Showing papers in "Intensive Care Medicine in 2017"

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial

Abstract: Purpose Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

Abstract: Purpose To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.

The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

Abstract: Functional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay. Ten observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p < 0.00001; I 2 = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p < 0.00001; I 2 = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p < 0.00001; I 2 = 12%). Frailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).

Acute kidney injury in sepsis.

Abstract: Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.

Erratum to: Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial.

Abstract: PurposeCare bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.MethodsIn this single-center trial, we examined the effect of a “KDIGO bundle” consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.ResultsAKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5–27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.ConclusionAn implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.

The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review

Abstract: Early active mobilisation and rehabilitation in the intensive care unit (ICU) is being used to prevent the long-term functional consequences of critical illness. This review aimed to determine the effect of active mobilisation and rehabilitation in the ICU on mortality, function, mobility, muscle strength, quality of life, days alive and out of hospital to 180 days, ICU and hospital lengths of stay, duration of mechanical ventilation and discharge destination, linking outcomes with the World Health Organization International Classification of Function Framework. A PRISMA checklist-guided systematic review and meta-analysis of randomised and controlled clinical trials. Fourteen studies of varying quality including a total of 1753 patients were reviewed. Active mobilisation and rehabilitation had no impact on short- or long-term mortality (p > 0.05). Meta-analysis showed that active mobilisation and rehabilitation led to greater muscle strength (body function) at ICU discharge as measured using the Medical Research Council Sum Score (mean difference 8.62 points, 95% confidence interval (CI) 1.39–15.86), greater probability of walking without assistance (activity limitation) at hospital discharge (odds ratio 2.13, 95% CI 1.19–3.83), and more days alive and out of hospital to day 180 (participation restriction) (mean difference 9.69, 95% CI 1.7–17.66). There were no consistent effects on function, quality of life, ICU or hospital length of stay, duration of mechanical ventilation or discharge destination. Active mobilisation and rehabilitation in the ICU has no impact on short- and long-term mortality, but may improve mobility status, muscle strength and days alive and out of hospital to 180 days. CRD42015029836.

The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years)

Abstract: Very old critical ill patients are a rapid expanding group in the ICU Indications for admission, triage criteria and level of care are frequently discussed for such patients However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population A transnational prospective cohort study from October 2016 to May 2017 with 30 days follow-up was set up by the European Society of Intensive Care Medicine In total 311 ICUs from 21 European countries participated The ICUs included the first consecutive 20 very old (≥ 80 years) patients admitted to the ICU within a 3-month inclusion period Frailty, SOFA score and therapeutic procedures were registered, in addition to limitations of care For measurement of frailty the Clinical Frailty Scale was used at ICU admission The main outcomes were ICU and 30-day mortality and survival at 30 days A total of 5021 patients with a median age of 84 years (IQR 81–86 years) were included in the final analysis, 2404 (479%) were women Admission was classified as acute in 4215 (839%) of the patients Overall ICU and 30-day mortality rates were 221% and 326% During ICU stay 238% of the patients did not receive specific ICU procedures: ventilation, vasoactive drugs or renal replacement therapy Frailty (values ≥ 5) was found in 431% and was independently related to 30-day survival (HR 154; 95% CI 138–173) for frail versus non-frail Among very old patients (≥ 80 years) admitted to the ICU, the consecutive classes in Clinical Frailty Scale were inversely associated with short-term survival The scale had a very low number of missing data These findings provide support to add frailty to the clinical assessment in this patient group ClinicalTrialsgov (ID: NCT03134807)

Renal recovery after acute kidney injury.

Abstract: Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.

Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis.

Abstract: It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients. To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness. We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. We included randomised trials comparing fluid regimens with differing fluid balances between groups, and observational studies investigating the relationship between fluid balance and clinical outcomes. Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident. In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, we found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR) 0.92, 95 % confidence interval (CI) 0.82–1.02, I 2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53–3.10, I 2 = 9 %) and reduced length of ICU stay (mean difference −1.88 days, 95 % CI −0.12 to −3.64, I 2 = 75 %) compared with a liberal strategy or standard care. In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.

Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database

Abstract: The optimal strategy of fluid resuscitation in the early hours of severe sepsis and septic shock is controversial, with both an aggressive and conservative approach being recommended. We used the 2013 Premier Hospital Discharge database to analyse the administration of fluids on the first ICU day, in 23,513 patients with severe sepsis and septic shock, who were admitted to an ICU from the emergency department. Day 1 fluid was grouped into categories 1 L wide, starting with 1–1.99 L up to ≥9 L, to examine the effect of day 1 fluids on patient mortality. We built binary response models for hospital mortality and the propensity for receiving more than 5 L of fluids on day 1, using patient age and acute conditions present on admission. Patients were grouped by the requirement for mechanical ventilation and the presence or absence of shock. We assessed trends in the difference between actual and expected mortality, in the low fluid range (1–5 L day 1 fluids) and the high fluid range (5 to ≥9 L day 1 fluids) categories, using weighted linear regression controlling for the effects of sample size and variation within the day 1 fluid category. Day 1 fluid administration averaged 4.4 L being lowest in the group with no mechanical ventilation and no shock (3.6 L) and highest (5.4 L) in the group receiving mechanical ventilation and in shock. The administration of day 1 fluids was remarkably consistent on the basis of hospital size, teaching status, rural/urban location, and region of the country. The hospital mortality in the entire cohort was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1 days, respectively. In the entire cohort, low volume resuscitation (1–4.99 L) was associated with a small but significant reduction in mortality, of −0.7% per litre (95% CI −1.0%, −0.4%; p = 0.02). However, in patients receiving high volume resuscitation (5 to ≥9 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%; p = 0.0003) for each additional litre above 5 L. Total hospital cost increased by $999 for each litre of fluid above 5 L (adjusted R 2 = 92.7%, p = 0.005). The mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines. The administration of more than 5 L of fluid during the first ICU day is associated with a significantly increased risk of death and significantly higher hospital costs.

Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017 : Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine.

Abstract: Background Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity

Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC)

Abstract: Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children. The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms. The Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with “strong agreement”. The final iteration of the recommendations had none with equipoise or disagreement. These recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.

Critical illness-associated diaphragm weakness

Abstract: Diaphragm weakness is highly prevalent in critically ill patients. It may exist prior to ICU admission and may precipitate the need for mechanical ventilation but it also frequently develops during the ICU stay. Several risk factors for diaphragm weakness have been identified; among them sepsis and mechanical ventilation play central roles. We employ the term critical illness-associated diaphragm weakness to refer to the collective effects of all mechanisms of diaphragm injury and weakness occurring in critically ill patients. Critical illness-associated diaphragm weakness is consistently associated with poor outcomes including increased ICU mortality, difficult weaning, and prolonged duration of mechanical ventilation. Bedside techniques for assessing the respiratory muscles promise to improve detection of diaphragm weakness and enable preventive or curative strategies. Inspiratory muscle training and pharmacological interventions may improve respiratory muscle function but data on clinical outcomes remain limited.

Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review.

Abstract: Diaphragmatic dysfunction (DD) has a high incidence in critically ill patients and is an under-recognized cause of respiratory failure and prolonged weaning from mechanical ventilation. Among different methods to assess diaphragmatic function, diaphragm ultrasonography (DU) is noninvasive, rapid, and easy to perform at the bedside. We systematically reviewed the current literature assessing the usefulness and accuracy of DU in intensive care unit (ICU) patients. Pubmed, Cochrane Database of Systematic Reviews, Embase, Scopus, and Google Scholar Databases were searched for pertinent studies. We included all original, peer-reviewed studies about the use of DU in ICU patients. Twenty studies including 875 patients were included in the final analysis. DU was performed with different techniques to measure diaphragmatic inspiratory excursion, thickness of diaphragm (Tdi), and thickening fraction (TF). DU is feasible, highly reproducible, and allows one to detect diaphragmatic dysfunction in critically ill patients. During weaning from mechanical ventilation and spontaneous breathing trials, both diaphragmatic excursion and diaphragmatic thickening measurements have been used to predict extubation success or failure. Optimal cutoffs ranged from 10 to 14 mm for excursion and 30–36 % for thickening fraction. During assisted mechanical ventilation, diaphragmatic thickening has been found to be an accurate index of respiratory muscles workload. Observational studies suggest DU as a reliable method to assess diaphragm atrophy in patients undergoing mechanical ventilation. Current literature suggests that DU could be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients, to predict extubation success or failure, to monitor respiratory workload, and to assess atrophy in patients who are mechanically ventilated.

