Showing papers in "Critical Care in 2016"

The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition

Abstract: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient's blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

Acute kidney injury following cardiac surgery: current understanding and future directions.

Abstract: Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2–5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.

The value of blood lactate kinetics in critically ill patients: a systematic review

Abstract: The time course of blood lactate levels could be helpful to assess a patient’s response to therapy. Although the focus of published studies has been largely on septic patients, many other studies have reported serial blood lactate levels in different groups of acutely ill patients. We performed a systematic search of PubMed, Science Direct, and Embase until the end of February 2016 plus reference lists of relevant publications. We selected all observational and interventional studies that evaluated the capacity of serial blood lactate concentrations to predict outcome. There was no restriction based on language. We excluded studies in pediatric populations, experimental studies, and studies that did not report changes in lactate values or all-cause mortality rates. We separated studies according to the type of patients included. We collected data on the number of patients, timing of lactate measurements, minimum lactate level needed for inclusion if present, and suggested time interval for predictive use. A total of 96 studies met our criteria: 14 in general ICU populations, five in general surgical ICU populations, five in patients post cardiac surgery, 14 in trauma patients, 39 in patients with sepsis, four in patients with cardiogenic shock, eight in patients after cardiac arrest, three in patients with respiratory failure, and four in other conditions. A decrease in lactate levels over time was consistently associated with lower mortality rates in all subgroups of patients. Most studies reported changes over 6, 12 or 24 hrs, fewer used shorter time intervals. Lactate kinetics did not appear very different in patients with sepsis and other types of patients. A few studies suggested that therapy could be guided by these measurements. The observation of a better outcome associated with decreasing blood lactate concentrations was consistent throughout the clinical studies, and was not limited to septic patients. In all groups, the changes are relatively slow, so that lactate measurements every 1–2 hrs are probably sufficient in most acute conditions. The value of lactate kinetics appears to be valid regardless of the initial value.

Acute kidney injury 2016: diagnosis and diagnostic workup

Abstract: Acute kidney injury (AKI) is common and is associated with serious short- and long-term complications. Early diagnosis and identification of the underlying aetiology are essential to guide management. In this review, we outline the current definition of AKI and the potential pitfalls, and summarise the existing and future tools to investigate AKI in critically ill patients.

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

Abstract: For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.

Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study

Abstract: Intense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake. Included patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed. A total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p 70 % was associated with an increased LOS and LOV. The findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements.

Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice.

Abstract: Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream. There is a great heterogeneity in the literature regarding definition, epidemiology, and treatment. The aim of this systematic literature review was to summarize the current state of knowledge regarding the epidemiologic data, definition, and management of rhabdomyolysis. A systematic search was conducted using the keywords “rhabdomyolysis” and “crush syndrome” covering all articles from January 2006 to December 2015 in three databases (MEDLINE, SCOPUS, and ScienceDirect). The search was divided into two steps: first, all articles that included data regarding definition, pathophysiology, and diagnosis were identified, excluding only case reports; then articles of original research with humans that reported epidemiological data (e.g., risk factors, common etiologies, and mortality) or treatment of rhabdomyolysis were identified. Information was summarized and organized based on these topics. The search generated 5632 articles. After screening titles and abstracts, 164 articles were retrieved and read: 56 articles met the final inclusion criteria; 23 were reviews (narrative or systematic); 16 were original articles containing epidemiological data; and six contained treatment specifications for patients with rhabdomyolysis. Most studies defined rhabdomyolysis based on creatine kinase values five times above the upper limit of normal. Etiologies differ among the adult and pediatric populations and no randomized controlled trials have been done to compare intravenous fluid therapy alone versus intravenous fluid therapy with bicarbonate and/or mannitol.

Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review

Abstract: Traditionally seen as a sudden, brutal event with short-term impairment, traumatic brain injury (TBI) may cause persistent, sometimes life-long, consequences While mortality after TBI has been reduced, a high proportion of severe TBI survivors require prolonged rehabilitation and may suffer long-term physical, cognitive, and psychological disorders Additionally, chronic consequences have been identified not only after severe TBI but also in a proportion of cases previously classified as moderate or mild This burden affects the daily life of survivors and their families; it also has relevant social and economic costsOutcome evaluation is difficult for several reasons: co-existing extra-cranial injuries (spinal cord damage, for instance) may affect independence and quality of life outside the pure TBI effects; scales may not capture subtle, but important, changes; co-operation from patients may be impossible in the most severe cases Several instruments have been developed for capturing specific aspects, from generic health status to specific cognitive functions Even simple instruments, however, have demonstrated variable inter-rater agreementThe possible links between structural traumatic brain damage and functional impairment have been explored both experimentally and in the clinical setting with advanced neuro-imaging techniques We briefly report on some fundamental findings, which may also offer potential targets for future therapiesBetter understanding of damage mechanisms and new approaches to neuroprotection-restoration may offer better outcomes for the millions of survivors of TBI

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials.

Abstract: Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients. An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias. A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2–12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I2 = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I2 = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I2 = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I2 = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference [WMD] -0.80, 95 % CI −1.23, −0.37, P = 0.0003, I2 = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed. In critically ill patients, the use of EN as compared to PN has no effect on overall mortality but decreases infectious complications and ICU LOS. This may be explained by the benefit of reduced macronutrient intake rather than the enteral route itself.

Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis

Abstract: Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness. Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes. Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I 2 = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I 2 = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists. Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.

Antibiotic strategies in the era of multidrug resistance

Abstract: The rapid emergence and dissemination of antibiotic-resistant microorganisms in ICUs worldwide threaten adequate antibiotic coverage of infected patients in this environment. The causes of this problem are multifactorial, but the core issues are clear: the emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Because a significant increase in mortality is observed when antibiotic therapy is delayed in infected ICU patients, initial therapy should be broad enough to cover all likely pathogens. Receipt of unnecessary prolonged broad-spectrum antibiotics, however, should be avoided. Local microbiologic data are extremely important to predict the type of resistance that may be present for specific causative bacteria, as is prior antibiotic exposure, and antibiotic choices should thus be made at an individual patient level.

Optimizing sedation in patients with acute brain injury.

Abstract: Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.

The role of neutrophils in immune dysfunction during severe inflammation

Abstract: Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.

The pathophysiological basis and consequences of fever.

Abstract: There are numerous causes of a raised core temperature. A fever occurring in sepsis may be associated with a survival benefit. However, this is not the case for non-infective triggers. Where heat generation exceeds heat loss and the core temperature rises above that set by the hypothalamus, a combination of cellular, local, organ-specific, and systemic effects occurs and puts the individual at risk of both short-term and long-term dysfunction which, if severe or sustained, may lead to death. This narrative review is part of a series that will outline the pathophysiology of pyrogenic and non-pyrogenic fever, concentrating primarily on the pathophysiology of non-septic causes.

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016

Abstract: [This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Ultrasonography in the emergency department

Abstract: Point-of-care ultrasonography (POCUS) is a useful imaging technique for the emergency medicine (EM) physician. Because of its growing use in EM, this article will summarize the historical development, the scope of practice, and some evidence supporting the current applications of POCUS in the adult emergency department. Bedside ultrasonography in the emergency department shares clinical applications with critical care ultrasonography, including goal-directed echocardiography, echocardiography during cardiac arrest, thoracic ultrasonography, evaluation for deep vein thrombosis and pulmonary embolism, screening abdominal ultrasonography, ultrasonography in trauma, and guidance of procedures with ultrasonography. Some applications of POCUS unique to the emergency department include abdominal ultrasonography of the right upper quadrant and appendix, obstetric, testicular, soft tissue/musculoskeletal, and ocular ultrasonography. Ultrasonography has become an integral part of EM over the past two decades, and it is an important skill which positively influences patient outcomes.

Current evidence for the effectiveness of heated and humidified high flow nasal cannula supportive therapy in adult patients with respiratory failure.

