Elucidating the fuzziness in physician decision making in ARDS.
ABSTRACT: The current standard of care for patients suffering from acute respiratory distress syndrome (ARDS) is ventilation with a tidal volume of 6 ml/kg predicted body weight (PBW), but variability remains in the tidal volumes that are actually used. This study aims to identify patient scenarios for which there is discordance between physicians in choice of tidal volume and positive end-expiratory pressure (PEEP) in ARDS patients. We developed an algorithm based on fuzzy logic for encapsulating the expertise of individual physicians regarding their use of tidal volume and PEEP in ARDS patients. The algorithm uses three input measurements: (1) peak airway pressure (PAP), (2) PEEP, and (3) arterial oxygen saturation (SaO?). It then generates two output parameters: (1) the deviation of tidal volume from 6 ml/kg PBW, and (2) the change in PEEP from its current value. We captured 6 realizations of intensivist expertise in this algorithm and assessed their degree of concordance using a Monte Carlo simulation. Variability in the tidal volume recommended by the algorithm increased for PAP > 30 cmH?O and PEEP > 5 cmH?O. Tidal volume variability decreased for SaO? > 90 %. Variability in the recommended change in PEEP increased for PEEP > 5 cmH?O and for SaO? near 90 %. Intensivists vary in their management of ARDS patients when peak airway pressures and PEEP are high, suggesting that the current goal of 6 ml/kg PBW may need to be revisited under these conditions.
Project description:<h4>Background</h4>Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients.<h4>Methods</h4>This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1-15, 2002 (SOAP study, n = 3147), and May 8-18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO<sub>2</sub> corresponding to the most abnormal value of arterial PO<sub>2</sub> were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days.<h4>Results</h4>The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1-7) days after admission in SOAP and 2 (1-6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH<sub>2</sub>O) and driving pressure (> 14 cmH<sub>2</sub>O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death.<h4>Conclusion</h4>The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH<sub>2</sub>O and driving pressure > 14 cmH<sub>2</sub>O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.
Project description:The current ventilatory care goal for acute respiratory distress syndrome (ARDS) and the only evidence-based approach for managing ARDS is to ventilate with a tidal volume (VT) of 6 mL/kg predicted body weight (PBW). However, it is not uncommon for some caregivers to feel inclined to deviate from this strategy for one reason or another. To accommodate this inclination in a rationalized manner, we previously developed an algorithm that allows for VT to depart from 6 mL/kg PBW based on physiological criteria. The goal of the present study was to test the feasibility of this algorithm in a small retrospective study.Current values of peak airway pressure, positive end-expiratory pressure (PEEP), and arterial oxygen saturation are used in a fuzzy logic algorithm to decide how much VT should differ from 6 mL/kg PBW and how much PEEP should change from its current setting. We retrospectively tested the predictions of the algorithm against 26 cases of decision making in 17 patients with ARDS.Differences between algorithm and physician VT decisions were within 2.5 mL/kg PBW, except in 1 of 26 cases, and differences between PEEP decisions were within 2.5 cm H2O, except in 3 of 26 cases. The algorithm was consistently more conservative than physicians in changing VT but was slightly less conservative when changing PEEP.Within the limits imposed by a small retrospective study, we conclude that our fuzzy logic algorithm makes sensible decisions while at the same time keeping practice close to the current ventilatory care goal.
