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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 Clinical Centers and a Data and Coordinating Center
critical care and trauma in 2004, ranging from new re- that will provide the necessary infrastructure to conduct
search findings to critical care workforce issues and dis- multiple collaborative trials to aid rapid translation of
cussions regarding optimal education and training in promising scientific and clinical advances to improve
trauma and surgical critical care. We have made great resuscitation outcomes. The ongoing direct study com-
advances in a number of areas, and additional initiatives mitment of the sponsors is for at least 5 years of funding
to expand research efforts in trauma and critical care are at approximately $10 million per year. Information re-
ongoing. garding the specific participating centers can be ob-
tained on the ROC Web site.2 Others contributing sup-
Research port to this initiative include the US Department of
There are a number of obstacles to performing clinical Defense, other institutes within the NIH, the Institute of
trials and outcomes studies involving critically ill and Circulatory and Respiratory Health from the Canadian In-
injured patients with complex syndromes that currently stitutes of Health Research, the Canadian Defense Re-
lack effective treatments. The Canadian Critical Care search and Development Program, and the National Insti-
Trials Group and the Australia and New Zealand Inten- tute of Neurological Disorders and Stroke.
sive Care Society Clinical Trials Group have established There is significant concern that it has become in-
comprehensive research efforts in this regard. The Acute creasingly difficult to conduct clinical research in trauma
Respiratory Distress Syndrome (ARDS) Clinical Net- and critical care, and that it may negatively impact on
work (ARDSNet) was the first organized US national future efforts.3 Difficulties in obtaining patient or sur-
effort to conduct multicenter clinical trials in critical rogate consent and in determining the standard of care
care, established in 1994.1 for the control group are relevant issues.4 An important
The US and Canada launched a major collaborative statement from the American Thoracic Society regard-
research program in 2004. The leading federal health ing the ethical conduct of clinical research involving
research agencies in the US and Canada—the National critically ill patients was published in 2004, providing
Institutes of Health (NIH) and the Canadian Institutes some principles and guidance in this difficult area.5
of Health Research (CIHR)—formed a partnership to
advance research in cardiovascular and respiratory Education and resident training
diseases. The Guidelines for Critical Care Medicine Training and
Three research programs were initiated in 2004, in- Continuing Medical Education were published this year
cluding “Clinical Research Consortium to Improve Re- by the American College of Critical Care Medicine.6
suscitation Outcomes,” which will address novel strate- Guidelines for the continuum of education in critical
gies to resuscitate heart attack and trauma patients. This care, from residency training through specialty training
is the first organized multicenter effort to perform resus- and ongoing through practice, will facilitate standard-
citation research in trauma in the US. The Resuscitation ization of physician education in critical care medicine.
Outcomes Consortium (ROC) consists of 10 Regional 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.
Received February 11, 2005; Accepted February 11, 2005. In 2004, a number of national organizations established
From the Department of Surgery, University of Michigan School of Medi-
cine, Ann Arbor, MI. an initiative to collaborate and coordinate with all of the
Correspondence address: Lena M Napolitano, MD, FACS, FCCP, FCCM, professional societies that represent surgical critical care,
University of Michigan School of Medicine, Department of Surgery, Section
of General Surgery, University of Michigan Health System,1500 E Medical
trauma, and acute surgery. This effort includes the
Center Dr, Ann Arbor, MI 48109-0331. American Board of Surgery, American Association for

© 2005 by the American College of Surgeons ISSN 1072-7515/05/$30.00


Published by Elsevier Inc. 755 doi:10.1016/j.jamcollsurg.2005.02.018
756 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg

Numerous studies demonstrate that critical care ser-


Abbreviations and Acronyms vices directed by physicians formally trained in critical
CCM ⫽ critical care medicine care medicine reduce mortality in the ICU and reduce
CRB ⫽ catheter-related bacteremia
health-care costs. To address the shortage, the critical
ECG ⫽ electrocardiographic
HBOC ⫽ hemoglobin-based oxygen carrier care professional societies recommend that steps be
HR ⫽ hazard ratio taken to improve the efficiency of critical care providers,
NPPV ⫽ noninvasive positive pressure ventilation to increase the number of critical care providers, and to
NTDB ⫽ National Trauma Data Bank
PEEP ⫽ positive end-expiratory pressure address the demand for critical care services.
rFVIIa ⫽ recombinant factor VIIa
TBI ⫽ traumatic brain injury Critical care use in the US
TRISS ⫽ Trauma and Injury Severity Score
VAP ⫽ ventilator-associated pneumonia
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-
the Surgery of Trauma, the American College of Sur- tal beds decreased substantially, by 26.4% (889,600 to
geons Committee on Trauma, the Eastern Association 654,400) in these hospitals. In contrast, CCM beds in-
for the Surgery of Trauma, the Surgical Section of the creased by 26.2% (69,300 to 87,400) and CCM bed
Society of Critical Care Medicine, the American Burn costs per day increased by 126% ($1,185 to $2,674 US).
