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Impact on ICU mortality of moderate alcohol consumption in patients admitted with infection
Journal of Critical Care 57 (2020) 91–96
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Journal of Critical Care journal homepage: www.journals.elsevier.com/journal-of-critical-care
Impact on ICU mortality of moderate alcohol consumption in patients admitted with infection Arnaud Gacouin, MD a,b,c,⁎, Benoit Painvin, MD a,b, Valentin Coirier, MD a,b, Quentin Quelven, MD a,b, Boris Delange, MD a,b, Vincent Joussellin, MD a,b, Félicie Belicard, MD a,b, Floriane L'her, MD a,b, Adel Maamar, MD a,b, Yves Le Tulzo, MD PhD a,b,c, Jean Marc Tadié, MD PhD a,b,c a b c
CHU Rennes, Maladies Infectieuses et Réanimation Médicale, F-35033 Rennes, France Université Rennes1, Faculté de Médecine, Biosit, F-35043 Rennes, France Inserm-CIC-1414, Faculté de Médecine, Université Rennes I, IFR 140, F-35033 Rennes, France
a r t i c l e
i n f o
Available online xxxx
Keywords: Infection Alcohol consumption Critical illness Cohort study Mortality
a b s t r a c t Purpose: Alcohol dependence is associated with poor prognosis in the intensive care unit (ICU), but it remains uncertain whether moderate alcohol consumption negatively affects the prognosis of critically ill patients admitted with infection. Materials and methods: In a prospective observational cohort study performed in 478 patients admitted with documented infection, mortality at day 28 in the group of abstainers and nontrauma patients with estimated alcohol consumption lower than 100 g/week was compared with that in non-alcohol-dependent patients with estimated alcohol consumption between 100 and 350 g/week. Results: In 97 patients (20%), alcohol consumption was estimated to be over 100 g/week, and in 391 patients (80%), alcohol consumption was estimated to be 100 g/week or less. The pathogens identified did not significantly differ between the two groups of patients. After adjusted analysis, alcohol consumption between 100 and 350 g/week remained significantly associated with mortality at day 28 (hazard ratio (HR): 1.67; 95% confidence interval (CI): 1.01–2.77; p = .04). Conclusion: Alcohol consumption between 100 and 350 g/week was independently associated with mortality at day 28. Our results suggest that in critically ill patients admitted with infection, moderate alcohol consumption is associated with a poorer prognosis. © 2020 Elsevier Inc. All rights reserved.
1. Introduction Current chronic or acute alcohol exposures are frequently encountered in critically ill patients [1,2]. In the intensive care unit (ICU) setting, the negative impact of alcohol on the outcome of patients with infection is mainly assessed in patients with alcohol use disorders (AUDs), defined by marked and repeated negative social and/or physical repercussions of their alcohol use [3] and consequent suffering from an advanced form of the disease. The impact of alcohol on outcomes of critically ill patients with infection has been less assessed in patients who currently consume alcohol but without evidence of alcohol-related social or physical consequences. It was recently demonstrated that the threshold for lowest risk of all-cause mortality
⁎ Corresponding author at: Service des Maladies Infectieuses et Réanimation Médicale, CHU Rennes, F-35033 Rennes, France. E-mail address: [email protected] (A. Gacouin).
https://doi.org/10.1016/j.jcrc.2020.02.008 0883-9441/© 2020 Elsevier Inc. All rights reserved.
was only approximately 100 g/week of alcohol [4], while patients with AUDs generally consume twice as much alcohol. Consequently, there is a need to assess in the ICU setting the impact of alcohol consumption not only in patients with alcohol abuse or dependence but also in those with less severe consumption but who are still at risk of alcohol-related complications. In addition, recent data examining the impact of alcohol use in critically ill patients admitted to the ICU with infection are limited, and definitions for sepsis and septic shock were recently updated [5]. We hypothesized that in critically ill patients, as reported outside of the ICU, the risk of poor outcome begins from lower doses of alcohol consumption than previously described. To test this hypothesis, we performed a prospective observational study to determine whether patients who consumed more than 100 g/week of alcohol, with no criteria for alcohol dependence, and admitted to the ICU with documented infection significantly differ in pathogens involved, severity of infection, and outcomes from abstainers and patients with alcohol consumption lower than 100 g/week.
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2. Materials and methods 2.1. Patients and setting Baseline characteristics of the patients and prognostic data were collected prospectively from October 15, 2015 to October 15, 2018. The study was approved by the ethics committee of the CHU de Rennes (avis No. 15.103), which waived the need for signed informed consent. Adults with microbiologically documented infections were eligible for the study. Patients with liver cirrhosis and liver transplant recipients were not screened for the study, to focus on patients with less advanced liver disease than those with cirrhosis, for which the negative impact of infection on the prognosis in the ICU is already clearly established [6]. 2.2. Assessment of alcohol consumption and exclusion of patients with criteria for alcohol dependence Alcohol consumption was assessed as previously described, and the assessment of alcohol consumption has been routine since 2005 in our ICU [7]. Some of the data analyzed here were collected during another observational study [8]. We systematically interviewed the patient and/or their closest relative about alcohol consumption. In practice, most alcohol consumers and/or relatives of alcohol consumers are not able to precisely recall the different types of drinks and their amounts. Consequently, patients and relatives were asked about the number of drinks consumed on a typical day, and as proposed by the World Health Organization, we assumed that one drink contained 10 g of pure alcohol. Patients who consumed 5 drinks or more per day, more than 350 g/ week, were excluded from the study with the aim of avoiding including patients at high risk of alcohol dependence [9]. Because we were concerned with studying patients without alcohol dependence, we also used the Alcohol Use Disorders Identification Test (AUDIT) to detect alcohol-related dependence in patients with an average consumption of 3 or 4 drinks per day. However, in some patients, alcohol consumption could be estimated only by interviewing close relatives, and consequently, in a few patients, the AUDIT score was not available. Previous medical records were also systematically reviewed for the diagnosis of chronic alcohol abuse or prior hospital stay for alcohol withdrawal. 2.3. Microbiologically documented infections Infection was defined as microbiologically documented based on the association of a clinical/radiological focus of infection and isolation of an associated pathogen and in accordance with published guidelines for utilization of the microbiology laboratory for diagnosis of infectious diseases, healthcare-associated and hospital-acquired infections, infections in patients with cancer or hematological diseases, and infections in neutropenic patients [10-13]. In short, bacterial infection was considered microbiologically documented in patients with bacteremia or evidence of bacteria in normally sterile sites, including cerebrospinal fluid or brain biopsy, joint and peritoneal fluid, heart valve, and soft tissues obtained after a sterile procedure. For some sites (e.g., prosthetic material, bone), two different tissue samples or two consecutive blood samples were required for pathogens that were not highly virulent, such as coagulase-negative staphylococci. Bacterial pneumonia was also considered as documented in patients positive for urinary antigen for Legionella sp. or Streptococcus pneumonia and in patients with a positive semiquantitative culture from a tracheal aspirate (cutoff 106 colonyforming units/mL) or bronchoalveolar lavage (BAL) (cutoff 104 colonyforming units/mL). Patients with fever, diarrhea, abdominal pain or detection of Clostridium difficile, Campylobacter jejuni, or Escherichia coli with Shiga toxin were diagnosed as having documented gut infection. Urinary tract infection was documented mainly in patients with pyelonephritis. Viral infections were documented mainly based on polymerase chain reaction (PCR) or reverse transcription (RT) PCR tests performed on blood, respiratory samples, or tissues, especially
