Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study.

OBJECTIVES: Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission. DESIGN: Prospective multicenter cohort study. SETTING: Three mixed ICU from April 2014 to December 2017. PATIENTS: Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: "State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg). CONCLUSIONS: Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.

Dysglycemia and Neurologic Outcome in Mechanically Ventilated Patients With Guillain-Barré Syndrome.

OBJECTIVES: Acute respiratory failure is a frequent complication of Guillain-Barré syndrome, associated with high morbidity and mortality. Adjuvant treatments are needed to improve the outcome of Guillain-Barré syndrome. Since dysglycemia is a risk factor for development of axonal polyneuropathy in critically ill patients and since insulin therapy may be neuroprotective, we sought to explore the association between dysglycemia and neurologic status in Guillain-Barré syndrome patients. DESIGN: Retrospective study. SETTING: Single-center study. INTERVENTIONS: All plasma levels of glycemia measured by enzymatic technique as well as capillary glycemia were collected in a cohort of mechanically ventilated Guillain-Barré syndrome patients. Insulin administration and dysglycemia were correlated to neurologic status at discharge defined by disability grade and arm grade. MEASUREMENTS AND MAIN RESULTS: In a multivariate analysis, disability grade and arm grade at ICU discharge were independently and inversely correlated with mean blood glucose. Disability grade and arm grade did not correlate with any other dysglycemic variables or with insulin administration or length of stay. CONCLUSIONS: In the present study, we found that neurologic disability at ICU discharge correlated with dysglycemia in mechanically ventilated Guillain-Barré syndrome patients. These finding indicates that dysglycemia may delay motor recovery and impact the functional outcome of Guillain-Barré syndrome. Blood glucose control might be an adjuvant therapy for improving Guillain-Barré syndrome recovery.

Comparison of Left Atrial Measurements Using 2- and 3-Dimensional Transesophageal Echocardiography.

OBJECTIVES: To assess the correlation between left atrial measurements using 2- and 3-dimensional transesophageal echocardiography. DESIGN: Prospective, observational study. SETTING: Single, tertiary care, academic medical center. PARTICIPANTS: The study comprised 63 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass and intraoperative transesophageal echocardiography. INTERVENTIONS: In addition to the standard comprehensive intraoperative transesophageal examination, study images were obtained by designated anesthesiologists from the study team. MEASUREMENTS AND MAIN RESULTS: The 2-dimensional transesophageal echocardiography views included 4-chamber, 2-chamber, aortic valve short axis, and aortic valve long axis. For the 3-dimensional images, full-volume (90 × 90) data sets were acquired from 4-chamber and aortic valve short-axis views over 4 beats with apnea. Left atrial height, mediolateral length, anteroposterior length, and area were measured in 2- and 3-dimensional images. Left atrial length in the short- and long-axis views of the aortic valve also were measured in 2- and 3-dimensional images. Results indicate that for all patients in this study, the 2- and 3-dimensional measurements correlate well and the 2 observers were in agreement with each other. CONCLUSIONS: Two- and 3-dimensional measurements of the left atrium correlated well. Measurements made using 3-dimensional transesophageal echocardiography were subject to similar limitations as those made using 2-dimensional echocardiography. The benefits of 3-dimensional transesophageal echocardiography and multiplanar reconstruction could be expanded by improvements in ultrasound technology and software.

Aldosterone and Vascular Mineralocorticoid Receptors in Murine Endotoxic and Human Septic Shock.

OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients. SUBJECTS: Adult male C57Black 6 mice, adult patients with septic shock. INTERVENTIONS: Mice were injected with lipopolysaccharide and/or aldosterone. Human endothelial and smooth muscle cells were treated with pro-inflammatory cytokines with or without aldosterone, nuclear factor-κB inhibitor BAY 11-7082, or plasma from septic patients. MEASUREMENTS AND MAIN RESULTS: Aldosterone improved 5-day survival, invasive arterial pressure, and in vivo and ex vivo arterial response to phenylephrine at 18 hours after induction of murine endotoxic shock. Both α1-adrenoceptor and mineralocorticoid receptor expressions studied in mouse aortas were down-regulated at 6 and 18 hours in endotoxemic mice and restored in aldosterone-treated mice. Furthermore, tumor necrosis factor-α decreased both mineralocorticoid receptor and α1-adrenoceptor expressions within 5 hours in human vascular cells in a nuclear factor-κB pathway-dependent manner. Mineralocorticoid receptor expression was also blunted in human cells treated with plasma from septic patients. CONCLUSION: We found a beneficial effect of mineralocorticoids on survival, blood pressure, and vascular reactivity, associated with a restoration of α1-adrenoceptor expression in endotoxic shock. Furthermore, blunted vascular mineralocorticoid receptor expression might participate in hemodynamic failure during sepsis.

Pharmacokinetics of oral fludrocortisone in septic shock.

AIM: The combination of hydrocortisone and fludrocortisone improved outcomes in septic shock. However, the specific role of fludrocortisone remains controversial and its pharmacokinetics (PK) has never been investigated in septic shock. This study aimed at characterizing the PK of fludrocortisone in septic shock. METHODS: This was a single-centre ancillary PK study of a large multinational trial of crystalloids versus colloids for acute hypovolemia in intensive care unit (ICU) patients. In 21 adults with septic shock, fludrocortisone plasma concentrations were measured by liquid chromatography-mass spectrometry tandem analysis, before and repeatedly until 18 h after an oral dose of 50 µg. PK parameters were estimated using a nonlinear mixed-effects modelling. RESULTS: Undetectable plasma concentrations were observed in 7 out of 21 patients. In the remaining 14 patients, plasma fludrocortisone concentrations were best described by a one-compartmental model with first-order absorption, a lag time (Tlag ) before the absorption phase, and first-order elimination. Severity of illness, as quantified by Simplified Acute Physiology Score II, significantly increased Tlag and apparent clearance. There was a large inter-individual variability in PK parameters. The population estimates of PK parameters (inter-individual variability) were: Tlag 0.65 h (98%), apparent clearance 40 l h-1 (49%) and apparent volume of distribution 78 l (75%). Plasma half-life was estimated at 1.35 h (95% CI, 0.84-2.03) and area under the curve of plasma concentrations was estimated at 1.25 µg h l-1 (95% CI, 1.09-1.46). CONCLUSIONS: A single oral dose of fludrocortisone yielded undetectable plasma concentrations in one-third of adults with septic shock. Fludrocortisone PK showed a short plasma elimination half-life and a large inter-individual variability.

Experimental and clinical evidences for glucose control in intensive care: is infused glucose the key point for study interpretation?

Stress-induced hyperglycemia has been considered an adaptive mechanism to stress up to the first intensive insulin therapy trial, which showed a 34% reduction in relative risk of in-hospital mortality when normalizing blood glucose levels. Further trials had conflicting results and, at present, stress-induced hyperglycemia management remains non-consensual. These findings could be explained by discrepancies in trials, notably regarding the approach to treat hyperglycemia: high versus restrictive caloric intake. Stress-induced hyperglycemia is a frequent complication during intensive care unit stay and is associated with a higher mortality. It results from an imbalance between insulin and counter-regulatory hormones, increased neoglucogenesis, and the cytokine-induced insulin-resistant state of tissues. In this review, we summarize detrimental effects of hyperglycemia on organs in the critically ill (peripheric and central nervous, liver, immune system, kidney, and cardiovascular system). Finally, we show clinical and experimental evidence of potential benefits from glucose and insulin administration, notably on metabolism, immunity, and the cardiovascular system.

Association of Lack of Fear of Dying With New Organ Failure: Results of a Multicenter Prospective Cohort Study.

