Neuromuscular blockade in patients with ARDS: a rapid practice guideline.

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) is to formulate an evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adults with acute respiratory distress syndrome (ARDS). The panel comprised 20 international clinical experts from 12 countries, and 2 patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines and followed a strict conflict of interest policy. We convened panelists through teleconferences and web-based discussions. Guideline experts from the guidelines in intensive care, development, and evaluation Group provided methodological support. Two content experts provided input and shared their expertise with the panel but did not participate in drafting the final recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence and grade recommendations and suggestions. We used the evidence to decision framework to generate recommendations. The panel provided input on guideline implementation and monitoring, and suggested future research priorities. The overall certainty in the evidence was low. The ICM-RPG panel issued one recommendation and two suggestions regarding the use of NMBAs in adults with ARDS. Current evidence does not support the early routine use of an NMBA infusion in adults with ARDS of any severity. It favours avoiding a continuous infusion of NMBA for patients who are ventilated using a lighter sedation strategy. However, for patients who require deep sedation to facilitate lung protective ventilation or prone positioning, and require neuromuscular blockade, an infusion of an NMBA for 48 h is a reasonable option.

Sociodemographic differences in early access to liver transplantation services.

The question of whether health care inequities occur before patients with end-stage liver disease (ESLD) are waitlisted for transplantation has not previously been assessed. To determine the impact of gender, race and insurance on access to transplantation, we linked Pennsylvania sources of data regarding adult patients discharged from nongovernmental hospitals from 1994 to 2001. We followed the patients through 2003 and linked information to records from five centers responsible for 95% of liver transplants in Pennsylvania during this period. Using multinomial logistic regressions, we estimated probabilities that patients would undergo transplant evaluation, transplant waitlisting and transplantation itself. Of the 144,507 patients in the study, 4361 (3.0%) underwent transplant evaluation. Of those evaluated, 3071 (70.4%) were waitlisted. Of those waitlisted, 1537 (50.0%) received a transplant. Overall, 57,020 (39.5%) died during the study period. Patients were less likely to undergo evaluation, waitlisting and transplantation if they were women, black and lacked commercial insurance (p < 0.001 each). Differences were more pronounced for early stages (evaluation and listing) than for the transplantation stage (in which national oversight and review occur). For early management and treatment decisions of patients with ESLD to be better understood, more comprehensive data concerning referral and listing practices are needed.

Point-of-care sensors for the management of sepsis.

Point-of-care sensors that enable the fast collection of information relevant to a patient's health state can facilitate improved health access, reduce healthcare costs and improve the quality of healthcare delivery. In the diagnosis of sepsis - defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and the leading cause of in-patient death and of hospital readmission in the United States - predicting which infections will lead to life-threatening organ dysfunction and developing specific anti-sepsis treatments remain challenging because of the significant heterogeneity of the host response. Yet the use of point-of-care devices could reduce the time from the onset of a patient's infection to the administration of appropriate therapeutics. In this Perspective, we describe the current state of point-of-care sensors for the diagnosis and monitoring of sepsis, and outline opportunities in the use of these devices to dramatically improve patient care.

A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. METHODS: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

The influence of high-frequency jet ventilation with varying cardiac-cycle specific synchronization on cardiac output in ARDS.

BACKGROUND: Previous studies have shown "beat-to-beat" variation in systemic BP with high-frequency jet ventilation (HFJV). However, it is not clear if such changes are paralleled by changes in cardiac output. OBJECTIVE: To characterize the effect of HFJV near or equal to the heart rate (HR) on beat-to-beat cardiac output in an adult human subject with ARDS. DESIGN: Case study. SETTING: ICU, university teaching hospital. PATIENTS: One patient with end-stage liver disease complicated by sepsis, severe pancreatitis, ARDS, and multisystem organ failure. METHODS: The patient was intubated, sedated, paralyzed, and ventilated with controlled mechanical ventilation (CMV). Ventilatory mode was then switched to HFJV at fixed frequencies (f) near but not equal to the HR (f= 100, 110, and 120 beats/min; HR=108/min). HFJV was then synchronized to the ECG such that f and HR were equal. Continuous cardiac output (COc) was monitored during change of ventilator mode from CMV to fixed-rate HFJV to synchronized HFJV, then followed through progressive delays in jet triggering within the cardiac cycle during the synchronous HFJV mode. COc was monitored by arterial pulse-contour analysis, allowing assessment of beat-to-beat changes in cardiac output. MEASUREMENTS AND MAIN RESULTS: A cyclic variation in COc equal to the beat frequency difference between f and HR was observed (harmonic interaction) during fixed-rate HFJV. This COc oscillation was abolished during synchronous HFJV. COc was significantly greater during systolic synchronous HFJV as compared to diastolic synchronous HFJV or fixed-rate HFJV (10.1 to 9.0 [p<0.05] and to 8.6 [p<0.05] L/min, systolic synchronous to diastolic synchronous and to fixed-rate HFJV, respectively). CONCLUSIONS: This study demonstrates instantaneous variations in cardiac output in a human subject with fixed rates of HFJV near to the HR in humans. These variations are abolished by synchronous HFJV but cardiac output was dependent on the timing of the HFJV inspiration in relation to the cardiac cycle. COc is a potentially valuable method to monitor sudden changes in cardiac output and facilitate attempts to maximize cardiac output during synchronized HFJV.

