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BACKGROUND: : Catheter-related bloodstream infections are an important cause of morbidity and mortality in hospitalized patients. Current guidelines recommend that femoral venous access should be avoided to reduce this complication (1A recommendation). However, the risk of catheter-related bloodstream infections from femoral as compared to subclavian and internal jugular venous catheterization has not been systematically reviewed. OBJECTIVE: : A systematic review of the literature to determine the risk of catheter-related bloodstream infections related to nontunneled central venous catheters inserted at the femoral site as compared to subclavian and internal jugular placement. DATA SOURCES: : MEDLINE, Embase, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles, and an Internet search (Google). STUDY SELECTION: : Randomized controlled trials and cohort studies that reported the frequency of catheter-related bloodstream infections (infections per 1,000 catheter days) in patients with nontunneled central venous catheters placed in the femoral site as compared to subclavian or internal jugular placement. DATA EXTRACTION: : Data were abstracted on study design, study size, study setting, patient population, number of catheters at each insertion site, number of catheter-related bloodstream infections, and the prevalence of deep venous thrombosis. Studies were subgrouped according to study design (cohort and randomized controlled trials). Meta-analytic techniques were used to summarize the data. DATA SYNTHESIS: : Two randomized controlled trials (1006 catheters) and 8 cohort (16,370 catheters) studies met the inclusion criteria for this systematic review. Three thousand two hundred thirty catheters were placed in the subclavian vein, 10,958 in the internal jugular and 3,188 in the femoral vein for a total of 113,652 catheter days. The average catheter-related bloodstream infections density was 2.5 per 1,000 catheter days (range 0.6-7.2). There was no significant difference in the risk of catheter-related bloodstream infections between the femoral and subclavian/internal jugular sites in the two randomized controlled trials (i.e., no level 1A evidence). There was no significant difference in the risk of catheter-related bloodstream infections between the femoral and subclavian sites. The internal jugular site was associated with a significantly lower risk of catheter-related bloodstream infections compared to the femoral site (risk ratio 1.90; 95% confidence interval 1.21-2.97, p = .005, I = 35%). This difference was explained by two of the studies that were statistical outliers. When these two studies were removed from the analysis there was no significant difference in the risk of catheter-related bloodstream infections between the femoral and internal jugular sites (risk ratio 1.35; 95% confidence interval 0.84-2.19, p = 0.2, I = 0%). Meta-regression demonstrated a significant interaction between the risk of infection and the year of publication (p = .01), with the femoral site demonstrating a higher risk of infection in the earlier studies. There was no significant difference in the risk of catheter-related bloodstream infection between the subclavian and internal jugular sites. The risk of deep venous thrombosis was assessed in the two randomized controlled trials. A meta-analysis of this data demonstrates that there was no difference in the risk of deep venous thrombosis when the femoral site was compared to the subclavian and internal jugular sites combined. There was, however, significant heterogeneity between studies. CONCLUSIONS: : Although earlier studies showed a lower risk of catheter-related bloodstream infections when the internal jugular was compared to the femoral site, recent studies show no difference in the rate of catheter-related bloodstream infections between the three sites. [ABSTRACT FROM AUTHOR]

