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Purpose: To investigate the effect of prolonged glucocorticoid treatment for patients with acute respiratory distress syndrome (ARDS)., Methods: We conducted two sets of intention-to-treat analyses: (1) a primary analysis of individual patients' data (IPD) of four randomized controlled trials (RCTs) which investigated methylprednisolone treatment (n = 322) and (2) a trial-level meta-analysis incorporating four additional RCTs which investigated hydrocortisone treatment in early ARDS (n = 297). We standardized definitions to derive outcomes in all datasets. The primary outcome for the IPD analysis was time to achieving unassisted breathing (UAB) by study day 28. Secondary outcomes included mechanical ventilation (MV) and intensive care unit (ICU)-free days, hospital mortality, and time to hospital mortality by day 28., Results: By study day 28, compared to the placebo group, the methylprednisolone group had fewer patients who died before achieving UAB (12 vs. 29 %; p < 0.001) and more patients who achieved UAB (80 vs. 50 %; p < 0.001). In the methylprednisolone group, time to achieving UAB was shorter [hazard ratio 2.59, 95 % confidence interval (CI) 1.95-3.43; p < 0.001], and hospital mortality was decreased (20 vs. 33 %; p = 0.006), leading to increased MV (13.3 ± 11.8 vs. 7.6 ± 5.7; p < 0.001) and ICU-free days (10.8 ± 0.71 vs. 6.4 ± 0.85; p < 0.001). In those patients randomized before day 14 of ARDS onset, the trial-level meta-analysis indicated decreased hospital mortality (36 vs. 49 %; risk ratio 0.76, 95 % CI 0.59-0.98, I (2) = 17 %, p = 0.035; moderate certainty). Treatment was not associated with increased risk for infections (risk ratio 0.77, 95 % CI 0.56-1.08, I (2) = 26 %; p = 0.13; moderate certainty)., Conclusions: Prolonged methylprednisolone treatment accelerates the resolution of ARDS, improving a broad spectrum of interrelated clinical outcomes and decreasing hospital mortality and healthcare utilization.

Introduction: Current clinical practice guidelines recommend providing ICU patients a daily caloric intake estimated to match 80-100 % of energy expenditure (normocaloric goals). However, recent clinical trials of intentional hypocaloric feeding question this approach., Methods: We performed a systematic review and meta-analysis to compare the outcomes of ICU patients randomized to intentional hypocaloric or normocaloric goals. We included randomized controlled trials that enrolled ICU patients and compared intentional hypocaloric with normocaloric nutritional goals. We included studies that evaluated both trophic feeding as well as permissive underfeeding. Data sources included MEDLINE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. The outcomes of interest included hospital acquired infection, hospital mortality, ICU length of stay (LOS) and ventilator-free days (VFDs)., Results: Six studies which enrolled 2517 patients met our inclusion criteria. The mean age and body mass index (BMI) across the studies were 53 ± 5 years and 29.1 ± 1.5 kg/m(2), respectively. Two studies compared normocaloric feeding (77% of goal) with trophic feeding (20% of goal), while four studies compared normocaloric feeding (72% of goal) with permissive underfeeding (49% of goal). Overall, there was no significant difference in the risk of infectious complications (OR 1.03; 95% CI 0.84-1.27, I(2) = 16%), hospital mortality (OR 0.91; 95% CI 0.75-1.11, I(2) = 8%) or ICU LOS (mean difference 0.05 days; 95% CI 1.33-1.44 days; I(2) = 37%) between groups. VFDs were reported in three studies with no significant difference between the normocaloric and intentional hypocaloric groups (data not pooled)., Conclusion: This meta-analysis demonstrated no difference in the risk of acquired infections, hospital mortality, ICU length of stay or ventilator-free days between patients receiving intentional hypocaloric as compared to normocaloric nutritional goals.

