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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2023.1100160</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cardiovascular Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Associations of albumin and nutritional index factors with delirium in patients admitted to the cardiac intensive care unit</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Tae Wan</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
<xref rid="fn0003" ref-type="author-notes"><sup>&#x2020;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2101649/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ko</surname>
<given-names>Ryoung Eun</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
<xref rid="fn0003" ref-type="author-notes"><sup>&#x2020;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1902844/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Na</surname>
<given-names>Soo Jin</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chung</surname>
<given-names>Chi Ryang</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Choi</surname>
<given-names>Ki Hong</given-names>
</name>
<xref rid="aff2" ref-type="aff"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Park</surname>
<given-names>Chi-Min</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Yang</surname>
<given-names>Jeong Hoon</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
<xref rid="aff2" ref-type="aff"><sup>2</sup></xref>
<xref rid="c001" ref-type="corresp"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1816850/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff>
<aff id="aff2"><sup>2</sup><institution>Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff>
<author-notes>
<fn id="fn0001" fn-type="edited-by"><p>Edited by: Thomas A. Zelniker, Medical University of Vienna, Austria</p></fn>
<fn id="fn0002" fn-type="edited-by"><p>Reviewed by: Jiuann Huey Lin, University of Pittsburgh, United States; Dae-Hwan Bae, Chungbuk National University Hospital, Republic of Korea</p></fn>
<corresp id="c001">&#x002A;Correspondence: Jeong Hoon Yang, <email>jhysmc@gmail.com</email></corresp>
<fn id="fn0003" fn-type="equal"><p><sup>&#x2020;</sup>These authors have contributed equally to this work</p></fn>
<fn id="fn0004" fn-type="other"><p>This article was submitted to Intensive Care Cardiovascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine</p></fn>
</author-notes>
<pub-date pub-type="epub">
<day>03</day>
<month>03</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>10</volume>
<elocation-id>1100160</elocation-id>
<history>
<date date-type="received">
<day>16</day>
<month>11</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>14</day>
<month>02</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2023 Kim, Ko, Na, Chung, Choi, Park and Yang.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Kim, Ko, Na, Chung, Choi, Park and Yang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Limited data are available on the association of malnutrition with the occurrence of delirium in the cardiac intensive care unit (CICU). Thus, we aimed to analyze whether nutritional indices and their components can predict the development of delirium in CICU.</p>
</sec>
<sec>
<title>Methods</title>
<p>We enrolled 2,783 patients admitted to the CICU of Samsung Medical Center for more than 24&#x2009;h between September 2012 and December 2018. We assessed the nutritional status at admission using three indices, the Prognostic Nutrition Index (PNI), the Geriatric Nutritional Risk Index (GNRI), and the Controlling Nutritional Status (CONUT). Then, we compared predictive performances for the occurrence of delirium among nutritional indices using Delong&#x2019;s test.</p>
</sec>
<sec>
<title>Results</title>
<p>Delirium developed in 678 patients (24.3%) assessed three times daily for 7&#x2009;days of CICU stay. Nutritional indices had fair predictive performance for development of delirium in critically ill cardiac patients using the area under the receiver-operating characteristic curve (AUROC: 0.729 for the GNRI, 0.728 for PNI, and 0.762 for CONUT). Furthermore, the AUROC of albumin alone (0.77, 95% CI, 0.75&#x2013;0.79) was significantly greater than that of either GNRI (<italic>p&#x2009;&#x003C;</italic> 0.001) or PNI (<italic>p&#x2009;&#x003C;</italic> 0.001). In a multivariable analysis including each component of nutritional indices, albumin was a significant predictor for delirium but not absolute lymphocyte count, bodyweight/ideal bodyweight, or total cholesterol level as a component of nutritional indices.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Predictive performances of nutritional indices for the occurrence of delirium were acceptable in patients admitted to CICU. Albumin alone might be a helpful and straightforward indicator for the occurrence of delirium.</p>
</sec>
</abstract>
<kwd-group>
<kwd>delirium</kwd>
<kwd>albumin</kwd>
<kwd>malnutrition</kwd>
<kwd>cardiac intensive care unit</kwd>
<kwd>nutrition indexes</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="31"/>
<page-count count="8"/>
<word-count count="5089"/>
</counts>
</article-meta>
</front>
<body>
<sec id="sec5" sec-type="intro">
<title>Introduction</title>
<p>Delirium is a frequent complication in patients admitted to the intensive care unit (ICU). It has been associated with increased risk of mortality, development of post-ICU cognitive impairment, and longer ICU and hospital stays (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref2">2</xref>). In recent decades, the application of advanced medical devices for the treatment of cardiovascular disease has been significantly expanded, and the number of critically ill patients with underlying cardiac disease has increased (<xref ref-type="bibr" rid="ref3">3</xref>). Accordingly, the incidence of delirium in the cardiac intensive care unit (CICU) has substantially increased and is comparable to that in other medical ICUs (<xref ref-type="bibr" rid="ref4">4</xref>). Furthermore, recent studies have reported associations between delirium and clinical outcomes in critically ill cardiac patients (<xref ref-type="bibr" rid="ref5">5</xref>, <xref ref-type="bibr" rid="ref6">6</xref>).</p>
