|
|
| |||||||||||||||||||||||||||||||||||||||||
Background Respiratory distress is a common symptom of patients transported to hospitals by emergency medical services (EMS) personnel. The benefit of advanced life support for such patients has not been established.
Methods The Ontario Prehospital Advanced Life Support (OPALS) Study was a controlled clinical trial that was conducted in 15 cities before and after the implementation of a program to provide advanced life support for patients with out-of-hospital respiratory distress. Paramedics were trained in standard advanced life support, including endotracheal intubation and the administration of intravenous drugs.
Results The clinical characteristics of the 8138 patients in the two phases of the study were similar. During the first phase, no patients were treated by paramedics trained in advanced life support; during the second phase, 56.6% of patients received this treatment. Endotracheal intubation was performed in 1.4% of the patients, and intravenous drugs were administered to 15.0% during the second phase. This phase of the study was also marked by a substantial increase in the use of nebulized salbutamol and sublingual nitroglycerin for the relief of symptoms. The rate of death among all patients decreased significantly, from 14.3% to 12.4% (absolute difference, 1.9%; 95% confidence interval [CI], 0.4 to 3.4; P=0.01) from the basic-life-support phase to the advanced-life-support phase (adjusted odds ratio, 1.3; 95% CI, 1.1 to 1.5).
Conclusions The addition of a specific regimen of out-of-hospital advanced-life-support interventions to an existing EMS system that provides basic life support was associated with a decrease in the rate of death of 1.9 percentage points among patients with respiratory distress.
In many cities in the United States and Canada, out-of-hospital care for critically ill and injured patients is provided by paramedics who are trained in advanced-life-support measures. Advanced life support includes endotracheal intubation and intravenous drug therapy.4 In contrast, paramedics who are trained in basic-life-support measures administer oxygen, bag–valve–mask ventilation, and in some cases nebulized bronchodilators and sublingual nitroglycerin, but they do not perform endotracheal intubation or administer intravenous drugs.
The benefit of advanced life support for patients with respiratory distress has not been established. There are few controlled clinical trials of out-of-hospital advanced life support and respiratory distress and, consequently, there is very little evidence regarding the optimal therapy for patients before they arrive at the hospital. To our knowledge, no studies have shown improved survival for patients with respiratory distress who receive advanced life support before they arrive at the hospital, and there is some evidence that inappropriate drug therapy in this setting may increase the rate of death.5,6,7,8,9,10,11,12
In Ontario, a Canadian jurisdiction of 12 million people, the provincial government has funded the Ontario Prehospital Advanced Life Support (OPALS) Study, a large, multicenter, controlled clinical trial. This multiphase study evaluated specific programs in several cities to determine the incremental benefit to survival and morbidity associated with out-of-hospital advanced life support for four major groups of critically ill and injured patients (those with cardiac arrest, major trauma, respiratory distress, and chest pain).3,13,14 We have shown that advanced-life-support programs have no significant effect on the outcomes of patients with cardiac arrest.15 The objective of the current study, the OPALS Respiratory Distress Study, was to assess the incremental benefit with respect to morbidity and mortality that results from the implementation of an advanced-life-support program for the evaluation and management of respiratory distress before patients arrive at the hospital.
Methods
Design
Detailed methods for the OPALS Respiratory Distress Study have been described previously.3 We performed a prospective "before-and-after" controlled trial (before and after advanced-life-support programs were instituted) among all eligible patients with respiratory distress seen during two distinct phases of the study: the basic-life-support phase (6 months) and the advanced-life-support phase (6 months). The study was funded by peer-reviewed grants from the Emergency Health Services Branch of the Ontario Ministry of Health and Long-Term Care and the Canadian Health Services Research Foundation.
Setting and Population
The study was conducted in 18 urban communities throughout Ontario under the medical direction of 11 base-hospital programs. The aggregate population was 2.5 million people, with the populations of individual cities ranging from 20,000 to 750,000. One community had a population of less than 30,000, five had populations of 30,000 to 99,999, four had populations of 100,000 to 199,999, four had populations of 200,000 to 500,000, and one had a population of more than 500,000. Each community was served by a Central Ambulance Communications Center, which provided the study with electronic and synchronized dispatch information regarding all patients transported by ambulance during the study. Out-of-hospital care was documented with the use of the standard Ontario Ambulance Call Report form, which included specific data regarding the call code, time of events, medications administered, and procedures performed.