Measuring resource use in the ICU with computerized therapeutic intervention scoring system-based data.

BACKGROUND AND OBJECTIVE: In this era of health-care reform, there is increasing need to monitor and control health-care resource consumption. This requires the development of measurement tools that are practical, uniform, reproducible, and of sufficient detail to allow comparison among institutions, among select groups of patients, and among individual patients. We explored the feasibility of generating an index of resource use based on the Therapeutic Intervention Scoring System (TISS) from hospital electronic billing data. Such an index is potentially comparable across institutions, allows assessment of care at many levels, is well understood by clinicians, and captures many of the resources relevant to the ICU. DESIGN: We developed an automated mapping of the hospital billing database into the different items of TISS and generated computerized active TISS scores on 1,372 ICU days. The computerized score was then validated by comparison to prospectively gathered active TISS scores by trained data collectors. SETTING: Eight ICUs within a university teaching institution. PATIENTS: We studied 1,229 general medical and surgical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Active TISS scores ranged from 0 to 31 points. The two scores were well correlated (R2=0.53) and highly calibrated (as assessed by regression of active TISS on mean computerized active TISS [R2=0.85]). The scores were identical on 756 days (55.6%) and differed by < or = 3 TISS points on an additional 387 (28.2%) days. Interreliability assessment suggested substantial agreement (kappa statistic=0.71). The discriminatory power of the computerized score to identify different levels of ICU resource use was excellent as assessed by area under the receiver operating characteristics curves at four threshold points (0.91, 0.87, 0.89, and 0.88). Performance of the computerized score was similar across medical, coronary, and surgical ICU patient groups. CONCLUSION: An automated algorithm can reproduce valid TISS scores from standard hospital billing data, allowing comparison of patients and groups of patients in order to better understand ICU resource use.

Community-wide assessment of intensive care outcomes using a physiologically based prognostic measure: implications for critical care delivery from Cleveland Health Quality Choice.

STUDY OBJECTIVES: To examine the applicability of a previously developed intensive care prognostic measure to a community-based sample of hospitals, and assess variations in severity-adjusted mortality across a major metropolitan region. DESIGN: Retrospective cohort study. SETTING: Twenty-eight hospitals with 38 ICUs participating in a community-wide initiative to measure performance supported by the business community, hospitals, and physicians. PATIENTS: Included in the study were 116,340 consecutive eligible patients admitted to medical, surgical, neurologic, and mixed medical/surgical ICUs between March 1, 1991, and March 31, 1995. MAIN OUTCOME MEASURES: The risk of hospital mortality was assessed using a previous risk prediction equation that was developed in a national sample, and a reestimated logistic regression model fit to the current sample. The standardized mortality ratio (SMR) (actual/predicted mortality) was used to describe hospital performance. RESULTS: Although discrimination of the previous national risk equation in the current sample was high (receiver operating characteristic [ROC] curve area = 0.90), the equation systematically overestimated the risk of death and was not as well calibrated (Hosmer-Lemeshow statistic, 2407.6, 8 df, p < 0.001). The locally derived equation had similar discrimination (ROC curve area = 0.91), but had improved calibration across all ranges of severity (Hosmer-Lemeshow statistic = 13.5, 8 df, p = 0.10). Hospital SMRs ranged from 0.85 to 1.21, and four hospitals had SMRs that were higher or lower (p < 0.01) than 1.0. Variation in SMRs tended to be greatest during the first year of data collection. SMRs also tended to decline over the 4 years (1.06, 1.02, 0.98, and 0.94 in years 1 to 4, respectively), as did mean hospital length of stay (13.0, 12.4, 11.6, and 11.1 days in years 1 to 4; p < 0.001). However, excluding the increasing (p < 0.001) number of patients discharged to skilled nursing facilities attenuated much of the decline in standardized mortality over time. CONCLUSIONS: A previously validated physiologically based prognostic measure successfully stratified patients in a large community-based sample by their risk of death. However, such methods may require recalibration when applied to new samples and to reflect changes in practice over time. Moreover, although significant variations in hospital standardized mortality were observed, changing hospital discharge practices suggest that in-hospital mortality may no longer be an adequate measure of ICU performance. Community-wide efforts with broad-based support from business, hospitals, and physicians can be sustained over time to assess outcomes associated with ICU care. Such efforts may provide important information about variations in patient outcomes and changes in practice patterns over time. Future efforts should assess the impact of such community-wide initiatives on health-care purchasing and institutional quality improvement programs.

