Out-of-Hospital Ventilation for Acute Respiratory Failure
Out-of-Hospital Ventilation for Acute Respiratory Failure
A single centre, prospective, randomised, intention-to-treat clinical trial, the study was approved by the ethics committee, complies with the Declaration of Helsinki and was registered at ClinicalTrials.gov (Protocol record 40/11/04).
To date there is no clinical experience published comparing the effects of NIV and SMT in OOH treatment of ARF. These first data will help to design an enlarged study powered to a primary endpoint.
The study was performed within the emergency medical system (EMS) of Goettingen, Germany, which is two tiered. The first tier is an ambulance staffed with paramedics. The second tier is a vehicle staffed with an emergency physician as well as a paramedic. National regulations require that both tiers must be dispatched immediately if symptoms of respiratory distress are present and that ambulance and emergency physicians will have to arrive on scene within 15 min. This implies that they arrive almost simultaneously on scene and that on-scene time is not extended by calling an emergency physician. Emergency physicians were residents of the Anaesthesiology Department of the university hospital with at least 1 year of experience in intensive care medicine and NIV.
All patients 18 years of age and older with respiratory distress caused by ACPE, COPD or pneumonia were eligible for the study if signs of hypoxic respiratory failure (peripheral oxygen saturation (SpO2) <90% while breathing room air) or ventilatory failure (SpO2 <90% and respiratory rate >20 breaths/min at rest) were present.
Patients were not enrolled if the initial SpO2 had not been documented by the paramedics and if SpO2 was 90% or greater with oxygen before the arrival of the emergency physician. Furthermore, patients were not enrolled if immediate endotracheal intubation was indicated due to respiratory arrest, breathing breaks, haemodynamic instability with blood pressure less than 70 mmsyst Hg, loss of consciousness with coma (Glasgow coma scale ≤8), or uncontrollable agitation.
Once a patient has been confirmed to meet the inclusion criteria and none of the exclusion criteria he/she was randomly assigned to receive either SMT or NIV. Randomisation was carried out by the emergency physician on scene using sequentially numbered envelopes with randomisation assignments provided in a 1:1 manner.
Patients were positioned and intravenous access was obtained. SpO2, heart rate (HR), ECG and non-invasive blood pressure (NIBP) were monitored using a monitor/defibrillator unit (Lifepak 12; Medtronic GmbH, Meerbusch, Germany). If there was a suspicion of acute coronary syndrome, a 12-lead ECG was performed to rule out acute myocardial ischaemia.
Patients assigned to SMT received oxygen with maximum flow (12 l/min) by facemask with a reservoir for the treatment of severe hypoxaemia. NIV was applied as soon as possible. Using a transport ventilator (Oxylog 3000; Draeger Medical Luebeck, Germany), NIV was started with fractional inspired oxygen (FiO2) 1.0 and CPAP 5 mbar. CPAP was adjusted according to a flow chart. Pressure support was started as soon as CPAP had been adjusted (figure 1).
(Enlarge Image)
Figure 1.
Flow chart for adjusting non-invasive ventilation parameters. BIPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; PEEP, positive end-expiratory pressure; PS, pressure support (mbar) above PEEP (mbar) level; RR, respiratory rate.
Medication was administered intravenously at the discretion of the emergency physician: in ACPE furosemide and/or urapidil (if hypertensive crisis was the underlying cause) and in COPD reproterol and dexamethasone were given. Occasional opioids were given titrated.
Five minutes after patients had received their treatment in the presence of the emergency physician the efficiency of SMT or NIV was evaluated. If the SpO2 was not greater than 85% or has dropped to 85% or less and/or if the respiratory rate was not 30 or less or had increased to 30 breaths/min or more, treatment was classified as inefficient. If SMT failed, patients were either intubated for invasive ventilation or received rescue NIV. NIV failure would have also been recorded if a patient had shown insufficient cooperation and/or uncontrollable aerophagy.
The need for intubation was indicated by the ongoing deterioration of consciousness, breathing breaks, respiratory arrest, a decrease in heart rate below 50 beats/min, or haemodynamic instability with blood pressure less than 70 mmsyst Hg. The decision regarding intubation was made by the emergency physician.
