Purpose of review: The aim of this review is to analyze innovative data pertaining to the clinical use of mechanical ventilation for children. Recent findings: The optimal definition and treatment of pediatric acute respiratory distress syndrome, the application of innovative ventilation modes in children to optimize child/ventilator interaction, and pediatric noninvasive ventilation, including specific interfaces, have been recently evaluated in the literature. Summary: Despite the improvement observed in the last decades in the treatment of pediatric acute respiratory failure and the diffusion of innovative modes of mechanical ventilation, there are no clear and consistent guidelines for the use of mechanical ventilation for children. In several areas data are still lacking, and in many others they are extrapolated from studies performed in adults; the direct evaluation of results obtained from studies specific to the pediatric population is therefore crucial.

Purpose of review: The purpose of the review is to summarize and discuss recent research regarding the role of mechanical ventilation in producing weakness and atrophy of the diaphragm in critically ill patients, an entity termed ventilator-induced diaphragmatic dysfunction (VIDD). Recent findings: Severe weakness of the diaphragm is frequent in mechanically ventilated patients, in whom it contributes to poor outcomes including increased mortality. Significant progress has been made in identifying the molecular mechanisms responsible for VIDD in animal models, and there is accumulating evidence for occurrence of the same cellular processes in the diaphragms of human patients undergoing prolonged mechanical ventilation. Summary: Recent research is pointing the way to novel pharmacologic therapies as well as nonpharmacologic methods for preventing VIDD. The next major challenge in the field will be to move these findings from the bench to the bedside in critically ill patients.

Purpose of review: Despite advances in extracorporeal membrane oxygenation (ECMO) technology, much is unknown about the optimal management strategies for patients receiving extracorporeal support. There is a growing body of literature investigating patient selection and outcomes, mechanical ventilation approaches, anticoagulation, pharmacokinetics, early mobilization, and the role of ECMO transport among others. Recent findings: Nonrandomized data suggest a survival advantage from ECMO compared with conventional management in acute respiratory distress syndrome, with mechanical ventilation practices varying widely across centers. A randomized controlled trial is currently ongoing with standardized ventilation approaches in both arms. Low-level anticoagulation appears to be well tolerated, and ECMO circuitry appears to affect the pharmacokinetics of certain drugs. Pilot and matched cohort studies suggest that extracorporeal carbon dioxide removal is effective in preventing intubation in chronic obstructive pulmonary disease, with larger randomized studies being planned. ECMO may be successful in bridging selected patients to lung transplantation, with early mobilization serving as a well tolerated and effective means of optimizing these patients. Regionalization of ECMO may maximize outcomes and is facilitated by the development of ECMO transport teams. Summary: Recently published data highlight the evolving management strategies of patients receiving extracorporeal support and help identify those patients most appropriate for ECMO and extracorporeal carbon dioxide removal. More data will ultimately be needed to develop an evidence-based consensus.

Purpose of review: The purpose is to review the development and current application of extracorporeal life support [ECLS, extracorporeal membrane oxygenation (ECMO)] in acute severe respiratory failure. Recent findings: Extracorporeal support (ECMO) is used for acute severe respiratory failure in advanced ICUs. The current survival rate is 60–70%. Three controlled trials all demonstrated 20–30% improvement in survival compared to conventional care. Patients may now be maintained awake and ambulatory with spontaneous breathing. Summary: ECMO is the next step in the algorithm for management of severe respiratory failure unresponsive to conventional care.