<p>Malnutrition is an essential risk factor for delirium in elderly patients (<xref ref-type="bibr" rid="ref7">7</xref>). Several nutritional indices have been developed to assess the risk of malnutrition in critically ill patients. First, the Prognostic Nutritional Index (PNI) was created in 1980 to evaluate preoperative nutritional conditions and surgical risk for gastrointestinal surgery (<xref ref-type="bibr" rid="ref8">8</xref>). The Geriatric Nutritional Risk Index (GNRI) was developed to estimate the risk of morbidity and mortality in elderly medical patients (<xref ref-type="bibr" rid="ref9">9</xref>). The Controlling Nutritional Status (CONUT) is widely used for daily assessment of the nutritional status of inpatients (<xref ref-type="bibr" rid="ref10">10</xref>).</p>
<p>Although several studies have reported an association of delirium with mortality in ICU patients, limited studies are available on the relationship between nutritional status and delirium in CICU patients. Therefore, the goal of the present study was (i) to assess the predictive performance of nutritional indices (PNI, GNRI, and CONUT) and their components in CICU patients and (ii) to investigate clinical factors associated with delirium in this population.</p>
</sec>
<sec id="sec6" sec-type="methods">
<title>Methods</title>
<sec id="sec7">
<title>Study population</title>
<p>All consecutive patients who were admitted to the CICU between September 1, 2012, and December 31, 2018, were eligible for the study. A total of 4,261 patients who were 18&#x2009;years old or older was admitted to the CICU at Samsung Medical Center in Seoul, Republic of Korea. We excluded 1,473 patients who stayed in the CICU for less than 24&#x2009;h and three patients for whom we were not able to calculate nutritional indices due to limited data. The Institutional Review Board of Samsung Medical Center approved this study (IRB. No. 2020&#x2013;10-102) and waived the requirement for informed consent because of the observational nature of the study. Patient information was anonymized and de-identified before analysis.</p>
</sec>
<sec id="sec8">
<title>Cardiac intensive care unit management</title>
<p>Our unit is a 12-bed ICU with a 1:2 nurse-to-patient ratio offering level 1 care for critically ill cardiac patients. To provide comprehensive critical care to patients with various cardiovascular diseases and complex comorbidities, the CICU is equipped with invasive and noninvasive devices to monitor patients&#x2019; hemodynamic status and provide advanced therapeutic technologies. With the high-intensity staffing model, patients are managed by a dedicated cardiac intensivist who is board certified in interventional cardiology and critical care medicine (<xref ref-type="bibr" rid="ref11">11</xref>). Cardiac surgery support is promptly assessable. In addition, multidisciplinary care is provided <italic>via</italic> consultation with a dietitian, pharmacist, and respiratory care practitioner.</p>
<p>The clinical practice guidelines published by The Society of Critical Care Medicine were adopted for general intensive care (<xref ref-type="bibr" rid="ref12">12</xref>). The Confusion Assessment Method for ICU (CAM-ICU) assessment was performed by nurses three times a day on patients with a Richmond Agitation-Sedation Scale of &#x2212;3 (indicating movement or eye-opening to voice but no eye contact) or higher. The recorded CAM-ICU results were re-checked every day by a senior nurse. Nutrition support team consultation was available for nutrition therapy.</p>
</sec>
<sec id="sec9">
<title>Nutritional indices</title>
<p>Nutritional status was assessed using the PNI, GNRI, and CONUT based on blood test results measured on the day of admission to CICU to identify risk scores of malnutrition in critically ill patients. The PNI is calculated as follows: 10 x serum albumin concentration (g/dL)&#x2009;+&#x2009;0.005 x absolute lymphocyte count (ALC, number/mm<sup>2</sup>) in peripheral blood (<xref ref-type="bibr" rid="ref13">13</xref>). Patients with a PNI score&#x2009;&#x003E;&#x2009;38 were considered normal, patients with a score of 35&#x2013;38 were at risk of moderate malnutrition, and patients with a score&#x2009;&#x003C;&#x2009;35 were classified as at risk of severe malnutrition. The GNRI is calculated as follows: 14.89 x serum albumin (g/dL)&#x2009;+&#x2009;41.7 x [bodyweight/ideal bodyweight (IBW)] (<xref ref-type="bibr" rid="ref9">9</xref>). Patients were categorized into four groups according to GNRI score: major risk (GNRI score&#x2009;&#x003C;&#x2009;82), moderate risk (82&#x2009;&#x2264;&#x2009;GNRI score&#x2009;&#x003C;&#x2009;92), low risk (92&#x2009;&#x2264;&#x2009;GNRI score&#x2009;&#x003C;&#x2009;98), and no risk (98&#x2009;&#x2264;&#x2009;GNRI score). The CONUT was obtained based on serum albumin concentration, cholesterol level, and ALC (<xref ref-type="bibr" rid="ref14">14</xref>). According to the CONUT score, patients were divided into four groups: normal (0&#x2013;1 point), mild risk (2&#x2013;4 points), moderate risk (5&#x2013;8 points), and severe risk (9&#x2013;12 points).</p>
</sec>
<sec id="sec10">
<title>Data collection</title>