The influence of clinical study design on cost-effectiveness projections for the treatment of gram-negative sepsis with human anti-endotoxin antibody.

PURPOSE: This study was performed to compare the effect of entry criteria, patient population, and study design on outcome and projected cost-effectiveness of human anti-endotoxin antibody (HA-1A). MATERIALS AND METHODS: Patients with suspected or documented gram-negative bacteremia (GNB) with sepsis syndrome or shock received HA-1A during an open-label protocol. The patient characteristics and outcome measures of this series were compared with those of a placebo-controlled randomized clinical trial (RCT) of HA-1A. Both data sets were subjected to three published cost-effectiveness models of anti-endotoxin therapy, which were derived from RCT data. RESULTS: One hundred thirty-one patients (43 with gram-negative bacteremia) received HA-1A during a 19-month open-label protocol. Comparison with the RCT results demonstrated greater severity of illness and higher 28-day mortality in the open-label protocol. When projected for open-label recipients, HA-1A was considerably less cost-effective than in the original projections based on RCT-derived data. This reduction in cost-effectiveness was consistent across all three models and their respective sensitivity analyses. CONCLUSIONS: Extrapolating cost-effectiveness from RCT-derived analyses to open-label usage may yield widely inaccurate projections because of only small differences in patient population and the drug administration protocol.

Organization and management of critical care systems in unconventional situations.

Critical care medicine is a field of medicine using the highest concentration of expensive diagnostic and life-support technology for the benefit of a single individual. Conventional use of this resource and specialty is clearly understood, despite the fact that it is not necessarily comparable among different institutions. Some of the major issues in using critical care as a medical tool during extraordinary stress on the hospital, and the potential for using it in unconventional environments outside an established institution, have been reviewed. It is clear that the expertise and multidisciplinary approach can be of great use in disaster response, and a national effort toward integrating critical care into overall medical response is in progress.

Using large-scale databases to measure outcomes in critical care.

The major intent of this article is to describe the availability and potential use of large-scale databases; however, it is first essential to know and understand the basic principles involved in the conduct and interpretation of observational outcomes studies. In this article, the authors briefly overview the design of observational outcomes studies as applied to critical care medicine. Then, criteria for evaluating data sources and for in-depth reviewing of the available data sources from which these observational studies can be conducted are discussed.

International comparisons of critical care outcome and resource consumption.

Though there are reasonable data to suggest that certain countries, such as the United States, spend considerably more money on the provision of critical care services than others, there is little information regarding the added benefits accrued with this additional expense. Studies to date have suggested little if no difference in outcome but have been limited in their size, design, and choice of outcome measures. Furthermore, significant underlying societal priorities and philosophy may dictate that the optimal critical care delivery system is different for different countries. With the increasing availability of large patient databases, however, it will be more feasible in the future to design and conduct assessments of critical care delivery systems between countries taking appropriate account of the choice of study design, definition of at-risk populations, and choice of valuable measures of output and cost. The results of such assessments will hopefully drive wiser decision making in the design and management of critical care delivery systems worldwide.

Incidence and definition of sepsis and associated organ dysfunction.

AIMS: To discuss the incidence, outcome and predisposing factors to systemic inflammatory response syndrome (SIRS), sepsis, and multiple organ failure. METHODS: A qualitative review of the literature. RESULTS: Case definitions of sepsis and severe sepsis, though clarified recently, are still arbitrary. It seems, however, that SIRS is not useful in identifying severe sepsis while organ failure has become a cornerstone for this definition. Incidence of severe sepsis appears to be approximately 10% of all ICU admissions, totaling nearly one million cases annually in the U.S. alone, and rising. Mortality associated with these events is still high, especially among ICU patients. Recent studies have been demonstrating an association between a variety of genetic polymorphisms and progression to and dying from sepsis. CONCLUSION: Recently there has been an increasing amount of information enabling characterization of the epidemiology of sepsis, which may help to direct appropriate care in the coming years.