BACKGROUND:: Red blood cell (RBC) transfusions are common in intensive care unit, trauma, and surgical patients. However, the hematocrit that should be maintained in any particular patient because the risks of further transfusion of RBC outweigh the benefits remains unclear. OBJECTIVE:: A systematic review of the literature to determine the association between red blood cell transfusion, and morbidity and mortality in high-risk hospitalized patients. DATA SOURCES:: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. STUDY SELECTION:: Cohort studies that assessed the independent effect of RBC transfusion on patient outcomes. From 571 articles screened, 45 met inclusion criteria and were included for data extraction. DATA EXTRACTION:: Forty-five studies including 272,596 were identified (the outcomes from one study were reported in four separate publications). The outcome measures were mortality, infections, multiorgan dysfunction syndrome, and acute respiratory distress syndrome. The overall risks vs. benefits of RBC transfusion on patient outcome in each study was classified as (i) risks outweigh benefits, (ii) neutral risk, and (iii) benefits outweigh risks. The odds ratio and 95% confidence interval for each outcome measure was recorded if available. The pooled odds ratios were determined using meta-analytic techniques. DATA SYNTHESIS:: Forty-five observational studies with a median of 687 patients/study (range, 63-78,974) were analyzed. In 42 of the 45 studies the risks of RBC transfusion outweighed the benefits; the risk was neutral in two studies with the benefits outweighing the risks in a subgroup of a single study (elderly patients with an acute myocardial infarction and a hematocrit <30%). Seventeen of 18 studies, demonstrated that RBC transfusions were an independent predictor of death; the pooled odds ratio (12 studies) was 1.7 (95% confidence interval, 1.4-1.9). Twenty-two studies examined the association between RBC transfusion and nosocomial infection; in all these studies blood transfusion was an independent risk factor for infection. The pooled odds ratio (nine studies) for developing an infectious complication was 1.8 (95% confidence interval, 1.5-2.2). RBC transfusions similarly increased the risk of developing multi-organ dysfunction syndrome (three studies) and acute respiratory distress syndrome (six studies). The pooled odds ratio for developing acute respiratory distress syndrome was 2.5 (95% confidence interval, 1.6-3.3). CONCLUSIONS:: Despite the inherent limitations in the analysis of cohort studies, our analysis suggests that in adult, intensive care unit, trauma, and surgical patients, RBC transfusions are associated with increased morbidity and mortality and therefore, current transfusion practices may require reevaluation. The risks and benefits of RBC transfusion should be assessed in every patient before transfusion. [ABSTRACT FROM AUTHOR]

Objective: Adrenal failure is common in critically ill patients, particularly those with sepsis. As liver failure and sepsis are both associated with increased circulating levels of endotoxin and proinflammatory mediators and reduced levels of apoprotein-1/high-density lipoprotein, we postulated that adrenal failure may be common in patients with liver disease.Design: Clinical study.Setting: Liver transplant intensive care unit.Patients: The study cohort included 340 patients with liver disease.Interventions: Based on preliminary observational data, all patients admitted to our 28-bed liver transplant intensive care unit (LTICU) undergo adrenal function testing. An honest broker system was used to extract clinical, hemodynamic, medication, and laboratory data on patients admitted to the LTICU from March 2002 to March 2004. A random (stress) cortisol level <20 microg/dL in a highly stressed patient (respiratory failure, hypotension) was used to diagnose adrenal insufficiency. In all other patients, a random cortisol level <15 microg/dL or a 30-min level <20 microg/dL post-low-dose (1 microg) cosyntropin was considered diagnostic of adrenal insufficiency. Patients were grouped as follows: a) chronic liver failure; b) fulminant hepatic failure; c) patients immediately status post-orthotopic liver transplantation receiving a steroid-free protocol of immunosuppression; and d) patients status post-remote liver transplant (>/=6 months). The decision to treat patients with stress doses of hydrocortisone was at the discretion of the treating intensivist and transplant surgeon.Measurements and Main Results: Two-hundred and forty-five (72%) patients met our criteria for adrenal insufficiency (the hepatoadrenal syndrome). Eight (33%) patients with fulminant hepatic failure, 97 (66%) patients with chronic liver disease, 31(61%) patients with a remote history of liver transplantation, and 109 (92%) patients who had undergone liver transplantation under steroid-free immunosuppression were diagnosed with adrenal insufficiency. The high-density lipoprotein level at the time of adrenal testing was the only variable predictive of adrenal insufficiency (p < .0001). In vasopressor-dependent patients with adrenal insufficiency, treatment with hydrocortisone was associated with a significant reduction (p = .02) in the dose of norepinephrine at 24 hrs, whereas the dose of norepinephrine was significantly higher (p = .04) in those patients with adrenal failure not treated with hydrocortisone. In vasopressor-dependent patients without adrenal insufficiency, treatment with hydrocortisone did not affect vasopressor dose at 24 hrs. One hundred and forty-one patients (26.4%) died during their hospitalization. The baseline serum cortisol was 18.8 +/- 16.2 microg/dL in the nonsurvivors compared with 13.0 +/- 11.8 microg/dL in the survivors (p < .001). Of those patients with adrenal failure who were treated with glucocorticoids, the mortality rate was 26% compared with 46% (p = .002) in those who were not treated. In those patients receiving vasopressor agents at the time of adrenal testing, the baseline cortisol was 10.0 +/- 4.8 microg/dL in those with adrenal insufficiency compared with 35.6 +/- 21.2 microg/dL in those with normal adrenal function. Vasopressor-dependent patients who did not have adrenal failure had a mortality rate of 75%.Conclusions: Patients with liver failure and patients post-liver transplantation have an exceedingly high incidence of adrenal failure, which may be pathophysiologically related to low levels of high-density lipoprotein. Treatment of patients with adrenal failure may improve outcome. High baseline serum cortisol levels may be a maker of disease severity and portend a poor prognosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To review the effect of an aging society on the utilization of critical care services and the physiology of aging as it applies to critical illness and prognosis and management issues in the intensive care unit (ICU). DATA SOURCE:: MEDLINE, Embase, and citation review of relevant primary and review articles. DATA SYNTHESIS:: Elderly patients (age of >65 yrs) currently account for 42-52% of ICU admissions and for almost 60% of all ICU days. Aging is associated with decreased cardiopulmonary and renal reserve and with a high rate of co-morbidities, increasing the risks of the elderly developing progressive organ failure. Elderly ICU patients are at a particularly high risk of developing delirium, which is associated with significant morbidity. Severity of illness and age are the important factors determining ICU survival. Age and functional status before ICU admission are the major determinants of survival at 6 and 12 months after ICU discharge. Age alone should not be used to triage ICU patients; the decision to admit an elderly patient to an ICU should be based on the patients co-morbidities, acuity of illness, prehospital functional status, and preferences with regard to life-sustaining treatment. CONCLUSIONS:: The management of critically ill elderly patients is a complex issue and involves an understanding of the changing demographics of our society and the physiology of aging. The reality of our aging society dictates that we must focus on how to best care for the elderly who develop critical illness. [ABSTRACT FROM AUTHOR]