Association, and the Western Trauma Association. These Although CCM costs increased by 190.4% ($19.1 bil-
organizations are examining options for linking the spe- lion to $55.5 billion US), the proportion of national
cialties of general surgery, trauma surgery, and surgical health expenditures allocated to CCM decreased by
critical care to create a career practice model for the 5.4%. In 2000, CCM costs represented 13.3% of hos-
future. pital costs, 4.2% of national health expenditures, and
0.56% of the gross domestic product. These authors
Critical care workforce and manpower issues concluded that CCM is increasingly used and promi-
The US is currently facing an unprecedented, and nent in a shrinking US hospital system.11
largely unrecognized, shortage of physicians trained to The Leapfrog Group has recommended that imple-
provide critical care services. This is one of the most mentation of the Intensive Care Unit Physician Staffing
pressing issues affecting the future of our aging popula- be standard in all hospitals.12 The ICU Physician Staff-
tion and American medicine. As initially described in a ing standard requires that intensive care units have a
study by the Committee on Manpower for Pulmonary dedicated intensivist present during daytime hours.
and Critical Care Societies (COMPACCS), future de- Outside of these hours, an intensivist must be immedi-
mand for critical care services in the US will soon exceed ately available by pager, and a physician or “physician
the capabilities of the current delivery system.7 The most extender” must be in the hospital and able to immedi-
alarming problem is the anticipated shortage of health- ately reach intensive care unit patients. Research shows
care professionals practicing critical care. that if the first three leaps (Computer Physician Order
This past year, the four major critical care societies in Entry, Intensive Care Unit Physician Staffing, and
the US (American Association of Critical Care Nurses, Evidence-Based Hospital Referral) were implemented in
American College of Chest Physicians, American Tho- all urban hospitals in the US, we could save up to 65,341
racic Society, and Society of Critical Care Medicine) lives and prevent as many as 907,600 serious medication
united in their efforts to address the shortage of health- errors each year.
care providers who care for the critically ill.8 The Critical A recent study using financial modeling examined
Care Workforce Partnership was established and the rec- hospital costs and savings over a 1-year period of imple-
ommendations for actions were reported by the FOCCUS menting the ICU Physician Staffing standard compared
(Framing Options for Critical Care in the United States) with the existing standard of nonintensivist staffing in
Task Force.9 An additional publication outlined federal adult ICUs using published data for nonrural hospi-
policy initiatives to address the shortage of critical care tals.13 Cost savings ranged from $510,000 to $3.3 mil-
providers.10 lion US for 6- to 18-bed intensive care units. The best-
Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care 757

case scenario demonstrated savings of $4.2 to $13 International consensus conference—pancreatitis


million US. Under the worst-case scenario, there was a Acute pancreatitis represents a spectrum of disease rang-
net cost of $890,000 to $1.3 million US. These eco- ing from a mild, self-limited course requiring only brief
nomic findings must be interpreted in the context of hospitalization to a rapidly progressive, fulminant illness
significant reductions in patient morbidity and mortal- resulting in multiple organ dysfunction syndrome, with
ity rates also associated with intensivist staffing. The au- or without accompanying sepsis. An international con-
thors concluded by stating that, given the magnitude of sensus conference was held in April 2004 to develop
its clinical and financial impact, hospital leaders should recommendations for the management of the critically
be asking “how to” rather than “whether to” implement ill patient with severe acute pancreatitis. Evidence-based
The Leapfrog Group’s ICU Physician Staffing standard. 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-
Surviving sepsis guidelines
tinent literature to address specific questions concerning
In 2003, critical care and infectious disease experts
the management of patients with severe acute pancreati-
representing 11 international organizations developed tis. There were a total of 23 recommendations developed
management guidelines for severe sepsis and septic to provide guidance to critical care clinicians caring for
shock that would be of practical use for the bedside the patient with severe acute pancreatitis.16
clinician, under the auspices of the Surviving Sepsis These included a recommendation against the rou-
Campaign, an international effort to increase awareness tine use of prophylactic systemic antibacterial or anti-
