The impact of beta-blocker therapy on anemia after traumatic brain injury.

BACKGROUND: An increase in endogenous catecholamine levels after traumatic brain injury (TBI) is well described. Animal studies suggest that postinjury anemia is exacerbated by a persistent hyperadrenergic state. This study aims to determine if beta-blocker (BB) exposure affects anemia after TBI. STUDY DESIGN AND METHODS: We reviewed a Level I trauma registry for patients with TBI, examining markers of anemia between patients who received BB with those who did not. RESULTS: A total of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean age in the BB+ group was 50 years (vs. 36 years in BB- group, p < 0.001). The mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs. 35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later day of hospitalization and their rate of decrease in Hb was significantly slower (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan-Meier demonstrated a significant delay in time to anemia. CONCLUSION: This study suggests beta-blockade delays anemia after TBI. Elaboration of this effect may demonstrate an additional benefit of beta-blockade after head injury.

High-dose antioxidant administration is associated with a reduction in post-injury complications in critically ill trauma patients.

BACKGROUND: We recently demonstrated a high-dose antioxidant (AO) protocol was associated with reduction in mortality. The purpose of this study was to evaluate the impact of AO on organ dysfunction and infectious complications following injury. PATIENTS AND METHODS: High-dose AO protocol: ascorbic acid 1000 mg q 8 h, alpha-tocopherol 1000 IU q 8 h, and selenium 200 mcg qd for 7-day course. Retrospective cohort study evaluating all patients admitted after protocol implementation (AO+), October 1, 2005 to September 30, 2006. Comparison cohort (AO-): all patients admitted in the year prior to implementation, October 1, 2004 to September 30, 2005. RESULTS: 2272 patients included in the AO+ group, 2022 patients in the AO- group. Demographics and injury severity were similar. Abdominal compartment syndrome (ACS) (2.9% vs. 0.7%, <0.001), surgical site infections (2.7% vs. 1.3%, p=0.002), pulmonary failure (27.6% vs. 17.4%, p<0.001), and ventilator-dependent respiratory failure (10.8% vs. 7.1%, p<0.001) were significantly less in the AO+ group. Multivariate regression showed 53% odds reduction in abdominal wall complications and 38% odds reduction in respiratory failure in the AO+ group. CONCLUSIONS: Implementation of a high-dose AO protocol was associated with a reduction in respiratory failure and ventilator-dependence. In addition, AO were associated with a marked decrease in abdominal wall complications, including ACS and surgical site infections.

Infection reduction strategies including antibiotic stewardship protocols in surgical and trauma intensive care units are associated with reduced resistant gram-negative healthcare-associated infections.

BACKGROUND: Resistance to broad-spectrum antibiotics by gram-negative organisms is increasing. Resistance demands more resource utilization and is associated with patient morbidity and death. We describe the implementation of infection reduction protocols, including antibiotic stewardship, and assess their impact on multi-drug-resistant (MDR) healthcare-acquired gram-negative infections. METHODS: Combined infection reduction and antibiotic stewardship protocols were implemented in the surgical and trauma intensive care units at Vanderbilt University Hospital beginning in 2002. The components of the program were: (1) Protocol-specific empiric and therapeutic antibiotics for healthcare-acquired infections; (2) surgical antibiotic prophylaxis protocols; and (3) quarterly rotation/limitation of dual antibiotic classes. Continuous healthcare-acquired infection surveillance was conducted by independent practitioners using National Heath Safety Network criteria. Linear regression analysis was used to estimate trends in MDR gram-negative healthcare-acquired infections. RESULTS: A total of 1,794 gram-negative pathogens were isolated from healthcare-acquired infections during the eight-year observation period. The proportion of healthcare-acquired infections caused by MDR gram-negative pathogens decreased from 37.4% (2001) to 8.5% (2008), whereas the proportion of healthcare-acquired infections caused by pan-sensitive pathogens increased from 34.1% to 53.2%. The rate of total healthcare-associated infections per 1,000 patient-days that were caused by MDR gram-negative pathogens declined by -0.78 per year (95% confidence interval [CI] -1.28, -0.27). The observed rate of healthcare-acquired infections per 1,000 patient days attributable to specific MDR gram-negative pathogens decreased over time: Pseudomonas -0.14 per year (95% CI -0.20, -0.08), Acinetobacter-0.49 per year (95% CI -0.77, -0.22), and Enterobacteriaceae -0.14 per year (95% CI -0.26, -0.03). CONCLUSION: Implementation of an antibiotic stewardship protocol as a component of an infection reduction campaign was associated with a decrease in resistant gram-negative healthcare-acquired infections in intensive care units. These results further support widespread implementation of such initiatives.

