Original Contribution

Circadian pattern of Intubation rates in ED patients with congestive heart failure^?

John R. Allegra MD, PhD?, Barnet Eskin MD, PhD, Jeffery Kleinberg MD, Dennis G. Cochrane MD

Morristown Memorial Hospital Residency in Emergency Medicine, Morristown, NJ 07962, USA

Received 12 March 2008; revised 26 October 2008; accepted 26 October 2008

Abstract

Purpose: A previous study showed that pulmonary edema patients presenting between noon and 4 PM have the highest rates of myocardial infarction and death. We hypothesized that the highest intubation rates would also occur at these times.

Basic Procedures: We performed a retrospective cohort study of consecutive patients seen by emergency department physicians in 15 hospital emergency departments (1996-2003).

Main Findings: Of 3.6 million visits in the database, 39,795 (1.1%) patients had congestive heart failure. We found statistically significant Circadian variations in intubation rates. Patients arriving between midnight and 4 AM had the highest intubation rates (4.1%), and those arriving between noon and 4 PM had the lowest (1.2%) (difference, 2.9%; 95% confidence interval, 2.4%-3.4%; P b .0001).

Conclusion: We found significant circadian variation in intubation rates, with a marked increase around midnight. Pathological mechanisms causing patients with congestive heart failure to require intubation may differ from those resulting in myocardial infarction or death.

(C) 2010

Introduction

There are many factors that have been proposed as triggers for exacerbation of congestive heart failure (CHF) [1]. circadian patterns in exacerbations of CHF may give clues to the contribution that each triggering mechanism makes to the onset of episodes of CHF. Earlier studies

^? The Emergency Medicine Associates Research Foundation provided us with the data and computer support.

* Corresponding author. Department of Emergency Medicine, Morris-

town Memorial Hospital, Morristown, NJ 07962, USA. Tel.: +1 973 971

8919; fax: +1 973 290 7202.

E-mail address: [email protected] (J.R. Allegra).

have revealed significant circadian patterns in the decom- pensation of CHF and exacerbation of its symptoms [2-5]. Understanding these circadian patterns may allow tailored therapy for different etiologies related to time of day. Furthermore therapeutic efficacy trials may have to account for circadian variations.

Barash et al [6] found significant circadian variations in the incidence of myocardial infarction (MI) and death and the time of presentation to the emergency department (ED) in 103 hospitalized CHF patients. Patients presenting to the ED between noon and 4 PM had a significantly higher incidence of acute MI (76% vs 28%, P = .03) and death (47% vs 9% P = .03) compared with patients presenting at other times. Although the Barash et al study was limited to hospitalized

0735-6757/$ - see front matter (C) 2010 doi:10.1016/j.ajem.2008.10.035

Circadian intubation pattern in ED CHF patients 167

patients, it probably applies broadly to all CHF patients with more severe exacerbations.

Assuming that the more severely ill CHF patients are most likely to be intubated, we hypothesized that the highest intubation rates would parallel the rates of MI and death and therefore also peak between noon and 4 PM. Our goal was to test this hypothesis in a large database of ED patients.

Methods

Study design

We performed a retrospective cohort study.

Study setting and population

We included consecutive patients seen by ED physicians in 15 hospital EDs in New Jersey state between January 1, 1996, and March 31, 2003. These EDs are staffed by physicians in one emergency medicine group, and all use the same billing service. The EDs are in both teaching and nonteaching hospitals and in urban and suburban areas and have 20 000 to 65 000 visits per year. Emergency physicians see 85% to 90% of all ED patients. Using the International Classification of Diseases, Ninth Revision, Clinical Mod- ification, coders in the ED physicians’ billing department assign up to 8 codes to each patient based primarily on the clinicians’ written diagnosis. All coders undergo an intensive 1-week training course and are reviewed for quality control by a supervisor. Using the computerized billing database of ED visits, we classified patients as having CHF if the first diagnosis was CHF, heart failure, or pulmonary edema or if

one of these was listed as the second diagnosis and the first diagnosis was a respiratory diagnosis (sob, dyspnea, respiratory failure, or wheezing).

Data analysis

For each CHF patient, we collected the following data: time of arrival (divided into both 1- and 4-hour intervals), sex, age, whether the patient was admitted or discharged, and whether the patient was intubated. We included 4-hour intervals to compare our findings with those of the previous study by Barash et al [6]. We used the ?2 and Student’s t tests to check for significant differences, with P b .05 taken as statistically significant. A hospital institutional review board approved the study.

Results

There were a total of 3.6 million patients in the database, of whom 39,795 (1.1%) had an ED diagnosis of CHF. Of these, 22,070 (55%) were women and 33,983 (85%) were admitted. The mean (SD) patient age was 75 (13) years.

We found significant circadian variation in the intubation rates as a function of time of arrival at the ED for both hourly and 4-hour periods (P b .0001, Fig. 1). Intubation rates were greater than 3% for the first 8 and last 3 hours of the day. The highest intubation rate, 4.5%, occurred in patients arriving at the ED during the first hour of the day, whereas the lowest intubation rates, an average of 1.2%, occurred for patients arriving between noon and 5 PM. When we examined the data in 4-hour periods, the patients arriving between midnight and 4 AM had the highest intubation rates (4.1%),

Fig. 1 Percentage of intubated CHF patients vs hour of day.

