Duration of Antibiotic Therapy for Early VAP Trial: Study Protocol for a Surgical Infection Society Multicenter, Pragmatic, Randomized Clinical Trial of Four versus Seven Days of Definitive Antibiotic Therapy for Early Ventilator-Associated Pneumonia in Surgical Patients.

Background: Current guidelines recommend a seven-day course of antibiotic therapy for patients with ventilator-associated pneumonia (VAP). However, clinical and microbiologic resolution of infection may occur much sooner than seven days, particularly in patients with early VAP. Shortening the course of antibiotic therapy for early VAP likely results in lower antibiotic-associated complications, but it is unclear whether VAP recurrence rates will be higher in patients receiving fewer days of therapy. We propose to compare four days versus seven days of antibiotic therapy for early VAP in surgical patients in a multicenter, pragmatic, randomized clinical trial. Patients and Methods: Eligible patients admitted to a surgical intensive care unit with early VAP, defined as VAP occurring within two to seven days of intubation, will be randomized to receive four or seven days of antibiotic therapy. The two primary outcomes are: VAP recurrence, defined as VAP occurring two to 14 days after completion of initial therapy and antibiotic-free days, defined as the number of days without receiving any antibiotic agents within 30 days from completion of initial therapy. Data will be analyzed using both intention-to-treat and per-protocol strategies. Power analysis was performed assuming non-inferiority of four days vs. seven days for VAP recurrence and superiority of four days versus seven days for antibiotic-free days. The total sample size to detect a 10% difference between groups with 80% power and assuming a 10% dropout rate is 458 patients. Three separate data analyses are planned throughout the trial and sample size will be re-calculated at each interim analysis. Conclusions: The Duration of Antibiotic Therapy for Early VAP (DATE) Trial will enroll surgical patients with early VAP to analyze whether a shorter duration of antibiotic therapy results in similar clinical outcomes while decreasing antibiotic exposure.

Recent Advances in Forward Surgical Team Training at the U.S. Army Trauma Training Department.

U.S. Army Forward Surgical Teams (FSTs) are elite, multidisciplinary units that are highly mobile, and rapidly deployable. The mission of the FST is to provide resuscitative and damage control surgery for stabilization of life-threatening injuries in austere environments. The Army Trauma Training Center began in 2001 at the University of Miami Ryder Trauma Center under the direction of COL T. E. Knuth, MC USA (Ret.), as a multimodality combination of lectures, laboratory exercises, and clinical experiences that provided the only predeployment mass casualty and clinical trauma training center for all FSTs. Each of the subsequent five directors has restructured the training based on dynamic feedback from trainees, current military needs, and on the rapid advances in combat casualty care. We have highlighted these evolutionary changes at the Army Trauma Training Center in previous reviews. Under the current director, LTC J. M. Seery, MC USA, there are new team-building exercises, mobile learning modules and simulators, and other alternative methods in the mass casualty exercise. This report summarizes the latest updates to the state of the art training since the last review.

An Interlaboratory Validation of the Radiation Dose Response Relationship (DRR) for H-ARS in the Rhesus Macaque.

The Medical Countermeasures against Radiological Threats (MCART) consortium has established a dose response relationship for the hematopoietic acute radiation syndrome (HARS) in the rhesus macaque conducted under an individualized supportive care protocol, including blood transfusions. Application of this animal model as a platform for demonstrating efficacy of candidate medical countermeasures is significantly strengthened when the model is independently validated at multiple institutions. The study reported here describes implementation of standard operating procedures at an institute outside the consortium in order to evaluate the ability to establish an equivalent radiation dose response relationship in a selected species. Validation of the animal model is a significant component for consideration of the model protocol as an FDA-recommended drug development tool in the context of the "Animal Rule." In the current study, 48 male rhesus macaques (4-8 kg) were exposed to total-body irradiation (TBI) using 6 MV photon energy at a dose rate of approximately 0.8 Gy min. Results show that onset and duration of the hematological response, including anemia, neutropenia, and thrombocytopenia, following TBI ranging from 6.25 to 8.75 Gy correlate well with previously reported findings. The lethality values at 60 d following TBI were estimated to be 6.88 Gy (LD30/60), 7.43 Gy (LD50/60), and 7.98 Gy (LD70/60). These values are equivalent to those published previously of 7.06 Gy (LD30/60), 7.52 Gy (LD50/60), and 7.99 Gy (LD70/60); the DRR slope (p = 0.68) and y-intercepts show agreement along the complete dose range for HARS. The ability to replicate the previously established institutional lethality profile (PROBIT) and model outcomes through careful implementation of defined procedures is a testament to the robustness of the model and highlights the need for consistency in procedures.

Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism.

We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 (P = 0.504). TPX was initiated 3.4 ± 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25-37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 (P < 0.001); correcting from 7.75 (6.45-8.90) minutes to 10.45 (7.90-15.25) minutes (P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 (P < 0.001); increasing from 61(55-65) mm to 75(69-80) mm (P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R(2) = 0.095, P = 0.008) and at Day 7 (r = 0.516, R(2) = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R(2) = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients.

Medical planning and response for a nuclear detonation: a practical guide.

This article summarizes major points from a newly released guide published online by the Office of the Assistant Secretary for Preparedness and Response (ASPR). The article reviews basic principles about radiation and its measurement, short-term and long-term effects of radiation, and medical countermeasures as well as essential information about how to prepare for and respond to a nuclear detonation. A link is provided to the manual itself, which in turn is heavily referenced for readers who wish to have more detail.

Insertion of central venous catheters induces a hypercoagulable state.

BACKGROUND: Central venous catheters (CVCs) increase the risk of venous thromboembolism. We have previously demonstrated that pulmonary artery catheters are associated with a hypercoagulable state in an animal model and in patients. The purpose of this study is to determine whether the insertion of a CVC is associated with a similar response. ANIMAL: 7F femoral artery catheters were placed in healthy anesthetized swine (N = 16). Serial arterial blood samples were drawn immediately before and after an 8.5F jugular vein CVC and then for 3 hours after CVC removal. Samples were analyzed using kaolin-activated thromboelastography (TEG) at precisely 2 minutes. Human: An institutional review board-approved prospective observational trial was conducted, with informed consent, in patients with critical illness (N = 8) at a Level I trauma center. Blood was drawn from indwelling arterial catheters immediately before and 60 minutes after CVC insertion. Samples were stored in sodium citrate for 15 minutes before TEG. Routine and special coagulation tests were performed on stored samples in the hospital pathology laboratory. RESULTS: Insertion of a CVC decreased TEG clotting time (R) by 55% in swine and by 29% in humans (p < 0.001 and 0.019, respectively). Initial clot formation time (K) was reduced by 41% in swine and by 36% in humans (p = 0.003 and 0.019). Fibrin cross-linking (α) was accelerated by 28% in swine and by 17% in humans (p = 0.007 and 0.896), but overall clot strength (maximum amplitude) was not affected. There was no change in routine or special coagulation factors, including von Willebrand factor, antithrombin III, prothrombin time, international normalized ratio, or activated partial thromboplastin time. In animals, the hypercoagulable TEG response was persistent for 3 hours after CVC removal and was prevented by pretreatment with enoxaparin (n = 4) but not heparin (n = 2). CONCLUSION: In healthy swine and patients with critical illness, a systemic hypercoagulable state occurred after CVC insertion, and this may partially account for an increased risk of venous thromboembolism. However, because the sample size was small and not powered to detect changes in coagulation proteins, no inferences can be made about the mechanism for the hypercoagulable response.

Heart rate variability is an independent predictor of morbidity and mortality in hemodynamically stable trauma patients.

BACKGROUND: Reduced heart rate variability (HRV) reflects autonomic dysfunction and can triage patients better than routine trauma criteria or vital signs. However, there is questionable specificity and no consensus measurement technique. The purpose of this study was to analyze whether factors that alter autonomic function affect the specificity of HRV for assessing traumatic injury. METHODS: We evaluated 216 hemodynamically stable adults (3:1 M:F; 97:3 blunt:penetrating; age 49 years ± 1 year, mean ± standard error) undergoing computed axial tomography (CT) scan to rule out traumatic brain injury (TBI). All were prospectively instrumented with a Mars Holter system (GE Healthcare, Milwaukee, WI). HRV was determined offline using time domain (standard deviation of normal-normal intervals, root-mean-square successive difference) and frequency domain (very low frequency [VLF], LF, wideband frequency, high frequency [HF], low to HF index ratio) calculations from 15-minute electrocardiogram and correlated with routine vital signs, mortality, TBI, morbidity, length of stay (LOS), and comorbidities. Significance (p ≤ 0.05) was determined using nonparametric analysis, Student's t test, analysis of variance, or multiple logistic regression. RESULTS: VLF alone predicted survival, severity of TBI, intensive care unit LOS, and hospital LOS (all p < 0.05). Beta-blockers or diabetes had no effect, whereas age, sedation, mechanical ventilation, spinal cord injury, and intoxication influenced one or more of the variables with age being the most powerful confounder (all p < 0.05). Except for the Glasgow Coma Scale, no other routine trauma or hemodynamic criteria correlated with any of these outcomes. CONCLUSIONS: Decreased VLF is an independent predictor of mortality and morbidity in hemodynamically stable trauma patients. Other time and other frequency domain variables correlated with some, but not all, outcomes. All were heavily influenced by factors that alter autonomic function, especially patient age.