The study population included all patients 16 years of age and older whose primary symptom was shortness of breath, including those who were assessed by EMS personnel but not transported to the hospital. Excluded were patients with full cardiac arrest before the arrival of EMS personnel, patients whose primary symptom was chest pain or any other nonrespiratory symptom, and patients with respiratory distress due to trauma, a postictal state, or another nonrespiratory illness, according to information available to paramedics at the time of the initial assessment of the patient in the field. The study received full approval of the Ottawa Hospital Research Ethics Board, and the requirement for informed consent was waived.
Intervention
During the basic-life-support phase, each community provided tiered EMS, with firefighters responding first, followed by "primary care" paramedics. These paramedics had previously graduated from a 10-month program at a community college and were trained to provide all basic-life-support measures, including oxygen, bag–valve–mask ventilation, and automated external defibrillation. All paramedics also had several years of experience (median, 5 years).
The study intervention consisted of an advanced-life-support program in which primary care paramedics were trained to perform endotracheal intubation, insert intravenous lines, and administer intravenous medications. After this training, they were called "advanced-care" paramedics. The Emergency Medical Technician Level III training program of the Canadian Medical Association involved 6 weeks of didactic instruction, 6 weeks of clinical instruction, and 12 weeks of preceptorship training in the field. To qualify for the advanced-life-support phase of the OPALS Study, each community had to meet four criteria with regard to patients with cardiac arrest. First, EMS technicians had to achieve a rapid-defibrillation response interval of 8 minutes or less for 90% of patients. Second, paramedics trained to provide advanced care had to respond for 95% of patients. Third, paramedics trained to provide advanced care had to respond to the scene within 11 minutes for 80% of patients. Finally, paramedics trained to provide advanced care had to successfully perform endotracheal intubation for 90% of patients. These criteria were monitored regularly, and data collection for the advanced-life-support phase of the study in each community did not begin until the criteria were met. The three communities that did not meet the standards were excluded from the study.
During the advanced-life-support phase, the decision to dispatch a crew trained to provide advanced life support was made by the dispatcher on the basis of information provided during the initial emergency call and the availability of a team that could provide this type of support at the time of the call. Medications administered to patients with respiratory distress during this phase included intravenous furosemide and morphine as well as nebulized salbutamol and sublingual nitroglycerin. In some instances, patients also received nebulized salbutamol and sublingual nitroglycerin during the basic-life-support phase as part of a "symptom relief" program. This program was gradually introduced to primary care paramedics throughout Ontario during the end of the basic-life-support phase of the OPALS Study.
Outcome Measures
The primary outcome measure was mortality, defined as the rate of death before hospital discharge regardless of the duration of admission. Secondary outcome measures included intubation in the emergency department, evidence of aspiration, admission to a hospital, the length of stay in the hospital, the patient's destination after discharge, and the patient's functional status according to a five-point cerebral-performance category scale.16 An additional end point was paramedic coding of the patient's status as being improved, unchanged, or worsened on the patient's arrival in the emergency department. Study data provided by each base-hospital program included ambulance call reports, dispatch reports, and a review of hospital records. Trained analysts determined the final discharge diagnoses on the basis of hospital records. For a few patients for whom hospital records were not available, data regarding survival to 30 days after the day of study enrollment was ascertained by a review of records from the Ontario Death Registry.
Statistical Analysis
For comparisons of mortality, the minimal sample size was estimated to be 4630 patients in the basic-life-support phase and 4630 patients in the advanced-life-support phase, on the basis of a type I error of 0.05, a type II error of 0.20, a baseline mortality of 17%, and a clinically important difference of 2%. We therefore defined the 6-month duration of each phase of the study based on the expectation that we would be able to enroll at least this number of patients in that time interval.