and improve outcomes in severe sepsis. These guidelines fungal agents in patients with or without necrotizing
were published in 2004.14 The impact of these guidelines pancreatitis. The jury also recommended against pancre-
will be formally tested and guidelines updated annually atic debridement or drainage for sterile necrosis, limiting
and even more rapidly as important new knowledge be- debridement or drainage to those with infected pancre-
comes available. atic necrosis or abscess confirmed by radiologic evidence
An effort to translate these evidence-based recom- of gas or results of fine needle aspiration. The jury also
mendations regarding many aspects of the acute man- recommended that whenever possible, operative necro-
agement of sepsis and septic shock into improved out- sectomy or drainage be delayed at least 2 to 3 weeks to
comes for the critically ill patient is under way by the use allow for demarcation of the necrotic pancreas. These
of “sepsis bundles.” A bundle is a selected set of inter- recommendations differ in several ways from previous
ventions or processes of care distilled from evidence- recommendations because of the release of recent data
based practice guidelines that, when implemented as a concerning the management of these patients and also
group, provides a more robust picture of the quality of because of the focus on the critically ill patient. There
care provided. The Severe Sepsis Bundles are a distilla- were a number of important questions that could not be
tion of the concepts and recommendations found in the answered using an evidence-based approach, and areas
practice guidelines published by the Surviving Sepsis in need of further research were identified.
Campaign in 2004.
The Severe Sepsis Bundles are designed to allow teams Resuscitation
to follow the timing, sequence, and goals of the individ- Two important clinical studies on fluid resuscitation
ual elements of care, in order to achieve the goal of a 25% were published in 2004. The Saline versus Albumin
reduction in mortality from severe sepsis. There are cur- Fluid Evaluation (SAFE) Study was a multicenter, ran-
rently two sepsis bundles recommended for use: domized, double-blind trial comparing the effect of
fluid resuscitation with albumin or saline on mortality in
Sepsis Resuscitation Bundle: Tasks that should begin im- a heterogeneous population of patients in the ICU.17
mediately but must be done within 6 hours for patients This study was a collaboration of the Australian and
with severe sepsis or septic shock. New Zealand Intensive Care Society Clinical Trials
Sepsis Management Bundle: Tasks that should begin im- Group, the Australian Red Cross Blood Service, and the
mediately but must be done within 24 hours for pa- George Institute for International Health. Patients were
tients with severe sepsis or septic shock.15 randomized to receive either 4% albumin or normal
758 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg

saline for intravascular-fluid resuscitation during the 28 Respiratory failure


days after ICU admission. Of the 6,997 patients who A number of studies have previously documented that
underwent randomization, 3,497 were assigned to re- the use of noninvasive positive pressure ventilation
ceive albumin and 3,500 to receive saline; the two (NPPV) for respiratory failure related to cardiogenic
groups had similar baseline characteristics. There was no pulmonary edema and COPD exacerbation is associated
difference in 28-day mortality identified (relative risk of with improved outcomes. But, does noninvasive positive
death, 0.99; 95% CI 0.91 to 1.09; p ⫽ 0.87). pressure ventilation improve outcomes in acute hypox-
Interestingly, among the 1,186 patients with trauma, emia respiratory failure unrelated to these diagnoses?21 A
albumin was associated with a trend toward increased systematic review of prospective randomized trials re-
mortality (relative risk of death in the albumin group, cently addressed this question. This study confirmed
1.36; 95% CI 0.99 to 1.86), possibly explained by the that the addition of NPPV to standard care in the setting
effect of trauma associated with brain injury (relative of acute hypoxemic respiratory failure reduced the rate
risk of death, 1.62; 95% CI 1.12 to 2.34). In contrast, of endotracheal intubation (absolute risk reduction
among 1,218 patients with severe sepsis, albumin was 23%, 95% CI 10% to 35%) and ICU length of stay
associated with a trend toward reduced mortality (rel- (absolute reduction 2 days, 95% CI 1 to 3 days); ICU
ative risk of death, 0.87; 95% CI 0.74 to 1.02). These mortality was less clear, and the heterogeneity found
subgroup analyses should be interpreted with cau- among studies suggested that effectiveness varies among
tion and will require validation in future different populations. As a result, the literature does not
studies. support the routine use of NPPV in all patients with
acute hypoxemic respiratory failure.