Abstract: High flow nasal cannula (HFNC) supportive therapy has emerged as a safe, useful therapy in patients with respiratory failure, improving oxygenation and comfort. Recently several clinical trials have analyzed the effectiveness of HFNC therapy in different clinical situations and have reported promising results. Here we review the current knowledge about HFNC therapy, from its mechanisms of action to its effects on outcomes in different clinical situations.

Reliability of standard pupillometry practice in neurocritical care: an observational, double-blinded study.

Abstract: In critical care units, pupil examination is an important clinical parameter for patient monitoring. Current practice is to use a penlight to observe the pupillary light reflex. The result seems to be a subjective measurement, with low precision and reproducibility. Several quantitative pupillometer devices are now available, although their use is primarily restricted to the research setting. To assess whether adoption of these technologies would benefit the clinic, we compared automated quantitative pupillometry with the standard clinical pupillary examination currently used for brain-injured patients. In order to determine inter-observer agreement of the device, we performed repetitive measurements in 200 healthy volunteers ranging in age from 21 to 58 years, providing a total of 400 paired (alternative right eye, left eye) measurements under a wide variety of ambient light condition with NeuroLight Algiscan pupillometer. During another period, we conducted a prospective, observational, double-blinded study in two neurocritical care units. Patients admitted to these units after an acute brain injury were included. Initially, nursing staff measured pupil size, anisocoria and pupillary light reflex. A blinded physician subsequently performed measurement using an automated pupillometer. In 200 healthy volunteers, intra-class correlation coefficient for maximum resting pupil size was 0.95 (IC: 0.93-0.97) and for minimum pupil size after light stimulation 0.87 (0.83–0.89). We found only 3-pupil asymmetry (≥1 mm) in these volunteers (1.5 % of the population) with a clear pupil asymmetry during clinical inspection. The mean pupil light reactivity was 40 ± 7 %. In 59 patients, 406 pupillary measurements were prospectively performed. Concordance between measurements for pupil size collected using the pupillometer, versus subjective assessment, was poor (Spearmen's rho = 0.75, IC: 0.70-0.79; P < 0.001). Nursing staff failed to diagnose half of the cases (15/30) of anisocoria detected using the pupillometer device. A global rate of discordance of 18 % (72/406) was found between the two techniques when assessing the pupillary light reflex. For measurements with small pupils (diameters <2 mm) the error rate was 39 % (24/61). Standard practice in pupillary monitoring yields inaccurate data. Automated quantitative pupillometry is a more reliable method with which to collect pupillary measurements at the bedside.

"Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering.

Abstract: Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure (“awake” ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient–ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv-ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient–ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years.

Long-term outcomes and healthcare utilization following critical illness – a population-based study

Abstract: The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. We conducted a retrospective cohort study of adults (age ≥18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84 %) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11 % and 29 % at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60–19.68) for those ≥85 years of age compared with those aged 18–24 years. Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post–ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients.

Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials

Abstract: Regional citrate or heparin is often prescribed as an anticoagulant for continuous renal replacement therapy (CRRT). However, their efficacy and safety remain controversial. Therefore, we performed this meta-analysis to compare these two agents and to determine whether the currently available evidence is sufficient and conclusive by using trial sequential analysis (TSA). We searched for relevant studies in PubMed, Embase, the Cochrane Library databases and the China National Knowledge Infrastructure (CNKI) Database from database inception until September 2015. We selected randomized controlled trials comparing regional citrate with heparin in adult patients with acute kidney injury (AKI) who were prescribed CRRT. Fourteen trials (n = 1134) met the inclusion criteria. Pooled analyses showed that there was no difference in mortality between the regional citrate and heparin groups (relative risk (RR) 0.97, 95 % confidence interval (CI) 0.84, 1.13, P > 0.05), which was confirmed by TSA. Compared with heparin, regional citrate significantly prolonged the circuit life span in the continuous venovenous haemofiltration (CVVH) subgroup (mean difference (MD) 8.18, 95 % CI 3.86, 12.51, P 0.05) or post-dilution subgroup (MD 13.06, 95 % CI −2.36, 28.48, P > 0.05). However, the results were not confirmed by TSA. A reduced risk of bleeding was found in the regional citrate compared with the systemic heparin group (RR 0.31, 95 % CI 0.19, 0.51, P < 0.01) and TSA provided conclusive evidence. Fewer episodes of heparin-induced thrombocytopoenia (HIT) (RR 0.41, 95 % CI 0.19, 0.87, P = 0.02) and a greater number of episodes of hypocalcaemia (RR 3.96, 95 % CI 1.50, 10.43, P < 0.01) were found in the regional citrate group. However, TSA did not provide conclusive evidence. In adult patients with AKI, there is no difference in mortality between the regional citrate and heparin treated groups. However, regional citrate is more efficacious in prolonging circuit life span and reducing the risk of bleeding and should be recommended as the priority anticoagulant for critically ill patients who require CRRT.

