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This page displays a RSS news feed from the current issue of several trauma journals. All articles are displayed in alphabetical order by title. To view the abstract, click the title of any article. If you are a journal subscriber, you may enter your registration information to view the full text or download a pdf file of the article in the abstract window.
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Shock
[beta]-BLOCKERS IN SEPSIS: REEXAMINING THE EVIDENCE | | Sepsis remains the leading cause for noncardiac intensive care unit deaths in the United States. Despite recent advances in the treatment of this devastating condition, mortality and morbidity remain unacceptably high. Sepsis is characterized by a multitude of pathophysiological changes that include inflammation, metabolic derangements, hemodynamic alterations, and multiorgan dysfunction. Unfortunately, several studies of treatment modalities aimed at correcting one or more of the underlying derangements have led to disappointing results. New treatment modalities are needed. [beta]-Receptor blockers have long been used for a variety of conditions such as coronary artery disease, congestive heart failure, and arterial hypertension. Recent data suggest that [beta]-blocker effects on metabolism, glucose homeostasis, cytokine expression, and myocardial function may be beneficial in the setting of sepsis. Although treating a potentially hypotensive condition with a drug with antihypertensive properties may initially seem counterintuitive, the metabolic and immunomodulatory properties of [beta]-blockers may be of benefit. It is the purpose of this review to discuss the effects of [beta]-blockers on the following: (1) metabolism, (2) glucose regulation, (3) the inflammatory response, (4) cardiac function, and (5) mortality in sepsis.
(C)2009The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
A history of resolving conflicts over end-of-life care in intensive care units in the United States * | | Objectives: To present a case of conflict over end-of-life care in the intensive care unit (ICU) and to describe how such conflicts have been resolved in the United States since the inception of ICUs.
Data Sources: A nonsystematically derived sample of published studies and professional and lay commentaries on end-of-life care, ethical principles, medical decision-making, medical futility, and especially conflict resolution in the ICU.
Study Selection: Some of those studies and commentaries dealing specifically with conflicts over end-of-life care in the ICU and their resolution.
Data Synthesis: An historical review of conflict resolution over end-of-life issues in U.S. ICUs.
Results and Conclusions: Conflict at the end of life in ICUs in the United States is relatively rare because most families and physicians agree about how patients should be treated. Nevertheless, conflict still exists over some patients whose families insist on care that physicians consider inappropriate and hence inadvisable, and over other patients whose families object to care that physicians prefer to provide. When such conflict occurs, mediation between families and physicians is usually successful in resolving it. Consultation from ethics committees also may be helpful in achieving resolution, and one state actually allows such committees to adjudicate disputes. Physicians who act unilaterally against family wishes run the risk of malpractice suits, although such suits usually are unsuccessful because the physicians are not shown to have violated standards of care.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
A low-fidelity simulation curriculum addresses needs identified by faculty and improves the comfort level of senior internal medicine resident physicians with inhospital resuscitation * | | Objective: The purpose of this study was to describe the essential elements of in hospital resuscitation knowledge and skills for senior internal medicine resident physicians and to evaluate a low-fidelity simulation course that incorporates these elements.
Design: In part 1, attending physicians were electronically surveyed using a modified Dillman method. A broad list of knowledge skills sets was gathered from recent resuscitation guidelines. In part 2, a 2-day, low-fidelity simulation, case-based curriculum was designed based on the results of part 1. Course participants were surveyed 1 month before and 1 month after the course.
Setting: Four academic teaching hospitals.
Participants: Attending physicians in cardiology, critical care, and internal medicine responded to the needs assessment survey. A convenience sample of internal medicine residents responded to the surveys before and after the course.
Measurements: Respondents ranked items on a 6-point Likert scale for all surveys. Responses were collated using descriptive statistics. This study met the requirements of the Research Ethics Board.
Main Results: In part 1, the response rate was 75% (n = 93), with the majority (52%) of respondents being internal medicine attending physicians. The top five knowledge sets were cardiac rhythm assessment, discussion of code status, delivery of bad news, management of wide complex tachycardia, and management of bradycardia. The top five skills were defibrillation, airway assessment, bag-mask ventilation, central venous access, and cardioversion. In part 2, the response rate was 93% (n = 27) before and 85% (n = 23) after course. Only 28% of residents felt prepared to lead resuscitations before the course. After the course, 45% of participants reporting using the knowledge and skills during a resuscitation. Significant changes in median confidence scores before to after the course occurred in important domains.
Conclusions: The results of the needs assessment should be used to tailor resuscitation education for residents. An educational need exists for resident physicians. This low-fidelity simulation course improves self-reported confidence in resuscitation knowledge and skills.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
A Major Metropolitan "Field Amputation" Team: A Call to Arms ... and Legs | | Background: As early as 1979, suggestions were made to establish amputation teams and protocols in major metropolitan areas. It was recognized that preplanning on such calls would be valuable to carrying out rescues of that nature. Since then, questionnaires and collegial conversations reveal the existence of such teams remains the exception in our nation's cities.
Methods: Our team was formed in 1984 after an emergency medical service request for a surgeon to perform an amputation on a person who had become entrapped with both arms in an industrial candy press was made. In its current form, the team consists of an attending trauma surgeon, a resident surgeon, a registered nurse, and a pilot, all hospital based. Equipment is limited to medications for sedation and pain control, two units of uncross-matched blood, and a prebundled duffle bag of bandages, a scalpel, various saws, and hemostats. Transportation to the scene is provided by the helicopter based at our level II trauma center.
Results: Since its inception, the team has been activated three to four times per year, resulting in nine amputation rescues. Three of these cases, presented here, are from an unusually busy 5 weeks during the spring of 2008. The first case involves a tree shredding device, the second, an industrial auger, and the third, a forklift and a steel toed boot. In these cases, the utilization of the amputation team resulted in successful patient rescues and outcomes.
Conclusion: A field amputation team can be an integral part of any emergency medical service system, filling an infrequently used but helpful adjunct to emergency care.
(C) 2009 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
A Modified Goal-Directed Protocol Improves Clinical Outcomes in Intensive Care Unit Patients With Septic Shock: A Randomized Controlled Trial | | We evaluated whether a goal-directed protocol, without measurement of central venous oxygen saturation, would improve survival in medical intensive care unit (ICU) patients with septic shock. This is a prospective, controlled study in a 24-bed medical ICU at a tertiary care hospital. From a total of 241 consecutive patients with septic shock, 224 were randomly assigned to receive therapy with or without a written protocol using central venous pressure, mean arterial pressure, and urine output as therapeutic goals. Baseline characteristics were similar between groups. Implementation of goal-directed therapy caused a more rapid reversal of persistent shock (47 +/- 22.8 vs. 65.4 +/- 32.1 h, P = 0.006) and decreases of ICU (50% vs. 67.2%, P = 0.009) and in-hospital (53.7% vs. 71.6%, P = 0.006) mortality rates compared with non-goal-directed therapy. Patients receiving goal-directed therapy also had less risk for developing central nervous system or renal failure than patients without. Patients with goal-directed therapy received more fluid during the period of persistent shock (136.2 +/- 119 vs. 88.6 +/- 57.7 mL h-1, P = 0.034) and less delay in vasopressor administration (78 +/- 22.2 vs. 104.4 +/- 29 min, P = 0.001) than patients with non-goal therapy. Implementation of a goal-directed protocol improves survival and clinical outcomes in ICU patients with septic shock. These benefits may arise from adequate fluid resuscitation, earlier vasopressor administration, rapid shock reversal, and protection of major organ function. With central venous oxygen saturation measurement to detect tissue perfusion, the clinical outcomes may be further improved.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
A Multidisciplinary Overview of Cardiogenic Shock | | Cardiogenic shock complicating acute myocardial infarction (AMI) is reviewed from multidisciplinary viewpoints encompassing both basic and clinical aspects. Insights into the absolute obligate aerobic nature of the heart which possesses neither facultative capability nor functional collateral channels, together with O2 diffusion gradients, mitochondrial O2 sensing and anaerobic ATP deficiencies, are described in some detail. Myocardial adaptive responses against energy crisis, termed the Pasteur Effect, and hypoxia inducible factor (HIF)-1[alpha] are implicated for cardiomyocyte viability. Oncosis and/or lysosomal autophagy cause such overwhelming numbers (several billions) of cardiomyocyte death, virtually simultaneously following coronary thrombotic occlusion. Apoptosis is briefly described and cardiogenic shock is discussed in terms of the diagnostic criteria by MIRU, unique hemodynamic manifestations, infarct sizes and border zone extension, and potentially jeopardized myocardium in the remote areas. Reperfusion injury, i.e., reactive oxygen species (ROS), is noted as a double-edged sword. The importance of early revascularization by means of PCI, CABG, and IABP support is emphasized according to current guidelines. For innovative promise in the future, de novo development of collateral channels by growth factors and trials of stem cell implantation aimed at myocardial regeneration are introduced.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis * | | Objective: To evaluate whether TAK-242, a small-molecule inhibitor of Toll-like receptor-4-mediated signaling, suppresses cytokine levels and improves 28-day all-cause mortality rates in patients with severe sepsis.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: A total of 93 intensive care units worldwide.
Patients: A total of 274 patients with severe sepsis and shock or respiratory failure.
Interventions: Patients were randomly assigned to receive a 30-min loading dose followed by 96-hr infusions of placebo, TAK-242 1.2 mg/kg/day, or TAK-242 2.4 mg/kg/day.
Measurements and Main Results: The primary pharmacodynamic end point was change in serum interleukin-6 levels relative to baseline, with 28-day all-cause mortality rate the primary clinical end point. The trial was terminated because of a lack of effect of TAK-242 in suppressing serum interleukin-6 levels. A total of 274 subjects were randomly assigned and treated. Clinical parameters at baseline were balanced across the three groups. TAK-242 did not suppress interleukin-6 as measured by 0- to 96.5-hr area under the interleukin-6 concentration curve at either dose. Specifically, the area under the effect curve increased by 9% and 26.9% in the TAK-242 1.2 and 2.4 mg/kg/day groups, respectively, which was not statistically different from placebo (p = .63 and .15, respectively). The 28-day mortality rate was 24% in the placebo, 22% in the low-dose, and 17% in the high-dose group (p = .26 for placebo vs. high dose). A nonsignificant reduction in mortality rate was observed in a subset of patients with both shock and respiratory failure (placebo [n = 51], 33%, vs. high dose [n = 52], 19%, p = .10). Transient, dose-related increases in methemoglobin levels were observed with TAK-242 treatment in 30.1% of the patients.
Conclusions: TAK-242 failed to suppress cytokine levels in patients with sepsis and shock or respiratory failure. Treatment with TAK-242 resulted in mild increases in serum methemoglobin levels but was otherwise well tolerated. Although observed mortality rates in patients with both shock and respiratory failure were lower with the 2.4 mg/kg/day dose, differences were not significant.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: A meta-analytic/meta-regression study | | Objective: To assess whether a potential benefit with combination antibiotic therapy is restricted to the most critically ill subset of patients, particularly those with septic shock.
Data Sources: OVID MEDLINE (1950-October 2009), EMBASE (1980-October 2009), the Cochrane Central Register of Controlled Trials (to third quarter 2009), the ClinicalTrial.gov database, and the SCOPUS database.
Study Selection: Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria.
Data Extraction: Study design, mortality/clinical response, and other variables were extracted independently by two reviewers. When possible, study datasets were split into mutually exclusive groups with and without shock or critical illness.
Data Synthesis: Although a pooled odds ratio indicated no overall mortality/clinical response benefit with combination therapy (odds ratio, 0.856; 95% confidence interval, 0.71-1.03; p = .0943; I2 = 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death >25%; odds ratio of death, 0.51; 95% confidence interval, 0.41-0.64; I2 = 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35-0.70; p < .0001; I2 = 0%). An increased risk of death was found in low-risk patients (risk of death <=15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16-2.03; p = .003; I2 = 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group.
Conclusion: Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury | | Objectives: Acute kidney injury occurs frequently after cardiac or major vascular surgery and is believed to be predominantly a consequence of impaired renal oxygenation. However, in patients with acute kidney injury, data on renal oxygen consumption (RVO2), renal blood flow, glomerular filtration, and renal oxygenation, i.e., the renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies.