BACKGROUND: Patients' anxiety on intensive care unit (ICU) admission is associated with subsequent deterioration. OBJECTIVE: To assess whether patients' fears/anxiety are predictive of new organ failure within 7 days of ICU admission. METHODS: In a prospective 3-center cohort study of non-comatose patients without delirium or invasive mechanical ventilation, 9 specific fears were evaluated through yes/no questions. Illness severity was assessed using the Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA). Intensity of acute and chronic anxiety was assessed with the state and trait components of the State-Trait Anxiety Inventory (STAI). Patients were followed up for 7 days. RESULTS: From April 2014 to December 2017, 373 patients (median [IQR] age, 63 [48-74] years; 152 [40.8%] women; median (IQR) SAPS II, 27 [19-37]) were included. Feelings of vulnerability and fear of dying were reported by 203 (54.4%) and 172 (46.1%) patients, respectively. The STAI-State score was 40 or greater in 192 patients (51.5%). Ninety-four patients (25.2%) had new organ failure. Feelings of vulnerability (odds ratio, 1.96 [95% CI, 1.12-3.43]; P=.02) and absence of fear of dying (odds ratio, 2.38 [95% CI, 1.37-4.17]; P=.002) were associated with new organ failure after adjustment for STAI-State score (≥40), SAPS II, and SOFA score. CONCLUSION: Absence of fear of dying is associated with new organ failure within the first 7 days after ICU admission. Fear of dying may protect against subsequent deterioration by mobilizing patients' homeostatic resources. ClinicalTrials.gov Identifier: NCT02355626.

Pattern of brain injury in the acute setting of human septic shock.

BACKGROUND: Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change. METHOD: Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS). RESULTS: We included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months. CONCLUSIONS: Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality.

StO2 guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial.

The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO2) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO2. StO2 was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO2 above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO2 over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO2 as a treatment goal. However, the protocol showed no clear trend for or against targeting StO2.

The interplay between previous infection and mental health condition on antibody response to COVID-19 mRNA vaccination.

Increasing evidence has been pointing towards the existence of a bi-directional interplay between mental health condition and immunity. Data collected during the COVID-19 outbreak suggest that depressive symptoms may impact the production of antibodies against SARS-CoV-2, while a previous infection could affect the immune response and cause neuropsychological disturbances. A prospective observational study was designed to investigate the association between mental health conditions and immune response over time. We analyzed the mental health at baseline and the antibodies before and after immunization with the COVID-19 mRNA vaccine in a cohort of healthcare professionals in southern Switzerland. One-hundred and six subjects were enrolled. Anxiety, distress and depression correlated to each other. There were no correlations between the mentioned variables and the vaccine induced IgG antibodies against the receptor binding domain (RBD) of the spike protein. For those who had a previous COVID-19 infection, the antibodies increased according to the grade of depression. For those who did not, the anti-RBD IgG levels remained similar when comparing presence or absence of depression symptoms. Our results show that previous SARS-CoV-2 natural infection in subjects with mental health conditions enhances the immune response to COVID-19 mRNA vaccination. The correlation between immune response to COVID-19 vaccination, a previous exposure to the virus, and symptoms of mood disorders, makes it necessary to explore the direction of the causality between immune response and depressive symptoms.

Masseter tissue oxygen saturation predicts normal central venous oxygen saturation during early goal-directed therapy and predicts mortality in patients with severe sepsis.