for influenza virus and other respiratory viruses, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein–Barr virus and/or serodiagnosis for the other hepatitis viruses. Fungal infection was documented based on positive culture from blood (especially for Candida spp.) or a site suspected of infection and/or positive Aspergillus antigen in blood and/or BAL. For documentation of Pneumocystis jiroveci pneumonia, cytological examination (Gomori-Grocott staining), immunofluorescence and PCR pneumonia were performed on BAL for the detection of Pneumocystis jiroveci. 2.4. Data collection On admission, the following data were recorded: age, sex, Simplified Acute Physiology Score (SAPS) II [14], Sequential Organ Failure Assessment (SOFA) score [15], type of admission (emergency surgery, elective surgery, or medical), operative admission diagnosis (respiratory, cardiovascular, neurological, renal, gastrointestinal, musculoskeletal/skin, and other), presence of community- or hospital-acquired infection, and comorbidities (i.e., diabetes mellitus, congestive heart failure, chronic heart and respiratory diseases, chronic kidney disease, and aplasia or solid tumor or hematological disease). The presence of septic shock [5,16], moderate or severe acute respiratory distress syndrome (ARDS) [17], and acute kidney injury [18] on admission to the ICU was also recorded. Serum lactate levels were recorded within the 4 h preceding and the 24 h following ICU admission. Patients were followed up for death until day 28 after admission to the ICU. 2.5. Definitions Known chronic kidney disease (CKD) was defined as glomerular filtration rate b 60 mL/min/1.73 m2, estimated based on known baseline serum creatinine [19]. ARDS was diagnosed according to the Berlin criteria [17]. In patients with community-acquired infection, the diagnosis of sepsis was retained in patients with SOFA score ≥ 2 points, assuming their baseline SOFA score was zero before hospital admission; in patients admitted with hospital-acquired infection, an acute change in total SOFA score ≥ 2 points was required [5]. Patients who required vasopressors after volume resuscitation and with serum lactate level ≥ 2 mmol/L were considered to have septic shock [5]. Acute kidney injury (AKI) was staged for severity based on the Kidney Disease Improving Global Outcome (KDIGO) criteria [18]. Chronic heart disease was considered in patients with previous coronary artery and/or valvular disease with treatment (e.g., diuretics, antiarrhythmic, antihypertensive medications). Chronic respiratory disease covered obstructive and restrictive diseases, including chronic obstructive pulmonary disease, kyphoscoliosis, and obesity-hypoventilation syndrome. Immunocompromised patients were those with aplasia and/or recent chemotherapy for solid tumor or hematologic disease and those who received 20 mg per day or more of prednisolone for two weeks or more or a lower daily dose for more than three weeks. Solid tumor and hematologic disease were considered when treated actively or diagnosed within the year before admission. The following causes of death were distinguished: primary infection-related multiple-organ failure, mesenteric ischemia, end-oflife decision, ARDS, central nervous system disorder, and others [20]. 2.6. End points The primary end point was the comparison, between patients who consumed more than 100 g/week and those who consumed 100 g/ week or less of alcohol, of the cumulative incidence of mortality until day 28 after admission to the ICU. Secondary end points included comparison of pathogens involved and the comparison of causes of death between the two groups of patients.
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2.7. Statistical analysis The study was designed to have 80% power to detect a 20% difference in mortality in patients with sepsis/septic shock with a confidence interval of 95% between patients who consumed less than 100 g/week (expected mortality of 15%) and those who consumed more than 100 g/week (expected mortality of 35%) [21], at a twosided error α of 5%. This generated the minimum sample size of 72 patients per group. Based on our previous studies, a three-year duration was estimated to be sufficient for the study. Continuous variables are expressed as median and interquartile range and were compared by the nonparametric Mann-Whitney U test. Proportions were compared by the chi-square test or Fisher's exact test when required. Tests were two-sided, and we considered p b .05 to be statistically significant. Survival curves were constructed until day 28 by using the KaplanMeier method and were compared by the log-rank test. Patients alive at day 28 were censored. Distributions between groups were compared by the log-rank test. We used a Cox proportional hazard model to determine whether at-risk drinking was a comorbidity independently associated with mortality at day 28. Variables were removed in a backward stepwise selection process on the basis of a significance level of 0.10 in the unadjusted analysis. The results were expressed as hazard ratios (HRs) with their 95% confidence intervals (CIs), and analysis was adjusted for the following variables recorded on the first day of ICU stay because they were associated with prognosis in critically ill patients with infection: SAPS II and SOFA scores, serum lactate level, treatment with vasopressors (i.e., epinephrine, norepinephrine, and dobutamine at any dose), and diagnoses of ARDS and KDIGO stage 2–3 AKI. In addition, the following comorbidities were considered for analysis because they were potentially confounding variables: age ≥ 65 years, diabetes mellitus, aplasia and/or recent chemotherapy for solid tumor or hematologic disease, chronic kidney disease, and chronic heart and/or respiratory disease.
3. Results During the 36-month study period, 586 patients with no liver cirrhosis and no liver transplantation were admitted to the ICU with microbiologically documented infection. Alcohol consumption could be assessed in 554 patients (94%). Among the 554 patients, 70 patients (10%) consumed 5 drinks per day or more (i.e., weekly estimated alcohol intake above 350 g), and the AUDIT score was found to be positive for dependence in 6 patients who consumed 4 drinks per day. A total of 478 patients were studied. In 97 patients (20%), alcohol consumption was estimated to be over 100 g/week, and in 391 patients (80%), alcohol consumption was estimated to be 100 g/week or less. Five patients among the 36 with estimated alcohol consumption over 100 g/week after interviewing their closest relatives could not be assessed for AUDIT.
3.1. Baseline characteristics of patients The baseline characteristics of the patients are compared between the two groups in Table 1. Weekly alcohol consumption was significantly higher in patients with estimated alcohol consumption over 100 g/week than in patients who consumed 100 g/week or less (median of 210 g/week (140–280) versus 0 g/week (0–70), p b .001). Organ dysfunctions as assessed by the SOFA score were significantly more severe in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less. The proportions of patients with pneumonia were similar in the two groups, and the proportion of patients with bacteremia was significantly higher in patients who consumed more than 100 g/week compared to other patients.