Design: Prospective, two-group comparative study.
Setting: Cardiothoracic intensive care unit of a tertiary center.
Patients: Postcardiac surgery patients with (n = 12) and without (n = 37) acute kidney injury were compared with respect to renal blood flow, glomerular filtration, RVO2, and renal oxygenation.
Interventions: None
Measurements and Main Results: Data on systemic hemodynamics (pulmonary artery catheter) and renal variables were obtained during two 30-min periods. Renal blood flow was measured using two independent techniques: the renal vein thermodilution technique and the infusion clearance of paraaminohippuric acid, corrected for renal extraction of paraaminohippuric acid. The filtration fraction was measured by the renal extraction of 51Cr-EDTA and the renal sodium resorption was measured as the difference between filtered and excreted sodium. Renal oxygenation was estimated from the renal oxygen extraction. Cardiac index and mean arterial pressure did not differ between the two groups. In the acute kidney injury group, glomerular filtration (-57%), renal blood flow (-40%), filtration fraction (-26%), and sodium resorption (-59%) were lower, renal vascular resistance (52%) and renal oxygen extraction (68%) were higher, whereas there was no difference in renal oxygen consumption between groups. Renal oxygen consumption for one unit of reabsorbed sodium was 2.4 times higher in acute kidney injury.
Conclusions: Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
An Extract of the Mushroom Agaricus Blazei Murill Protects Against Lethal Septicemia in A Mouse Model of Fecal Peritonitis | | Bacterial septicemia is frequently occurring during gastroenterological surgery. Because of increasing problems in hospitals with bacteria developing multiresistance against antibiotics, prophylactic treatment using immunomodulators is interesting. We have examined the putatively anti-infective immunomodulatory action of the edible mushroom, Agaricus blazei Murill (AbM), in an experimental peritonitis model in BALB/c mice. The mice were orally given an extract of AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various concentrations of feces from the mice. The state of septicemia, as measured by the number of colony-forming units of bacteria in blood, and the survival rate of the animals were compared between the groups. Mice that were orally treated with AbM extract before bacterial challenge showed significantly lower levels of septicemia and improved survival rates. Our findings suggest that the AbM extract, when given prophylactically, may improve health. Further studies are needed on humans when considering whether AbM could be used as an alternative treatment modality for patients at risk of contracting serious bacterial peritonitis.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
An Initiative by Midlevel Providers to Conduct Tertiary Surveys at a Level I Trauma Center | | Introduction: Increased patient volume and residents' work hour restrictions have escalated the workload at trauma centers. Because tertiary surveys (TSs) are integral to care, midlevel providers (MLPs) can help streamline this time-consuming process. In this study, we implemented a care plan in which MLPs conduct all TSs, initiate appropriate consultations, and offload residents' work hours.
Methods: From January 2007 to December 2008, we conducted a prospective evaluation of an initiative in which MLPs performed all TSs within 48 hours of admission. A TS consisted of a complete history and physical examination, follow-up of radiologic interpretations, and appropriate consultations. Data included patient demographics, incidence of additional diagnoses noted during TSs and reduction in residents' work hours. Data are presented as mean +/- standard error.
Results: During the 2-year period, there were 5,143 patients admitted to the trauma service. The mean age was 36 years +/- 4.8 years, and mean Injury Severity Score (ISS) was 14.2 +/- 4.2. Overall mortality was 5%. Blunt mechanisms accounted for 85%, and penetrating mechanisms resulted in 14% of injuries. MLPs conducted TSs in 56% of patients during the first year and 76% in the second year. In 80 patients (mean age of 44 years +/- 7.1 years, mean Injury Severity Score 21.7 +/- 2.8; p < 0.05 vs. entire cohort), TSs revealed additional injuries, for an incidence of 1.5%. The majority of these diagnoses were of "minor" fractures, half requiring consultations, and 9% necessitating operative intervention. Residents' workload was reduced by 1,802 hours.
Conclusions: Implementation of a MLP initiative to conduct TSs in trauma patients can achieve a consistent and comprehensive workup while offsetting residents' workload and helping to ensure compliance with the 80-hour resident work policy.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Animal Models for Trauma Research: What Are the Options? | | Even if trauma patients initially avoid death after trauma (due to massive blood volume loss, primary severe brain injury), they are still at risk for multiple organ failure. Thus, it is crucial to elucidate the underlying pathophysiological mechanisms of trauma/hemorrhagic shock and the immune response involved. As of now, many hemorrhagic shock/trauma studies have used various types of animal models. Despite a large number of results from these efforts, some authors have argued that animal model results are difficult to translate directly into the clinical scenario. This review summarizes the advantages and the disadvantages of using animal models in trauma/hemorrhagic shock studies and discusses the relevance of various animal studies to the clinical scenario.
(C)2009The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Assessing Intravascular Volume By Difference in Pulse Pressure in Pigs Submitted To Graded Hemorrhage | | We assessed changes in intravascular volume monitored by difference in pulse pressure (dPP%) after stepwise hemorrhage in an experimental pig model. Six pigs (23-25 kg) were anesthetized (isoflurane 1.5 vol%) and mechanically ventilated to keep end-tidal CO2 (etCO2) at 35 mmHg. A PA-catheter and an arterial catheter were placed via femoral access. During and after surgery, animals received lactated Ringer's solution as long as they were considered volume responders (dPP > 13%). Then animals were allowed to stabilize from the induction of anesthesia and insertion of catheters for 30 min. After stabilization, baseline measurements were taken. Five percent of blood volume was withdrawn, followed by another 5%, and then in 10%-increments until death from exsanguination occurred. After withdrawal of 5% of blood volume, all pigs were considered volume responders (dPP > 13%); dPP rose significantly from 6.1 +/- 3.3% to 19.4 +/- 4.2%. The regression analysis of stepwise hemorrhage revealed a linear relation between blood loss (hemorrhage in %) and dPP (y = 0.99* x + 14; R2 = 0.7764; P < .0001). In addition, dPP was the only parameter that changed significantly between baseline and a blood loss of 5% (P < 0.01), whereas cardiac output, stroke volume, heart rate, MAP, central venous pressure, pulmonary artery occlusion pressure, and systemic vascular resistance, respectively, remained unchanged. We conclude that in an experimental hypovolemic pig model, dPP correlates well with blood loss.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Biomarkers of Acute Renal Injury and Renal Failure | | Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes ([alpha]- and [pi]-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, [gamma]-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins ([alpha]1- and [beta]2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Clinical research ethics for critically ill patients: A pandemic proposal | | Pandemic H1N1 influenza is projected to be unprecedented in its scope, causing acute critical illness among thousands of young otherwise healthy adults, who will need advanced life support. Rigorous, relevant, timely, and ethical clinical and health services research is crucial to improve their care and outcomes. Studies designed and conducted during a pandemic should be held to the same high methodologic and implementation standards as during other times. However, unique challenges arise with the need to conduct investigations as efficiently as possible, focused on the optimal outcome for the individual patient, while balancing the need for maximal societal benefit. We believe that clinical critical care research during a pandemic must be approached differently from research undertaken under nonemergent circumstances. We propose recommendations to clinical investigators and research ethics committees regarding clinical and health services research on pandemic-related critical illness. We also propose strategies such as expedited and centralized research ethics committee reviews and alternate consent models.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Complications of seasonal and pandemic influenza | | Influenza is a seasonal viral infection associated with significant morbidity and mortality. In 2009, a novel H1N1 influenza A virus emerged and has been classified as a pandemic. In contrast to seasonal influenza, severe disease from pandemic H1N1 seems concentrated in older children and young adults, with almost no cases reported in patients older than 60 yrs. Although patients with underlying cardiopulmonary disease remain at risk, most complications have occurred among previously healthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation. Secondary bacterial infection is more common in children. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate. Treatment of pneumonia should include empirical coverage for this pathogen. Neuromuscular and cardiac complications are unusual but may occur.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
Copeptin, A Stable Peptide of the Arginine Vasopressin Precursor, Is Elevated in Hemorrhagic and Septic Shock | | Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable assay for the measurement of AVP release can also prove useful for the assessment of fluid and osmosis status in various diseases.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Coupled Plasma Filtration Adsorption in Experimental Peritonitis-Induced Septic Shock | | The coupled plasma filtration adsorption (CPFA) was developed as an adsorptive hemopurification method aimed at nonselective removal of circulating soluble mediators potentially involved in the pathogenesis of sepsis. We hypothesized that this nonselective hemopurification could protect from detrimental consequences of long-term, volume-resuscitated porcine septic shock. In 16 anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneally inoculating feces and maintained for 22 h with fluid resuscitation and norepinephrine infusion as needed to maintain MAP above 65 mmHg. After 12 h of peritonitis, animals were randomized to receive either supportive treatment (control, n = 8) or CPFA treatment (CPFA, n = 8). Systemic, hepatosplanchnic, and renal hemodynamics; oxygen exchange; energy metabolism (lactate/pyruvate and ketone body ratios); ileal mucosal and renal cortex microcirculation; systemic inflammation (TNF-[alpha], IL-6); nitrosative/oxidative stress (thiobarbituric acid reactive species, nitrates + nitrites); and endothelial/coagulation dysfunction (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin complexes, platelet count) were assessed before and 12, 18, and 22 h of peritonitis. Coupled plasma filtration adsorption neither delayed the development of hypotension nor reduced the dose of norepinephrine. The treatment failed to attenuate sepsis-induced alterations in microcirculation, surrogate markers of cellular energetics, endothelial injury, and systemic inflammation. Similarly, CPFA did not protect from lung and liver dysfunction and even aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress. In this porcine model of septic shock, the early treatment with CPFA was not capable of reversing the sepsis-induced disturbances in various biological pathways and organ systems. Both the efficacy and safety of this method require further rigorous experimental validation in clinically relevant models.
(C)2009The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Cranioplasty After Postinjury Decompressive Craniectomy: Is Timing of the Essence? | | Background: The appropriate timing of cranioplasty after decompressive craniectomy for trauma is unknown. Potential benefits of delayed intervention (>6 weeks) for reducing the risk of infection must be balanced by persistent altered cerebrospinal fluid dynamics leading to hydrocephalus. We reviewed our recent 5-year experience in an effort to improve patient throughput and develop a rational decision making plan.
Methods: A 5-year query (2003-2007) of our level I neurotrauma database. From 2,400 head injuries, we performed a total of 350 craniotomies. Of the 350 patients who underwent craniotomy for trauma, 70 patients (20%) underwent decompressive craniectomy requiring cranioplasty. Timing of cranioplasty, cranioplasty material, postoperative infections, and incidence of hydrocephalus were evaluated with logistic regression to study potential associations between complications and timing, adjusted for risk factors.
Results: No specific time frame was predictive of hydrocephalus or infection, and logistic regression failed to identify significant predictors among the collected variables.
Conclusion: In our experience, the prior practice of delayed cranioplasty (3-6 months postdecompressive craniectomy), requiring repeat hospital admission, does not seem to lower postcranioplasty infection rates nor the need for cerebrospinal fluid diversion procedures. Our current practice emphasizes cranioplasty during the initial hospital admission, as soon as there is resolution on computed tomography scan of brain swelling outside of the cranial vault with concurrent clinical examination. This occurs as early as 2 weeks postcraniectomy and should lower the overall cost of care by eliminating the need for additional hospital admissions.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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J Trauma
Creation, Implementation, and Maturation of a Massive Transfusion Protocol for the Exsanguinating Trauma Patient | | The majority of trauma patients (>90%) do not require any blood product transfusion and their mortality is <1%. However, 3% to 5% of civilian trauma patients will receive a massive transfusion (MT), defined as >10 units of packed red blood cells (PRBC) in 24 hours. In addition, more than 25% of these patients will arrive to emergency departments with evidence of trauma-associated coagulopathy. With this combination of massive blood loss and coagulopathy, it has become increasingly more common to transfuse early the trauma patients and with a combination of PRBC, plasma, and platelets. Given the inherent uncertainties common early in the care of patients with severe injuries, the efficient administration of massive amounts of PRBC and clotting factors tends to work best in a predefined, protocol driven system. Our purpose here is to (1) define the problem of massive hemorrhage and coagulopathy in the trauma patient, (2) identify which group of patients this type of protocol should be applied, (3) describe the extensive coordination required to implement this multispecialty MT protocol, (4) explain in detail how the MT was developed and implemented, and (5) emphasize the need for a robust performance improvement or quality improvement process to monitor the implementation of such a protocol and to help identify problems and deliver feedback in a "real-time" fashion. The successful implementation of such a complex process can only be accomplished in a multispecialty setting. Input and representation from departments of Trauma, Critical Care, Anesthesiology, Transfusion Medicine, and Emergency Medicine are necessary to successfully formulate (and implement) such a protocol. Once a protocol has been agreed upon, education of the entire nursing and physician staff is equally essential to the success of this effort. Once implemented, this process may lead to improved clinical outcomes and decreased overall blood utilization with extremely small wastage of vital blood products.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Critical care trial design and interpretation: A primer | | Objective: Better understanding of the pathophysiology of critical illness has led to an increase in clinical trials designed to improve the clinical care and outcomes of patients with life-threatening illness. Knowledge of basic principles of clinical trial design and interpretation will assist the clinician in better applying the results of these studies into clinical practice.
