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Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate.We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior.Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive. [ABSTRACT FROM AUTHOR]

BACKGROUND: Randomized controlled trials of how best to administer fresh frozen plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult to execute and have not been published. Meanwhile, coagulopathy remains a common occurrence during major trauma resuscitation and hemorrhage remains a major cause of traumatic deaths, suggesting that current coagulation factor replacement practices may be inadequate. METHODS: We used a pharmacokinetic model to simulate the dilutional component of coagulopathy during hemorrhage and compared different FFP transfusion strategies for the prevention or correction, or both, of dilutional coagulopathy. Assuming the rates of volume replacement and loss are roughly equal, we derived the hematocrit and plasma coagulation factor concentration over time based on the rate of blood loss and replacement, the hematocrit and coagulation factor concentration of the transfusate, and the hematocrit and plasma factor concentration at the time when FFP transfusion begins. RESULTS: Once excessive deficiency of factors has developed and bleeding is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood cells (PRBC) transfused. If FFP transfusion should start before plasma factor concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1 would prevent further dilution. CONCLUSION: During resuscitation of a patient who has undergone major trauma, the equivalent of whole-blood transfusion is required to correct or prevent dilutional coagulopathy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate, by systematic review, the efficacy of heliox on respiratory mechanics and outcomes in patients with acute asthma.Methods: The search strategy included searching electronic databases (MEDLINE, EMBASE, and The Cochrane Library) and the references of relevant articles. Study quality was assessed based on allocation concealment. Randomized controlled trials (RCTs) comparing heliox to an air-oxygen mixture (airO(2)) as an adjunct treatment in patients with acute asthmatic attacks were analyzed. For the qualitative portion of the analysis, all reports of the use of heliox in patients with acute asthma were included.Results: Four RCTs (n = 278) were found to have a common respiratory parameter (peak expiratory flow rate as a percentage of predicted) suitable for meta-analysis. Within the 92% confidence interval (CI), there was a small benefit with the use of heliox compared to airO(2) (weighted mean difference, + 3%; 95% CI, - 2 to + 8%). There was also a slight improvement in the dyspnea index (weighted mean difference, 0.60; 95% CI, 0.04 to 1.16) with the use of heliox over airO(2). Overall, five RCTs, one nonrandomized unblinded parallel trial, one retrospective case-matched control trial, three case series, and one case report had results in favor of heliox; one RCT and one case series showed no improvement with heliox; one RCT showed a possible detrimental effect with heliox; and 1 small RCT was inconclusive. Most investigators did not prevent entrainment of room air during heliox use or compensate for the lower nebulizing efficiency of heliox.Conclusion: Based on surrogate markers, heliox may offer mild-to-moderate benefits in patients with acute asthma within the first hour of use, but its advantages become less apparent beyond 1 h, as most conventionally treated patients improve to similar levels, with or without it. The effect of heliox may be more pronounced in more severe cases. There are insufficient data on whether heliox can avert tracheal intubation, or change intensive care and hospital admission rates and duration, or mortality. [ABSTRACT FROM AUTHOR]

Traditional transfusion guidelines suggest that fresh frozen plasma (FFP) should be given based on laboratory or clinical evidence of coagulopathy or acute loss of 1 blood volume. This approach tends to result in a significant lag time between the first units of erythrocytes and FFP in trauma requiring massive transfusion. In severe trauma, observational studies have found an association between increased survival and aggressive use of FFP and platelets such that FFP:platelet:erythrocyte ratio approaches 1:1:1 to 2 from the first units of erythrocytes given. There are considerable concerns over either approach, and no randomized controlled trials have been published comparing the 2 approaches. Nowadays, trauma clinicans are incorporating the strenghts of both approaches and are no longer treating them as a dichotomy. Specifically, "1:1:1" proponents have devised 1:1:1 activation criteria to minimize unnecessary FFP and platelet transfusion and are prepared to deactivate the protocol as soon as patient is stabilized. Similarly, 1:1:1 skeptics are more mindful of the need to be proactive about trauma coagulopathy and the inherent delays in FFP administration in trauma patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused., Methods: A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome., Results: Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation., Conclusion: Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

During trauma resuscitation involving massive transfusion, the best fresh-frozen plasma to packed red blood cells ratio is unknown. No randomised controlled trial (RCT) is available on this subject, although there are plenty of observational studies suggesting that the ratio should be about 1:1. This ratio also makes more physiological sense, and we suggest that in patients with massive and ongoing bleeding, it is a sensible strategy with which to start resuscitation., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Airway, breathing, and circulation are top priorities in any resuscitation. However, in cardiac tamponade, the decision to intubate the trachea and initiate positive pressure ventilation (PPV) should only be taken after consideration of the deleterious haemodynamic effects of positive intrathoracic pressure. We suggest that the threshold for intubation and PPV should be raised in tamponade and that intubation and PPV should, if possible, be timed so that relief of tamponade can immediately follow. In the trauma setting, emergency thoracotomy is the best approach. When intubation is unavoidable because of very low oxygen saturation or cardiac arrest, high ventilatory pressures should be avoided.

The laryngeal mask airway (LMA) is now standard airway management equipment in prehospital and Emergency Department (ED) care. Most providers may not be able to match the pediatric LMA sizes to the appropriate weights of pediatric patients. The exact inflation volumes are also difficult to memorize. To overcome this problem, we propose the following equations: Weight (kg) of patient = 2(2 x LMA), where LMA is the size; cuff inflation volume (mL) = 5 x LMA.

Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.

Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage and is commonly seen during major trauma resuscitation, suggesting that current practice of coagulation factor transfusion is inadequate. Reversal of coagulopathy involves normalization of body temperature, elimination of the causes of disseminated intravascular coagulation (DIC), and transfusion with fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be guided by clinical factors and laboratory results. However, in major trauma, clinical signs may be obscured and various factors conspire to make it difficult to provide the best transfusion therapy. Existing empiric transfusion strategies for, and prevailing teachings on, FFP transfusion appear to be based on old studies involving elective patients transfused with whole blood and may not be applicable to trauma patients in the era of transfusion with packed red blood cells (PRBCs). Perpetuation of such concepts is in part responsible for the common finding of refractory coagulopathy in major trauma patients today. In this review, we argue that coagulopathy can best be avoided or reversed when severe trauma victims are transfused with at least the equivalent of whole blood in a timely fashion.

Omission of a confidence interval (CI) associated with the risk of a serious complication can lead to inaccurate interpretation of risk data. The calculation of a CI for a risk or a single proportion typically uses the familiar Gaussian (normal) approximation. However, when the risk is small, "exact" methods or other special techniques should be used to avoid overshooting (risks that include values outside of [0,1]) and zero width interval degeneration. Computer programs and simple equations are available to construct CIs reasonably accurately. In the special case in which the complication has not occurred, the risk estimated with 95% confidence is no worse than 3/n, where n is the number of trials.

Heliox has a lower density than oxygen and nitrogen, and can improve ventilation rapidly in patients with critical upper airway obstruction. The choice of the best helium:oxygen ratio depends on whether the predominant problem is hypercarbia or hypoxia. In the former situation, 80% helium should be used, and in the latter, 100% oxygen is appropriate.

As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.

The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.