Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis

Purpose

Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials.

Methods

Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤8 ml/kg PBW) mean baseline tidal volume was planned a priori.

Results

Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95 % CI 0.68–1.02; p = 0.073; I ²  = 64 %). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95 % CI 0.50–0.86; p = 0.002; I ²  = 25 %). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis.

Conclusions

Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume.     

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study

Introduction

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

Aim

This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

Methods

The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st–3rd quartiles).

Results

Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16–23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO₂/F_IO₂ increased from 101 (76–136) to 171 (118–220) mmHg (P = 0.0001) driving pressure decreased from 14 [11–17] to 13 [10–16] cmH₂O (P = 0.001), and Pplat decreased from 26 [23–29] to 25 [23–28] cmH₂O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

Conclusions

In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

     

Effects of hydroxyethyl starch in subgroups of patients with severe sepsis: exploratory post-hoc analyses of a randomised trial

Purpose

It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.

Methods

This was a post-hoc, subgroup analysis of all 798 patients with severe sepsis randomised in the 6S trial according to time from ICU admission to randomisation, surgery and fluids given prior to randomisation and markers of shock at randomisation. Intervention effects estimated as risk ratios were analysed between the HES versus Ringer’s acetate groups to detect subgroup heterogeneity of the effects on 90-day mortality. Multiple logistic regression was used to adjust for risk factors.

Results

Most baseline characteristics were comparable between the HES and Ringer’s acetate groups in the different subgroups. There was no heterogeneity in the intervention effect on 90-day mortality in the following subgroups: randomisation earlier than 4 h after ICU admission versus later (test of interaction P = 0.85), surgery versus no surgery (P = 0.42), colloids given versus not given (P = 0.57), <2 l of crystalloids given prior to randomisation vs. >2 l (P = 0.88) or plasma lactate >4 mmol/l versus <4 mmol/l (P = 0.54), hypotension versus no hypotension (P = 0.32) or use of vasopressor or inotropic agents at randomisation versus no use (P = 0.10).

Conclusions

The increased 90-day mortality observed in patients with severe sepsis resuscitated with HES 130/0.42 did not appear to depend on time course, surgery or fluids given prior to randomisation or on markers of shock at randomisation. As the analyses were planned post hoc and their power is reduced, the results should be interpreted with caution.     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

Prone positioning in hypoxemic respiratory failure: Meta-analysis of randomized controlled trials

Purpose

Prone positioning is used to improve oxygenation in patients with hypoxemic respiratory failure (HRF). However, its role in clinical practice is not yet clearly defined. The aim of this meta-analysis was to assess the effect of prone positioning on relevant clinical outcomes, such as intensive care unit (ICU) and hospital mortality, days of mechanical ventilation, length of stay, incidence of ventilator-associated pneumonia (VAP) and pneumothorax, and associated complications.

Methods

We used literature search of MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials. We focused only on randomized controlled trials reporting clinical outcomes in adult patients with HRF. Four trials met our inclusion criteria, including 662 patients randomized to prone ventilation and 609 patients to supine ventilation.

Results

The pooled odds ratio (OR) for the ICU mortality in the intention-to-treat analysis was 0.97 (95% confidence interval [CI], 0.77-1.22), for the comparison between prone and supine ventilated patients. Interestingly, the pooled OR for the ICU mortality in the selected group of the more severely ill patients favored prone positioning (OR, 0.34; 95% CI, 0.18-0.66). The duration of mechanical ventilation and the incidence of pneumothorax were not different between the 2 groups. The incidence of VAP was lower but not statistically significant in patients treated with prone positioning (OR, 0.81; 95% CI, 0.61-1.10). However, prone positioning was associated with a higher risk of pressure sores (OR, 1.49; 95% CI, 1.17-1.89) and a trend for more complications related to the endotracheal tube (OR, 1.30; 95% CI, 0.94-1.80).

Conclusions

Despite the inherent limitations of the meta-analytic approach, it seems that prone positioning has no discernible effect on mortality in patients with HRF. It may decrease the incidence of VAP at the expense of more pressure sores and complications related to the endotracheal tube. However, a subgroup of the most severely ill patients may benefit most from this intervention.     

Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses

Purpose

Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.

Methods

We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.

Results

We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)—44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.

Conclusions

There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses.     

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

Purpose

To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.

Main outcomes

We included 1899 patients with ARDS in this study. The relationship between maximum PaCO₂ in the first 48 h and mortality suggests higher mortality at or above PaCO₂ of ≥50 mmHg. Patients with severe hypercapnia (PaCO₂ ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO₂/FiO₂ ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).

Conclusions

Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.

Trial registration

Clinicaltrials.gov identifier, NCT01093482.

