Septic Shock: Phenotypes and Outcomes.

INTRODUCTION: Sepsis is a heterogeneous syndrome that results in life-threatening organ dysfunction. Our goal was to determine the relevant variables and patient phenotypes to use in predicting sepsis outcomes. METHODS: We performed an ancillary study concerning 119 patients with septic shock at intensive care unit (ICU) admittance (T0). We defined clinical worsening as having an increased sequential organ failure assessment (SOFA) score of ≥ 1, 48 h after admission (ΔSOFA ≥ 1). We performed univariate and multivariate analyses based on the 28-day mortality rate and ΔSOFA ≥ 1 and determined three patient phenotypes: safe, intermediate and unsafe. The persistence of the intermediate and unsafe phenotypes after T0 was defined as a poor outcome. RESULTS: At T0, the multivariate analysis showed two variables associated with 28-day mortality rate: norepinephrine dose and serum lactate concentration. Regarding ΔSOFA ≥ 1, we identified three variables at T0: norepinephrine dose, lactate concentration and venous-to-arterial carbon dioxide difference (P(v-a)CO2). At T0, the three phenotypes (safe, intermediate and unsafe) were found in 28 (24%), 70 (59%) and 21 (18%) patients, respectively. We thus suggested using an algorithm featuring norepinephrine dose, lactate concentration and P(v-a)CO2 to predict patient outcomes and obtained an area under the curve (AUC) of 74% (63-85%). CONCLUSION: Our findings highlight the fact that identifying relevant variables and phenotypes may help physicians predict patient outcomes.

Ultra-early initiation of postoperative rehabilitation in the post-anaesthesia care unit after major thoracic surgery: case-control study.

BACKGROUND: Physiotherapy is a major cornerstone of enhanced rehabilitation after surgery (ERAS) and reduces the development of atelectasis after thoracic surgery. By initiating physiotherapy in the post-anaesthesia care unit (PACU), the aim was to evaluate whether the ultra-early initiation of rehabilitation (in the first hour following tracheal extubation) would improve the outcomes of patients undergoing elective thoracic surgery. METHODS: A case-control study with a before-and-after design was conducted. From a historical control group, patients were paired at a 3:1 ratio with an intervention group. This group consisted of patients treated with the ultra-early rehabilitation programme after elective thoracic surgery (clear fluids, physiotherapy, and ambulation). The primary outcome was the incidence of postoperative atelectasis and/or pneumonia during the hospital stay. RESULTS: After pairing, 675 patients were allocated to the historical control group and 225 patients to the intervention group. A significant decrease in the incidence of postoperative atelectasis and/or pneumonia was found in the latter (11.4 versus 6.7 per cent respectively; P = 0.042) and remained significant on multivariate analysis (OR 0.53, 95 per cent c.i. 0.26 to 0.98; P = 0.045). A subgroup analysis of the intervention group showed that early ambulation during the PACU stay was associated with a further significant decrease in the incidence of postoperative atelectasis and/or pneumonia (2.2 versus 9.5 per cent; P = 0.012). CONCLUSIONS: Ultra-early rehabilitation in the PACU was associated with a decrease in the incidence of postoperative atelectasis and/or pneumonia after major elective thoracic surgery.

Management of SARS-CoV-2 pneumonia in intensive care unit: An observational retrospective study comparing two bundles.

PURPOSE: To compare the effects of two therapeutic bundles of management in SARS-CoV2 ICU patients. MATERIALS AND METHODS: Our retrospective, observational study was performed in a university ICU from March to June 2020 (first wave) and from September 2020 to January 2021 (second wave). In first wave, patients received bundle 1 including early invasive ventilation, hydroxychloroquine, cefotaxime and azithromycin. In second wave, bundle 2 included non-invasive oxygenation support and dexamethasone. The main outcome was in-hospital mortality. Secondary outcomes included ICU and hospital length of stay, ICU supportive therapies, viral clearance and antimicrobial resistance emergence. RESULTS: 129 patients with SARS-CoV-2 pneumonia were admitted to our ICU. Thirty-five were treated according to bundle 1 and 76 to bundle 2. In-hospital mortality was similar in the two groups (23%, p = 1). The hospital (p = 0.003) and ICU (p = 0.01) length of stay and ventilator-free days at 28 days (p = 0.03) were significantly reduced in bundle 2. Increasing age, vasopressor use and PaO2/FiO2 ratio < 125 were associated with in-hospital mortality. CONCLUSION: Within the limitations of our study, changes in therapeutic bundles for SARS-Cov-2 ICU patients might have no effect on in-hospital mortality but were associated with less exposure to mechanical ventilation and reduced hospital length of stay.

Exacerbation of circadian rhythms of core body temperature and sepsis in trauma patients.