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: The worldwide prevalence of obesity has reached epidemic proportions. Obesity hypoventilation syndrome (OHS) is a common yet largely undiagnosed and mistreated condition that likely carries a high mortality. The aim of this study was to determine the clinical characteristics, hospital outcome, outcome following hospital discharge and predictors of death in a large cohort of patients hospitalized with OHS. OHS is an important condition as many patients with this syndrome are misdiagnosed and receive inappropriate treatment., Methods: We reviewed the electronic medical records of patients with unequivocal OHS admitted to a 525-bed tertiary-care teaching hospital over a 5-year period. Demographic and clinical data as well as hospital disposition were recorded. In order to determine the patients' post-discharge status, we linked our database to the database of death certificates of the State Registrar of Vital Records., Results: We identified 600 patients who met the inclusion criteria for this study. The patients' mean age was 58 ± 15 years with a mean body mass index of 48.2 ± 8.3 kg m -2 ; 64% were women. Thirty-seven percent had a history of diabetes and 43% had been misdiagnosed as having chronic obstructive pulmonary disease, while none had been previously diagnosed with OHS. The most common admission diagnoses were respiratory failure, heart failure and sepsis. Ninety (15%) patients died during the index hospitalization. The patients' age, S-creatinine, respiratory failure, sepsis and admission to the ICU were independent predictors of hospital mortality. The hospital survivors were followed for a mean of 1,174 ± 501 d (3.2 ± 1.3 years) from the index hospitalization. On follow-up, 98 of the 510 (19%) hospital survivors died, with an overall cumulative mortality of 31.3%. The patients' age, S-creatinine and admission to the ICU were independent predictors of post-hospital mortality., Conclusion: Obesity hypoventilation syndrome is a common disease that is frequently misdiagnosed and mistreated and carries a 3-year morality, which is significantly worse than that for most cancers combined. Considering the high mortality of this disease, all patients with a body mass index > 35 kg m -2 should be screened for OHS; those patients with both early and established OHS should be referred to a pulmonary and/or sleep specialist for evaluation for non-invasive positive pressure ventilation, to a dietician for dietary counseling and lifestyle modification and to a bariatric surgeon for evaluation for bariatric surgery.

Atrophy of skeletal muscle mass is an almost universal problem in survivors of critical illness and is associated with significant short- and long-term morbidity. Contrary to common practice, the provision of protein/amino acids as a continuous infusion significantly limits protein synthesis whereas intermittent feeding maximally stimulates skeletal muscle synthesis. Furthermore, whey-based protein (high in leucine) increases muscle synthesis compared to soy or casein-based protein. In addition to its adverse effects on skeletal muscle synthesis, continuous feeding is unphysiological and has adverse effects on glucose and lipid metabolism and gastrointestinal function. I propose that critically ill patients' be fed intermittently with a whey-based formula and that such an approach is likely to be associated with better glycemic control, less hepatic steatosis and greater preservation of muscle mass. This paper provides the scientific basis for my approach to intermittent feeding of critically ill patients.

Background: Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event., Objective: A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued., Data Sources: MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles., Study Selection: Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy., Data Extraction: Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent., Data Synthesis: Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm., Conclusions: VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences.

Elderly patients patients (older than 65 years) account for only 11% of the US population yet they account for 34% of health care expenditure. The disproportionate usage of health care costs by elderly patients is in striking contrast with that of other Western Nations. It is likely that these differences are largely due to variances in hospitalization and the use of high technology health care resources at the end of life. The United States has 8 times as many intensive care unit (ICU) beds per capita when compared to other Western Nations. In the United States, elderly patients currently account for 42% to 52% of ICU admissions and for almost 60% of all ICU days. A disproportionate number of these ICU days are spent by elderly patients before their death. In many instances, aggressive life supportive measures serve only to prolong the patient's death. Such treatment inflicts pain and suffering on the patient (with little prospects of gain) and incurs enormous financial costs to the health care system. We present the case of an 86-year-old female who spent almost 3 months in our ICU prior to her death. The fully allocated hospital costs for this patient were estimated to be US$254 945 (US$5100/d). With the increasing age of the population and the projected increased demand for ICU beds, we review the benefits and burdens of admitting elderly patients to the ICU., (© The Author(s) 2014.)

