Mechanically Ventilated Patients After Cardiac Arrest
Mechanically Ventilated Patients After Cardiac Arrest
In this large retrospective analysis of prospective observational cohort, we described the evolution of ventilator management, and the occurrence of pulmonary and other non-respiratory organ failure over time. Furthermore, we investigated variables associated with 28-day hospital mortality and the occurrence of ARDS and/or pneumonia acquired during ICU stay among cardiac arrest patients undergoing mechanical ventilation. We found that: the use of protective and assisted mechanical ventilation increased from 1998 to 2010; pulmonary complications decreased, while cardiovascular and neurological complications, and sepsis increased with years; independent risk factors for 28-day hospital mortality were older age, PaO2 <60 mmHg, less use of sedative drugs and the presence of cardiovascular dysfunction at 24 hours after ICU admission; and in patients without lung injury at ICU admission, higher tidal volume, higher plateau pressure and lower PEEP in the first 24 hours were independent potential risk factors for developing ARDS or pneumonia acquired during ICU stay.
To our knowledge, this is the first study describing ventilator management in a large sample of patients after cardiac arrest undergoing mechanical ventilation in ICU. Our results show that protective mechanical ventilation is increasingly used among patients after cardiac arrest. The implementation of protective mechanical ventilation was associated with a progressive reduction in pneumonia acquired during ICU stay over time, and a lower incidence of ARDS than that reported in mechanically ventilated patients. Similar changes in ventilation pattern have recently been shown in a general population of critically ill patients, associated with a reduction of development of ARDS. Protective ventilation with low tidal volume has been shown to be associated with a reduction in respiratory failure and mortality in non-ARDS lung patients, and postoperative complications after surgery. In donors, protective mechanical ventilation increased the number of lungs eligible to be harvested compared to traditional mechanical ventilation. The application of PEEP ranging from 5 to 8 cmH2O in non-hypoxemic patients decreased the incidence of ventilator-associated pneumonia. Moreover, protocols aimed to prevent ventilator-associated pneumonia have been more widely implemented in recent years.
On the other hand, we observed an increased incidence of non-pulmonary organ failure (sepsis, cardiovascular dysfunction and neurological failure) over time, which may increase the duration of mechanical ventilation. The increase in non-pulmonary complications may be explained by the implementation of targeted temperature management protocols, or by higher incidence of aspiration, and thus sicker patients, which might predispose to infection and consequent multiple organ failure. The significant differences in the duration of ventilatory support over time, with a longer duration in the most recent study of 2010, is probably because of the implementation of targeted temperature management protocols, and thus longer sedation.
A previous study demonstrated that changes in mechanical ventilation practice were associated with a significant decrease in mortality. In post-cardiac arrest patients, despite the introduction of temperature management, percutaneous coronary intervention and standard operating procedures, we did not observe any change in mortality over the years, likely due to the balance between decreased pulmonary and increased extra-pulmonary incidence of complication. We also found that the main independent predictors of 28-day in-hospital mortality were older age, PaO2 <60 mmHg, use of sedative drug, and cardiovascular dysfunction within 24 hours from admission, in line with previous reports.
In the present study, the analysis by logistic regression demonstrated that PaO2 <60 mmHg is a predictor of 28-day hospital mortality. This result is different from previous meta-analysis showing that not only hypoxemia but also hyperoxemia are associated with higher in-hospital mortality. The effects of high oxygen tension to increase neuronal damage after cardiac arrest are conflicting. We also found that higher or lower PaCO2 level had no detectable association with mortality. This was different from previous studies showing that hypocarbia defined by PaCO2 <35 mmHg was associated with higher in-hospital mortality, while hypercapnia defined by PaCO2 >45 mmHg was associated with better outcome.
Use of sedative drugs was associated with 28-day mortality in this cohort. This finding is in contrast to other studies showing that sedation protocols did not affect mortality in a general population of critically ill patients. We have no completed value of GCS for the three cohort years. The lower GCS on admission in the most recent cohort would indicate more severe brain injury, and thus a lower need for sedation and a higher risk of death. On the other hand, our data suggest that higher sedation in the early phase after cardiac arrest might promote less secondary brain injury and better implementation of protective mechanical ventilation. Furthermore, the use of sedative drugs may be related to the implementation of therapeutic hypothermia, which was associated with the improvement of outcome in ROSC patients.