OBJECTIVE: This study aimed to investigate, in patients with severe sepsis, the correlation between central venous oxygen saturation and tissue oxygen saturation at different levels. DESIGN: Prospective observational study. SETTING: General intensive care unit at an academic medical center in France. PATIENTS: Thirty-eight patients with underresuscitated severe sepsis and septic shock on intensive care unit admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During early resuscitation according to the 6-hr bundles of the Surviving Sepsis Campaign guidelines, tissue oxygen saturation was recorded every other hour at the level of the thenar, masseter, and deltoid muscles along with central hemodynamics, arterial lactate concentrations, and central venous oxygen saturation. Over the 6-hr resuscitation period, thenar tissue oxygen saturation was consistently higher than masseter tissue oxygen saturation (p = .04) and deltoid tissue oxygen saturation (p = .002), and masseter tissue oxygen saturation was consistently higher than deltoid tissue oxygen saturation (p = .04). Receiver operating characteristic curves analyses showed that masseter tissue oxygen saturation was better predictor of central venous oxygen saturation >70% than thenar tissue oxygen saturation (area under the curve, 0.80; 95% confidence interval 0.71-0.89 vs. 0.67; 95% confidence interval 0.56-0.77; p = .02). The crude 28-day mortality was 36.8%. Receiver operating characteristic curve analysis showed that masseter tissue oxygen saturation (area under the curve 0.87; 0.75-0.98) and deltoid tissue oxygen saturation (area under the curve 0.88; 0.77-0.98) but not thenar tissue oxygen saturation (area under the curve 0.66; 0.46-0.86) or central venous oxygen saturation (area under the curve 0.56; 0.38-0.80) were strong predictors of 28-day mortality. CONCLUSIONS: This study suggested that in the early 6-hr resuscitation period, masseter tissue oxygen saturation accurately identified patients with severe sepsis and central venous oxygen saturation >70%. Both masseter tissue oxygen saturation and deltoid tissue oxygen saturation but not central venous oxygen saturation or thenar tissue oxygen saturation are strong predictors of 28-day mortality.

Dyspnea in mechanically ventilated critically ill patients.

OBJECTIVES: Ensuring the comfort of intensive care unit patients is crucial. Although control of pain has been extensively addressed in this setting, data on dyspnea in mechanically ventilated patients are scant. The objective of this study was to assess the prevalence of dyspnea in mechanically ventilated patients, identify its clinical correlates, and examine its impact on clinical outcomes. DESIGN: Prospective 6-month observational study. SETTING: Two medical intensive care units within university hospitals. PARTICIPANTS: Intubated or tracheotomized patients who were mechanically ventilated for >24 hrs. We enrolled 96 patients (age, 61 ± 18 yrs; Simplified Acute Physiology Score II 43 [interquartile range, 31-60]) as soon as they could answer symptom-related questions. Dyspnea was evaluated on a "yes-no" basis; if yes, it was followed by a visual analog scale and descriptor choice ("air hunger" and/or "respiratory effort"). Pain and anxiety were also assessed by visual analog scales. INTERVENTIONS: Ventilator settings adjustment in dyspneic patients. MEASUREMENTS AND MAIN RESULTS: Forty-five patients (47%) reported dyspnea (respiratory effort in seven cases, air hunger in 15, both in 16, and neither of these in seven). Dyspneic and nondyspneic patients did not differ in terms of age, Simplified Acute Physiology Score II, indication for mechanical ventilation, respiratory rate, clinical examination, chest radiograph, or blood gases. Dyspnea was significantly associated with anxiety (odd ratio [OR], 8.84; 95% confidence interval [CI], 3.26-24.0), assist-control ventilation (OR, 4.77; 95% CI, 1.60-4.3), and heart rate (OR, 1.33 per 10 beats/min; 95% CI, 1.02-1.75). Adjusting ventilator settings improved dyspnea in 35% of patients. Successful extubation within 3 days was significantly less frequent in patients whose dyspnea failed to recede after adjusting ventilator settings (five [17%] vs. 27 [40%]; p = .034). CONCLUSIONS: Dyspnea is frequent, intense, and strongly associated with anxiety in mechanically ventilated patients. It can be sensitive to ventilator settings and seems to be associated with delayed extubation.

Brainstem responses can predict death and delirium in sedated patients in intensive care unit.