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.

The early initiation of enteral nutrition remains a fundamental component of the management of critically ill and injured patients in the intensive care unit. Trophic feeding is equivalent, if not superior, to full-dose feeding. Parenteral nutrition has no proved benefit over enteral nutrition, which is the preferred route of nutritional support in intensive care unit patients with a functional gastrointestinal tract. Continuous enteral and parental nutrition inhibits the release of important enterohormones. These changes are reversed with intermittent bolus feeding. Whey protein, which is high in leucine, has a greater effect on insulin release and protein synthesis than does a soy- or casein-based enteral formula., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A protocol for the quantitative resuscitation of severe sepsis and septic shock known as early goal-directed therapy (EGDT) was published in 2001. Despite serious limitations, this study became widely adopted around the world and formed the basis of the Surviving Sepsis Campaign 6 h resuscitation bundle. Subsequently, a large number of observational before-and-after studies were published which demonstrated that EGDT reduced mortality. However, during this time period, there has been a substantial reduction in the mortality from sepsis in many Western nations that appears unrelated to EGDT. Recently, the Protocolized Care for Early Septic Shock (ProCESS) and The Australasian Resuscitation in Sepsis Evaluation (ARISE) trials failed to demonstrate any outcome benefit from EGDT. These two large, multicenter, randomized controlled studies raise serious questions regarding the validity of the original EGDT study and the scientific rigor of the uncontrolled, largely retrospective before-after clinical studies. Furthermore, accruing data suggest an association between the amount of fluid administered in the first 72 h and the mortality of patients with severe sepsis. Patients in all arms of the ProCESS and ARISE trials received substantial and nearly equivalent amounts of fluid. It is proposed that a more conservative fluid strategy and the earlier use of norepinephrine in patients with septic shock may be associated with further improvements in the outcome of patients with sepsis., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Pneumonia is a common disease that carries a high mortality. Traditionally, pneumonia has been classified and treated according to the setting where the pneumonia develops, namely community-acquired pneumonia, health-care-associated pneumonia, and hospital-acquired pneumonia. This classification was based on the risk of a patient being infected with a hospital-acquired drug-resistant pathogen. A new treatment paradigm has been proposed based on the risk of the patient being infected with a community-acquired drug-resistant pathogen. The risk factors for infection with a community-acquired drug-resistant pathogen include (1) hospitalization for > 2 days during the previous 90 days, (2) antibiotic use during the previous 90 days, (3) nonambulatory status, (4) tube feeds, (5) immunocompromised status, (6) use of acid-suppressive therapy, (7) chronic hemodialysis during the preceding 30 days, (8) positive methicillin-resistant Staphylococcus aureus history within the previous 90 days, and (9) present hospitalization > 2 days. This article reviews this new treatment paradigm and other issues relevant to the diagnosis and management of pneumonia based on information from MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials.

