What’s New in General Surgery:
Critical Care and Trauma
Lena M Napolitano, MD, FACS, FCCP, FCCM
There have been a number o...
the Surgery of Trauma, the American College of Sur-
geons Committee on Trauma, the Eastern Association
for the Surgery of ...
case scenario demonstrated savings of $4.2 to $13
million US. Under the worst-case scenario, there was a
net cost of $890,...
saline for intravascular-fluid resuscitation during the 28
days after ICU admission. Of the 6,997 patients who
underwent r...
pendently associated with higher 6-month mortality
(adjusted hazard ratio [HR], 3.2; 95% CI, 1.4 to 7.7;
p ϭ 0.008), and l...
evidence-based guidelines for preventing CRB; and em-
powering nurses to stop the catheter insertion procedure
if a violat...
restrictive group were 10%, as compared with 9% in the
liberal group (p ϭ 0.81). The presence of multiple organ
significant differences were identified in the penetrating
trauma group. No safety issues were identified in either
improved nutrition support practice in ICUs and may
translate into better outcomes for critically ill patients
receiving n...
cine crisis: a call for federal action: a white paper from the critical
care professional societies. Chest 2004;125:1518–1...
and improved outcome associated with the use of recombinant
factor VIIa as an adjunct in trauma [abstract]. J Trauma
Upcoming SlideShare
Loading in …5

What's New in General Surgery: Critical Care and Trauma


Published on

Published in: Health & Medicine, Business
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

What's New in General Surgery: Critical Care and Trauma

  1. 1. What’s New in General Surgery: Critical Care and Trauma Lena M Napolitano, MD, FACS, FCCP, FCCM There have been a number of major developments in critical care and trauma in 2004, ranging from new re- search findings to critical care workforce issues and dis- cussions regarding optimal education and training in trauma and surgical critical care. We have made great advances in a number of areas, and additional initiatives to expand research efforts in trauma and critical care are ongoing. Research There are a number of obstacles to performing clinical trials and outcomes studies involving critically ill and injured patients with complex syndromes that currently lack effective treatments. The Canadian Critical Care Trials Group and the Australia and New Zealand Inten- sive Care Society Clinical Trials Group have established comprehensive research efforts in this regard. The Acute Respiratory Distress Syndrome (ARDS) Clinical Net- work (ARDSNet) was the first organized US national effort to conduct multicenter clinical trials in critical care, established in 1994.1 The US and Canada launched a major collaborative research program in 2004. The leading federal health research agencies in the US and Canada—the National Institutes of Health (NIH) and the Canadian Institutes of Health Research (CIHR)—formed a partnership to advance research in cardiovascular and respiratory diseases. Three research programs were initiated in 2004, in- cluding “Clinical Research Consortium to Improve Re- suscitation Outcomes,” which will address novel strate- gies to resuscitate heart attack and trauma patients. This is the first organized multicenter effort to perform resus- citation research in trauma in the US. The Resuscitation Outcomes Consortium (ROC) consists of 10 Regional Clinical Centers and a Data and Coordinating Center that will provide the necessary infrastructure to conduct multiple collaborative trials to aid rapid translation of promising scientific and clinical advances to improve resuscitation outcomes. The ongoing direct study com- mitment of the sponsors is for at least 5 years of funding at approximately $10 million per year. Information re- garding the specific participating centers can be ob- tained on the ROC Web site.2 Others contributing sup- port to this initiative include the US Department of Defense, other institutes within the NIH, the Institute of Circulatory and Respiratory Health from the Canadian In- stitutes of Health Research, the Canadian Defense Re- search and Development Program, and the National Insti- tute of Neurological Disorders and Stroke. There is significant concern that it has become in- creasingly difficult to conduct clinical research in trauma and critical care, and that it may negatively impact on future efforts.3 Difficulties in obtaining patient or sur- rogate consent and in determining the standard of care for the control group are relevant issues.4 An important statement from the American Thoracic Society regard- ing the ethical conduct of clinical research involving critically ill patients was published in 2004, providing some principles and guidance in this difficult area.5 Education and resident training The Guidelines for Critical Care Medicine Training and Continuing Medical Education were published this year by the American College of Critical Care Medicine.6 Guidelines for the continuum of education in critical care, from residency training through specialty training and ongoing through practice, will facilitate standard- ization of physician education in critical care medicine. The future of trauma care as a specialty and the opti- mal training paradigm for those interested in trauma and surgical critical care have come under great scrutiny. In 2004, a number of national organizations established an initiative to collaborate and coordinate with all of the professional societies that represent surgical critical care, trauma, and acute surgery. This effort includes the American Board of Surgery, American Association for Received February 11, 2005; Accepted February 11, 2005. From the Department of Surgery, University of Michigan School of Medi- cine, Ann Arbor, MI. Correspondence address: Lena M Napolitano, MD, FACS, FCCP, FCCM, University of Michigan School of Medicine, Department of Surgery, Section of General Surgery, University of Michigan Health System,1500 E Medical Center Dr, Ann Arbor, MI 48109-0331. 755 © 2005 by the American College of Surgeons ISSN 1072-7515/05/$30.00 Published by Elsevier Inc. doi:10.1016/j.jamcollsurg.2005.02.018