     

High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation

OBJECTIVE: The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High-frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position. DESIGN: Prospective, comparative randomized study. SETTING: A medical intensive care unit. PATIENTS: Forty-three ARDS patients with a Pao2/Fio2 ratio <150 at positive end-expiratory pressure > or =5 cm H2O. INTERVENTIONS: After an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (CV(prone)-CV(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CV(supine)-HFOV(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CV(prone)-HFOV(supine) group). MEASUREMENTS AND MAIN RESULTS: Pao2/Fio2 ratio was higher at the end of the study period in the CV(prone)-HFOV(supine) group than in the CV(prone)-CV(supine) group (p < .02). Venous admixture at the end of the study period was lower in the CV(prone)-HFOV(supine) group than in the two other groups. CONCLUSIONS: HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.     

Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

Purpose

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.

Methods

Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.

Results

Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10^?4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10^?3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10^?5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10^?3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10^?3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10^?3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313).

Conclusions

Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

     

Extended prone position ventilation in severe acute respiratory distress syndrome: A pilot feasibility study

Objectives

The aim of the study was to evaluate the safety of extended prone position ventilation (PPV) and its impact on respiratory function in patients with severe acute respiratory distress syndrome (ARDS).

Design

This was a prospective interventional study.

Setting

Patients were recruited from a mixed medical-surgical intensive care unit in a university hospital.

Patients

Fifteen consecutive patients with severe ARDS, previously unresponsive to positive end-expiratory pressure adjustment, were treated with PPV.

Intervention

Prone position ventilation for 48 hours or until the oxygenation index was 10 or less (extended PPV).

Results

The elapsed time from the initiation of mechanical ventilation to pronation was 35 ± 11 hours. Prone position ventilation was continuously maintained for 55 ± 7 hours. Two patients developed grade II pressure ulcers of small extent. None of the patients experienced life-threatening complications or hemodynamic instability during the procedure. The patients showed a statistically significant improvement in Pao₂/Fio₂ (92 ± 12 vs 227 ± 43, P < .0001) and oxygenation index (22 ± 5 vs 8 ± 2, P < .0001), reduction of PaCo₂ (54 ± 9 vs 39 ± 4, P < .0001) and plateau pressure (32 ± 2 vs 27 ± 3, P < .0001), and increment of the static compliance (21 ± 3 vs 37 ± 6, P < .0001) with extended PPV. All the parameters continued to improve significantly while they remained in prone position and did not change upon returning the patients to the supine position.

Conclusions

The results obtained suggest that extended PPV is safe and effective in patients with severe ARDS when it is carried out by a trained staff and within an established protocol. Extended PPV is emerging as an effective therapy in the rescue of patients from severe ARDS.     

Pressure ulcers in patients with COVID-19 acute respiratory distress syndrome undergoing prone positioning in the intensive care unit: A pre- and post-intervention study

Background

Prone positioning has been widely used to improve oxygenation and reduce ventilator-induced lung injury in patients with severe COVID-19 acute respiratory distress syndrome (ARDS). One major complication associated with prone positioning is the development of pressure ulcers (PUs).

Aim

This study aimed to determine the impact of a prevention care bundle on the incidence of PUs in patients with COVID-19 ARDS undergoing prone positioning in the intensive care unit.

Study Design

This was a single-centre pre and post-test intervention study which adheres to the Standards for Reporting Implementation Studies (StaRI) guidelines. The intervention included a care bundle addressing the following: increasing frequency of head turns, use of an open gel head ring, application of prophylactic dressings to bony prominences, use of a pressure redistribution air mattress, education of staff in the early identification of evolving PUs through regular and rigorous skin inspection and engaging in bedside training sessions with nursing and medical staff. The primary outcome of interest was the incidence of PU development. The secondary outcomes of interest were severity of PU development and the anatomical location of the PUs.

Results

In the pre-intervention study, 20 patients were included and 80% (n = 16) of these patients developed PUs, comprising 34 ulcers in total. In the post-intervention study, a further 20 patients were included and 60% (n = 12) of these patients developed PUs, comprising 32 ulcers in total. This marks a 25% reduction in the number of patients developing a PU, and a 6% decrease in the total number of PUs observed. Grade II PUs were the most prevalent in both study groups (65%, n = 22; 88%, n = 28, respectively). In the post-intervention study, there was a reduction in the incidence of grade III and deep tissue injuries (pre-intervention 6%, n = 2 grade III, 6% n = 2 deep tissue injuries; post-intervention no grade III ulcers, grade IV ulcers, or deep tissues injuries were recorded). However, there was an increase in the number of unstageable PUs in the post-intervention group with 6% (n = 2) of PUs being classified as unstageable, meanwhile there were no unstageable PUs in the pre-intervention group. This is an important finding to consider as unstageable PUs can indicate deep tissue damage and therefore need to be considered alongside PUs of a more severe grade (grade III, grade IV, and deep tissue injuries).