Background: After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials., Areas of Uncertainty: The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses., Data Sources: Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns., Therapeutic Advances: A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large "natural experiments" occurred in regions that initiated "ivermectin distribution" campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns., Conclusions: Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Shock, best defined as acute circulatory failure is classified into four major groups, namely hypovolemic, cardiogenic, obstructive, and distributive (vasodilatory). The purpose of this review is to provide a practical approach to fluid optimization in patients with the four types of shock., Recent Findings: Large-volume fluid resuscitation has traditionally been regarded as the cornerstone of resuscitation of shocked patients. However, in many instances, aggressive fluid resuscitation may be harmful, increasing morbidity and mortality., Summary: We believe that the approach to fluid therapy must be individualized based on the cause of shock as well as the patient's major diagnosis, comorbidities and hemodynamic and respiratory status. A conservative, physiologically guided approach to fluid resuscitation likely improves patient outcomes.

Objective: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI)., Participants: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine., Data Sources: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews., Results: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity., Conclusions: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.

Objective: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients., Participants: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine., Design/methods: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members., Results: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 μg/dL) after cosyntropin (250 μg) administration and a random plasma cortisol of < 10 μg/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence)., Conclusions: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Objective: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites., Methods: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the "levels" of quality of evidence into high (A), moderate (B), or low (C) and to determine the "strength" of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six "grades" of recommendations (1A-1B-1C-2A-2B-2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias., Results: Forty-five statements were considered. Among these statements, six did not achieve agreement based on RAND appropriateness method rules (majority of at least 70%). Fifteen statements were approved as conditional recommendations (strength class 2). The rest (24 statements) were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence and the required level of echo expertise of the intensivist. Key recommendations, listed by category, included the use of cardiac ultrasonography to assess preload responsiveness in mechanically ventilated (1B) patients, left ventricular (LV) systolic (1C) and diastolic (2C) function, acute cor pulmonale (ACP) (1C), pulmonary hypertension (1B), symptomatic pulmonary embolism (PE) (1C), right ventricular (RV) infarct (1C), the efficacy of fluid resuscitation (1C) and inotropic therapy (2C), presence of RV dysfunction (2C) in septic shock, the reason for cardiac arrest to assist in cardiopulmonary resuscitation (1B-2C depending on rhythm), status in acute coronary syndromes (ACS) (1C), the presence of pericardial effusion (1C), cardiac tamponade (1B), valvular dysfunction (1C), endocarditis in native (2C) or mechanical valves (1B), great vessel disease and injury (2C), penetrating chest trauma (1C) and for use of contrast (1B-2C depending on indication). Finally, several recommendations were made regarding the use of bedside cardiac ultrasound in pediatric patients ranging from 1B for preload responsiveness to no recommendation for RV dysfunction., Conclusions: There was strong agreement among a large cohort of international experts regarding several class 1 recommendations for the use of bedside cardiac ultrasound, echocardiography, in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients and guiding appropriate integration of ultrasound into critical care practice.

