The effect of prolonged ED stay on outcome in patients with necrotizing fasciitis

American Journal of Emergency Medicine (2009) 27, 385–390

www.elsevier.com/locate/ajem

Original Contribution

The effect of prolonged ED stay on outcome in patients with necrotizing fasciitis Yu-Cheng Hong MD a,1 , Meng-Hua Chou MD a,1 , Estella H. Liu MS b , Cheng-Ting Hsiao MD a , Jen-Tse Kuan MD c , Ju-Chan Lin MD c , I-Chuan Chen MD a,⁎ a

Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chiayi County 613, Taiwan b University at Buffalo, The State University of New York, Buffalo, NY 14214, USA c Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan County 333, Taiwan Received 14 November 2007; revised 3 March 2008; accepted 4 March 2008

Abstract Objective: Overcrowding in hospitals, especially in EDs, is a serious problem in the United States, Europe, and Taiwan. However, the association between prolonged ED boarding stay and mortality in patients with necrotizing fasciitis remains underinvestigated. Methods: This was a retrospective study. A total of 195 patients were enrolled and analyzed.The sample was divided into 2 groups: nonmortality and mortality. A stepwise logistic regression model was developed to investigate 3 factors of clinical relevance predicting patient mortality. Result: The results of the stepwise logistic regression analysis revealed that hypotension (odds ratio [OR], 32.9; 95% confidence interval [CI], 6.9-156.0) and prolonged ED boarding stay (OR, 3.4; 95% CI 1.3-8.6) were both associated with higher mortality. Early operation (OR: 0.16; 95% CI: 0.06 – 0.45) was associated with lower mortality. Conclusion: Prolonged ED boarding stay was associated with increased mortality in patients with necrotizing fasciitis. Early operation (within 24 hours of ED arrival) was associated with decreased mortality. © 2009 Elsevier Inc. All rights reserved.

1. Introduction 1.1. Background and importance Overcrowding in hospitals, especially in EDs, is a serious problem in the United States, Europe, and Taiwan [1-5]. ⁎ Corresponding author. Tel.: +886 5 362100x2639; fax: +886 5 3623002. E-mail addresses: [email protected], [email protected] (I.-C. Chen). 1 Yu-Cheng Hong and Meng-Hua Chou are both first author of this manuscript due to equal contribution. 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.ajem.2008.03.010

Previous studies have shown that prolonged ED stay may result from a variety of factors, such as the increasing number of critical patients presenting to EDs, hospital and/or ED overcrowding, poor access to primary health care providers, and limited bed availability owing to either low capacity or hospital policy [6-9]. The impact of prolonged ED stay and delayed transfer was also discussed in these studies. More recent investigations have demonstrated a relationship between prolonged ED stay and increases in morbidity and mortality in unclassified patients, intensive care unit (ICU) patients, and patients with non–ST-segment elevation myocardial infarction [10-12]. Common among these

386 patients is that their outcomes depend heavily on when they receive quality care. However, overcrowded EDs may be unable to provide prompt and sufficient quality care because of frequent distractions and added complexity due to the patient load. In this study, we were particularly interested in factors that determine the outcomes of patients with necrotizing fasciitis in EDs. Necrotizing fasciitis is an uncommon but lifethreatening soft tissue infection. The mortality rate of necrotizing fasciitis remains high (ranging from 6% to 76%) despite advancements in modern medical care [13-15]. Prior research has associated both delayed diagnosis and delayed operation of necrotizing fasciitis with higher mortality rates [13,16-20]. Difficulty in early diagnosis of necrotizing fasciitis can result from a lack of experience and knowledge of the various presentations and minute clinical signs/symptoms in the early course of the disease, which in turn leads to delayed operation. However, in the case where patients with necrotizing fasciitis are first sent to the ED, it remains unclear whether it is delayed diagnosis or, rather, the prolonged time waiting in the ED for an operation that is the major determinant of poor prognosis. In this case, both factors lead to delayed operation, and an overall measure of the total length of ED stay will confound delayed diagnosis with prolonged waiting in the ED. In an attempt to address this question, we distinguished between the time it took to confirm the diagnosis in the ED, and the length of ED boarding stay, which refers to the period when an admitted patient is held in the ED for an available ICU or ward bed. We hypothesized that if an accurate diagnosis of necrotizing fasciitis could be confirmed in the ED, the association between in-hospital mortality and the timing of the diagnosis should be trivial. In contrast, the mortality rate should correlate positively with prolonged ED boarding stay and negatively with early operation.