A prehospital trial of hypertonic saline resuscitation
In patients who require intubation for respiratory fail-
in patients with hypotension (systolic blood pressure
ure, there appears to be accumulating evidence in favor
⬍ 100 mmHg) and severe traumatic brain injury (Glasgow
of early tracheostomy. A prospective randomized study
Coma Scale score ⬍ 9, n ⫽ 229) was conducted in
in 120 patients projected to need mechanical ventilation
Australia.18 Patients were randomly assigned to receive a
for less than 14 days was randomized to early percuta-
rapid intravenous infusion of either 250 mL of 7.5%
neous tracheotomy within 48 hours or delayed trache-
saline (n ⫽ 114) or 250 mL of Ringer’s lactate solution
otomy at days 14 to 16. The early tracheotomy group
(n ⫽ 115; controls) in addition to conventional intrave- had significantly less mortality (31.7% versus 61.7%),
nous fluid and resuscitation protocols administered by pneumonia (5% versus 25%), and accidental extuba-
paramedics. No significant differences in survival at tions (0 versus 6) compared with the prolonged transla-
hospital discharge, 6-month survival, or functional ryngeal group. The early tracheotomy group spent less
neurologic outcomes at 6 months after injury were time in the ICU (4.8 ⫾ 1.4 days versus 16.2 ⫾ 3.8 days)
identified. and on mechanical ventilation (7.6 ⫾ 2.0 days versus
There is still great interest in the use of hypertonic 17.4 ⫾ 5.3 days). There was also significantly more
saline for resuscitation in shock, because of its ability to damage to the mouth and larynx in the prolonged trans-
modulate the inflammatory response19 and reduce fluid laryngeal intubation group.22
resuscitation volume requirements.20 In fact, two multi- We have now recognized the high incidence of delir-
center clinical trials under consideration by the Resusci- ium as a common form of organ dysfunction in the ICU,
tation Outcomes Consortium seek to determine the im- especially in patients requiring mechanical ventilation.
pact of hypertonic resuscitation on survival in In a prospective cohort study of 224 mechanically ven-
hypovolemic shock in trauma, and on longterm neuro- tilated patients, 81.5% developed delirium at some
logic outcomes in blunt severe traumatic brain injury. point during the ICU stay.23 Patients who developed
Both studies will be three arm, randomized, blinded delirium had higher 6-month mortality rates (34% ver-
intervention trials comparing hypertonic saline/dextran sus 15%, p ⫽ 0.03) and spent 10 days longer in the
(7.5% saline, 6% dextran 70), hypertonic saline alone hospital than those who never developed delirium (p ⬍
(7.5% saline), and normal saline as the initial resuscita- 0.001). After adjusting for covariates (including age, se-
tion fluid administered to these patients in the prehos- verity of illness, comorbid conditions, coma, and use of
pital setting. sedatives or analgesic medications), delirium was inde-
Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care 759

pendently associated with higher 6-month mortality Infections


(adjusted hazard ratio [HR], 3.2; 95% CI, 1.4 to 7.7; Prevention of health care–associated infections contin-
p ⫽ 0.008), and longer hospital stay (adjusted HR, 2.0; ues to be a primary goal in the care of all critically ill and
95% CI, 1.4 to 3.0; p ⬍ 0.001). Delirium in the ICU injured patients.
was also independently associated with a longer post- Health care–associated pneumonia
ICU stay (adjusted HR, 1.6; 95% CI, 1.2 to 2.3; p ⫽ Pneumonia continues to be a leading cause of health
0.009), fewer median days alive and without mechanical care–associated infection in the ICU, and all efforts to
ventilation (19 days [interquartile range, 4 to 23 days] prevent pneumonia should be implemented. The CDC
versus 24 days [interquartile range 19 to 26 days]; ad- Guidelines for the Prevention of Healthcare-Associated Pneu-
justed p ⫽ 0.03), and a higher incidence of cognitive monia were published in 2004.27 Most recently, the Guide-
impairment at hospital discharge (adjusted HR, 9.1; lines for the Management of Adults with Hospital-Acquired,
95% CI, 2.3 to 35.3; p ⫽ 0.002). Ventilator-Associated, and Healthcare-Associated Pneumonia
The ARDSNet trial previously documented that in were published by the American Thoracic Society and the
patients with acute lung injury and the acute respiratory Infectious Diseases Society of America.28 These two docu-
distress syndrome, mechanical ventilation with a lower ments provide comprehensive and current information
tidal volume (6 versus 12 mL/kg) resulted in decreased regarding evidence-based practices for prevention, diag-
mortality and increased the number of days without nosis, and treatment of pneumonia in critically ill and
ventilator use.24 In 2004, the ARDSNet group published injured patients.