Postoperative neuromuscular blocker use is associated with higher primary fascial closure rates after damage control laparotomy.

BACKGROUND: Failure to achieve fascial primary closure after damage control laparotomy (DCL) is associated with increased morbidity, higher healthcare expenditures, and a reduction in quality of life. The use of neuromuscular blocking agents (NMBA) to facilitate closure remains controversial and poorly studied. The purpose of this study was to determine whether exposure to NMBA is associated a higher likelihood of primary fascial closure. METHODS: All adult trauma patients admitted between January 2002 and May 2008 who (1) went directly to the operating room, (2) were managed initially by DCL, and (3) survived to undergo a second laparotomy. Study group (NMBA+): those receiving NMBA in the first 24 hours after DCL. Comparison group (NMBA-): those not receiving NMBA in the first 24 hours after DCL. Primary fascial closure defined as fascia-to-fascia approximation by hospital day 7. RESULTS: One hundred ninety-one patients met inclusion (92 in NMBA+ group, 99 in NMBA- group). Although the NMB+ patients were younger (31 years vs. 37 years, p = 0.009), there were no other differences in demographics, severity of injury, or lengths of stay between the groups. However, NMBA+ patients achieved primary closure faster (5.1 days vs. 3.5 days, p = 0.046) and were more likely to achieve closure by day 7 (93% vs. 83%, p = 0.023). After controlling for age, gender, race, mechanism, and severity of injury, logistic regression identified NMBA use as an independent predictor of achieving primary fascial closure by day 7 (OR, 3.24, CI: 1.15-9.16; p = 0.026). CONCLUSIONS: Early NMBA use is associated with faster and more frequent achievement of primary fascial closure in patients initially managed with DCL. Patients exposed to NMBA had a three times higher likelihood of achieving primary fascial closure by hospital day 7.

Vasopressin use is associated with death in acute trauma patients with shock.

PURPOSE: Traumatic hemodynamic instability is associated with high mortality if not expeditiously corrected. Hypotension despite adequate volume resuscitation is treated with vasopressors. Although catecholamines are typically the first agent used, arginine vasopressin (AVP) is increasingly been used as an adjuvant agent. Mortality with refractory hypotension and vasopressin use in trauma patients is unknown. MATERIALS AND METHODS: A retrospective cohort analysis of trauma patients requiring vasopressors within 72 hours of admission was performed. Two groups were identified: patients who received AVP (AVP+) and those who did not (AVP-). Primary outcome was mortality. RESULTS: Five hundred thirty nine patients met the criteria with 189 patients receiving AVP. Demographics, Injury Severity Score, minimum hemoglobin, and blood volume resuscitation (packed red blood cell, fresh frozen plasma, and platelets) were similar between groups. Trauma and Injury Severity Score suggested a higher probability of survival in AVP+ (0.88 vs 0.73, P < .001); however, the observed mortality was higher (55% vs 41%, P = .002). The age, Injury Severity Score, initial lactate, and severe head injury adjusted odds ratio of death for AVP+ patients was 1.6 (95% confidence interval, 1.1-2.4; P = .02). CONCLUSIONS: Arginine vasopressin is associated with increased mortality in trauma patients with refractory hypotension. Arginine vasopressin may be a marker of illness or possibly play a causal role in adverse outcomes. Clinicians should reconsider expanding the indications of AVP use.

