Variability among Online Opioid Conversion Calculators Performing Common Palliative Care Conversions.

Introduction: Online opioid conversion calculators (OOCCs) are commonly used to aid conversion between opioids to overcome tolerance, reduce adverse effects, or challenges related to administration. The purpose of this study was to describe and characterize variability among OOCC used by health care practitioners when converting common opioids and doses encountered in the hospice and palliative care setting. Methods: We collected 58 quantitative surveys and performed sentiment analysis on 62 qualitative responses from adult learners primarily practicing in the palliative care setting and enrolled in an online palliative care Master of Science program through the University of Maryland, Baltimore, who were asked to perform opioid conversion calculations using realistic patient cases. Results: OOCC have substantial variability leading to a wide range of outputs, which may put patients at risk for opioid-related harm. Assessing participant sentiment toward OOCC showed most participants held a "Negative Sentiment" toward these calculators after the activity. Conclusion: Overall, findings reveal that given the same information, clinicians can come to widely different opioid doses and these differences can be amplified by OOCC. These differences can be particularly dangerous given the higher opioid doses commonly used in the palliative care setting. Considering the significant harm that can arise from an error when converting between opioids, clinicians should avoid the routine use of OOCC in real-world patient care settings. If an OOCC is used, organizations should endorse a specific calculator, provide training and education about the algorithm that supports the calculations, and encourage clinicians to use it only after their own manual calculation, which should be documented in the medical record.

Dental Caries Risk in the U.S. Air Force: 2009 to 2017.

INTRODUCTION: The Air Force uses dental caries risk assessments (CRA) to determine which active duty Air Force (ADAF) members are at high caries risk (HCR) and will benefit from additional preventive and restorative dental care. The purpose of this study is to describe the caries risk of ADAF from 2009 to 2017 and determine how demographic, military, and tobacco-use characteristics affect caries risk. MATERIALS AND METHODS: Data from ~300,000 ADAF annual dental examinations from 2009 to 2017 were used. The outcome variable investigated was dental caries risk (high, moderate, or low). Independent variables analyzed were: age, sex, race, education, marital status, military rank, service years, flying status, and tobacco use. Descriptive and multivariable analyses were performed to explore associations between potential risk indicators and caries risk outcomes. RESULTS: From 2009 to 2013, there was a steady decline in ADAF that were diagnosed as low caries risk (LCR), from 80.3% to 67.7%. Since 2013, the prevalence of ADAF that are LCR has remained unchanged at about two-thirds of the force. The proportion of the ADAF that are moderate caries risk (MCR) increased from 15.7% in 2009 to 25.3% in 2013 and remained unchanged affecting about a quarter of the force since then. The proportion that was diagnosed as HCR increased from 3.9% in 2009 to 7.1% in 2013 and declined slightly in 2017 (6.0%). After controlling for other covariates, younger age (<20 years old: odds ratio [OR], 4.4; 95% confidence interval [CI], 3.3-5.8), less time in service (≤4 years: OR, 2.1; 95% CI, 1.7-2.6), junior rank (E-1-E-4: OR, 1.6; 95% CI, 1.3-1.8), less education (high-school graduate: OR, 2.3; 95% CI, 2.0-2.6), using tobacco (Smoker: OR, 1.6; 95% CI, 1.5-1.7), being a nonflyer (OR, 1.2; 95% CI, 1.1-1.3), being male (OR, 1.1; 95% CI, 1.1-1.2), or being black (OR, 1.2; 95% CI, 1.1-1.2) were each associated with being HCR. Among the cohort of Airmen who were LCR at baseline, the majority (75.9%) remained at low risk, but for nearly a quarter (24.1%), their risk of caries increased over 9 years. Among those who were originally MCR in 2009, 61.5% improved to LCR, whereas 4.6% progressed to HCR; among those identified as high risk for caries in 2009, a substantial majority (89.1%) improved over 9 years, but 10.9% remained unchanged. CONCLUSIONS: The prevalence of HCR and MCR service members increased from 2009 to 2013 but has remained consistent since 2013. Overall caries risk in the Air Force is lower compared to previously published findings from 2001 to 2004. This suggests that CRA and prevention programs have been effective at helping to reduce caries prevalence among Airmen. Smoking prevalence among ADAF has also declined substantially over the past 16 years which may contribute to overall caries risk reductions. Using a CRA approach may be an effective tool for helping to identify and develop strategies to manage dental caries risk in patients.

