Authors: Robert Brown, MD; Adeolu Ogunbodede, MD; Megan Donohue, MD; Hannah Goldberg, MD; Erica Bates, MD
Editors: Michael C. Bond, MD FAAEM; Kelly Maurelus, MD FAAEM
Originally Published: Common Sense November/December 2017
An increasing number of ED patients require critical care time and ICU admission.1 The ED length of stay for these patients has increased by 60 minutes and the median boarding time is now over five hours with nearly a third of patients waiting more than 6 hours.[1,2] Mortality of critically ill patients, including mechanically ventilated patients, in the ED correlates with increased ED length of stay. Instead of just making the decision to intubate, ED physicians must now manage ventilators for critical hours. This review discusses some of the risks, best practices, and future directions of ED ventilator management.
Bellani G, Laffey JG et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA: Journal of the American Medical Association, 2016, 315(8), 788-800.
Take home point: Acute Respiratory Distress Syndrome (ARDS) in under-recognized and has a 40% mortality rate.
In this observational prospective cohort study of 12,096 ICU patients from 50 countries, the diagnosis of ARDS was made by a computer algorithm that utilized the Berlin Criteria: (1) presence of acute hypoxemic respiratory failure, (2) which was not the result of cardiac failure, (3) with onset within one week of worsening respiratory symptoms or the initial insult, and (4) bilateral airspace disease on chest X-ray or CT not fully explained by effusions, lobar collapse, or nodules. It compared the algorithmic diagnosis with physicians’ clinical impressions at two points in time: on the first day patients developed hypoxemia and on the day patients exited the study. Investigators were asked to indicate the cause for hypoxemia and then asked if the patient had ARDS at any stage during their ICU stay.
Acute hypoxic respiratory failure developed in 4,499 patients with 3,022 having ARDS according to the algorithm. The majority, 2,813 patients, had ARDS on day 1 or 2. The rate of clinician recognition of ARDS was only 40% for all cases. As would be expected, clinician recognition of ARDS increased with increasing severity of ARDS. The patients who tended to develop the most severe ARDS tended to be the youngest patients (those younger than 16 were excluded). The authors attempted to control for population confounders by sampling from 459 ICUs on five continents, and attempted to control for differing disease processes by enrolling patients during winter months in the respective hemispheres for each hospital.
In conclusion, more important that making the diagnosis of ARDS, is treating all mechanically ventilated patients as having an increased risk of developing ARDS.
Fuller BM, Ferguson IT, et al. Pulmonary/Original research: Lung-protective ventilation initiated in the emergency department (LOV-ED): A quasi-experimental, before-after trial. Annals of Emergency Medicine 2017
Take home point: Despite evidence of a mortality benefit by avoiding supraphysiologic volumes, the adoption of “lung protective” ventilator settings is not yet usual care for all mechanically ventilated patients in the ED. The individual components of lung protective ventilation strategies include low plateau pressure, low tidal volumes, and higher PEEP.[4,5,6]
Since publication of the ARMA trial in 2000, tidal volumes of 12mL/kg ideal body weight have been thought to contribute to ventilator-induced lung injury due to some combination of volutrauma (over-distention of alveoli), barotrauma (high pressure), biotrauma (release of cytokines causing downstream end organ damage), and atelectrauma (opening and closing trauma to alveoli).
Patients who are intubated and mechanically ventilated in the ED are at risk for subsequent development of ARDS and other ventilator-associated complications. Research in other settings has demonstrated reduction in ventilator-associated lung injury with lung protective ventilation strategies. In the quasi-experimental, before-after LOV-ED study, the authors examined a four-part mechanical ventilator protocol that included lung protective tidal volume, positive end expiratory pressure (PEEP) parameters, rapid oxygen weaning, and elevation of the head of the bed for patients being ventilated in the ED.
Initially data was collected on 1,192 adult patients >18 years old who were intubated and mechanically ventilated through an endotracheal tube in the ED. Patients were excluded if they died or were extubated within 24 hours of presentation, had a tracheostomy or baseline long term ventilator requirement, transferred to another facility, or met criteria for ARDS during their ED course. A lung protective ventilator protocol was then implemented by respiratory therapy per the study protocol, which included tidal volumes of 6-8 ml/kg ideal body weight, guidelines for PEEP 5-10 cm H2O, goal plateau pressure <30 cm H2O, and FiO2 titration to goals of 90-95% by pulse oximetry.