The U.S. government's medical countermeasure portfolio management for nuclear and radiological emergencies: synergy from interagency cooperation.

Following the attacks of 11 September 2001, emergency preparedness within the U.S. Department of Health and Human Services, as well as at the Department of Defense and other federal agencies, received higher visibility, new mandates and increased funding. Emergency deployment teams increased the frequency of drills to enable better response to the health consequences of mass-casualty incidents. Interagency coordination has also continued to increase to more efficiently and effectively leverage federal resources toward emergency medical preparedness for both civilian and military populations.

First report on safety and efficacy of hetastarch solution for initial fluid resuscitation at a level 1 trauma center.

BACKGROUND: For logistics, the US Army recommends Hextend (Hospira; 6% hetastarch in buffered electrolyte, HET) for battlefield resuscitation. To support this practice, there are laboratory data, but none in humans. To test the hypothesis that HET is safe and effective in trauma, we reviewed our first 6 months of use at a civilian level 1 trauma center. STUDY DESIGN: From June 2008 to December 2008, trauma patients received standard of care (SOC) +/- 500 to 1,000 mL of HET within 2 hours of admission at surgeon discretion. Each case was reviewed, with waiver of consent. RESULTS: There were 1,714 admissions; 805 received HET and 909 did not. With HET versus SOC, overall mortality was 5.2% versus 8.9% (p = 0.0035) by univariate analysis. Results were similar after penetrating injury only (p = 0.0016) and in those with severe injury, defined by Glasgow Coma Scale <9 (p = 0.0013) or Injury Severity Score >26 (p = 0.0142). After HET, more patients required ICU admission (40.9% vs. 34.5%; p = 0.0334) and transfusions of blood (34.4% vs. 20.2%; p = 0.0014) or plasma (20.7% vs. 12.2%; p = 0.0251), but there were no treatment-related differences in prothrombin time or partial thromboplastin time. The 24-hour urine outputs and requirements for blood, plasma, and other fluids were similar. However, increased early deaths with SOC implicate possible selection bias. If that factor was controlled for with multivariate analysis, the same trends were present, but the apparent treatment effects of HET were no longer statistically significant. CONCLUSIONS: In the first trial to date in hemodynamically unstable trauma patients, and the largest trial to date in any population of surgical patients, initial resuscitation with HET was associated with reduced mortality and no obvious coagulopathy. A randomized blinded trial is necessary before these results can be accepted with confidence.

Rapid radiation dose assessment for radiological public health emergencies: roles of NIAID and BARDA.

A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals to allow for prompt triage and appropriate medical treatment. Measuring absorbed doses of ionizing radiation will require a system architecture or a system of platforms that contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents, rapidity and ease of screening are essential. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health is the focal point within the Department of Health and Human Services (HHS) for basic research and development of medical countermeasures for radiation injuries. The Biomedical Advanced Research and Development Authority within the HHS Office of the Assistant Secretary for Preparedness and Response coordinates and administers programs for the advanced development and acquisition of emergency medical countermeasures for the Strategic National Stockpile. Using a combination of funding mechanisms, including funds authorized by the Project BioShield Act of 2004 and those authorized by the Pandemic and All-Hazards Preparedness Act of 2006, HHS is enhancing the nation's preparedness by supporting the radiation dose assessment capabilities that will ensure effective and appropriate use of medical countermeasures in the aftermath of a radiological or nuclear incident.

Heart rate variability as a triage tool in patients with trauma during prehospital helicopter transport.