Conclusion

The use of a new evidence-based care bundle for the prevention of PUs in the management of patients in the prone position has the potential to reduce the incidence of PU development. Although improvements were observed following alterations to standard practice, further research is needed to validate these findings.

Relevance to Clinical Practice

The use of a new, evidence-based care bundle in the management of patients in the prone position has the potential to reduce the incidence of PUs.     

The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome

Purpose

This study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.

Methods

Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.

Results

Main ARDS etiologies were bacterial (45 %), influenza A[H₁N₁] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively.

Conclusions

The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.     

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital

Purpose

The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition.

Methods

We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO₂/FiO₂ <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion.

Results

During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH₂O and 20 (7.2 %) had PaO₂/FiO₂ ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28.

Conclusions

The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO₂/FiO₂ at study entry was independently associated with mortality.     

Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis

Background

Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe.

Objective

To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO₂)/inspired fraction of oxygen (FiO₂) <100 mmHg] compared with moderate hypoxemia (100 mmHg ≤ PaO₂/FiO₂ ≤ 300 mmHg).

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases (to November 2009) and conference proceedings.

Methods

Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO₂/FiO₂ <100 mmHg. Meta-analyses used study-level random-effects models.

Results

Ten trials (N = 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO₂/FiO₂ <100 mmHg [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74–0.96; p = 0.01; seven trials, N = 555] but not in patients with PaO₂/FiO₂ ≥100 mmHg (RR 1.07, 95% CI 0.93–1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed significantly between subgroups (interaction p = 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO₂/FiO₂ thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27–39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16–1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24–2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02–9.69). There was no statistical between-trial heterogeneity for most clinical outcomes.

Conclusions

Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.     

Knowledge,attitudes, and practice related to the prone positioning of patients among intensive care unit nurses working in COVID-19 units: A cross-sectional study in China

Background

An increasing number of studies persistently demonstrate that prone position ventilation can significantly improve the oxygenation index and blood oxygen saturation for most patients (70–80%) with acute respiratory distress syndrome (ARDS). Studies have also shown that the awake prone position was both safe and effective in helping patients with coronavirus disease 2019 (COVID-19) breathe spontaneously. However, the prone position is not widely adopted when treating patients with COVID-19 or ARDS from other causes. Basic knowledge, positive attitudes, and correct practices among the nursing staff are necessary to increase the use of prone positions, reduce the incidence of complications associated with prone positions, and improve the quality and safety of health care.

Aim

This study aimed to investigate the knowledge, attitudes, and practice of prone positioning of patients among intensive care unit (ICU) nurses working in COVID-19 units and provide suggestions for improvement.

Study design

ICU nurses were recruited from two designated tertiary hospitals for COVID-19 treatment in Shanghai, China, in April 2022, using convenience sampling. A questionnaire survey focusing on the dimensions of knowledge, attitudes, and practice of the prone position with 42 items, was conducted.

Results

A total of 132 ICU nurses participated. The scores on the overall questionnaire and the dimensions of knowledge, attitudes, and practice of prone position were 167.28 (95% CI, 161.70–172.86), 78.35 (95% CI, 76.04–80.66), 32.08 (95% CI, 31.51–32.65), and 56.85 (95% CI, 52.42–61.28) respectively. The overall average score was 79.66% (95% CI, 0.77–0.82). The results of multiple linear regression analysis showed that prior experience in treating patients with COVID-19 and professional titles were related to the level of knowledge, attitudes, and practice of prone position.

Conclusions

The ICU nurses strongly believed in the effectiveness of prone positioning, but their knowledge and practice levels need improvement. The experience in treating patients with COVID-19 and professional titles were related to the level of knowledge, attitudes, and practice of prone position. Nursing managers should ensure that ICU nurses are well trained in prone positioning and help enhance the knowledge and attitudes toward prone positioning to promote its widespread use.

Relevance to clinical practice

Clinical guidelines and in-service training modules need to be developed to promote the use of prone positioning and reduce prone position-related complications.     

Influence of abdominal obesity on multiorgan dysfunction and mortality in acute respiratory distress syndrome patients treated with prone positioning

Purpose

Obesity is a worldwide pandemic, and obese patients face an increased risk of developing acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a frequently used intervention in the treatment of ARDS. There are no data describing the impact of PP on morbidity and mortality in abdominally obese patients. We report our observations in abdominally obese ARDS patients treated with PP.

Materials and methods

Patients with ARDS (n = 82) were retrospectively divided into 2 groups characterized by presence (n = 41) or absence (n = 41) of abdominal obesity as defined by a sagittal abdominal diameter of 26 cm or more.