qSOFA does not replace SIRS in the definition of sepsis

Abstract: The recently published consensus definitions for sepsis [1] have raised a lot of discussion and controversy. We had the privilege of being part of this consensus group and fully support the final definitions. We are pleased that a definition has been developed that closely reflects everyday clinical language, recognizing that sepsis is most simply described as a “bad infection” associated with some degree of organ dysfunction, as proposed earlier [2]. The article conveying the consensus definition [1] also emphasizes that sepsis is more often recognized from the associated organ dysfunction than from the more difficult to identify infection, so that sepsis can be defined as “life-threatening organ dysfunction caused by a dysregulated host response to an infection”. The proposition of the 1992 North American consensus document [3] that sepsis be defined by a combination of the systemic inflammatory response syndrome (SIRS) and the presence of an infection raised confusion, because the SIRS criteria (especially fever, tachycardia, and altered white blood cell count) are themselves typical features of infection [3]. As the majority of infected patients will therefore meet the SIRS criteria, they would also be considered to have sepsis by this 1992 definition. This approach to defining sepsis has resulted in a dramatic increase in the number of patients diagnosed with sepsis over the years [4]; however, these patients may have less severe disease so that reported parallel reductions in mortality rates [5] may be deceptive [6]. The recent “new” definitions are not so novel, more a return to the traditional use of the term to indicate patients with a substantial and deleterious response to an infection. We doubt that this will change further over time, exactly as the meaning of other words like pneumonia, peritonitis, or meningitis has not changed. We all agree on the fundamental importance of identifying sepsis early and of applying effective and complete treatment to minimize complications. However, the SIRS criteria were too sensitive and not sufficiently specific for this purpose. Rangel-Frausto et al. [7] reported that 68 % of patients admitted to three intensive care units (ICUs) and three general wards met the SIRS criteria; in 198 ICUs in 24 European countries, Sprung et al. [8] reported that 93 % of ICU patients had at least two SIRS criteria at some point during their ICU stay; and in a database of patients in 23 Australian and New Zealand ICUs, Dulhunty et al. [9] reported that 88.4 % of patients had at least two SIRS criteria on ICU admission. In a recent analysis of a large US database, Churpek et al. [10] reported that almost half of the 270,000 patients hospitalized on regular wards met the SIRS criteria at one time or another. Our consensus definition paper suggested the quick sequential organ failure assessment (qSOFA) as an effective way of raising suspicion of sepsis on the regular floor [1]. Evaluating all six components of the SOFA score can be time consuming, and some require laboratory measurements. By analyzing a large database of hospitalized patients, three clinical elements (hypotension, altered mentation, and tachypnea) were identified that could be used at the bedside to recognize those infected patients who are at risk of deteriorating or having a complicated course (death or ICU stay ≥ 3 days). The presence of two or more of these criteria can be used to prompt clinicians to further evaluate the patient for the presence of infection and/or organ dysfunction, to start or adapt treatment, and to consider transfer to an ICU. Importantly, this approach is designed to be an early warning system, and a patient with less than two qSOFA criteria may still raise concern. Clinical judgment should always supersede tools designed to help improve patient care, such as qSOFA. We would like to stress that, although SIRS was part of the definition of sepsis in 1992 [3], the qSOFA is not part of the new sepsis definitions. This important difference is illustrated in Fig. 1, with panel A showing that infection and sepsis (by the 1992 definition) are virtually the same—infection without SIRS can be found, but it is relatively rare. By contrast, panel B shows that sepsis (by the new SEPSIS-3 definition) represents only a minority of cases of infection. Moreover, panel B illustrates important aspects of the sepsis definition vis-a-vis infection and qSOFA. For example, sepsis can be present without a qSOFA score ≥ 2 because different forms of organ dysfunction may be present than are assessed using the qSOFA, such as hypoxemia, renal failure, coagulopathy, or hyperbilirubinemia. In addition, a patient may have a qSOFA ≥ 2 without infection; for example, in other acute conditions, such as hypovolemia, severe heart failure, or large pulmonary embolism. Further work remains to be done to determine the predictive validity of qSOFA in such patients. Finally, infected patients may have a qSOFA ≥ 2 and not be septic because the degree of hypotension, tachycardia, and/or altered mentation needed to fulfill qSOFA criteria is not the same as that needed to meet the SOFA organ dysfunction criteria necessary for a diagnosis of sepsis; the qSOFA criteria are thus clinically valuable but imperfect markers of sepsis. Nevertheless, in an analysis of a database of more than 74,000 patients, Seymour et al. [11] recently reported that 75 % of patients with suspected infection who had two or more qSOFA points also had at least two SOFA points. Fig. 1 Schematic representation illustrating a the almost complete overlap of sepsis and infection when the SIRS criteria of the 1992 criteria [3] are used and b the differences between qSOFA and sepsis. qSOFA quick sequential organ failure assessment, SIRS ... We hope this editorial will clarify that the qSOFA is meant to be used to raise suspicion of sepsis and prompt further action—it is not a replacement for SIRS and is not part of the definition of sepsis.

Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials.

Abstract: Driving pressure (ΔPrs) across the respiratory system is suggested as the strongest predictor of hospital mortality in patients with acute respiratory distress syndrome (ARDS). We wonder whether this result is related to the range of tidal volume (VT). Therefore, we investigated ΔPrs in two trials in which strict lung-protective mechanical ventilation was applied in ARDS. Our working hypothesis was that ΔPrs is a risk factor for mortality just like compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system. We performed secondary analysis of data from 787 ARDS patients enrolled in two independent randomized controlled trials evaluating distinct adjunctive techniques while they were ventilated as in the low VT arm of the ARDSnet trial. For this study, we used VT, positive end-expiratory pressure (PEEP), Pplat,rs, Crs, ΔPrs, and respiratory rate recorded 24 hours after randomization, and compared them between survivors and nonsurvivors at day 90. Patients were followed for 90 days after inclusion. Cox proportional hazard modeling was used for mortality at day 90. If colinearity between ΔPrs, Crs, and Pplat,rs was verified, specific Cox models were used for each of them. Both trials enrolled 805 patients of whom 787 had day-1 data available, and 533 of these survived. In the univariate analysis, ΔPrs averaged 13.7 ± 3.7 and 12.8 ± 3.7 cmH2O (P = 0.002) in nonsurvivors and survivors, respectively. Colinearity between ΔPrs, Crs and Pplat,rs, which was expected as these variables are mathematically coupled, was statistically significant. Hazard ratios from the Cox models for day-90 mortality were 1.05 (1.02–1.08) (P = 0.005), 1.05 (1.01–1.08) (P = 0.008) and 0.985 (0.972–0.985) (P = 0.029) for ΔPrs, Pplat,rs and Crs, respectively. PEEP and VT were not associated with death in any model. When ventilating patients with low VT, ΔPrs is a risk factor for death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials from which most ARDS patients were excluded due to strict inclusion and exclusion criteria, these findings must be validated in independent observational studies in patients ventilated with a lung protective strategy. Clinicaltrials.gov NCT00299650 . Registered 6 March 2006 for the Acurasys trial. Clinicaltrials.gov NCT00527813 . Registered 10 September 2007 for the Proseva trial.

