Scientific Letter
Toward a personalized response approach in sepsis 4.0
Hacia una estrategia de respuesta personalizada en sepsis 4.0
C. de Haroa, E. Torrentsa, R. Ferrerb, A. Artigasa, A. Rodriguezc, I. Martin-Loechesd,
Autor para correspondencia
a Critical Care Center, Parc Taulí Hospital-Sabadell, CIBERes, Parc Tauli s/n. Sabadell, Barcelona, Spain
b Critical Care Center, Vall d’Hebron Hospital, CIBERes, Pss Villanova s/n, Barcelona, Spain
c Critical Care Department, Joan XXIII University Hospital, CIBERes, Dr. Mallafrè Guasch, 4, Tarragona, Spain
d Multidisciplinary Intensive Care Research Organization (MICRO), CIBERes, Wellcome Trust HRB Clinical Research, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James's University Hospital, St James's Street, Dublin, Ireland
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"apellidos" => "Martin-Loeches" "email" => array:1 [ 0 => "drmartinloeches@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Critical Care Center, Parc Taulí Hospital-Sabadell, CIBERes, Parc Tauli s/n. Sabadell, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Critical Care Center, Vall d’Hebron Hospital, CIBERes, Pss Villanova s/n, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Critical Care Department, Joan XXIII University Hospital, CIBERes, Dr. Mallafrè Guasch, 4, Tarragona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Multidisciplinary Intensive Care Research Organization (MICRO), CIBERes, Wellcome Trust HRB Clinical Research, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James's University Hospital, St James's Street, Dublin, Ireland" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hacia una estrategia de respuesta personalizada en sepsis 4.0" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 779 "Ancho" => 1622 "Tamanyo" => 45466 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Odds ratio for mortality in patients included in the study. <span class="elsevierStyleItalic">Abbreviation</span>: OR, odds ratio.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Sepsis is one of the leading causes of mortality worldwide.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> However, mortality rates widely vary among different countries when patients have been enrolled in prospective septic shock trials.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> For this and other reason, including sepsis recognition, new definitions of septic shock were launched. Now, shock is a clinical condition defined by a vasopressor requirement to maintain a mean arterial pressure of 65<span class="elsevierStyleHsp" style=""></span>mm Hg or greater and serum lactate level greater than 2<span class="elsevierStyleHsp" style=""></span>mmol/L (>18<span class="elsevierStyleHsp" style=""></span>mg/dL) in the absence of hypovolemia.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Our hypothesis is that lactate level is not sufficient for defining shock progression but timing within the first 24<span class="elsevierStyleHsp" style=""></span>h of resuscitation. The aim of the present study is to determine the prognostic value of a predefined lactate clearance in the first 24<span class="elsevierStyleHsp" style=""></span>h of sepsis. A total of 544 consecutive patients with sepsis were included from a tertiary University Hospital (Parc Tauli Hospital, Sabadell, Spain). The vast majority presented an abdominal (37.9%) or respiratory source of sepsis (31.3%) and 62.8% were admitted through emergency department. Patients presented were 66.6 (SD 14.8) years old, 63.2% male and presented an APACHE II score of 18.4 (SD 7.7) with a mortality rate of 29.8%. We calculated the optimal cutoff for a lower mortality during the first 24<span class="elsevierStyleHsp" style=""></span>h of sepsis using the Youden index. With our data, this optimal cutoff was 10%, with a sensitivity of 51% and specificity of 71%. Patients with a lactate clearance<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10% within the first 24<span class="elsevierStyleHsp" style=""></span>h of sepsis had a lower mortality in a univariate analysis than patients without that clearance (21.2% vs. 39.1%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). We adjusted lactate clearance for confounding factors, as initial lactate value and severity (APACHE II score), and we observed that lactate clearance<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10% during the first 24<span class="elsevierStyleHsp" style=""></span>h of sepsis was identified as a protective factor for mortality (OR 0.49: 95% CI 0.30–0.81; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). We, therefore, analyzed the relationship between lactate clearance and the fulfillment of the Surviving Sepsis Campaign (SSC) bundles. The group of patients with a lactate clearance<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10% trended toward a better fulfillment of SCC bundles (5.1% vs. 2.2%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.12). We performed a multivariate analysis including all the SCC bundles (antibiotic treatment, fluid administration, vasopressors and initial lactate value and fluid administration) and lactate clearance<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10% (OR 6.41; 95% CI 2.01–20.45; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) was associated independently with a lower mortality. Despite the new incorporation of serum lactate levels for shock definition, we consider that the most important approach to reflect current ICU mortality would be the use of lactate clearance in the definition.