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Table 1 Baseline characteristics of patients at admission to the ICU, infections, and death in the ICU compared whether patients consumed less or more than 100 g/week of alcohol. Whole population
Assessment of alcohol consumption, n (%) Self-reported only Self-reported and closest relatives Closest relatives only Age ≥ 65 years, n (%) Male gender SAPS II score, points median (IQR) SOFA score, points median (IQR) Admission type, n (%) Medical Emergency surgery Elective surgery Diabetes mellitus, n (%) Chronic heart or lung disease, n (%) Immunocompromised, n (%) Chronic kidney disease, n (%) Serum lactates level, mmol/L median (IQR) Community-acquired infection, n (%) Site of infection, n (%) Pneumonia Urinary tract Central nervous system Endocarditis Skin and soft tissues Digestive tract Other or unknown Bacteremia, n (%) ARDS KDIGO AKI stage 2.3 Sepsis and septic shock, n (%) Sepsis Septic shock Death in ICU Death at day-28
Weekly consumption of alcohol
P Value
n = 478
N 100 g n = 97
≤ 100 g n = 381
81 (17) 239 (50)
15 (16) 46 (47)
66 (17) 193 (51)
158 (33) 226 (47) 269 (56) 44 (32–60) 8 (4–10)
36 (37) 54 (56) 77 (79) 48 (36–62) 9 (5–11)
122 (32) 172 (45) 192 (50) 44 (32–59) 7 (4–10)
438 (92) 34 (7) 6 (1) 64 (13) 207 (43)
87 (90) 8 (8) 2 (2) 17 (17) 47 (48)
351 (92) 26 (7) 4 (1) 47 (12) 160 (42)
95 (20) 73 (15) 1.7 (1.2–2.8) 414 (87)
24 (25) 10 (10) 1.9 (1.3–3.4) 84 (86)
71 (19) 63 (17) 1.7 (1.2–2.7) 330 (87)
0.19 0.18 0.12
237 (50) 56 (12) 33 (7) 43 (9) 30 (6) 43 (9) 34 (7) 136 (28) 86 (18) 146 (30)
49 (50) 10 (10) 4 (2) 9 (9) 13 (8) 8 (6) 6 (4) 36 (37) 17 (17) 50 (32)
188 (50) 46 (12) 31 (8) 34 (9) 17 (4) 35 (9) 28 (8) 10 (26) 69 (18) 96 (25)
0.02
358 (75) 120 (25) 99 (21) 99 (21)
68 (70) 29 (30) 33 (28) 29 (29)
290 (76) 91 (24) 68 (18) 70 (19)
0.62
0.07 b0.0001 0.14 0.002 0.66
0.18 0.25
0.99
0.04 0.89 b0.0001 0.23 0.02 0.03
Abbreviations: IQR, interquartile range; SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; ARDS, acute respiratory distress syndrome; ICU, Intensive Care Unit.
3.2. Mortality at day 28 after admission to the ICU in the whole population Of note, the proportion of patients with septic shock at admission to the ICU did not differ significantly between the two groups of patients. The same was true of ARDS. However, when organ dysfunctions were considered, sub-SOFA scores for cardiovascular dysfunction and subSOFA scores for non-cardiovascular dysfunctions were significantly higher in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less (4 points (1–4) vs 3 points (1–4), p = .04 and 5 points (4–7) vs 5 points (3–7), p = .01, respectively). The ICU mortality rate was significantly higher in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less (28% versus 18%, p = .02). Survival at day 28 was significantly lower in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less, as determined by the logrank test (p = .03, Fig. 1). Alcohol consumption greater than 100 g/week remained independently associated with mortality after adjustment for other comorbidities recorded at admission to the ICU (HR: 1.67; 95% CI: 1.01–2.77; p = .04) (Table 2). Six of the 20 women (30%) and 22 of the 77 males (29%) who consumed more than 100 g/week died within the
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Fig. 1. Cumulative 28-day mortality from admission to the ICU.
28 days following ICU admission (p = .86 after comparison). Of note, 28 patients (6%) stopped their excessive alcohol consumption six months or more before admission to the ICU, a characteristic not associated with 28-day mortality (HR = 0.83, 95% CI 0.34–2.05, p = .69). 3.3. Pathogens involved between at-risk and not at-risk drinkers The pathogens involved are listed and compared between groups in Table 3. We found no significant differences after comparisons regarding the pathogens involved, including multidrug-resistant (MDR) bacteria. 3.4. Causes of death Among the 33 patients who consumed less than 100 g/week who died in the ICU, the cause of death was primary infection-related multiple-organ failure in 14 patients (42%), ARDS in 5 patients (15%), central nervous system disorder in 5 patients (15%), end-of-life decision in 3 patients (9%), mesenteric ischemia in 2 patients (6%), and other reasons in 4 patients (12%). Among patients who consumed 100 g/week or more who died in the ICU, the cause of death was primary infectionrelated multiple-organ failure in 27 patients (33%), ARDS in 12 patients (15%), central nervous system disorder in 13 patients (16%), end-of-life decision in 14 patients (17%), mesenteric ischemia in 6 patients (7%), and other reasons in 9 patients (11%). Proportions for causes of death did not differ significantly between patients who consumed 100 g/ week or less and those who consumed more than 100 g/week (p = .89).
4. Discussion In this three-year prospective observational study performed on patients with microbiologically documented infection at admission to the ICU, weekly alcohol intake between 100 g and 350 g/week and no criteria for alcohol dependence were independently associated with 28-day mortality, while the pathogens involved, severity of infection at admission to the ICU, and causes of death in the ICU did not significantly differ whether patients consumed less or more than 100 g/ week of alcohol. Similar to the adverse association of moderate but regular alcohol consumption with mortality reported outside the ICU, alcohol consumption lower than that generally encountered in patients with alcohol dependence critically places patients with documented infection at higher risk of mortality. To our knowledge, this is the first study designed to investigate the impact of chronic alcohol consumption at doses lower than those generally encountered in patients with dependence on alcohol on the outcomes of critically ill patients admitted with documented infection in whom sepsis and septic shock were distinguished from each other, based on a recent classification [5]. A study that used a large database reported that critically ill patients with alcohol dependence had higher rates of sepsis, organ failure, septic shock, and hospital mortality [22], a finding reported by other authors [23]. Accordingly, we found that chronic alcohol consumption was associated with a poorer prognosis among critically ill patients with infection, but our results also suggest that the negative impact of alcohol on outcomes begins from levels of consumption lower than those generally encountered in patients with
Table 2 Unadjusted and adjusted hazard ratios for 28-day mortality from ICU admission. Variables
Unadjusted hazard ratio (95% CI)
p Value
Adjusted hazard ratio (95% CI)
p Value
Alcohol consumption over 100 g/week SAPS II score (1-point increment) SOFA score (1-point increment) Serum lactates level (1 mmol/L increment) ARDS KDIGO stage 2–3 AKI Treatment with vasopressors Age ≥ 65 years Diabetes mellitus Immunocompromised Chronic respiratory and/or cardiovascular disease Chronic kidney disease
2.03 (1.31–3.14) 1.043 (1.035–1.052) 1.267 (1.200–1.337) 1.218 (1.152–1.288) 1.35 (0.83–2.18) 2.35 (1.58–3.48) 2.51 (1.69–3.74) 2.41 (1.58–3.65) 1.83 (1.12–2.99) 2.20 (1.45–3.34) 1.42 (0.96–2.11) 1.75 (1.09–2.78)
0.001 b0.0001 b0.0001 b0.0001 0.22 b0.0001 b0.0001 b0.0001 0.02 0.0002 0.08 0.02
1.67 (1.01–2.77) 1.021 (1.007–1.035) 1.178 (1.075–1.291) 1.079 (1.001–1.164)
0.04 0.003 0.0005 0.047
1.71 (1.03–2.95) 1.79 (1.12–2.86)
0.04 0.01
CI, Confident interval Abbreviations: SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; ARDS, acute respiratory distress syndrome; AKI, Acute Kidney Injury; KDIGO, Kidney Disease Improving Global Outcomes.