Background: Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with sepsis will accumulate bodily fluids. The aim of this study was to systematically review the association between a positive fluid balance/fluid overload and outcomes in critically ill adults, and to determine whether interventions aimed at reducing fluid balance may be linked with improved outcomes., Methods: We searched MEDLINE, PubMed, EMBASE, Web of Science, The Cochrane Database, clinical trials registries, and bibliographies of included articles. Two authors independently reviewed citations and selected studies examining the association between fluid balance and outcomes or where the intervention was any strategy or protocol that attempted to obtain a negative or neutral cumulative fluid balance after the third day of intensive care compared to usual care. The primary outcomes of interest were the incidence of IAH and mortality., Results: Among all identified citations, one individual patient meta-analysis, 11 randomised controlled clinical trials, seven interventional studies, 24 observational studies, and four case series met the inclusion criteria. Altogether, 19,902 critically ill patients were studied. The cumulative fluid balance after one week of ICU stay was 4.4 L more positive in non-survivors compared to survivors. A restrictive fluid management strategy resulted in a less positive cumulative fluid balance of 5.6 L compared to controls after one week of ICU stay. A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001). Patients with intra-abdominal hypertension (IAH) had a more positive cumulative fluid balance of 3.4 L after one week of ICU stay. Interventions to decrease fluid balance resulted in a decrease in intra-abdominal pressure (IAP): an average total body fluid removal of 4.9 L resulted in a drop in IAP from 19.3 ± 9.1 mm Hg to 11.5 ± 3.9 mm Hg., Conclusions: A positive cumulative fluid balance is associated with IAH and worse outcomes. Interventions to limit the development of a positive cumulative fluid balance are associated with improved outcomes. In patients not transgressing spontaneously from the Ebb to Flow phases of shock, late conservative fluid management and late goal directed fluid removal (de-resuscitation) should be considered.

The early detection and treatment of sepsis are the most important factors in improving the outcome of patients with this condition. However, many patients admitted to hospital experience a long delay in the diagnosis of sepsis. Furthermore, it is not uncommon for febrile patients to be sent home from the Emergency Department or the physician's office with the diagnosis of 'flu' only to return hours or days later in overt septic shock. The early diagnosis of sepsis may be challenging as many of the signs and symptoms are non-specific. Clinical studies suggest that early diagnosis of sepsis requires a high index of suspicion and comprehensive clinical evaluation together with laboratory tests, including a complete blood count with differential, lactate and procalcitonin levels.

Contemporary data suggest that approximately 18% of patients undergoing surgery will develop a major postoperative complication, and 3% to 5% will die prior to hospital discharge. Patients who develop a postoperative complication are at an increased risk of long-term mortality. Multiple studies have shown that perioperative hemodynamic optimization reduces the risk of postoperative complications and death in elective noncardiac surgical patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The Acute Respiratory Distress Syndome (ARDS) Network low tidal volume (VT) trial paved the ground for mechanically ventilating ARDS patients with a VT of 6 mL/kg ideal body weight (IBW). Although there is no consensus that a low VT is advantageous in non-ARDS patients,it is accepted that high VT should be avoided. Because compliance rates with ventilator recommendations are 30%, there is a need for process improvement. We postulated that a computerized screen prompt that recommended VT based on height would improve compliance with low VT.During ventilator order entry, the computerized decision tool prompts the clinician and encourages ventilation of patients at 8 mL/kg IBW, and 6 mL/kg IBW for patients with ARDS., Methods: A retrospective review was performed on patients who required volume controlled mechanical ventilation over a 3-y period. Subjects were chosen randomly from the respiratory records of 6 different ICUs at a single tertiary care academic center. Half of the charts selected were before intervention of on-screen prompt, and the other half were after implementation of the computerized decision tool., Results: The initial set VT ranged from 6.26 to 13.45 mL/kg IBW, with a mean of 8.92 mL/kg. After implementation of the on-screen prompt, mean VT decreased by 0.84 mL/kg to 8.07 mL/kg (P= .001) with a lower range of 4.73-11.56 mL/kg IBW. We also noted a significant decrease in the number of subjects placed on an initial VT > 10 mL/kg IBW from 20% to 4% (P= .003)., Conclusions: A computerized clinical decision tool with the preferred initial VT settings based on the patients' sex and height is a safe and reliable way to increase low VT strategy compliance across multiple ICUs. Its limitations are similar to those shared by other computer-generated prompts.