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> Therefore, a personalized approach is lacking in the current definitions and a lactate clearance equal or greater than 10% within the first 24<span class="elsevierStyleHsp" style=""></span>h of sepsis evolution is independently associated with lower mortality. Nguyen et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> discovered that early lactate clearance within the first 6<span class="elsevierStyleHsp" style=""></span>h was associated with a decrease mortality however the 10% decrease was chosen after analyzing sensitivity and specificity of different thresholds. In our study, the implementation of a mathematical model (Youden index) helped us to find the “ideal threshold”. Interestingly, in accordance with recently published studies, in our cohort, fluid administration during the first hours of sepsis is independently associated with lactate clearance.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> Effort should be done to identify patients with shock and determinant of response, rather than to flag them only shocked.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0010" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0015" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to disclose.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 779 "Ancho" => 1622 "Tamanyo" => 45466 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Odds ratio for mortality in patients included in the study. <span class="elsevierStyleItalic">Abbreviation</span>: OR, odds ratio.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of severe sepsis: advances, challenges, and current status" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "I. Martin-Loeches" 1 => "M.M. Levy" 2 => "A. Artigas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Drug Des Dev Ther" "fecha" => "2015" "volumen" => "9" "paginaInicial" => "2079" "paginaFinal" => "2088" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.M. Levy" 1 => "A. Rhodes" 2 => "G.S. Phillips" 3 => "S.R. Townsend" 4 => "C.A. Schorr" 5 => "R. 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De Backer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-015-3906-y" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2015" "volumen" => "41" "paginaInicial" => "1620" "paginaFinal" => "1628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26109396" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02105691/0000004100000001/v3_201702170036/S0210569116301334/v3_201702170036/en/main.assets" "Apartado" => array:4 [ "identificador" => "19505" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas Científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105691/0000004100000001/v3_201702170036/S0210569116301334/v3_201702170036/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116301334?idApp=WMIE" ]
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| 2023 Abril | 36 | 27 | 63 |
| 2023 Marzo | 50 | 37 | 87 |
| 2023 Febrero | 41 | 39 | 80 |
| 2023 Enero | 34 | 35 | 69 |
| 2022 Diciembre | 54 | 31 | 85 |
| 2022 Noviembre | 48 | 40 | 88 |
| 2022 Octubre | 77 | 50 | 127 |
| 2022 Septiembre | 43 | 37 | 80 |
| 2022 Agosto | 56 | 47 | 103 |
| 2022 Julio | 39 | 32 | 71 |
| 2022 Junio | 30 | 27 | 57 |
| 2022 Mayo | 51 | 44 | 95 |
| 2022 Abril | 40 | 48 | 88 |
| 2022 Marzo | 46 | 45 | 91 |
| 2022 Febrero | 41 | 41 | 82 |
| 2022 Enero | 39 | 38 | 77 |
| 2021 Diciembre | 62 | 53 | 115 |
| 2021 Noviembre | 70 | 43 | 113 |
| 2021 Octubre | 49 | 85 | 134 |
| 2021 Septiembre | 56 | 44 | 100 |
| 2021 Agosto | 38 | 53 | 91 |
| 2021 Julio | 32 | 34 | 66 |
| 2021 Junio | 50 | 45 | 95 |
| 2021 Mayo | 45 | 64 | 109 |
| 2021 Abril | 94 | 97 | 191 |
| 2021 Marzo | 110 | 38 | 148 |
| 2021 Febrero | 79 | 38 | 117 |
| 2021 Enero | 59 | 25 | 84 |
| 2020 Diciembre | 66 | 38 | 104 |
| 2020 Noviembre | 23 | 23 | 46 |
| 2020 Octubre | 42 | 26 | 68 |
| 2020 Septiembre | 35 | 31 | 66 |
| 2020 Agosto | 40 | 17 | 57 |
| 2020 Julio | 34 | 31 | 65 |
| 2020 Junio | 30 | 19 | 49 |
| 2020 Mayo | 17 | 10 | 27 |
| 2020 Abril | 62 | 19 | 81 |
| 2020 Marzo | 33 | 11 | 44 |
| 2020 Febrero | 59 | 36 | 95 |
| 2020 Enero | 39 | 38 | 77 |
| 2019 Diciembre | 52 | 30 | 82 |
| 2019 Noviembre | 48 | 23 | 71 |
| 2019 Octubre | 44 | 13 | 57 |
| 2019 Septiembre | 36 | 21 | 57 |
| 2019 Agosto | 44 | 28 | 72 |
| 2019 Julio | 31 | 25 | 56 |
| 2019 Junio | 14 | 13 | 27 |
| 2019 Mayo | 38 | 32 | 70 |
| 2019 Abril | 15 | 19 | 34 |
| 2019 Marzo | 14 | 32 | 46 |
| 2019 Febrero | 21 | 34 | 55 |
| 2019 Enero | 25 | 40 | 65 |
| 2018 Diciembre | 46 | 35 | 81 |
| 2018 Noviembre | 43 | 69 | 112 |
| 2018 Octubre | 41 | 27 | 68 |
| 2018 Septiembre | 19 | 17 | 36 |
| 2018 Agosto | 23 | 14 | 37 |
| 2018 Julio | 26 | 14 | 40 |
| 2018 Junio | 34 | 16 | 50 |
| 2018 Mayo | 13 | 12 | 25 |
| 2018 Abril | 28 | 14 | 42 |
| 2018 Marzo | 20 | 8 | 28 |
| 2018 Febrero | 25 | 7 | 32 |
| 2018 Enero | 52 | 21 | 73 |
| 2017 Diciembre | 32 | 12 | 44 |
| 2017 Noviembre | 35 | 14 | 49 |
| 2017 Octubre | 25 | 19 | 44 |
| 2017 Septiembre | 25 | 17 | 42 |
| 2017 Agosto | 31 | 14 | 45 |
| 2017 Julio | 23 | 11 | 34 |
| 2017 Junio | 38 | 22 | 60 |
| 2017 Mayo | 45 | 25 | 70 |
| 2017 Abril | 56 | 5 | 61 |
| 2017 Marzo | 1 | 1 | 2 |
| 2017 Febrero | 14 | 4 | 18 |
| 2017 Enero | 0 | 3 | 3 |
| 2016 Noviembre | 0 | 1 | 1 |
| 2016 Octubre | 0 | 3 | 3 |
| 2016 Septiembre | 2 | 3 | 5 |
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