Results

There was no difference in cumulative time abdominally obese patients were placed in prone position from admission to day 7 (41.0 hours [interquartile range, 50.5 hours] vs 39.5 hours [interquartile range, 61.5 hours]; P = .65) or in overall intensive care unit mortality (34% vs 34%; P = 1). However, abdominally obese patients developed renal failure (83% vs 35%; P < .001) and hypoxic hepatitis (22% vs 2%; P = .015) more frequently. A significant interaction effect between abdominal obesity and prone position with respect to mortality risk (likelihood ratio, P = .0004) was seen if abdominally obese patients were treated with prolonged cumulative PP.

Conclusion

A cautious approach to PP should be considered in abdominally obese patients.     

Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome

Purpose

To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P _L).

Methods

A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P _L and driving pressure, were assessed and compared. Delta P _L (?P _L) was defined as inspiratory P _L minus expiratory P _L.

Results

Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P _L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ?P _L related to NMBA administration.

Conclusions

NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts.

     

Complications of prone positioning in patients with COVID-19: A cross-sectional study

ObjectiveTo determine the prevalence of complications in patients with COVID-19 undergone prone positioning, focusing on the development of prone-related pressure ulcers.MethodsCross-sectional study conducted in the hub COVID-19 centre in Milan (Italy), between March and June 2020. All patients with COVID-19 admitted to intensive care unit on invasive mechanical ventilation and treated with prone positioning were included. Association between prone-related pressure ulcers and selected variables was explored by the means of logistic regression.ResultsA total of 219 proning cycles were performed on 63 patients, aged 57.6 (10.8) and predominantly obese males (66.7%). The main complications recorded were: prone-related pressure ulcers (30.2%), bleeding (25.4%) and medical device displacement (12.7%), even if no unplanned extubation was recorded. The majority of patients (17.5%) experienced bleeding of upper airways. Only 15 prone positioning cycles (6.8%) were interrupted, requiring staff to roll the patient back in the supine position. The likelihood of pressure ulcers development was independently associated with the duration of prone positioning, once adjusting for age, hypoxemic level, and nutritional status (OR 1.9, 95%CI 1.04–3.6).ConclusionThe use of prone positioning in patients with COVID-19 was a safe and feasible treatment, also in obese patients, who might deserve more surveillance and active prevention by intensive care unit staff.     

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting—a prospective, multicenter validation study

Purpose

The PaO₂/FiO₂ is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO₂/FiO₂ calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification.

Methods

We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO₂/FiO₂ ≤ 200. In the derivation cohort (n = 170), we measured PaO₂/FiO₂ with two levels of positive end-expiratory pressure (PEEP) (≥5 and ≥10 cmH₂O) and two levels of FiO₂ (≥0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO₂ response, patients were reclassified into three groups: mild (PaO₂/FiO₂ > 200), moderate (PaO₂/FiO₂ 101–200), and severe (PaO₂/FiO₂ ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282).

Results

The only standard ventilatory setting that identified the three PaO₂/FiO₂ risk categories in the derivation cohort was PEEP ≥ 10 cmH₂O and FiO₂ ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001).

Conclusions

Our method for assessing PaO₂/FiO₂ greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.     

Pediatric ARDS: effect of supine-prone postural changes on oxygenation

OBJECTIVE: To determine the effect of repeated prone positioning (supine-prone/prone-supine) on oxygenation in children suffering from ARDS. DESIGN: Single-center prospective case series. SETTING: University pediatric ICU. PATIENTS: Consecutive pediatric patients with severe ARDS (PaO(2)/FiO(2) <200, Murray score >2.5). INTERVENTIONS: Patients were treated as soon as possible with supine-prone/prone-supine positioning every 8 h until clinical improvement or death occurred. MEASUREMENTS AND RESULTS: Twenty-three patients who had ARDS (0.5-months to 12.6-years-old), were placed in the prone position within 56+/-109 h after the diagnosis of ARDS. Prone-supine/supine-prone postural changes were repeated every 8 h for 9.7+/-5.5 days. Changes in PaO(2)/FiO(2) ratio during supine-prone and prone-supine positioning were evaluated. A positive change was defined as an increase of 15% of baseline value. The patient was classified as a responder when the mean increase in the prone position was greater than 15%. There were 18 responders and five non-responders. The responders showed an increase in PaO(2)/FiO(2) ratio of 22%, from 91+/-33 to 112+/-43 (P <0.001), when they were placed from the supine to the prone position. Their PaO(2)/FiO(2) ratio dropped from 109+/- 37 to 94 +/-36, P = 0.011, when changed from the prone to supine position. The overall mortality rate in this series was 48% (11 patients), which was higher in the non-responders (80%) than in the responders (39%), although this difference was not statistically significant (P = 0.95). CONCLUSIONS: The prone position improves oxygenation in a significant proportion of children with ARDS. Although no statistically significant difference was found for the mortality rate, it was higher for the non-responders (80%) vs the responders (39%).