A laparoscopic swine model of noncompressible torso hemorrhage.

BACKGROUND: Hemorrhage persists as the leading cause of potentially preventable civilian and military death. Noncompressible torso hemorrhage (NCTH) is a particularly lethal injury complex, with few contemporary prehospital interventions available. Various porcine models of hemorrhage have been developed for civilian and military trauma research. However, the predominant contemporary models lack key physiologic characteristics including the natural tamponade provided by an intact abdominal wall.To improve physiologic and clinical relevance, we developed a laparoscopic model of NCTH. This approach maintains both the integrity of the peritoneum and the natural tamponade effect of an intact abdominal wall while preserving the intrinsic physiologic responses to hemorrhage. Furthermore, we present data quantifying the contribution of the swine contractile spleen in the context of uncontrolled hemorrhage. METHODS: Anesthetized adult male Yorkshire swine underwent a laparoscopic Grade V liver injury, with or without open preinjury splenectomy. Animals were observed without intervention for a total of 120 minutes after injury to simulate point of injury, transport time, and arrival at hospital. RESULTS: Shed blood-to-body weight ratio did not differ among groups; however, mortality was higher in splenectomized animals (67% vs. 33%). Cox regression modeling demonstrated a critical time point of 45 minutes and blood pressure as significant predictors of mortality. CONCLUSION: This study describes a model of NCTH that reflects clinically relevant physiology in trauma and uncontrolled hemorrhage. In addition, it quantitatively assesses the role of the swine contractile spleen in the described model.

Lineage of origin in rhabdomyosarcoma informs pharmacological response.

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.

Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma.

BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) is a myogenic childhood sarcoma frequently associated with a translocation-mediated fusion gene, Pax3:Foxo1a. METHODS: We investigated the complementary role of Rb1 loss in aRMS tumor initiation and progression using conditional mouse models. RESULTS: Rb1 loss was not a necessary and sufficient mutational event for rhabdomyosarcomagenesis, nor a strong cooperative initiating mutation. Instead, Rb1 loss was a modifier of progression and increased anaplasia and pleomorphism. Whereas Pax3:Foxo1a expression was unaltered, biomarkers of aRMS versus embryonal rhabdomyosarcoma were both increased, questioning whether these diagnostic markers are reliable in the context of Rb1 loss. Genome-wide gene expression in Pax3:Foxo1a,Rb1 tumors more closely approximated aRMS than embryonal rhabdomyosarcoma. Intrinsic loss of pRb function in aRMS was evidenced by insensitivity to a Cdk4/6 inhibitor regardless of whether Rb1 was intact or null. This loss of function could be attributed to low baseline Rb1, pRb and phospho-pRb expression in aRMS tumors for which the Rb1 locus was intact. Pax3:Foxo1a RNA interference did not increase pRb or improve Cdk inhibitor sensitivity. Human aRMS shared the feature of low and/or heterogeneous tumor cell pRb expression. CONCLUSIONS: Rb1 loss from an already low pRb baseline is a significant disease modifier, raising the possibility that some cases of pleomorphic rhabdomyosarcoma may in fact be Pax3:Foxo1a-expressing aRMS with Rb1 or pRb loss of function.

Feasibility of video-assisted thoracoscopic surgery lobectomy in Veterans Administration patients.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) pulmonary lobectomy has been associated with decreased complication rates and length of stay compared with lobectomy by thoracotomy. No studies have addressed VATS lobectomy in Veterans Administration (VA) patients. METHODS: A retrospective review was undertaken of 50 VATS lobectomies performed between August 2007 and June 2009 by one surgeon in a VA hospital, a university-affiliated county hospital, and a private community hospital. RESULTS: VA patients had more medical comorbidities, poorer lung function, greater current smoker status, and fewer preoperative biopsies. Pleural adhesions or hilar lymphadenopathy were encountered more commonly in VA than nonfederal patients. Surgical times and number of procedures performed were greater in VA patients. There was no statistically significant difference in the risk of postoperative complications or chest tube duration although length of stay was longer for VA patients. CONCLUSIONS: VATS lobectomy is feasible in a VA setting. The evidence strongly suggests that veterans can benefit from VATS lobectomy in terms of improved outcomes and diminished length of stay compared with thoracotomy.