Data Sources: We review selected clinical trials to highlight important design features that will improve understanding of the results of critical care clinical trials designed to improve clinical care of the critically ill.
Results: Trial design features such as patient selection, bias, sample size calculation, selection of subjects and controls, and primary outcome measure may influence the results of a critical care clinical trial designed to test a therapy targeting improved clinical care. In conjunction with trial design knowledge, understanding the size of the anticipated treatment effect, the importance of any clinical end point achieved, and whether patients in the trial are representative of typical patients with the illness will assist the reader in determining whether the results should be applied to specific patients or usual clinical practice.
Conclusions: Better understanding of important aspects of trial design and interpretation, such as whether patients enrolled in both intervention arms were comparable and whether the primary outcome of the trial is clinically important, will assist the bedside clinician in determining whether to apply the findings from the clinical study into clinical practice.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Delaware's Inclusive Trauma System: Impact on Mortality | | Background: The impact of implementing an inclusive state trauma system on injury-related mortality for patients with life-threatening injuries was assessed.
Methods: Using the state trauma registry, trauma patients evaluated in all of Delaware's acute care hospitals from 1998 to 2007 were identified. Patients were categorized by injury severity score (ISS) groups (1-9, 10-15, 16-24, and >24). Each category was analyzed by mortality and interfacility transfer rate to the Level I trauma center for each year. An analysis of the National Trauma Data Bank (NTDB) for these ISS groups and mortality was performed to provide a comparative benchmark. [chi]2 and analysis of variance were used where appropriate (p <= 0.05).
Results: A total of 40,063 entries were identified within the state trauma registry for the 10-year study period. Mortality rates did not significantly differ for ISS categories except for ISS >24 group. For this group, there was an incremental mortality decrease from 45.7% (1998) to 20.5% (2007) (p <= 0.0005). This rate of decrease in mortality was significantly greater than that displayed in the NTDB. The rate for the aggregate of all interfacility transfers and ISS >24 group managed at the Level I hospital significantly increased over the same period.
Conclusion: Since its inception, Delaware's trauma system, in which all acute care hospitals participate, has been associated with an incremental, significant decrease in mortality of the most critically injured patients. This decrease is more substantial than that experienced nationally as depicted within the NTDB. These findings and our evolving experience support the concept and benefits of an "inclusive" trauma system.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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J Trauma
Delay to Therapeutic Interventional Radiology Postinjury: Time Is of the Essence | | Objective: Hemorrhage remains a leading cause of early death in injured patients, and definitive control of bleeding remains a fundamental principle of trauma management. Therapeutic interventional radiology (IR) procedures have increasingly become essential in the acute management of traumatic injury. The importance of time to control of hemorrhage for therapeutic IR procedures has not been adequately characterized.
Methods: A retrospective analysis was performed by using data derived from the National Trauma Data Bank, version 7.1. Inclusion criteria included the following: adult, hypotensive patients, scene admission, patients who underwent early therapeutic IR vascular occlusive procedures within in 3 hours of admission at a level I or II designated trauma center (n = 1,748). Exclusion criteria included intracranial or venous occlusion procedures, patients who underwent any abdominal, thoracic, vascular, or intracranial operative procedures throughout their entire hospital stay. Logistic regression analysis was used to analyze the independent mortality risk associated with DELAY to IR procedures after controlling for important confounders.
Results: The majority of patients who died did so within the first 48 hours from injury (80%). Regression analysis revealed that DELAY to IR was independently associated with more than a twofold higher risk of mortality (odds ratio 2.7, 95% confidence interval 1.6-4.9, p < 0.001). For every hour delay, the risk of mortality increased by 47%. These findings were independent of injury mechanism and most pertinent to level I trauma centers.
Conclusion: In hemodynamically unstable trauma patients undergoing therapeutic catheter-based IR procedures, delay to IR was independently associated with more than a twofold higher risk of mortality. These results suggest that therapeutic IR procedures should be performed as expeditiously as possible and held to the same dogma as applied to definitive operative control of hemorrhage.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Delirium as a predictor of long-term cognitive impairment in survivors of critical illness | | Objective: To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation.
Design: Prospective cohort study.
Setting: Medical intensive care unit in a large community hospital in the United States.
Patients: Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessments 3 and 12 mos after discharge.
Measurements and Main Results: Of 126 eligible patients, 99 survived >=3 months after critical illness; long-term cognitive outcomes were obtained for 77 (78%) patients. Median age was 61 yrs, 51% were admitted with sepsis/acute respiratory distress syndrome, and median duration of delirium was 2 days. At 3-mo and 12-mo follow-up, 79% and 71% of survivors had cognitive impairment, respectively (with 62% and 36% being severely impaired). After adjusting for age, education, preexisting cognitive function, severity of illness, severe sepsis, and exposure to sedative medications in the intensive care unit, increasing duration of delirium was an independent predictor of worse cognitive performance-determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition-at 3-mo (p = .02) and 12-mo follow-up (p = .03). Duration of mechanical ventilation, alternatively, was not associated with long-term cognitive impairment (p = .20 and .58).
Conclusions: In this study of mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was independently associated with long-term cognitive impairment, a common public health problem among intensive care unit survivors. (Crit Care Med 2010; 38:1513-1520
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
Diagnostic Accuracy of Left Ventricular Function for Identifying Sepsis Among Emergency Department Patients With Nontraumatic Symptomatic Undifferentiated Hypotension | | : The hypothesis of this study states that in emergency department (ED) patients with nontraumatic symptomatic hypotension, the presence of hyperdynamic left ventricular function (LVF) is specific for sepsis as the etiology of shock. We performed a secondary analysis of patients with nontraumatic symptomatic hypotension enrolled in a randomized, clinical diagnostic trial. The study was done in an urban tertiary ED with a census over 100,000 visits per year. Inclusion criteria were nontrauma ED patients aged >17 years, initial vital signs consistent with shock (systolic blood pressure <100 mm Hg or shock index >1.0), and agreement of two independent observers for one sign and symptom of circulatory shock. All patients underwent focused ED echocardiography (echo) during initial resuscitation. Echos were reviewed post-hoc by a blinded physician and categorized by qualitative LVF as hyperdynamic (ejection fraction [EF] >55%), normal to moderate impairment (EF 30%-55%), and severe impairment (EF <30%). Main outcome was the criterion standard diagnosis of septic shock. Analyses include the diagnostic performance of LVF, Cohen's [kappa] for interobserver agreement of LVF, and logistic regression for independent predictors of sepsis. There were 103 echos that were adequate for analysis. The mean age was 57 +/- 16.7 years, 59% were male, and the mean initial systolic blood pressure was 83 +/- 11.3 mm Hg. A final diagnosis of septic shock was made in 38% (39/103) of patients. Seventeen of 103 (17%) patients had hyperdynamic LVF with an interobserver agreement of [kappa] = 0.8. The sensitivity and specificity of hyperdynamic LVF for predicting sepsis were 33% (95% CI 19%-50%) and 94% (85%-98%), respectively. Hyperdynamic LVF had a positive likelihood ratio of 5.3 for the diagnosis of sepsis and was a strong independent predictor of sepsis as the final diagnosis with an odds ratio of 5.5 (95% CI 1.1-45). Among ED patients with nontraumatic undifferentiated symptomatic hypotension, the presence of hyperdynamic LVF on focused echo is highly specific for sepsis as the etiology of shock.
(C)2005The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: A propensity-matched analysis * | | Background: Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern.
Objective: To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock.
Design: Retrospective, propensity matched, multicenter, cohort study.
Setting: Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007.
Subjects: A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated.
Measurements and Main Results: The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with [beta]-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.
Conclusion: Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Early extracorporeal membrane oxygenator-assisted primary percutaneous coronary intervention improved 30-day clinical outcomes in patients with ST-segment elevation myocardial infarction complicated with profound cardiogenic shock | | Objectives: This study tested the hypothesis that early extracorporeal membrane oxygenator offered additional benefits in improving 30-day outcomes in patients with acute ST-segment elevation myocardial infarction complicated with profound cardiogenic shock undergoing primary percutaneous coronary intervention.
Methods: Between May 1993 and July 2002, 920 patients with acute ST-segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 12.5% (115) with cardiogenic shock were enrolled in this study (group 1). Between August 2002 and December 2009, 1650 patients with acute ST-segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 13.3% (219) complicated with cardiogenic shock were enrolled (group 2).
Results: The incidence of profound shock (defined as systolic blood pressure remaining <=75 mm Hg after intra-aortic balloon pump and inotropic agent supports) was similar in both groups (21.7% vs. 21.0%, p > .5). Extracorporeal membrane oxygenator support, which was available only for patients in group 2, was performed in the catheterization room. The results demonstrated that final thrombolysis in myocardial infarction grade 3 flow in infarct-related artery was similar between the two groups (p = .678). However, total 30-day mortality and the mortality of patients with profound shock were lower in group 2 than in group 1 (all p < .04). Additionally, the hospital survival time was remarkably longer in patients in group 2 than in patients in group 1 (p = .0005). Furthermore, multivariate analysis demonstrated that unsuccessful reperfusion, presence of advanced congestive heart failure, profound shock, and age were independent predictors of 30-day mortality (all p < .02).
Conclusion: Early extracorporeal membrane oxygenator-assisted primary percutaneous coronary intervention improved 30-day outcomes in patients with ST-segment elevation myocardial infarction with complicated with profound cardiogenic shock.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Early observational research and registries during the 2009-2010 influenza A pandemic | | As a critical care community, we have an obligation to provide not only clinical care but also the research that guides initial and subsequent clinical responses during a pandemic. There are many challenges to conducting such research. The first is speed of response. However, given the near inevitability of certain events, for example, viral respiratory illness such as the 2009 pandemic, geographically circumscribed natural disasters, or acts of terror, many study and trial designs should be preplanned and modified quickly when specific events occur. Template case report forms should be available for modification and web entry; centralized research ethics boards and funders should have the opportunity to preview and advise on such research beforehand; and national and international research groups should be prepared to work together on common studies and trials for common challenges. We describe the early international critical care research response to the influenza A 2009 (H1N1) pandemic, including specifics of observational study case report form, registry, and clinical trial design, cooperation of international critical care research organizations, and the early results of these collaborations.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Educational Initiative on Critical Bleeding in Trauma: Chicago, July 11-13, 2008 | | The Educational Initiative on Critical Bleeding in Trauma was formed to assess current data and to guide future research and practice in the management of coagulopathy after severe trauma. The Educational Initiative on Critical Bleeding in Trauma recently published structured literature reviews on animal models and mechanisms of trauma-associated coagulopathy and the results of a survey of international clinical practice. The authors convened a symposium in July 2008 and invited researchers and opinion leaders in trauma care, transfusion medicine, and coagulation research to discuss current understanding and management and to identify future areas of exploration. This document reviews the content and conclusions of the meeting. The association between trauma and bleeding from patient registries, basic science, and clinical studies was confirmed, as was the association between the coagulopathy that presents early after major injury and excess mortality. Meeting participants identified the need for consensus definitions and common terminology to describe coagulopathy after trauma, including the term acute coagulopathy of trauma shock to describe the early coagulopathy induced by tissue injury/shock and the global term trauma-induced coagulopathy to describe coagulopathy after injury and its sequelae (loss, consumption, acidemia, acute coagulopathy, and dilution). Other conclusions included the need for increased clinical awareness, new methods and tools for early diagnosis, consistent early preventative strategies, and evidence-based therapies for these conditions.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Endogenous Retroviruses in Systemic Response To Stress Signals | | Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ failure in these patients.