  2. 2. the Surgery of Trauma, the American College of Sur- geons Committee on Trauma, the Eastern Association for the Surgery of Trauma, the Surgical Section of the Society of Critical Care Medicine, the American Burn Association, and the WesternTrauma Association.These organizations are examining options for linking the spe- cialties of general surgery, trauma surgery, and surgical critical care to create a career practice model for the future. Critical care workforce and manpower issues The US is currently facing an unprecedented, and largely unrecognized, shortage of physicians trained to provide critical care services. This is one of the most pressing issues affecting the future of our aging popula- tion and American medicine. As initially described in a study by the Committee on Manpower for Pulmonary and Critical Care Societies (COMPACCS), future de- mand for critical care services in the US will soon exceed the capabilities of the current delivery system.7 The most alarming problem is the anticipated shortage of health- care professionals practicing critical care. This past year, the four major critical care societies in the US (American Association of Critical Care Nurses, American College of Chest Physicians, American Tho- racic Society, and Society of Critical Care Medicine) united in their efforts to address the shortage of health- care providers who care for the critically ill.8 The Critical Care Workforce Partnership was established and the rec- ommendations for actions were reported by the FOCCUS (Framing Options for Critical Care in the United States) Task Force.9 An additional publication outlined federal policy initiatives to address the shortage of critical care providers.10 Numerous studies demonstrate that critical care ser- vices directed by physicians formally trained in critical care medicine reduce mortality in the ICU and reduce health-care costs. To address the shortage, the critical care professional societies recommend that steps be taken to improve the efficiency of critical care providers, to increase the number of critical care providers, and to address the demand for critical care services. Critical care use in the US A recent analysis of nonfederal acute care hospitals in the US documented that the number of hospitals offering critical care medicine (CCM) between 1985 and 2000 decreased by 13.7% (4,150 to 3,581). Also, total hospi- tal beds decreased substantially, by 26.4% (889,600 to 654,400) in these hospitals. In contrast, CCM beds in- creased by 26.2% (69,300 to 87,400) and CCM bed costs per day increased by 126% ($1,185 to $2,674 US). Although CCM costs increased by 190.4% ($19.1 bil- lion to $55.5 billion US), the proportion of national health expenditures allocated to CCM decreased by 5.4%. In 2000, CCM costs represented 13.3% of hos- pital costs, 4.2% of national health expenditures, and 0.56% of the gross domestic product. These authors concluded that CCM is increasingly used and promi- nent in a shrinking US hospital system.11 The Leapfrog Group has recommended that imple- mentation of the Intensive Care Unit Physician Staffing be standard in all hospitals.12 The ICU Physician Staff- ing standard requires that intensive care units have a dedicated intensivist present during daytime hours. Outside of these hours, an intensivist must be immedi- ately available by pager, and a physician or “physician extender” must be in the hospital and able to immedi- ately reach intensive care unit patients. Research shows that if the first three leaps (Computer Physician Order Entry, Intensive Care Unit Physician Staffing, and Evidence-Based Hospital Referral) were implemented in all urban hospitals in the US, we could save up to 65,341 lives and prevent as many as 907,600 serious medication errors each year. A recent study using financial modeling examined hospital costs and savings over a 1-year period of imple- menting the ICU Physician Staffing standard compared with the existing standard of nonintensivist staffing in adult ICUs using published data for nonrural hospi- tals.13 Cost savings ranged from $510,000 to $3.3 mil- lion US for 6- to 18-bed intensive care units. The best- Abbreviations and Acronyms CCM ϭ critical care medicine CRB ϭ catheter-related bacteremia ECG ϭ electrocardiographic HBOC ϭ hemoglobin-based oxygen carrier HR ϭ hazard ratio NPPV ϭ noninvasive positive pressure ventilation NTDB ϭ National Trauma Data Bank PEEP ϭ positive end-expiratory pressure rFVIIa ϭ recombinant factor VIIa TBI ϭ traumatic brain injury TRISS ϭ Trauma and Injury Severity Score VAP ϭ ventilator-associated pneumonia 756 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg
  3. 3. case scenario demonstrated savings of $4.2 to $13 million US. Under the worst-case scenario, there was a net cost of $890,000 to $1.3 million US. These eco- nomic findings must be interpreted in the context of significant reductions in patient morbidity and mortal- ity rates also associated with intensivist staffing. The au- thors concluded by stating that, given the magnitude of its clinical and financial impact, hospital leaders should be asking “how to” rather than “whether to” implement The Leapfrog Group’s ICU Physician Staffing standard. Surviving sepsis guidelines In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcomes in severe sepsis. These guidelines were published in 2004.14 The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as important new knowledge be- comes available. An effort to translate these evidence-based recom- mendations regarding many aspects of the acute man- agement of sepsis and septic shock into improved out- comes for the critically ill patient is under way by the use of “sepsis bundles.” A bundle is a selected set of inter- ventions or processes of care distilled from evidence- based practice guidelines that, when implemented as a group, provides a more robust picture of the quality of care provided. The Severe Sepsis Bundles are a distilla- tion of the concepts and recommendations found in the practice guidelines published by the Surviving Sepsis Campaign in 2004. The Severe Sepsis Bundles are designed to allow teams to follow the timing, sequence, and goals of the individ- ual elements of care, in order to achieve the goal of a 25% reduction in mortality from severe sepsis. There are cur- rently two sepsis bundles recommended for use: Sepsis Resuscitation Bundle: Tasks that should begin im- mediately but must be done within 6 hours for patients with severe sepsis or septic shock. Sepsis Management Bundle: Tasks that should begin im- mediately but must be done within 24 hours for pa- tients with severe sepsis or septic shock.15 International consensus conference—pancreatitis Acute pancreatitis represents a spectrum of disease rang- ing from a mild, self-limited course requiring only brief hospitalization to a rapidly progressive, fulminant illness resulting in multiple organ dysfunction syndrome, with or without accompanying sepsis. An international con- sensus conference was held in April 2004 to develop recommendations for the management of the critically ill patient with severe acute pancreatitis. Evidence-based recommendations were developed by a jury of 10 per- sons representing surgery, internal medicine, and critical care after conferring with experts and reviewing the per- tinent literature to address specific questions concerning the management of patients with severe acute pancreati- tis.There were a total of 23 recommendations developed to provide