After a run-in period, data was collected on 513 consecutive patients who met inclusion criteria. Data included baseline demographics, comorbidities, laboratory values, initial vital signs, APACHE score, indication for ventilation, ventilator settings including airway pressures, ED length of stay, fluid and blood products received, central line placement, antibiotic use, and pressor requirements. Patients were then followed to death or discharge and ventilator settings and fluid balance were recorded for up to two weeks in the ICU. The primary outcomes were ARDS or another ventilator associated condition, which was defined as two days of stable ventilator settings followed by two days of worsening oxygenation requiring increases in FiO2 or PEEP. Hospital mortality and ventilator-, ICU-, or hospital-free days were secondary outcomes.
Several variables were identified as important factors which were unbalanced between the two groups, including illness severity, age, body mass index (BMI), trauma, and sepsis, so a propensity score was developed and outcome analysis was done using a final matched sample of 490 patients in each cohort. Lung protective ventilation in the ED increased by 48.5% in the intervention group, and lung protective ventilation increased 30.7%, while in the ICU (OR 5.1, 95% CI 3.76-6.98). Absolute risk reduction for ARDS or ventilator-associated conditions was 7.1% (OR 0.47, CI 0.3-0.7) and absolute risk reduction for mortality was 14.5% (OR 0.47, CI 0.35-0.63). The intervention group also experienced more ventilator free days (mean difference 3.7, CI 2.3-5.1), ICU free days (2.4, CI 1.0-3.7), and hospital free days (2.4, CI 1.2-3.6).
Strengths of the study include a large sample size, broad inclusion criteria, and applicability to an ED population but it had several limitations. The before-after design and relatively long study period (approximately 52 months pre-intervention, 6-month run-in period, and 18-month intervention period) raise the possibility that uncaptured practice changes over time may have independently influenced care and outcomes. There were also some significant differences between the pre-and-post intervention groups. Even after propensity scores were used, there were differences in the number of patients with congestive heart failure, pulmonary edema, and dialysis dependence. The ventilator study protocol itself included goals for several different ventilator settings, so it is not possible to determine which of these variables contributed to the positive outcomes.
In conclusion, evidence supports implementation of an early lung-protective ventilator protocol in the ED to reduce ventilator related complications, mortality, and length of ICU and hospital stay, but the relative importance of each component of lung protective ventilation has not yet been determined.
Chiumello D, Carlesso E, Brioni M, Cressoni M. Airway driving pressure and lung stress in ARDS patients. Crit Care. 2016;20:276-276.
Amato MB, Meade MO, Slutsky AS, et al. (2015). Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med, 372(8), 747-55.
Take home point: The amount of lung available to ventilate varies not just by ideal body weight but also by disease state. The proportion of lung available for ventilation in ARDS patients is markedly decreased, resulting in lower respiratory-system compliance. A new index measurement of functional lung size may be a better guide for adjusting mechanical ventilation in the ED and beyond.
This study by Chiumello et al. is a prospective and retrospective study of 150 patients with ARDS which measured lung stress, driving pressure (the difference between plateau pressure and PEEP), lung compliance, and chest wall compliance at 5-10 cm H2O of PEEP. Lung gas volume was also measured by one of two ways: a helium dilution technique or whole lung CT scan. Patients were divided into high and low driving pressure groups (above or below 15 cm H2O) and the higher driving pressures were associated with higher mortality and higher evidence of lung stress and elasticity with lower lung volumes. Lung stress was not directly related to tidal volume, even when strictly adhering to lung protective volumes. This study suggests that driving pressure may in fact be a better marker of lung stress and can be used as an adjunct during the management of patients with ARDS.
Amato et al. hypothesized that driving pressure in a mechanically ventilated patient who is not spontaneously breathing gives the best estimate of when we have reached the maximum recruitment of the functional lung volume. They hypothesized that this tidal volume divided by respiratory-system compliance would be more strongly associated with survival than tidal volume or PEEP alone.
