Article, Emergency Medicine

IV crystalloid fluid for acute alcoholic intoxication prolongs ED length of stay

a b s t r a c t

Objectives: acute alcohol intoxication is often treated in emergency departments by Intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the as- sociation of IVF infusion and length of stay in the ED.

Methods: This single-center retrospective cohort study was conducted in Japan and included patients aged

>= 20 years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis.

Results: A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan-Meier analysis and the generalized Wilcoxon test found no significant difference be- tween the two treatments in the time to ED discharge. The median time was 189 (IQR 160-230) minutes without IVF and 254.5 (203-267 minutes with IVF; p = 0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35-0.84, p = 0.006).

Conclusions: IVF for treatment of Acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care.

(C) 2017

Introduction

The number of alcohol Intoxicated patients transferred to hospitals by ambulance is increasing annually [1-3], and is the most frequent al- cohol-related disorder to present in emergency departments (EDs) [4]. These patients occupy ED observation beds [5], require substantial healthcare provider time and effort [6], and increase Medical costs [7]. In many countries, treatment of patients with acute alcohol intoxication includes intravenous crystalloid fluid (IVF) [3,8,9]. Most physicians be- lieve that IVF infusion promotes alcohol metabolism and shortens the time until awakening from alcohol intoxication [5,10]. However, data on the effectiveness of IVF for treatment of acute alcoholic intoxication is limited [11,12], and IVF may not affect long-term (4-6 h) blood alco- hol clearance [3]. Whether IVF speeds awakening of patients with acute alcohol intoxication or shortens ED stay is not clear, and confirmation is

* Corresponding author at: Department of Emergency Medicine and Critical Care, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32, Todaijima, Urayasu-city, Chiba, Japan.

E-mail address: [email protected] (Y. Homma).

of importance. This study assessed the association of IVF treatment fol- lowing acute alcoholic intoxication and length of ED stay.

Methods

Study design

The study was approved by the ethics committee of the Tokyo Bay Urayasu Ichikawa Medical Center and was conducted following the eth- ical guidelines of the Declaration of Helsinki. As the analysis was retro- spective and patient information was anonymized and de-identified prior to analysis, the need for patient consent was waived. The study was conducted at a single-center, Tokyo Bay Urayasu Ichikawa Medical Center, a 344 bed urban acute care community hospital in eastern Tokyo, with an annual ED census of 29,938. It is a regional trauma center and designated stroke/cardiovascular center with a 24-h capability of percutaneous coronary artery intervention and infusion of tissue plas- minogen activator.

https://doi.org/10.1016/j.ajem.2017.12.054

0735-6757/(C) 2017

674 Y. Homma et al. / American Journal of Emergency Medicine 36 (2018) 673676

Study setting and population

In Japan, alcohol can be legally consumed beginning at 20 years of age. Patients with acute alcohol intoxication seen at the hospital be- tween April 1, 2013 and March 31, 2015; who were >= 20 years of age, had a laboratory-estimated blood alcohol concentration , and re- quired observation in the ED were eligible. Patients who were admitted to the hospital, with trauma or other medical problems that required ED observation, who had taken sedating medications in combination with alcohol, or with aggressive behavior that prevented compliance with medical instructions were excluded.

Study protocol

Uncomplicated alcohol intoxication was diagnosed by patient histo- ry, physical examination, and laboratory testing that excluded patients with the criteria listed above. Histories were obtained by interviewing patients, others in attendance, and ED medical staff. Patient evaluation included 11 signs of alcohol intoxication. These were the smell of alco- hol, impaired fine motor control, impaired gross motor control, slurred speech, change in speech volume, decreased alertness, sweating, slow and/or shallow breathing, sleepiness, change in speech speed, and red eyes [13]. Patients were also evaluated for trauma. BAC was estimated as follows [1,14].

BAC (mg/dl) = serum osmolar gap x 4.6 (1)

Serum osmolar gap

= measured plasma osmolality (mOsm/kg)-2 Na+ (mEq/L)

+ urea concentration (mg/dL)/2.8

+ glucose concentration (mg/dL)/18 (2)

Laboratory testing was performed with a TMA\\2000FR chemistry analyzer (Toshiba Medical Systems Corporation, Japan), Centaur CP im- munoassay system (Siemens Healthineers, Germany), and an OM-6060 osmometer (Arkray, Japan). IVF and imaging were performed at the dis- cretion of the treating physician. Normal saline was used for IVF. Patient blood pressure, heart rate, respiratory rate, and oxygen saturation were continuously monitored. Responsiveness was monitored routinely, and Glasgow Coma Scale scores were recorded until clear conscious- ness was achieved.

Measurements

Data were obtained from hospital medical records and included ten variables that might affect the study outcome. These were sex, age, ini- tial GCS, time of ED visit, trauma, computed tomography (CT) scans, es- cort when leaving the hospital, estimated BAC, IVF, and length of stay (LOS) in the ED. The variables were chosen by clinical relevance and previous studies [11,15]. The number of self-removals of peripheral in- travenous catheters by patients given IVF infusions was also recorded.