guidance to critical care clinicians caring for the patient with severe acute pancreatitis.16 These included a recommendation against the rou- tine use of prophylactic systemic antibacterial or anti- fungal agents in patients with or without necrotizing pancreatitis.The jury also recommended against pancre- atic debridement or drainage for sterile necrosis, limiting debridement or drainage to those with infected pancre- atic necrosis or abscess confirmed by radiologic evidence of gas or results of fine needle aspiration. The jury also recommended that whenever possible, operative necro- sectomy or drainage be delayed at least 2 to 3 weeks to allow for demarcation of the necrotic pancreas. These recommendations differ in several ways from previous recommendations because of the release of recent data concerning the management of these patients and also because of the focus on the critically ill patient. There were a number of important questions that could not be answered using an evidence-based approach, and areas in need of further research were identified. Resuscitation Two important clinical studies on fluid resuscitation were published in 2004. The Saline versus Albumin Fluid Evaluation (SAFE) Study was a multicenter, ran- domized, double-blind trial comparing the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU.17 This study was a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian Red Cross Blood Service, and the George Institute for International Health. Patients were randomized to receive either 4% albumin or normal 757Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care
  4. 4. saline for intravascular-fluid resuscitation during the 28 days after ICU admission. Of the 6,997 patients who underwent randomization, 3,497 were assigned to re- ceive albumin and 3,500 to receive saline; the two groups had similar baseline characteristics.There was no difference in 28-day mortality identified (relative risk of death, 0.99; 95% CI 0.91 to 1.09; p ϭ 0.87). Interestingly, among the 1,186 patients with trauma, albumin was associated with a trend toward increased mortality (relative risk of death in the albumin group, 1.36; 95% CI 0.99 to 1.86), possibly explained by the effect of trauma associated with brain injury (relative risk of death, 1.62; 95% CI 1.12 to 2.34). In contrast, among 1,218 patients with severe sepsis, albumin was associated with a trend toward reduced mortality (rel- ative risk of death, 0.87; 95% CI 0.74 to 1.02). These subgroup analyses should be interpreted with cau- tion and will require validation in future studies. A prehospital trial of hypertonic saline resuscitation in patients with hypotension (systolic blood pressure Ͻ100mmHg)andseveretraumaticbraininjury(Glasgow Coma Scale score Ͻ 9, n ϭ 229) was conducted in Australia.18 Patients were randomly assigned to receive a rapid intravenous infusion of either 250 mL of 7.5% saline (n ϭ 114) or 250 mL of Ringer’s lactate solution (n ϭ 115; controls) in addition to conventional intrave- nous fluid and resuscitation protocols administered by paramedics. No significant differences in survival at hospital discharge, 6-month survival, or functional neurologic outcomes at 6 months after injury were identified. There is still great interest in the use of hypertonic saline for resuscitation in shock, because of its ability to modulate the inflammatory response19 and reduce fluid resuscitation volume requirements.20 In fact, two multi- center clinical trials under consideration by the Resusci- tation Outcomes Consortium seek to determine the im- pact of hypertonic resuscitation on survival in hypovolemic shock in trauma, and on longterm neuro- logic outcomes in blunt severe traumatic brain injury. Both studies will be three arm, randomized, blinded intervention trials comparing hypertonic saline/dextran (7.5% saline, 6% dextran 70), hypertonic saline alone (7.5% saline), and normal saline as the initial resuscita- tion fluid administered to these patients in the prehos- pital setting. Respiratory failure A number of studies have previously documented that the use of noninvasive positive pressure ventilation (NPPV) for respiratory failure related to cardiogenic pulmonary edema and COPD exacerbation is associated with improved outcomes. But, does noninvasive positive pressure ventilation improve outcomes in acute hypox- emia respiratory failure unrelated to these diagnoses?21 A systematic review of prospective randomized trials re- cently addressed this question. This study confirmed that the addition of NPPV to standard care in the setting of acute hypoxemic respiratory failure reduced the rate of endotracheal intubation (absolute risk reduction 23%, 95% CI 10% to 35%) and ICU length of stay (absolute reduction 2 days, 95% CI 1 to 3 days); ICU mortality was less clear, and the heterogeneity found among studies suggested that effectiveness varies among different populations. As a result, the literature does not support the routine use of NPPV in all patients with acute hypoxemic respiratory failure. In patients who require intubation for respiratory fail- ure, there appears to be accumulating evidence in favor of early tracheostomy. A prospective randomized study in 120 patients projected to need mechanical ventilation for less than 14 days was randomized to early percuta- neous tracheotomy within 48 hours or delayed trache- otomy at days 14 to 16. The early tracheotomy group had significantly less mortality (31.7% versus 61.7%), pneumonia (5% versus 25%), and accidental extuba- tions (0 versus 6) compared with the prolonged transla- ryngeal group. The early tracheotomy group spent less time in the ICU (4.8 Ϯ 1.4 days versus 16.2 Ϯ 3.8 days) and on mechanical ventilation (7.6 Ϯ 2.0 days versus 17.4 Ϯ 5.3 days). There was also significantly more damage to the mouth and larynx in the prolonged trans- laryngeal intubation group.22 We have now recognized the high incidence of delir- ium as a common form of organ dysfunction in the ICU, especially in patients requiring mechanical ventilation. In a prospective cohort study of 224 mechanically ven- tilated patients, 81.5% developed delirium at some point during the ICU stay.23 Patients who developed delirium had higher 6-month mortality rates (34% ver- sus 15%, p ϭ 0.03) and spent 10 days longer in the hospital than those who never developed delirium (p Ͻ 0.001). After adjusting for covariates (including age, se- verity of illness, comorbid conditions, coma, and use of sedatives or analgesic medications), delirium was inde- 758 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg
  5. 5. pendently associated with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% CI, 1.4 to 7.7; p ϭ 0.008), and longer hospital stay (adjusted HR, 2.0; 95% CI, 1.4 to 3.0; p Ͻ 0.001). Delirium in the ICU was also independently associated with a longer post- ICU stay (adjusted HR, 1.6; 95% CI, 1.2 to 2.3; p ϭ 0.009), fewer median days alive and without mechanical ventilation (19 days [interquartile range, 4 to 23 days] versus 24 days [interquartile range 19 to 26 days]; ad- justed p ϭ 0.03), and a higher incidence of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3 to 35.3; p ϭ 0.002). The ARDSNet trial previously documented that in patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume (6 versus 12 mL/kg) resulted in decreased mortality and increased the number of days without ventilator use.24 In 2004, the ARDSNet group published the trial comparing the effects of higher and lower pos- itive end-expiratory pressure (PEEP) levels on clinical outcomes in ARDS patients (n ϭ 549).25 This study documented that in patients with acute lung injury and ARDS who received mechanical ventilation with a tidal- volume goal of 6 mL/kg of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes were similar whether lower or higher PEEP levels were used. Two multicenter, randomized, double-blind phase trials of a protein-containing surfactant in adults with ARDS from various causes (n ϭ 448) compared stan- dard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C–based surfactant given within a period of 24 hours.26 There was no significant difference between the groups in terms of mortality or the need for mechanical venti- lation. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and mul- tivariate analyses. Surfactant replacement therapy for ARDS in neo- nates is standard of care. Future studies with surfactant therapy in ARDS may consider alternative formulations of recombinant surfactant, earlier initiation of surfactant therapy, studies in more homogenous patient groups, and different methods of delivery of surfactant to the injured lung. Infections Prevention of health care–associated infections contin- ues to be a primary goal in the care of all critically ill and injured patients. Health care–associated pneumonia Pneumonia continues to be a leading cause of health care–associated infection in the ICU, and all efforts to prevent pneumonia should be implemented. The CDC Guidelines for the Prevention of Healthcare-Associated Pneu- monia were published in 2004.27 Most recently, the Guide- lines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia were published by the American Thoracic Society and the Infectious Diseases Society of America.28 These two docu- ments provide comprehensive and current information regarding evidence-based practices for prevention, diag- nosis, and treatment of pneumonia in critically ill and injured patients. An important study examined the optimal duration of antimicrobial therapy for the treatment of ventilator- associated pneumonia (VAP).29 A prospective, random- ized, double-blind clinical trial conducted in 51 French ICUs enrolled 401 patients diagnosed with VAP by quantitative culture of bronchoscopic specimens and who had received initial appropriate empirical antimi- crobial therapy. Patients were randomized to receive 8 or 15 days of antibiotic therapy. This study documented comparable clinical effectiveness against VAP with the 8- and 15-day antibiotic treatment regimens, and de- creased antibiotic use in the 8-day group. Importantly, patients with VAP caused by nonfermenting gram- negative bacilli, including Pseudomonas aeruginosa, did have a higher pulmonary infection-recurrence rate com- pared with those receiving 15 days of treatment (40.6% versus 25.4%; difference, 15.2%, 90% CI, 3.9% to 26.6%). Catheter-related bacteremia The importance of education and process improvement in prevention of catheter-related bacteremia (CRB) has been documented in a number of studies. A new bench- mark has recently been set, with complete elimination of CRB in the surgical ICU in a single institution study over 5 years (1998 to 2002).30 To eliminate CRB, a qual- ity improvement team implemented five interventions: educating the staff; creating a catheter insertion cart; asking providers daily whether catheters could be re- moved; implementing a checklist to ensure adherence to 759Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care
  6. 6. evidence-based guidelines for preventing CRB; and em- powering nurses to stop the catheter insertion procedure if a violation of the guidelines was observed. During the intervention time period, the CRB rate decreased from 11.3 of 1,000 catheter days in the first quarter of 1998 to 0 of 1,000 catheter days in the fourth quarter of 2002. These interventions may have prevented 43 CRB, 8 deaths, and $1,945,922 in additional costs per year.This rate of zero CRB has been maintained over the next 2 years. Multifaceted interventions that helped to ensure adherence with evidence-based infection control guide- lines to eliminate CRB should be implemented in all ICUs. Glucose control Insulin resistance and hyperglycemia are common in critical illness. Increasing evidence has documented that hyperglycemia is associated with adverse outcomes in both critically ill and injured patients.31 Unraveling the molecular mechanisms of glucose toxicity and the salu- tary effects of insulin will provide new insights and open avenues for novel therapeutic strategies.32 Efforts to es- tablish safe and effective protocols for tight glucose con- trol in these patients are continuing. Cardiac issues Experts from the American Heart Association’s Coun- cils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young and the Interna- tional Society of Computerized Electrocardiology pub- lished a comprehensive consensus document to provide recommendations for best practices in electrocardio- graphic (ECG) monitoring in the hospital setting.33 This consensus document represents the first attempt in the literature to encompass all areas of hospital cardiac mon- itoring, including arrhythmia, ischemia, and QT- interval monitoring in both children and adults. This report focuses on real-time ECG monitoring, and em- phasis is on the information clinicians need to know to monitor patients safely and effectively. Recommenda- tions are made with regard to indications, time frames, and strategies to improve the diagnostic accuracy of car- diac arrhythmia, ischemia, and QT-interval monitoring. Currently available ECG lead systems are described, and recommendations related to staffing, training, and meth- ods to improve quality are provided. A randomized controlled trial recently compared goal-directed therapy guided by a pulmonary-artery catheter with standard care without the use of a pulmonary-artery catheter.34 The subjects were high-risk patients 60 years of age or older, with American Society of Anesthesiologists class III or IV risk, who were sched- uled for urgent or elective major surgery, followed by a stay in an ICU. Outcomes were