PURPOSE: This study aimed to describe by mathematical modeling an accurate course of core body temperature (CBT) in severe trauma patients and its relation to sepsis. METHODS: In a cohort of severe trauma, the CBT measurements were collected for 24 h on day 2 after admission and rhythmicity assessed by Fourier transform and Cosinor analysis to describe circadian features (frequency and amplitude). CBT was compared between patients who developed sepsis or not during the early ICU stay. RESULTS: 33 patients were included in this analysis. 24 patients (73%) had a predominant rhythm of 24 h (period). The main period was lower in the 9 remaining patients (6 of 12 h, 1 of 8 h, and 2 of 6 h). Other significant frequencies of oscillation (second and third frequencies) were found, which showed an association of several well-marked rhythms. Patients with sepsis (n = 12) had a significantly higher level of CBT, but also more intense rhythms and higher amplitudes of CBT. CONCLUSION: Trauma patients exhibit complex temperature circadian rhythms. Early exacerbation of the temperature rhythmicity (in frequency and amplitude) is associated with the development of sepsis. This observation accentuates the concept of circadian disruption and sepsis in ICU patients.

Circadian disruption of core body temperature in trauma patients: a single-center retrospective observational study.

BACKGROUND: Circadian clock alterations were poorly reported in trauma patients, although they have a critical role in human physiology. Core body temperature is a clinical variable regulated by the circadian clock. Our objective was to identify the circadian temperature disruption in trauma patients and to determine whether these disruptions were associated with the 28-day mortality rate. METHODS: A retrospective and observational single-center cohort study was conducted. All adult severe trauma patients admitted to the intensive care unit of Aix Marseille University, North Hospital, from November 2013 to February 2018, were evaluated. The variations of core body temperature for each patient were analyzed between days 2 and 3 after intensive care unit admission. Core body temperature variations were defined by three parameters: mesor, amplitude, and period. A logistic regression model was used to determine the variables influencing these three parameters. A survival analysis was performed assessing the association between core body temperature rhythm disruption and 28-day mortality rate. A post hoc subgroup analysis focused on the patients with head trauma. RESULTS: Among the 1584 screened patients, 248 were included in this study. The period differed from 24 h in 177 (71%) patients. The mesor value (°C) was associated with body mass index and ketamine use. Amplitude (°C) was associated with ketamine use only. The 28-day mortality rate was 18%. For all trauma patients, age, body mass index, intracranial hypertension, and amplitude were independent risk factors. The patients with a mesor value < 36.9 °C (p < 0.001) and an amplitude > 0.6 °C (p < 0.001) had a higher 28-day mortality rate. Among the patients with head trauma, mesor and amplitude were identified as independent risk factors (HR = 0.40, 95% CI [0.23-0.70], p = 0.001 and HR = 4.73, 95% CI [1.38-16.22], p = 0.01). CONCLUSIONS: Our results highlight an association between core body temperature circadian alteration and 28-day mortality rate. This association was more pronounced in the head trauma patients than in the non-head trauma patients. Further studies are needed to show a causal link and consider possible interventions.

Circadian Rhythm Disruption and Sepsis in Severe Trauma Patients.

BACKGROUND: Circadian rhythms are important regulators of immune functions. Admission to an intensive care unit may impact molecular clock activity and host response. Our objective was to assess and compare the immune circadian rhythms in trauma patients who develop and in those who do not develop sepsis. METHODS: Blood samples were collected from severe trauma patients within 4 days after admission, with collections taking place every 4 h over a 24-h period. Cortisol and cytokines were measured with immunoassays. Whole-blood expression of 3 clock genes (Bmal1, Per2, and Per3) was studied by reverse transcription quantitative polymerase chain reaction. Neutrophils, monocytes, and lymphocytes were analyzed by flow cytometry. Patients with and without sepsis were compared with the cosinor mixed model to estimate mesors, amplitudes, and acrophases. RESULTS: Thirty-eight patients were enrolled in the study, and 13 developed at least 1 septic episode. The septic patients had higher levels of cortisol than the nonseptic patients (mesor at 489 nmol/L vs. 405 nmol/L, P < 0.05) and delayed acrophases (22 h vs. 15 h, P < 0.05). They also had lower lymphocyte counts (mesor at 785 vs. 1,012 cells/µL, P < 0.05), higher neutrophil counts (mesor at 7,648 vs. 7,001 cells/µL, P < 0.05), and monocyte counts (mesor at 579 vs. 473 cells/µL, P < 0.05) than the nonseptic patients. Although no amplitude difference was identified, the acrophases were significantly different between the 2 groups for lymphocytes, interleukin 10 and tumor necrosis factor. CONCLUSION: We demonstrated that all trauma patients had impaired circadian rhythms of cortisol, cytokines, leukocytes, and clock genes. Early circadian disruption was associated with the occurrence of sepsis and might be a marker of sepsis severity.