Current teaching and guidelines suggest that aggressive fluid resuscitation is the best initial approach to the patient with hemodynamic instability. The source of this wisdom is difficult to discern, however, Early Goal Directed therapy (EGDT) as championed by Rivers et al. and the Surviving Sepsis Campaign Guidelines appears to have established this as the irrefutable truth. However, over the last decade it has become clear that aggressive fluid resuscitation leading to fluid overload is associated with increased morbidity and mortality across a diverse group of patients, including patients with severe sepsis as well as elective surgical and trauma patients and those with pancreatitis. Excessive fluid administration results in increased interstitial fluid in vital organs leading to impaired renal, hepatic and cardiac function. Increased extra-vascular lung water (EVLW) is particularly lethal, leading to iatrogenic salt water drowning. EGDT and the Surviving Sepsis Campaign Guidelines recommend targeting a central venous pressure (CVP) > 8 mmHg. A CVP > 8 mmHg has been demonstrated to decrease microcirculatory flow, as well as renal blood flow and is associated with an increased risk of renal failure and death. Normal saline (0.9% salt solution) as compared to balanced electrolyte solutions is associated with a greater risk of acute kidney injury and death. This paper reviews the adverse effects of large volume resuscitation, a high CVP and the excessive use of normal saline.

We report a case of a 77-year-old Asian man with a history significant for type II diabetes mellitus and chronic kidney disease who presented with abdominal pain, nausea, vomiting and a 20-pound weight loss of 3 weeks' duration. Further evaluation revealed an infected mycotic aneurysm and distal abdominal aortitis as a result of Salmonella. This case demonstrates an interesting case of aortitis and a successful therapeutic approach., (2014 BMJ Publishing Group Ltd.)

Sepsis is among the most common reasons for admission to ICUs throughout the world, and it is believed to be the third most common cause of death in the United States. The pathogenetic mechanism and physiologic changes associated with sepsis are exceedingly complex, but our understanding is evolving rapidly. The major pathophysiologic changes in patients with septic shock include vasoplegic shock (distributive shock), myocardial depression, altered microvascular flow, and a diffuse endothelial injury. These pathophysiologic changes play a central role in the management of sepsis. The early management of patients with severe sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains highly controversial. This review provides a practical and physiologic-based approach to the early management of sepsis and explores the controversies surrounding the management of this complex condition.

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.

Background: Few attempts have been made to evaluate the physiology of traditional Eastern health practices. The goal of this study was to evaluate the hemodynamic effects of the mysterious Buddhist practice of tumo. Tumo is a meditative practice that produces inner heat through the alleged cultivation of body energy-channels., Methods: This study was performed by members of an international expedition to the Himalayan Mountains in the Republic of India. The study was performed in an unpopulated outdoor mountainous area at an altitude of 16,400 ft with ambient temperatures between -10 and -15(°)C. Two (2) cohorts of subjects were studied: healthy non-yogi volunteers and tumo practitioners. All of the subjects were stripped down to their underclothes and exposed to the subzero atmospheric temperatures for 5 minutes. The volunteers were then passively rewarmed while the tumo practitioners performed tumo for up to 10 minutes. Blood pressure, heart rate, and stroke volume index (SVI) and cardiac index were measured noninvasively using a NICOM™ hemodynamic monitor, while carotid blood flow and biventricular performance were determined echocardiographically at each stage of the experiment. The total peripheral resistance index (TPRI), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion (TAPSE) were determined using standard formula., Results: Fourteen (14) subjects (six volunteers and eight tumo practitioners) completed the study. There was one female subject in each group. With cold exposure, the SVI and carotid blood flow decreased while the TPRI increased significantly in both groups. In the volunteer group, these changes retuned to baseline with rewarming. Following tumo, the cardiac index (4.8±0.6 versus 4.0±0.5 l/m(2); p<0.01), carotid blood flow (445±127 versus 325±100 mL/min/m(2), p<0.01), LVEF (68±5 versus 64±7%; p<0.05) and TAPSE (2.9±0.4 versus 2.4±0.5 cm; p<0.01) were significantly higher when compared with baseline, while the TPRI was significantly lower (1786±189 versus 2173±281; p<0.01)., Conclusions: Tumo was associated with a hyperdynamic vasodilated state with increased biventricular performance. We postulate that tumo results in a massive increase in sympathetic activity with activation of brown adipose tissue and marked heat production. The increased heat production may explain the paradoxical vasodilatation in tumo practitioners exposed to subzero temperatures.