(C)2008The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Fluid Resuscitation in Severe Sepsis and Septic Shock: Albumin, Hydroxyethyl Starch, Gelatin or Ringer's Lactate-Does It Really Make A Difference? | | The aim of this study was to investigate whether the type of i.v. fluid administered has an impact on outcome in an animal model of septic shock. The study included 28 anesthetized, invasively monitored, mechanically ventilated female sheep (29.5 +/- 4.0 kg), which received 0.5 g/kg body weight of feces into the abdominal cavity to induce peritonitis. During the surgical operation and 4 h after feces spillage, only Ringer's lactate (RL) was administered in all animals. Thereafter, animals were randomized to receive continuous infusions of RL (n = 7) alone or combined with either 20% albumin (n = 7, volume ratio to RL 1:10) or 6% hydroxyethyl starch (HES) (n = 7, volume ratio to RL 1:1), or gelatin alone (n= 7, no volume limitation). Fluid resuscitation was titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. No antibiotics or vasoactive drugs were administered, and animals were monitored until their spontaneous death. Hemodynamic variables were better with HES and albumin than with the other fluids, as reflected by higher stroke volume, cardiac index, and oxygen delivery (all P < 0.05). Hydroxyethyl-starch-treated animals also had lower arterial lactate concentrations (P < 0.01). However, times to develop hypotension and oliguria were similar in all groups. Blood interleukin (IL) 6 concentrations were significantly increased in all groups. The mean survival time was similar in all groups. In this clinically relevant model of prolonged septic shock, albumin and HES solution resulted in higher cardiac output, oxygen delivery, and lower blood lactate levels than gelatin and RL; however, the choice of i.v. fluid did not affect outcome.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
GLYCOGEN SYNTHASE KINASE 3[beta] AS A TARGET FOR THE THERAPY OF SHOCK AND INFLAMMATION | | After the discovery that glycogen synthase kinase (GSK) 3[beta] plays a fundamental role in the regulation of the activity of nuclear factor [kappa]B, a number of studies have investigated the effects of this protein kinase in the regulation of the inflammatory process. The GSK-3[beta] inhibition, using genetically modified cells and chemically different pharmacological inhibitors, affects the regulation of various inflammatory mediators in vitro and in vivo. Insulin, an endogenous inhibitor of GSK-3 in the pathway leading to the regulation of glycogen synthase activity, has recently been clinically used in the therapy for septic shock. The beneficial anti-inflammatory effects of insulin in preclinical and clinical studies could possibly be due, at least in part, to the inhibition of GSK-3 and not directly correlated to the regulation of blood glucose. We describe the latest studies describing the effects of GSK-3 inhibition as potential target of the therapy for diseases associated with inflammation, ischemia/reperfusion, and shock.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
H1N1 novel influenza A in pregnant and immunocompromised patients | | Objective: To describe the increased risk of severe disease and the appropriate management of patients at high risk such as pregnant women and immunosuppressed patients who acquire novel influenza A (H1N1).
Design: Review of the literature regarding influenza A in these patient groups, and review of published and unpublished data with regard to novel influenza A (H1N1).
Main Results: Pregnant women are at increased risk for severe pneumonitis and respiratory failure from influenza infection, particularly during pandemics, including the current pandemic. Fetal morbidity is significant, usually resulting from maternal fever and severe hypoxemia. Early antiviral therapy using oseltamivir may be beneficial, and intensive care unit support should target adequate oxygenation at all times. Immunosuppressed patients are at increased risk for influenza, as well as at risk for more severe or prolonged infection. Patients after hematopoietic stem cell transplantation, after lung transplantation, and those receiving chemotherapy for leukemia are at highest risk, whereas the risk for human immunodeficiency virus-infected individuals appears relatively low. Treatment with antiviral therapy may be beneficial, even after the usual cut-off of 48 hrs after symptom onset.
Conclusions: Optimal management of these patients is preventive by influenza vaccination, but the neuraminidase inhibitor antiviral agents provide effective treatment.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Healthcare personnel and nosocomial transmission of pandemic 2009 influenza | | Knowledge regarding the modes of transmission of pandemic 2009 H1N1 influenza continues to develop, as do recommendations for the prevention of spread within healthcare facilities. The adoption of the most prudent, multifaceted approaches is recommended until there is significant evidence to reduce protective measures. The greatest threat to healthcare personnel and patients appears to be exposure to patients, healthcare personnel, or visitors who have not been recognized as contagious. The processes used within healthcare facilities must hold this concept central to any infection control plan and act in a preventive manner. This article focuses on the development of an algorithm for intensive care unit intake precautions, based on the early identification of potential source patients, as well as appropriate selection and adequate use of personal protective equipment. Visitor management, hand and respiratory hygiene, and cough etiquette have been used as measures to decrease the spread of infection. Vaccination of healthcare personnel, combined with work furlough for ill workers, is also explored. Recommendations include the elimination of potential exposures, engineering and administrative controls, and utilization of personal protective equipment.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Heart-Rate Complexity for Prediction of Prehospital Lifesaving Interventions in Trauma Patients | | Background: Traditional vital signs often fail to identify critically injured patients soon enough to permit timely intervention. To improve our ability to forecast the need for prehospital lifesaving interventions (LSIs), we applied heart-rate complexity (HRC) analysis to the electrocardiogram (ECG) of patients en route to trauma centers.
Methods: Analysis of ECG and clinical data from 374 patients en route by helicopter to three urban Level I trauma centers was conducted. Waveforms from 182 patients were excluded (because of ectopy, noise, or inadequate length). Of the remaining 192 patients, 54 received 66 LSIs in the field (LSI group): intubation (n = 52), cardiopulmonary resuscitation (n = 5), cricothyroidotomy (n = 2), and pneumothorax decompression (n = 7); 138 patients did not (non-LSI group). In the field, heart rate, blood pressure, and the Glasgow Coma Scale score (GCSTOTAL) and its motor component (GCSMOTOR) were recorded. ECG was recorded during flight. Ectopy-free, 800-beat sections of ECG were identified off-line and analyzed by HRC methods including Sample Entropy (SampEn) and Detrended Fluctuations Analysis (DFA).
Results: There was no difference between LSI and non-LSI patients in heart rate or blood pressure. SampEn was lower in LSI than in non-LSI (0.88 +/- 0.03 vs. 1.11 +/- 0.03), as was DFA (1.09 +/- 0.05 vs. 1.33 +/- 0.03) and GCSMOTOR (3.4 +/- 0.4 vs. 5.7 +/- 0.1) (all p < 0.0001). By logistic regression, SampEn, DFA, and GCSMOTOR were independently associated with LSIs (area under the receiver operating characteristic curve, 0.897).
Conclusions: Decreased HRC is associated with LSIs in prehospital trauma patients. HRC may be useful as a new vital sign for identification of the severely injured.
(C) 2008 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Hexosamine Biosynthesis and Protein O-Glycosylation: the First Line of Defense Against Stress, Ischemia, and Trauma | | An early and rapid response to severe injury or trauma is the development of hyperglycemia, which has long been thought to be an essential survival response by providing fuel for vital organ systems and facilitating mobilization of interstitial fluid reserves by increasing osmolarity. However, glucose can also be metabolized via the hexosamine biosynthesis pathway (HBP), leading to the synthesis of uridine diphosphate N-acetyl-glucosamine (UDP-GlcNAc). UDP-GlcNAc is a substrate for the addition, via an O-linkage, of a single N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins (O-glycosylation, O-GlcNAc). There is increasing appreciation that protein O-glycosylation is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Sustained increases in O-GlcNAc have been implicated in the development of diabetes and diabetic complications; however, recent studies have demonstrated that stress leads to a transient increase in O-GlcNAc levels that is associated with increased tolerance to stress. Indeed, activation of pathways leading to O-GlcNAc formation improves cell survival after I/R injury, whereas inhibition of O-GlcNAc formation decreases cell survival. In addition, in rodent models of trauma-hemorrhage, increasing O-GlcNAc levels during resuscitation improves cardiac function and organ perfusion and attenuates the inflammatory response. At the cellular level, increasing O-GlcNAc levels attenuates nuclear factor-[kappa]B activation. It is noteworthy that other metabolic-based treatments for severe injury such as glucose-insulin-potassium and glutamine also lead to increased HBP flux and O-GlcNAc levels. The goal of this review is to summarize our current understanding of the role of the HBP and O-GlcNAc on the regulation of cell function and survival and to present evidence to support the notion that activation of these pathways represents a novel treatment strategy for severe injury and trauma.
(C)2008The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
High Passage Number of Stem Cells Adversely Affects Stem Cell Activation and Myocardial Protection | | Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean +/- SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and -dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Hilar Control in Penetrating Chest Trauma: A Simplified Approach to an Underutilized Maneuver | | Background: In both urban and military settings, penetrating thoracic injuries remain a significant source of trauma-related mortality, and many patients require resuscitative thoracotomy. Existing literature emphasizes relief of pericardial tamponade and aortic clamp application as the key therapeutic maneuvers. The purpose of this report is to revisit pulmonary hilar clamping and highlight its application for hemorrhage control, air embolism prevention, and other benefits in the setting of massive hemothorax.
Methods: Records from an urban, American College of Surgeons verified level I trauma center were evaluated over a six-month period. Patients who underwent early pulmonary hilar clamping were identified.
Results: Twenty-four patients with trauma presented during the study period required thoracotomy. Of these, three (13%) underwent early pulmonary hilar clamping for massive hemothorax. Trauma mechanism was penetrating in each instance. Injuries included pulmonary lobe destruction, subclavian artery disruption, and internal thoracic artery transection. These cases illustrate the utility of early pulmonary hilar clamping for hemorrhage control, prevention of air embolization, and improved exposure.
Conclusion: To decrease morbidity and mortality at our institution, a method of pulmonary hilar control has evolved using an organized, "hand-over-hand" approach that controls hemorrhage, prevents fatal air embolism, protects against blood spillage into contralateral airways, and facilitates pulmonary surgery. Several features distinguish our approach from those previously reported.
(C) 2009 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Hmgb1 Signals Through Toll-Like Receptor (Tlr) 4 and Tlr2 | | In response to bacterial endotoxin (e.g., LPS) or endogenous proinflammatory cytokines (e.g., TNF and IL-1[beta]), innate immune cells release HMGB1, a late cytokine mediator of lethal endotoxemia and sepsis. The delayed kinetics of HMGB1 release makes it an attractive therapeutic target with a wider window of opportunity for the treatment of lethal systemic inflammation. However, the receptor(s) responsible for HMGB1-mediated production of proinflammatory cytokines has not been well characterized. Here we demonstrate that in human whole blood, neutralizing antibodies against Toll-like receptor 4 (TLR4, but not TLR2 or receptor for advanced glycation end product) dose-dependently attenuate HMGB1-induced IL-8 release. Similarly, in primary human macrophages, HMGB1-induced TNF release is dose-dependently inhibited by anti-TLR4 antibodies. In primary macrophages from knockout mice, HMGB1 activates significantly less TNF release in cells obtained from MyD88 and TLR4 knockout mice as compared with cells from TLR2 knockout and wild-type controls. However, in human embryonic kidney 293 cells transfected with TLR2 or TLR4, HMGB1 effectively induces IL-8 release only from TLR2 overexpressing cells. Consistently, anti-TLR2 antibodies dose-dependently attenuate HMGB1-induced IL-8 release in human embryonic kidney/TLR2-expressing cells and markedly reduce HMGB1 cell surface binding on murine macrophage-like RAW 264.7 cells. Taken together, our data suggest that there is a differential usage of TLR2 and TLR4 in HMGB1 signaling in primary cells and in established cell lines, adding complexity to studies of HMGB1 signaling which was not previously expected.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Improved Characterization of Combat Injury | | Background: Combat injury patterns differ from civilian trauma in that the former are largely explosion-related, comprising multiple mechanistic and fragment injuries and high-kinetic-energy bullets. Further, unlike civilians, U.S. armed forces combatants are usually heavily protected with helmets and Kevlar body armor with ceramic plate inserts. Searchable databases providing actionable, statistically valid knowledge of body surface entry wounds and resulting organ injury severity are essential to understanding combat trauma.
