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The Association of Early Transfusion with Acute Lung Injury in Patients with Severe Injury
574 fell from five or more stairs. Children in the current study population most often fell from furniture such as beds (33.0%), couches (18.9%), chairs (17.9%), tables (9.7%), and bunk beds (6.9%). More children who fell from stairs than from furniture had a loss of consciousness (12.9% vs. 4.1%, p < 0.001). There were no differences between the groups in intensive care unit treatment, operative care, length of hospital stay, Injury Severity Score, or total hospital cost per patient. There was a significant difference (p < 0.001) in sustaining injuries to more than one body region in those that fell from stairs (19.3% or n = 33) compared to those that fell from furniture (6.3% or n = 20). Children who fell from stairs were more likely (p < 0.001) to have head injuries (64.3% vs. 38.1%). Children who fell from furniture were more likely (p < 0.001) to injure their arms (33.3% vs. 9.9%). Over the study period, statistically insignificant (p < 0.09) trends were identified such that falls from stairs declined and falls from furniture increased. The authors addressed the limitations of the study, which included the retrospective design and the inability to generalize the conclusions to patients with injuries not severe enough for hospitalization. [Kathlynn M. Dominguez, MD Denver Health Medical Center, Denver, CO] Comment: This study argues for the need to give anticipatory guidance and information surrounding injury prevention to parents and caregivers regarding not only falls from stairs or windows, but also falls from furniture. The study also addresses common injury patterns associated with falls from furniture vs. stairs. , IDENTIFYING THE LOWEST EFFECTIVE DOSE OF ACETAZOLAMIDE FOR THE PROPHYLAXIS OF ACUTE MOUNTAIN SICKNESS: SYSTEMATIC REVIEW AND META-ANALYSIS. Low EV, Avery AJ, Gupta V, et al. BMJ 2012;345:e6779:1–14. As visits and treks to high-altitude locations become increasingly popular, medications to counteract the physiological effects of rapid ascent beyond 3000 m are likewise becoming of greater interest. Acetazolamide, a carbonic anhydrase inhibitor, is widely used as prophylaxis for the physiological effects of acute mountain sickness, though the proper and lowest effective dosing remains under debate. The last systematic review published in 2000 found 750 mg daily to be the lowest effective dose for preventing acute mountain sickness, though this high dosing has been disputed by general specialists as well as mountain enthusiasts. The current study aimed to analyze and summarize current literature regarding daily dosing of 250, 500, and 750 mg acetazolamide to determine the lowest effective dose for preventing acute mountain sickness at high altitude. A formal systematic review of 3133 articles extracted from Medline and Embase was performed. Inclusion and exclusion criteria were established. The current study focused on analyzing randomized controlled trials on adults older than 16 years with an outcome measure the absence of acute mountain sickness as defined by the Lake Louise scoring system, the general high altitude questionnaire, the acute mountain sicknesscerebral score, or a clear definition of acute mountain sickness
Abstracts predetermined by the original study authors. High altitude was defined as > 3000 m. Studies that recruited indigenous or local populations were excluded. After criteria were applied, 11 articles (with 12 intervention arms) published from 1976 to 2011 were included. Additional trials were found by searching bibliographies of included papers, known reviews, and relevant articles, and unpublished studies were found via correspondence with each primary author of the aforementioned included studies. Two reviewers independently extracted relevant data from included studies and independently assessed risk of bias of each study. Data from the 11 articles were used in a meta-analysis. Quantitative and qualitative analyses of intervention effects were performed. Intervention with acetazolamide was consistently more effective than placebo at all doses for prevention of acute mountain sickness with a combined odds ratio (OR) of 0.36, 95% confidence interval (CI) 0.28–0.46. The combined estimate for studies analyzing the effect of 250 mg daily indicated a statistically significant treatment effect (OR 0.41, 95% CI 0.26–0.64). The overall combined estimate for dosing of 500 mg daily also showed a significant reduction of risk (OR 0.37, 95% CI 0.26–0.52). For dosing at 