In Table 1, 26% (63 out of 239) of the patients in the 2004 study had a GCS of 15. The study population included patients who developed cardiac arrest and needed mechanical ventilation due to sudden and unexpected cessation of cardiopulmonary functions in any rhythms (referred to any rhythms that cause cessation of cardiopulmonary functions i.e. Pulseless electrical activity, asystole, ventricular fibrillation and ventricular tachycardia); this is not the population included in target temperature management studies, therefore we expect that a higher percentage of patients awake upon arrival in ICU. Our study is comparable with the study by Gold et al. on patients with out-of-hospital cardiac arrest of any rhythm, which demonstrated that of the 185 survivors, 96 patients (50%) were sufficiently awake upon arrival to the ICU so they did not meet the targeted temperature management protocol inclusion criteria, but data on GCS were not reported.
In our study, we evaluated the potential independent risk factors for development of pulmonary complications in patients without pre-existing lung injury at ICU admission. We found that higher tidal volume and higher plateau pressure with lower PEEP were associated with occurrence of lung worsening during ICU stay. These findings are in line with those reported in patients without lung injury in the perioperative period, and in the ICU, showing that protective ventilation by low tidal volume and plateau pressure <20 cmH2O resulted in a decreased incidence of pulmonary complications after initiation of mechanical ventilation. We also found that tidal volume was similar, while PEEP was slightly higher in patients with ARDS compared to those without ARDS at ICU admission. This suggests that protective ventilation should include lower tidal volume than actually used in daily clinical practice in cardiac arrest patients with ARDS.
The use of controlled mechanical ventilation decreased, while pressure support increased with years. The use of assisted ventilation may be associated with potential advantages like the use of less sedative agents, better hemodynamic stability, less atrophy of respiratory muscles and ventilator-associated lung injury. The rate of tracheostomy was 12 to 14.5% higher than that reported in a general population of critically ill patients (11%), and comparable to that reported in neurological patients (13%). This might be explained by the possible occurrence of residual neurological deficits in cardiac arrest patients due brain hypoxia impairing cough, swallowing and secretion clearance.
Our study has some limitations. First, this was a post-hoc analysis of previously collected available data, where the statistically significant predictors of mortality might have been influenced by undefined confounding factors, that is, site, cause and initial rhythm of the cardiac arrest. A statistical post-hoc analysis on 28-day hospital mortality was performed to assess the power of mortality variation among the years, and showed a power of less than 50%, so the variation of mortality over years should be interpreted with caution. Second, our study focused on the details related to mechanical ventilation. Thus, we did not record possible implementation of targeted temperature management, including the details related to the causes of cardiac arrest. However, a recent study showed that moderate hypothermia did not affect mortality compared to mild hypothermia. Third, although the GCS was found to be associated with 28-day mortality in the univariate analysis, we did not include GCS in the multivariate analysis. Since the evaluation of GCS is not reliable within the first 72 hours during mechanical ventilation with sedation, and data were not collected in 1998. The lower GCS on admission in the most recent cohort would indicate more severe brain injury, and thus lower need for sedation and higher risk of death.
Fourth, we also did not have access to cardiac arrest-related variables, like whether the arrest was witnessed or not, whether bystander cardiopulmonary resuscitation was performed, initial presenting rhythm and the time of resuscitation commencement or return of spontaneous circulation. Fifth, in the multivariate logistic regression analysis defining risk factors associated with 28-day hospital mortality and the development of ARDS and/or pneumonia acquired in ICU, we used data collected within 24 hours after admission, therefore there were very few missing data. Nevertheless, we used variables regardless of the different years, which might have been affected by the change of clinical management, and the number of patients with development of ARDS and/or pneumonia acquired in ICU is a small portion of the whole population (5% of the total population). For this reason, the results of multivariate analysis should be interpreted with caution.