Toxic epidermal necrolysis: five years of treatment experience from a burn unit.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a serious drug eruption that results in death in approximately 25% to 50% of patients. There is controversy over whether SCORTEN accurately predicts mortality or if treatment interventions such as intravenous immunoglobulin (IVIg) can alter mortality. OBJECTIVES: We sought to determine whether SCORTEN accurately predicts mortality in this cohort, whether IVIg improved survival, and which drugs and medical comorbidities impacted mortality. METHODS: We summarize our experience prospectively over 5 years and 82 patients. Patients either received supportive care, intravenous immunoglobulin, or cyclosporine as treatment. All patients had a SCORTEN on admission, an offending drug on record, and a list of medical comorbidities. RESULTS: Of the 82 patients, 29% died from TEN. SCORTEN accurately predicted mortality in this cohort with an area under the curve (AUC) of 0.83 in a receiver operator curve (ROC) analysis. A Kaplan-Meier curve did not show improved mortality if patients received IVIg versus supportive care (P = .9). Medications most often responsible for TEN were trimethoprim/sulfamethoxazole, followed by anticonvulsants, nonsteroidal anti-inflammatories, and allopurinol. LIMITATIONS: This prospective cohort study design is not as ideal as patients presenting for a randomized controlled trial. CONCLUSIONS: SCORTEN was an accurate predictor of mortality in this cohort. Age older than 40 years, the presence of metabolic syndrome and/or gout, higher body surface area involvement, higher SCORTEN, and higher number of medical comorbidities statistically significantly increased risk of death. IVIg did not significantly alter mortality. Although the highest number of cases was due to trimethoprim/sulfamethoxazole, the greatest proportion of deaths was due to allopurinol.

18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models.

BACKGROUND: Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) are among the most common and most treatment resistant soft tissue sarcomas of childhood. Here, we evaluated the potential of (18)F-Fluorodeoxyglucose (FDG) as a marker of therapeutic response to picropodophyllin (PPP), an IGF1R inhibitor, in a conditional mouse model of ARMS and a conditional model of ERMS/undifferentiated pleomorphic sarcoma (UPS). PROCEDURE: Primary tumor cell cultures from Myf6Cre,Pax3:Fkhr,p53 and Pax7CreER,Ptch1,p53 conditional models of ARMS and ERMS/UPS were found to be highly sensitive to PPP (IC(50) values 150 and 200 nM, respectively). Animals of each model were then treated with 80 mg/kg/day PPP by intraperitoneal injection for 12 days and imaged by (18)F-FDG microPET. RESULTS: Tumor volumes on day 4 for PPP-treated ARMS and ERMS mice were lower than untreated control mouse tumor volumes, although treated tumors were larger than day 0. However, tumor FDG uptake was significantly reduced on day 4 for PPP-treated mice compared to pretreatment baseline or untreated control mice on day 4 (P < 0.05). Nevertheless, by day 12 tumor volumes and FDG uptake for treated mice had increased significantly, indicating rapidly evolving resistance to therapy. CONCLUSIONS: (18)F-FDG PET imaging is a potential imaging biomarker of molecular susceptibility to targeted agents early in treatment for this aggressive form of sarcoma, but may find best use serially for Phase I/II studies where chemotherapy and targeted agents are combined to cytoreduce tumors and abrogate Igf1r inhibitor resistance.

IL-4R drives dedifferentiation, mitogenesis, and metastasis in rhabdomyosarcoma.