Recommendations for Life-Supporting First-Aid training of the lay public for disaster preparedness.

In catastrophic disasters such as major earthquakes in densely populated regions, effective Life-Supporting First-Aid (LSFA) and basic rescue can be administered to the injured by previously trained, uninjured survivors (co-victims). Administration of LSFA immediately after disaster strikes can add to the overall medical response and help to diminish the morbidity and mortality that result from these events. Widespread training of the lay public also may improve bystander responses in everyday emergencies. However, for this scheme to be effective, a significant percentage of the lay population must learn in eight basic steps of LSFA. These have been developed by the International Resuscitation Research Center in collaboration with the World Association for Emergency and Disaster Medicine, the City of Pittsburgh Department of Public Safety, and the American Red Cross (Pennsylvania chapter). They include: 1) scene survey; 2) airway control; 3) rescue breathing (mouth-to-mouth); 4) circulation (chest compressions; may be omitted for disasters, but should be retained for everyday bystander response); 5) abdominal thrusts for choking (may be omitted for disasters, but retained for everyday bystander response); 6) control of external bleeding; 7) positioning for shock; and 8) call for help.

Epidemiologic assessment of mortality, building collapse pattern, and medical response after the 1992 earthquake in Turkey. Disaster Reanimatology Study Group (DRSG).

BACKGROUND: Post-earthquake engineering and epidemiologic assessments are important for the development of injury prevention strategies. This paper describes mortality and its relationship to building collapse patterns and initial medical responses following the 1992 earthquake in Erzincan, Turkey. METHODS: The study consisted of: 1) background data collection and review; 2) design and implementation of a field survey; and 3) site inspection of building collapse patterns. The survey included: 1) national (n = 11) and local (n = 17) officials; 2) medical and search and rescue (SAR) workers (n = 38); and 3) a geographically stratified random sample of lay survivors (n = 105). The survey instruments were designed to gather information regarding location, injuries, initial actions and prior training of survivors and responders, and the location, injuries, and management of dead and dying victims. A case-control design was constructed to assess the relationship between mortality, location, and building collapse pattern. RESULTS: There was extensive structural damage throughout the region, especially in the city where mid-rise, unreinforced masonry buildings (MUMBs) incorporating a "soft" first floor design (large store windows for commercial use) and one story adobe structures were most vulnerable to collapse. Of 526 people who died in the city, 87% (n = 456) were indoors at the time of the earthquake. Of these, 92% (n = 418) died in MUMBs. Of 54 witnessed deaths, 55% (n = 28) of victims died slowly, the majority of whom (n = 26) were pinned or trapped (p < 0.05). Of 42 MUMB occupants identified through the survey, those who died (n = 25) were more likely to have been occupying the ground floor when compared with survivors (n = 28) (p < 0.01). Official medical and search and rescue responders arrived after most deaths had occurred. Prior first-aid or rescue training of lay, uninjured survivors was associated with a higher likelihood of rescuing and resuscitating others (p < 0.001). CONCLUSIONS: During an earthquake, MUMBs with soft ground floor construction are highly lethal, especially for occupants on the the ground floor, suggesting that this building type is inappropriate for areas of seismic risk. The vulnerability of MUMBs appears due to a lack of lateral force resistance as a result of the use of glass store front windows and the absence of shear walls. The prevalence of this building type in earthquake-prone regions needs to be investigated further. A large portion of victims dying in an earthquake die slowly at the scene of injury. Prior public first-aid and rescue training programs increase participation in rescue efforts in major earthquakes and may improve survival.

An analysis of prehospital mortality in an earthquake. Disaster Reanimatology Study Group.