Methods: Two tools were developed to address these unique aspects of combat injury: (1) the Surface Wound Mapping (SWM) database and Surface Wound Analysis Tool (SWAT) software that were developed to generate 3D density maps of point-of-surface wound entry and resultant anatomic injury severity; and (2) the Abbreviated Injury Scale (AIS) 2005-Military that was developed by a panel of military trauma surgeons to account for multiple injury etiology from explosions and other high-kinetic- energy weapons. Combined data from the Joint Theater Trauma Registry, Navy/Marine Combat Trauma Registry, and the Armed Forces Medical Examiner System Mortality Trauma Registry were coded in AIS 2005-Military, entered into the SWM database, and analyzed for entrance site and wounding path.
Results: When data on 1,151 patients, who had a total of 3,500 surface wounds and 12,889 injuries, were entered into SWM, surface wounds averaged 3.0 per casualty and injuries averaged 11.2 per casualty. Of the 3,500 surface wounds, 2,496 (71%) were entrance wounds with 6,631 (51%) associated internal injuries, with 2.2 entrance wounds and 5.8 associated injuries per casualty (some details cannot be given because of operational security). Crude deaths rates were calculated using Maximum AIS-Military.
Conclusion: These new tools have been successfully implemented to describe combat injury, mortality, and distribution of wounds and associated injuries. AIS 2005-Military is a more precise assignment of severity to military injuries. SWM has brought data from all three combat registries together into one analyzable database. SWM and SWAT allow visualization of wounds and associated injuries by region on a 3D model of the body.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
In Silico Models of Acute Inflammation in Animals | | Trauma and hemorrhagic shock elicit an acute inflammatory response, predisposing patients to sepsis, organ dysfunction, and death. Few approved therapies exist for these acute inflammatory states, mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Various animal models have been used to simulate these phenomena, but these models often do not replicate the clinical setting of multiple overlapping insults. Mathematical modeling of complex systems is an approach for understanding the interplay among biological interactions. We constructed a mathematical model using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction. The model was calibrated in C57Bl/6 mice subjected to (1) various doses of lipopolysaccharide (LPS) alone, (2) surgical trauma, and (3) surgery + hemorrhagic shock. We tested the model's predictive ability in scenarios on which it had not been trained, namely, (1) surgery +/- hemorrhagic shock + LPS given at times after the beginning of surgical instrumentation, and (2) surgery + hemorrhagic shock + bilateral femoral fracture. Software was created that facilitated fitting of the mathematical model to experimental data, as well as for simulation of experiments with various inflammatory challenges and associated variations (gene knockouts, inhibition of specific cytokines, etc.). Using this software, the C57Bl/6-specific model was recalibrated for inflammatory analyte data in CD14-/- mice and was used to elucidate altered features of inflammation in these animals. In other experiments, rats were subjected to surgical trauma +/- LPS or to bacterial infection via fibrin clots impregnated with various inocula of Escherichia coli. Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Inefficiencies in a Rural Trauma System: The Burden of Repeat Imaging in Interfacility Transfers | | Background: Local hospitals (LHs) transferring patients to regional trauma centers (TCs) often obtain CT scans to diagnose injuries and justify transfer. However, these imaging studies are often repeated at the receiving TCs. This study was performed to examine how frequently computed tomography (CT) scans were repeated in interfacility transfers in a rural trauma system and to identify the most common reason for repeating the studies.
Methods: Patients transferred to a rural Level I TC from October 2007 through February 2008 were prospectively evaluated. Data abstracted included CT scans performed at LHs and CT scans repeated at the TC. Additionally, the reason for repeating each study was recorded as follows: (1) scan not sent, (2) software not compatible, (3) inadequate technique (no intravenous contrast), (4) inadequate technique (no reconstructions), and (5) clinically indicated.
Results: During the study period, 138 patients were transferred to the TC. Of these, 104 (75%) underwent CT imaging before transfer. Sixty of these patients (58%) underwent repeat CT imaging at the TC. Overall, 98 of 243 (40%) scans were repeated. Head CT scans were repeated predominantly because of clinical indications. All other body region CT scans were repeated predominantly because of inadequate technique at the LHs.
Conclusions: CT scans were repeated in 58% of interfacility transfers. Repeat CT scans inevitably result in increased radiation exposure to patients as well as additional charges and may be an important patient safety and cost issue for trauma systems.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Infection control in mass respiratory failure: Preparing to respond to H1N1 | | The first hints of a global public health crisis emerged with the identification of a new strain of H1N1 influenza A in March and April 2009 in Mexico City. By June 11, the World Health Organization had declared the outbreak of 2009 H1N1 a global pandemic. Now, with the continued growing presence of 2009 H1N1 on the global scene, much attention has been focused on the key role of personal protective equipment in healthcare infection control. Much less emphasis has been placed on specific interventions that may minimize the increased infectious risk commonly associated with critical care delivery. Given the frequency of high-risk respiratory procedures such as intubation and delivery of aerosolized medications in the intensive care unit, the delivery of critical care presents unique infection control challenges and unique opportunities to augment usual infection control practice with specific source-control efforts. Here, we summarize data regarding risks to critical care healthcare workers from previous respiratory virus outbreaks, discuss findings from the early 2009 H1N1 experience that suggest reasons for increased concern for those delivering critical care, and review best available evidence regarding strategies for source control in respiratory and critical care delivery.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Inferior Vena Cava Filters in Trauma Patients: Efficacy, Morbidity, and Retrievability | | Background: Thromboembolic events are potentially devastating sources of morbidity in trauma patients. With increasing experience and the introduction of retrievable devices, there has been a renewed interest in inferior vena cava (IVC) filters in trauma patients.
Methods: The records for consecutive trauma patients undergoing IVC filter placement during the years 2001 to 2005 were reviewed, and clinical, demographic, and procedural data were evaluated for associations with thromboembolic events and device complications.
Results: During the study years, 226 trauma patients had IVC filters inserted, and 140 of these patients (62%) had retrievable IVC filters placed. Six patients (3%) had a pulmonary embolism with the filter in place, and two patients (1%) had a pulmonary embolism after filter removal. The most common complication was thrombosis in 27 patients (12%), with clinically significant thrombus occurring in 15 patients (7%). There was no association between the type of filter (permanent or retrievable) or the brand of retrievable filter and thrombosis. Specific risk factors for thrombosis could not be identified. Retrievable filters were successfully removed in 61% of patients with retrievable filters. Technical success rate was 97% in those patients who underwent attempted removal. Removal was completed at a median of 21 days (range, 2-292 days).
Conclusions: Retrievable IVC filters in trauma patients are safe, but complications do occur with thrombosis being the most common. Retrieval has a high technical success rate when attempted. However, a significant number of trauma patients are lost to follow-up and this may impact the utilization of retrievable filters in this patient population.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Influenza epidemiology-past, present, and future | | In April 2009, Mexican, American, and Canadian authorities announced that a novel influenza virus with pandemic potential had been identified in large segments of the population. Within weeks, it became apparent that the world was dealing with the first influenza pandemic in >40 yrs. Despite the unpredictable nature of influenza severity and spread in the pandemics of the 20th century, understanding the epidemiology of the past pandemics and current influenza pandemic will help prepare physicians, hospitals, and governments to predict and prepare for the subsequent waves and subsequent pandemics. We present a summary of the biology that predisposes influenza to cause sudden pandemics, as well as a summary of the epidemiology of the 20th century pandemics. We also report on the epidemiology, disease severity, and risk factors for severe disease and intensive care admission from the first wave of the current pandemic (April-August 2009). Last, we provide a mathematical model based on transmission dynamics of the H1N1 influenza virus that may provide some guidance in terms of disease incidence and hospital impact.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Influenza pathogenesis: Lessons learned from animal studies with H5N1, H1N1 Spanish, and pandemic H1N1 2009 influenza | | Because cases of highly pathogenic influenza are rare, no systematic clinical studies have evaluated different therapeutic approaches. Instead, treatment recommendations are aimed at the alleviation of clinical signs and symptoms, especially the restoration of respiratory function, and at the inhibition of virus replication, assuming viral load is responsible for disease phenotype. Studies of highly pathogenic influenza in different animal models, especially nonhuman primates and ferrets, reproduce many of the key observations from clinical cases. Host-response kinetics reveal a delayed but broad activation of genes involved in the innate and acquired immune responses (innate responses produce inflammatory responses), which continue after the virus has been cleared and may contribute importantly to the clinical signs observed.
Experimental animal models point to an important role for immune dysregulation in the pathogenesis of highly pathogenic influenza. The use of these models to develop and validate therapeutic approaches is just beginning, but published studies reveal the importance of early treatment with antivirals and show the potential and limitations of approaches aimed at the host response.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Intensive care unit quality improvement: A "how-to" guide for the interdisciplinary team * | | Objective: Quality improvement is an important activity for all members of the interdisciplinary critical care team. Although an increasing number of resources are available to guide clinicians, quality improvement activities can be overwhelming. Therefore, the Society of Critical Care Medicine charged this Outcomes Task Force with creating a "how-to" guide that focuses on critical care, summarizes key concepts, and outlines a practical approach to the development, implementation, evaluation, and maintenance of an interdisciplinary quality improvement program in the intensive care unit.
Data Sources and Methods: The task force met in person twice and by conference call twice to write this document. We also conducted a literature search on "quality improvement" and "critical care or intensive care" and searched online for additional resources.
Data Synthesis and Overview: We present an overview of quality improvement in the intensive care unit setting and then describe the following steps for initiating or improving an interdisciplinary critical care quality improvement program: a) identify local motivation, support teamwork, and develop strong leadership; b) prioritize potential projects and choose the first target; c) operationalize the measures, build support for the project, and develop a business plan; d) perform an environmental scan to better understand the problem, potential barriers, opportunities, and resources for the project; e) create a data collection system that accurately measures baseline performance and future improvements; f) create a data reporting system that allows clinicians and others to understand the problem; g) introduce effective strategies to change clinician behavior. In addition, we identify four steps for evaluating and maintaining this program: a) determine whether the target is changing with periodic data collection; b) modify behavior change strategies to improve or sustain improvements; c) focus on interdisciplinary collaboration; and d) develop and sustain support from the hospital leadership. We also identify a number of online resources to complement this overview.
Conclusions: This Society of Critical Care Medicine Task Force report provides an overview for clinicians interested in developing or improving a quality improvement program using a step-wise approach. Success depends not only on committed interdisciplinary work that is incremental and continuous but also on strong leadership. Further research is needed to refine the methods and identify the most cost-effective means of improving the quality of health care received by critically ill patients and their families.
(C) 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Intensive care unit-acquired weakness | | Objective: Severe weakness is being recognized as a complication that impacts significantly on the pace and degree of recovery and return to former functional status of patients who survive the organ failures that mandate life-support therapies such as mechanical ventilation. Despite the apparent importance of this problem, much remains to be understood about its incidence, causes, prevention, and treatment.
Design: Review from literature and an expert round-table.
Setting: The Brussels Round Table Conference in 2009 convened more than 20 experts in the fields of intensive care, neurology, and muscle physiology to review current understandings of intensive care unit-acquired weakness and to improve clinical outcome.
Main Results: Formal electrophysiological evaluation of patients with intensive care unit-acquired weakness can identify peripheral neuropathies, myopathies, and combinations of these disorders, although the correlation of these findings to weakness measurable at the bedside is not always precise. For routine clinical purposes, bedside assessment of neuromuscular function can be performed but is often confounded by complicating factors such as sedative and analgesic administration. Risk factors for development of intensive care unit-acquired weakness include bed rest itself, sepsis, and corticosteroid exposure. A strong association exists between weakness and long-term ventilator dependence; weakness is a major determinant of patient outcomes after surviving acute respiratory failure and may be present for months, or indefinitely, in the convalescence phase of critical illness.
