Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.

Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study.

BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.

Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.

Circulating microRNAs improve bacterial infection diagnosis and overall survival prediction in acute decompensation of liver cirrhosis.

Bacterial infections are the most frequent precipitating event in patients with acute decompensation of cirrhosis (AD) and are associated with high mortality. Early diagnosis is challenging due to cirrhosis-related systemic inflammation. Here we investigated the potential of circulating microRNAs to diagnose bacterial infections and predict survival in cirrhotic patients with AD. High throughput profiling of circulating microRNAs was performed using the Nanostring technology in 57 AD patients and 24 patients with compensated cirrhosis (CC). Circulating miRs profiling showed that: (a) miRs differentially detected in AD vs. CC were mostly down-regulated; (b) a composite score including absolute neutrophil count, C reactive protein and miR-362-3p could diagnose bacterial infection with an excellent performance (AUC of 0.825 [95% CI = 0.671-0.980; p < 0.001]); (c) a composite score including miR-382-5p, miR-592 and MELD-Na improved 6-month survival prediction. Circulating miRs are strongly dysregulated in patients with AD and may help to improve bacterial infection diagnosis and survival prediction.

Use of 1,3-Beta-D-Glucan concentration in peritoneal fluid for the diagnosis of intra-abdominal Candidiasis in Critically-ill patients.

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401.

Intra-Abdominal Candidiasis (IAC) is associated with a high mortality in Intensive Care Unit (ICU) patients. 1,3-Beta-D-Glucan (BDG), a component of Candida cell wall, was prospectively measured in peritoneal fluid from ICU patients Low peritoneal BDG concentrations may be used to rule out IAC.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis.

BACKGROUND: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. METHODS: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. RESULTS: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). CONCLUSIONS: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Prognosis of Old Intensive Care COVID-19 Patients at a Glance: The Senior COVID Study.

OBJECTIVE: Admission in the intensive care unit of the old patient with coronavirus disease 19 raises an ethical question concerning the scarce resources and their short-term mortality. METHODS: Patients aged over 60 from 7 different intensive care units admitted between March 1, 2020 and May 6, 2020, with a diagnosis of coronavirus disease 19 were included in the cohort. Twenty variables were collected during the admission, such as age, severity (Simplified Acute Physiology Score [SAPS] II), several data on physiological status before intensive care unit comorbidities, evaluation of autonomy, frailty, and biological variables. The objective was to model the 30-day mortality with relevant variables, compute their odds ratio associated with their 95% CI, and produce a nomogram to easily estimate and communicate the 30-day mortality. The performance of the model was estimated with the area under the receiving operating curve. RESULTS: We included 231 patients, among them 60 (26.0%) patients have died on the 30th day. The relevant variables selected to explain the 30-day mortality were Instrumental Activities of Daily Living (IADL) score (0.82 [0.71-0.94]), age 1.12 (1.07-1.18), SAPS II 1.05 (1.02-1.08), and dementia 6.22 (1.00-38.58). A nomogram was computed to visually represent the final model. Area under the receiving operating curve was at 0.833 (0.776-0.889). CONCLUSIONS: Age, autonomy, dementia, and severity at admission were important predictive variables for the 30-day mortality status, and the nomogram could help the physician in the decision-making process and the communication with the family.

Senior-COVID-Rea Cohort Study: A Geriatric Prediction Model of 30-day Mortality in Patients Aged over 60 Years in ICU for Severe COVID-19.