BACKGROUND: Prehospital triage of patients with trauma is routinely challenging, but more so in mass casualty situations and military operations. The purpose of this study was to prospectively test whether heart rate variability (HRV) could be used as a triage tool during helicopter transport of civilian patients with trauma. METHODS: After institutional review board approval and waiver of informed consent, 75 patients with trauma requiring prehospital helicopter transport to our level I center (from December 2007 to November 2008) were prospectively instrumented with a 2-Channel SEER Light recorder (GE Healthcare, Milwaukee, WI). HRV was analyzed with a Mars Holter monitor system and proprietary software. SDNN (standard deviation [SD] of the normal-to-normal R-R interval), as an index of HRV, was correlated with prehospital trauma triage criteria, base deficit, seriousness of injury, operative interventions, outcome, and other data extracted from the patients' medical records. There were no interventions or medical decisions based on HRV. Data were excluded only if there was measurement artifact or technical problems with the recordings. RESULTS: The demographics were mean age 47 years, 63% men, 88% blunt, 25% traumatic brain injury, 9% mortality. Prehospital SDNN predicted patients with base excess < or = -6, those defined as seriously injured and benefiting from trauma center care, as well as patients requiring a life-saving procedure in the operating room. No other available data, including prehospital en-route vital signs, predicted any of these. The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 75%, 33%, 96%, respectively, with and an overall accuracy of 76% for predicting a life-saving intervention in the operating room. CONCLUSIONS: This is the first demonstration that prehospital HRV (specifically SDNN) predicts base excess and operating room life-saving opportunities. HRV triages and discriminates severely injured patients better than routine trauma criteria or en-route prehospital vital signs. HRV may be a useful civilian or military triage tool to avoid unnecessary helicopter evacuation for minimally injured patients. A prospective, randomized trial in a larger patient population is indicated.

Prehospital intubations and mortality: a level 1 trauma center perspective.

BACKGROUND: Ryder Trauma Center is a Level 1 trauma center with approximately 3800 emergency admissions per year. In this study, we sought to determine the incidence of failed prehospital intubations (PHI), its correlation with hospital mortality, and possible risk factors associated with PHI. METHODS: A prospective observational study was conducted evaluating trauma patients who had emergency prehospital airway management and were admitted during the period between August 2003 and June 2006. The PHI was considered a failure if the initial assessment determined improper placement of the endotracheal tube or if alternative airway management devices were used as a rescue measure after intubation was attempted. RESULTS: One-thousand-three-hundred-twenty patients had emergency airway interventions performed by an anesthesiologist upon arrival at the trauma center. Of those, 203 had been initially intubated in the field by emergency medical services personnel, with 74 of 203 (36%) surviving to discharge. When evaluating the success of the intubation, 63 of 203 (31%) met the criteria for failed PHI, all of them requiring intubation, with only 18 of 63 (29%) surviving to discharge. These patients had rescue airway management provided either via Combitube (n = 28), Laryngeal Mask Airway (n = 6), or a cricothyroidotomy (n = 4). An additional 25 of 63 patients (12%) had unrecognized esophageal intubations discovered upon the initial airway assessment performed on arrival. We found no difference in mortality between those patients who were properly intubated and those who were not. Several other variables, including age, gender, weight, mechanism of injury, presence of facial injuries, and emergency medical services were not correlated with an increased incidence of failed intubations. CONCLUSION: This prospective study showed a 31% incidence of failed PHI in a large metropolitan trauma center. We found no difference in mortality between patients who were properly intubated and those who were not, supporting the use of bag-valve-mask as an adequate method of airway management for critically ill trauma patients in whom intubation cannot be achieved promptly in the prehospital setting.

The USP Performance Verification Test, Part I: USP Lot P Prednisone Tablets: quality attributes and experimental variables contributing to dissolution variance.

PURPOSE: Beyond instrumental qualification, proficiency testing is not usually a prerequisite for many analytical procedures, given reliance on a manufacturer's assay validation coupled with regulatory review and inspection. Given the special features of the dissolution procedure, proficiency testing was put in place initially by pharmaceutical manufacturers and carried on by USP. Proficiency testing is designed to help ensure that execution of a dissolution procedure for solid oral dosage forms adequately supports administrative and legal decisions so that measurements made at different times, by different analysts, or with different methods can be confidently compared. USP has applied metrological principles to aid practitioners in carrying out the dissolution procedure alone and in collaborative studies to facilitate understanding potential sources of variability. MATERIALS AND METHODS: The present study aimed to identify key dissolution variables associated with USP Lot P Prednisone Tablets in conjunction with the USP Performance Verification Test (PVT). Using five dissolution test assemblies from different manufacturers, at least four of six analysts determined percents prednisone dissolved on dissolution Apparatus 1 (basket) and Apparatus 2 (paddle) on each assembly. Six replicate experiments were performed on each analyst-assembly combination with a set of six to eight tablets in each experiment. RESULTS AND CONCLUSIONS: Statistical analysis demonstrated that dissolution test assemblies were the largest factor contributing to dissolution variability. Inherent tablet variability was low, and USP Lot P Prednisone Tablets did not contribute importantly to dissolution variability. Contributions from analyst and analytical procedure also were estimated to be low.