OBJECTIVES: In critically ill patients, the assessment of neurologic function can be difficult because of the use of sedative agents. It is not known whether neurologic signs observed under sedation can predict short-term outcomes. The objective of this study was to assess whether abnormal brainstem responses within the first 24 hrs of sedation are associated with mortality and altered mental status postsedation. DESIGN: Observational prospective study including an initial single-center and a subsequent multicenter study to develop and then validate the prognostic models. SETTING: Three mixed and two medical intensive care units. PATIENTS: Mechanically ventilated intensive care unit patients sedated with midazolam (± sufentanyl). INTERVENTIONS: Neurologic examination including the Glasgow Coma Scale, the Assessment to Intensive Care Environment score, cranial nerve examination, response to noxious stimuli, and the cough reflex was performed. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included in the initial group and 72 in a subsequent validation study. Neurologic responses were independent of sedative dose. Twenty-two patients in the development cohort and 21 (29%) in the validation group died within 28 days of inclusion. Adjusted for Simplified Acute Physiology Score II score, absent cough reflex was independently associated with 28-day mortality in the development (adjusted odds ratio [OR], 7.80; 95% confidence interval [CI], 2.00-30.4; p = .003) and validation groups (adjusted OR, 5.44; 95% CI, 1.35-22.0; p = .017). Absent oculocephalic response, adjusted for Simplified Acute Physiology Score II score, was independently associated with altered mental status after the withdrawal of sedation in the development (adjusted OR, 4.54; 95% CI, 1.34-15.4; p = .015) and validation groups (adjusted OR, 6.10; 95% CI, 1.18-25.5; p = .012). CONCLUSIONS: Assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status.

Hormonal status in protracted critical illness and in-hospital mortality.

INTRODUCTION: The aim of this study was to determine the relationship between hormonal status and mortality in patients with protracted critical illness. METHODS: We conducted a prospective observational study in four medical and surgical intensive care units (ICUs). ICU patients who regained consciousness after 7 days of mechanical ventilation were included. Plasma levels of insulin-like growth factor 1 (IGF-1), prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured on the first day patients were awake and cooperative (day 1). Mean blood glucose from admission to day 1 was calculated. RESULTS: We studied 102 patients: 65 men and 37 women (29 of the women were postmenopausal). Twenty-four patients (24%) died in the hospital. The IGF-1 levels were higher and the cortisol levels were lower in survivors. Mean blood glucose was lower in women who survived, and DHEA and DHEAS were higher in men who survived. CONCLUSIONS: These results suggest that, on the basis of sex, some endocrine or metabolic markers measured in the postacute phase of critical illness might have a prognostic value.

Hyperglycaemia and apoptosis of microglial cells in human septic shock.

INTRODUCTION: The effect of hyperglycaemia on the brain cells of septic shock patients is unknown. The objective of this study was to evaluate the relationship between hyperglycaemia and apoptosis in the brains of septic shock patients. METHODS: In a prospective study of 17 patients who died from septic shock, hippocampal tissue was assessed for neuronal ischaemia, neuronal and microglial apoptosis, neuronal Glucose Transporter (GLUT) 4, endothelial inducible Nitric Oxide Synthase (iNOS), microglial GLUT5 expression, microglial and astrocyte activation. Blood glucose (BG) was recorded five times a day from ICU admission to death. Hyperglycaemia was defined as a BG 200 mg/dL g/l and the area under the BG curve (AUBGC) > 2 g/l was assessed. RESULTS: Median BG over ICU stay was 2.2 g/l. Neuronal apoptosis was correlated with endothelial iNOS expression (rho = 0.68, P = 0.04), while microglial apoptosis was associated with AUBGC > 2 g/l (rho = 0.70; P = 0.002). Neuronal and microglial apoptosis correlated with each other (rho = 0.69, P = 0.006), but neither correlated with the duration of septic shock, nor with GLUT4 and 5 expression. Neuronal apoptosis and ischaemia tended to correlate with duration of hypotension. CONCLUSIONS: In patients with septic shock, neuronal apoptosis is rather associated with iNOS expression and microglial apoptosis with hyperglycaemia, possibly because GLUT5 is not downregulated. These data provide a mechanistic basis for understanding the neuroprotective effects of glycemic control.

Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU.