Outcomes

The primary outcome was the LOS, defined as the time from the ini- tial medical staff contact to ED discharge. Intoxicated patients were discharged if they were alert, had a GCS of 15, were able to walk inde- pendently and safely, had no condition or injury requiring further eval- uation or treatment, and were judged as safe for discharge by the attending physician. IVF was discontinued when the attending physi- cian judged the patient safe for discharge.

Data analysis

Based on a pilot evaluation, we expected that by 200 min of a total 700 min of observation, 55% of those without IVF, and 30% of those

with IVF would be discharged. It was estimated that a sample of 102 pa- tients would be needed to detect the difference between those groups with a power of 80% and a two-sided significance level of 0.05. Contin- uous values were expressed as medians and interquartile range (IQR). Categorical values were expressed as n (%). Patient characteristics and outcomes were evaluated using the chi-square test for categorical vari- ables and the Mann-Whitney U test for continuous variables, including the outcome, as appropriate. A time-to-event analysis was performed to evaluate the effects of IVF on LOS, medians and IQRs were obtained by Kaplan-Meier analysis, and the generalized Wilcoxon test were used to assess the effect of IVF administration. Adjusted Hazard ratios (HRs) of ED discharge time were obtained with Cox proportional haz- ards regression adjusted for potential confounding factors. HRs and their 95% confidence intervals (CI) for the study outcome were calculat- ed. The potential confounders, factors that were biologically relevant, considered as possibly associated with outcome were included in the Cox proportional hazards model. They were sex, age, initial GCS, visit time (daytime was 8 am to 8 pm and nighttime was 8 pm to 8 am), trau- ma (yes/no), head CT scan (yes/no), escorted when leaving the hospital (yes/no), and estimated BAC. The statistical analysis was performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R 3.3.4 (R Foundation for Statistical Computing, Vienna, Austria) that adds statistical functions frequently used in biostatistics [16]. A p-value b 0.05 was considered statistically significant. A sensitivity analysis was used to determine the consistency of the association between the IVF and LOS. The multi- ple Linear regression analysis was repeated with LOS in the ED as a con- tinuous variable.

Results

Characteristics of study population

During the study period, 286 patients presenting in the ED were di- agnosed with acute alcohol intoxication; 106 were found eligible and were included in the analysis. Patient selection and disposition are shown in Fig. 1. The baseline characteristics of the included patients are shown in Table 1. Sixty-four (60.4%) patients were treated with IVF, and there were no statistically significant differences in any of the demographic or clinical variables in the two study groups, and univari- ate analysis found that the two groups were similar at baseline. No pa- tients had hypoglycemia or electrolyte abnormalities that needed treatment.

Main results

The median LOS was 189 min (142.5-266.75) for patients with IVF and 254.50 min (171.5-296.25) for those without IVF. The difference in LOS was not significantly different (Mann-Whitney U test, p = 0.057). The number of patients and their LOS are shown in Fig. 2. Four patients in the IVF group (6.3%) removed the peripheral intravenous catheter by themselves. As shown in Fig. 3, the effect of IVF infusion on LOS was estimated by the Kaplan-Meier method and the outcomes in the two study groups were compared by the generalized Wilcoxon test. The difference in cumulative probability of ED discharge of patients in the two study groups was not significant. The median minutes to dis- charge was 189 (160-230) minutes without IVF infusion and 254.5 (203-267) minutes with IVF (p = 0.052). When adjusted for potential confounding variables, Cox proportional hazards regression (Table 2) indicated that patients treated with IVF were less likely to discharged from the ED sooner than patients treated without IVF (HR 0.54, 95% CI: 0.35-0.84, p = 0.006).

The result of a sensitivity analysis was consistent with multiple line- ar regressions. A time-to-event analysis with the LOS as a continuous variable confirmed that IVF infusion prolonged the LOS (beta coefficient 56.83, 95% CI 17.08-96.58, p = 0.006).

Y. Homma et al. / American Journal of Emergency Medicine 36 (2018) 673676 675

Fig. 2. Emergency department length of stay of patients with or without IVF infusion. IVF, intravenous crystalloid fluid.

Alcohol metabolism

Alcohol is absorbed primarily by the stomach and the duodenum with small amounts excreted in the urine and sweat and by the lungs. The amounts excreted depend on blood alcohol concentration, but 90%-98% of ingested alcohol is converted to acetaldehyde in the liver by three Enzymatic pathways [2,17,18].

Disadvantages of intravenous fluid for acute alcohol intoxication

Discussion

Fig. 1. Patient selection and disposition.

