Long-term patient-important outcomes after septic shock : A protocol for 1-year follow-up of the CLASSIC trial

BackgroundIn patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes. AimTo assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial. MethodsIn this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. DiscussionWith this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock.Peer reviewe

Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial

BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation

Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient.

International audienceBACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI and PWI were performed in 11 patients 1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically

Correlation between diffusion- and perfusion-weighted MRI and neurological deficit measured by the Scandinavian Stroke Scale and Barthel Index in hyperacute subcortical stroke (< or = 6 hours).

International audienceOBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction

Prediction of tissue survival after middle cerebral artery occlusion based on changes in the apparent diffusion of water.

International audienceOBJECT: In this study the authors tested the hypothesis that the estimate of the apparent diffusion coefficient (ADC) of water is a reliable pathophysiological index of the viability of ischemic brain tissue. METHODS: Cerebral blood flow (CBF) and the cerebral metabolic rates of oxygen and glucose (CMRO2 and CMRglc, respectively) were measured using positron emission tomography (PET) scanning before and after permanent middle cerebral artery occlusion (MCAO) or reperfusion in pigs. The ADC value, which was measured using diffusion-weighted magnetic resonance (DW MR) imaging was compared with physiological variables obtained by PET scanning and with histological findings. After both permanent MCAO and reperfusion, the decrease in the ADC was significantly correlated with decrease in the CMRO2 and CMRglc. The infarction coincided with a CMRO2 threshold of 50% of the value measured on the contralateral side. Thus, an ADC value of 80% or 75% of the contralateral value reflected the CMRO2 threshold after permanent MCAO or reperfusion, respectively. On DW MR images, lesions with ADC values above 80% of the contralateral value are potentially reversible until 6 hours after MCAO, whereas lesions with ADC values below 75% of the contralateral value are irreversible as early as 2 hours after MCAO. CONCLUSIONS: The ADC of water provides a reliable pathophysiological index for tailoring therapy to the condition of individual stroke patients in clinical practice