BACKGROUND: To assess the ability of procalcitonin (PCT) to distinguish between bacterial and nonbacterial causes of patients with severe acute exacerbation of COPD (AECOPD) admitted to the ICU, we conducted a retrospective analysis of two prospective studies including 375 patients with severe AECOPD with suspected lower respiratory tract infections. PCT levels were sequentially assessed at the time of inclusion, 6 h after and at day 1, using a sensitive immunoassay. The patients were classified according to the presence of a documented bacterial infection (including bacterial and viral coinfection) (BAC + group), or the absence of a documented bacterial infection (i.e., a documented viral infection alone or absence of a documented pathogen) (BAC- group). The accuracy of PCT levels in predicting bacterial infection (BAC + group) vs no bacterial infection (BAC- group) at different time points was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Regarding the entire cohort (n = 375), at any time, the PCT levels significantly differed between groups (Kruskal-Wallis test, p < 0.001). A pairwise comparison showed that PCT levels were significantly higher in patients with bacterial infection (n = 94) than in patients without documented pathogens (n = 218) (p < 0.001). No significant difference was observed between patients with bacterial and viral infection (n = 63). For example, the median PCT-H0 levels were 0.64 ng/ml [0.22-0.87] in the bacterial group vs 0.24 ng/ml [0.15-0.37] in the viral group and 0.16 ng/mL [0.11-0.22] in the group without documented pathogens. With a c-index of 0.64 (95% CI; 0.58-0.71) at H0, 0.64 [95% CI 0.57-0.70] at H6 and 0.63 (95% CI; 0.56-0.69) at H24, PCT had a low accuracy for predicting bacterial infection (BAC + group). CONCLUSION: Despite higher PCT levels in severe AECOPD caused by bacterial infection, PCT had a poor accuracy to distinguish between bacterial and nonbacterial infection. Procalcitonin might not be sufficient as a standalone marker for initiating antibiotic treatment in this setting.

Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock.

OBJECTIVE: To determine whether septic shock patients have an abnormal reponse to increasing osmolarity. DESIGN: Prospective interventional study. SETTING: Intensive care unit at Raymond Poincaré and Etampes Hospitals. PATIENTS: Normonatremic patients at > 72 hrs from septic shock onset. INTERVENTION: Osmotic challenge consisting of infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 mins. MEASUREMENTS AND MAIN RESULTS: Plasma arginine vasopressin levels were measured 15 mins before the test and then four times every 30 mins. A slope of the relation between arginine vasopressin and plasma sodium levels of < 0.5 pg/mEq defined nonresponders. Among the 33 included patients, 17 (52%) were nonresponders. During osmotic challenge, variations throughout the test in plasma sodium levels, blood pressure, and central venous pressure were comparable between the two groups. Arginine vasopressin increased from 4.8 pg/mL [3.3-6.4 pg/mL] to 14.4 pg/mL [11.2-23.3 pg/mL] in responders but only from 2.8 pg/mL [2.3-4.0 pg/mL] to 4.0 pg/mL [3.1-5.3 pg/mL] in nonresponders (p < .0001). Responders had a higher plasma arginine vasopressin levels at baseline and a more severe hematosis alteration. Nonresponders had more frequently bacteremia and liver dysfunction, been referred from the ward and undergone surgery. Critical illness severity, hemodynamic alteration, hydroelectrolytic disturbances, treatment, and outcome did not differ between the two groups. CONCLUSION: Osmoregulation is dramatically altered in half of patients with prolonged septic shock.

Septic-associated encephalopathy--everything starts at a microlevel.

Sepsis-associated encephalopathy is associated with increased mortality and morbidity. Its pathophysiology remains insufficiently elucidated, although there is evidence for a neuroinflammatory process sequentially involving endothelial activation, blood-brain barrier alteration and cellular dysfunction and alteration in neurotransmission. Experimental studies have shown that microcirculatory dysfunction, a consequence of endothelial activation, is an early pathogenic step. To date, we do not know whether it is present in septic patients, whether it accounts for clinical features and whether it is treatable.