The birth of the intermittent injectate-based conventional pulmonary artery catheter (fondly nicknamed PAC) was proudly announced in the New England Journal of Medicine in 1970 by his parents HJ Swan and William Ganz. PAC grew rapidly, reaching manhood in 1986 where, in the US, he was shown to influence the management of over 40% of all ICU patients. His reputation, however, was tarnished in 1996 when Connors and colleagues suggested that he harmed patients. This was followed by randomized controlled trials demonstrating he was of little use. Furthermore, reports surfaced suggesting that he was unreliable and inaccurate. It also became clear that he was poorly understood and misinterpreted. Pretty soon after that, a posse of rivals (bedside echocardiography, pulse contour technology) moved into the neighborhood and claimed they could assess cardiac output more easily, less invasively and no less reliably. To make matter worse, dynamic assessment of fluid responsiveness (pulse pressure variation, stroke volume variation and leg raising) made a mockery of his 'wedge' pressure. While a handful of die-hard followers continued to promote his mission, the last few years of his existence were spent as a castaway until his death in 2013. His cousin (the continuous cardiac output PAC) continues to eke a living mostly in cardiac surgery patients who need central access anyway. This paper reviews the rise and fall of the conventional PAC.

Isolated subclavian artery dissection is a very rare condition in the absence of trauma or procedures. A 36-year-old woman with a history significant for uncontrolled hypertension presented with a sudden onset of left shoulder and neck pain that woke the patient from sleep. A CT angiogram of the chest revealed a left subclavian artery dissection. The patient was admitted to the hospital for blood pressure control.

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.

Objective: The purpose of this study was to determine whether changes in PETCO2 and exhaled CO2 (VCO2) can predict fluid responsiveness after a preload challenge., Design: A retrospective review of prospectively recorded data., Setting: A medical intensive care unit of a university-affiliated tertiary care hospital., Participants: Mechanically ventilated patients undergoing a preload challenge., Interventions: In the authors' intensive care unit, fluid responsiveness is determined by a passive leg raising (PLR) maneuver and/or a 500-mL crystalloid challenge. An increase in the stroke volume index >10% as measured by a NICOM bioreactance cardiac output monitor (Cheetah Medical, Inc, Vancouver, WA) is used to determine fluid responsiveness. PETCO2 and volumetric capnography (VCO2) were monitored via a combined CO2 and flow sensor capnostat (Respironics NM3 Monitor; Philips Healthcare, Eindhoven, Netherlands). Patients were mechanically ventilated with tidal volumes controlled at 8 mL/kg, allowing for consistent minute ventilation., Measurements and Main Results: During the study period, 44 challenges (10 PLR and 34 fluid boluses) were performed on 34 patients. There were 24 (54%) positive "fluid" responses. PETCO2 increased by 5.9% ± 7.6% in the responders compared with 1.4% ± 4.4% in the nonresponders (p = 0.02). Similarly, VCO2 increased by 11.0% ± 8.6% in the responders compared with 0.8% ± 5.6% in the nonresponders (p = 0.001). The area under the receiver operating characteristic curve was 0.67 (95% confidence interval, 0.48-0.80) for PETCO2 and 0.79 (95% confidence interval, 0.63-0.89) for VCO2. PETCO2 and VCO2 were predictive of fluid responsiveness only in those patients without underlying lung disease. The stroke volume variation was 15.8 ± 3.7 in the responders compared with 13.6 ± 4.8 in the nonresponders (p = 0.15)., Conclusions: Dynamic changes in PETCO2 and VCO2 may be used as adjunctive indicators of fluid responsiveness in patients without underlying lung disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.