A. Gacouin et al. / Journal of Critical Care 57 (2020) 91–96 Table 3 Microbiological data compared whether patients consumed less or more than 100 g/week of alcohol. Whole Weekly population consumption of alcohol
Class of pathogens involved, n (%)⁎ Bacteria Virus Fungi Main classes of pathogens detected, n (%)a Gram-positive cocci Streptococcus pneumoniae, Staphylococcus aureus Streptococcus Other gram positive cocci Gram negative bacilli Escherichia coli Haemophilus Influenza Pseudomonas aeruginosa Other gram negative bacilli Intracellular bacteria Particular bacteria b Influenza virus Viruses other than influenza Pneumocystis jiroveci or Aspergillusfumigatus Multi-drug resistant bacteria, n (%)
P value
n = 478
N 100 g ≤ 100 g n = 97 n = 381
376 (79) 94 (19) 35 (7)
77 (79) 299 (78) 0.85 19 (15) 81 (21) 0.19 6 (7) 29 (8) 0.78
60 (13) 78 (16) 45 (9) 5 (1)
12 (12) 10 (10) 10 (10) 3 (2)
40 (12) 62 (16) 35 (9) 2 (0.05)
0.94 0.99 0.73 0.30
80 (16) 26 (5) 21 (4) 51 (11) 11 (2) 24 (5) 59 (12) 35 (7) 35 (7)
25 (16) 8 (8) 3 (3) 14 (14) 2 (1) 4 (4) 13 (13) 6 (6) 6 (6)
65 (16) 18 (5) 18 (5) 37 (10) 9 (2) 20 (5) 46 (12) 29 (8) 29 (8)
0.82 0.17 0.68 0.17 0.99 0.79 0.73 0.41 0.82
56 (15)
12 (12) 45 (15)
0.86
a
Some patients had mixed infection. b Mycobacterium tuberculosis, n = 4; Mycobacterium avium, n = 1; leptospirosis, n = 5; Clostridium difficile, n = 4; Neisseiria meningitides, n = 3; Listeria monocytogenes, n = 2; Nocardia, n = 1; Salmonella paratyphi, n = 1; Clostridium tetani, n = 1; Pasteurella multicoda, n = 1; Bartonella henslea, n = 1.
dependence. Our results are in agreement with those reported outside the ICU and especially with those of a large, recently published epidemiological study, since the threshold for lowest risk of all-cause mortality was 100 g/week [4]. However, the negative impact on outcomes of low or moderate amounts of alcohol intake is less clearly established for critically ill patients. In one study [24], excessive alcohol consumption increased short- and long-term mortality only in critically ill patients with chronic complications of their alcoholism. The proportion of patients with alcohol intake between 100 g and 350 g/week admitted to the ICU with septic shock, diagnosed based on updated criteria, was not significantly higher than that of patients who consumed no alcohol or less than 100 g/week. However, when patients were assessed in terms of organ dysfunctions using the SOFA score, cardiovascular and noncardiovascular organ dysfunctions were significantly more severe in patients who consumed between 100 and 350 g/week. It is generally considered that infections are more frequent at many sites (e.g., lungs, blood, skin, wounds, or sites of surgery) in alcohol abusers than moderate or abstinent drinkers and that the pathogens involved differ if patients are excessive alcohol consumers. Our results suggest that these data are not accurate when considering alcohol abusers without alcohol dependence, and we believe that patients admitted to the ICU should be screened not only for AUDs but also for moderate alcohol consumption. Overall, our results suggest that empirical microbiological treatment should not be different whether patients consume moderate amounts of alcohol. Consequently, we make the assumption that improvement of the ICU outcome of the patients with moderate alcohol consumption and infection could be obtained more by a prompt support of organ dysfunctions than particular practices in the management of antibiotics. Of note, we consider that inclusion of patients with undocumented infection would have induced a bias due to a more intensive research on pathogens involved in more severe patients, since we suspected that patients who consumed more than
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100 g/week would have worse severity scores on admission to the ICU than those with alcohol consumption lower than 100 g/week. Previous studies have suggested that chronic alcohol consumption predisposes patients to ARDS [25]. In our study, the proportion of patients with ARDS was not significantly higher among those who consumed more than 100 g/week than among those who consumed less or no alcohol. This may be explained by the fact that patients were defined as ARDS patients at admission to the ICU and not throughout the entire ICU stay. Furthermore, our study focused on documented infectionrelated ARDS, excluding other causes of ARDS, and patients with alcohol dependence were excluded from our study. The deleterious effects of chronic alcohol exposure on immunity are well identified, although they were not assessed in our study. Chronic alcohol consumption alters liver function, even in the absence of cirrhosis [26], and it has been demonstrated that the capacity of the liver to clear bacteria is an important determinant of the outcome in sepsis [27]. Chronic alcohol consumption alters innate and adaptive immunity, including changes in the number and function of immune cells [28,29,30,31,32]. The question arises whether the alterations in immunity are the same in critically ill patients depending on whether alcohol consumption is moderate or heavy. The arrest of excessive alcohol consumption six months before admission to the ICU was not associated with the prognosis. Some have demonstrated that the monocyte response to infection is partially restored after two weeks of alcohol withdrawal [31]. Our study had several limitations. The data were collected at a single site, and the results may not be generalizable. Because of the observational nature of the study, we cannot exclude uncontrolled confounders. Risk factors for delirium and preexisting psychiatric disorders were not assessed but were associated with poorer outcomes. There were no trauma patients, and our center is localized in an area where alcoholism is a major public health problem. Alcohol consumption was assessed by interviewing patients and/or their relatives, and the validity of this information may thus be open to doubt. Therefore, the assessment of alcohol consumption could have been less accurate when those relatives did not live with the patient. However, the quantification of alcohol consumption in ICU patients is not easy in clinical practice, especially because there is currently no simple test that can confirm the diagnosis of excessive alcohol consumption [4,32]. In addition, patients were classified based on the assumption that a drink contained 10 g of alcohol, but according to studies, “a drink” can contain from 6 to 16 g of alcohol. 5. Conclusion Several studies have suggested that moderate drinking, usually defined by the daily consumption of one to two drinks per day, may exert beneficial effects on immunity and consequently diminish the risk and severity of infections [30]. In contrast, our results suggest that critically ill patients with documented infection are at a higher risk of a poor prognosis starting from a level of alcohol consumption that is lower than those generally reported in studies performed in the ICU. Nonetheless, we did not find that alcohol consumption was associated with any particular pathogens when infections were microbiologically documented, nor with a particular cause of death. Our results suggest that low levels of alcohol consumption put critically ill patients admitted to the ICU with infection at a higher risk of a poor outcome, a finding previously reported outside of the ICU. Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None.