168 J.R. Allegra et al.

Fig. 2 CHF and intubated CHF patients vs hour of day.

whereas those arriving between noon and 4 PM had the lowest rate (1.2%) (difference, 2.9%; 95% confidence inter- val, 2.4%-3.4%; P b .0001).

We also noted significant circadian variation in the total number of CHF visits and CHF patients intubated (Fig. 2). The total number of CHF visits varied significantly by hour of day (P b .0001). The total number of CHF visits rose rapidly between 8 and 11 AM and then gradually decreased. The peak number of visits was greatest between 10 and 11 AM (2584 patients); and the least, between 4 and 5 AM (1098 patients). The number of CHF patients intubated was least for those presenting to the ED during the time period between noon and 8 PM.

Discussion

Contrary to our hypothesis, we found the highest rates of intubation between midnight and 4 AM. We expected that the highest rates of intubation would be at the same time of day that Barash et al [6] found the peak incidence of MI and death, namely, between noon and 4 PM. However, severe dyspnea as found in acute pulmonary edema patients requiring intubation may not necessarily correlate with acute MI and death. In fact, the discrepancy between our findings and those of Barash et al suggests that the pathophysiologic basis for onset of severe dyspnea in CHF patients is different from that causing acute MI and death. This leads us to believe that there are different physiologic triggering factors for CHF that vary by time of day. Barash et al [6] speculated that the high mortality rate that they noted in the early afternoon was the result of a thrombogenic event leading to cardiac ischemia and acute pulmonary edema. We

speculate that the increase in intubation rates may be due to increased venous return and fluid overload when in the recumbent position during the late evening and early morning hours. The increase in intubation rates may also be due to the increase in blood pressures and heart rates overnight that are found in CHF patients compared with controls [7].

Others in Mediterranean countries have also looked at circadian patterns in onset of acute pulmonary edema and found results that are similar to those we found in this study. Cugini et al [5] reported the highest rate of onset of acute pulmonary edema between 10 PM and 2 AM in 73 hospitalized patients in Rome. Fava and Azzopardi [4] found a peak incidence of acute pulmonary edema in 93 patients admitted to a Maltese hospital between 6 PM and 6 AM, and Pasqualetti and Casale [2] found a peak in onset of acute pulmonary edema between 10 PM and 4 AM in 1204 hospitalized patients in L’Aquila, Italy.

In our study, the circadian pattern of total incidence of CHF was similar to that of the study by Allegra et al [3] with 26,224 CHF patients in New Jersey using a different database, with a peak in the total number of CHF patients around 10 AM. The difference in circadian patterns between the total incidence of CHF patients found in the New Jersey studies and the incidence in the Mediterranean studies is most likely because of the inclusion of less severe cases of CHF in the New Jersey studies. Our database did not contain information on severity of illness other than intubation, so we could not analyze patients with pulmonary edema separately from those with mild to moderate CHF.

Because demonstrating differences in therapeutic inter- ventions is easier in patients with more severe disease, studies on therapies for CHF patients should take into account the disease process being addressed and the circadian rhythm of

Circadian intubation pattern in ED CHF patients 169

that disease process. We speculate that therapies aimed at treating respiratory events should focus on patients in the early morning hours, whereas therapies aimed at treating thrombotic events should focus on patients in the early afternoon. Furthermore, corrections for time of day should be made in therapeutic trials if intubation rates are used as an outcome measure for therapies for CHF. These considerations apply to clinical practice as well as to research trials.

There were several limitations to our study. Our methodology captured only intubations performed by the ED physicians. Although in these EDs, 10% to 15% of all patients are seen by their private physicians, in our experience, they are seldom in attendance when these patients present acutely. Our database would not capture those patients intubated by other health care providers such as anesthesiologists. To determine whether the availability of other providers would influence our results, we surveyed physicians in the ED group by e-mail on their Intubation practices. We received responses from 96 (59%) of the 162 physicians surveyed. We asked these physicians the fraction of patients they intubated themselves without involving other health care providers and also whether their practice varied by time of day. The response from these ED physicians was that, on average, they intubated 98% of their CHF patients themselves. Only 1 physician stated that the decision to intubate by himself depended on the time of day. Therefore, we do not believe it likely that these results would be influenced by the availability of other health care providers. Our database did not contain information on whether the patient was intubated in the prehospital setting. Thus, prehospital intubations were not accounted for in this study, so we do not know whether this varies by time of day. However, in our experience, the quality and medical practice of the Prehospital providers do not change by time of day.

We did not identify whether patients were transported to the ED by ambulance, nor did we evaluate interventions that they may have received during this transport. We used the discharge diagnosis from the ED to identify the patients in this study. It is likely that some of these patients who were admitted to the hospital with a diagnosis of CHF may have been given a different diagnosis on discharge from the hospital. We also did not follow the patients who were

admitted to see if they were intubated during their inpatient course. We think that it would be unlikely for any of these potentially confounding factors to affect the circadian pattern we found.

Although it is possible that the circadian pattern found reflects different practices between physicians working at night from those working during the day, in the EDs included in this study, most physicians work both day and night shifts.

Conclusion

We found significant circadian variation in intubation rates, with a marked increase in intubation rates in patients presenting to the ED from midnight to 4 AM. A previous study showed the highest incidence of MI and death from noon to 4 PM, the time we found the lowest intubation rates. Pathological mechanisms in CHF patients requiring intuba- tion may differ from those who are having an MI or are at risk for death. therapeutic interventions and therapeutic trials need to take into account these circadian patterns.

References

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