INTRODUCTION: Anecdotal observations about prehospital emergency medical care in major natural and human-made disasters, such as earthquakes, have suggested that some injured victims survive the initial impact, but eventually die because of a delay in the application of life-saving medical therapy. METHODS: A multidisciplinary, retrospective structured interview methodology to investigate injury risk factors, and causes and circumstances of prehospital death after major disasters was developed. In this study, a team of United States researchers and Costa Rican health officials conducted a survey of lay survivors and health care professionals who participated in the emergency medical response to the earthquake in Costa Rica on 22 April 1991. RESULTS: Fifty-four deaths occurred prior to hospitalization (crude death rate = 0.4/1,000 population). Seventeen percent of these deaths (9/54) were of casualties who survived the initial impact but died at the scene or during transport. Twenty-two percent (2/9) were judged preventable if earlier emergency medical care had been available. Most injuries and deaths occurred in victims who were inside wooden buildings (p < .01) as opposed to other building types or were pinned by rubble from building collapse. Autopsies performed on a sample of victims showed crush injury to be the predominant cause of death. CONCLUSIONS: A substantial proportion of earthquake mortality in Costa Rica was protracted. Crush injury was the principal mechanism of injury and cause of death. The rapid institution of enhanced prehospital emergency medical services may be associated with a significant life-saving potential in these events.

Post-preparedness medical disaster response in Costa Rica.

INTRODUCTION: The 1991 earthquake in the Limón area of Costa Rica presented the opportunity to examine the effectiveness of a decade of disaster preparedness. HYPOTHESIS: Costa Rica's concentrated work in disaster preparedness would result in significantly better management of the disaster response than was evident in earlier disasters in Guatemala and Nicaragua, where disaster preparedness largely was absent. METHODS: Structured interviews with disaster responders in and outside of government, and with victims and victims' neighbors. Clinical and epidemiologic data were collected through provider agencies and the coroner's office. RESULTS: Medical aspects of the disaster response were effective and well-managed through a network of clinic-based radio communications. Nonmedical aspects showed confusion resulting from: 1) poor government understanding of the roles and responsibilities of the central disaster coordinating agency; and 2) poor extension of disaster preparedness activities to the rural area that was affected by the earthquake. CONCLUSION: To be effective, disaster preparedness activities need to include all levels of government and rural, as well as urban, populations.

Severity scoring systems in the modern intensive care unit.

In recent years, several factors have led to increasing focus on the meaning of appropriateness of care and clinical performance in the intensive care unit (ICU). The emergence of new and expensive treatment modalities, a deeper reflection on what constitutes a desirable outcome, increasing financial pressure from cost containment efforts, and new attitudes regarding end-of-life decisions are reshaping the delivery of intensive care worldwide. This quest for a measure of ICU performance has led to the development of severity adjustment systems that will allow standardised comparisons of outcome and resource use across ICUs. These systems, for many years used only in the research setting, have evolved to become sophisticated, computer-based decision-support tools, in some instances commercially developed, and capable of predicting a diverse set of outcomes. Their application has broadened to include ICU performance assessment, individual patient decision-making, and pre- and post-hoc risk stratification in randomised trials. In this paper, we review the popular scoring systems currently in use; design issues in the development and evaluation of new scoring systems; current applications of scoring systems; and future directions.

A review of therapeutic attempts to recruit the microcirculation in patients with sepsis.

Microcirculatory dysfunction is a pivotal element of the pathogenesis of severe sepsis and septic shock. Technological development, including sidestream darkfield videomicroscopy, now allows for bedside assessment of the microcirculation. A number of clinical studies have established the importance of the microcirculation in sepsis. The objective of this review is to discuss human trials that have assessed interventions aimed at improving microcirculatory flow in patients with sepsis.

Acute care practices relevant to quality end-of-life care: a survey of Pennsylvania hospitals.

BACKGROUND: Improving end-of-life care in the hospital is a national priority. PURPOSE: To explore the prevalence and reasons for implementation of hospital-wide and intensive care unit (ICU) practices relevant to quality care in key end-of-life care domains and to discern major structural determinants of practice implementation. DESIGN: Cross-sectional mixed-mode survey of chief nursing officers of Pennsylvania acute care hospitals. RESULTS: The response rate was 74% (129 of 174). The prevalence of hospital and ICU practices ranged from 95% for a hospital-wide formal code policy to 6% for regularly scheduled family meetings with an attending physician in the ICU. Most practices had less than 50% implementation; most were implemented primarily for quality improvement or to keep up with the standard of care. In a multivariable model including hospital structural characteristics, only hospital size independently predicted the presence of one or more hospital initiatives (ethics consult service, OR 6.13, adjusted p = 0.02; private conference room in the ICU for family meetings, OR 4.54, adjusted p<0.001). CONCLUSIONS: There is low penetration of hospital practices relevant to quality end-of-life care in Pennsylvania acute care hospitals. Our results may serve to inform the development of future benchmark goals. It is critical to establish a strong evidence base for the practices most associated with improved end-of-life care outcomes and to develop quality measures for end-of-life care to complement existing hospital quality measures that primarily focus on life extension.