Purpose of Review: Anorexia is a preserved evolutionally response that may be beneficial during acute illness. Yet current clinical practice guidelines recommend early and targeted enteral nutritional support. However, the optimal timing of the initiation of enteral nutrition and the caloric and protein requirements of critically ill patients is controversial., Recent Findings: Starvation promotes autophagy and this may play a key role in promoting host defenses and the immune response to intracellular pathogens. Because of the perceived benefits of early enteral nutrition and the lack of clinical equipoise, randomized controlled trials comparing short-term starvation to targeted normocaloric enteral nutrition have until recently not been performed. The results of the recently reported PYTHON trial (Pancreatitis, Very Early Compared with Selective Delayed Start of Enteral Feeding) dispel the notion that short-term starvation is harmful. Furthermore, six recent randomized controlled trials that compared trophic and permissive underfeeding to normocaloric goals, failed to demonstrate any outcome benefit from the more aggressive approach. In addition, recent evidence suggests that intermittent enteral nutation may be preferable to continuous tube feeding., Summary: Limiting nutrient intake during the first 48-72 h of acute illness may be beneficial; in those patients who are unable to resume an oral diet after this time period intermittent enteral nutrition targeting 20-25 cal/kg/day is recommended.

Objective: To establish evidence-based guidelines for the use of bedside ultrasound by intensivists and specialists in the ICU and equivalent care sites for diagnostic and therapeutic purposes for organs of the chest, abdomen, pelvis, neck, and extremities., Methods: The Grading of Recommendations, Assessment, Development and Evaluation system was used to determine the strength of recommendations as either strong or conditional/weak and to rank the "levels" of quality of evidence into high (A), moderate (B), or low (C) and thus generating six "grades" of recommendation (1A-1B-1C-2A-2B-2C). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for all questions with clinically relevant outcomes. RAND appropriateness method, incorporating modified Delphi technique, was used in steps of GRADE that required panel judgment and for those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. The process was conducted independent of industry funding., Results: Twenty-four statements regarding the use of ultrasound were considered-three did not achieve agreement and nine were approved as conditional recommendations (strength class 2). The remaining 12 statements were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence. Key strong recommendations included the use of ultrasonography for ruling-in pleural effusion and assisting its drainage, ascites drainage, ruling-in pneumothorax, central venous cannulation, particularly for internal jugular and femoral sites, and for diagnosis of deep venous thrombosis. Conditional recommendations were given to the use of ultrasound by the intensivist for diagnosis of acalculous cholecystitis, renal failure, and interstitial and parenchymal lung diseases. No recommendations were made regarding static (vs dynamic) ultrasound guidance of vascular access or the use of needle guide devices., Conclusions: There was strong agreement among a large cohort of international experts regarding several recommendations for the use of ultrasound in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients.

Objective: To study the effect of stress hyperlactatemia on the association between stress hyperglycemia and mortality., Design: Retrospective cross-sectional observation study., Setting: Three ICUs using arterial blood gases with simultaneous glucose and lactate measurements during ICU stay., Patients: Cohort of 7,925 consecutive critically ill patients., Interventions: None., Measurements and Main Results: We analyzed 152,349 simultaneous measurements of glucose and lactate. We performed multivariable analysis to study the association of different metrics of glucose and lactate with hospital mortality. On day 1, first (p = 0.013), highest (p = 0.001), mean (p = 0.019), and time-weighted mean (p = 0.010) glucose levels were associated with increased mortality. A similar, but stronger, association was seen for corresponding lactate metrics (p < 0.0001 for all). However, once glucose and lactate metrics were entered into the multivariable logistic regression model simultaneously, all measures of glycemia ceased to be significantly associated with hospital mortality regardless of the metrics being used (first, highest, mean, time-weighed; p > 0.05 for all), whereas all lactate metrics remained associated with mortality (p < 0.0001 for all). In patients with at least one episode of moderate hypoglycemia (glucose ≤ 3.9 mmol/L), glucose metrics were not associated with mortality when studied separately (p > 0.05 for all), whereas lactate was (p < 0.05 for all), but when incorporated into a model simultaneously, highest glucose on day 1 was associated with mortality (p< 0.05), but not other glucose metrics (p > 0.05), whereas all lactate metrics remained associated with mortality (p < 0.05 for all)., Conclusions: Stress hyperlactatemia modifies the relationship between hyperglycemia and mortality. There is no independent association between hyperglycemia and mortality once lactate levels are considered.