The primary outcome measure of death before hospital discharge was assessed with chi-square analysis. Ninety-five percent confidence intervals were calculated for the absolute difference in mortality between phases. Stepwise logistic-regression analysis was performed to control for possible confounding variables. These variables included age, sex, initial respiratory rate, initial pulse rate, EMS priority return code (a measure of urgency assigned by the on-site paramedic after initial assessment of the patient's condition), treatment administered, and final diagnosis. Comparisons of the rates of death between the two phases were made for the following subgroups: community size, discharge diagnosis, and EMS return code. Differences between the phases for data other than mortality were analyzed with the Wilcoxon signed rank-sum test, the chi-square test, Fisher's exact test, or Student's t-test, as appropriate. All reported P values are two-sided and not adjusted for multiple testing.
Results
The study enrolled 8138 patients from 15 communities: 3920 in the 6-month basic-life-support phase (from January 1995 to February 1998) and 4218 in the advanced-life-support phase (from February 1998 to November 2000). In each community, the two phases were separated by a run-in period of 6 to 36 months to allow for training in advanced life support. In general, patients in the two phases had similar characteristics (Table 1).
|
|
|
We evaluated a number of clinically important subgroups (Table 4). A reduction in mortality during the advanced-life-support phase was suggested for patients with the final diagnosis of congestive heart failure (15.1% vs. 10.9%) but not for those with other discharge diagnoses. However, a test for interaction did not confirm a statistically demonstrable difference between the effect of out-of-hospital advanced-life-support measures in patients with congestive heart failure and in patients with other diagnoses.
|
Discussion
In this trial, we evaluated the effect of out-of-hospital advanced life support on the outcomes of patients with respiratory distress. Although there was a significant reduction in overall mortality during the advanced-life-support phase of the trial, the magnitude of the observed decrease did not exceed the prespecified, minimal, clinically important difference of 2 percentage points. In addition, there was a significant increase in the proportion of patients with a cerebral-performance category score of level 1. These improvements in outcome were achieved despite the fact that providers of advanced life support attended fewer than 60% of patients in the second phase of the study and the two advanced-life-support interventions (endotracheal intubation and the administration of intravenous medication) were performed in only 1.4% and 15.0% of patients, respectively.
We performed subgroup analyses to determine whether the survival benefit varied from group to group. The subgroup of patients with a discharge diagnosis of congestive heart failure, as compared with those with other diagnoses, was more likely to have a reduction in mortality during the advanced-life-support phase. However, an interaction test did not confirm a significant difference in effect among patients with the most common discharge diagnoses. Patients in cities with a population of more than 100,000 were also more likely to benefit during the second phase of the trial, as were patients with an EMS return code of "not urgent."
Previous data regarding the benefit of advanced life support for patients with shortness of breath are limited. To our knowledge, there have been no previous controlled trials and no previous studies that clearly show improved survival with advanced airway measures or the administration of medication for patients with congestive heart failure.6,7,12,17 Three small studies evaluated the feasibility but not the effectiveness of techniques to maintain positive airway pressure in patients being transported in ambulances.18,19,20 For patients with asthma, several small studies evaluated the administration of beta-agonists in out-of-hospital settings and showed an improvement in the peak expiratory flow rate but no improvement in the rate of deaths among patients.5,8,9
An important potential limitation of our study is that it was designed as a before-and-after controlled trial rather than as a randomized trial and, as such, it had a historical rather than a contemporaneous control group. It was not possible for individual patients to undergo randomization because the paramedics considered the random withholding of potentially lifesaving procedures to be unethical. Such a study would have been logistically difficult to carry out in any case. In addition, the primary outcome measure, death, was not subject to ascertainment bias. Selection bias was minimized by the population-based approach of including all patients from the study communities. A program to administer medications for symptom relief (nebulized salbutamol and sublingual nitroglycerin) was introduced toward the end of the first phase of this study. Although this program was not specifically related to advanced life support, it may have been a factor that influenced the benefit in the second phase of the study. Positive-airway-pressure therapy was also introduced in some emergency departments during the study period; this could have influenced the outcome for some of the patients in the study.
The implications of this study require careful consideration. The patients in the second phase of the study had a significantly lower mortality than those in the first phase. We estimate that 53 is the number needed to treat for the entire cohort with shortness of breath, and in the study regions with 2.5 million people, approximately 161 lives would be saved each year.