750 mg daily, there was a significant risk reduction with an overall combined OR of 0.20 (95% CI 0.10–0.41). The numbers needed to treat for the 250-mg, 500-mg, and 750-mg daily groups were 6 (95% CI 5–11), 7 (95% CI 6–9), and 3 (95% CI 3–5), respectively. Heterogeneity and sensitivity analyses were performed to look at studies’ qualitative characteristics. The authors concluded that all three doses of acetazolamide were efficacious in preventing acute mountain sickness above 3000 m, with acetazolamide 250 mg daily the lowest effective dose where side effects of the drug could also be minimized. Limitations discussed by the authors included not having a standard definition of acute mountain sickness amongst all studies, inclusion of studies where participants were already at 4000 m elevation (therefore risking partial pre-acclimatization), a mean altitude amongst the studies included (3800–5000 m) higher than that where symptoms of acute mountain sickness can already be seen, the inability to generalize study conclusions to those treated below 3800 m, and that only two studies met criteria to be included in the 750-mg dosing group. [Kathlynn M. Dominguez, MD Denver Health Medical Center, Denver, CO] Comment: This study helps to establish that a lower effective dose of acetazolamide at 250 mg daily vs. the prior published 750 mg daily can be used to prevent acute mountain illness in ascent to high altitude. This lower dosing will minimize the unpleasant side effects experienced in taking higher doses. , THE ASSOCIATION OF EARLY TRANSFUSION WITH ACUTE LUNG INJURY IN PATIENTS WITH SEVERE INJURY. Holena DN, Netzer G, Localio R. J Trauma Acute Care Surg 2012;73:825–31. Injury from major trauma remains a significant source of morbidity and mortality worldwide. Lifesaving therapies such as early blood transfusion after traumatic injury have enabled survival or improved morbidity. As a result of the increased use of early blood transfusion after traumatic injury, the
The Journal of Emergency Medicine incidence of adverse effects resulting from such early transfusion has also increased, including an increase in the incidence of post-transfusion acute lung injury (ALI). Prior studies demonstrated an overall risk for development of ALI after transfusion in the first 24–48 h of hospitalization, yet did not assess if the association varied with exact time of transfusion after traumatic injury. The current study aimed to better delineate this relationship. A prospective cohort study was conducted at the Hospital of the University of Pennsylvania (Level I trauma center) from June 28,1999 to November 20, 2002 and again from October 1, 2005 to April 30, 2010 using data from the adult respiratory distress syndrome (ARDS) I and II studies. All patients older than 13 years with critical illness and severe trauma (Injury Severity Score [ISS] > 16) that presented to the Emergency Department (ED) and were subsequently admitted to a surgical Intensive Care Unit (ICU) were studied. Exclusion criteria were also established. All patients were followed for the first 5 days after ICU admission after acute trauma for the development of ALI. Blood gas, laboratory, and ventilator data were collected and subjects were determined to have ALI as defined by the American-European Consensus Conference by two independent physician investigators trained in standardized chest radiograph interpretation. Physician interpreters were blinded to knowledge of transfusion and other clinical variables. Logistic regression models were used to test the association of recent blood transfusion with the development of ALI while adjusting for potential baseline confounding factors, and were also used to analyze the relationship between transfusion product ratios (blood to fresh frozen plasma [FFP] to platelets) and development of ALI in instances of mass-transfusion protocols. Discreet time failure model statistical modeling and analyses were used to derive an odds ratio for developing ALI on any given day after initial transfusion. There were 602 patients who met eligibility criteria and for whom transfusion data were available included in the analysis. Demographics included a median age of 33 years, a mostly male cohort (77%), and patients who were equally black and white. Patients in the ALI group were more likely to be older (median age 38 [interquartile range (IQR) 23–50 years] vs. 33 years [IQR 23–47]), were more likely to have a blunt mechanism of injury (73% vs. 66%), were more likely to be severely injured (median ISS 25 [IQR 20–29] vs. 22 [IQR 18–27]), and were more likely to have a greater degree of physiologic derangement (Acute Physiology and Chronic Health Evaluation [APACHE] III median score, 65 [IQR 52–77] vs. 58 [IQR 48–71]). APACHE III