adjudicated by observers who were unaware of the treatment group assignments. Of 3,803 eligible patients, 1,994 (52.4%) underwent randomization. No difference in hospital mortality rates was identified (7.7% in control group veresus 7.8% in pulmonary-artery catheter group, 95% CI, Ϫ2.3 to 2.5). Furthermore, no difference in 6- or 12-month sur- vival rates was identified. This study found no benefit to therapy directed by pulmonary-artery catheter over standard care in elderly, high-risk surgical patients re- quiring intensive care. But it also questions whether the physiologic end points used in the group that received a pulmonary-artery catheter were appropriate. Clearly, additional research is warranted in this important area. The use of perioperative beta-blockers is standard for patients with cardiac risk. Animal studies suggest that the beta-blocker propranolol increases bone formation. An interesting recent study documented that the use of beta-blockers alone and in combination therapy with thiazides in humans is associated with a reduced risk of fractures.35 Blood transfusion Consistent evidence has emerged regarding the risks and adverse outcomes associated with blood transfusion in trauma and critical care. Published data regarding the efficacy of red blood cell transfusion in the critically ill confirms that transfusion does not improve tissue oxy- gen consumption consistently in critically ill patients, either globally or at the level of the microcirculation. Lack of efficacy of RBC transfusion likely is related to storage time, increased endothelial adherence of stored RBCs, nitric oxide binding by free hemoglobin in stored blood, donor leukocytes, host inflammatory response, and reduced red cell deformability.36 Despite the frequent use of red cell transfusions, only one large randomized trial (Transfusion in Critical Care trial) has examined red cell administration in the critical care setting, documenting the safety of a restrictive trans- fusion strategy (transfuse only if hemoglobin Ͻ 7 g/ dL).37 A recent post hoc analysis of the trauma patient co- hort (n ϭ 203) from the Transfusion in Critical Care trial documented that 30-day all-cause mortality rates in the 760 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg
  7. 7. restrictive group were 10%, as compared with 9% in the liberal group (p ϭ 0.81). The presence of multiple organ dysfunction, the changes in multiple organ dysfunction from baseline scores adjusted for death, and the length of stay in the ICU and hospital also were similar between the restrictive and liberal transfusion groups. This study con- firmed that a restrictive red blood cell transfusion strategy appears to be safe for critically ill multiple-trauma patients.38 The Surviving Sepsis Guidelines also concluded that “In the absence of extenuating circumstances and fol- lowing resolution of tissue hypoperfusion, red blood cell transfusion should be targeted to maintain hemoglobin at 7.0 g/dL or greater.”39 Continued efforts to reduce blood transfusion in critically ill patients are required. These strategies will require education, unit and institu- tional protocols, and reduction of phlebotomy for diag- nostic laboratory testing in the ICU. We also have an increased understanding of the pathophysiology of the anemia associated with critical care, related to the inflammatory response, downregula- tion of erythropoietin, and lack of iron availability from macrophage sequestration. Clinical trials are under way to confirm the efficacy of recombinant erythropoietin in the treatment of critically ill patients with anemia.40 Hemoglobin-based oxygen carriers Alternatives to blood transfusion in the form of hemoglobin-based oxygen carriers (HBOC) continue to undergo intense investigation.41 A prehospital trial has recently been initiated with the human HBOC Poly- Heme (Northfield Labs). Patient enrollment is under way in the landmark phase III study designed to evaluate the safety and efficacy of PolyHeme when used to treat patients in hemorrhagic shock following traumatic inju- ries.Treatment begins at the scene of injury, continues in the ambulance during transport, and for 12 hours postinjury in the hospital. This is the first US trial of a blood substitute in which treatment begins at the scene of injury. The trial will be conducted in approximately 20 to 25 Level I trauma centers throughout the US and 720 patients will be enrolled in the trial. A prehospital clinical trial with the bovine HBOC- 201 Hemopure (Biopure) for resuscitation of patients with severe hemorrhagic shock is also planned. Entitled “Restore Effective Survival in Shock” (RESUS), the trial is intended to support an indication for out-of-hospital military and civilian trauma applications. The scientific advisory committee for this protocol includes navy, army, and air force medical researchers and academic experts in trauma, emergency medicine, critical care, and statistics. We anticipate that risks and benefits of alternatives to red blood cell transfusion will be eluci- dated in the coming years. Recombinant factor VIIa for hemorrhage control Recombinant FVIIa (rFVIIa) has been approved for treatment of bleeding in hemophilia patients with inhib- itors and in nonhemophilia patients with acquired anti- bodies against FVIII (acquired hemophilia). Pharmaco- logic doses of rFVIIa have been found to enhance thrombin generation on activated platelets and may also likely be of benefit in providing hemostasis in other sit- uations characterized by profuse bleeding and impaired thrombin generation, such as in patients with thrombo- cytopenia and in those with functional platelet defects. Additionally, it has been used successfully in a variety of less well-characterized bleeding situations and in pa- tients with impaired liver function and trauma.42 To date, case reports, case series, anecdotal experience, and limited clinical trials describe these uses of rFVIIa; data from randomized clinical trials are limited. A small double-blind, randomized placebo-controlled trial (n ϭ 36) documented that an intravenous bolus (20 or 40 ␮g/kg)) of rFVIIa significantly reduced perioper- ative median blood loss and reduced the need for allo- geneic blood transfusion in patients undergoing retro- pubic prostatectomy, which is often associated with major blood loss and need for transfusion. In fact, no patients who received 40 ␮g/kg of rFVIIa needed blood transfusion, and no associated adverse events were identified.43 The results of a phase II multicenter, multinational, pro- spective, randomized, double-blind, placebo-controlled trial (n ϭ 301) regarding the efficacy and safety of rFVIIa as adjunctive therapy for control of severe traumatic hemorrhage were reported in 2004. Patients with blunt or penetrating trauma and blood loss, requiring transfu- sion of 8 units of red blood cells, were randomized to receive 3 infusions of rFVIIa (200 ␮g/kg, 100 ␮g/kg, and 100 ␮g/kg) or placebo at entry, 1, and 3 hours in addition to standard surgical treatment. The primary study outcomes measure was total transfusion require- ment. In blunt trauma, there was a significant decrease in the number of transfusions required within 48 hours and a trend to reduced organ failure and ARDS. No 761Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care