Regulation of the cerebral circulation: bedside assessment and clinical implications

Abstract: Regulation of the cerebral circulation relies on the complex interplay between cardiovascular, respiratory, and neural physiology. In health, these physiologic systems act to maintain an adequate cerebral blood flow (CBF) through modulation of hydrodynamic parameters; the resistance of cerebral vessels, and the arterial, intracranial, and venous pressures. In critical illness, however, one or more of these parameters can be compromised, raising the possibility of disturbed CBF regulation and its pathophysiologic sequelae. Rigorous assessment of the cerebral circulation requires not only measuring CBF and its hydrodynamic determinants but also assessing the stability of CBF in response to changes in arterial pressure (cerebral autoregulation), the reactivity of CBF to a vasodilator (carbon dioxide reactivity, for example), and the dynamic regulation of arterial pressure (baroreceptor sensitivity). Ideally, cerebral circulation monitors in critical care should be continuous, physically robust, allow for both regional and global CBF assessment, and be conducive to application at the bedside. Regulation of the cerebral circulation is impaired not only in primary neurologic conditions that affect the vasculature such as subarachnoid haemorrhage and stroke, but also in conditions that affect the regulation of intracranial pressure (such as traumatic brain injury and hydrocephalus) or arterial blood pressure (sepsis or cardiac dysfunction). Importantly, this impairment is often associated with poor patient outcome. At present, assessment of the cerebral circulation is primarily used as a research tool to elucidate pathophysiology or prognosis. However, when combined with other physiologic signals and online analytical techniques, cerebral circulation monitoring has the appealing potential to not only prognosticate patients, but also direct critical care management.

Volume and its relationship to cardiac output and venous return.

Abstract: Volume infusions are one of the commonest clinical interventions in critically ill patients yet the relationship of volume to cardiac output is not well understood. Blood volume has a stressed and unstressed component but only the stressed component determines flow. It is usually about 30 % of total volume. Stressed volume is relatively constant under steady state conditions. It creates an elastic recoil pressure that is an important factor in the generation of blood flow. The heart creates circulatory flow by lowering the right atrial pressure and allowing the recoil pressure in veins and venules to drain blood back to the heart. The heart then puts the volume back into the systemic circulation so that stroke return equals stroke volume. The heart cannot pump out more volume than comes back. Changes in cardiac output without changes in stressed volume occur because of changes in arterial and venous resistances which redistribute blood volume and change pressure gradients throughout the vasculature. Stressed volume also can be increased by decreasing vascular capacitance, which means recruiting unstressed volume into stressed volume. This is the equivalent of an auto-transfusion. It is worth noting that during exercise in normal young males, cardiac output can increase five-fold with only small changes in stressed blood volume. The mechanical characteristics of the cardiac chambers and the circulation thus ultimately determine the relationship between volume and cardiac output and are the subject of this review.

Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome

Abstract: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

Skeletal muscle quality as assessed by CT-derived skeletal muscle density is associated with 6-month mortality in mechanically ventilated critically ill patients