Background: Nutritional support is an essential component of the management of critically ill and injured ICU patients. Optimal provision of calories and protein has been demonstrated to reduce morbidity, mortally, and length of ICU and hospital stay. Yet, a large proportion of ICU patients receive inadequate nutrition., Objective: To provide an evidence-base assessment of factors leading to inadequate enteral nutrition support in critically ill patients., Data Source: Search of PubMed database and manual review of bibliographies from selected articles., Data Synthesis and Conclusions: A number of common myths and misconceptions appear to play a major role in limiting the provision of enteral nutrition in the critically ill. This article provides scientific data to debunk the most common myths and misconceptions related to enteral nutrition.

Objectives: Acute respiratory distress syndrome is characterized by diffuse alveolar damage and increased extravascular lung water levels. However, there is no threshold extravascular lung water level that can indicate diffuse alveolar damage in lungs. We aimed to determine the threshold extravascular lung water level that discriminates between normal lungs and lungs affected with diffuse alveolar damage., Design: A retrospective analysis of normal lungs and lungs affected with diffuse alveolar damage was performed., Setting: Normal lung cases were taken from published data. Lung cases with diffuse alveolar damage were taken from a nationwide autopsy database. All cases of autopsy followed hospital deaths in Japan from more than 800 hospitals between 2004 and 2009; complete autopsies with histopathologic examinations were performed by board-certified pathologists authorized by the Japanese Society of Pathology., Patients: Normal lungs: 534; lungs with diffuse alveolar damage: 1,688., Interventions: We compared the postmortem weights of both lungs between the two groups. These lung weights were converted to extravascular lung water values using a validated equation. Finally, the extravascular lung water value that indicated diffuse alveolar damage was estimated using receiver operating characteristic analysis., Measurements and Main Results: The extravascular lung water values of the lungs showing diffuse alveolar damage were approximately two-fold higher than those of normal lungs (normal group, 7.3±2.8 mL/kg vs diffuse alveolar damage group 13.7±4.5 mL/kg; p<0.001). An extravascular lung water level of 9.8 mL/kg allowed the diagnosis of diffuse alveolar damage to be established with a sensitivity of 81.3% and a specificity of 81.2% (area under the curve, 0.90; 95% CI, 0.88-0.91). An extravascular lung water level of 14.6 mL/kg represented a 99% positive predictive value., Conclusions: This study may provide the first validated quantitative bedside diagnostic tool for diffuse alveolar damage. Extravascular lung water may allow the detection of diffuse alveolar damage and may support the clinical diagnosis of acute respiratory distress syndrome. The best extravascular lung water cut-off value to discriminate between normal lungs and lungs with diffuse alveolar damage is around 10 mL/kg.

Background: Despite a previous meta-analysis that concluded that central venous pressure should not be used to make clinical decisions regarding fluid management, central venous pressure continues to be recommended for this purpose., Aim: To perform an updated meta-analysis incorporating recent studies that investigated indices predictive of fluid responsiveness. A priori subgroup analysis was planned according to the location where the study was performed (ICU or operating room)., Data Sources: MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles., Study Selection: Clinical trials that reported the correlation coefficient or area under the receiver operating characteristic curve (AUC) between the central venous pressure and change in cardiac performance following an intervention that altered cardiac preload. From 191 articles screened, 43 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, and included healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20) patients., Data Extraction: Data were abstracted on study characteristics, patient population, baseline central venous pressure, the correlation coefficient, and/or the AUC between central venous pressure and change in stroke volume index/cardiac index and the percentage of fluid responders. Meta-analytic techniques were used to summarize the data., Data Synthesis: Overall 57% ± 13% of patients were fluid responders. The summary AUC was 0.56 (95% CI, 0.54-0.58) with no heterogenicity between studies. The summary AUC was 0.56 (95% CI, 0.52-0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54-0.58) for those done in the operating room. The summary correlation coefficient between the baseline central venous pressure and change in stroke volume index/cardiac index was 0.18 (95% CI, 0.1-0.25), being 0.28 (95% CI, 0.16-0.40) in the ICU patients, and 0.11 (95% CI, 0.02-0.21) in the operating room patients., Conclusions: There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.