1.2. Goals of this investigation In a sample of patients with necrotizing fasciitis, we assessed the timing of confirmed ED diagnosis of necrotizing fasciitis, the length of ED boarding stay, the timing of operation, and the patient outcomes. Our goal was to report the associations among the timing of confirmed diagnosis, prolonged ED boarding stay, and in-hospital mortality, and to determine what factors were clinically relevant to the treatment of necrotizing fasciitis.

2. Methods 2.1. Study design This was a retrospective study. An electronic search was made of the medical record database of Linkou Chang-Gung

Y.-C. Hong et al. Memorial Hospital, for all adult patients (N18 years of age) with a discharge diagnosis of necrotizing fasciitis admitted to the ED between January 1, 2002, and December 31, 2005. The study was approved by the institutional review board of the hospital.

2.2. Setting The study site, Linkou Chang-Gung Memorial Hospital, is a tertiary medical center. It serves a population of approximately 1 million, with an annual ED census of 180 000 visits. The ED maintains a 24-hour in-hospital staff of a senior surgery resident (plastic or orthopedic coverage) and attending emergency physicians. An attending plastic or orthopedic surgeon is available within 30 minutes.

2.3. Selection of participants We included patients with a discharge diagnosis of necrotizing fasciitis (International Classification of Diseases, Ninth Revision [ICD-9] code 72886). Patients were excluded if they (a) developed necrotizing fasciitis in the ward or ICU, (b) were admitted to the hospital through outpatient departments, (c) were not initially evaluated in the ED, (d) were transferred from another hospital, (e) did not receive an operation, or (f) were younger than 19 years. In addition, if a patient had multiple admissions for necrotizing fasciitis, only the first admission was included.

2.4. Data collection and processing For each patient, we reviewed a number of demographic and clinical variables, including age, sex, comorbid illness, clinical presentation, site(s) and etiology of infection, laboratory findings on admission, medication taken before admission, and the microbiology of wound and blood cultures. Hypotension was defined as having a systolic pressure (SBP) less than 90 mm Hg at ED triage. The number of surgical debridements, the need for amputation, the length of hospitalization, and mortality were also documented. Furthermore, based on the hospital record, we calculated the time elapsed between the following events: symptom onset, patient arrival to the ED, confirmed diagnosis, and operation. To anchor the time of confirmed diagnosis, we used the time when a surgical consultant confirmed the diagnosis of necrotizing fasciitis for a patient in the ED. The hospital's standard procedure requires that the consultant report to the ED within 30 minutes after being called, and record the diagnosis and the time in the computer database. In addition, we used the time when the patient was transferred to the operating room as the time of the operation. This was because in the current study site, an operation is only performed after a patient is assigned a bed in the ward or ICU; and the patient is transferred to the operating room soon after the assignment. Three dichotomous variables were

Prolonged ED stay in necrotizing fasciitis derived from the lengths of time between these events. Early ED diagnosis was defined as a confirmed diagnosis of necrotizing fasciitis within 3 hours of ED arrival. A prolonged ED boarding stay was defined as a boarding stay where the time between confirmed diagnosis and operation exceeded 8 hours. Finally, an early operation was defined as a debridement or amputation within 24 hours of ED arrival. Enrolled patients were divided into 2 groups: nonmortality (group 1) and mortality (group 2). The following variables were compared between groups: age, sex, clinical presentation, comorbid illness, length of hospitalization, number of surgical debridements, and need for amputation, as well as the proportions of prolonged ED boarding stay, early diagnosis, and early operation. Mann-Whitney U tests (for categorical variables) and Student t tests (for continuous variables) were used to determine whether the betweengroup differences were statistically significant (P b .05). All analyses were performed with SPSS 12.0 (SPSS, Inc, Chicago, IL). A stepwise logistic regression model was developed to investigate factors relevant to patient mortality. All variables with a P b .25 in the previous univariate analyses were included in the maximum model. Next, the 3 most important variables, picked a priori by the investigators based on their empirical relevance, were entered into a stepwise backward elimination model. The model was iterated until all covariates with a multivariate P N .10 were eliminated [21,22]. In-hospital mortality was used as the dependent variable. Model calibration was assessed with the HomerLemeshow goodness-of-fit statistic.