Acute adrenal insufficiency may affect outcome in the trauma patient.

Acute adrenal insufficiency in the trauma patient is underrecognized and the impact poorly understood. Our hypothesis was that the identification and treatment of acute adrenal insufficiency reduces mortality in trauma patients. Institutional Review Board approval for the retrospective review of a prospective database from a Level 1 trauma center for 2002 to 2004 was obtained. The study population included patients receiving a cosyntropin stimulation test (250 microg) and/or random cortisol level based on our practice management guideline and an intensive care unit stay longer than 24 hours. Demographic, acuity, and outcome data were collected. The nonresponders had baseline cortisol levels less than 20 microg/dL or poststimulation rise less than 9 microg/dL. Independent t tests and chi2 statistics were used. One hundred thirty-seven patients had cosyntropin stimulation tests performed. Eighty-two (60%) patients were nonresponders of which 66 were treated with hydrocortisone and 16 went untreated as a result of the discretion of the attending physician. The 55 (40%) responders showed no statistical differences in outcome variables whether or not they received hydrocortisone. The untreated adrenal-insufficient patients had significantly higher mortality, longer hospital length of stay, intensive care unit days, and ventilator-free days. Conclusions were: (1) treatment of acute adrenal insufficiency reduces mortality by almost 50 per cent in the trauma patient; and (2) acute adrenal insufficiency recognized by low random cortisol levels or nonresponse to a stimulation tests should be considered for treatment.

Impact of high-dose antioxidants on outcomes in acutely injured patients.

BACKGROUND: The profound oxidative stress that occurs following injury results in significant depletion of many endogenous antioxidants (vitamin C, E, selenium). Increasing evidence suggests antioxidant supplementation reduces infectious complications and organ dysfunction following injury and hemorrhagic shock. The purpose of this study was to evaluate the impact of high-dose antioxidant administration on the mortality rate of acutely injured patients. METHODS: In October 2005, we implemented a 7-day high-dose antioxidant protocol for acutely injured patients admitted to our trauma center. A retrospective cohort study, evaluating all patients admitted to the trauma service between October 2005 and September 2006 following protocol implementation (AO+), was performed. The comparison cohort (AO-) was made up of those patients admitted in the year prior to protocol implementation. RESULTS: A total of 4,294 patients met criteria (AO+, N = 2,272; AO-, N = 2022). Hospital (4 vs 3 days, P < .001) and ICU (3 vs 2 days, P = .001) median length of stays were significantly shorter in the AO+ group. Mortality was significantly lower in the AO+ group (6.1% vs 8.5%, P = .001), translating into a 28% relative risk reduction for mortality in patients exposed to high-dose antioxidants. After adjusting for age, gender, and probability of survival, AO exposure was associated with even lower mortality (OR 0.32, 95% CI 0.22-0.46). Patients with an expected survival <50% benefited most (OR 0.24, 95% CI 0.15-0.37). CONCLUSIONS: A high-dose antioxidant protocol resulted in a 28% relative risk reduction in mortality and a significant reduction in both hospital and ICU length of stay. This protocol represents an inexpensive intervention to reduce mortality/morbidity in the trauma patient.

Implementation, reliability testing, and compliance monitoring of the Confusion Assessment Method for the Intensive Care Unit in trauma patients.