<p>After reviewing the medical records, a trained study coordinator retrospectively collected clinical, laboratory, and outcome data. To accurately evaluate the total number of days at risk of delirium, we did not include days when the patient was in a coma as defined by a Richmond Agitation-Sedation Scale assessment of &#x2212;4 (unresponsive to voice but responded to physical stimulation) or&#x2009;&#x2212;&#x2009;5 (unresponsive to voice and physical stimulation) (<xref ref-type="bibr" rid="ref15">15</xref>). Delirium was defined as CAM-ICU positivity at any time during the assessment three times daily for up to 7&#x2009;days of CICU stay. Polypharmacy was defined as the routine use of five or more medications (<xref ref-type="bibr" rid="ref16">16</xref>).</p>
</sec>
<sec id="sec11">
<title>Statistical analysis</title>
<p>Descriptive statistics were performed to compare the clinical characteristics and outcomes between the delirium and non-delirium groups. Continuous variables were presented as median and interquartile range or mean&#x2009;&#x00B1;&#x2009;standard deviation and were compared with a Mann&#x2013;Whitney <italic>U</italic> test. Categorical variables were expressed as number and percentage and were analyzed using Chi-square tests or Fisher&#x2019;s exact tests, where applicable. The model&#x2019;s predictive ability to discriminate between patients who had and did not have delirium was estimated using the receiver operating characteristic curve. The receiver operating characteristic curve is presented to demonstrate the performance of delirium for the area under the curve (AUROC) and 95% confidence interval (CI). Discriminant functions were compared by a 2-tailed paired comparison of the ROC curve by DeLong&#x2019;s method (<xref ref-type="bibr" rid="ref17">17</xref>). Variables with a <italic>p</italic> value less than 0.05 on univariate analyzes and clinically relevant <italic>a priori</italic> variables were entered into the multiple logistic regression model. Results were reported as each variable&#x2019;s odds ratio (OR) with 95% CI. A two-tailed <italic>p</italic> value less than 0.05 was considered statistically significant for all analyzes. Data were analyzed using R Statistical Software (Version 3.2.5; R Foundation for Statistical Computing, Vienna, Austria).</p>
</sec>
</sec>
<sec id="sec12" sec-type="results">
<title>Results</title>
<sec id="sec13">
<title>Clinical characteristics</title>
<p>During the study period, 2,783 patients were finally enrolled in this analysis; 678 patients (24.3%) have occurred delirium during CICU admission. The characteristics of the patients are shown in <xref rid="tab1" ref-type="table">Table 1</xref>. Patients in the delirium group were older and higher-risk subjects with lower body mass index and more comorbidities than those in the non-delirium group. There was no difference between the two groups in the CICU admission diagnosis and polypharmacy. Cardiac arrest before CICU admission (20.9% vs. 6.3%; <italic>p&#x2009;&#x003C;</italic> 0.001) and Sequential Organ Failure Assessment score (6.97&#x2009;&#x00B1;&#x2009;3.47 vs. 3.39&#x2009;&#x00B1;&#x2009;2.71; <italic>p&#x2009;&#x003C;</italic> 0.001) were higher in the delirium group than in the non-delirium group. In the laboratory findings at CICU admission, ALC [1.13 (0.7&#x2013;1.8) x10<sup>3</sup>/&#x03BC;L vs. 1.62 (1.1&#x2013;2.3) x10<sup>3</sup>/&#x03BC;L; <italic>p&#x2009;&#x003C;</italic> 0.001], albumin [3.2 (2.8&#x2013;3.6) g/dL vs. 3.9 (3.4&#x2013;4.2) g/dL; <italic>p&#x2009;&#x003C;</italic> 0.001], and total cholesterol [119.5 (94.0&#x2013;152.0) mg/dL vs. 150.0 (121.5&#x2013;183.0) mg/dL; <italic>p&#x2009;&#x003C;</italic> 0.001] were significantly lower in the delirium group.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Baseline characteristics of CICU patients.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="left" valign="top">Delirium (<italic>n&#x2009;=</italic> 678)</th>
<th align="left" valign="top">Non-delirium (<italic>n&#x2009;=</italic> 2,105)</th>
<th align="left" valign="top"><italic>P</italic> value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Age, years</td>
<td align="char" valign="top" char="(">69.25&#x2009;&#x00B1;&#x2009;14.7</td>
<td align="char" valign="top" char="(">63.24&#x2009;&#x00B1;&#x2009;14.7</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Sex, male</td>
<td align="char" valign="top" char="(">384 (56.6)</td>
<td align="char" valign="top" char="(">1,416 (67.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Body mass index, kg/m<sup>2</sup></td>
<td align="char" valign="top" char="(">23.29&#x2009;&#x00B1;&#x2009;4.08</td>
<td align="char" valign="top" char="(">24.04&#x2009;&#x00B1;&#x2009;3.80</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top" colspan="4">Comorbidities</td>
</tr>
<tr>
<td align="left" valign="top">Hypertension</td>
<td align="char" valign="top" char="(">417 (61.5)</td>
<td align="char" valign="top" char="(">1,127 (53.5)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Diabetes mellitus</td>
<td align="char" valign="top" char="(">265 (39.1)</td>
<td align="char" valign="top" char="(">637 (30.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Previous coronary disease</td>
<td align="char" valign="top" char="(">214 (31.6)</td>
<td align="char" valign="top" char="(">509 (24.2)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Chronic kidney disease<sup>&#x002A;</sup></td>
<td align="char" valign="top" char="(">34 (5.0)</td>
<td align="char" valign="top" char="(">81 (3.8)</td>
<td align="char" valign="top" char=".">0.184</td>
</tr>
<tr>
<td align="left" valign="top">Stroke</td>
<td align="char" valign="top" char="(">154 (22.7)</td>
<td align="char" valign="top" char="(">213 (10.1)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Dementia</td>
<td align="char" valign="top" char="(">30 (4.4)</td>