Conclusion: Although much has been learned about the physiology and cell and molecular biology of skeletal and diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis, the application of these understandings to the bedside requires more study in both bench models and patients. Although a trend toward greater immobilization and sedation of patients has characterized the past several decades of intensive care unit care, recent studies have demonstrated that early physical and occupational therapy, including during the period of intubation and ventilator support, can be safely performed and will likely improve patient outcomes with regard to functional status.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Intensive Insulin Therapy in Severe Traumatic Brain Injury: A Randomized Trial | | Background: Intensive insulin therapy (IIT) has been shown to reduce morbidity and mortality in critically ill patients. Little investigation has been done to find out whether it improves the prognosis of patients with severe traumatic brain injury (STBI).
Methods: We conducted a prospective controlled study where adult patients with blunt STBI, with Glasgow Coma Scale <=8, admitted to the intensive care unit (ICU) were randomly assigned to receive either IIT (maintenance of blood glucose between 80 mg/dL and 110 mg/dL with continuous insulin infusion) or conventional glycemic therapy (CGT) (maintenance of blood glucose below 180 mg/dL with subcutaneous insulin and insulin infusion only if blood glucose levels exceeded 220 mg/dL). The main outcome was Glasgow outcome scale 6 months after trauma. Secondary measures were hypoglycemia, incidence of infections, and days in ICU.
Results: Of the 88 patients randomized, 42 were assigned to IIT and 46 to CGT. There was no difference (p = 0.63) in neurologic outcomes between the treatment groups: Glasgow outcome scale >3 was observed in 16 patients (41%) in the IIT and in 13 patients (32.5%) in the CGT group. More patients in the IIT group had hypoglycemia: 32 (82.1%), compared with 7 (17.5%) in the CGT group (p < 0.001). There were no differences in the number of days spent in the ICU (18.2 +/- 27.6 vs. 12.9 +/- 12.7) or in the sepsis rates (84.6% vs. 80%) between the groups.
Conclusion: In our study, IIT did not improve the neurologic outcome of patients with STBI but did increase the risk of hypoglycemia compared with CGT.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Interleukin 18 in the Heart | | IL-18, originally termed as interferon [gamma] (IFN-[gamma]) inducing factor, is a proinflammatory cytokine that belongs to the IL-1 cytokine superfamily. IL-18 plays an important role in immune, infectious, and inflammatory diseases due to its induction of IFN-[gamma]. However, accumulated evidence has demonstrated that other effects of IL-18 are independent of IFN-[gamma]. Here, we reviewed the current literatures regarding the role of IL-18 in the heart and cardiovascular system. Infiltrated neutrophils, resident macrophages, endothelial cells, smooth muscle cells, and cardiomyocytes in the heart are able to produce IL-18 in response to injury. IL-18 is produced as a biologically inactive precursor (pro-IL-18) that is activated by caspase 1 (the IL-1[beta] converting enzyme). Elevated IL-18 levels have been observed in cardiac tissue and circulation after myocardial I/R and sepsis. The possible cellular and molecular mechanisms concerning IL-18-induced myocardial injury include induction of inflammation, increased apoptosis, a cardiac hypertrophy effect, modulation of mitogen activated protein kinase activation, and changes in intracellular calcium. Finally, we briefly reviewed the therapeutic strategies for inhibiting IL-18's biological activity to protect cardiac tissue from injury.
(C)2008The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Jak/Stat/Socs Signaling Circuits and Associated Cytokine-Mediated Inflammation and Hypertrophy in the Heart | | Cytokines are important mediators of cardiac disease. Accumulating evidence indicates that members of the interleukin-6 family of cytokines promote cardiac hypertrophy through the activation of the Janus kinase-signal transducer and activator of transcription (Jak/STAT) pathway. Aberrant Jak/STAT signaling may promote progression from hypertrophy to heart failure. Suppressor of cytokine signaling (SOCS) proteins are underexplored, negative regulators of Jak/STAT signaling. SOCS proteins may also interact with other inflammatory pathways known to affect cardiac function. A better understanding of the therapeutic potential of these proteins may lead to the controlled progression of heart failure and the limitation of myocardial depression. This review summarizes the cardiophysiological effect of the IL-6 cytokine family, outlines the mechanistic pathway of Jak/STAT signaling, explores the regulatory role of SOCS proteins in the heart, and discusses the potential of using SOCS proteins clinically.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Just One Drop: The Significance of a Single Hypotensive Blood Pressure Reading During Trauma Resuscitations | | Background: Single, isolated hypotensive blood pressure (BP) measurements frequently are ignored or considered "erroneous." Although their clinical significance remains unknown, we hypothesized that single, isolated hypotensive BP readings during trauma resuscitations signify the presence of severe injuries that often warrant immediate intervention.
Methods: A prospective observational study was performed on all trauma patients admitted from June 2008 to January 2009. Patients with a single systolic blood pressure (SBP) reading <110 mm Hg during their trauma resuscitation were evaluated, and demographics, hemodynamics, resuscitation (fluids, blood products, and duration), injuries, and operative or endovascular management were analyzed. Single and multiple variable logistic regression analyses were performed. Cutpoint analysis of the entire range of lowest single SBP measurements determined which SBP value best predicted the need for immediate therapeutic intervention.
Results: Patients (n = 145) were predominantly male (77.2%) but age (mean, 35.1 +/- 15.3 years) and injury mechanisms varied (penetrating, 46.2%; blunt, 53.8%). Cutpoint analysis determined that a single SBP reading <105 mm Hg best predicted the need for immediate therapeutic intervention. Although 38.1% patients with isolated SBP <105 mm Hg measurements underwent immediate therapeutic operative or endovascular procedures, only 10.4% (p < 0.001) with isolated SBP >=105 mm Hg required these procedures. Patients were 12.4 times (confidence interval: 2.6-59.2; p = 0.002) more likely to undergo immediate therapeutic intervention than those with a single SBP >=105 mm Hg.
Conclusions: Single, isolated hypotensive BP measurements during trauma resuscitations should not be ignored or dismissed. Instead, our results suggest that a single SBP reading <105 mm Hg is associated with severe injuries that often require immediate operative or endovascular treatment and surgical intensive care unit admission.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Key Inflammatory Signaling Pathways Are Regulated By the Proteasome | | Lipopolysaccharide (LPS) is a major structural component of all Gram-negative organisms and has been implicated in Gram-negative sepsis and septic shock. In the present study, Affymetrix microarray analysis of RNA derived from murine macrophages treated with LPS in the absence or presence of the proteasome inhibitor lactacystin revealed that the vast majority of genes regulated by LPS is under control of the proteasome. Analysis of the data has revealed that the products of these genes participate in 14 distinct signaling pathways. This represents a novel approach to the identification of signaling pathways that are both toll-like receptor 4- and proteasome-dependent and may lead to the development of new drug targets in Gram-negative sepsis and septic shock.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Shock
Key Issues in Advanced Bleeding Care in Trauma | | The incidence of hemostatic abnormalities in the early hours after traumatic incident is high and represents an independent predictor of mortality. Key factors in the development of traumatic coagulopathy include the severity of injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the mechanism of injury, vital signs, biochemistry, detection of external and internal bleeding sources, injuries found upon secondary investigation, and response to treatment. Priority in treating the bleeding trauma patient should be given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and maintenance of tissue oxygenation, achieved by careful physical handling, damage control surgery, analgesia, maintenance of normothermia, correction of coagulopathy, control of blood pH, and serum calcium. Priority during initial treatment is to restore tissue perfusion and achieve hemostasis in vital functions; other nonvital procedures may generally be delayed. This state-of-the-art review aims to address key issues in acute control of bleeding in the trauma patient.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Laboratory diagnosis of 2009 H1N1 influenza A virus | | The emergence of 2009 pandemic influenza H1N1 has necessarily led to the rapid evolution of sensitive, specific, and high-throughput molecular diagnostic assays for this virus at the same time that clinical laboratories attempt to cope with increasing demands in the setting of resource limitations. This situation has given rise to testing algorithms focusing on priority, clinical relevance, and appropriate surveillance. We describe the current state of understanding around diagnostic testing and laboratory detection of 2009 H1N1 influenza A virus.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: A systematic review and meta-analysis * | | Introduction: Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. However, clinical superiority has not been demonstrated.
Objective: To test the hypothesis that linezolid may be superior to glycopeptides.
Methods: Prospective randomized trials that tested linezolid vs. vancomycin or teicoplanin for treatment of nosocomial pneumonia were included. Heterogeneity was analyzed by I2 and Q statistics. Meta-analysis relative risks were based on fixed and random-effects models. Outcomes evaluated consisted of clinical cure, microbiological eradication, and side effects.
Results: Nine linezolid trials (vancomycin [7]; teicoplanin [2]) were included (n = 2329). The linezolid vs. glycopeptide analysis shows clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I2 = 0%) and microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98 -1.22; p = .10; I2 = 0%). Methicillin-resistant Staphylococcus aureus subgroup analysis yielded a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.87-1.38; p = .44; I2 = 16%). If linezolid is compared with vancomycin only, then clinical cure relative risk is 1.00 (95% confidence interval, 0.90-1.12), microbiological eradication and methicillin-resistant Staphylococcus aureus relative risks are 1.07 (95% confidence interval, 0.90-1.26; p = .45) and 1.05 (95% confidence interval, 0.82-1.33; p = .71). The risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = .001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = .02) are higher with linezolid, but no differences are seen for renal dysfunction (relative risk, 0.89; 95% confidence interval, 0.56-1.43; p = .64) or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = .63).
Conclusions: Our study does not demonstrate clinical superiority of linezolid vs. glycopeptides for the treatment of nosocomial pneumonia despite a statistical power of 95%. Linezolid shows a significant two-fold increase in the risk of thrombocytopenia and gastrointestinal events. Vancomycin and teicoplanin are not associated with more renal dysfunction than linezolid.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Long-Term Survival and Return On Investment After Nonneurologic Injury: Implications for the Elderly Trauma Patient | | Background: As the population of the United States ages and as the healthcare system undergoes significant change, cost effectiveness of care will become more important, particularly for older injured patients. The purpose of this study was to evaluate the cost per 2-year survivor stratified by age after moderate- to severe-nonneurologic injury.
Methods: The trauma registry from a Level I trauma center was queried for adults (older than 18 years), discharged alive after blunt injury (Injury Severity Score >15), without significant neurologic injury, and with hospital charge data. Survival was determined using the Social Security Death Master File. Patients were stratified by age. Hospital costs were calculated by multiplying hospital charge by the cost to charge ratio.
Results: One thousand nine hundred fourteen patients made up the study population. Mean hospital cost per patient was $10,021. Mean cost per 2-year survivor was $10,328. Overall 2-year survival was 97%. (*p < 0.05 vs. youngest). When broken down by age group, there were no significant differences in hospital costs. However, 2-year survival was significantly less in those who were 55.1 years to 75 years old and those older than 75 years, when compared with those aged 18 years to 25 years. Thus, median cost per 2-year survivor was highest in those older than 75 years ($8,911).