To test this hypothesis, data from nine randomized control trials was gathered. Individual data from 3,562 patients with ARDS was analyzed via stepwise multivariate regression modeling and multilevel mediation analysis. The primary outcome was survival in the hospital at 60 days.
The initial survival-prediction model was based on a cohort of 336 patients. This model was then tested and refined from a validation cohort of 861 patients, and retested with a final validation cohort of 2,365 patients. Patient data was classified as either lung protective or control, based on ventilator settings. Patient characteristics, APACHE or SAPS score, PaO2:FiO2 were averaged over the first 24 hours and examined as covariates. Age, APACHE or SAPS score, arterial pH, PaO2:FiO2 and driving pressure were all independently significant in univariate analysis with p<0.001 for each variable respectively. Relative risk of death for driving pressure was 1.41. Stratified analysis examined tidal volume and PEEP studies separately, but again all examined variables were statistically significant with p<0.05 and relative risk of driving pressure was 1.35 and 1.50 respectively.
These statistically significant variables (age, APACHE or SAPS, arterial pH, PaO2:FiO2 and driving pressure) were then entered into further multivariate models which included tidal volume and PEEP as additional covariates. When driving pressure was included in the model, other ventilation variables including tidal volume and PEEP no longer conferred independent survival benefit. Driving pressure; however, continued to have a statistically significant relationship with survival with a relative risk of 1.40 and 1.41 when examined with tidal volume and PEEP, respectively. Again, both relative risks had a calculated p<0.001.
Mediation analysis was then performed to determine whether a specific variable, strongly affected by treatment-group assignments, had an effect on outcomes that explained in whole or in part the effects resulting from the treatment-group assignment. For this level of analysis, the nine original studies were separated into tidal volume or PEEP strategies for analysis. Tidal volume, plateau pressure, PEEP and driving pressure were all examined as mediator candidates. Driving pressure was the only mediator candidate that consistently passed stepwise mediation, and was found to mediate 75% of the benefits in the tidal volume trials. Survival benefits in PEEP and tidal volume trials were proportional to reduction in driving pressure rather than PEEP or tidal volume.
In all models, driving pressure was a strong and non-redundant predictor of survival as higher driving pressures consistently predicted lower survival. Higher plateau pressures were associated with higher mortality, but only when driving pressure was also high. Similarly, the survival benefit associated with higher PEEP was only noted when driving pressure was low. This analysis indicates that driving pressure is the most important component of lung protective ventilation strategies.
These results suggest that aerated lung in ARDS patients is not stiff, but small with nearly normal compliance. Furthermore, functional lung size during this state is better quantified by lower respiratory system compliance than by predicted body weight.
It is important to remember that mediation analysis cannot establish causality, but provides a plausible link. The results of this study are also limited in that they are only applicable to patients not making independent respiratory efforts, as driving pressure is difficult to interpret during spontaneous respiration. This makes measurements taken directly following intubation in the ED with rapid sequence intubation some of the most important for determining future ventilator settings. These findings are the result of post hoc observational analysis and clinical trials are needed.
As we care for more critically ill patients in the ED and they remain in the ED for longer periods of time, our management of mechanical ventilation takes on greater importance for patient survival. Lung protective ventilator settings likely give our patients the best chance of survival and the latest data suggest we may be able to tailor those settings to the individual patient using driving pressure.
1 Lilly, C. M., Swami, S., Liu, X., Riker, R. R., & Badawi, O. Five year trends of critical care practice and outcomes. Chest.2017.06.050
2. Mullins PM, Goyal M, Pines JM. National growth in intensive care unit admissions from emergency departments in the United States from 2002 to 2009. Acad Emerg Med. 2013;20(5):479-486.
3. Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP, group D-Es. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med. 2007;35(6):1477-1483
5. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N England J Med., 342, 1301-1308.
4. Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338: 347-54.
5. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 2010; 303: 865-73.
6. Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 2006; 34: 1311-8.
7. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N England J Med., 342, 1301-1308.