The SARS-COV2 pandemic induces tensions on health systems and ethical dilemmas. Practitioners need help tools to define patients not candidate for ICU admission. A multicentre observational study was performed to evaluate the impact of age and geriatric parameters on 30-day mortality in patients aged ≥60 years of age. Patients or next of kin were asked to answer a phone questionnaire assessing geriatric covariates 1 month before ICU admission. Among 290 screened patients, 231 were included between March 7 and May 7, 2020. In univariate, factors associated with lower 30-day survival were: age (per 10 years increase; OR 3.43, [95%CI: 2.13-5.53]), ≥3 CIRS-G grade ≥2 comorbidities (OR 2.49 [95%CI: 1.36-4.56]), impaired ADL, (OR 4.86 [95%CI: 2.44-9.72]), impaired IADL8 (OR 6.33 [95%CI: 3.31-12.10], p<0.001), frailty according to the Fried score (OR 4.33 [95%CI: 2.03-9.24]) or the CFS ≥5 (OR 3.79 [95%CI: 1.76-8.15]), 6-month fall history (OR 3.46 [95%CI: 1.58-7.63]). The final multivariate model included age (per 10 years increase; 2.94 [95%CI:1.78-5.04], p<0.001) and impaired IADL8 (OR 5.69 [95%CI: 2.90-11.47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85]. Age and IADL8 provide independent prognostic factors for 30-day mortality in the considered population. Considering a risk of death exceeding 80% (82.6% [95%CI: 61.2% - 95.0%]), patients aged over 80 years with at least 1 IADL impairment appear as poor candidates for ICU admission.

Intensive care-related loss of quality of life and autonomy at 6 months post-discharge: Does COVID-19 really make things worse?

OBJECTIVE: To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. DESIGN: Comparison of two prospective multi-centric studies. SETTING: This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). PATIENTS: We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. CONCLUSIONS: COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.

PCO2 gap, its ratio to arteriovenous oxygen content, ScvO2 and lactate in high-risk abdominal surgery patients: An observational study.

BACKGROUND: The difference between arterial and central venous carbon dioxide partial pressure (PCO2 gap), a marker of oxygen delivery (DO2) and oxygen consumption (VO2) adequacy, has been evaluated as a promising prognostic tool in intensive care unit (ICU) patients. We therefore sought to study the association between intraoperative PCO2 gap and postoperative complications (POC) in the perioperative setting of elective major abdominal surgery. METHODS: We conducted a single-centre prospective observational study. All adult patients who underwent major planned abdominal surgery were eligible. PCO2 gap was measured every 2 h during surgery, at ICU admission and repeated 12 h and 24 h later. Severe POC within 28 days after surgery were defined as complications graded 3 or more according to Clavien-Dindo classification. Following a univariate analysis, a multivariable analysis using a logistic regression model was performed. RESULTS: Ninety patients were included and divided into two groups according to the occurrence of POC. No significant difference was found between groups regarding baseline characteristics at inclusion. Thirty-nine (43%) patients developed postoperative complications. The median [IQR] intraoperative PCO2 gap was significantly higher in patients who had complications (6.5 [5.5-7.3] mmHg) compared to those who did not (5.0 [3.9-5.8] mmHg; p < 0.001). The area under the receiver operating characteristic curve for occurrence of POC was 0.78 for the PCO2 gap. After multivariable analysis, PCO2 gap was found independently associated with POC (OR: 14.9, 95% CI [4.68-60.1], p < 0.001) with a threshold value of 6.2 mmHg. The duration of surgery (OR: 1.01, 95% CI [1.00; 1.01], p = 0.04) and the need for vasoactive support during surgery (OR: 5.76, 95% CI [1.72; 24.1], p = 0.006) were also independently associated with POC. CONCLUSION: Intraoperative PCO2 gap is a relevant predictive factor of severe postoperative complications in high-risk elective surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03914976.

Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial.

INTRODUCTION: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 µmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 µmol/L after MARS; -122 ± 118 µmol/L after SPAD session), conjugated bilirubin (-82 ± 61 µmol/L after MARS; -105 ± 96 µmol/L after SPAD session), and bile acid levels (-64 ± 75 µmol/L after MARS; -56 ± 56 µmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol.

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.

Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS-CoV-2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS-CoV-2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS-CoV-2 screening strategy prior to transplantation; and definition of optimal recipient-donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS-CoV-2 infection during follow-up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves.

Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis.

BACKGROUND: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. METHODS: A 3-year (2015-2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan-Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. FINDINGS: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan-Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. INTERPRETATION: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs.

Heat map for data visualization in infection control epidemiology: An application describing the relationship between hospital-acquired infections, Simplified Acute Physiological Score II, and length of stay in adult intensive care units.

