratory and expiratory phases) were also documented. The application of prone ventilation was documented. Participants were monitored throughout illness in the ICU and their outcomes were evaluated in terms of length of ICU stay, duration of mechanical ventilation, and ICU mortality. Participants with missing data points were not to be included in the final analysis.
The inclusion criteria were adults (aged 18 years and above), mechanically ventilated participants in ICU fulfilling criteria for moderate-to-severe ARDS according to Berlin definition.[13] The exclusion criteria were all participants with cardiac causes of respiratory failure (ruled out by history and echocardiography findings), participants with preexisting pulmonary disease (e.g. chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis), immunocompromised patients, and patients with a do not resuscitate status on admission.
Statistical analysis
The data were collected using Microsoft Excel® 2010 (Microsoft Corp., Redmond, USA) and analysis was done using the program SSPS version 20.0 (SPSS, Inc., Chicago, IL, USA). Continuous variables were expressed as mean (standard deviation), standard error of the mean (SEM), and ranges, and categorical variables were expressed as numbers and percentages. The association between categorical variables with age and discharged status was assessed using the Chi-Square test or Fisher’s exact test as appropriate. A P < 0.05 was considered statistically significant in the study.
RESULTS
The number of eligible participants with a diagnosis of moderate-to-severe ARDS requiring mechanical ventilation during the study was 32. No participants were excluded, and thus, 32 were included in the final analysis. Out of this, 56% were male and the average age of the study population was 54 years. Septic shock (other than pneumonia) was the most common cause of ARDS (46.8%) followed by community-acquired pneumonia (25%), tropical infection (15.63%), trauma (6.25%), pancreatitis (3.13%), and aspiration pneumonia (3.13%). The mean duration of ICU stay was 6.13 (±5.4) days (SEM = 0.97), mean ventilator days were 3.66 (±3.75) days (SEM = 0.66), and mortality rate of 71.8% [Table 1]. Adherence to mechanical ventilation with low-tidal volume was observed in 78.12% of the study population, which was associated with an improved outcome in 36% of the group where a tidal volume of 6ml/kg of PBW was adhered to (P = 0.06). There were no survivors in the group where low-tidal volume mechanical ventilation was not adhered to [Table 2 and Figure 1]. Adherence with high PEEP was 34.38% with a survival of 73% in the study population where recommended PEEP was followed (P = 0.0004). Nonadherence to recommended PEEP was seen in 65.62% of the study population and this was associated with 5% survival [Table 2 and Figure 2]. Similarly, adherence to Pplat below 30 cm H2O was 75% which was associated with survival in 38% of the adherent group (P = 0.04). All participants in whom Pplat below 30 cm H2O was not adhered to expired [Table 2 and Figure 3]. Adherence to driving pressure less than 15 cm H2O was achieved in 34.38% of the study population with a survival of 72% in the adherent group (P = 0.0004) [Table 2 and Figure 4]. Adherence with prone ventilation was 18.75% with favorable outcome of 33% in the adherent group (P = 0.7). Nonadherence with prone ventilation was 81.25% with a survival of 27% [Table 2 and Figure 5]. The SAPS II score on admission showed a positive correlation with mortality, i.e. higher scores had higher mortality rates [Figure 6]. All participants with a SAPS II score of 37 and above (SAPS II score range: 0–163) did not survive.
Table 1.
Study population, intensive care unit stay, and cause of acute respiratory distress syndrome
| Variable | Observation |
|---|---|
| Average age (SEM) | 54±20.95 years (SEM=3.7) (study population range: 18–84 yearsw) |
| Sex (%) | 56 males, 44 females |
| Simplified Acute Physiology Score II (score range: 0–163) | Study mean score: 49.09±9.7 (SEM=1.7) (study population score range: 27–74) |
| Mean duration of ICU stay | 6.13±5.48 days (SEM=0.97) |
| Mean duration of mechanical ventilation | 3.66±3.75 days (SEM=0.66) |
| Mean duration of ventilator-free days | 2.47±3.7 days (SEM=0.42) |
| Mortality rate (%) | 71.8 |
| Cause of ARDS, number of patients (%) | |
| Septic shock (other than pneumonia) | 15 (46.88) |
| Community-acquired pneumonia | 8 (25) |
| Tropical infection | 5 (15.63) |
| Trauma | 2 (6.25) |
| Pancreatitis | 1 (3.13) |
| Aspiration pneumonia | 1 (3.13) |
SEM: Standard error of mean, ICU: Intensive care unit, ARDS: Acute respiratory distress syndrome
Table 2.
Adherence with lung-protective strategies for respective parameters and survival
| Parameter | Adherence with lung-protective strategies (%) | Survival in adherent population (%) | Survival in nonadherent population (%) | P | |
|---|---|---|---|---|---|
|
| |||||
| Yes | No | ||||
| Tidal volume | 78.12 | 21.88 | 36 | 0 | 0.06 |
| PEEP | 34.38 | 65.62 | 73 | 5 | 0.0004 |
| Pplat | 75 | 25 | 38 | 0 | 0.04 |
| Driving pressure | 34.38 | 65.62 | 72 | 5 | 0.0004 |
| Prone position | 18.75 | 81.25 | 33 | 27 | 0.7 |
PEEP: Positive end-expiratory pressure, Pplat: Plateau pressure
Figure 1.
Tidal volume – overall adherence and outcome
Figure 2.
PEEP – overall adherence and outcome. PEEP: Positive end-expiratory pressure
Figure 3.
Pplat – overall adherence and outcome Pplat: Plateau pressure
Figure 4.