2.5. Outcome measures The outcome measure was in-hospital mortality.

3. Results 3.1. Sample characteristics A total of 195 patients were enrolled and analyzed, among whom 137 were male (70.3%) and 58 were female (29.7%). The mean age was 55.3 ± 16.1 years. The median time from symptom onset to ED arrival was 3 days (interquartile range [IQR], 2-4). The most common comorbidity was diabetes mellitus (120 cases, 61.5%). Other comorbidities included liver cirrhosis (77 cases; 39.5%), renal disease (52 cases, 26.7%), heart disease (29 cases, 14.9%), and peripheral vascular disease (23 cases, 11.8%). Thirty-two patients (16.4%) had no comorbidity. Of the 195 total patients, 136 (69.7%) had a confirmed diagnosis of necrotizing fascitiis within 3 hours of ED arrival (early diagnosis), and 61 (31.3%) needed amputation. The major clinical presentations on admission were tenderness

387 (191 cases, 97.9%), erythema (185 cases, 94.9%), tachycardia (101 cases, 51.8%), bullae formation (108 cases, 55.4%), and fever (48 cases, 24.6%). In order, the median times from ED arrival to confirmed diagnosis, from confirmed diagnosis to operation, and from ED arrival to operation were 120 minutes (IQR, 60-270), 300 minutes (IQR, 120-840), and 540 minutes (IQR, 240-1380). The median number of surgical debridements was 3 (IQR, 2-4), and 161 patients (82.6%) received early operation. The median length of hospitalization was 33.0 days (IQR, 20-51). In total, 28 patients (14.4%) died in the study sample.

3.2. Main results A comparison of the demographic, clinical, and treatment variables between group 1 and group 2 is presented in Table 1. Significant between-group differences were noted for hypotension (P b .001), heart disease (P = .006), liver disease (P = .01), renal disease (P = .04), the number of surgical debridements (P = .04), the length of hospitalization (P = .02), the proportion of early operation (P = .006), and the proportion of prolonged ED boarding stay (P = .04). The 2 groups did not differ significantly in terms of age, sex, clinical presentation, need for amputation, or early diagnosis. The 3 variables submitted to the final multivariate logistic regression model were hypotension, prolonged ED

Table 1 Demographic and clinical characteristics of the nonmortality (n= 167) and mortality (n= 28) groups of patients with necrotizing fascitiis Variables

Nonmortality Mortality (n = 167) (n = 28)

P value

Male sex Hypotension Diabetes mellitus Heart disease Peripheral vascular disease Renal disease Liver disease Tenderness Erythema Fever Tachycardia Bullae formation Early operation Early diagnosis Prolonged ED boarding stay (N8 h) Amputation Age (y) (mean ± SD ) No. of debridements (times) (mean ± SD) Length of hospitalization (d) (mean ± SD)

116 (69.5%) 21 (75.0%) .55 3 (1.8%) 7 (25.0%) b.001 102 (61.1%) 18 (64.3%) .75 20 (12.08%) 9 (32.1%) .006 21 (12.6%) 2 (7.1%) .41 40 (24.0%) 60 (35.9%) 164 (98.2%) 158 (94.6%) 41 (24.6%) 90 (53.9%) 88 (52.7%) 143 (85.6%) 119 (71.3%) 55 (32.9%)