the trial comparing the effects of higher and lower pos- An important study examined the optimal duration
itive end-expiratory pressure (PEEP) levels on clinical of antimicrobial therapy for the treatment of ventilator-
outcomes in ARDS patients (n ⫽ 549).25 This study associated pneumonia (VAP).29 A prospective, random-
documented that in patients with acute lung injury and ized, double-blind clinical trial conducted in 51 French
ARDS who received mechanical ventilation with a tidal- ICUs enrolled 401 patients diagnosed with VAP by
volume goal of 6 mL/kg of predicted body weight and an quantitative culture of bronchoscopic specimens and
end-inspiratory plateau-pressure limit of 30 cm of water, who had received initial appropriate empirical antimi-
clinical outcomes were similar whether lower or higher crobial therapy. Patients were randomized to receive 8 or
PEEP levels were used. 15 days of antibiotic therapy. This study documented
Two multicenter, randomized, double-blind phase comparable clinical effectiveness against VAP with the
trials of a protein-containing surfactant in adults with 8- and 15-day antibiotic treatment regimens, and de-
ARDS from various causes (n ⫽ 448) compared stan- creased antibiotic use in the 8-day group. Importantly,
dard therapy alone with standard therapy plus up to four patients with VAP caused by nonfermenting gram-
intratracheal doses of a recombinant surfactant protein negative bacilli, including Pseudomonas aeruginosa, did
C–based surfactant given within a period of 24 hours.26 have a higher pulmonary infection-recurrence rate com-
There was no significant difference between the groups pared with those receiving 15 days of treatment (40.6%
in terms of mortality or the need for mechanical venti- versus 25.4%; difference, 15.2%, 90% CI, 3.9% to
lation. Patients receiving surfactant had a significantly 26.6%).
greater improvement in blood oxygenation during the Catheter-related bacteremia
initial 24 hours of treatment than patients receiving The importance of education and process improvement
standard therapy, according to both univariate and mul- in prevention of catheter-related bacteremia (CRB) has
tivariate analyses. been documented in a number of studies. A new bench-
Surfactant replacement therapy for ARDS in neo- mark has recently been set, with complete elimination of
nates is standard of care. Future studies with surfactant CRB in the surgical ICU in a single institution study
therapy in ARDS may consider alternative formulations over 5 years (1998 to 2002).30 To eliminate CRB, a qual-
of recombinant surfactant, earlier initiation of surfactant ity improvement team implemented five interventions:
therapy, studies in more homogenous patient groups, educating the staff; creating a catheter insertion cart;
and different methods of delivery of surfactant to the asking providers daily whether catheters could be re-
injured lung. moved; implementing a checklist to ensure adherence to
760 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg

evidence-based guidelines for preventing CRB; and em- catheter with standard care without the use of a
powering nurses to stop the catheter insertion procedure pulmonary-artery catheter.34 The subjects were high-risk
if a violation of the guidelines was observed. During the patients 60 years of age or older, with American Society
intervention time period, the CRB rate decreased from of Anesthesiologists class III or IV risk, who were sched-
11.3 of 1,000 catheter days in the first quarter of 1998 to uled for urgent or elective major surgery, followed by a
0 of 1,000 catheter days in the fourth quarter of 2002. stay in an ICU. Outcomes were adjudicated by observers
These interventions may have prevented 43 CRB, 8 who were unaware of the treatment group assignments.
deaths, and $1,945,922 in additional costs per year. This Of 3,803 eligible patients, 1,994 (52.4%) underwent
rate of zero CRB has been maintained over the next 2 randomization. No difference in hospital mortality rates
years. Multifaceted interventions that helped to ensure was identified (7.7% in control group veresus 7.8% in
adherence with evidence-based infection control guide- pulmonary-artery catheter group, 95% CI, ⫺2.3 to
lines to eliminate CRB should be implemented in all 2.5). Furthermore, no difference in 6- or 12-month sur-
ICUs. vival rates was identified. This study found no benefit to
therapy directed by pulmonary-artery catheter over
Glucose control standard care in elderly, high-risk surgical patients re-
Insulin resistance and hyperglycemia are common in quiring intensive care. But it also questions whether the
critical illness. Increasing evidence has documented that physiologic end points used in the group that received a
hyperglycemia is associated with adverse outcomes in pulmonary-artery catheter were appropriate. Clearly,
both critically ill and injured patients.31 Unraveling the additional research is warranted in this important area.