Abstract: Muscle quantity at intensive care unit (ICU) admission has been independently associated with mortality. In addition to quantity, muscle quality may be important for survival. Muscle quality is influenced by fatty infiltration or myosteatosis, which can be assessed on computed tomography (CT) scans by analysing skeletal muscle density (SMD) and the amount of intermuscular adipose tissue (IMAT). We investigated whether CT-derived low skeletal muscle quality at ICU admission is independently associated with 6-month mortality and other clinical outcomes. This retrospective study included 491 mechanically ventilated critically ill adult patients with a CT scan of the abdomen made 1 day before to 4 days after ICU admission. Cox regression analysis was used to determine the association between SMD or IMAT and 6-month mortality, with adjustments for Acute Physiological, Age, and Chronic Health Evaluation (APACHE) II score, body mass index (BMI), and skeletal muscle area. Logistic and linear regression analyses were used for other clinical outcomes. Mean APACHE II score was 24 ± 8 and 6-month mortality was 35.6%. Non-survivors had a lower SMD (25.1 vs. 31.4 Hounsfield Units (HU); p < 0.001), and more IMAT (17.1 vs. 13.3 cm2; p = 0.004). Higher SMD was associated with a lower 6-month mortality (hazard ratio (HR) per 10 HU, 0.640; 95% confidence interval (CI), 0.552–0.742; p < 0.001), and also after correction for APACHE II score, BMI, and skeletal muscle area (HR, 0.774; 95% CI, 0.643–0.931; p = 0.006). Higher IMAT was not significantly associated with higher 6-month mortality after adjustment for confounders. A 10 HU increase in SMD was associated with a 14% shorter hospital length of stay. Low skeletal muscle quality at ICU admission, as assessed by CT-derived skeletal muscle density, is independently associated with higher 6-month mortality in mechanically ventilated patients. Thus, muscle quality as well as muscle quantity are prognostic factors in the ICU. Retrospectively registered (initial release on 06/23/2016) at ClinicalTrials.gov: NCT02817646 .

The neurological and cognitive consequences of hyperthermia

Abstract: An elevated temperature has many aetiologies, both infective and non-infective, and while the fever of sepsis probably confers benefit, there is increasing evidence that the central nervous system is particularly vulnerable to damage from hyperthermia. A single episode of hyperthermia may cause short-term neurological and cognitive dysfunction, which may be prolonged or become permanent. The cerebellum is particularly intolerant to the effects of heat. Hyperthermia in the presence of acute brain injury worsens outcome. The thermotoxicity involved occurs via cellular, local, and systemic mechanisms. This article reviews both the cognitive and neurological consequences and examines the mechanisms of cerebral damage caused by high temperature.

Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes

Abstract: Sepsis is the focus of national quality improvement programs and a recent public reporting measure from the Centers for Medicare and Medicaid Services. However, diagnosing sepsis requires interpreting nonspecific signs and can therefore be subjective. We sought to quantify interobserver variability in diagnosing sepsis. We distributed five case vignettes of patients with suspected or confirmed infection and organ dysfunction to a sample of practicing intensivists. Respondents classified cases as systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or none of the above. Interobserver variability was calculated using Fleiss’ κ for the five-level classification, and for answers dichotomized as severe sepsis/septic shock versus not-severe sepsis/septic shock and any sepsis category (sepsis, severe sepsis, or septic shock) versus not-sepsis. Ninety-four physicians completed the survey. Most respondents (88 %) identified as critical care specialists; other specialties included pulmonology (39 %), anesthesia (19 %), surgery (9 %), and emergency medicine (9 %). Respondents had been in practice for a median of 8 years, and 90 % practiced at academic hospitals. Almost all respondents (83 %) felt strongly or somewhat confident in their ability to apply the traditional consensus sepsis definitions. However, overall interrater agreement in sepsis diagnoses was poor (Fleiss’ κ 0.29). When responses were dichotomized into severe sepsis/septic shock versus not-severe sepsis/septic shock or any sepsis category versus not-sepsis, agreement was still poor (Fleiss’ κ 0.23 and 0.18, respectively). Seventeen percent of respondents classified one of the five cases as severe sepsis/septic shock, 27.7 % rated two cases, 33.0 % respondents rated three cases, 19.2 % rated four cases, and 3.2 % rated all five cases as severe sepsis/septic shock. Among respondents who felt strongly confident in their ability to use sepsis definitions (n = 45), agreement was no better (Fleiss’ κ 0.28 for the five-category classification, and Fleiss’ κ 0.21 for the dichotomized severe sepsis/septic shock classification). Cases were felt to be extremely or very realistic in 74 % of responses; only 3 % were deemed unrealistic. Diagnosing sepsis is extremely subjective and variable. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, benchmarking, and reporting.