PURPOSE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. The alveolar subtype of rhabdomyosarcoma (ARMS) is a paradigm for refractory and incurable solid tumors because more than half of the children at diagnosis have either regional lymph node or distant metastases. These studies follow our previous observation that Interleukin-4 receptor α (IL-4Rα) is upregulated in both human and murine ARMS, and that the IL-4R signaling pathway may be a target for abrogating tumor progression. EXPERIMENTAL DESIGN: By in vitro biochemical and cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of IL-4 and IL-13 in IL-4R-mediated mitogenesis, myodifferentiation, and tumor progression. RESULTS: IL-4 and IL-13 ligands accelerated tumor cell growth and activated STAT6, Akt, or MAPK signaling pathways in the human RMS cell lines, RD and Rh30, as well as in mouse primary ARMS cell cultures. IL-4 and IL-13 treatment also decreased protein expression of myogenic differentiation factors MyoD and Myogenin, indicating a loss of muscle differentiation. Using a genetically engineered mouse model of ARMS, we have shown that inhibition of IL-4R signaling pathway with a neutralizing antibody has a profound effect on the frequency of lymph node and pulmonary metastases, resulting in significant survival extension in vivo. CONCLUSIONS: Our results indicate that an IL-4R-dependent signaling pathway regulates tumor cell progression in RMS, and inhibition of this pathway could be a promising adjuvant therapeutic approach.

Preclinical testing of erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model.

Rhabdomyosarcoma is an aggressive childhood malignancy, accounting for more than 50% of all soft-tissue sarcomas in children. Even with extensive therapy, the survival rate among alveolar rhabdomyosarcoma patients with advanced disease is only 20%. The receptor tyrosine kinase Epidermal Growth Factor Receptor (EGFR) has been found to be expressed and activated in human rhabdomyosarcomas. In this study we have used a genetically engineered mouse model for alveolar rhabdomyosarcoma (ARMS) which faithfully recapitulates the human disease by activating the pathognomic Pax3:Fkhr fusion gene and inactivating p53 in the maturing myoblasts. We have demonstrated that tumors from our mouse model of alveolar rhabdomyosarcoma express EGFR at both the mRNA and protein levels. We then tested the EGFR inhibitor, Erlotinib, for its efficacy in this mouse model of alveolar rhabdomyosarcoma. Surprisingly, Erlotinib had no effect on tumor progression, yet mice treated with Erlotinib showed 10-20% loss of body weight. These results suggest that EGFR might not be an a priori monotherapy target in alveolar rhabdomyosarcoma.

Evidence for an unanticipated relationship between undifferentiated pleomorphic sarcoma and embryonal rhabdomyosarcoma.

Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.

MicroCT-based virtual histology evaluation of preclinical medulloblastoma.

PURPOSE: The purpose of this paper is to validate a rapid and cost-effective ex vivo technique, microCT-based virtual histology, as an alternative to MRI imaging for assessing the therapeutic response in genetically engineered mouse models of cancer. PROCEDURES: All animal procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Texas Health Science Center at San Antonio. MRI imaging was performed on 6-week-old, bortezomib-treated genetically engineered Patched1, p53 mice that recapitulate the characteristics of human medulloblastoma. After MRI scans, the same mice were euthanized to collect brain or spine samples for virtual histology staining followed by microCT scanning. RESULTS: Nine-micrometer resolution ex vivo micro X-ray computed tomography (microCT)-based virtual histology images were qualitatively reflective of high-field live animal images obtained with magnetic resonance imaging (MRI) and histopathology. Cerebellar volumes on microCT-based virtual histology correlated closely with MRI cerebellar volumes (R = 0.998). MRI and microCT-based virtual histology both indicated a significant difference between cerebellar volumes of untreated and treated mice (p = 0.02 and p = 0.04, respectively). The ex vivo microCT method also allowed a 7,430-fold improvement in voxel resolution (voxel volume of 729 µm³ for 9-µm isometric resolution microCT vs. 5,416,800 µm³ for 400 × 111 × 122 µm resolution MRI) at a 28% cost savings ($400 vs. $555 per animal). CONCLUSION: The ex vivo, en bloc technique of microCT-based virtual histology matched MRI in reflecting histopathology. MicroCT-based virtual histology proved to be a more cost-effective technique and less labor-intensive. On the other hand, MRI provides ability to perform in vivo imaging, faster scanning and lower radiation dose by sacrificing the spatial resolution. Thus, both in vivo MRI and ex vivo microCT-based virtual histology are effective means of quantitatively evaluating therapeutic response in preclinical models of cerebellar tumors including the childhood cancer, medulloblastoma.