Background: High sound pressure levels may be harmful to the maturing newborn. Current guidelines suggest that the sound pressure levels within a neonatal intensive care unit should not exceed 45 dB(A). It is likely that environmental noise as well as the noise generated by the incubator fan and respiratory equipment may contribute to the total sound pressure levels. Knowledge of the contribution of each component and source is important to develop effective strategies to reduce noise within the incubator., Aims: The objectives of this study were to determine the sound levels, sound spectra, and major sources of sound within a modern neonatal incubator (Giraffe Omnibed; GE Healthcare, Helsinki, Finland) using a sound simulation study to replicate the conditions of a preterm infant undergoing high-frequency jet ventilation (Life Pulse, Bunnell, UT)., Methods: Using advanced sound data acquisition and signal processing equipment, we measured and analyzed the sound level at a dummy infant's ear and at the head level outside the enclosure. The sound data time histories were digitally acquired and processed using a digital Fast Fourier Transform algorithm to provide spectra of the sound and cumulative sound pressure levels (dBA). The simulation was done with the incubator cooling fan and ventilator switched on or off. In addition, tests were carried out with the enclosure sides closed and hood down and then with the enclosure sides open and the hood up to determine the importance of interior incubator reverberance on the interior sound levels, Results: With all the equipment off and the hood down, the sound pressure levels were 53 dB(A) inside the incubator. The sound pressure levels increased to 68 dB(A) with all equipment switched on (approximately 10 times louder than recommended). The sound intensity was 6.0 × 10(-8) watts/m(2); this sound level is roughly comparable with that generated by a kitchen exhaust fan on high. Turning the ventilator off reduced the overall sound pressure levels to 64 dB(A) and the sound pressure levels in the low-frequency band of 0 to 100 Hz were reduced by 10 dB(A). The incubator fan generated tones at 200, 400, and 600 Hz that raised the sound level by approximately 2 dB(A)-3 dB(A). Opening the enclosure (with all equipment turned on) reduced the sound levels above 50 Hz by reducing the revereberance within the enclosure., Conclusion: The sound levels, especially at low frequencies, within a modern incubator may reach levels that are likely to be harmful to the developing newborn. Much of the noise is at low frequencies and thus difficult to reduce by conventional means. Therefore, advanced forms of noise control are needed to address this issue.

Purpose of Review: Systemic hypertension (HTN) is a common medical condition affecting over 1 billion people worldwide. One to two percent of patients with HTN develop acute elevations of blood pressure (hypertensive crises) that require medical treatment. However, only patients with true hypertensive emergencies require the immediate and controlled reduction of blood pressure with an intravenous antihypertensive agent., Recent Findings: Although the mortality from hypertensive emergencies has decreased, the prevalence and demographics of this disorder have not changed over the last 4 decades. Clinical experience and reported data suggest that patients with hypertensive urgencies are frequently inappropriately treated with intravenous antihypertensive agents, whereas patients with true hypertensive emergencies are overtreated with significant complications., Summary: Despite published guidelines, most patients with hypertensive crises are poorly managed with potentially severe outcomes.

Purpose of Review: Pulmonary aspiration syndromes are a common cause of morbidity and mortality. These syndromes are often misdiagnosed and their management is frequently suboptimal. This paper reviews the clinical features and management of the most common aspiration syndromes., Recent Findings: Pulmonary aspiration syndromes refer to a group of pulmonary diseases resulting from aspiration of foreign material into the lung. The type of syndrome depends on the quantity and nature of the aspirated material as well as its chronicity. The most common syndromes include aspiration pneumonia, diffuse aspiration bronchiolitis, and aspiration pneumonitis. Aspiration pneumonia and diffuse aspiration bronchiolitis generally occur in elderly, debilitated patients with dysphagia and usually present as 'community acquired pneumonia', which tends to be recurrent in patients with diffuse aspiration bronchiolitis. Treatment consists of broad-spectrum antibiotics and management of the underlying dysphagia. Aspiration pneumonitis follows the aspiration of gastric contents, usually in patients with a marked decreased level of consciousness. Treatment of aspiration pneumonitis is essentially supportive; however, corticosteroids and other immunomodulating agents may have a role in these patients., Summary: Aspiration syndromes are common with their management dictated by the type of aspiration syndrome.