<td align="char" valign="top" char="(">11 (0.5)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Smoking</td>
<td align="char" valign="top" char="(">120 (17.8)</td>
<td align="char" valign="top" char="(">477 (22.7)</td>
<td align="char" valign="top" char=".">0.008</td>
</tr>
<tr>
<td align="left" valign="top">Reason for CICU admission</td>
<td/>
<td/>
<td align="char" valign="top" char=".">0.257</td>
</tr>
<tr>
<td align="left" valign="top">Acute coronary syndrome</td>
<td align="char" valign="top" char="(">332 (49.0)</td>
<td align="char" valign="top" char="(">1,006 (47.8)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Heart failure</td>
<td align="char" valign="top" char="(">164 (24.2)</td>
<td align="char" valign="top" char="(">574 (27.3)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Arrhythmia</td>
<td align="char" valign="top" char="(">96 (14.2)</td>
<td align="char" valign="top" char="(">230 (10.9)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Aortic disease</td>
<td align="char" valign="top" char="(">33 (4.9)</td>
<td align="char" valign="top" char="(">125 (5.9)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Pulmonary hypertension</td>
<td align="char" valign="top" char="(">28 (4.1)</td>
<td align="char" valign="top" char="(">88 (4.2)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Pericardial disease</td>
<td align="char" valign="top" char="(">22 (3.2)</td>
<td align="char" valign="top" char="(">64 (3.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Others</td>
<td align="char" valign="top" char="(">1 (0.1)</td>
<td align="char" valign="top" char="(">10 (0.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Admission route</td>
<td/>
<td/>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Emergency room</td>
<td align="char" valign="top" char="(">304 (44.8)</td>
<td align="char" valign="top" char="(">1,340 (63.7)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">General ward</td>
<td align="char" valign="top" char="(">143 (21.1)</td>
<td align="char" valign="top" char="(">260 (12.4)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Outpatient department</td>
<td align="char" valign="top" char="(">127 (18.7)</td>
<td align="char" valign="top" char="(">161 (7.6)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Other intensive care units</td>
<td align="char" valign="top" char="(">2 (0.3)</td>
<td align="char" valign="top" char="(">2 (0.1)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Polypharmacy<sup>&#x002A;&#x002A;</sup></td>
<td align="char" valign="top" char="(">94 (13.9)</td>
<td align="char" valign="top" char="(">350 (16.6)</td>
<td align="char" valign="top" char=".">0.099</td>
</tr>
<tr>
<td align="left" valign="top">Cardiac arrest before CICU admission</td>
<td align="char" valign="top" char="(">142 (20.9)</td>
<td align="char" valign="top" char="(">133 (6.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">SOFA score at CICU admission</td>
<td align="char" valign="top" char="(">6.97 (&#x00B1;3.47)</td>
<td align="char" valign="top" char="(">3.39 (&#x00B1;2.71)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top" colspan="4">Laboratory findings</td>
</tr>
<tr>
<td align="left" valign="top">White blood cell count, 10<sup>3</sup>/&#x03BC;L</td>
<td align="char" valign="top" char="(">12.92 (9.7&#x2013;17.1)</td>
<td align="char" valign="top" char="(">9.21 (7.1&#x2013;12.4)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">ALC, x10<sup>3</sup>/&#x03BC;L</td>
<td align="char" valign="top" char="(">1.13 (0.7&#x2013;1.8)</td>
<td align="char" valign="top" char="(">1.62 (1.1&#x2013;2.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Hemoglobin, g/dL</td>
<td align="char" valign="top" char="(">10.10 (8.8&#x2013;11.8)</td>
<td align="char" valign="top" char="(">12.40 (10.5&#x2013;14.0)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Platelet, x10<sup>3</sup>/&#x03BC;L</td>
<td align="char" valign="top" char="(">146.0 (93.0&#x2013;207.0)</td>
<td align="char" valign="top" char="(">188.0 (146.0&#x2013;230.0)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Total bilirubin, mg/dL</td>
<td align="char" valign="top" char="(">1.10 (0.7&#x2013;2.0)</td>
<td align="char" valign="top" char="(">0.90 (0.6&#x2013;1.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Albumin, g/dL</td>
<td align="char" valign="top" char="(">3.20 (2.8&#x2013;3.6)</td>
<td align="char" valign="top" char="(">3.90 (3.4&#x2013;4.2)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Blood urea nitrogen, mg/dL</td>
<td align="char" valign="top" char="(">29.40 (20.5&#x2013;46.9)</td>
<td align="char" valign="top" char="(">19.10 (14.2&#x2013;28.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Creatinine, mg/dL</td>
<td align="char" valign="top" char="(">1.48 (1.0&#x2013;2.3)</td>
<td align="char" valign="top" char="(">1.01 (0.8&#x2013;1.4)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Total cholesterol, mg/dL</td>
<td align="char" valign="top" char="(">119.5 (94.0&#x2013;152.0)</td>
<td align="char" valign="top" char="(">150.0 (121.5&#x2013;183.0)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">LDL cholesterol, mg/dL</td>
<td align="char" valign="top" char="(">73.00 (49.0&#x2013;107.0)</td>
<td align="char" valign="top" char="(">98.00 (73.0&#x2013;126.0)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">HDL cholesterol, mg/dL</td>
<td align="char" valign="top" char="(">38.00 (30.0&#x2013;48.0)</td>
<td align="char" valign="top" char="(">44.00 (36.0&#x2013;53.0)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Triglycerides, mg/dL</td>
<td align="char" valign="top" char="(">99.0 (70.0&#x2013;135.0)</td>
<td align="char" valign="top" char="(">106.0 (75.0&#x2013;155.0)</td>
<td align="char" valign="top" char=".">0.004</td>