Conclusion: Although costs are similar by age at time of discharge, cost per 2-year survivor increases as age increases. However, cost per 2-year survivor does not exceed current cost-utility thresholds for any age group. Any future healthcare financing reforms should include aggressive funding for injury prevention efforts aimed at vulnerable populations instead of rationing care once an injury occurs.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Low-Volume Resuscitation Cocktail Extends Survival After Severe Hemorrhagic Shock | | After severe hemorrhage, low-volume resuscitation with hypertonic fluids is increasingly preferred to more aggressive resuscitation strategies. Oxygen delivery to the tissues may be improved by augmentation with hemoglobin [Hb]-based oxygen-carrying compounds (HBOCs); however, previous studies have reported negative outcomes presumably related to extravasation of tetrameric Hb. The purpose of this study was to evaluate a novel large molecular weight polymer of cross-linked bovine Hb (OxyVita; OXYVITA Inc, New Windsor, NY) in a cocktail of hypertonic saline and Hextend (HX; HBOC-C) as an alternative to standard small-volume resuscitation using Hextend (HX) only. Outcomes were survival to 3 h and duration of MAP support more than 60 mmHg without additional fluid support. Conscious male Long-Evans rats were hemorrhaged to 60% total blood volume over 40 min. There were 4 groups: HBOC-C administered in a pressure-titrated infusion, HX titration, HBOC-C administered as a bolus, and HX bolus. Cardiovascular parameters, arterial gases, acid-base status, metabolites, electrolytes, Hb level, and oxygen saturation were measured at baseline, during each 20% hemorrhage increment, and 1, 2, and 3 h after the initiation of hemorrhage. Small-volume resuscitation with HBOC-C significantly improved survival to 3 h and improved MAP support times regardless of method of administration. However, physiological status at the end of hemorrhage significantly influenced survival regardless of resuscitation treatment. These results suggest that HBOC-augmented hypertonic cocktails are of promise in improving survival and providing target MAP support during small-volume resuscitation. Experimental evaluation of any resuscitation therapy should account for the degree of preexisting physiological compromise before therapy is initiated.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Management of Patients With Anterior Abdominal Stab Wounds: A Western Trauma Association Multicenter Trial | | Background: The optimal management of hemodynamically stable, asymptomatic patients with anterior abdominal stab wounds (AASWs) remains controversial. The goal is to identify and treat injuries in a safe, cost-effective manner. Common evaluation strategies include local wound exploration (LWE)/diagnostic peritoneal lavage (DPL), serial clinical assessments (SCAs), and computed tomography (CT) imaging. The purpose of this multicenter study was to evaluate the clinical course of patients managed by the various strategies, to determine whether there are differences in associated nontherapeutic laparotomy (NONTHER LAP), emergency department (ED) discharge, or complication rates.
Methods: A multicenter, Institutional Review Board-approved study enrolled patients with AASWs. Management was individualized according to surgeon/institutional protocols. Data on the presentation, evaluation, and clinical course were recorded prospectively.
Results: Three hundred fifty-nine patients were studied. Eighty-one had indications for immediate LAP, of which 84% were therapeutic. ED D/C was facilitated by LWE, CT, and DPL in 23%, 21%, and 16% of patients, respectively. On the other hand, LAP based on abnormalities on LWE, CT, and DPL were NONTHER in 57%, 24%, and 31% of patients, respectively. Twelve percent of patients selected for SCA ultimately had LAP (33% were NONTHER); there was no apparent morbidity due to delay in intervention.
Conclusions: Shock, evisceration, and peritonitis warrant immediate LAP after AASW. Patients without these findings can be safely observed for signs or symptoms of bleeding or hollow viscus injury. To limit the number of hospital admissions, we propose a uniform strategy using LWE to ascertain the depth of penetration; the patient may be safely discharged in the absence of peritoneal violation. Peritoneal penetration, absent evidence of ongoing hemorrhage or hollow viscus injury, should not be considered an indication for LAP, but rather an indication for admission for SCAs. We suggest that a prospective multicenter trial be performed to document the safety and cost-effectiveness of such an approach.
(C) 2009 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Managing antimicrobial resistance in intensive care units | | The challenges in managing patients with infection in the intensive care unit are increased in an era where there are dwindling antimicrobial choices for multidrug-resistant pathogens. Clinicians in the intensive care unit must balance between choosing appropriate antimicrobial treatment for patients with suspected infection and utilizing antimicrobials in a judicious fashion. Improving antimicrobial utilization is a critical component to reducing antimicrobial resistance. Although providing effective antimicrobial therapy and improving antimicrobial utilization may seem to be competing goals, there are effective strategies to accomplish both. Antimicrobial stewardship programs provide an organized way to implement these strategies and can enhance the intensive care unit physician's success in improving patient outcomes and combating antimicrobial resistance in the intensive care unit.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Massive Transfusion Practices Around the Globe and a Suggestion for a Common Massive Transfusion Protocol | | Background: Massive transfusion, the administration of 10 to more than 100 units of red blood cells (RBC) in less than 24 hours, can be a life saving therapy in the treatment of severe injury. The rapid administration of large numbers of RBC, along with sufficient plasma and platelets to treat or prevent coagulopathy, is frequently a disorderly process. Patient care and collaborative research might be aided with a common protocol.
Methods: The authors polled trauma organizations and trauma centers to find examples of massive transfusion protocols. The goals and ease of use of these protocols were evaluated.
Results: Massive transfusion protocols exist at a relatively small number of large and well-organized trauma centers. Most of these protocols are designed to treat pre-existing and/or ongoing coagulopathy.
Conclusions: The evidence would suggest that prevention of coagulopathy is superior to its treatment. Simple ratios such as 1:1:1 RBC:plasma:platelets have the benefit of ease of use and the relatively higher plasma and platelet doses appear to be associated with improved outcome. Such a standard protocol can foster multicenter research on resuscitation and hemorrhage control. The fixed volume ratios might allow the number and rate of administered units of RBC to be used as surrogates for blood loss and primary treatment effect.
(C) 2006 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Shock
Mitochondrial Dysfunction, Bioenergetic Impairment, and Metabolic Down-Regulation in Sepsis | | Mitochondrial dysfunction is thought to play an important role in the pathogenesis of many different disease states. It has been proposed that an acquired defect in oxidative phosphorylation prevents cells from using molecular oxygen for adenosine triphosphate production and potentially causes sepsis-induced organ dysfunction. This concept, termed cytopathic hypoxia, however, has been difficult to prove because impaired oxidative phosphorylation has never been shown to cause sepsis-induced organ failure or to be a reversible phenomenon. Presented here is areview of oxidative phosphorylation, evidence of defective electron-transport-chain function in the heart and otherorgan systems during sepsis, and support for a link between mitochondrial dysfunction and pathologic metabolic down-regulation.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Models for structuring a clinical initiative to enhance palliative care in the intensive care unit: A report from the IPAL-ICU Project (Improving Palliative Care in the ICU) * | | Objective: To describe models used in successful clinical initiatives to improve the quality of palliative care in critical care settings.
Data Sources: We searched the MEDLINE database from inception to April 2010 for all English language articles using the terms "intensive care," "critical care," or "ICU" and "palliative care"; we also hand-searched reference lists and author files. Based on review and synthesis of these data and the experiences of our interdisciplinary expert Advisory Board, we prepared this consensus report.
Data Extraction and Synthesis: We critically reviewed the existing data with a focus on models that have been used to structure clinical initiatives to enhance palliative care for critically ill patients in intensive care units and their families.
Conclusions: There are two main models for intensive care unit-palliative care integration: 1) the "consultative model," which focuses on increasing the involvement and effectiveness of palliative care consultants in the care of intensive care unit patients and their families, particularly those patients identified as at highest risk for poor outcomes; and 2) the "integrative model," which seeks to embed palliative care principles and interventions into daily practice by the intensive care unit team for all patients and families facing critical illness. These models are not mutually exclusive but rather represent the ends of a spectrum of approaches. Choosing an overall approach from among these models should be one of the earliest steps in planning an intensive care unit-palliative care initiative. This process entails a careful and realistic assessment of available resources, attitudes of key stakeholders, structural aspects of intensive care unit care, and patterns of local practice in the intensive care unit and hospital. A well-structured intensive care unit-palliative care initiative can provide important benefits for patients, families, and providers.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
Mof, Mods, and Sirs: What Is in A Name or An Acronym? | | The most prominent contributions to multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome are described in this article. However, it is quite possible that there are others that have been missed. The problem of organ failure continues to perplex clinicians and scientists, and it contributes to fatal outcomes for patients with illnesses, infections, and injuries after operations. Although we know a fair bit about these problems, we frequently can do little about it. The best approach remains support to prevent failure.
(C)2006The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Neurally adjusted ventilatory assist in patients recovering spontaneous breathing after acute respiratory distress syndrome: Physiological evaluation * | | Objective: Pressure-support ventilation is widely used during the weaning phase in patients with acute respiratory distress syndrome. The pressure-support level is adjusted to prevent ventilator-induced lung injury while limiting the patient's work of breathing. Neurally adjusted ventilatory assist is an assist mode that applies a positive pressure proportional to the integral of the electrical activity of the diaphragm. The objective was to assess the physiologic response to varying pressure-support ventilation and neurally adjusted ventilatory assist levels in selected acute respiratory distress syndrome patients and to evaluate the effect of neural triggering.
Methods: We prospectively assessed 11 consecutive patients with acute respiratory distress syndrome attributable to pulmonary diseases. Pressure-support ventilation and neurally adjusted ventilatory assist were used in random order. Neurally adjusted ventilatory assist was used with a low electrical activity of the diaphragm trigger (neurally adjusted ventilatory assist-electrical activity of the diaphragm) and with a high electrical activity of the diaphragm trigger that led to rescue triggering by inspiratory flow (neurally adjusted ventilatory assist-inspiratory flow). With each ventilation modality, four levels of assistance (100%, 120%, 140%, and 160%) were used in random order. Statistical analysis was performed using analysis of variance for repeated measurements and mixed models.
Main Results: Contrary to pressure-support ventilation, neurally adjusted ventilatory assist-electrical activity of the diaphragm and neurally adjusted ventilatory assist-inspiratory flow were associated with stable tidal volume levels despite increasing assistance. For the asynchrony index, an interaction was present between ventilation mode and assist level (p = .0076) because asynchrony index increased significantly with the pressure-support ventilation level (p = .004), but not with the neurally adjusted ventilatory assist-electrical activity of the diaphragm or neurally adjusted ventilatory assist-inspiratory flow level. The lowest asynchrony index was obtained with neurally adjusted ventilatory assist-electrical activity of the diaphragm.
Conclusion: Compared to pressure-support ventilation, neurally adjusted ventilatory assist in acute respiratory distress syndrome patients holds promise for limiting the risk of overassistance, preventing patient-ventilator asynchrony, and improving overall patient-ventilator interactions. Neural triggering (neurally adjusted ventilatory assist-electrical activity of the diaphragm) considerably decreased patient-ventilator asynchrony. (Crit Care Med 2010; 38:1830-1837)
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
NEUTROPHIL-DERIVED CIRCULATING FREE DNA (cf-DNA/NETs): A POTENTIAL PROGNOSTIC MARKER FOR POSTTRAUMATIC DEVELOPMENT OF INFLAMMATORY SECOND HIT AND SEPSIS | | The release of "neutrophil extracellular traps" (NETs) has been identified as a novel immune response in innate immunity. Neutrophil extracellular traps are composed of neutrophil-derived circulating free DNA (cf-DNA), histones, and neutrophil cytoplasm-derived proteins such as proteases. Here, we studied the putative predictive value of plasma cf-DNA/NETs for the development of sepsis and mortality after multiple trauma. In a prospective pilot study with 45 multiple trauma (Injury Severity Score >16) patients, cf-DNA was directly quantified in plasma. Blood samples were sequentially obtained daily from admission to our Trauma Center until day 10. Because of limited intensive care unit (ICU) stay of less than 3 days, 8 patients have been excluded, resulting in 37 patients that were evaluated. Time kinetics of cf-DNA/NETs was compared with C-reactive protein (CRP), interleukin (IL) 6, leukocyte counts, and myeloperoxidase. The severity of the injury was calculated on the basis of the Injury Severity Score, as well as Multiple Organ Dysfunction Score, Sequential Organ Failure Assessment, and Simplified Acute Physiology Score II on ICU. Initially high cf-DNA/NETs values (>800 ng/mL) with recurrent increased values between days 5 to 9 were associated with subsequent sepsis, multiple organ failure, and death. In conjunction with cf-DNA/NETs, IL-6 was significantly elevated after admission. However, the development of a second hit was not indicated by IL-6. In contrast to cf-DNA/NETs, no difference in CRP kinetics was observed between patients with and without development of sepsis. Circulating free DNA/NETs kinetics rather followed kinetics of Multiple Organ Dysfunction Score, Sepsis-related Organ Failure Assessment, leukocyte counts, and partially of myeloperoxidase. Circulating free DNA/NETs seems to be a valuable additional marker for the calculation of injury severity and/or prediction of inflammatory second hit on ICU. However, a large clinical trial with severely injured patients should confirm the prognostic value of neutrophil-derived cf-DNA/NETs.