The USP Performance Verification Test, Part II: collaborative study of USP's Lot P Prednisone Tablets.

PURPOSE: Periodic performance verification testing (PVT) is used by laboratories to assess and demonstrate proficiency and for other purposes as well. For dissolution, the PVT is specified in the US Pharmacopeia General Chapter Dissolution <711> under the title Apparatus Suitability Test. For Apparatus 1 and 2, USP provides two reference standard tablets for this purpose. For each new lot of these reference standards, USP conducts a collaborative study. METHODS: For new USP Lot P Prednisone Tablets, 28 collaborating laboratories provided data. The study was conducted with three sets of tablets: Lot O open label, Lot O blinded, and Lot P blinded. The blinded Lot O data were used for apparatus suitability testing. RESULTS: Acceptance limits were determined after dropping data due to failure of apparatus suitability, identification of data as unusual on control charts, or protocol violations. CONCLUSIONS: Results yielded acceptance criteria of (47, 82) for Apparatus 1 and (37, 70) for Apparatus 2. Results generally were similar for Lot P compared to results from Lot O except that the average percent dissolved for Lot P is greater than for Lot O with Apparatus 2.

Outcomes of Acinetobacter baumannii infection in critically ill surgical patients.

BACKGROUND: Multi-drug resistant (MDR) organisms in intensive care units (ICUs) are a growing concern. The emergence of several infections with MDR Acinetobacter baumannii prompted a review of cases and evaluation of the efficacy of intervention. OBJECTIVE: To determine the rate of clinical cure, the incidence of drug resistance, and the mortality rate associated with A. baumannii infection. METHOD: Retrospective review of A. baumannii infections in three surgical ICUs between January, 2004 and November, 2005. Infection was identified in 291 patients, 20 of whom were excluded because of incomplete documentation. Of the remaining 271 patients, 71% were male, and the mean age was 47 +/- 18 years (range 13-90 years). RESULTS: Patients had a mean length of stay in the ICU of 14 days (range 0-136 days) before infection. The initial positive cultures were from bronchoalveolar lavage fluid (BAL) in 72.3%, blood in 16.2%, a catheter tip in 6.3%, urine in 1.8%, wound in 2.2%, and abscess in 1.1%. In 46.9% of patients, the first culture was polymicrobial. The Acinetobacter isolates were resistant or intermediate-resistant to imipenem-cilastatin in 81.2% of cases; 19.9% were resistant to all drugs except colistin, and two were resistant to all tested drugs. Colistin was used in 75.6% of patients (intravenous 61.5%, nebulized 38.5%). The mean duration of treatment was 13 +/- 8.9 days (range 0-56 days), and clinical cure was achieved in 73.8% of patients. Recurrent infection after initial cure was found in 19.2% of patients. There was no significant difference in clinical cure rates between patients treated with colistin and those treated with other culture-directed drugs (75.1% vs. 69.7%), or between patients treated with intravenous vs. nebulized colistin (72.4% vs. 79.5%). The mortality rate was 26.2% for the entire group and was significantly higher in the subgroup of transplant patients (n = 31) (64.5% vs. 21.4%; p < 0.001). CONCLUSION: The majority of A. baumannii isolates were MDR, and a significant proportion were sensitive only to colistin. Treatment of A. baumannii infection with colistin is effective by both intravenous and nebulized routes of administration. However, infection with A. baumannii in critically ill surgical patients is associated with a high mortality rate, particularly in transplant patients.

Aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study.