However, it is less clear which interventions should be considered essential and how they should be implemented. In this study, very few patients underwent intubation, and of the intravenous medications, only furosemide was given to a large number of patients (14.4%). The most substantial change in therapeutic intervention was the marked increase in the use of medications for symptom relief; this intervention is not a component of advanced life support, and it was implemented as part of a separate program. Thus, the benefit of the intervention in this trial may have been primarily due not to the availability of advanced-life-support techniques but to the use of nebulized salbutamol and sublingual nitroglycerin. However, it is difficult to analyze the effect of individual measures in this study, since the patients treated with any given intervention likely differed from those who did not receive that intervention and it would be difficult to define a comparable subgroup within the control sample. The reduction in mortality among patients in this study was entirely due to a reduction in the in-hospital mortality, with no change in the mortality in the emergency department. Although many of the patients who died presumably did so soon after admission, these data do raise the question of whether other interventions occurring after the patients arrived at the hospital played a role in the improvement in outcome.
Analyses of the benefit for patients with specific discharge diagnoses are of some interest, but the decision to dispatch an advanced-life-support team cannot be made on the basis of a subsequently determined discharge diagnosis. There was more evidence of a survival benefit among patients with an EMS return code of "not urgent" than among those with a code of "urgent," so it is unclear whether patients were more likely to benefit if they were less ill. Finally, the benefit of an advanced-life-support program must be balanced against the relatively high cost of its implementation.
The OPALS Respiratory Distress Study showed that the introduction of an EMS advanced-life-support program and interventions for symptom relief significantly reduced mortality for patients with shortness of breath. It is unclear whether these data are sufficient to justify implementation of the entire program of interventions described here. Further research should target populations and evaluate the optimal treatment regimens for patients with out-of-hospital respiratory distress.
Supported by peer-reviewed grants from the Emergency Health Services Branch of the Ontario Ministry of Health and Long-Term Care and the Canadian Health Services Research Foundation and by a Distinguished Investigator Award from the Canadian Institutes of Health Research (to Dr. Stiell).
No potential conflict of interest relevant to this article was reported.
We thank the OPALS Study Group investigators and other members of the OPALS Study Coordinating Center: Tammy Beaudoin (research coordinator), David Brisson (research coordinator), Irene Harris (administrative secretary), and My-Linh Tran (database coordinator). We thank Cathy Francis of the Ministry of Health and Long-Term Care for her support.
Source Information
From the Department of Emergency Medicine (I.G.S., J.M.), Department of Epidemiology and Community Medicine (G.A.W.), Clinical Epidemiology Program (L.P.N.), Ottawa Health Research Institute, University of Ottawa, Ottawa; the Department of Emergency Medicine, University of Arizona, Tucson (D.W.S.); the Department of Emergency Medicine, Queens University, Kingston, ON, Canada (E.D.); Emergency Health Services, Ontario Ministry of Health and Long-Term Care, Toronto (T.C.); Niagara Regional Base Hospital, Niagara Falls, ON, Canada (D.M., L.L.T.); the Division of Emergency Medicine, University of Western Ontario, London, ON, Canada (J.D.); Joseph Brant Memorial Hospital, Burlington, ON, Canada (M.L.); and Interdev Technologies, Toronto (B.F.).
References
The OPALS Study Group investigators from the following base hospital programs participated in the study: Burlington — M.W. Stempien, C.I. Parkinson; Cambridge — D. Waldbillig, K.W. Ballah; Kingston — G.J. Jones, M.R. Halladay; London — J.F. Dreyer, K.A. Boyle; Niagara — D.P. Munkley, L.G. Luinstra Toohey; Ottawa — J.P. Maloney, J.P. Trickett; Peterborough — V. Arcieri, J.W. Fader; Sarnia — M.G.J. Lees, D.D. LaBarre; Sudbury — R.S. Lepage, S. Michaud; Thunder Bay — A.W. Affleck, T.A. Tyson; Windsor — J.C. Fedoruk, M. Gobet.
| |||||||||||||||||||||||||||||||||||||||||
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2008 Massachusetts Medical Society. All rights reserved. |
Previous