</tr>
<tr>
<td align="left" valign="top">Troponin I, ng/mL</td>
<td align="char" valign="top" char="(">1.75 (0.2&#x2013;18.4)</td>
<td align="char" valign="top" char="(">1.00 (0.1&#x2013;18.0)</td>
<td align="char" valign="top" char=".">0.002</td>
</tr>
<tr>
<td align="left" valign="top">NT&#x2013;pro BNP, pg./mL</td>
<td align="char" valign="top" char="(">7, 428(1,856&#x2013;18,114)</td>
<td align="char" valign="top" char="(">1,388(246&#x2013;6,286)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">C&#x2013;reactive protein, mg/dL</td>
<td align="char" valign="top" char="(">4.0 (0.9&#x2013;10.1)</td>
<td align="char" valign="top" char="(">0.5 (0.1&#x2013;3.3)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Serum glucose maximum, mg/dL</td>
<td align="char" valign="top" char="(">169.0 (121.0&#x2013;230.0)</td>
<td align="char" valign="top" char="(">135.0 (113.0&#x2013;178.5)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Values are the mean&#x2009;&#x00B1;&#x2009;standard deviation, median (interquartile range), or <italic>n</italic> (%). <sup>&#x002A;</sup>Chronic kidney disease is defined as end-stage renal disease on hemodialysis or peritoneal dialysis. <sup>&#x002A;&#x002A;</sup>Polypharmacy is defined as the routine use of five or more medications. ALC, absolute lymphocyte count; CICU, cardiac intensive care unit; HDL, high density lipoprotein; LDL, low density lipoprotein; NT pro-BNP, N-terminal pro-brain natriuretic peptide; SOFA score, Sequential Organ Failure Assessment score.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec14">
<title>Cardiac intensive care unit management and clinical outcomes</title>
<p>Patients in the delirium group were more likely to receive vasopressor, mechanical ventilator, intraaortic balloon pump, and extracorporeal membrane oxygenator interventions than were those in the non-delirium group during the CICU stay (<xref rid="tab2" ref-type="table">Table 2</xref>). Compared with the non-delirium group, CICU length of stay (8.15&#x2009;&#x00B1;&#x2009;11.35&#x2009;days vs. 2.88&#x2009;&#x00B1;&#x2009;3.52&#x2009;days; <italic>p&#x2009;&#x003C;</italic> 0.001), CICU mortality (11.4% vs. 1.8%; <italic>p&#x2009;&#x003C;</italic> 0.001), and in-hospital mortality (18.3% vs. 3.1%; <italic>p&#x2009;&#x003C;</italic> 0.001) were higher in the delirium group.</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>In-hospital management and clinical outcomes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="left" valign="top">Delirium (<italic>n&#x2009;=</italic> 678)</th>
<th align="left" valign="top">Non&#x2013;delirium (<italic>n&#x2009;=</italic> 2,105)</th>
<th align="left" valign="top"><italic>P</italic> value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" colspan="4">In-hospital management</td>
</tr>
<tr>
<td align="left" valign="top">Vasopressor</td>
<td align="char" valign="top" char="(">360 (53.1)</td>
<td align="char" valign="top" char="(">467 (22.2)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Mechanical ventilation</td>
<td align="char" valign="top" char="(">346 (51.0)</td>
<td align="char" valign="top" char="(">520 (24.7)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Renal replacement therapy</td>
<td align="char" valign="top" char="(">57 (8.4)</td>
<td align="char" valign="top" char="(">208 (9.9)</td>
<td align="char" valign="top" char=".">0.285</td>
</tr>
<tr>
<td align="left" valign="top">Intraaortic balloon pump</td>
<td align="char" valign="top" char="(">32 (4.7)</td>
<td align="char" valign="top" char="(">47 (2.2)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">ECMO</td>
<td align="char" valign="top" char="(">138 (20.4)</td>
<td align="char" valign="top" char="(">179 (8.5)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top" colspan="4">Medical events during CICU</td>
</tr>
<tr>
<td align="left" valign="top">Sepsis</td>
<td align="char" valign="top" char="(">22 (3.2)</td>
<td align="char" valign="top" char="(">13 (0.6)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Bleeding</td>
<td align="char" valign="top" char="(">7 (1.0)</td>
<td align="char" valign="top" char="(">7 (0.3)</td>
<td align="char" valign="top" char=".">0.054</td>
</tr>
<tr>
<td align="left" valign="top">Stroke</td>
<td align="char" valign="top" char="(">11 (1.6)</td>
<td align="char" valign="top" char="(">3 (0.1)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top" colspan="4">Clinical outcomes</td>
</tr>
<tr>
<td align="left" valign="top">Length of stay in CICU, days</td>
<td align="char" valign="top" char="(">8.15 (&#x00B1; 11.35)</td>
<td align="char" valign="top" char="(">2.88 (&#x00B1; 3.52)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">CICU mortality</td>
<td align="char" valign="top" char="(">77 (11.4)</td>
<td align="char" valign="top" char="(">38 (1.8)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">In-hospital mortality</td>
<td align="char" valign="top" char="(">124 (18.3)</td>
<td align="char" valign="top" char="(">65 (3.1)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Values are the mean&#x2009;&#x00B1;&#x2009;standard deviation, median (interquartile range), or <italic>n</italic> (%). CICU, cardiac intensive care unit; ECMO, extracorporeal membrane oxygenation.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec15">
<title>Predictive performance for delirium</title>