Background: Patients receiving intravenous thrombolysis (IVT) for acute ischemic stroke are at risk of developing complications, commonly necessitating admission to an intensive care unit (ICU). At present, most IVT is administered in the Emergency Department or in dedicated stroke units, but no evidence-based criteria exist that allow for early identification of patients at increased risk of developing ICU needs. The present study describes a novel prediction score aiming to identify a subpopulation of post-IVT patients at high risk for critical care interventions. Methods: We retrospectively analyzed data from 301 patients undergoing IVT at our institutions during a 5-year period. Two hundred and ninety patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of critical care needs based on strength of association. Results: Seventy-two patients (24.8 %) required critical care interventions. Black race (odds ratio [OR] 3.81, p?=0.006), male sex (OR 3.79, p?=0.008), systolic blood pressure (SBP; OR 1.45 per 10 mm Hg increase in SBP, p?<0.001), and NIH stroke scale (NIHSS; OR 1.09 per 1 point increase in NIHSS, p?=0.071) were independent predictors of critical care needs. The optimal model for score development, predicting critical care needs, achieved an AUC of 0.782 in the validation group. The score was named the ICAT (Intensive Care After Thrombolysis) score, assigning the following points: black race (1 point), male sex (1 point), SBP (2 points if 160–200 mm Hg; 4 points if >200 mm Hg), and NIHSS (1 point if 7–12; 2 points if >12). Each 1-point increase in the score was associated with 2.22-fold increased odds for critical care needs (95 % CI 1.78–2.76, p?<0.001). A score ?2 was associated with over 13 times higher odds of critical care needs compared to a score <2 (OR 13.60, 95 % CI 3.23–57.19), predicting critical care with 97.2 % sensitivity and 28.0 % specificity. Conclusion: The ICAT score, combining information about race, sex, SBP, and NIHSS, predicts critical care needs in post-IVT patients and may be helpful when triaging post-IVT patients to the appropriate monitoring environment.

Background: Two clinical scoring systems, the status epilepticus severity score (STESS) and the epidemiology-based mortality score in status epilepticus (EMSE), are used to predict mortality in patients with status epilepticus (SE). The aim of this study was to compare the outcome-prediction function of the two scoring systems regarding in-hospital mortality using a multicenter large cohort of adult patients with SE. Moreover, we studied the potential role of these two scoring systems in predicting the functional outcome in patients with SE. Methods: The SE cohort consisted of patients from the epilepsy centers of eight academic tertiary medical centers in South Korea. The clinical and electroencephalography data for all adult patients with SE from January 2013 to December 2014 were derived from a prospective SE database. The primary outcome variable was defined as in-hospital death. The secondary outcome variable was defined as a poor functional outcome, i.e., a score of 1–3 on the Glasgow Outcome Scale, at discharge. Results: Among the 120 non-hypoxic patients with SE recruited into the study, 16 (13.3 %) died in the hospital and 64 (53.3 %) were discharged with a poor functional outcome. The receiver-operating characteristic (ROC) curve for prediction of in-hospital death based on the STESS had an area under the curve of 0.673 with an optimal cutoff value for discrimination (best match for both sensitivity (0.56) and specificity (0.70)) that was ?4 points. The two combinations of elements of the EMSE system (EMSE-ALDEg and EMSE-ECLEg) predicted not only in-hospital mortality with the best match for sensitivity (more than 0.6) and specificity (more than 0.6), but also a poor functional outcome with the best match for both sensitivity (>0.7) and specificity (>0.6). STESS did not predict a poor functional outcome (area under the ROC, 0.581; P?=?0.23). Conclusion: Although the EMSE is a clinical scoring system that focuses on individual mortality, we did not find differences between the EMSE and STESS in the prediction of in-hospital death. The EMSE was useful in predicting poor functional outcome, as it was significantly better than STESS.