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Contents lists available at ScienceDirect
Journal of Critical Care journal homepage: www.journals.elsevier.com/journal-of-critical-care
Impact on ICU mortality of moderate alcohol consumption in patients admitted with infection Arnaud Gacouin, MD a,b,c,⁎, Benoit Painvin, MD a,b, Valentin Coirier, MD a,b, Quentin Quelven, MD a,b, Boris Delange, MD a,b, Vincent Joussellin, MD a,b, Félicie Belicard, MD a,b, Floriane L'her, MD a,b, Adel Maamar, MD a,b, Yves Le Tulzo, MD PhD a,b,c, Jean Marc Tadié, MD PhD a,b,c a b c
CHU Rennes, Maladies Infectieuses et Réanimation Médicale, F-35033 Rennes, France Université Rennes1, Faculté de Médecine, Biosit, F-35043 Rennes, France Inserm-CIC-1414, Faculté de Médecine, Université Rennes I, IFR 140, F-35033 Rennes, France
a r t i c l e
i n f o
Available online xxxx
Keywords: Infection Alcohol consumption Critical illness Cohort study Mortality
a b s t r a c t Purpose: Alcohol dependence is associated with poor prognosis in the intensive care unit (ICU), but it remains uncertain whether moderate alcohol consumption negatively affects the prognosis of critically ill patients admitted with infection. Materials and methods: In a prospective observational cohort study performed in 478 patients admitted with documented infection, mortality at day 28 in the group of abstainers and nontrauma patients with estimated alcohol consumption lower than 100 g/week was compared with that in non-alcohol-dependent patients with estimated alcohol consumption between 100 and 350 g/week. Results: In 97 patients (20%), alcohol consumption was estimated to be over 100 g/week, and in 391 patients (80%), alcohol consumption was estimated to be 100 g/week or less. The pathogens identified did not significantly differ between the two groups of patients. After adjusted analysis, alcohol consumption between 100 and 350 g/week remained significantly associated with mortality at day 28 (hazard ratio (HR): 1.67; 95% confidence interval (CI): 1.01–2.77; p = .04). Conclusion: Alcohol consumption between 100 and 350 g/week was independently associated with mortality at day 28. Our results suggest that in critically ill patients admitted with infection, moderate alcohol consumption is associated with a poorer prognosis. © 2020 Elsevier Inc. All rights reserved.
1. Introduction Current chronic or acute alcohol exposures are frequently encountered in critically ill patients [1,2]. In the intensive care unit (ICU) setting, the negative impact of alcohol on the outcome of patients with infection is mainly assessed in patients with alcohol use disorders (AUDs), defined by marked and repeated negative social and/or physical repercussions of their alcohol use [3] and consequent suffering from an advanced form of the disease. The impact of alcohol on outcomes of critically ill patients with infection has been less assessed in patients who currently consume alcohol but without evidence of alcohol-related social or physical consequences. It was recently demonstrated that the threshold for lowest risk of all-cause mortality
⁎ Corresponding author at: Service des Maladies Infectieuses et Réanimation Médicale, CHU Rennes, F-35033 Rennes, France. E-mail address: [email protected] (A. Gacouin).
https://doi.org/10.1016/j.jcrc.2020.02.008 0883-9441/© 2020 Elsevier Inc. All rights reserved.
was only approximately 100 g/week of alcohol [4], while patients with AUDs generally consume twice as much alcohol. Consequently, there is a need to assess in the ICU setting the impact of alcohol consumption not only in patients with alcohol abuse or dependence but also in those with less severe consumption but who are still at risk of alcohol-related complications. In addition, recent data examining the impact of alcohol use in critically ill patients admitted to the ICU with infection are limited, and definitions for sepsis and septic shock were recently updated [5]. We hypothesized that in critically ill patients, as reported outside of the ICU, the risk of poor outcome begins from lower doses of alcohol consumption than previously described. To test this hypothesis, we performed a prospective observational study to determine whether patients who consumed more than 100 g/week of alcohol, with no criteria for alcohol dependence, and admitted to the ICU with documented infection significantly differ in pathogens involved, severity of infection, and outcomes from abstainers and patients with alcohol consumption lower than 100 g/week.
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2. Materials and methods 2.1. Patients and setting Baseline characteristics of the patients and prognostic data were collected prospectively from October 15, 2015 to October 15, 2018. The study was approved by the ethics committee of the CHU de Rennes (avis No. 15.103), which waived the need for signed informed consent. Adults with microbiologically documented infections were eligible for the study. Patients with liver cirrhosis and liver transplant recipients were not screened for the study, to focus on patients with less advanced liver disease than those with cirrhosis, for which the negative impact of infection on the prognosis in the ICU is already clearly established [6]. 2.2. Assessment of alcohol consumption and exclusion of patients with criteria for alcohol dependence Alcohol consumption was assessed as previously described, and the assessment of alcohol consumption has been routine since 2005 in our ICU [7]. Some of the data analyzed here were collected during another observational study [8]. We systematically interviewed the patient and/or their closest relative about alcohol consumption. In practice, most alcohol consumers and/or relatives of alcohol consumers are not able to precisely recall the different types of drinks and their amounts. Consequently, patients and relatives were asked about the number of drinks consumed on a typical day, and as proposed by the World Health Organization, we assumed that one drink contained 10 g of pure alcohol. Patients who consumed 5 drinks or more per day, more than 350 g/ week, were excluded from the study with the aim of avoiding including patients at high risk of alcohol dependence [9]. Because we were concerned with studying patients without alcohol dependence, we also used the Alcohol Use Disorders Identification Test (AUDIT) to detect alcohol-related dependence in patients with an average consumption of 3 or 4 drinks per day. However, in some patients, alcohol consumption could be estimated only by interviewing close relatives, and consequently, in a few patients, the AUDIT score was not available. Previous medical records were also systematically reviewed for the diagnosis of chronic alcohol abuse or prior hospital stay for alcohol withdrawal. 2.3. Microbiologically documented infections Infection was defined as microbiologically documented based on the association of a clinical/radiological focus of infection and isolation of an associated pathogen and in accordance with published guidelines for utilization of the microbiology laboratory for diagnosis of infectious diseases, healthcare-associated and hospital-acquired infections, infections in patients with cancer or hematological diseases, and infections in neutropenic patients [10-13]. In short, bacterial infection was considered microbiologically documented in patients with bacteremia or evidence of bacteria in normally sterile sites, including cerebrospinal fluid or brain biopsy, joint and peritoneal fluid, heart valve, and soft tissues obtained after a sterile procedure. For some sites (e.g., prosthetic material, bone), two different tissue samples or two consecutive blood samples were required for pathogens that were not highly virulent, such as coagulase-negative staphylococci. Bacterial pneumonia was also considered as documented in patients positive for urinary antigen for Legionella sp. or Streptococcus pneumonia and in patients with a positive semiquantitative culture from a tracheal aspirate (cutoff 106 colonyforming units/mL) or bronchoalveolar lavage (BAL) (cutoff 104 colonyforming units/mL). Patients with fever, diarrhea, abdominal pain or detection of Clostridium difficile, Campylobacter jejuni, or Escherichia coli with Shiga toxin were diagnosed as having documented gut infection. Urinary tract infection was documented mainly in patients with pyelonephritis. Viral infections were documented mainly based on polymerase chain reaction (PCR) or reverse transcription (RT) PCR tests performed on blood, respiratory samples, or tissues, especially