Project description:<h4>Background</h4>Chest wall loading has been shown to paradoxically improve respiratory system compliance (C<sub>RS</sub>) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The most likely, albeit unconfirmed, mechanism is relief of end-tidal overdistension in 'baby lungs' of low-capacity. The purpose of this study was to define how small changes of tidal volume (V<sub>T</sub>) and positive end-expiratory pressure (PEEP) affect C<sub>RS</sub> (and its associated airway pressures) in patients with ARDS who demonstrate a paradoxical response to chest wall loading. We hypothesized that small reductions of V<sub>T</sub> or PEEP would alleviate overdistension and favorably affect C<sub>RS</sub> and conversely, that small increases of V<sub>T</sub> or PEEP would worsen C<sub>RS</sub>.<h4>Methods</h4>Prospective, multi-center physiologic study of seventeen patients with moderate to severe ARDS who demonstrated paradoxical responses to chest wall loading. All patients received mechanical ventilation in volume control mode and were passively ventilated. Airway pressures were measured before and after decreasing/increasing V<sub>T</sub> by 1 ml/kg predicted body weight and decreasing/increasing PEEP by 2.5 cmH<sub>2</sub>O.<h4>Results</h4>Decreasing either V<sub>T</sub> or PEEP improved C<sub>RS</sub> in all patients. Driving pressure (DP) decreased by a mean of 4.9 cmH<sub>2</sub>O (supine) and by 4.3 cmH<sub>2</sub>O (prone) after decreasing V<sub>T</sub>, and by a mean of 2.9 cmH<sub>2</sub>O (supine) and 2.2 cmH<sub>2</sub>O (prone) after decreasing PEEP. C<sub>RS</sub> increased by a mean of 3.1 ml/cmH<sub>2</sub>O (supine) and by 2.5 ml/cmH<sub>2</sub>O (prone) after decreasing V<sub>T.</sub> C<sub>RS</sub> increased by a mean of 5.2 ml/cmH<sub>2</sub>O (supine) and 3.6 ml/cmH<sub>2</sub>O (prone) after decreasing PEEP (P < 0.01 for all). Small increments of either V<sub>T</sub> or PEEP worsened C<sub>RS</sub> in the majority of patients.<h4>Conclusion</h4>Patients with a paradoxical response to chest wall loading demonstrate uniform improvement in both DP and C<sub>RS</sub> following a reduction in either V<sub>T</sub> or PEEP, findings in keeping with prior evidence suggesting its presence is a sign of end-tidal overdistension. The presence of 'paradox' should prompt re-evaluation of modifiable determinants of end-tidal overdistension, including V<sub>T</sub>, PEEP, and body position.
Project description:<h4>Background</h4>In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).<h4>Methods</h4>IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO<sub>2</sub>/FiO<sub>2</sub> ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH<sub>2</sub>O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH<sub>2</sub>O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH<sub>2</sub>O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH<sub>2</sub>O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.<h4>Discussion</h4>The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.<h4>Trial registration</h4>ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.
Project description:<h4>Introduction</h4>Lung-protective ventilation aims at using low tidal volumes (VT) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of VT and PEEP on ventilation distribution, regional respiratory system compliance (C(RS)), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation.<h4>Methods</h4>EIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight VT and 5 cmH2O PEEP. After ALI induction, 10 ml/kg VT and 10 cmH2O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high VT ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional C(RS) and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high VT ventilation (6 and 10 (8) ml/kg) at three PEEP levels.<h4>Results</h4>In healthy animals, high compared to low VT increased C(RS) and ventilation in dependent lung regions implying tidal recruitment. ALI reduced C(RS) and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH2O (mean±SD) resulted in comparable increase in C(RS) in dependent and decrease in non-dependent regions at both VT. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of VT. In patients, regional C(RS) differences between low and high VT revealed high degree of tidal recruitment and low overinflation at 3±1 cmH2O PEEP. Tidal recruitment decreased at 10±1 cmH2O and was further reduced at 15±2 cmH(2)O PEEP.<h4>Conclusions</h4>Tidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional C(RS).