No description available

Background: The outcomes of patients admitted to the intensive care unit (ICU) for acute manifestation of small-vessel vasculitis are poorly reported. The aim of the present study was to determine the mortality rate and prognostic factors of patients admitted to the ICU for acute small-vessel vasculitis. Methods: This retrospective, multicenter study was conducted from January 2001 to December 2014 in 20 ICUs in France. Patients were identified from computerized registers of each hospital using the International Classification of Diseases, Ninth Revision (ICD-9). Inclusion criteria were (1) known or highly suspected granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis (respectively, ICD-9 codes M31.3, M30.1, and M31.7), or anti–glomerular basement membrane antibody disease (ICD-9 codes N08.5X-005 or M31.0+); (2) admission to the ICU for the management of an acute manifestation of vasculitis; and (3) administration of a cyclophosphamide pulse in the ICU or within 48 h before admission to the ICU. The primary endpoint was assessment of mortality rate 90 days after admission to the ICU. Results: Eighty-two patients at 20 centers were included, 94 % of whom had a recent (<6 months) diagnosis of small-vessel vasculitis. Forty-four patients (54 %) had granulomatosis with polyangiitis. The main reasons for admission were respiratory failure (34 %) and pulmonary-renal syndrome (33 %). Mechanical ventilation was required in 51 % of patients, catecholamines in 31 %, and renal replacement therapy in 71 %. Overall mortality at 90 days was 18 % and the mortality in ICU was 16 %. The main causes of death in the ICU were disease flare in 69 % and infection in 31 %. In univariable analysis, relevant factors associated with death in nonsurvivors compared with survivors were Simplified Acute Physiology Score II (median [interquartile range] 51 [38–82] vs. 36 [27–42], p?=?0.005), age (67 years [62–74] vs. 58 years [40–68], p?<?0.003), Sequential Organ Failure Assessment score on the day of cyclophosphamide administration (11 [6–12] vs. 6 [3–7], p?=?0.0004), and delayed administration of cyclophosphamide (5 days [3–14] vs. 2 days [1–5], p?=?0.0053). Conclusions: Patients admitted to the ICU for management of acute small-vessel vasculitis benefit from early, aggressive intensive care treatment, associated with an 18 % death rate at 90 days.

No description available

Aneurysmal subarachnoid haemorrhage is a neurological syndrome with complex systemic complications. The rupture of an intracranial aneurysm leads to the acute extravasation of arterial blood under high pressure into the subarachnoid space and often into the brain parenchyma and ventricles. The haemorrhage triggers a cascade of complex events, which ultimately can result in early brain injury, delayed cerebral ischaemia, and systemic complications. Although patients with poor-grade subarachnoid haemorrhage (World Federation of Neurosurgical Societies 4 and 5) are at higher risk of early brain injury, delayed cerebral ischaemia, and systemic complications, the early and aggressive treatment of this patient population has decreased overall mortality from more than 50 % to 35 % in the last four decades. These management strategies include (1) transfer to a high-volume centre, (2) neurological and systemic support in a dedicated neurological intensive care unit, (3) early aneurysm repair, (4) use of multimodal neuromonitoring, (5) control of intracranial pressure and the optimisation of cerebral oxygen delivery, (6) prevention and treatment of medical complications, and (7) prevention, monitoring, and aggressive treatment of delayed cerebral ischaemia. The aim of this article is to provide a summary of critical care management strategies applied to the subarachnoid haemorrhage population, especially for patients in poor neurological condition, on the basis of the modern concepts of early brain injury and delayed cerebral ischaemia.

Critical care physicians have debated an appropriate term for the clinical phase preceding acute kidney injury (AKI). The recent development of cell cycle arrest biomarkers that signal the potential development of AKI is part of an evolution in the molecular diagnosis and understanding of AKI. It is proposed that the pre-injury phase that leads to AKI can be described as “acute kidney stress”. This term has the potential to expand horizons in regard to the early detection of situations that will lead to AKI and the early implementation of corrective measures.

Background: Assessment of pulmonary edema is a key factor in monitoring and guidance of therapy in critically ill patients. To date, methods available at the bedside for estimating the physiologic correlate of pulmonary edema, extravascular lung water, often are unreliable or require invasive measurements. The aim of the present study was to develop a novel approach to reliably assess extravascular lung water by making use of the functional imaging capabilities of electrical impedance tomography. Methods: Thirty domestic pigs were anesthetized and randomized to three different groups. Group 1 was a sham group with no lung injury. Group 2 had acute lung injury induced by saline lavage. Group 3 had vascular lung injury induced by intravenous injection of oleic acid. A novel, noninvasive technique using changes in thoracic electrical impedance with lateral body rotation was used to measure a new metric, the lung water ratio EIT , which reflects total extravascular lung water. The lung water ratio EIT was compared with postmortem gravimetric lung water analysis and transcardiopulmonary thermodilution measurements. Results: A significant correlation was found between extravascular lung water as measured by postmortem gravimetric analysis and electrical impedance tomography (r?=?0.80; p?<?0.05). Significant changes after lung injury were found in groups 2 and 3 in extravascular lung water derived from transcardiopulmonary thermodilution as well as in measurements derived by lung water ratio EIT . Conclusions: Extravascular lung water could be determined noninvasively by assessing characteristic changes observed on electrical impedance tomograms during lateral body rotation. The novel lung water ratio EIT holds promise to become a noninvasive bedside measure of pulmonary edema.