molecular mechanisms of glucose toxicity and the salu- The use of perioperative beta-blockers is standard for
tary effects of insulin will provide new insights and open patients with cardiac risk. Animal studies suggest that
avenues for novel therapeutic strategies.32 Efforts to es- the beta-blocker propranolol increases bone formation.
tablish safe and effective protocols for tight glucose con- An interesting recent study documented that the use of
trol in these patients are continuing. beta-blockers alone and in combination therapy with
thiazides in humans is associated with a reduced risk of
Cardiac issues fractures.35
Experts from the American Heart Association’s Coun-
cils on Cardiovascular Nursing, Clinical Cardiology, and Blood transfusion
Cardiovascular Disease in the Young and the Interna- Consistent evidence has emerged regarding the risks and
tional Society of Computerized Electrocardiology pub- adverse outcomes associated with blood transfusion in
lished a comprehensive consensus document to provide trauma and critical care. Published data regarding the
recommendations for best practices in electrocardio- efficacy of red blood cell transfusion in the critically ill
graphic (ECG) monitoring in the hospital setting.33 This confirms that transfusion does not improve tissue oxy-
consensus document represents the first attempt in the gen consumption consistently in critically ill patients,
literature to encompass all areas of hospital cardiac mon- either globally or at the level of the microcirculation.
itoring, including arrhythmia, ischemia, and QT- Lack of efficacy of RBC transfusion likely is related to
interval monitoring in both children and adults. This storage time, increased endothelial adherence of stored
report focuses on real-time ECG monitoring, and em- RBCs, nitric oxide binding by free hemoglobin in stored
phasis is on the information clinicians need to know to blood, donor leukocytes, host inflammatory response,
monitor patients safely and effectively. Recommenda- and reduced red cell deformability.36
tions are made with regard to indications, time frames, Despite the frequent use of red cell transfusions, only
and strategies to improve the diagnostic accuracy of car- one large randomized trial (Transfusion in Critical Care
diac arrhythmia, ischemia, and QT-interval monitoring. trial) has examined red cell administration in the critical
Currently available ECG lead systems are described, and care setting, documenting the safety of a restrictive trans-
recommendations related to staffing, training, and meth- fusion strategy (transfuse only if hemoglobin ⬍ 7 g/
ods to improve quality are provided. dL).37 A recent post hoc analysis of the trauma patient co-
A randomized controlled trial recently compared hort (n ⫽ 203) from the Transfusion in Critical Care trial
goal-directed therapy guided by a pulmonary-artery documented that 30-day all-cause mortality rates in the
Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care 761

restrictive group were 10%, as compared with 9% in the advisory committee for this protocol includes navy,
liberal group (p ⫽ 0.81). The presence of multiple organ army, and air force medical researchers and academic
dysfunction, the changes in multiple organ dysfunction experts in trauma, emergency medicine, critical care,
from baseline scores adjusted for death, and the length of and statistics. We anticipate that risks and benefits of
stay in the ICU and hospital also were similar between the alternatives to red blood cell transfusion will be eluci-
restrictive and liberal transfusion groups. This study con- dated in the coming years.
firmed that a restrictive red blood cell transfusion strategy
appears to be safe for critically ill multiple-trauma Recombinant factor VIIa for hemorrhage control
patients.38 Recombinant FVIIa (rFVIIa) has been approved for
The Surviving Sepsis Guidelines also concluded that treatment of bleeding in hemophilia patients with inhib-
“In the absence of extenuating circumstances and fol- itors and in nonhemophilia patients with acquired anti-
lowing resolution of tissue hypoperfusion, red blood cell bodies against FVIII (acquired hemophilia). Pharmaco-
transfusion should be targeted to maintain hemoglobin logic doses of rFVIIa have been found to enhance
at 7.0 g/dL or greater.”39 Continued efforts to reduce thrombin generation on activated platelets and may also
blood transfusion in critically ill patients are required. likely be of benefit in providing hemostasis in other sit-
These strategies will require education, unit and institu- uations characterized by profuse bleeding and impaired
tional protocols, and reduction of phlebotomy for diag- thrombin generation, such as in patients with thrombo-
nostic laboratory testing in the ICU. cytopenia and in those with functional platelet defects.