Driving pressure – overall adherence and outcome
Figure 5.
Prone ventilation – overall adherence and outcome
Figure 6.
SAPS II versus Percentage of predicted mortality. SAPS II: Simplified Acute Physiology Score II
DISCUSSION
Ware and Matthay stated in their study that tropical infections (malaria and dengue), viral infections (H1N1), and septic shock were found to be most commonly associated with ARDS in India, followed by pneumonia, urinary tract infections, and pancreatitis.[14] A similar trend was observed in our study population wherein septic shock was the most common cause of ARDS followed by pneumonia.
It has been shown in various studies that only 25% of participants have a mild form of ARDS, whereas the predominant manifestation in the remaining 75% is a moderate or severe form.[1,15] Hospital mortality was about 40% and reached 45% in participants presenting with severe ARDS.[3,16,17] As far as Indian data are concerned, two studies conducted in tertiary care hospitals found the mortality rate to be around 57%.[18,19] Our hospital is a tertiary referral care center which had a large number of participants who presented in rapidly deteriorating hemodynamic condition with advanced severe illness and hence probably had a higher mortality (71.8%) than international standards. This is also explained by the highly correlated SAPS II score and low mean duration of ICU stay and mechanical ventilation.
A completely “safe” ventilation strategy does not exist for all; therefore, the support must be tailored to individual patients, based on their hemodynamics, gas exchange, and lung recruitment.[1] Ventilation strategies such as lung-protective ventilation using low-tidal volume and high PEEP have shown mortality benefits.[4] The approach of ventilating a patient in prone position has demonstrated a mortality benefit which can largely be credited to the PROSEVA (proning severe ARDS patients) trial which was not seen in the earlier studies.[9] Other treatment options which include a fluid conservative strategy and glucocorticoids were not found beneficial in various studies.[20,21]
Our study showed, as displayed in Table 2 and Figures 1-5, that there was a better trend toward targeting low-tidal volume ventilation and Pplat less than 30 cm H2O for the study population, but appropriate driving pressure and PEEP targets were achieved to a lesser extent in view of the patient’s hemodynamic conditions and refractory shock. Prone positioning was not given to most participants in our study in the background of hemodynamic instability which would explain the low level of adherence.
In addition, our study also states that adherence with driving pressures, Pplat below 30 cm H2O and high PEEP showed a statistically significant survival benefit than adherence with low-tidal volume and prone positioning, which showed a statistically less significant benefit, as shown in Table 2.
A study done by Bellani et al. called the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was comparable to our study. The authors showed that the ventilator strategies adopted for participants with ARDS most often did not adhere to the recommendations for lung-protective ventilation made by the ARDS Network. Pplat was measured only in 40% of ARDS participants and there was a lack of correlation between PEEP and PaO2/FIO2 ratio. Prone positioning was given to only 8% of participants and more so as a form of salvage therapy.[3]
An ancillary study of LUNG SAFE has shown that Pplat strongly and positively correlated with mortality.[22] In practical terms, it would be best to first measure and limit Pplat, an approach which the LUNG SAFE study has clearly shown is insufficiently used. Sometimes, it is not possible to provide the recommended PEEP as per the PaO2:FIO2 ratio due to severely altered lung compliance. Under such circumstances, it may be useful to reduce the driving pressure by further limiting the tidal volume while simultaneously increasing the PEEP. This maneuver may be successful if the patient continues to remain hemodynamically stable and tolerates a high level of PEEP.[23]
Multilevel median analysis of ARDS participants enrolled in nine previously reported randomized studies was done by Amato et al. who found that among various ventilation variables, decrease in driving pressure owing to ventilator setting was strongly associated with increased survival reported at 60 days. Driving pressure of more than 15 cm of water was associated with a higher mortality and an increased risk of pneumothorax.[8]
The use of an excessive tidal volume in mechanically ventilated participants increases the risk of developing ARDS, while the exposure to high tidal volumes in participants with established ARDS increases mortality.[1] Meta-analyses of tidal volume reduction have often included rather heterogeneous studies.[24,25] The use of lower tidal volumes in participants with severe ARDS may involve potentially confounding effects, which are difficult to analyze completely in purely observational data. In all analyses, however, the pressures (Ppeak, Pplat, driving pressure, and PEEP) carried more significant weight than tidal volume in the prognosis which was observed in our study as well.[22] None of the participants in our study developed complications such as pneumothorax or accidental extubation.
The limitations of our study were that our study population and duration were small. Our evaluation on admission did not include assessment of the participant’s preillness functional status or Charlson Comorbidity Index. The number of participants ventilated in the prone position was few and the delayed referrals to our tertiary care center attributed to increased mortality, low duration of mechanical ventilation, and ICU stay for moderate-to-severe ARDS patients. As this was a pre-COVID-19 study, the information derived may not be applicable to patients with COVID ARDS and warrants further studies.
CONCLUSION
Adherence with recommended ARDS lung-protective strategies is associated with improved survival. Ventilator strategies and protocols should focus toward increasing adherence to the current recommendations. Intensivists should take an extra effort to focus on evidence-based ventilator strategies and increase adherence to these recommendations in their ICUs to improve patient survival.
Research quality and ethics statement
This study was approved by the Institutional Review Board/Ethics Committee at P. D. Hinduja Hospital and Medical Research Center (Approval #1014 16 SiSi; Approval date April 1, 2017). The authors followed the applicable EQUATOR Network (http://www.equator- network.org/) guidelines, specifically the STROBE Guidelines, during the conduct of this research project.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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