12 (42.9%) 17 (60.7%) 27 (96.4%) 27 (96.4%) 7 (25.0%) 11 (39.3%) 20 (71.4%) 18 (64.3%) 17 (60.7%) 15 (53.6%)

.04 .01 .54 .69 .96 .15 .07 .006 .26 .04

48 (28.7%) 55.5 ± 16.4 3.6 ± 2.4

13 (46.4%) 54.0 ± 14.5 2.6 ± 2.1

.06 .63 .04

41.7 ± 29.0

28.0 ± 27.8

.02

388 Table 2

Y.-C. Hong et al. Stepwise logistic regression for in-hospital mortality

Variable

OR

Hypotension Prolonged ED boarding stay (N8 h) Early operation

32.9 3.4 0.16

95% CI 6.9-156.0 1.3-8.6 0.06-0.45

P value b.001 .012

of confirmed diagnosis in this study was an accurate estimate, or if it was “still delayed.”

5. Discussion

b.001

boarding stay, and early operation. The final model had a goodness-of-fit χ2 statistic of 1.32 (P= .52), indicating an adequate model fit. The results of the stepwise logistic regression analysis are summarized in Table 2. Hypotension (odds ratio [OR], 32.9; 95% confidence interval [CI], 6.9-156.0) and prolonged ED boarding stay (OR, 3.4; 95% CI, 1.3-8.6) were both associated with higher in-hospital mortality. Early operation (OR, 0.16; 95% CI, 0.06-0.45) was associated with lower inhospital mortality.

4. Limitations This study has several limitations. First of all, we did not document the time and location of antibiotic treatments. Therefore we were unable to evaluate the effect of the timing of antibiotic treatment on patient outcomes. However, in the treatment of necrotizing fasciitis, administration of antibiotics is only an adjunct, and no standard antibiotic treatment has been established for the infection [23,24]. In fact, multiple broad-spectrum antibiotic regimens had been administered to all 195 patients in our sample. We therefore believe that the impact of antibiotic treatment did not systematically bias the current results. Second, because this was a retrospective study, the reviewed medical charts may not have included all variables of research interest and may have contained inconsistent information. To alleviate these problems, all medical records used in this study were jointly reviewed by 2 principal investigators. In addition, the investigators used a number of techniques recommended for chart reviews [25], to avoid unreliable or biased abstractions that may result from undefined chart review procedures. Those techniques helped increase the validity and reliability of the review process. Third, because only one medical center was included in the study, the current findings may not generalize to other institutions with different settings and patient patterns. Fourth, although the time elapsed from ED arrival to confirmed diagnosis in our sample was not very long (median, 120 minutes), the timing of confirmed diagnosis was still complicated by a number of factors, such as the time spent waiting for laboratory results, radiographic examinations, surgical consultations, and emergency physicians. As these times were not documented, it was impossible for us to evaluate the potential effects of ED crowding on the timing of diagnosis in patients with necrotizing fasciitis. Thus, it was unclear whether the timing