The need for insertion of intravenous catheters and the additional care needed to administer IVF compared with conservative treatment increase the cost and complexity of managing alcohol intoxication [6]. For example, alcohol intoxication decreases patient attentiveness [13] and that often leads to self-removal of peripheral intravenous catheters. This should be prevented, which further increases the burden on health care providers and their frustration [6]. In addition, most patients are

Treatment of acute alcoholic intoxication with IVF infusion prolonged the LOS in the ED. In contrast to previous studies, the analysis was adjusted by Cox regression and time-to-event analysis for potential confounding factors known to be independently associated with LOS, including BAC and level of consciousness. IVF infusion by itself might have increased the confidence of the attending physician, leading to an increased LOS. Although it is short, the time required for removal of the peripheral intravenous catheter and hemostasis might have in- creased the LOS. However, it is not likely that either had a large influ- ence of the study results. The study indicates that treatment of uncomplicated alcohol intoxication with IVF infusion is not only ineffec- tive, but also unfavorable, because it Prolonged ED stay.

Table 1

Bivariate analysis of patient characteristics and IVF infusion for treating acute alcoholic intoxication

Characteristics

Without IVF

With IVF

p

value?

N

42

64

Male sex (%)

35 (83.3)

46 (71.9)

0.24

Age, median (IQR), y

29.5 (23.0-42.5)

34.5 (24.0-45.0)

0.18

GCS, median (IQR)

9 (7-14)

12 (9-14)

0.11

Visited at night time (%)

36 (85.7)

52 (81.2)

0.61

With trauma (%)

3 (7.1)

14 (21.9)

0.058

CT scans (%)

21 (50.0)

32 (50.0)

1

Escort (%)

29 (69.0)

41 (64.1)

0.68

Estimated BAC, median (IQR),

265.01

254.72

0.40

mg/dl

(207.29-310.68)

(200.81-295.67)

LOS at ED, median (IQR), min

189.00

254.50

0.057

(142.50-266.75)

(171.50-296.25)

IVF, intravenous crystalloid fluid; IQR, interquartile range; GCS, Glasgow Coma Scale; BAC, blood alcohol concentration; LOS, length of stay; ED, emergency department.

* chi-square or Mann-Whitney U test.

healthy, and unnecessary fluid overload could lead to decreased pulmo- nary function [19].

Effect of intravenous fluid on alcohol clearance

IVF infusion has been reported to reduce BAC of acute alcohol intox- icated patients [5,10,20], but the evidence for this is not consistent [11, 12,21]. Following redistribution, approximately 25% of the infused vol- ume of normal saline remains in the circulating blood after 30-60 min [22]. Consequently, the alcohol dilution effect decreases shortly after Bolus infusion. IVF may increase blood flow to the liver, but has only a

Fig. 3. Kaplan-Meier estimates of the probability of emergency department discharge with and without IVF infusion. ED, emergency department; IVF, intravenous crystalloid fluid.

676 Y. Homma et al. / American Journal of Emergency Medicine 36 (2018) 673676

Table 2 Cox proportional hazards regression of the association between discharge from ED and IVF treatment of acute alcoholic intoxication

Outcome

HR (95% CI) for discharge from ED

p-value

Unadjusted

0.70 (0.47-1.03)

0.08

Adjusted?

0.54 (0.35-0.84)

0.006

CI, confidence interval; LOS, length of stay; ED, emergency department.

* Adjusted for sex, age, initial GCS, visit time, trauma, Head CT scans, escort when leaving the ED, and estimated BAC.

limited effect on increasing alcohol clearance. Furthermore, BAC is poor- ly correlated with the clinical signs of acute alcohol intoxication [23,24]. Temporary declines of BAC that do not correlate with clinical symptoms do not demonstrate that intoxicated patients become sober earlier. Emergency physicians decide whether to discharge patients based on clinical signs, not decreased BAC [25]. IVF is only necessary for alcohol intoxicated patients with hypoglycemia, hypotension, or other compli- cations [3].

Limitations

The study was limited by its single-center design, which may have affected the generalizability of findings. However, this hospital accepts patients from both rural and urban areas regardless of the severity of in- toxication, and the population pyramid of the Urayasu Ichikawa area is similar to that of the national population pyramid. Therefore, at a mini- mum, the findings can be generalized to the general population in Japan. Second, BAC was estimated from the values of other blood tests, and there may be a difference between the real and estimated BAC. Howev- er, a good correlation has been previously demonstrated [14,26]. Finally, selection bias may have affected the treatment of study participants, as physicians might have administered IVF to patients assumed to require longer observation. However, the data analysis was adjusted for initial GCS and estimated BAC.

Conclusions

We conclude from our results that IVF for treatment of acute alcohol- ic intoxication prolonged the ED LOS even after adjusting for potential confounders and common side effects. Routine use of IVF for uncompli- cated alcohol intoxication should be avoided, and administered with care to patients who have medical conditions in addition to alcohol in- toxication. Patients given IVF to treat alcohol intoxication should be ob- served carefully and frequently.

Conflict of interest

All authors report no conflict of interest.

Financial support

No grant or other financial support.

Presentation

I presented this study at the 44th annual meeting of the Japanese as- sociation for acute medicine in 2016, Tokyo, Japan.

Acknowledgments

We thank the staff of the Graduate School of Public Health, St. Luke’s International University for assistance with the statistical analysis.

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