RESUMO
The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. We compared blood gene expression (whole-genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total, 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up- and downregulation of canonical signalling pathways. In the matched analysis, the top upregulated gene was cold-inducible mRNA binding protein (CIRBP) which plays a role in cold-induced suppression of cell proliferation. In addition, we found three signalling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. In conclusion, there are distinct signalling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression, providing a possible link to the modulation of body temperature and early immunosuppression. Future studies may focus on the canonical signalling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis.
Assuntos
Hipotermia , Sepse , Febre/genética , Humanos , Hipotermia/complicações , Hipotermia/genética , Proteínas de Ligação a RNA/metabolismo , Sepse/complicações , Sepse/genética , Transcriptoma/genética , TriptofanoRESUMO
BACKGROUND: Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers. METHODS: Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg-1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model. RESULTS: In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L-1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide. CONCLUSION: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
Assuntos
Coagulação Sanguínea , Coagulação Intravascular Disseminada/prevenção & controle , Endotoxemia/terapia , Hipotermia Induzida , Adolescente , Adulto , Biomarcadores/sangue , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , Endotoxemia/sangue , Endotoxemia/induzido quimicamente , Endotoxemia/diagnóstico , Endotoxinas/administração & dosagem , Voluntários Saudáveis , Humanos , Hipotermia Induzida/efeitos adversos , Infusões Parenterais , Masculino , Fatores de Tempo , Adulto JovemRESUMO
AIMS: Infectious complications frequently occur in intensive care unit patients admitted after out-of-hospital cardiac arrest. There is debate on the effects of temperature management on the incidence of infections, as well as on the efficacy and choice of antibiotic prophylaxis. In this substudy of the targeted temperature management (TTM) trial, we describe the microbiological profile of infectious complications in patients with cardiac arrest and examined the impact of TTM at 33⯰C compared to TTM at 36⯰C. Furthermore we aimed to determine the association between antibiotic prophylaxis and the incidence of infections. METHODS: This is a posthoc analysis of the TTM cohort. Microbiological data was retrospectively collected for the first 14-days of ICU-admission. Logistic regression was used to determine the relationship between antibiotic prophylaxis and pneumonia adjusted for mortality. RESULTS: Of 696 patients included in this analysis, 158 (23%) developed pneumonia and 28 (4%) had bacteremia with a clinically relevant pathogen. Staphylococcus aureus was the most common pathogen isolated in patients with pneumonia (23%) and in patients with bacteremia (24%). Gram-negative pathogens were most common overall. TTM did not have an impact on the microbiological profile. The use of antibiotic prophylaxis was significantly associated with a reduced risk of infection (OR 0.59, 95%CI 0.43-0.79, pâ¯=â¯0.0005). This association remained significant after correcting for confounders (OR 0.64, 95%CI 0.46-0.90; pâ¯=â¯0.01). The association is not present in a model after correction for clustering within centers (aOR 0.55, 95%CI 0.20-1.47, pâ¯=â¯0.22). Adjustment for mortality did not influence the outcome. CONCLUSION: Gram-negative pathogens are the most common causes of nosocomial infections following cardiac arrest. TTM does not impact the microbiological profile. It remains unclear whether patients in ICUs using antibiotic prophylaxis have a reduced risk of pneumonia and bacteremia that is unrelated to center effects.
Assuntos
Infecção Hospitalar , Hipotermia Induzida , Parada Cardíaca Extra-Hospitalar , Infecção Hospitalar/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Parada Cardíaca Extra-Hospitalar/terapia , Estudos RetrospectivosRESUMO
Hypothermia is associated with high mortality in sepsis, but it is now recognized that this association may simply reflect its higher prevalence in sicker patients. Furthermore, there is evidence to suggest that hypothermia may not represent a dysfunction in sepsis. In this study, we conducted a survey to assess how this scientific evidence relates to the perceptions of health care professionals regarding septic hypothermia, and how such perceptions drive clinical conduct concerning the use of active rewarming in this population. A survey with questions on opinions and management of spontaneous hypothermia in sepsis was developed and posted online at the European Society of Intensive Care Medicine (ESICM) website from March 24th, 2017 to the June 26th, 2017 and distributed by electronic email. Respondents were asked to fill in the survey from the perspective of their usual or average practice in their intensive care unit. In total, there were 440 survey respondents. Respondents were predominantly from Europe (66%) The majority of respondents were intensivists (78%) and worked in an academic hospital (66%). One percent of respondents were nurses. Most respondents (96%) reported that there was no protocol for the management of hypothermic sepsis. Of the respondents, 62% actively rewarmed patients with hypothermic sepsis. Hypothermia was defined as a temperature below 36°C (44%) and below 35°C (15%). Rewarming practices showed large variation in terms of the temperature, at which respondents initiate rewarming as well as the target temperature to which patients are rewarmed. The most predominant first-line rewarming method was forced-warm air followed by warm IV fluids. Rewarming decisions were mostly physician driven (58%). Most respondents thought rewarming was beneficial (43%), a small proportion thought rewarming to be harmful (9%). In conclusion, policies, procedures, and beliefs about spontaneous hypothermia and active rewarming in patients with sepsis are variable. This must be taken into consideration in designing future trials. We propose a working group to define hypothermic sepsis to improve comparability of research.
Assuntos
Hipotermia Induzida , Hipotermia , Sepse , Humanos , Hipotermia/terapia , Reaquecimento , Sepse/diagnóstico , Sepse/epidemiologia , Sepse/terapia , Inquéritos e QuestionáriosRESUMO
AIMS: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33⯰C versus 36⯰C) on mechanical ventilation settings. METHODS: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33⯰C (TTM33) and 36⯰C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. RESULTS: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7â¯ml/kg predicted body weight (PBW)(6.4-8.7) and 60% of patients were ventilated with a tidal volume ≤ 8â¯ml/kg PBW. Median PEEP was 7.7cmH2O (6.4-8.7) and mean driving pressure was 14.6 cmH2O (±4.3). The median FiO2 fraction was 0.35 (0.30-0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO2 (Pgroupâ¯=â¯0.0003) and higher alveolar dead space fraction (Pgroupâ¯=â¯0.003) compared to TTM36, while PCO2 levels and respiratory minute volume were similar between groups. CONCLUSIONS: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO2 levels and a higher alveolar dead space fraction compared to TTTM36.