Discussion
In this large retrospective analysis of prospective observational cohort, we described the evolution of ventilator management, and the occurrence of pulmonary and other non-respiratory organ failure over time. Furthermore, we investigated variables associated with 28-day hospital mortality and the occurrence of ARDS and/or pneumonia acquired during ICU stay among cardiac arrest patients undergoing mechanical ventilation. We found that: the use of protective and assisted mechanical ventilation increased from 1998 to 2010; pulmonary complications decreased, while cardiovascular and neurological complications, and sepsis increased with years; independent risk factors for 28-day hospital mortality were older age, PaO2 <60 mmHg, less use of sedative drugs and the presence of cardiovascular dysfunction at 24 hours after ICU admission; and in patients without lung injury at ICU admission, higher tidal volume, higher plateau pressure and lower PEEP in the first 24 hours were independent potential risk factors for developing ARDS or pneumonia acquired during ICU stay.
To our knowledge, this is the first study describing ventilator management in a large sample of patients after cardiac arrest undergoing mechanical ventilation in ICU. Our results show that protective mechanical ventilation is increasingly used among patients after cardiac arrest. The implementation of protective mechanical ventilation was associated with a progressive reduction in pneumonia acquired during ICU stay over time, and a lower incidence of ARDS than that reported in mechanically ventilated patients. Similar changes in ventilation pattern have recently been shown in a general population of critically ill patients, associated with a reduction of development of ARDS. Protective ventilation with low tidal volume has been shown to be associated with a reduction in respiratory failure and mortality in non-ARDS lung patients, and postoperative complications after surgery. In donors, protective mechanical ventilation increased the number of lungs eligible to be harvested compared to traditional mechanical ventilation. The application of PEEP ranging from 5 to 8 cmH2O in non-hypoxemic patients decreased the incidence of ventilator-associated pneumonia. Moreover, protocols aimed to prevent ventilator-associated pneumonia have been more widely implemented in recent years.
On the other hand, we observed an increased incidence of non-pulmonary organ failure (sepsis, cardiovascular dysfunction and neurological failure) over time, which may increase the duration of mechanical ventilation. The increase in non-pulmonary complications may be explained by the implementation of targeted temperature management protocols, or by higher incidence of aspiration, and thus sicker patients, which might predispose to infection and consequent multiple organ failure. The significant differences in the duration of ventilatory support over time, with a longer duration in the most recent study of 2010, is probably because of the implementation of targeted temperature management protocols, and thus longer sedation.
A previous study demonstrated that changes in mechanical ventilation practice were associated with a significant decrease in mortality. In post-cardiac arrest patients, despite the introduction of temperature management, percutaneous coronary intervention and standard operating procedures, we did not observe any change in mortality over the years, likely due to the balance between decreased pulmonary and increased extra-pulmonary incidence of complication. We also found that the main independent predictors of 28-day in-hospital mortality were older age, PaO2 <60 mmHg, use of sedative drug, and cardiovascular dysfunction within 24 hours from admission, in line with previous reports.
In the present study, the analysis by logistic regression demonstrated that PaO2 <60 mmHg is a predictor of 28-day hospital mortality. This result is different from previous meta-analysis showing that not only hypoxemia but also hyperoxemia are associated with higher in-hospital mortality. The effects of high oxygen tension to increase neuronal damage after cardiac arrest are conflicting. We also found that higher or lower PaCO2 level had no detectable association with mortality. This was different from previous studies showing that hypocarbia defined by PaCO2 <35 mmHg was associated with higher in-hospital mortality, while hypercapnia defined by PaCO2 >45 mmHg was associated with better outcome.
Use of sedative drugs was associated with 28-day mortality in this cohort. This finding is in contrast to other studies showing that sedation protocols did not affect mortality in a general population of critically ill patients. We have no completed value of GCS for the three cohort years. The lower GCS on admission in the most recent cohort would indicate more severe brain injury, and thus a lower need for sedation and a higher risk of death. On the other hand, our data suggest that higher sedation in the early phase after cardiac arrest might promote less secondary brain injury and better implementation of protective mechanical ventilation. Furthermore, the use of sedative drugs may be related to the implementation of therapeutic hypothermia, which was associated with the improvement of outcome in ROSC patients.