We also have an increased understanding of the Additionally, it has been used successfully in a variety of
pathophysiology of the anemia associated with critical less well-characterized bleeding situations and in pa-
care, related to the inflammatory response, downregula- tients with impaired liver function and trauma.42 To
tion of erythropoietin, and lack of iron availability from date, case reports, case series, anecdotal experience, and
macrophage sequestration. Clinical trials are under way limited clinical trials describe these uses of rFVIIa; data
to confirm the efficacy of recombinant erythropoietin in from randomized clinical trials are limited.
the treatment of critically ill patients with anemia.40 A small double-blind, randomized placebo-controlled
trial (n ⫽ 36) documented that an intravenous bolus (20
Hemoglobin-based oxygen carriers or 40 ␮g/kg)) of rFVIIa significantly reduced perioper-
Alternatives to blood transfusion in the form of ative median blood loss and reduced the need for allo-
hemoglobin-based oxygen carriers (HBOC) continue to geneic blood transfusion in patients undergoing retro-
undergo intense investigation.41 A prehospital trial has pubic prostatectomy, which is often associated with
recently been initiated with the human HBOC Poly- major blood loss and need for transfusion. In fact, no
Heme (Northfield Labs). Patient enrollment is under patients who received 40 ␮g/kg of rFVIIa needed blood
way in the landmark phase III study designed to evaluate transfusion, and no associated adverse events were
the safety and efficacy of PolyHeme when used to treat identified.43
patients in hemorrhagic shock following traumatic inju- The results of a phase II multicenter, multinational, pro-
ries. Treatment begins at the scene of injury, continues in spective, randomized, double-blind, placebo-controlled
the ambulance during transport, and for 12 hours trial (n ⫽ 301) regarding the efficacy and safety of rFVIIa
postinjury in the hospital. This is the first US trial of a as adjunctive therapy for control of severe traumatic
blood substitute in which treatment begins at the scene hemorrhage were reported in 2004. Patients with blunt
of injury. The trial will be conducted in approximately or penetrating trauma and blood loss, requiring transfu-
20 to 25 Level I trauma centers throughout the US and sion of 8 units of red blood cells, were randomized to
720 patients will be enrolled in the trial. receive 3 infusions of rFVIIa (200 ␮g/kg, 100 ␮g/kg,
A prehospital clinical trial with the bovine HBOC- and 100 ␮g/kg) or placebo at entry, 1, and 3 hours in
201 Hemopure (Biopure) for resuscitation of patients addition to standard surgical treatment. The primary
with severe hemorrhagic shock is also planned. Entitled study outcomes measure was total transfusion require-
“Restore Effective Survival in Shock” (RESUS), the trial ment. In blunt trauma, there was a significant decrease
is intended to support an indication for out-of-hospital in the number of transfusions required within 48 hours
military and civilian trauma applications. The scientific and a trend to reduced organ failure and ARDS. No
762 Napolitano What’s New in Trauma and Critical Care J Am Coll Surg

significant differences were identified in the penetrating longer be routinely used in patients with TBI.51 New
trauma group. No safety issues were identified in either advances in both invasive52 and noninvasive53 monitor-
group.44 ing devices for measurement of cerebral oxygenation54
It is important to recognize that efficacy of rFVIIa is and level of consciousness55 in TBI patients continue to
reduced significantly with hypothermia and acidosis. emerge. In addition, significant advances in surgical
The recommended dose of rFVIIa in patients with he- therapy of severe TBI, including decompressive craniec-
mophilia is 90 ␮g/kg, and the optimal dosing of rFVIIa tomy, have been reported.56 Guidelines for the surgical
in trauma and other ICU patients with coagulopathy management of TBI are under development by the Brain
and bleeding is not known at present. The optimal tim- Trauma Foundation.