(C)2008The Shock Society | | 9/6/2010 1:04:01 PM |
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Crit Care Med
Nonventilatory strategies for patients with life-threatening 2009 H1N1 influenza and severe respiratory failure | | Severe respiratory failure (including acute lung injury and acute respiratory distress syndrome) caused by 2009 H1N1 influenza infection has been reported worldwide. Refractory hypoxemia is a common finding in these patients and can be challenging to manage. This review focuses on nonventilatory strategies in the advanced treatment of severe respiratory failure and refractory hypoxemia such as that seen in patients with severe acute respiratory distress syndrome attributable to 2009 H1N1 influenza. Specific modalities covered include conservative fluid management, prone positioning, inhaled nitric oxide, inhaled vasodilatory prostaglandins, and extracorporeal membrane oxygenation and life support. Pharmacologic strategies (including steroids) investigated for the treatment of severe respiratory failure are also reviewed.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Nurse staffing and patient outcomes in critical care: A concise review | | Background: Studies over the past several decades have shown an association between nurse staffing and patient outcomes. Most of those studies were generated from general acute care units. Critically ill patients demand increased nurse staffing resources and nurses who have specialized knowledge and skills. Appropriate nurse staffing in critical care units may improve the quality of care of critically ill patients.
Objectives: To review the literature evaluating the association of nurse staffing with patient outcomes in critical care units and populations.
Methods: An annotated review of major nursing and medical literature from 1998 to 2008 was performed to find research studies conducted in intensive care units or critical care populations where nurse staffing and patient outcomes were addressed.
Results: Twenty-six studies met inclusion for this review. Most were observational studies in which outcomes were retrieved from existing large databases. There was variation in the measurement of nurse staffing and outcomes. Outcomes most frequently studied were infections, mortality, postoperative complications, and unplanned extubation. Most studies suggested that decreased nurse staffing is associated with adverse outcomes in intensive care unit patients.
Conclusions: Findings from this review demonstrate an association of nurse staffing in the intensive care unit with patient outcomes and are consistent with findings in studies of the general acute care population. A better understanding of nurse staffing needs for intensive care unit patients is important to key stakeholders when making decisions about provision of nurse resources. Additional research is necessary to demonstrate the optimal nurse staffing ratios of intensive care units.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Shock
Pancreatic Cellular Injury After Cardiac Surgery With Cardiopulmonary Bypass: Frequency, Time Course and Risk Factors | | Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation ([alpha]1-protease inhibitor, [alpha]2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and [alpha]1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >=40 ng/mL, amylase >=42 IU/mL, and pancreatic isoamylase >=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, [alpha]1-protease inhibitor, and [alpha]2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.
(C)2007The Shock Society | | 9/6/2010 1:04:01 PM |
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J Trauma
Pentobarbital Coma For Refractory Intra-Cranial Hypertension After Severe Traumatic Brain Injury: Mortality Predictions and One-Year Outcomes in 55 Patients | | Objective: To identify predictors of mortality and long-term outcomes in survivors after pentobarbital coma (PBC) in patients failing current treatment standards for severe traumatic brain injuries (TBI). This is a retrospective cohort study of severe TBI patients receiving PBC at Level I Trauma Center and tertiary university hospital.
Methods: Four thousand nine hundred thirty-four patients were admitted to the trauma intensive care unit with severe TBI (head Abbreviated Injury Scale >= 3) between April 1998 and December 2004. Six hundred eleven received intracranial pressure (ICP) monitoring and 58 received PBC. Three patients underwent craniotomy for intracranial mass lesion and were excluded. The study group received standardized medical management for severe TBI including opiates, benzodiazepines, elevation of the head of bed, avoidance of hypotension and hypercapnia and hyperosmolar therapy (HOsmRx). In addition, 31 of 55 patients (56%) underwent placement of intraventricular catheters for cerebrospinal fluid drainage. If routine medical management and cerebrospinal fluid diversion failed to control ICP, then the patient was determined to have refractory intracranial hypertension (RICH) and PBC treatment was initiated. PBC was performed with pentobarbital infusion with continuous electroencephalogram monitoring to ensure adequate burst suppression. The measurements include serum sodium (Na+) and osmolality (Osm) were assessed as indicators for initiation of PBC and to estimate the 50% mortality cut-points when controlling for ICP. Follow-up functional outcomes were assessed using the Glasgow Outcome Scale and stratified according to admission Glasgow Coma Scale score and Marshall computed tomography classification. Of the 55 PBC patients, 22 (40%) survived at discharge. 19 of 22 had long-term follow-up (1 year or more) available. Of these, 13 (68%) were normal or functionally independent (Glasgow Outcome Scale score 4 or 5). Serum Na+ and Osm were associated with death (p < 0.05) when controlling for ICP. The 50% mortality cut-points were Na+ of 160 mEq/L and Osm of 330 mOsm/kg H2O. Median minimum cerebral perfusion pressure after PBC was 42 mm Hg in survivors and 34 mm Hg in nonsurvivors (p = 0.013).
Conclusions: In patients with severe TBI and RICH, survival at discharge of 40% with good functional outcomes in 68% of survivors at 1 year or more can be achieved with PBC after failure of HOsmRx. Based on 50% mortality cut-points, analysis suggests the limits of HOsmRx to be Na+ of 160 mEq/L and Osm of 330 mOsm/Kg H2O. Maintenance of higher cerebral perfusion pressure after PBC is associated with survival. PBC treatment of RIH may be even more important when other treatments of RIH, such as decompressive craniectomy, are not available.
(C) 2010 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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Crit Care Med
Practical lessons from the first outbreaks: Clinical presentation, obstacles, and management strategies for severe pandemic (pH1N1) 2009 influenza pneumonitis | | During the initial spring wave of novel influenza pH1N1 (2009), several North American cities experienced localized epidemics that served as a harbinger of the larger second Fall wave of infection. The city of Winnipeg, the capital of the province of Manitoba in central Canada, was one of the first in North America to deal with a rapid presentation of large numbers of patients requiring critical care services resulting from pandemic (pH1N1) 2009 influenza-associated respiratory failure. Mexico City, Orlando, FL, and Salt Lake City, UT, were other Northern Hemisphere sites of heavy disease activity during the spring wave of the pandemic. This article is written in a narrative format that allows the reader to understand the problems (both major and mundane, anticipated and unexpected) experienced by healthcare workers in these sites during this pandemic. Descriptions cover a range of issues and difficulties that caused significant stress to the operations of intensive care units in these cities. We hope to offer some insight into potential pitfalls and problems that may be experienced by other centers and provide some potential approaches to addressing these issues.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Prediction of cardiogenic shock using plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations in ST elevation myocardial infarction: An analysis from the ASSENT-4 Percutaneous Coronary Intervention Trial | | Objective: Cardiogenic shock is a major cause of death in ST elevation myocardial infarction. We investigated whether determination of B-type natriuretic peptide and the N-terminal fragment of its pro-hormone in the acute phase of ST elevation myocardial infarction could identify patients prone to development of cardiogenic shock.
Design: Retrospective analysis of a multicenter, randomized open-label trial (ASSENT-4 PCI; ClinicalTrials.gov Identifier: NCT00168792).
Methods: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone were determined in available stored samples of 1016 ST elevation myocardial infarction patients without signs of cardiogenic shock at randomization to primary percutaneous coronary intervention or to full-dose tenecteplase before percutaneous coronary intervention. The end point of the present analysis was in-hospital cardiogenic shock.
Interventions: None.
Measurements and Main Results: In total, 57 (5.6%) patients had cardiogenic shock during index hospitalization. In-hospital cardiogenic shock increased precipitously with higher baseline concentrations of plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone (B-type natriuretic peptide and the N-terminal fragment of its pro-hormone <=67 pg/mL: 1.9%; 68-1482 pg/mL: 5.9%; >1482 pg/mL: 14.9%; p < .001). Higher B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations were predictors of in-hospital shock, especially among those patients with relatively low clinical risk (no requirement of inotropic support before angiography, systolic blood pressure >100 mm Hg, heart rate <100 bpm, Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score of <122). In multivariate Cox regression analysis, higher plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations remained significant predictors of shock, in addition to age, systolic blood pressure, heart rate, and randomization to facilitated percutaneous coronary intervention and Killip classification. Furthermore, plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone significantly predicted in-hospital shock independently of the validated Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score (p = .014).
Conclusion: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations measured early in the acute phase of ST elevation myocardial infarction are useful in predicting the development of in-hospital cardiogenic shock.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Preparing your intensive care unit for the second wave of H1N1 and future surges | | Faced with increased demands for critical care services as a result of the novel H1N1 pandemic, hospitals must prepare a surge response in an attempt to manage these needs. In preparing for a surge response, factors to consider are staff, stuff (supplies and equipment), space, and systems necessary to respond to the event. This article uses this general framework to discuss surge issues in the context of H1N1 challenges that we are facing currently and to provide specific advice for hospitals. Particular attention is given to how hospitals can estimate the potential impact of H1N1 and pharmaceutical stockpiling.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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Crit Care Med
Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome * | | Objective: Right-to-left shunting across a patent foramen ovale may occur in acute respiratory distress syndrome as a result of pulmonary hypertension and positive-pressure mechanical ventilation. The shunt may worsen the hypoxemia. The objective of our study was to determine the prevalence, clinical implications, and prognosis of patent foramen ovale shunting during acute respiratory distress syndrome.
Design: Prospective study.
Setting: Medical intensive care unit of a university hospital in Creteil, France.
Patients: Two hundred three consecutive patients with acute respiratory distress syndrome.
Interventions: Patent foramen ovale shunting was detected by using transesophageal echocardiography with modified gelatin contrast. Moderate-to-large shunting was defined as right-to-left passage of at least 10 bubbles through a valve-like structure within three cardiac cycles after complete opacification of the right atrium. In 85 patients without and 31 with shunting, the influence of the positive end-expiratory pressure level on shunting was studied.
Measurements and Results: The prevalence of moderate-to-large patent foramen ovale shunting was 19.2% (39 patients). Compared to those in the group without shunting, the patients in group with shunting had larger right ventricle dimensions, higher pulmonary artery systolic pressure, and a higher prevalence of cor pulmonale. Compared to patients without shunting, patients with shunting had a poorer Pao2/Fio2 ratio response to positive end-expiratory pressure, more often required prone positioning and nitric oxide as adjunctive interventions, and had fewer ventilator-free and intensive care unit-free days within the first 28 days.
Conclusions: Moderate-to-large patent foramen ovale shunting occurred in 19.2% of patients with acute respiratory distress syndrome, in keeping with findings from autopsy studies. Patent foramen ovale was associated with a poor oxygenation response to positive end-expiratory pressure, greater use of adjunctive interventions, and a longer intensive care unit stay.
(C) 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins | | 9/6/2010 1:03:54 PM |
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J Trauma
Prevalence of Tension Pneumothorax in Fatally Wounded Combat Casualties | | Background: Tension pneumothorax is a potential cause of death in victims of penetrating chest trauma, but little is known about its actual prevalence.
Methods: Data that are part of the Vietnam Wound Data and Munitions Effectiveness Team study were analyzed to address this question. Radiographs of 978 casualties were examined for evidence of tension pneumothorax using standard radiologic criteria such as pleural separation, displacement of the mediastinum and diaphragm, trachea deviation, and compression of the contralateral lung
Results: Some or all of the radiographic changes were found in 198 casualties. Autopsy evidence indicated that 79 of these casualties died solely due to a chest wound. The fatal chest injury involved only the lungs in 55 casualties and caused a tension pneumothorax in 26. Fifteen of the 26 lived long enough to receive first aid from a medic or corpsman.
Conclusion: Tension pneumothorax was the cause of death in 3 to 4% of fatally wounded combat casualties. Some may be temporarily helped by battlefield thoracentesis.
(C) 2006 Lippincott Williams & Wilkins, Inc. | | 9/6/2010 1:03:57 PM |
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