  8. 8. significant differences were identified in the penetrating trauma group. No safety issues were identified in either group.44 It is important to recognize that efficacy of rFVIIa is reduced significantly with hypothermia and acidosis. The recommended dose of rFVIIa in patients with he- mophilia is 90 ␮g/kg, and the optimal dosing of rFVIIa in trauma and other ICU patients with coagulopathy and bleeding is not known at present. The optimal tim- ing and redosing are also unclear, because the half-life of rFVIIa is approximately 2 hours. Discussions regarding initiation of a US trial of rFVIIa in trauma are under way. Hemorrhage control—hemostatic agents Significant advances have been made in local hemor- rhage control with the development of new hemostatic agents for application in traumatic injury. The first FDA-approved product is QuikClot (Z-Medica), which has documented efficacy in a number of preclinical tri- als.45 A number of other hemostatic products are under- going both preclinical46,47 and clinical investigation.48 Traumatic brain injury Traumatic brain injury (TBI) is a leading cause of death and disability in trauma. Despite the publication and dissemination of traumatic brain injury treatment guidelines in 1995, it has been documented that imple- mentation is infrequent, with only 16% of 433 surveyed trauma centers in full compliance with the Guidelines.49 A single-institution study documented that implemen- tation of these Guidelines was associated with both im- proved patient outcomes and decreased hospital charg- es.50 These findings indicate the need to focus on changing practice to provide Guideline-compliant care and improve patient outcomes. In 2004 the BrainTrauma Foundation announced the National Quality Improvement TBI Initiative, aimed at increasing the quality of care provided to severe TBI patients. The Initiative combines the use of an Internet- based database to collect real-time patient data, Web conferencing, and quality improvement strategies to help trauma centers analyze their care processes and make im- provements where necessary (www.braintrauma.org). The recent comprehensive Cochrane Database Sys- tematic Review reviewed 20 trials with 12,303 random- ized participants in the study of corticosteroids for acute TBI. This group concluded that steroids should no longer be routinely used in patients with TBI.51 New advances in both invasive52 and noninvasive53 monitor- ing devices for measurement of cerebral oxygenation54 and level of consciousness55 in TBI patients continue to emerge. In addition, significant advances in surgical therapy of severe TBI, including decompressive craniec- tomy, have been reported.56 Guidelines for the surgical management ofTBI are under development by the Brain Trauma Foundation. Trauma outcomes—National Trauma Data Bank (NTDB) The NTDB has provided us with an opportunity to critically examine patient outcomes using very large pa- tient cohorts. A number of clinical studies on a variety of interesting topics were published in 2004. The tradi- tional Trauma and Injury Severity Score (TRISS) re- mains a standard method for survival prediction and correction for severity in trauma outcomes analyses. In the NTDB, the traditional TRISS had limited ability to predict survival after trauma. Accuracy of prediction was improved by recalculating the TRISS coefficients, but further improvements were not seen with models that included information about comorbidities.57 A large de- scriptive study of outcomes of patients with combined burn and trauma injuries documented increased mortal- ity despite similar total body surface area burned when compared with patients with burn injury as the sole mechanism.58 The largest study of motorcycle trauma performed using the NTDB documented that nonhel- meted motorcyclists have worse outcomes than their helmeted counterparts independent of the use of alcohol or drugs. They monopolize more hospital resources, in- cur higher hospital charges, and because nonhelmeted motorcyclists frequently do not have insurance, reim- bursement in this group of patients is poor. So the bur- den of caring for these patients is transmitted to society as a whole.59 Nutrition A prospective validation of the Canadian clinical prac- tice guidelines for nutrition support in mechanically ventilated, critically ill adult patients was reported from 59 ICUs across Canada.60 Intensive care units that were more consistent with the Canadian clinical practice guidelines were more likely to successfully feed patients by enteral nutrition. This study documented that adop- tion of the clinical practice guidelines should lead to 762 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg
  9. 9. improved nutrition support practice in ICUs and may translate into better outcomes for critically ill patients receiving nutrition support. A common practice in ICU patients is to provide a combination of enteral and parenteral nutrition when full caloric goal requirements are unable to be achieved by enteral nutrition alone. A systematic review of five randomized prospective trials that compared combina- tion nutrition to enteral nutrition alone confirmed no difference between the groups in rates of mortality, in- fectious complications, length of hospital stay, or venti- lator days.61 So in critically ill patients who are not mal- nourished and have an intact gastrointestinal tract, the use of parenteral nutrition in combination with enteral nutrition provides no benefit in clinical outcomes over enteral nutrition alone. End-of-life issues There is increasing concern over the appropriateness and quality of care provided in the ICU at the end of life.The first review of the number of Americans who receive ICU care at the end of life was published in 2004, using hospital discharge data from 1999 for 6 states and the National Death Index.There were 552,157 deaths in the 6 states in 1999, of which 38.3% occurred in the hospi- tal and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 peo- ple die after ICU admission each year. Average length of stay and costs were 12.9 days and $24,541, respectively, for terminal ICU hospitalizations and 8.9 days and $8,548, respectively, for non-ICU terminal hospitaliza- tions.This study documented that one in five Americans dies using ICU services. The authors concluded