ing and redosing are also unclear, because the half-life of
rFVIIa is approximately 2 hours. Discussions regarding Trauma outcomes—National Trauma Data
initiation of a US trial of rFVIIa in trauma are under Bank (NTDB)
way. The NTDB has provided us with an opportunity to
critically examine patient outcomes using very large pa-
Hemorrhage control— hemostatic agents tient cohorts. A number of clinical studies on a variety of
Significant advances have been made in local hemor- interesting topics were published in 2004. The tradi-
rhage control with the development of new hemostatic tional Trauma and Injury Severity Score (TRISS) re-
agents for application in traumatic injury. The first mains a standard method for survival prediction and
FDA-approved product is QuikClot (Z-Medica), which correction for severity in trauma outcomes analyses. In
has documented efficacy in a number of preclinical tri- the NTDB, the traditional TRISS had limited ability to
als.45 A number of other hemostatic products are under- predict survival after trauma. Accuracy of prediction was
going both preclinical46,47 and clinical investigation.48 improved by recalculating the TRISS coefficients, but
further improvements were not seen with models that
Traumatic brain injury included information about comorbidities.57 A large de-
Traumatic brain injury (TBI) is a leading cause of death scriptive study of outcomes of patients with combined
and disability in trauma. Despite the publication and burn and trauma injuries documented increased mortal-
dissemination of traumatic brain injury treatment ity despite similar total body surface area burned when
guidelines in 1995, it has been documented that imple- compared with patients with burn injury as the sole
mentation is infrequent, with only 16% of 433 surveyed mechanism.58 The largest study of motorcycle trauma
trauma centers in full compliance with the Guidelines.49 performed using the NTDB documented that nonhel-
A single-institution study documented that implemen- meted motorcyclists have worse outcomes than their
tation of these Guidelines was associated with both im- helmeted counterparts independent of the use of alcohol
proved patient outcomes and decreased hospital charg- or drugs. They monopolize more hospital resources, in-
es.50 These findings indicate the need to focus on cur higher hospital charges, and because nonhelmeted
changing practice to provide Guideline-compliant care motorcyclists frequently do not have insurance, reim-
and improve patient outcomes. bursement in this group of patients is poor. So the bur-
In 2004 the Brain Trauma Foundation announced the den of caring for these patients is transmitted to society
National Quality Improvement TBI Initiative, aimed at as a whole.59
increasing the quality of care provided to severe TBI
patients. The Initiative combines the use of an Internet- Nutrition
based database to collect real-time patient data, Web A prospective validation of the Canadian clinical prac-
conferencing, and quality improvement strategies to help tice guidelines for nutrition support in mechanically
trauma centers analyze their care processes and make im- ventilated, critically ill adult patients was reported from
provements where necessary (www.braintrauma.org). 59 ICUs across Canada.60 Intensive care units that were
The recent comprehensive Cochrane Database Sys- more consistent with the Canadian clinical practice
tematic Review reviewed 20 trials with 12,303 random- guidelines were more likely to successfully feed patients
ized participants in the study of corticosteroids for acute by enteral nutrition. This study documented that adop-
TBI. This group concluded that steroids should no tion of the clinical practice guidelines should lead to
Vol. 200, No. 5, May 2005 Napolitano What’s New in Trauma and Critical Care 763

improved nutrition support practice in ICUs and may tion increased during the postorder form period with-
translate into better outcomes for critically ill patients out evidence of significantly hastening death.
receiving nutrition support. Another prospective cohort study by the Canadian
A common practice in ICU patients is to provide a Critical Care Trials Group examined physician estimates
combination of enteral and parenteral nutrition when of ICU survival and patient outcomes. Daily assessment
full caloric goal requirements are unable to be achieved of intensivist and bedside ICU nurse estimates of prob-
by enteral nutrition alone. A systematic review of five ability of ICU survival were measured in 851 consecu-
randomized prospective trials that compared combina- tive mechanically ventilated adult patients. ICU mortal-
tion nutrition to enteral nutrition alone confirmed no ity rate was 35.7%, and 341 patients (40.1%) were
difference between the groups in rates of mortality, in- assessed by a physician at least once to have a ⬍ 10%
fectious complications, length of hospital stay, or venti- ICU survival probability. Independent predictors of
lator days.61 So in critically ill patients who are not mal- ICU mortality were baseline APACHE II score and daily
nourished and have an intact gastrointestinal tract, the factors such as multiple organ dysfunction syndrome,
use of parenteral nutrition in combination with enteral use of inotropes or vasopressors, dialysis, patient prefer-
nutrition provides no benefit in clinical outcomes over ence to limit life support, and physician but not nurse
enteral nutrition alone. prediction of ⬍ 10% survival. This study documented
that physician estimates of ICU survival ⬍ 10% were
associated with subsequent life support limitation and
End-of-life issues
more powerfully predicted ICU mortality than illness
There is increasing concern over the appropriateness and
severity, evolving or resolving organ dysfunction, and
quality of care provided in the ICU at the end of life. The
use of inotropes or vasopressors.64
first review of the number of Americans who receive
ICU care at the end of life was published in 2004, using
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