OBJECTIVE: To evaluate the efficacy and safety of inhaled tobramycin (TOBI) in the treatment of ventilator-associated pneumonia (VAP) in a randomized, double-blind pilot study. PATIENTS AND METHODS: Ten patients from a cohort of 108 mechanically ventilated patients with documented clinical and bacteriological evidence of VAP caused by Pseudomonas aeruginosa or Acinetobacter spp. in the surgical and trauma intensive care units of a university teaching hospital were randomized to receive either TOBI (n = 5) or intravenous tobramycin (TOBRA; n = 5). The two groups were similar in their Acute Physiology and Chronic Health Evaluation (APACHE) score, Clinical Pulmonary Infection Score (CPIS), and Multiple Organ Dysfunction Score (MODS) prior to randomization. The primary outcome measure was resolution of pneumonia. The CPIS and MODS were used as objective indicators of clinical progress. RESULTS: All TOBI patients had clinical resolution of VAP. Two TOBRA patients were considered failures. One had deterioration in MODS, and the other had doubling of his serum creatinine concentration. The patients treated with TOBI may have had more ventilator-free days than those receiving TOBRA, but the difference was not statistically significant owing to the small sample size (24 +/- 3 vs. 14 +/- 13 days; p = 0.12). CONCLUSION: Aerosolized tobramycin for the treatment of VAP appeared safe and effective in this pilot study. A larger study is warranted to determine if aerosolized tobramycin will lead to better outcomes than intravenous tobramycin when used for the treatment of VAP.

Survival after prolonged length of stay in a trauma intensive care unit.

BACKGROUND: Intensive care unit (ICU) patients comprise a small proportion of patients in the hospital but consume a disproportionate amount of hospital resources. In our cost-conscious environment, it becomes necessary to address the overall performance of our ICUs. This study was designed to analyze survival among trauma ICU (TICU) patients with a length of stay (LOS) >1 month. METHODS: We retrospectively reviewed the prospectively collected Trauma Registry Database between January 1, 1995, and January 1, 2005, in an adult TICU from a Level I trauma center. Data on demographics, mechanism of injury, Injury Severity Score (ISS), LOS, and in-hospital survival was collected. Descriptive statistics were calculated and student's t test and comparison of proportions were performed where appropriate. Logistic regression was performed to analyze independent predictors of mortality with significance when p < 0.05. RESULTS: The initial cohort consisted of 3,556 patients with a mean LOS of 9.8 days (range, 0-274 days). Sixty-nine percent were men, mean age was 44.3 years (range, 0-104 years), and mean ISS was 18 (range, 0-75). The mechanism of injury was blunt trauma in 75%, burns in 15%, and penetrating trauma in 10%. Overall survival was 87%. A total of 339 patients had a LOS >1 month. There was no difference in survival between patients with a LOS <1 month and those with a LOS >1 month (87.1% versus 86.7%). Patients >50 years old (n = 1,251) had a longer LOS (12.5 versus 8.4 days; p < 0.001) and increased mortality (22.1% versus 8.0%; p < 0.001). Age remained an independent predictor of mortality when controlling for ISS. CONCLUSION: In our TICU population, extended LOS did not preclude a significant chance of survival. Patients >50 years old had longer LOS and increased mortality. This suggests that the utilization of resources in patients with a prolonged LOS is reasonable and justified.

A stability-indicating HPLC assay for metronidazole benzoate.

A simple and rapid stability-indicating HPLC assay procedure has been developed and validated for metronidazole benzoate. The HPLC conditions were as follows, column: Waters Symmetry C8, 5 microm packing, 4.6 mm x 250 mm; detection: UV at 271 nm; injection volume: 20 microl; mobile phase: acetonitrile-0.1% glacial acetic acid in monobasic potassium phosphate (0.01 M) (40:60, v/v); isocratic elution under ambient temperature at 2.0 ml min(-1). The procedure separated metronidazole benzoate and its potential degradation products, metronidazole and benzoic acid, in an overall analysis time of about 6 min with metronidazole benzoate eluting at about 5 min. The injection repeatability was 0.03%, and the intraday and interday repeatability were 0.4 and 0.7%, respectively. The procedure provided a linear response over the concentration range 0.2-800 microg ml(-1) (r=1.0000) with the limits of detection and quantitation 0.03 and 0.2 microg ml(-1), respectively. The solubilities of metronidazole benzoate in water, 0.01 M hydrochloric acid and 0.05 M phosphate buffer, pH 6.8, determined each in triplicate using the procedure, were 0.2 mg ml(-1) (R.S.D. 7%), 0.4 mg ml(-1) (R.S.D. 2%) and 0.2 mg ml(-1) (R.S.D. 8%), respectively. The results show no detectable hydrolysis of metronidazole benzoate in 0.01 M hydrochloric acid at 37 degrees C or in the mobile phase at ambient temperature in 10 h.