LATENT RANK CHANGE DETECTION FOR ANALYSIS OF SPLICE-JUNCTION MICROARRAYS WITH NONLINEAR EFFECTS.

Alternative splicing of gene transcripts greatly expands the functional capacity of the genome, and certain splice isoforms may indicate specific disease states such as cancer. Splice junction microarrays interrogate thousands of splice junctions, but data analysis is difficult and error prone because of the increased complexity compared to differential gene expression analysis. We present Rank Change Detection (RCD) as a method to identify differential splicing events based upon a straightforward probabilistic model comparing the over- or underrepresentation of two or more competing isoforms. RCD has advantages over commonly used methods because it is robust to false positive errors due to nonlinear trends in microarray measurements. Further, RCD does not depend on prior knowledge of splice isoforms, yet it takes advantage of the inherent structure of mutually exclusive junctions, and it is conceptually generalizable to other types of splicing arrays or RNA-Seq. RCD specifically identifies the biologically important cases when a splice junction becomes more or less prevalent compared to other mutually exclusive junctions. The example data is from different cell lines of glioblastoma tumors assayed with Agilent microarrays.

Growth in children with acute lymphoblastic leukemia during treatment.

Obesity is increasingly prevalent in affluent societies and portends considerable morbidity. This is especially true in children with acute lymphoblastic leukemia (ALL) in whom the metabolic syndrome may begin during therapy, demanding clarification of the trajectory of weight gain so that effective interventions may be developed. In this retrospective study of body mass index from a single institution over a 20-year period, almost 15% of children with ALL were at risk of overweight or frankly overweight (body mass index >85th centile) at diagnosis. This proportion increased steadily, reaching 40% at the end of treatment. Strategies to limit weight gain will have to be instituted early in the management of children with ALL, and will probably have to be maintained throughout and after the completion of active treatment.

Surgeons' performance during critical situations: competence, confidence, and composure.

BACKGROUND: Little is known about surgeons' performance during critical situations. We hypothesized that there are methods and techniques used by surgeons that facilitate performance during critical situations. METHODS: Surgical faculty and senior general surgery residents from a single academic health center were surveyed. RESULTS: Twenty-six surgeons participated. With respect to critical situations, the surgeons felt confident (96%), expected to be successful (96%), and most did not find these situations particularly stressful (62%). The majority reported using learned skills (92%) and agree their skills can be taught (82%). Practice and preparation were reported as very important (89%). A majority use pre-emptive visualization (68%). Competence, confidence, composure, preparation, and experience were most commonly listed as characteristics or behaviors that should be encouraged in aspiring surgeons. Anger, panic, indecision, fear, and chaos were the most commonly listed characteristics that should be discouraged. CONCLUSIONS: Surgeons' response to performance under pressure is complex; however, surgeons report using simple, learned techniques that seem to be targeted toward eliminating the "fight or flight" sympathetic nervous system response.

Effect of temporary shunting on extremity vascular injury: an outcome analysis from the Global War on Terror vascular injury initiative.