Previous studies have emphasized the importance of early diagnosis and early operation, especially that of the former, in improving the morbidity and mortality of necrotizing fasciitis [13,16-20]. Without early recognition and diagnosis of the infection, early operation is out of the question. However, in this study, the timing of confirmed diagnosis may not have been the key to patient outcomes. The median time from symptom onset to ED arrival was 3 days, which is consistent with prior studies [15,16,26]. In addition, the majority (69.7%) of our patients had their diagnosis of necrotizing fasciitis confirmed within 3 hours of ED arrival, and we did not find a statistically meaningful relationship between early diagnosis and in-hospital mortality. Therefore, although delayed diagnosis does inevitably lead to delayed operation, this was not the case in the current study. In previous investigations, some patients had delayed operation because they were not diagnosed as necrotizing fasciitis on admission in the first place [16]. Unfortunately, in this study, we were unable to determine the effects of missed diagnosis on the treatment of necrotizing fasciitis because we did not include patients who were diagnosed with necrotizing fasciitis until after leaving the ED. Nevertheless, the results of our study revealed that the timing of the diagnosis was not associated with mortality when the diagnosis of necrotizing fasciitis could be confirmed initially in the ED. The timing of adequate treatment is critical to certain patients, such as those with acute myocardial infarction and ischemic cerebrovascular events who are candidates for reperfusion therapy [27,28]. Likewise, trauma patients have been reported to benefit from qualified trauma centers that are properly staffed [29]. Common among these patients is the need for both time-sensitive treatments and continuous monitoring, which are difficult to implement in a crowded ED. As a result, it is not surprising that prolonged stay in an ED, especially because of “boarding,” is associated with higher mortality rates. Once patients have boarded in the ED, the involvement of specialized experts becomes very important [12]. These studies all exemplify the importance of sustained attention and treatments to patients with critical conditions. In this study of high-risk patients with necrotizing fasciitis, we reported an association between prolonged ED boarding stay and increased mortality. Converging evidence of this relationship has been reported previously, for instance, in another study showing an association between in-hospital survival and delayed transfer from ED to ICU (OR for delayed transfer, 0.709; 95% CI, 0.561-0.895; P= .004). In this study, delayed transfer was defined as transfer from ED to ICU 6 hours and later after the decision of ICU admission was made [12]. There are various possibilities

Prolonged ED stay in necrotizing fasciitis why prolonged ED boarding stay is associated with increased mortality. For example, it has been indicated that prolonged ED stay may imply delayed implementation of inpatient orders [30]. It has also been pointed out that ED crowding may reduce the quality of provided care [31]. The concern with prolonged ED boarding reflects the current condition and perplexity of ED and hospital crowding. Although ED overcrowding can be intensified by a wide range of factors, such as the increased number and complexity of patients sent to the ED, poor access to primary health care providers, insufficient bed availability, and delays in radiology and laboratory services [6-9], it appeared to us that hospital crowding was the fundamental determinant of the prolonged ED boarding stay observed in this study. Prior research has pointed out that ED overcrowding is caused mainly by inpatient “access block” [32-34], defined as the proportion of ED patients requiring admission who have stayed in the ED for a total of more than 8 hours [10]. Other investigations have suggested that for every 10% of increase in hospital occupancy, an admitted patient waits 18 minutes (95% CI, 12-24 minutes) longer in the ED for the inpatient bed [35], and the length of ED stay increases dramatically when the rate of hospital occupancy exceeds 90% [36]. A cross-institutional study in Western Australia illustrated a clear relationship among hospital overcrowding, mortality, and prolonged ED stay. In comparison to dying patients who experienced low hospital occupancy, those who experienced high hospital occupancy also had longer ED stay (risk ratio per hour of ED stay, 1.1; 95% CI, 1.1-1.1; Pb .001) [10]. This study also demonstrated that early operation was associated with decreased mortality in patients with necrotizing fasciitis, regardless of prolonged length of ED boarding stay. This finding is consistent with previous studies showing a connection between early operation and lower mortality rates in patients with necrotizing fasciitis [13,16,19,37]. In one study, for example, the average time from admission to operation was 90 hours in nonsurvivors vs 25 hours in survivors (P = .0002) [13]. Because necrotizing fasciitis is a surgical emergency, extensive and aggressive surgical intervention is crucial and time is critical. Even though early operation was a weaker determinant of mortality in the present study for patients with necrotizing fasciitis, the consistent finding of a link between early operation and decreased mortality across studies suggests that early operation is still an important factor to optimal outcomes in these patients. With only intravenous antibiotics treatment, the mortality rate of necrotizing fasciitis is nearly as high as 100% [24]. Close monitoring with physiologic support has also been recommended because organ failure is common [24].

6. Conclusion In summary, we report an association between prolonged ED boarding stay and increased mortality in patients with

389 necrotizing fasciitis. The timing of diagnosis was not critical to mortality if an accurate diagnosis of necrotizing fasciitis could be confirmed in the ED. Early operation within 24 hours of ED arrival was still recommended for optimal patient outcome.

Acknowledgments We thank Micah Geer, Ph.D., Department of Psychology, University at Buffalo for his valuable comments to this manuscript.

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