OBJECTIVE: To implement delirium monitoring, test reliability, and monitor compliance of performing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in trauma patients. DESIGN AND SETTING: Prospective, observational study in a level 1 trauma unit of a tertiary care, university-based medical center. PATIENTS: Acutely injured patients admitted to the trauma unit between 1 February 2006 and 16 April 2006. MEASUREMENTS AND RESULTS: Following web-based teaching modules and group in-services, bedside nurses evaluated patients daily for depth of sedation with the Richmond Agitation-Sedation Scale (RASS) and for the presence of delirium with the CAM-ICU. On randomly assigned days over a 10-week period, evaluations by nursing staff were followed by evaluations by an expert evaluator of the RASS and the CAM-ICU to assess compliance and reliability of the CAM-ICU in trauma patients. Following the audit period the nurses completed a postimplementation survey. The expert evaluator performed 1,011 random CAM-ICU assessments within 1h of the bedside nurse's assessments. Nurses completed the CAM-ICU assessments in 84% of evaluations. Overall agreement (kappa) between nurses and expert evaluator was 0.77 (0.721-0.822; p < 0.0001), in TBI patients 0.75 (0.667-0.829; p < 0.0001) and in mechanically ventilated patients 0.62 (0.534-0.704; p < 0.0001). The survey revealed that nurses were confident in performing the CAM-ICU, realized the importance of delirium, and were satisfied with the training that they received. It also acknowledged obstacles to implementation including nursing time and failure of physicians/surgeons to address treatment approaches for delirium. CONCLUSIONS: The CAM-ICU can be successfully implemented in a university-based trauma unit with high compliance and reliability. Quality improvement projects seeking to implement delirium monitoring would be wise to address potential pitfalls including time complaints and the negative impact of physician indifference regarding this form of organ dysfunction.

Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients.

BACKGROUND: Timely diagnosis and treatment of adrenal insufficiency (AI) dramatically reduces mortality in trauma patients. We sought to identify risk factors and populations with a high risk of developing AI. DESIGN: Retrospective registry study. SETTING: Academic level I trauma center. PATIENTS: All trauma patients in the intensive care unit who underwent cosyntropin stimulation testing (CST) for presumed AI from January 1, 2002, through December 31, 2004. INTERVENTIONS: Cosyntropin stimulation testing, in which response was defined as an increase of 9 mug/dL (248 nmol/L) or more in cortisol level. MAIN OUTCOME MEASURES: Risk factors for developing AI in critically ill trauma patients. RESULTS: In 137 patients, CST was performed; 83 (60.6%) were nonresponders and 54 (39.4%) were responders. Age, sex, race, trauma mechanism, Injury Severity Score, and Revised Trauma Score were not statistically different between the groups. Rates of sepsis/septic shock, mechanical ventilation, and mortality were also similar between the 2 groups. However, rates of hemorrhagic shock on admission (45 [54%] vs 16 [30%]), requirement of vasopressor support (65 [78%] vs 28 [52%]), and etomidate exposure (59 [71%] vs 28 [52%]) were all significantly higher in the nonresponder group (P < .01). The increased risk of AI remained after controlling for potential confounding covariates (age, mechanism, Injury Severity Score, and Revised Trauma Score). CONCLUSIONS: Exposure to etomidate is a modifiable risk factor for the development of AI in this sample of critically injured patients. The use of etomidate for procedural sedation and rapid-sequence intubation in this patient population should be reevaluated.

Beta-blocker exposure is associated with improved survival after severe traumatic brain injury.