BACKGROUND: Hospital-acquired infections (HAIs) in intensive care units (ICUs) are associated with increased length of stay (LOS). The objective of this study was to graphically describe by heat mapping LOS of patients hospitalized in ICUs related to the occurrence of HAI and severity at admission measured by the Simplified Acute Physiological Score II (SAPSII). METHODS: Adult patients hospitalized in ICUs of Lyon University Hospitals (France) were included in an active standardized surveillance study of HAI from January 1, 1995-December 31, 2012. Surveillance included adult patients aged ≥18 years hospitalized ≥2 days. Patient follow-up ended at ICU discharge or death. LOS was calculated in days from differences between dates of entry and discharge from ICUs. HAIs recorded were pneumonia, bacteremia, and urinary tract infection. The heat map was designed with a spreadsheet software. RESULTS: A total of 34,694 patients were analyzed. Among infected patients, 72.3% had 1 infected site (IS), 23% had 2 ISs, and 4.7% had 3 ISs. Median LOS was 24 days in infected patients (20.4 days among patients with 1 IS, 34.2 days among patients with 2 ISs, and 45.3 days among patients with 3 ISs) and 5 days in noninfected patients (P < .001). Two groups of multi-infected patients with long LOSs were identified with the heat map. CONCLUSIONS: The heat map facilitated easy-to-implement semi-quantitative visualization of increasing LOS through the SAPSIIs and number of ISs.

The Use of Milrinone in Patients with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage: A Systematic Review.

OBJECTIVE: The purpose of this article is to provide a systematic review of the evidence supporting the use of milrinone for the management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). DESIGN: Primary outcomes were functional neurological status and the incidence of cerebral infarction. Search strategies adapted to the different databases were developed by a professional librarian. Medline, EMBASE, the Cochrane Library database, Web of Science, SCOPUS, BIOSIS, Global Health, Health Star, Open SIGLE, Google Scholar and the New York Academy of Medicine Gray Literature were searched as well as clinical trials databases and the proceedings of several scientific meetings. Quality of the evidence for these outcomes across studies was adjudicated using the GRADE Working Group criteria. RESULTS: The search resulted in 284 citations after elimination of duplicates. Of those 9 conference proceedings and 15 studies met inclusion criteria and consisted of case reports, case series and two comparative studies: one non-randomized study with physiological outcomes only and a case series with historical controls. There was considerable variation in dosing and in co-interventions and no case control or randomized controlled studies were found. CONCLUSION: There is currently only very low quality evidence to support the use of milrinone to improve important outcomes in patients with delayed cerebral ischemia secondary to subarachnoid hemorrhage. Further research is needed to clarify the value and risks of this medication in patients with SAH.

Hyperinsulinemic-normoglycemic clamp administered together with amino acids induces anabolism after cardiac surgery.

Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-2H2]glucose and l-[1-13C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 µmol·kg-1·h-1, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 µmol·kg-1·min-1, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.

Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm.

BACKGROUND: Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels. METHODS AND RESULTS: Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2-4 and 12-74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (Kact), force redevelopment after a shortening protocol (Ktr) and relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed. CONCLUSIONS: Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels.

Active prospective surveillance study with post-discharge surveillance of surgical site infections in Cambodia.

Barriers to the implementation of the Centers for Disease Control and Prevention (CDC) guidelines for surgical site infection (SSI) surveillance have been described in resource-limited settings. This study aimed to estimate the SSI incidence rate in a Cambodian hospital and to compare different modalities of SSI surveillance. We performed an active prospective study with post-discharge surveillance. During the hospital stay, trained surveyors collected the CDC criteria to identify SSI by direct examination of the surgical site. After discharge, a card was given to each included patient to be presented to all practitioners examining the surgical site. Among 167 patients, direct examination of the surgical site identified a cumulative incidence rate of 14 infections per 100 patients. An independent review of medical charts presented a sensitivity of 16%. The sensitivity of the purulent drainage criterion to detect SSIs was 83%. After hospital discharge, 87% of the patients provided follow-up data, and nine purulent drainages were reported by a practitioner (cumulative incidence rate: 20%). Overall, the incidence rate was dependent on the surveillance modalities. The review of medical charts to identify SSIs during hospitalization was not effective; the use of a follow-up card with phone calls for post-discharge surveillance was effective.