that the doubling of persons older than 65 by 2030 will require a system-wide expansion in ICU care for dying patients unless the health-care system pursues rationing, more effective advanced care planning, and augmented capac- ity to care for dying patients in other settings.62 A large proportion of deaths in the ICU are preceded by withdrawal of life support. One important publica- tion in this area documented the usefulness of a stan- dardized order form for the withdrawal of life support in the ICU.63 This “withdrawal of life support order form” was not documented to improve quality of end-of-life care in the ICU, which may be difficult to achieve. The standardized order form was noted to be helpful by both nurses and physicians. Medications for seda- tion increased during the postorder form period with- out evidence of significantly hastening death. Another prospective cohort study by the Canadian Critical CareTrials Group examined physician estimates of ICU survival and patient outcomes. Daily assessment of intensivist and bedside ICU nurse estimates of prob- ability of ICU survival were measured in 851 consecu- tive mechanically ventilated adult patients. ICU mortal- ity rate was 35.7%, and 341 patients (40.1%) were assessed by a physician at least once to have a Ͻ 10% ICU survival probability. Independent predictors of ICU mortality were baseline APACHE II score and daily factors such as multiple organ dysfunction syndrome, use of inotropes or vasopressors, dialysis, patient prefer- ence to limit life support, and physician but not nurse prediction of Ͻ 10% survival. This study documented that physician estimates of ICU survival Ͻ 10% were associated with subsequent life support limitation and more powerfully predicted ICU mortality than illness severity, evolving or resolving organ dysfunction, and use of inotropes or vasopressors.64 REFERENCES 1. ARDS Clinical Network. Available at: http://www.ardsnet.org/. Accessed February 17, 2005. 2. Resuscitation Outcomes Consortium. Available at: https:// roc.uwctc.org. Accessed February 17, 2005. 3. Truog RD. Will ethical requirements bring critical care research to a halt? Intensive Care Med 2004 Nov 4; [Epub ahead of print]. 4. Miller FG, Silverman HJ. The ethical relevance of the standard of care in the design of clinical trials. Am J Respir Crit Care Med 2004;169:562–564. 5. Luce JM, Cook DJ, Martin TR, et al, American Thoracic Soci- ety.The ethical conduct of clinical research involving critically ill patients in the United States and Canada: principles and recom- mendations. Am J Respir Crit Care Med 2004;170:1375–1384. 6. Dorman T, Angood PB, Angus DC, et al, American College of Critical Care Medicine. Guidelines for critical care medicine training and continuing medical education. Crit Care Med 2004;32:263–272. 7. Angus DC, Kelley MA, Schmitz RJ, et al, Committee on Manpower for Pulmonary and Critical Care Societies (COMPACCS). Caring for the critically ill patient. Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: can we meet the requirements of an aging population? JAMA 2000;284:2762–2770. 8. Irwin RS, Marcus L, Lever A. The critical care professional so- cieties address the critical care crisis in the United States. Chest 2004;125:1512–1513. 9. Kelley MA, Angus D, Chalfin DB, et al.The critical care crisis in the United States: a report from the profession. Chest 2004;125: 1514–1517. 10. Ewart GW, Marcus L, Gaba MM, et al. The critical care medi- 763Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care
  10. 10. cine crisis: a call for federal action: a white paper from the critical care professional societies. Chest 2004;125:1518–1521. 11. Halpern NA, Pastores SM, Greenstein RJ. Critical care medi- cine in the United States 1985–2000: an analysis of bed num- bers, use, and costs. Crit Care Med 2004;32:1254–1259. 12. ICU Physician Staffing. Available at: http://www.leapfroggroup. org/for_hospitals/leapfrog_safety_practices/icu_physician_staffing. Accessed February 17, 2005. 13. Pronovost PJ, Needham DM, Waters H, et al. Intensive care unit physician staffing: financial modeling of the Leapfrog stan- dard. Crit Care Med 2004;32:1247–1253. 14. Dellinger RP, Carlet JM, Masur H, et al, Surviving Sepsis Cam- paign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858–873. 15. Levy MM, Pronovost PJ, Dellinger RP, et al. Sepsis change bun- dles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med 2004;32[Suppl 11]:S595– 597. 16. Nathens AB, Curtis JR, Beale RJ, et al. Management of the critically ill patient with severe acute pancreatitis. Crit Care Med 2004;32:2524–2536. 17. Finfer S, Bellomo R, Boyce N, et al, SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247–2256. 18. Cooper DJ, Myles PS, McDermott FT, et al, HTS Study Inves- tigators. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a random- ized controlled trial. JAMA 2004;29:1350–1357. 19. Attuwaybi B, Kozar RA, Gates KS, et al. Hypertonic saline prevents inflammation, injury, and impaired intestinal transit after gut ischemia/reperfusion by inducing heme oxygenase 1 enzyme. J Trauma 2004;56:749–758; discussion 758–759. 20. Moore FA, McKinley BA, Moore EE. The next generation in shock resuscitation. Lancet 2004;363:1988–1996. 21. Keenan SP, Sinuff T, Cook DJ, Hill NS. Does noninvasive pos- itive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med 2004;32: 2516–2523. 22. Rumbak MJ, Newton M, Truncale T, et al. A prospective, ran- domized, study comparing early percutaneous dilational trache- otomy to prolonged translaryngeal intubation (delayed trache- otomy) in critically ill medical patients. Crit Care Med 2004; 32:1689–1694. 23. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753–1762. 24. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal vol- umes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–1308. 25. Brower RG, Lanken PN, MacIntyre N, et al, National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:327–336. 26. Spragg RG, Lewis JF, Walmrath HD, et al. Effect of recombi- nant surfactant protein C-based surfactant on the acute respira- tory distress syndrome. N Engl J Med 2004;351:884–892. 27. Centers for Disease Control and Prevention. Guidelines for pre- venting health–care–associated pneumonia, 2003: recommen- dations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR 2004 March;53 (No. RR-3): [1–36]. Available at: http://www.cdc.gov/ncidod/hip/pneumonia/ default.htm. Accessed February 17, 2005. 28. Niederman MS, Craven DE, and the ATS and IDSA Committee members. Guidelines for the management of adults with hospital- acquired, ventilator-associated, and healthcare-associated pneumo- nia. Am J Respir Crit Care Med 2005;171:388–416. 29. Chastre J, Wolff M, Fagon JY, et al, PneumATrial Group. Com- parison of 8 vs 15 days of antibiotic therapy for ventilator- associated pneumonia in adults: a randomized trial. JAMA 2003;290:2588–2598. 