for influenza virus and other respiratory viruses, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein–Barr virus and/or serodiagnosis for the other hepatitis viruses. Fungal infection was documented based on positive culture from blood (especially for Candida spp.) or a site suspected of infection and/or positive Aspergillus antigen in blood and/or BAL. For documentation of Pneumocystis jiroveci pneumonia, cytological examination (Gomori-Grocott staining), immunofluorescence and PCR pneumonia were performed on BAL for the detection of Pneumocystis jiroveci. 2.4. Data collection On admission, the following data were recorded: age, sex, Simplified Acute Physiology Score (SAPS) II [14], Sequential Organ Failure Assessment (SOFA) score [15], type of admission (emergency surgery, elective surgery, or medical), operative admission diagnosis (respiratory, cardiovascular, neurological, renal, gastrointestinal, musculoskeletal/skin, and other), presence of community- or hospital-acquired infection, and comorbidities (i.e., diabetes mellitus, congestive heart failure, chronic heart and respiratory diseases, chronic kidney disease, and aplasia or solid tumor or hematological disease). The presence of septic shock [5,16], moderate or severe acute respiratory distress syndrome (ARDS) [17], and acute kidney injury [18] on admission to the ICU was also recorded. Serum lactate levels were recorded within the 4 h preceding and the 24 h following ICU admission. Patients were followed up for death until day 28 after admission to the ICU. 2.5. Definitions Known chronic kidney disease (CKD) was defined as glomerular filtration rate b 60 mL/min/1.73 m2, estimated based on known baseline serum creatinine [19]. ARDS was diagnosed according to the Berlin criteria [17]. In patients with community-acquired infection, the diagnosis of sepsis was retained in patients with SOFA score ≥ 2 points, assuming their baseline SOFA score was zero before hospital admission; in patients admitted with hospital-acquired infection, an acute change in total SOFA score ≥ 2 points was required [5]. Patients who required vasopressors after volume resuscitation and with serum lactate level ≥ 2 mmol/L were considered to have septic shock [5]. Acute kidney injury (AKI) was staged for severity based on the Kidney Disease Improving Global Outcome (KDIGO) criteria [18]. Chronic heart disease was considered in patients with previous coronary artery and/or valvular disease with treatment (e.g., diuretics, antiarrhythmic, antihypertensive medications). Chronic respiratory disease covered obstructive and restrictive diseases, including chronic obstructive pulmonary disease, kyphoscoliosis, and obesity-hypoventilation syndrome. Immunocompromised patients were those with aplasia and/or recent chemotherapy for solid tumor or hematologic disease and those who received 20 mg per day or more of prednisolone for two weeks or more or a lower daily dose for more than three weeks. Solid tumor and hematologic disease were considered when treated actively or diagnosed within the year before admission. The following causes of death were distinguished: primary infection-related multiple-organ failure, mesenteric ischemia, end-oflife decision, ARDS, central nervous system disorder, and others [20]. 2.6. End points The primary end point was the comparison, between patients who consumed more than 100 g/week and those who consumed 100 g/ week or less of alcohol, of the cumulative incidence of mortality until day 28 after admission to the ICU. Secondary end points included comparison of pathogens involved and the comparison of causes of death between the two groups of patients.
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2.7. Statistical analysis The study was designed to have 80% power to detect a 20% difference in mortality in patients with sepsis/septic shock with a confidence interval of 95% between patients who consumed less than 100 g/week (expected mortality of 15%) and those who consumed more than 100 g/week (expected mortality of 35%) [21], at a twosided error α of 5%. This generated the minimum sample size of 72 patients per group. Based on our previous studies, a three-year duration was estimated to be sufficient for the study. Continuous variables are expressed as median and interquartile range and were compared by the nonparametric Mann-Whitney U test. Proportions were compared by the chi-square test or Fisher's exact test when required. Tests were two-sided, and we considered p b .05 to be statistically significant. Survival curves were constructed until day 28 by using the KaplanMeier method and were compared by the log-rank test. Patients alive at day 28 were censored. Distributions between groups were compared by the log-rank test. We used a Cox proportional hazard model to determine whether at-risk drinking was a comorbidity independently associated with mortality at day 28. Variables were removed in a backward stepwise selection process on the basis of a significance level of 0.10 in the unadjusted analysis. The results were expressed as hazard ratios (HRs) with their 95% confidence intervals (CIs), and analysis was adjusted for the following variables recorded on the first day of ICU stay because they were associated with prognosis in critically ill patients with infection: SAPS II and SOFA scores, serum lactate level, treatment with vasopressors (i.e., epinephrine, norepinephrine, and dobutamine at any dose), and diagnoses of ARDS and KDIGO stage 2–3 AKI. In addition, the following comorbidities were considered for analysis because they were potentially confounding variables: age ≥ 65 years, diabetes mellitus, aplasia and/or recent chemotherapy for solid tumor or hematologic disease, chronic kidney disease, and chronic heart and/or respiratory disease.
3. Results During the 36-month study period, 586 patients with no liver cirrhosis and no liver transplantation were admitted to the ICU with microbiologically documented infection. Alcohol consumption could be assessed in 554 patients (94%). Among the 554 patients, 70 patients (10%) consumed 5 drinks per day or more (i.e., weekly estimated alcohol intake above 350 g), and the AUDIT score was found to be positive for dependence in 6 patients who consumed 4 drinks per day. A total of 478 patients were studied. In 97 patients (20%), alcohol consumption was estimated to be over 100 g/week, and in 391 patients (80%), alcohol consumption was estimated to be 100 g/week or less. Five patients among the 36 with estimated alcohol consumption over 100 g/week after interviewing their closest relatives could not be assessed for AUDIT.
3.1. Baseline characteristics of patients The baseline characteristics of the patients are compared between the two groups in Table 1. Weekly alcohol consumption was significantly higher in patients with estimated alcohol consumption over 100 g/week than in patients who consumed 100 g/week or less (median of 210 g/week (140–280) versus 0 g/week (0–70), p b .001). Organ dysfunctions as assessed by the SOFA score were significantly more severe in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less. The proportions of patients with pneumonia were similar in the two groups, and the proportion of patients with bacteremia was significantly higher in patients who consumed more than 100 g/week compared to other patients.