Background: Critical illness and the problems faced after ICU discharge do not only affect the patient, it also negatively impacts patients’ informal caregivers. There is no review which summarizes all types of burden reported in informal caregivers of ICU survivors. It is important that the burdens these informal caregivers suffer are systematically assessed so the caregivers can receive the professional care they need. We aimed to provide a complete overview of the types of burdens reported in informal caregivers of adult ICU survivors, to make recommendations on which burdens should be assessed in this population, and which tools should be used to assess them.MethodWe performed a systematic search in PubMed and CINAHL from database inception until June 2014. All articles reporting on burdens in informal caregivers of adult ICU survivors were included. Two independent reviewers used a standardized form to extract characteristics of informal caregivers, types of burdens and instruments used to assess these burdens. The quality of the included studies was assessed using the Newcastle-Ottawa and the PEDro scales. Results: The search yielded 2704 articles, of which we included 28 in our review. The most commonly reported outcomes were psychosocial burden. Six months after ICU discharge, the prevalence of anxiety was between 15 % and 24 %, depression between 4.7 % and 36.4 % and post-traumatic stress disorder (PTSD) between 35 % and 57.1 %. Loss of employment, financial burden, lifestyle interference and low health-related quality of life (HRQoL) were also frequently reported. The most commonly used tools were the Hospital Anxiety and Depression Scale (HADS), Centre for Epidemiological Studies-Depression questionnaire, and Impact of Event Scale (IES). The quality of observational studies was low and of randomized studies moderate to fair. Conclusions: Informal caregivers of ICU survivors suffer a substantial variety of burdens. Although the quality of the included studies was poor, there is evidence that burden in the psychosocial field is most prevalent. We suggest screening informal caregivers of ICU survivors for anxiety, depression, PTSD, and HRQoL using respectively the HADS, IES and Short Form 36 and recommend a follow-up period of at least 6 months.

No description available

Background: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. Methods: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. Results: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). Conclusions: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder.

No description available

Background: Patients with subarachnoid haemorrhage (SAH) frequently develop cardiac complications in the acute phase after the bleeding. Although a number of studies have shown that increased levels of cardiac biomarkers after SAH are associated with a worse short-term prognosis, no prospective, consecutive study has assessed the association between biomarker release and long-term outcome. We aimed to evaluate whether the cardiac biomarkers, high-sensitive troponin T (hsTnT) and N-terminal pro B-type natriuretic peptide (NTproBNP), were associated with poor 1-year neurological outcome and cerebral infarction due to delayed cerebral ischaemia (CI-DCI). Methods: In this single-centre prospective observational study, all consecutive patients admitted to our neurointensive care unit from January 2012 to December 2013 with suspected/verified SAH with an onset of symptoms <72 hours were enrolled. Blood samples for hsTnT and NTproBNP were collected during three consecutive days following admission. Patients were followed-up after 1 year using the Glasgow Outcome Scale Extended (GOSE). Poor neurological outcome was defined as GOSE ?4. Results: One hundred and seventy seven patients with suspected SAH were admitted during the study period; 143 fulfilled inclusion criteria and 126 fulfilled follow-up. Forty-one patients had poor 1-year outcome and 18 had CI-DCI. Levels of hsTnT and NTproBNP were higher in patients with poor outcome and CI-DCI. In multivariable logistic regression modelling age, poor neurological admission status, cerebral infarction of any cause and peak hsTnT were independently associated with poor late outcome. Both peak hsTnT and peak NTproBNP were independently associated with CI-DCI. Conclusion: Increased serum levels of the myocardial damage biomarker hsTnT, when measured early after onset of SAH, are independently associated with poor 1-year outcome. Furthermore, release of both hsTnT and NTproBNP are independently associated with CI-DCI. These findings render further support to the notion that troponin release after SAH is an ominous finding. Future studies should evaluate whether there is a causal relationship between early release of biomarkers of myocardial injury after SAH and neurological sequelae.