In Table 1, 26% (63 out of 239) of the patients in the 2004 study had a GCS of 15. The study population included patients who developed cardiac arrest and needed mechanical ventilation due to sudden and unexpected cessation of cardiopulmonary functions in any rhythms (referred to any rhythms that cause cessation of cardiopulmonary functions i.e. Pulseless electrical activity, asystole, ventricular fibrillation and ventricular tachycardia); this is not the population included in target temperature management studies, therefore we expect that a higher percentage of patients awake upon arrival in ICU. Our study is comparable with the study by Gold et al. on patients with out-of-hospital cardiac arrest of any rhythm, which demonstrated that of the 185 survivors, 96 patients (50%) were sufficiently awake upon arrival to the ICU so they did not meet the targeted temperature management protocol inclusion criteria, but data on GCS were not reported.
In our study, we evaluated the potential independent risk factors for development of pulmonary complications in patients without pre-existing lung injury at ICU admission. We found that higher tidal volume and higher plateau pressure with lower PEEP were associated with occurrence of lung worsening during ICU stay. These findings are in line with those reported in patients without lung injury in the perioperative period, and in the ICU, showing that protective ventilation by low tidal volume and plateau pressure <20 cmH2O resulted in a decreased incidence of pulmonary complications after initiation of mechanical ventilation. We also found that tidal volume was similar, while PEEP was slightly higher in patients with ARDS compared to those without ARDS at ICU admission. This suggests that protective ventilation should include lower tidal volume than actually used in daily clinical practice in cardiac arrest patients with ARDS.
The use of controlled mechanical ventilation decreased, while pressure support increased with years. The use of assisted ventilation may be associated with potential advantages like the use of less sedative agents, better hemodynamic stability, less atrophy of respiratory muscles and ventilator-associated lung injury. The rate of tracheostomy was 12 to 14.5% higher than that reported in a general population of critically ill patients (11%), and comparable to that reported in neurological patients (13%). This might be explained by the possible occurrence of residual neurological deficits in cardiac arrest patients due brain hypoxia impairing cough, swallowing and secretion clearance.
Our study has some limitations. First, this was a post-hoc analysis of previously collected available data, where the statistically significant predictors of mortality might have been influenced by undefined confounding factors, that is, site, cause and initial rhythm of the cardiac arrest. A statistical post-hoc analysis on 28-day hospital mortality was performed to assess the power of mortality variation among the years, and showed a power of less than 50%, so the variation of mortality over years should be interpreted with caution. Second, our study focused on the details related to mechanical ventilation. Thus, we did not record possible implementation of targeted temperature management, including the details related to the causes of cardiac arrest. However, a recent study showed that moderate hypothermia did not affect mortality compared to mild hypothermia. Third, although the GCS was found to be associated with 28-day mortality in the univariate analysis, we did not include GCS in the multivariate analysis. Since the evaluation of GCS is not reliable within the first 72 hours during mechanical ventilation with sedation, and data were not collected in 1998. The lower GCS on admission in the most recent cohort would indicate more severe brain injury, and thus lower need for sedation and higher risk of death.
Fourth, we also did not have access to cardiac arrest-related variables, like whether the arrest was witnessed or not, whether bystander cardiopulmonary resuscitation was performed, initial presenting rhythm and the time of resuscitation commencement or return of spontaneous circulation. Fifth, in the multivariate logistic regression analysis defining risk factors associated with 28-day hospital mortality and the development of ARDS and/or pneumonia acquired in ICU, we used data collected within 24 hours after admission, therefore there were very few missing data. Nevertheless, we used variables regardless of the different years, which might have been affected by the change of clinical management, and the number of patients with development of ARDS and/or pneumonia acquired in ICU is a small portion of the whole population (5% of the total population). For this reason, the results of multivariate analysis should be interpreted with caution.
Source...