OBJECTIVE: Extremity vascular injury during the current war has been defined by anecdotal description and case series. These reports focused on estimation of short-term limb viability and technical description of commonly used adjuncts. Temporary vascular shunting (TVS) has been advocated in current care structures, yet mostly due to war environments, broader statistical scrutiny is lacking. This study's purpose is to provide perspective on TVS's impact on limb salvage, and estimate longer-term freedom from amputation. METHODS: Data from the Joint Theater Trauma Registry (JTTR), Balad Vascular Registry (BVR), Walter Reed Vascular Registry (WRVR), electronic medical records, and patient interviews were collected on American Troops sustaining extremity vascular injury from June 2003 through December 2007. Those in whom arterial TVS utilization was identified comprise the TVS group. These were compared with controls with similar injury date and anatomic location managed without TVS. Descriptive statistics were employed establishing overall univariate predictors of amputation and comparison between groups. Proportional-hazards modeling, with propensity score adjustment for systemic injury severity and Level 2 care, characterized risk factors of limb loss and effect of TVS. Freedom from amputation was estimated using Kaplan Meier log-rank methods. RESULTS: Cases and controls consisted of 64 and 61 extremity arterial injuries, respectively. Mean follow-up was 22 months (range: 1-54 months). The TVS group was more severely injured (mean injury severity score [ISS]: 18 [SD = 10] TVS vs. 15 [SD = 10] control, P = .05) and more likely to receive Level 2 care (TVS: 26%; control: 10%, P = .02). Overall, a total of 26 amputations occurred (21%). Penetrating blasts, compared with gunshot wounds, were associated with amputation (30% vs. 6%, P = .002). After propensity score adjustment, use of TVS suggested a reduced risk of amputation (relative risk [RR] = 0.47; 95% confidence interval [CI] [0.18-1.19]; P = .11). Venous repair was associated with limb salvage (RR = 0.2; 95% CI [0.04-0.99], P = .05). Associated fracture (RR = 5.0; 95% CI [1.45-17.28], P = .01), and elevated mangled extremity severity score (MESS) ([MESS 5-7] RR = 3.5, 95% CI [0.97-12.36], P = .06; [MESS 8-12] RR = 16.4; 95% CI (3.79-70.79), P < .001) predicted amputation. Amputation-free survival was 78% in the TVS group and 77% in the control group at three years (P = .5). CONCLUSION: Temporary vascular shunting used as a damage control adjunct in management of wartime extremity vascular injury does not lead to worse outcomes. Benefit from TVS is suggested, but not statistically significant. Injury specific variables of venous ligation, associated fracture, and penetrating blast mechanism are associated with amputation. Amputation-free survival after vascular injury in Operation Iraqi Freedom is 79% at three years. Further studies to statistically define any possible benefits of TVS are needed.

Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring.

BACKGROUND: The ARDS Clinical Trials Network Fluid and Catheter Treatment Trial (FACTT) addressed fluid management and central monitoring of patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI). Because surgical patients may have been fundamentally different from the overall FACTT cohort, we set out to separately analyze the surgery patients in the trial. STUDY DESIGN: We performed a posthoc, surgical subgroup analysis of 1,000 patients enrolled in the FACTT. Patients were randomized using a 2x2 factorial design comparing a conservative (CON) versus a liberal (LIB) strategy of fluid management and the use of a pulmonary artery catheter (PAC) or a central venous catheter (CVC). The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days, ICU-free days, and dialysis-free days until hospital discharge up to day 90. We defined surgical patients as those admitted to a surgical ICU, burn ICU, or cardiac surgical ICU; trauma patients; or those with an APACHE III surgical admission type. RESULTS: There were 244 surgical patients. Risk of death within 60 days of randomization did not vary with catheter or fluid management, and a corresponding lack of effect was evident with regard to dialysis-free days. Ventilator-free days were increased in the fluid-conservative group (LIB, 13+/-1 days; CON, 15+/-1 days; p=0.04) at 28 days. CVC patients had more ventilator-free days at 28 and 90 days (28 days: CVC, 16+/-1 days; PAC, 13+/-1 days; p=0.03; 90 days: CVC, 64+/-3 days; PAC, 57+/-4 days; p=0.03). CVC patients had more ICU-free days at 90 days (90 days: CVC, 63+/-3 days; PAC, 55+/-3 days; p=0.04). CONCLUSIONS: The risk of death did not vary with fluid management or catheter. A conservative fluid-administration strategy and central venous catheter monitoring resulted in more ventilator-free and ICU-free days in surgical patients with acute lung injury, and conservative fluid administration did not result in more renal failure.

Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.

OBJECTIVE: To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization. SUMMARY BACKGROUND DATA: Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear. METHODS: Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed. RESULTS: Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio. CONCLUSIONS: Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.