Project description:The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was suggested to be unreliable in low tidal volume (VT) ventilation. However, high PEEP can cause ARDS patients relatively hypovolemic and more fluid responsive. We hypothesized that high PEEP 15 cmH<sub>2</sub>O can offset the disadvantage of low VT and improve the predictive performance of PPV. We prospectively enrolled 27 hypovolemic ARDS patients ventilated with low VT 6 ml/kg and three levels of PEEP (5, 10, 15 cmH<sub>2</sub>O) randomly. Each stage lasted for at least 5 min to allow for equilibration of hemodynamics and pulmonary mechanics. Then, fluid expansion was given with 500 ml hydroxyethyl starch (Voluven 130/70). The hemodynamics and PPV were automatically measured with a PiCCO2 monitor. The PPV values were significantly higher during PEEP15 than those during PEEP5 and PEEP10. PPV during PEEP15 precisely predicts fluid responsiveness with a cutoff value 8.8% and AUC (area under the ROC curve) of ROC (receiver operating characteristic curve) 0.847, higher than the AUC during PEEP5 (0.81) and PEEP10 (0.668). Normalizing PPV with driving pressure (PPV/Driving-P) increased the AUC of PPV to 0.875 during PEEP15. In conclusions, high PEEP 15 cmH<sub>2</sub>O can counteract the drawback of low VT and preserve the predicting accuracy of PPV in ARDS patients.
Project description:<h4>Background</h4>Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes.<h4>Methods</h4>Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH<sub>2</sub>O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO<sub>2</sub>/FiO<sub>2</sub>, FiO<sub>2</sub>, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study.<h4>Results</h4>Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO<sub>2</sub>/FiO<sub>2</sub> in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH<sub>2</sub>O [32-52] vs. 36 ml/cmH<sub>2</sub>O [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO<sub>2</sub>/FiO<sub>2</sub> was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO<sub>2</sub>/FiO<sub>2</sub> in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP.<h4>Conclusions</h4>Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.
Project description:Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1?+ or 1?-); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2?+ or 2?-); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP?>?5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.
Project description:<h4>Background</h4>We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH<sub>2</sub>O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO<sub>2</sub> table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients.<h4>Methods</h4>Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO<sub>2</sub>/FiO<sub>2</sub> 113 [79-158] mmHg and PEEP 10 [10-10] cmH<sub>2</sub>O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH<sub>2</sub>O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO<sub>2</sub> table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected.<h4>Results</h4>At 15 cmH<sub>2</sub>O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH<sub>2</sub>O. The PaO<sub>2</sub>/FiO<sub>2</sub>, arterial carbon dioxide and ventilatory ratio increased at 15 cmH<sub>2</sub>O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH<sub>2</sub>O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH<sub>2</sub>O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH<sub>2</sub>O. The empirical PEEP significantly increased the PaO<sub>2</sub>/FiO<sub>2</sub> but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH<sub>2</sub>O of PEEP.<h4>Conclusions</h4>In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.
Project description:We describe the practice of ventilation and mortality rates in invasively ventilated normal-weight (18.5 ≤ BMI ≤ 24.9 kg/m<sup>2</sup>), overweight (25.0 ≤ BMI ≤ 29.9 kg/m<sup>2</sup>), and obese (BMI > 30 kg/m<sup>2</sup>) COVID-19 ARDS patients in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. The primary outcome was a combination of ventilation variables and parameters over the first four calendar days of ventilation, including tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure in normal-weight, overweight, and obese patients. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and mortality rates. Between 1 March 2020 and 1 June 2020, 1122 patients were included in the study: 244 (21.3%) normal-weight patients, 531 (47.3%) overweight patients, and 324 (28.8%) obese patients. Most patients received a tidal volume < 8 mL/kg PBW; only on the first day was the tidal volume higher in obese patients. PEEP and driving pressure were higher, and compliance of the respiratory system was lower in obese patients on all four days. Adjunctive therapies for refractory hypoxemia were used equally in the three BMI groups. Adjusted mortality rates were not different between BMI categories. The findings of this study suggest that lung-protective ventilation with a lower tidal volume and prone positioning is similarly feasible in normal-weight, overweight, and obese patients with ARDS related to COVID-19. A patient's BMI should not be used in decisions to forgo or proceed with invasive ventilation.