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Table 1 Baseline characteristics of patients at admission to the ICU, infections, and death in the ICU compared whether patients consumed less or more than 100 g/week of alcohol. Whole population
Assessment of alcohol consumption, n (%) Self-reported only Self-reported and closest relatives Closest relatives only Age ≥ 65 years, n (%) Male gender SAPS II score, points median (IQR) SOFA score, points median (IQR) Admission type, n (%) Medical Emergency surgery Elective surgery Diabetes mellitus, n (%) Chronic heart or lung disease, n (%) Immunocompromised, n (%) Chronic kidney disease, n (%) Serum lactates level, mmol/L median (IQR) Community-acquired infection, n (%) Site of infection, n (%) Pneumonia Urinary tract Central nervous system Endocarditis Skin and soft tissues Digestive tract Other or unknown Bacteremia, n (%) ARDS KDIGO AKI stage 2.3 Sepsis and septic shock, n (%) Sepsis Septic shock Death in ICU Death at day-28
Weekly consumption of alcohol
P Value
n = 478
N 100 g n = 97
≤ 100 g n = 381
81 (17) 239 (50)
15 (16) 46 (47)
66 (17) 193 (51)
158 (33) 226 (47) 269 (56) 44 (32–60) 8 (4–10)
36 (37) 54 (56) 77 (79) 48 (36–62) 9 (5–11)
122 (32) 172 (45) 192 (50) 44 (32–59) 7 (4–10)
438 (92) 34 (7) 6 (1) 64 (13) 207 (43)
87 (90) 8 (8) 2 (2) 17 (17) 47 (48)
351 (92) 26 (7) 4 (1) 47 (12) 160 (42)
95 (20) 73 (15) 1.7 (1.2–2.8) 414 (87)
24 (25) 10 (10) 1.9 (1.3–3.4) 84 (86)
71 (19) 63 (17) 1.7 (1.2–2.7) 330 (87)
0.19 0.18 0.12
237 (50) 56 (12) 33 (7) 43 (9) 30 (6) 43 (9) 34 (7) 136 (28) 86 (18) 146 (30)
49 (50) 10 (10) 4 (2) 9 (9) 13 (8) 8 (6) 6 (4) 36 (37) 17 (17) 50 (32)
188 (50) 46 (12) 31 (8) 34 (9) 17 (4) 35 (9) 28 (8) 10 (26) 69 (18) 96 (25)
0.02
358 (75) 120 (25) 99 (21) 99 (21)
68 (70) 29 (30) 33 (28) 29 (29)
290 (76) 91 (24) 68 (18) 70 (19)
0.62
0.07 b0.0001 0.14 0.002 0.66
0.18 0.25
0.99
0.04 0.89 b0.0001 0.23 0.02 0.03
Abbreviations: IQR, interquartile range; SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; ARDS, acute respiratory distress syndrome; ICU, Intensive Care Unit.
3.2. Mortality at day 28 after admission to the ICU in the whole population Of note, the proportion of patients with septic shock at admission to the ICU did not differ significantly between the two groups of patients. The same was true of ARDS. However, when organ dysfunctions were considered, sub-SOFA scores for cardiovascular dysfunction and subSOFA scores for non-cardiovascular dysfunctions were significantly higher in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less (4 points (1–4) vs 3 points (1–4), p = .04 and 5 points (4–7) vs 5 points (3–7), p = .01, respectively). The ICU mortality rate was significantly higher in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less (28% versus 18%, p = .02). Survival at day 28 was significantly lower in patients who consumed more than 100 g/week than in patients who consumed 100 g/week or less, as determined by the logrank test (p = .03, Fig. 1). Alcohol consumption greater than 100 g/week remained independently associated with mortality after adjustment for other comorbidities recorded at admission to the ICU (HR: 1.67; 95% CI: 1.01–2.77; p = .04) (Table 2). Six of the 20 women (30%) and 22 of the 77 males (29%) who consumed more than 100 g/week died within the
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Fig. 1. Cumulative 28-day mortality from admission to the ICU.
28 days following ICU admission (p = .86 after comparison). Of note, 28 patients (6%) stopped their excessive alcohol consumption six months or more before admission to the ICU, a characteristic not associated with 28-day mortality (HR = 0.83, 95% CI 0.34–2.05, p = .69). 3.3. Pathogens involved between at-risk and not at-risk drinkers The pathogens involved are listed and compared between groups in Table 3. We found no significant differences after comparisons regarding the pathogens involved, including multidrug-resistant (MDR) bacteria. 3.4. Causes of death Among the 33 patients who consumed less than 100 g/week who died in the ICU, the cause of death was primary infection-related multiple-organ failure in 14 patients (42%), ARDS in 5 patients (15%), central nervous system disorder in 5 patients (15%), end-of-life decision in 3 patients (9%), mesenteric ischemia in 2 patients (6%), and other reasons in 4 patients (12%). Among patients who consumed 100 g/week or more who died in the ICU, the cause of death was primary infectionrelated multiple-organ failure in 27 patients (33%), ARDS in 12 patients (15%), central nervous system disorder in 13 patients (16%), end-of-life decision in 14 patients (17%), mesenteric ischemia in 6 patients (7%), and other reasons in 9 patients (11%). Proportions for causes of death did not differ significantly between patients who consumed 100 g/ week or less and those who consumed more than 100 g/week (p = .89).
4. Discussion In this three-year prospective observational study performed on patients with microbiologically documented infection at admission to the ICU, weekly alcohol intake between 100 g and 350 g/week and no criteria for alcohol dependence were independently associated with 28-day mortality, while the pathogens involved, severity of infection at admission to the ICU, and causes of death in the ICU did not significantly differ whether patients consumed less or more than 100 g/ week of alcohol. Similar to the adverse association of moderate but regular alcohol consumption with mortality reported outside the ICU, alcohol consumption lower than that generally encountered in patients with alcohol dependence critically places patients with documented infection at higher risk of mortality. To our knowledge, this is the first study designed to investigate the impact of chronic alcohol consumption at doses lower than those generally encountered in patients with dependence on alcohol on the outcomes of critically ill patients admitted with documented infection in whom sepsis and septic shock were distinguished from each other, based on a recent classification [5]. A study that used a large database reported that critically ill patients with alcohol dependence had higher rates of sepsis, organ failure, septic shock, and hospital mortality [22], a finding reported by other authors [23]. Accordingly, we found that chronic alcohol consumption was associated with a poorer prognosis among critically ill patients with infection, but our results also suggest that the negative impact of alcohol on outcomes begins from levels of consumption lower than those generally encountered in patients with
Table 2 Unadjusted and adjusted hazard ratios for 28-day mortality from ICU admission. Variables
Unadjusted hazard ratio (95% CI)
p Value
Adjusted hazard ratio (95% CI)
p Value
Alcohol consumption over 100 g/week SAPS II score (1-point increment) SOFA score (1-point increment) Serum lactates level (1 mmol/L increment) ARDS KDIGO stage 2–3 AKI Treatment with vasopressors Age ≥ 65 years Diabetes mellitus Immunocompromised Chronic respiratory and/or cardiovascular disease Chronic kidney disease
2.03 (1.31–3.14) 1.043 (1.035–1.052) 1.267 (1.200–1.337) 1.218 (1.152–1.288) 1.35 (0.83–2.18) 2.35 (1.58–3.48) 2.51 (1.69–3.74) 2.41 (1.58–3.65) 1.83 (1.12–2.99) 2.20 (1.45–3.34) 1.42 (0.96–2.11) 1.75 (1.09–2.78)
0.001 b0.0001 b0.0001 b0.0001 0.22 b0.0001 b0.0001 b0.0001 0.02 0.0002 0.08 0.02
1.67 (1.01–2.77) 1.021 (1.007–1.035) 1.178 (1.075–1.291) 1.079 (1.001–1.164)
0.04 0.003 0.0005 0.047
1.71 (1.03–2.95) 1.79 (1.12–2.86)
0.04 0.01
CI, Confident interval Abbreviations: SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; ARDS, acute respiratory distress syndrome; AKI, Acute Kidney Injury; KDIGO, Kidney Disease Improving Global Outcomes.
