The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data.

BACKGROUND: This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). METHODS: A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). RESULTS: 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25-1.44), p < 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26-1.45), p < 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4-5, 6, and ≥ 7 was associated with a significantly worse outcome compared to CFS of 1-3. CONCLUSIONS: Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately. TRIAL REGISTRATION: Open Science Framework (OSF: https://osf.io/8buwk/ ).

Acute kidney injury after aneurysmal subarachnoid hemorrhage: is chloride really responsible?

Sadan et al. find an association between acute kidney injury and high chloride containing a hypertonic solution. Recent large prospective non-randomized studies bring conflicting results on the relationship between chloride and acute kidney injury. We discuss Sadan et al.'s results according to the recent literature.

Being Convinced and Taking Responsibility: A Qualitative Study of Family Members' Experience of Organ Donation Decision and Bereavement After Brain Death.

OBJECTIVES: Family members of brain dead patients experience an unprecedented situation in which not only they are told that their loved one is dead but are also asked to consider organ donation. The objective of this qualitative study was to determine 1) what it means for family members to make the decision and to take responsibility, 2) how they interact with the deceased patient in the ICU, 3) how family members describe the impact of the process and of the decision on their bereavement process. DESIGN: Qualitative study using interviews with bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). SETTING: Family members from 13 ICUs in France. SUBJECTS: Bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). INTERVENTION: None. MEASUREMENTS AND RESULTS: Twenty-four interviews were conducted with 16 relatives of organ donor patients and with eight relatives of nonorgan donor patients. Three themes emerged: 1) taking responsibility-relatives explain how they endorse decisional responsibility but do not experience it as a burden, on the contrary; 2) ambiguous perceptions of death-two groups of relatives emerge: those for whom ambiguity hinders their acceptance of the patient's death; those for whom ambiguity is an opportunity to accept the death and say goodbye; and 3) donation as a comfort during bereavement. CONCLUSIONS: In spite of caregivers' efforts to focus organ donation discussions and decision on the patient, family members feel a strong decisional responsibility that is not experienced as a burden but a proof of their strong connection to the patient. Brain death however creates ambivalent experiences that some family members endure whereas others use as an opportunity to perform separation rituals. Last, organ donation can be experienced as a form of comfort during bereavement provided family members remain convinced their decision was right.

Grief Symptoms in Relatives Who Experienced Organ Donation Requests in the ICU.

RATIONALE: Studies show that the quality of end-of-life communication and care have a significant impact on the living long after the death of a relative and have been implicated in the burden of psychological symptoms after the ICU experience. In the case of organ donation, the patient's relatives are centrally involved in the decision-making process; yet, few studies have examined the impact of the quality of communication on the burden of psychological symptoms after death. OBJECTIVES: To assess the experience of the organ donation process and grief symptoms in relatives of brain-dead patients who discussed organ donation in the ICU. METHODS: We conducted a multicenter longitudinal study in 28 ICUs in France. Participants were the relatives of brain-dead patients who were approached to discuss organ donation. Relatives were followed-up by phone at three time points: at 1 month, to complete a questionnaire describing their experience of the organ donation process; at 3 months, to complete the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised; and at 9 months, to complete the Impact of Event Scale-Revised and the Inventory of Complicated Grief. MEASUREMENTS AND MAIN RESULTS: In total, 202 relatives of 202 patients were included, of whom 158 consented to and 44 refused organ donation. Interviews were conducted at 1, 3, and 9 months with 78%, 68%, and 58% of relatives, respectively. The overall experience of the organ donation process was significantly more burdensome for relatives of nondonors. They were more dissatisfied with communication (27% vs. 10%; P = 0.021), more often shocked by the request (65% vs. 19%; P < 0.0001), and more often found the decision difficult (53% vs. 27%; P = 0.017). However, there were no significant differences in grief symptoms measured at 3 and 9 months between the two groups. Understanding of brain death was associated with grief symptoms; our results show a higher prevalence of complicated grief symptoms among relatives who did not understand the brain death process than among those who did (75% vs. 46.1%; P = 0.026). CONCLUSIONS: Experience of the organ donation process varied between relatives of donor versus nondonor patients, with relatives of nondonors experiencing lower-quality communication, but the decision was not associated with subsequent grief symptoms. Importantly, understanding of brain death is a key element of the organ donation process for relatives.

Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial.

BACKGROUND: Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia. METHODS: We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 µg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261. FINDINGS: From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio [HR] 0.75; 95% CI 0.55-1.03, p=0.07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment. INTERPRETATION: Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed. FUNDING: Société Française d'Anesthésie Réanimation.

Prevalence and impact of frailty on mortality in elderly ICU patients: a prospective, multicenter, observational study.

PURPOSE: Frailty is a recent concept used for evaluating elderly individuals. Our study determined the prevalence of frailty in intensive care unit (ICU) patients and its impact on the rate of mortality. METHODS: A multicenter, prospective, observational study performed in four ICUs in France included 196 patients aged ≥65 years hospitalized for >24 h during a 6-month study period. Frailty was determined using the frailty phenotype (FP) and the clinical frailty score (CFS). The patients were separated as follows: FP score <3 or ≥3 and CFS <5 or ≥5. RESULTS: Frailty was observed in 41 and 23% of patients on the basis of an FP score ≥3 and a CFS ≥5, respectively. At admission to the ICU, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores did not differ between the frail and nonfrail patients. In the multivariate analysis, the risk factors for ICU mortality were FP score ≥3 [hazard ratio (HR), 3.3; 95% confidence interval (CI), 1.6-6.6; p < 0.001], male gender (HR, 2.4; 95% CI, 1.1-5.3; p = 0.026), cardiac arrest before admission (HR, 2.8; 95% CI, 1.1-7.4; p = 0.036), SAPS II score ≥46 (HR, 2.6; 95% CI, 1.2-5.3; p = 0.011), and brain injury before admission (HR, 3.5; 95% CI, 1.6-7.7; p = 0.002). The risk factors for 6-month mortality were a CFS ≥5 (HR, 2.4; 95% CI, 1.49-3.87; p < 0.001) and a SOFA score ≥7 (HR, 2.2; 95% CI, 1.35-3.64; p = 0.002). An increased CFS was associated with significant incremental hospital and 6-month mortalities. CONCLUSIONS: Frailty is a frequent occurrence and is independently associated with increased ICU and 6-month mortalities. Notably, the CFS predicts outcomes more effectively than the commonly used ICU illness scores.

Effect of osmotherapy on optic nerve sheath diameter in patients with increased intracranial pressure.

The measurement of ocular nerve sheath diameter (ONSD) via ocular ultrasound scanning is a recent non-invasive method for intracranial pressure (ICP) assessment. Few clinical studies have assessed ONSD variations during osmotherapy for the treatment of sustained increased ICP episodes. The aim of our study was to determine the rate of ONSD variation after mannitol administration for increased ICP episodes. We consecutively included in a prospective, observational study, the patients who had severe acute brain injury and monitored with an invasive ICP monitor. For each episode of sustained elevated ICP, the ONSD was measured in the right and left eye with a 7.5-MHz echography probe, and the mean value was reported. Simultaneously, ICP and cerebral perfusion pressure (CPP) were recorded. All measurements were performed just before and 20 minutes following a 20% mannitol infusion. Data were expressed as medians and interquartile ranges. Thirteen patients were included and analysed (traumatic brain injury, n=10; subarachnoid haemorrhage, n=3). The median value of the mannitol dose infused was 0.54 g/kg (0.49-0.80 g/kg). In all cases, the ONSD was greater than 5.8 mm before osmotherapy. The ONSD significantly decreased after mannitol infusion from 6.3 (6.1-6.7) to 5. mm (5.5-6.3) (p=0.0007). Concomitantly, the intracranial pressure decreased from 35 (32-41) to 25 (22-29) mmHg (p=0.001) and the CPP increased from 47 (50-60) to 66 (59-69) mmHg (p=0.003). The variations of ONSD appear to be an interesting parameter to evaluate the efficacy of osmotherapy for elevated ICP episodes in patients with acute brain injury.

Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers.

AIMS: A single administration of hydrocortisone has been shown to enhance the pressor response to phenylephrine in healthy volunteers and to norepinephrine in septic shock patients. Similar data do not exist for fludrocortisone. Since there continues to be disagreement about the utility of fludrocortisone in septic shock, we assessed the effects of a single administration of low doses of hydrocortisone (50 mg intravenously) and fludrocortisone (50 µg orally), given either alone or in combination, on phenylephrine mean arterial pressure and cardiac systolic and diastolic function dose-response relationships in 12 healthy male volunteers with hypo-aldosteronism induced by intravenous sodium loading. METHODS: This was a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 × 2 factorial design. Subjects received first a 2000 ml infusion of NaCl 0.9% during 2 h. Then fludrocortisone 50 µg (or its placebo) was administered orally and hydrocortisone 50 mg (or its placebo) was injected intravenously. At 1.5 h after treatment administration, incremental doses of phenylephrine were infused (from 0.01 to 3 µg kg(-1) min(-1)), each dose being infused during 5 min. RESULTS: Both fludrocortisone (P < 0.001) and hydrocortisone (P = 0.002) induced a significant decrease in pressor response to phenylephrine, their effects being additive (fludrocortisone × hydrocortisone interaction, P = 0.792). The two drugs did not induce any detectable cardiac effect. CONCLUSIONS: Single administrations of fludrocortisone and hydrocortisone decreased the pressor response to phenylephrine in healthy volunteers with hypo-aldosteronism. These similar effects of hydrocortisone and fludrocortisone probably express a rapid non-genomic vasodilating effect of the two steroids in the context of acute volume loading.

Risk factors and outcomes for prolonged versus brief fever: a prospective cohort study.

INTRODUCTION: Prolonged fever occurs with infectious and noninfectious diseases but is poorly studied in intensive care units. The aims of this prospective multicenter noninterventional study were to determine the incidence and etiologies of prolonged fever in critically ill patients and to compare outcomes for prolonged fever and short-lasting fever. METHODS: The study involved two periods of 2 months each, with 507 patients hospitalized ≥ 24 hours. Fever was defined by at least one episode of temperature ≥ 38.3 °C, and prolonged fever, as lasting > 5 days. Backward stepwise logistic regression was performed to identify the independent factors associated with prolonged fever versus short-lasting fever. RESULTS: Prolonged or short-lasting fever occurred in 87 (17%) and 278 (55%) patients, respectively. Infectious and noninfectious causes were found in 54 (62%) and 27 (31%) of 87 patients, respectively; in six patients (7%), prolonged fever remained unexplained. The two most common sites of infection were ventilator-associated pneumonia (n = 25) and intraabdominal infection (n = 13). Noninfectious fever (n = 27) was neurogenic in 19 (70%) patients and mainly associated with cerebral injury (84%). Independent risk factors for prolonged fever were cerebral injury at admission (OR = 5.03; 95% CI, 2.51 to 10.06), severe sepsis (OR = 2.79; 95% CI, 1.35 to 5.79), number of infections (OR = 2.35; 95% CI, 1.43 to 3.86), and mechanical-ventilation duration (OR = 1.05; 95% CI, 1.01 to 1.09). Older patients were less likely to develop prolonged fever. ICU mortality did not differ between the two groups. CONCLUSIONS: Prolonged fever was common, mainly due to severe infections, particularly ventilator-associated pneumonia, and mixed infectious causes were frequent, warranting systematic and careful search for multiple causes. Neurogenic fever was also especially frequent.