Indications for intensive care unit (ICU) admission were the deterioration of vital parameters (fall in SpO2 ≤90% despite oxygen, increase of heart rate ≥100 beats/min) when NIV has been stopped or invasive mechanical ventilation and/or a need for catecholamine therapy (dobutamine–norepinephrine or epinephrine) for haemodynamic stabilisation.
All vital parameters (heart rate (HR), non-invasive blood pressure (NIBP), SpO2, respiratory rate, Glasgow coma scale) were documented per the EMS protocol. In addition, these values and ventilator settings (CPAP, positive end-expiratory pressure (PEEP), pressure support, FiO2) were recorded every 5 min in the study documentation.
Samples for blood gas analysis were taken immediately and every 10 min until hospital admission via venous cannula using a heparinised syringe (Pico 50; Radiometer Medical ApS, Brønshøj, Denmark). Five millilitres of blood were discarded before sampling to avoid probe dilution. Probes were immediately analysed upon arrival at the hospital (Radiometer ABL 700 Series; Radiometer Medical ApS). The initial arterial oxygen pressure (PaO2)/FiO2 index was calculated from SpO2 breathing room air, and the final PaO2/FiO2 index was calculated from arterial blood gas analysis at admission and FiO2.
The simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA) score, the incidence of intubation, respiratory therapy (invasive, non-invasive), 28 and 90-day mortality, the number of hospital and ICU days and complications were assessed.
The endpoint was the efficiency of the treatment method. Secondary endpoints were changes in SpO2 and respiratory rate, the frequency and length of ICU stay and the number of days spent in the hospital.
Categorical clinical parameters between the two treatment groups were compared using Fisher's exact test. Metric parameters were compared either by the t test or the Mann–Whitney U test. The normality assumption for the t test was first checked by quantile–quantile plots.
Significance analysis of vital and blood gas parameters was performed by a two-way analysis of variance for repeated measurements, with analysis of group and time effects as well as their interaction. In the case of significant time effects, all data points in time were individually compared to time 0. Patients who were treated other than by randomisation of protocol were analysed according to the intention-to-treat principle.
The significance level was set to α=5% for all tests. Post-hoc tests were performed at the Bonferroni-corrected significance level. Analyses were carried out with the free software R (version 2.8, http://www.r-project.org).
Methods
Design
A single centre, prospective, randomised, intention-to-treat clinical trial, the study was approved by the ethics committee, complies with the Declaration of Helsinki and was registered at ClinicalTrials.gov (Protocol record 40/11/04).
To date there is no clinical experience published comparing the effects of NIV and SMT in OOH treatment of ARF. These first data will help to design an enlarged study powered to a primary endpoint.
EMS System
The study was performed within the emergency medical system (EMS) of Goettingen, Germany, which is two tiered. The first tier is an ambulance staffed with paramedics. The second tier is a vehicle staffed with an emergency physician as well as a paramedic. National regulations require that both tiers must be dispatched immediately if symptoms of respiratory distress are present and that ambulance and emergency physicians will have to arrive on scene within 15 min. This implies that they arrive almost simultaneously on scene and that on-scene time is not extended by calling an emergency physician. Emergency physicians were residents of the Anaesthesiology Department of the university hospital with at least 1 year of experience in intensive care medicine and NIV.
Patient Inclusion
All patients 18 years of age and older with respiratory distress caused by ACPE, COPD or pneumonia were eligible for the study if signs of hypoxic respiratory failure (peripheral oxygen saturation (SpO2) <90% while breathing room air) or ventilatory failure (SpO2 <90% and respiratory rate >20 breaths/min at rest) were present.
Patients were not enrolled if the initial SpO2 had not been documented by the paramedics and if SpO2 was 90% or greater with oxygen before the arrival of the emergency physician. Furthermore, patients were not enrolled if immediate endotracheal intubation was indicated due to respiratory arrest, breathing breaks, haemodynamic instability with blood pressure less than 70 mmsyst Hg, loss of consciousness with coma (Glasgow coma scale ≤8), or uncontrollable agitation.
Once a patient has been confirmed to meet the inclusion criteria and none of the exclusion criteria he/she was randomly assigned to receive either SMT or NIV. Randomisation was carried out by the emergency physician on scene using sequentially numbered envelopes with randomisation assignments provided in a 1:1 manner.