A. Gacouin et al. / Journal of Critical Care 57 (2020) 91–96 Table 3 Microbiological data compared whether patients consumed less or more than 100 g/week of alcohol. Whole Weekly population consumption of alcohol
Class of pathogens involved, n (%)⁎ Bacteria Virus Fungi Main classes of pathogens detected, n (%)a Gram-positive cocci Streptococcus pneumoniae, Staphylococcus aureus Streptococcus Other gram positive cocci Gram negative bacilli Escherichia coli Haemophilus Influenza Pseudomonas aeruginosa Other gram negative bacilli Intracellular bacteria Particular bacteria b Influenza virus Viruses other than influenza Pneumocystis jiroveci or Aspergillusfumigatus Multi-drug resistant bacteria, n (%)
P value
n = 478
N 100 g ≤ 100 g n = 97 n = 381
376 (79) 94 (19) 35 (7)
77 (79) 299 (78) 0.85 19 (15) 81 (21) 0.19 6 (7) 29 (8) 0.78
60 (13) 78 (16) 45 (9) 5 (1)
12 (12) 10 (10) 10 (10) 3 (2)
40 (12) 62 (16) 35 (9) 2 (0.05)
0.94 0.99 0.73 0.30
80 (16) 26 (5) 21 (4) 51 (11) 11 (2) 24 (5) 59 (12) 35 (7) 35 (7)
25 (16) 8 (8) 3 (3) 14 (14) 2 (1) 4 (4) 13 (13) 6 (6) 6 (6)
65 (16) 18 (5) 18 (5) 37 (10) 9 (2) 20 (5) 46 (12) 29 (8) 29 (8)
0.82 0.17 0.68 0.17 0.99 0.79 0.73 0.41 0.82
56 (15)
12 (12) 45 (15)
0.86
a
Some patients had mixed infection. b Mycobacterium tuberculosis, n = 4; Mycobacterium avium, n = 1; leptospirosis, n = 5; Clostridium difficile, n = 4; Neisseiria meningitides, n = 3; Listeria monocytogenes, n = 2; Nocardia, n = 1; Salmonella paratyphi, n = 1; Clostridium tetani, n = 1; Pasteurella multicoda, n = 1; Bartonella henslea, n = 1.
dependence. Our results are in agreement with those reported outside the ICU and especially with those of a large, recently published epidemiological study, since the threshold for lowest risk of all-cause mortality was 100 g/week [4]. However, the negative impact on outcomes of low or moderate amounts of alcohol intake is less clearly established for critically ill patients. In one study [24], excessive alcohol consumption increased short- and long-term mortality only in critically ill patients with chronic complications of their alcoholism. The proportion of patients with alcohol intake between 100 g and 350 g/week admitted to the ICU with septic shock, diagnosed based on updated criteria, was not significantly higher than that of patients who consumed no alcohol or less than 100 g/week. However, when patients were assessed in terms of organ dysfunctions using the SOFA score, cardiovascular and noncardiovascular organ dysfunctions were significantly more severe in patients who consumed between 100 and 350 g/week. It is generally considered that infections are more frequent at many sites (e.g., lungs, blood, skin, wounds, or sites of surgery) in alcohol abusers than moderate or abstinent drinkers and that the pathogens involved differ if patients are excessive alcohol consumers. Our results suggest that these data are not accurate when considering alcohol abusers without alcohol dependence, and we believe that patients admitted to the ICU should be screened not only for AUDs but also for moderate alcohol consumption. Overall, our results suggest that empirical microbiological treatment should not be different whether patients consume moderate amounts of alcohol. Consequently, we make the assumption that improvement of the ICU outcome of the patients with moderate alcohol consumption and infection could be obtained more by a prompt support of organ dysfunctions than particular practices in the management of antibiotics. Of note, we consider that inclusion of patients with undocumented infection would have induced a bias due to a more intensive research on pathogens involved in more severe patients, since we suspected that patients who consumed more than
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100 g/week would have worse severity scores on admission to the ICU than those with alcohol consumption lower than 100 g/week. Previous studies have suggested that chronic alcohol consumption predisposes patients to ARDS [25]. In our study, the proportion of patients with ARDS was not significantly higher among those who consumed more than 100 g/week than among those who consumed less or no alcohol. This may be explained by the fact that patients were defined as ARDS patients at admission to the ICU and not throughout the entire ICU stay. Furthermore, our study focused on documented infectionrelated ARDS, excluding other causes of ARDS, and patients with alcohol dependence were excluded from our study. The deleterious effects of chronic alcohol exposure on immunity are well identified, although they were not assessed in our study. Chronic alcohol consumption alters liver function, even in the absence of cirrhosis [26], and it has been demonstrated that the capacity of the liver to clear bacteria is an important determinant of the outcome in sepsis [27]. Chronic alcohol consumption alters innate and adaptive immunity, including changes in the number and function of immune cells [28,29,30,31,32]. The question arises whether the alterations in immunity are the same in critically ill patients depending on whether alcohol consumption is moderate or heavy. The arrest of excessive alcohol consumption six months before admission to the ICU was not associated with the prognosis. Some have demonstrated that the monocyte response to infection is partially restored after two weeks of alcohol withdrawal [31]. Our study had several limitations. The data were collected at a single site, and the results may not be generalizable. Because of the observational nature of the study, we cannot exclude uncontrolled confounders. Risk factors for delirium and preexisting psychiatric disorders were not assessed but were associated with poorer outcomes. There were no trauma patients, and our center is localized in an area where alcoholism is a major public health problem. Alcohol consumption was assessed by interviewing patients and/or their relatives, and the validity of this information may thus be open to doubt. Therefore, the assessment of alcohol consumption could have been less accurate when those relatives did not live with the patient. However, the quantification of alcohol consumption in ICU patients is not easy in clinical practice, especially because there is currently no simple test that can confirm the diagnosis of excessive alcohol consumption [4,32]. In addition, patients were classified based on the assumption that a drink contained 10 g of alcohol, but according to studies, “a drink” can contain from 6 to 16 g of alcohol. 5. Conclusion Several studies have suggested that moderate drinking, usually defined by the daily consumption of one to two drinks per day, may exert beneficial effects on immunity and consequently diminish the risk and severity of infections [30]. In contrast, our results suggest that critically ill patients with documented infection are at a higher risk of a poor prognosis starting from a level of alcohol consumption that is lower than those generally reported in studies performed in the ICU. Nonetheless, we did not find that alcohol consumption was associated with any particular pathogens when infections were microbiologically documented, nor with a particular cause of death. Our results suggest that low levels of alcohol consumption put critically ill patients admitted to the ICU with infection at a higher risk of a poor outcome, a finding previously reported outside of the ICU. Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None.
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