30. Berenholtz SM, Pronovost PJ, Lipsett PA, et al. Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care Med 2004;32:2014–2020. 31. Jeremitsky E, Omert LA, Dunham CM, et al. The impact of hyperglycemia on patients with severe brain injury. J Trauma 2005;58:47–50. 32. Van den Berghe G. How does blood glucose control with insulin save lives in intensive care? J Clin Invest 2004;114:1187–1195. 33. Drew BJ, Califf RM, Funk M, et al, American Heart Associa- tion; Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young; International Society of Computerized Electrocardiology; American Association of Critical-Care Nurses. Practice standards for electrocardio- graphic monitoring in hospital settings: an American Heart As- sociation scientific statement from the Councils on Cardiovas- cular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Comput- erized Electrocardiology and the American Association of Critical-Care Nurses. Circulation 2004;110:2721–2746. 34. Sandham JD, Hull RD, Brant RF, et al, Canadian Critical Care Clinical Trials Group. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 2003;348:5–14. 35. Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of beta- blockers and risk of fractures. JAMA 2004;292:1326–1332. 36. Napolitano LM, Corwin HL. Efficacy of red blood cell transfu- sion in the critically ill. Crit Care Clin 2004;20:255–268. 37. Hebert PC, McDonald BJ, Tinmouth A. Clinical consequences of anemia and red cell transfusion in the critically ill. Crit Care Clin 2004;20:225–235. 38. McIntyre L, Hebert PC, Wells G, et al, Canadian Critical Care Trials Group. Is a restrictive transfusion strategy safe for resusci- tated and critically ill trauma patients? J Trauma 2004;57:563– 568; discussion 568. 39. Zimmerman JL. Use of blood products in sepsis: an evidence- based review. Crit Care Med 2004;32[Suppl 11]:S542–547. 40. Napolitano LM. Current status of blood component therapy in surgical critical care. Curr Opin Crit Care 2004;10:311– 317. 41. Kim HW, Greenburg AG. Artificial oxygen carriers as red blood cell substitutes: a selected review and current status. Artif Organs 2004;28:813–828. 42. Goodnough LT, Lublin DM, Zhang L, et al. Transfusion med- icine service policies for recombinant factor VIIa administra- tion. Transfusion 2004;44:1325–1331. 43. Friederich PW, Henny CP, Messelink EJ, et al. Effect of recom- binant activated factor VII on perioperative blood loss in pa- tients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 2003;361:201– 205. 44. Boffard KD, Warren B, Iau P. Decreased transfusion utilization 764 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg
  11. 11. and improved outcome associated with the use of recombinant factor VIIa as an adjunct in trauma [abstract]. J Trauma 2004;57:451. 45. Pusateri AE, Delgado AV, Dick EJ Jr, et al. Application of a granular mineral-based hemostatic agent (QuikClot) to reduce blood loss after grade V liver injury in swine. J Trauma 2004;57: 555–562; discussion 562. 46. Alam HB, Chen Z, Jaskille A, et al. Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin injury in swine. J Trauma 2004;56:974–983. 47. Schwaitzberg SD, Chan MW, Cole DJ, et al. Comparison of poly-N-acetyl glucosamine with commercially available topical hemostats for achieving hemostasis in coagulopathic models of splenic hemorrhage. J Trauma 2004;57[Suppl 1]:S29–32. 48. Najjar SF, Healey NA, Healey CM, et al. Evaluation of poly-N- acetyl glucosamine as a hemostatic agent in patients undergoing cardiac catheterization: a double-blind, randomized study. J Trauma 2004;57[Suppl 1]:S38–41. 49. Hesdorffer DC, Ghajar J, Iacono L. Predictors of compliance with the evidence-based guidelines for traumatic brain injury care: A survey of United States trauma centers. J Trauma 2002; 52:1202–1209. 50. Fakhry SM, Trask AL, Waller MA, et al, IRTC Neurotrauma Task Force. Management of brain-injured patients by an evidence-based medicine protocol improves outcomes and de- creases hospital charges. JTrauma 2004;56:492–499; discussion 499–500. 51. Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev 2005;1:CD000196. 52. Gracias VH, Guillamondegui OD, Stiefel MF, et al. Cerebral cortical oxygenation: a pilot study. J Trauma 2004;56:469–472; discussion 472–474. 53. Edouard AR, Vanhille E, Le Moigno S, et al. Non-invasive as- sessment of cerebral perfusion pressure in brain injured patients with moderate intracranial hypertension. Br J Anaesth 2005;94: 216–221. 54. Dunham CM, Ransom KJ, Flowers LL, et al. Cerebral hypoxia in severely brain-injured patients is associated with admission Glasgow Coma Scale score, computed tomographic severity, ce- rebral perfusion pressure, and survival. J Trauma 2004;56: 482–489; discussion 489–491. 55. Deogaonkar A, Gupta R, DeGeorgia M, et al. Bispectral index monitoring correlates with sedation scales in brain-injured pa- tients. Crit Care Med 2004;32:2403–2406. 56. Stiefel MF, Heuer GG, Smith MJ, et al. Cerebral oxygenation following decompressive hemicraniectomy for the treatment of refractory intracranial hypertension. J Neurosurg 2004;101: 241–247. 57. Millham FH, LaMorte WW. Factors associated with mortality in trauma: re-evaluation of the TRISS method using the Na- tional Trauma Data Bank. J Trauma 2004;56:1090–1096. 58. Santaniello JM, Luchette FA, Esposito TJ, et al. Ten year expe- rience of burn, trauma, and combined burn/trauma injuries comparing outcomes. J Trauma 2004;57:696–701. 59. Hundley JC, Kilgo PD, Miller PR, et al. Non-helmeted motor- cyclists: a burden to society? A study using the national trauma data bank. J Trauma 2004;57:944–949. 60. Heyland DK, Dhaliwal R, Day A, et al. Validation of the Cana- dian clinical practice guidelines for nutrition support in me- chanically ventilated, critically ill adult patients: results of a pro- spective observational study. Crit Care Med 2004;32:2260– 2266. 61. Dhaliwal R, Jurewitsch B, Harrietha D, Heyland DK. Combi- nation enteral and parenteral nutrition in critically ill patients: harmful or beneficial? A systematic review of the evidence. In- tensive Care Med 2004;30:1666–1671. 62. Angus DC, Barnato AE, Linde-Zwirble WT, et al, Robert Wood Johnson Foundation ICU End-Of-Life Peer Group. Use of in- tensive care at the end of life in the United States: an epidemi- ologic study. Crit Care Med 2004;32:638–643. 63. Treece PD, Engelberg RA, Crowley L, et al. Evaluation of a standardized order form for the withdrawal of life support in the intensive care unit. Crit Care Med 2004;32:1141–1148. 64. Rocker G, Cook D, Sjokvist P, et al, Level of Care Study Inves- tigators; Canadian Critical Care Trials Group. Clinician predic- tions of intensive care unit mortality. Crit Care Med 2004;32: 1149–1154. 765Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care