<p>The distribution of delirium according to the value of each component in the three nutritional indices is shown in cubic spline curves (<xref rid="fig1" ref-type="fig">Figure 1</xref>). According to the increasing level of albumin, the occurrence of delirium tended to decrease linearly (<xref rid="fig1" ref-type="fig">Figure 1A</xref>). However, U-shaped correlation was observed for increased level of ALC, bodyweight/IBW, and total cholesterol with delirium (<xref rid="fig1" ref-type="fig">Figures 1B</xref>&#x2013;<xref rid="fig1" ref-type="fig">D</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Restricted cubic spline plot of the relationships between components of nutrition indices and delirium. The solid line is the log odds, and the dashed lines are the upper and lower 95% confidence limits. <bold>(A)</bold> Restricted cubic spline plot for the association between albumin (g/dL) and delirium. <bold>(B)</bold> Restricted cubic spline for the association between bodyweight/ideal bodyweight and delirium. <bold>(C)</bold> Restricted cubic spline for the association between absolute lymphocyte count (x10<sup>3</sup>/&#x03BC;L) and delirium. <bold>(D)</bold> Restricted cubic spline for the association between total cholesterol (ml/dL) and delirium.</p>
</caption>
<graphic xlink:href="fcvm-10-1100160-g001.tif"/>
</fig>
<p>The performances of albumin, PNI, GNRI, and CONUT for delirium prediction were compared and are shown in <xref rid="fig2" ref-type="fig">Figure 2</xref>. Among three nutritional indices, the AUROC of the CONUT was higher than those of the PNI and GNRI. Algorithm discrimination performance of albumin alone (AUC&#x2009;=&#x2009;0.770; 95% CI, 0.750&#x2013;0.790) and CONUT (AUC&#x2009;=&#x2009;0.762; 95% CI, 0.750&#x2013;0.790; <italic>p&#x2009;=</italic> 0.275) for delirium were not significantly different; however, discrimination was superior to that of the GNRI (AUC&#x2009;=&#x2009;0.729; 95% CI, 0.706&#x2013;0.753; <italic>p&#x2009;&#x003C;</italic> 0.001) and PNI (AUC&#x2009;=&#x2009;0.728; 95% CI, 0.706&#x2013;0.751; <italic>p&#x2009;&#x003C;</italic> 0.001).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>The receiver-operating characteristic curve comparing the predictive performances for delirium. The predictive performances of nutritional indices were calculated using Delong&#x2019;s test and compared to those of albumin. AUC, area under the curve; CONUT, Controlling Nutritional Status; GNRI, Geriatric Nutritional Risk Index; PNI, Prognostic Nutritional Index.</p>
</caption>
<graphic xlink:href="fcvm-10-1100160-g002.tif"/>
</fig>
</sec>
<sec id="sec16">
<title>Factors associated with delirium</title>
<p>Univariable logistic regression analysis indicated that 15 characteristics of CICU patients were associated with delirium (<xref rid="tab3" ref-type="table">Table 3</xref>). In multivariable analysis, age, sex, smoking, stroke, dementia, Sequential Organ Failure Assessment score, mechanical ventilation, and white blood cell were associated with increased risk of delirium, while albumin level at CICU admission (adjusted OR 0.555; 95% CI 0.402&#x2013;0.767; <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001) was associated with decreased risk of delirium.</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Factors associated with delirium.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="left" valign="top">OR (95% CI)</th>
<th align="left" valign="top"><italic>p</italic>-value</th>
<th align="left" valign="top"><sup>&#x002A;</sup>Adjusted OR (95% CI)</th>
<th align="left" valign="top"><italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Age, years</td>
<td align="char" valign="top" char="(">1.031 (1.024&#x2013;1.037)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.030 (1.020&#x2013;1.039)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Sex, male</td>
<td align="char" valign="top" char="(">1.573 (1.318&#x2013;1.878)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.894 (1.457&#x2013;2.462)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Smoking</td>
<td align="char" valign="top" char="(">0.737 (0.590&#x2013;0.920)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.602 (1.143&#x2013;2.244)</td>
<td align="char" valign="top" char=".">0.006</td>
</tr>
<tr>
<td align="left" valign="top">Hypertension</td>
<td align="char" valign="top" char="(">1.386 (1.162&#x2013;1.655)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Diabetes mellitus</td>
<td align="char" valign="top" char="(">1.479 (1.235&#x2013;1.771)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Stroke</td>
<td align="char" valign="top" char="(">2.611 (2.077&#x2013;3.282)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">2.106 (1.537&#x2013;2.886)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Dementia</td>
<td align="char" valign="top" char="(">8.813 (4.392&#x2013;17.684)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">8.636 (3.406&#x2013;21.898)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Previous coronary disease</td>
<td align="char" valign="top" char="(">1.446 (1.196&#x2013;1.749)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Chronic kidney disease<sup>&#x2020;</sup></td>
<td align="char" valign="top" char="(">1.319 (0.875&#x2013;1.988)</td>
<td align="char" valign="top" char=".">0.186</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">History of cardiac arrest</td>
<td align="char" valign="top" char="(">3.928 (3.044&#x2013;5.069)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.537 (1.052&#x2013;2.247)</td>
<td align="char" valign="top" char=".">0.026</td>
</tr>
<tr>
<td align="left" valign="top">SOFA score at admission</td>
<td align="char" valign="top" char="(">1.408 (1.363&#x2013;1.455)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.335 (1.279&#x2013;1.393)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Polypharmacy<sup>&#x2020;&#x2020;</sup></td>
<td align="char" valign="top" char="(">0.807 (0.631&#x2013;1.032)</td>
<td align="char" valign="top" char=".">0.088</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Mechanical ventilation</td>