High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (TRAMONTANE study)

Abstract: Nasal continuous positive airway pressure (nCPAP) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (AVB). Although oxygen delivery via high flow nasal cannula (HFNC) is increasingly used, evidence of its efficacy and safety is lacking in infants. A randomized controlled trial was performed in five pediatric intensive care units (PICUs) to compare 7 cmH2O nCPAP with 2 L/kg/min oxygen therapy administered with HFNC in infants up to 6 months old with moderate to severe AVB. The primary endpoint was the percentage of failure within 24 h of randomization using prespecified criteria. To satisfy noninferiority, the failure rate of HFNC had to lie within 15% of the failure rate of nCPAP. Secondary outcomes included success rate after crossover, intubation rate, length of stay, and serious adverse events. From November 2014 to March 2015, 142 infants were included and equally distributed into groups. The risk difference of −19% (95% CI −35 to −3%) did not allow the conclusion of HFNC noninferiority (p = 0.707). Superiority analysis suggested a relative risk of success 1.63 (95% CI 1.02–2.63) higher with nCPAP. The success rate with the alternative respiratory support, intubation rate, durations of noninvasive and invasive ventilation, skin lesions, and length of PICU stay were comparable between groups. No patient had air leak syndrome or died. In young infants with moderate to severe AVB, initial management with HFNC did not have a failure rate similar to that of nCPAP. This clinical trial was recorded in the National Library of Medicine registry (NCT 02457013).

Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial

Abstract: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients. We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders. We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI −5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days. EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients. Clinicaltrials.gov identifier no. NCT01372176.

Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach.

Abstract: To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field. Review of medical literature and expert opinion were used in the development of this review. There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus, and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions. Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy.

Assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients.

Abstract: To develop and validate a scale using variables easily obtained at the bedside for prediction of failure of noninvasive ventilation (NIV) in hypoxemic patients. The test cohort comprised 449 patients with hypoxemia who were receiving NIV. This cohort was used to develop a scale that considers heart rate, acidosis, consciousness, oxygenation, and respiratory rate (referred to as the HACOR scale) to predict NIV failure, defined as need for intubation after NIV intervention. The highest possible score was 25 points. To validate the scale, a separate group of 358 hypoxemic patients were enrolled in the validation cohort. The failure rate of NIV was 47.8 and 39.4% in the test and validation cohorts, respectively. In the test cohort, patients with NIV failure had higher HACOR scores at initiation and after 1, 12, 24, and 48 h of NIV than those with successful NIV. At 1 h of NIV the area under the receiver operating characteristic curve was 0.88, showing good predictive power for NIV failure. Using 5 points as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for NIV failure were 72.6, 90.2, 87.2, 78.1, and 81.8%, respectively. These results were confirmed in the validation cohort. Moreover, the diagnostic accuracy for NIV failure exceeded 80% in subgroups classified by diagnosis, age, or disease severity and also at 1, 12, 24, and 48 h of NIV. Among patients with NIV failure with a HACOR score of >5 at 1 h of NIV, hospital mortality was lower in those who received intubation at ≤12 h of NIV than in those intubated later [58/88 (66%) vs. 138/175 (79%); p = 0.03). The HACOR scale variables are easily obtained at the bedside. The scale appears to be an effective way of predicting NIV failure in hypoxemic patients. Early intubation in high-risk patients may reduce hospital mortality.

The status of intensive care medicine research and a future agenda for very old patients in the ICU

Abstract: The "very old intensive care patients" (abbreviated to VOPs; greater than 80 years old) are probably the fastest expanding subgroup of all intensive care unit (ICU) patients. Up until recently most ICU physicians have been reluctant to admit these VOPs. The general consensus was that there was little survival to gain and the incremental life expectancy of ICU admission was considered too small. Several publications have questioned this belief, but others have confirmed the poor long-term mortality rates in VOPs. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making and improved prediction models are also needed for this particular patient group. Here, an expert panel proposes a research agenda for VOPs for the coming years.

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study

Abstract: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86–0.99), day-1 SOFA (1.09/point, 1.06–1.13), day-1 PaO2/FiO2 (1.47, 1.05–2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42–3.14), invasive pulmonary aspergillosis (1.85, 1.21–2.85), and undetermined cause (1.46, 1.09–1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59–1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09–1.27), direct admission to the ICU (0.69, 0.54–0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08–1.16), PaO2/FiO2 < 100 (1.60, 1.03–2.48), and undetermined ARF etiology (1.43, 1.04–1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09–4.91), first-line IMV (2.55, 1.94–3.29), NIV failure (3.65, 2.05–6.53), standard oxygen failure (4.16, 2.91–5.93), and HFNC failure (5.54, 3.27–9.38). HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

Abstract: Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10–14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP–FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes. Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8–22] vs. 2 (IQR 0–15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.

Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates.

Abstract: Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients. A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure–time product (PTPPes), and lung volume, by electrical impedance tomography. Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly. In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome.

Abstract: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032). Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS. Clinicaltrials.gov identifier, NCT01093482.

Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.

Abstract: Purpose The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting. Methods In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated. Results A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up >50% of the gut microbiota; in 4 patients this was even >75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival. Conclusions We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.

Increased incidence of co-infection in critically ill patients with influenza.

Abstract: Co-infection is frequently seen in critically ill patients with influenza, although the exact rate is unknown. We determined the rate of co-infection, the risk factors and the outcomes associated with co-infection in critically ill patients with influenza over a 7-year period in 148 Spanish intensive care units (ICUs). This was a prospective, observational, multicentre study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint of this analysis was the presence of community-acquired co-infection, with secondary endpoints including ICU, 28-day and hospital mortality. Of 2901 ICU patients diagnosed with influenza, 482 (16.6 %) had a co-infection. The proportion of cases of co-infection increased from 11.4 % (110/968) in 2009 to 23.4 % (80/342) in 2015 (P < 0.001). Compared with patients without co-infection, patients with co-infection were older [adjusted odds ratio (aOR) 1.1, 95 % confidence interval 1.1–1.2; P < 0.001] and were more frequently immunosuppressed due to existing HIV infection (aOR 2.6 [1.5–4.5]; P < 0.001) or preceding medication (aOR 1.4 [1.1–1.9]; P = 0.03). Co-infection was an independent risk factor for ICU mortality (aOR 1.4 [1.1–1.8]; P < 0.02), 28-day mortality (aOR 1.3 [1.1–1.7]; P = 0.04) and hospital mortality (aOR 1.9 [1.5–2.5]; P < 0.001). Co-infection in critically ill patients with influenza has increased in recent years. In this Spanish cohort, age and immunosuppression were risk factors for co-infection, and co-infection was an independent risk factor for ICU, 28-day and hospital mortality.

The intensive care medicine research agenda in nutrition and metabolism

Abstract: The objectives of this review are to summarize the current practices and major recent advances in critical care nutrition and metabolism, review common beliefs that have been contradicted by recent trials, highlight key remaining areas of uncertainty, and suggest recommendations for the top 10 studies/trials to be done in the next 10 years. Recent literature was reviewed and developments and knowledge gaps were summarized. The panel identified candidate topics for future trials in critical care nutrition and metabolism. Then, members of the panel rated each one of the topics using a grading system (0–4). Potential studies were ranked on the basis of average score. Recent randomized controlled trials (RCTs) have challenged several concepts, including the notion that energy expenditure must be met universally in all critically ill patients during the acute phase of critical illness, the routine monitoring of gastric residual volume, and the value of immune-modulating nutrition. The optimal protein dose combined with standardized active and passive mobilization during the acute phase and post-acute phase of critical illness were the top ranked studies for the next 10 years. Nutritional assessment, nutritional strategies in critically obese patients, and the effects of continuous versus intermittent enteral nutrition were also among the highest-ranking studies. Priorities for clinical research in the field of nutritional management of critically ill patients were suggested, with the prospect that different nutritional interventions targeted to the appropriate patient population will be examined for their effect on facilitating recovery and improving survival in adequately powered and properly designed studies, probably in conjunction with physical activity.

The intensive care delirium research agenda: a multinational, interprofessional perspective.

Abstract: Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.

The ICM research agenda on intensive care unit-acquired weakness

Abstract: We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

Current challenges in the management of sepsis in ICUs in resource-poor settings and suggestions for the future

Abstract: Sepsis is a major cause of critical illness worldwide, especially in resource-poor settings. Intensive care units (ICUs) in low- and middle-income countries (LMICs) face many challenges that could affect patient outcome. The aim of this review is to describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics, and research aspects of sepsis. We restricted this manuscript to the ICU setting although we are aware that many sepsis patients in LMICs are treated outside an ICU. Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can be more important than the host response. There are differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in resource-rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and important differences in resources. Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both a macro- and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.