Background: The aim of the present study was to investigate the incidence of adverse events (AEs) during intra-hospital transport (IHT) of critically ill patients and evaluate the risk factors associated with these events. Methods: This prospective multicenter observational study was performed in 34 intensive care units in China during 20 consecutive days from 5 November to 25 November 2012. All consecutive patients who required IHT for diagnostic testing or therapeutic procedures during the study period were included. All AEs that occurred during IHT were recorded. The incidence of AEs was defined as the rate of transports with at least one AE. The statistical analysis included a description of demographic and clinical characteristics of the cohort as well as identification of risk factors for AEs during IHT by univariate and multivariate logistic regression analyses. Results: In total, 441 IHTs of 369 critically ill patients were analyzed. The overall incidence of AEs was 79.8 % (352 IHTs). The proportion of equipment- and staff-related adverse events was 7.9 % (35 IHTs). The rate of patient-related adverse events (P-AEs) was 79.4 % (349 IHTs). The rates of vital sign–related P-AEs and arterial blood gas analysis–related P-AEs were 57.1 % (252 IHTs) and 46.9 % (207 IHTs), respectively. The incidence of critical P-AEs was 33.1 % (146 IHTs). The rates of vital sign–related critical P-AEs and arterial blood gas analysis–related critical P-AEs were 22.9 % (101 IHTs) and 15.0 % (66 IHTs), respectively. All data collected in our study were considered potential risk factors. In the multivariate analysis, predictive factors for P-AEs were pH, partial pressure of carbon dioxide in arterial blood, lactate level, glucose level, and heart rate before IHT. Furthermore, the Acute Physiology and Chronic Health Evaluation II score, partial pressure of oxygen in arterial blood, lactate level, glucose level, heart rate, respiratory rate, pulse oximetry, and sedation before transport were independent influential factors for critical P-AEs during IHT. Conclusions: The incidence of P-AEs during IHT of critically ill patients was high. Risk factors for P-AEs during IHT were identified. Strategies are needed to reduce their frequency.Trial registrationChinese Clinical Trial Register identifier ChiCTR-OCS-12002661. Registered 5 November 2012.

No description available

Background: High serum lactate is associated with increased mortality in septic shock patients. Metformin alters lactate metabolism, and may affect its prognostic value. We compared, between metformin users and nonusers, the prognosis of extremely elevated plasma lactate levels in patients with septic shock. Methods: The electronic medical records (EMR) of patients admitted to the emergency room between January 2011 and June 2013 were reviewed. The study cohort comprised patients with an initial diagnosis of septic shock and blood lactate higher than 10 mmol/L. The selected population was divided into two groups: metformin users (exposed) and metformin nonusers (unexposed). The primary outcome measured was inhospital mortality. Results: The study included 44 metformin users and 118 nonusers. Metformin users were similar to nonusers with respect to levels of lactate, HCO 3 , and blood pH; however, they were older and had higher incidence rates of cardiovascular disease and acute kidney injury at admission, compared to nonusers. Inhospital mortality rates were significantly lower in the metformin-treated group, 56.8 % vs. 88.1 %, p <0.0001. Conclusions: Though high lactate concentration indicates poor prognosis in septic patients, mortality rate was found to be significantly lower in those who were treated with metformin. This finding may help clinicians in deciding treatment for these patients, who could otherwise be considered too ill for real treatment benefit.