<td align="char" valign="top" char="(">3.173 (2.649&#x2013;3.799)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.529 (1.071&#x2013;2.181)</td>
<td align="char" valign="top" char=".">0.019</td>
</tr>
<tr>
<td align="left" valign="top">Renal replacement therapy</td>
<td align="char" valign="top" char="(">0.836 (0.615&#x2013;1.136)</td>
<td align="char" valign="top" char=".">0.253</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Intraaortic balloon pump</td>
<td align="char" valign="top" char="(">2.167 (1.371&#x2013;3.425)</td>
<td align="char" valign="top" char=".">0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">ECMO</td>
<td align="char" valign="top" char="(">2.747 (2.157&#x2013;3.498)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">White blood cell count, 10<sup>3</sup>/&#x03BC;L</td>
<td align="char" valign="top" char="(">1.115 (1.097&#x2013;1.133)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">1.058 (1.030&#x2013;1.088)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Hemoglobin, g/dL</td>
<td align="char" valign="top" char="(">0.727 (0.699&#x2013;0.757)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top" colspan="5">Blood urea nitrogen, mg/dL</td>
</tr>
<tr>
<td align="left" valign="top">Serum glucose maximum, mg/dL</td>
<td align="char" valign="top" char="(">1.004 (1.002&#x2013;1.005)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top" colspan="5">Component of nutritional indices</td>
</tr>
<tr>
<td align="left" valign="top">Albumin, g/dL</td>
<td align="char" valign="top" char="(">0.199 (0.169&#x2013;0.234)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td align="char" valign="top" char="(">0.409 (0.328&#x2013;0.510)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">ALC, x10<sup>3</sup>/&#x03BC;L</td>
<td align="char" valign="top" char="(">0.800 (0.739&#x2013;0.867)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Total cholesterol, mg/dL</td>
<td align="char" valign="top" char="(">0.986 (0.984&#x2013;0.988)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Bodyweight/IBW</td>
<td align="char" valign="top" char="(">0.332 (0.189&#x2013;0.583)</td>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
<td/>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>ALC, absolute lymphocyte count; CI, confidence interval; CICU, cardiac intensive care unit; IBW, ideal bodyweight; OR, odds ratio; SOFA, Sequential Organ Failure Assessment. <sup>&#x002A;</sup>Adjusted covariates were age, sex, smoking, hypertension, diabetes mellitus, stroke, dementia, previous coronary disease, chronic kidney disease, history of cardiac arrest, SOFA score, albumin, ALC, total cholesterol, and bodyweight/IBW. <sup>&#x2020;</sup>Chronic kidney disease is defined as end-stage renal disease on hemodialysis or peritoneal dialysis. <sup>&#x2020;&#x2020;</sup>Polypharmacy is defined as the routine use of five or more medications.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="sec17" sec-type="discussions">
<title>Discussion</title>
<p>We investigated the associations of nutritional indices and their components with delirium in CICU patients from a single-center registry. The major findings were as follows: (i) nutritional indices (PNI, GNRI, and CONUT) had fair predictive performances for delirium in CICU patients; (ii) predictive performance of albumin alone for delirium was superior to those of PNI and GNRI and similar to that of CONUT; and (iii) among the components of nutritional indices, albumin was an independent predictor of delirium, whereas ALC, bodyweight/IBW, and total cholesterol were not.</p>
<p>Delirium is an emerging complication of CICU stay, with a reported incidence range from 5.7 to 40% (<xref ref-type="bibr" rid="ref18">18</xref>&#x2013;<xref ref-type="bibr" rid="ref20">20</xref>). There are several possible causes for the increased incidence of delirium in CICU. First of all, acute respiratory failure caused by cardiac origin has been a leading indication for CICU admission, and recent studies have described temporal increases in mechanical ventilation support in CICU populations (<xref ref-type="bibr" rid="ref21">21</xref>). Although the clinical practice guidelines for adult patients in the ICU recommend light sedation, some mechanically ventilated patients require deep sedation to control pain and agitation during the early phase of respiratory failure (<xref ref-type="bibr" rid="ref12">12</xref>). For deep sedation, intravenous administration of opioids and benzodiazepines is often used, and their use is associated with delirium (<xref ref-type="bibr" rid="ref22">22</xref>). Furthermore, the CICU has become considerably more complex with advanced medical devices, increasing CICU patient complications (<xref ref-type="bibr" rid="ref3">3</xref>). Therefore, delirium has recently been recognized as a common comorbidity for CICU patients.</p>
<p>Several prospective cohort studies have evaluated the incidence of postoperative delirium in malnourished patients undergoing coronary artery bypass grafting and have found that malnutrition is associated with postoperative delirium (<xref ref-type="bibr" rid="ref7">7</xref>, <xref ref-type="bibr" rid="ref23">23</xref>). Meta-analysis to determine the risk factors of delirium after orthopedic surgery in elderly patients has also shown malnutrition as an important factor for delirium after surgery (<xref ref-type="bibr" rid="ref24">24</xref>). In CICU patients, Sugita et al. conducted a prospective cohort study to evaluate the association between malnutrition and delirium in critically ill cardiac patients (<xref ref-type="bibr" rid="ref25">25</xref>). Of 653 CICU patients, 58 (8.9%) developed delirium, for which PNI and CONUT were both reported to be independent predictors of delirium, but GNRI was not. They suggested that ALC, included in PNI and CONUT but not in GNRI, might be an important prognostic factor associated with inflammation in delirium patients. However, in the present study, U-shaped correlation was observed between increased level of ALC and delirium. Furthermore, the discrimination performance of PNI for delirium was similar to those of CONUT and GNRI.</p>