BACKGROUND: Beta-blocker use in elective noncardiac surgery has been associated with a reduction in mortality and cardiovascular complications. Traumatic brain injury (TBI) is often associated with a hyperadrenergic state. We hypothesized that adrenergic blockade would confer improved survival among TBI patients. METHODS: Retrospective review of the Trauma Registry of the American College of Surgeons database at a Level I trauma center was conducted. All trauma patients admitted from January 2004 to March 2005 with head Abbreviated Injury Scale score of 3 or greater were evaluated. Patients with length of stay <4 or >30 days were excluded. Beta-blocker exposure was defined as receiving beta-blockers for 2 or more consecutive days. RESULTS: In all, 420 patients met inclusion criteria: 174 patients exposed to beta-blockers [BB(+)] and 246 not exposed [BB(-)]. Mean age in BB(+) group was 50 years and 36 years in BB(-) group (p < 0.001). Mean Injury Severity Score was 33.6 for BB(+) group and 30.8 for BB(-) group (p = 0.01). Predicted survival (by Trauma and Injury Severity Score) for BB(+) group was 59.1% compared with 70.3% for BB(-) group (p < 0.001). Observed mortality for BB(+) group was 5.1%, 10.8% for BB(-) group (p = 0.036). Adjusted incidence rate ratio of mortality among those exposed to beta-blockers compared with those not exposed was 0.29 (95% confidence interval). CONCLUSIONS: Beta-blocker exposure was associated with a significant reduction in mortality in patients with severe TBI. This reduction in mortality is even more impressive, considering that the BB(+) group was older, more severely injured, and had lower predicted survival.

Influence of broad-spectrum antibiotic prophylaxis on intracranial pressure monitor infections and subsequent infectious complications in head-injured patients.

BACKGROUND: The benefit of antibiotic prophylaxis for intracranial pressure (ICP) monitors remains controversial, and clinical practice varies widely. Whether any antibiotic coverage, particularly broad-spectrum coverage, reduces monitor-related infections remains unproved, and exposure to antibiotics may affect the susceptibility patterns of pathogens producing subsequent infectious complications. Despite the lack of data supporting its use, our level I trauma center had a long-standing ICP monitor prophylaxis protocol that provided broad-spectrum coverage that included ceftriaxone. In April 2002, a protocol change was instituted that substituted cefazolin for ceftriaxone as single-agent prophylaxis for ICP monitors. HYPOTHESIS: Broader-spectrum antibiotic prophylaxis does not reduce ICP monitor-related infections but is associated with acquisition of more drug-resistant infections than narrow-spectrum prophylaxis. METHODS: To evaluate the influence of broad- versus narrow-spectrum prophylaxis, a three year period encompassing each practice was selected. All injured patients with ICP monitors placed between January 1, 2001, and December 31, 2003 (n = 279), were identified using the Vanderbilt trauma database. Antibiotic prophylaxis for ICP monitors was determined using the hospital financial database to identify all antibiotics given to individual patients and subsequent chart review to identify those antibiotics given solely for ICP prophylaxis. A total of 119 patients received narrow-spectrum (either cefazolin or vancomycin; n = 100) or no (n = 19) prophylaxis, whereas 160 received broad-spectrum prophylaxis (ceftriaxone or ciprofloxacin). The two groups did not differ with respect to baseline demographics, type of ICP monitor, or duration of monitor placement. Infectious complications were determined by continuous infection surveillance utilizing standard U.S. Centers for Disease Control and Prevention National Nosocomial Infection Surveillance System (CDC-NNIS) definitions and maintained in a contemporary database. The influence of broad-spectrum antibiotic prophylaxis on both ICP monitor infections and subsequent infections outside the central nervous system (CNS) was determined. RESULTS: Nine patients (3.2%) developed CNS infections; two of 119 patients (1.7%) who received narrow-spectrum or no prophylaxis versus seven of 160 patients (4.4%) who received broad-spectrum prophylaxis (p = NS). Only the duration of monitor placement and Injury Severity Score were associated with the infection rate. In the total population, 185 infections occurred in 93 patients (33%). Infection rates did not differ between patients who received narrow-spectrum or no prophylaxis (32%) and those who received broad-spectrum prophylaxis (34%). However, patients who received broad-spectrum prophylaxis acquired gram-negative infections with significantly greater antibiotic resistance. CONCLUSIONS: Broad-spectrum antibiotic prophylaxis of ICP monitors does not reduce CNS infections, but is associated with a shift to resistant gram-negative pathogens in subsequent infectious complications. Thus, broad-spectrum antibiotic prophylaxis of ICP monitors should be eliminated or minimized unless data from randomized trials prove its utility.