Treatment
Patients were positioned and intravenous access was obtained. SpO2, heart rate (HR), ECG and non-invasive blood pressure (NIBP) were monitored using a monitor/defibrillator unit (Lifepak 12; Medtronic GmbH, Meerbusch, Germany). If there was a suspicion of acute coronary syndrome, a 12-lead ECG was performed to rule out acute myocardial ischaemia.
Patients assigned to SMT received oxygen with maximum flow (12 l/min) by facemask with a reservoir for the treatment of severe hypoxaemia. NIV was applied as soon as possible. Using a transport ventilator (Oxylog 3000; Draeger Medical Luebeck, Germany), NIV was started with fractional inspired oxygen (FiO2) 1.0 and CPAP 5 mbar. CPAP was adjusted according to a flow chart. Pressure support was started as soon as CPAP had been adjusted (figure 1).
(Enlarge Image)
Figure 1.
Flow chart for adjusting non-invasive ventilation parameters. BIPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; PEEP, positive end-expiratory pressure; PS, pressure support (mbar) above PEEP (mbar) level; RR, respiratory rate.
Medication was administered intravenously at the discretion of the emergency physician: in ACPE furosemide and/or urapidil (if hypertensive crisis was the underlying cause) and in COPD reproterol and dexamethasone were given. Occasional opioids were given titrated.
Five minutes after patients had received their treatment in the presence of the emergency physician the efficiency of SMT or NIV was evaluated. If the SpO2 was not greater than 85% or has dropped to 85% or less and/or if the respiratory rate was not 30 or less or had increased to 30 breaths/min or more, treatment was classified as inefficient. If SMT failed, patients were either intubated for invasive ventilation or received rescue NIV. NIV failure would have also been recorded if a patient had shown insufficient cooperation and/or uncontrollable aerophagy.
The need for intubation was indicated by the ongoing deterioration of consciousness, breathing breaks, respiratory arrest, a decrease in heart rate below 50 beats/min, or haemodynamic instability with blood pressure less than 70 mmsyst Hg. The decision regarding intubation was made by the emergency physician.
Indications for intensive care unit (ICU) admission were the deterioration of vital parameters (fall in SpO2 ≤90% despite oxygen, increase of heart rate ≥100 beats/min) when NIV has been stopped or invasive mechanical ventilation and/or a need for catecholamine therapy (dobutamine–norepinephrine or epinephrine) for haemodynamic stabilisation.
Data Collection
All vital parameters (heart rate (HR), non-invasive blood pressure (NIBP), SpO2, respiratory rate, Glasgow coma scale) were documented per the EMS protocol. In addition, these values and ventilator settings (CPAP, positive end-expiratory pressure (PEEP), pressure support, FiO2) were recorded every 5 min in the study documentation.
Samples for blood gas analysis were taken immediately and every 10 min until hospital admission via venous cannula using a heparinised syringe (Pico 50; Radiometer Medical ApS, Brønshøj, Denmark). Five millilitres of blood were discarded before sampling to avoid probe dilution. Probes were immediately analysed upon arrival at the hospital (Radiometer ABL 700 Series; Radiometer Medical ApS). The initial arterial oxygen pressure (PaO2)/FiO2 index was calculated from SpO2 breathing room air, and the final PaO2/FiO2 index was calculated from arterial blood gas analysis at admission and FiO2.
The simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA) score, the incidence of intubation, respiratory therapy (invasive, non-invasive), 28 and 90-day mortality, the number of hospital and ICU days and complications were assessed.
The endpoint was the efficiency of the treatment method. Secondary endpoints were changes in SpO2 and respiratory rate, the frequency and length of ICU stay and the number of days spent in the hospital.
Statistics
Categorical clinical parameters between the two treatment groups were compared using Fisher's exact test. Metric parameters were compared either by the t test or the Mann–Whitney U test. The normality assumption for the t test was first checked by quantile–quantile plots.
Significance analysis of vital and blood gas parameters was performed by a two-way analysis of variance for repeated measurements, with analysis of group and time effects as well as their interaction. In the case of significant time effects, all data points in time were individually compared to time 0. Patients who were treated other than by randomisation of protocol were analysed according to the intention-to-treat principle.
The significance level was set to α=5% for all tests. Post-hoc tests were performed at the Bonferroni-corrected significance level. Analyses were carried out with the free software R (version 2.8, http://www.r-project.org).