<p>Albumin is the most abundant protein in the plasma and is a major transporter of many compounds in blood (<xref ref-type="bibr" rid="ref26">26</xref>). A recent study of surgical ICU patients by Yeh DD, et al. found that serum albumin levels and pre-albumin levels may reflect baseline nutrition status. However, changes in serum albumin and pre-albumin levels during ICU stays may not indicate nutritional adequacy in the ICU (<xref ref-type="bibr" rid="ref27">27</xref>). This is because albumin synthesis can be affected by numerous acute and chronic disease processes, and serum albumin level can provide predictive insights into the effects of disease on protein metabolism. Hypoalbuminemia can be observed in acute illness due to increased capillary leakage or decreased synthesis due to inflammation, underlying malnutrition, or hepatic synthetic dysfunction (<xref ref-type="bibr" rid="ref28">28</xref>). Therefore, albumin is a well-known predictor of mortality in critically ill patients (<xref ref-type="bibr" rid="ref29">29</xref>). Recent studies have reported the association between albumin level and delirium, and meta-analysis of risk factors of delirium occurrence among elderly patients in medical ICUs has found that low albumin level is associated with delirium (<xref ref-type="bibr" rid="ref30">30</xref>). Zhang et al. analyzed 700 elderly patients admitted to the ICU after non-cardiac surgery and found that preoperative hypoalbuminemia was associated with an increased risk of postoperative delirium (<xref ref-type="bibr" rid="ref31">31</xref>). Similarly, we found the decrease in albumin level is a risk factor of developing delirium in CICU patients. Furthermore, albumin alone revealed an inverse linear correlation with delirium, and its predictive performance was superior to those of PNI and GNRI and similar to that of CONUT. Compared with other variables included in nutritional indices, only albumin showed a linear correlation with delirium. Therefore, albumin might be a helpful and simple indicator for predicting delirium in CICU patients. This finding should be validated in future studies, and the mechanism of the relationship between albumin and delirium should be investigated further.</p>
<p>Although this study provides additional information on the associations of albumin and nutritional indices with delirium in CICU patients, several limitations should be noted. First, our study used nonrandomized registry data. Therefore, selection bias and confounding factors might have affected our results. Second, we evaluated delirium only using CAM-ICU. However, the CAM-ICU is generally used for delirium assessment in general ICUs, and we used this tool for routine practice in ICU management including CICU. Finally, we did not include individual information on nutritional support during CICU management collect pre albumin level for comparing albumin for nutritional status. Further studies including detailed knowledge of nutritional support would be informative.</p>
</sec>
<sec id="sec18" sec-type="conclusions">
<title>Conclusion</title>
<p>Predictive performances of nutritional indices for the occurrence of delirium were acceptable, and albumin alone as a component of nutritional indices might be a simple and helpful indicator of delirium in patients admitted to a CICU.</p>
</sec>
<sec id="sec19" sec-type="data-availability">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="sec20">
<title>Ethics statement</title>
<p>The studies involving human participants were reviewed and approved by the Institutional Review Board of Samsung Medical Center approved this study (IRB. No. 2020-10-102) and waived the requirement for informed consent because of the observational nature of the study.</p>
</sec>
<sec id="sec21">
<title>Author contributions</title>
<p>TK, RK, SN, CC, KC, C-MP, and JY contributed to conception and design of the study. TK, SN, CC, and KC organized the database. TK, RK, and JY performed the data analysis and interpretation. TK wrote the first draft of the manuscript. TK, RK, C-MP, and JY revised the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.</p>
</sec>
<sec id="conf1" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="sec100" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
</body>
<back>
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</ref-list>
<glossary>
<def-list>
<title>Abbreviations</title>
<def-item><term>ALC</term><def><p>absolute lymphocyte count</p></def></def-item>
<def-item><term>AUROC</term><def><p>area under the receiver operating characteristic curve</p></def></def-item>
<def-item><term>CAM-ICU</term><def><p>confusion assessment method for the intensive care unit</p></def></def-item>
<def-item><term>CI</term><def><p>confidence interval</p></def></def-item>
<def-item><term>CICU</term><def><p>cardiac intensive care unit</p></def></def-item>
<def-item><term>CONUT</term><def><p>Controlling Nutritional Status</p></def></def-item>
<def-item><term>GNRI</term><def><p>Geriatric Nutritional Risk Index</p></def></def-item>
<def-item><term>IBW</term><def><p>ideal bodyweight</p></def></def-item>
<def-item><term>ICU</term><def><p>intensive care unit</p></def></def-item>
<def-item><term>OR</term><def><p>odds ratio</p></def></def-item>
<def-item><term>PNI</term><def><p>Prognostic Nutrition Index</p></def></def-item>
</def-list>
</glossary>
</back>
</article>