575 score, ISS, pulmonary contusion, and blood products delivered at resuscitation were associated with development of ALI. ISS of < 28 was not found to be significantly associated with development of ALI, whereas ISS of 28 or higher was found to contribute significantly to the development of ALI (odds ratio 1.2 per 5 ISS points; 95% confidence interval 1.01– 1.60). Patients who developed ALI received > 6 U of packed red blood cells (PRBC) more often than patients who did not develop ALI (20% vs. 7%); the number of FFP transfusion units were greater in those who developed ALI than those who did not (50% vs. 33%). Ratios of FFP/PRBC were not significantly different between those who did and did not develop ALI and were not themselves associated with the development of ALI. The current study also found a significant interaction between blood transfusion and time, implying that the effect of transfusion on ALI risk was modified by day of transfusion (c24 = 819.70, p < 0.0001). This effect was found to be driven by the amount of PRBC delivered during the first 24 h. Specifically, with each additional unit of PRBC given at resuscitation during the initial 24 h, the odds of subsequent ALI development increased by 7%. PRBC transfusion beyond the first 24 h after ED admission was not consistently associated with subsequent ALI development. In conclusion, the authors stated that in patients who sustained severe trauma, early transfusion of PRBC, especially in the first 24 h after injury, was associated with an increased risk of development of ALI. The authors determined the strengths of the study to be their rigorous definition of ALI and being the first study to use a discreet time failure model methodology to prospectively look at the time-dependent relationship between transfusion and risk of ALI. Limitations discussed included the observational nature of the study, which therefore prevented conclusion of a causal relationship between early PRBC transfusion and development of ALI. [Kathlynn M. Dominguez, MD Denver Health Medical Center, Denver, CO] Comment: The above study demonstrated a correlation between early (within the first 24 h) blood transfusion and the subsequent development of ALI. It also found the larger early transfusions to be associated with increased risk of development of ALI. Yet, any potential practice shift toward less aggressive blood transfusion after severe trauma must be balanced with the risk of withholding transfusion in the acutely hemorrhaging and severely injured trauma patient.
Abstracts predetermined by the original study authors. High altitude was defined as > 3000 m. Studies that recruited indigenous or local populations were excluded. After criteria were applied, 11 articles (with 12 intervention arms) published from 1976 to 2011 were included. Additional trials were found by searching bibliographies of included papers, known reviews, and relevant articles, and unpublished studies were found via correspondence with each primary author of the aforementioned included studies. Two reviewers independently extracted relevant data from included studies and independently assessed risk of bias of each study. Data from the 11 articles were used in a meta-analysis. Quantitative and qualitative analyses of intervention effects were performed. Intervention with acetazolamide was consistently more effective than placebo at all doses for prevention of acute mountain sickness with a combined odds ratio (OR) of 0.36, 95% confidence interval (CI) 0.28–0.46. The combined estimate for studies analyzing the effect of 250 mg daily indicated a statistically significant treatment effect (OR 0.41, 95% CI 0.26–0.64). The overall combined estimate for dosing of 500 mg daily also showed a significant reduction of risk (OR 0.37, 95% CI 0.26–0.52). For dosing at 750 mg daily, there was a significant risk reduction with an overall combined OR of 0.20 (95% CI 0.10–0.41). The numbers needed to treat for the 250-mg, 500-mg, and 750-mg daily groups were 6 (95% CI 5–11), 7 (95% CI 6–9), and 3 (95% CI 3–5), respectively. Heterogeneity and sensitivity analyses were performed to look at studies’ qualitative characteristics. The authors concluded that all three doses of acetazolamide were efficacious in preventing acute mountain sickness above 3000 m, with acetazolamide 250 mg daily the lowest effective dose where side effects of the drug could also be minimized. Limitations discussed by the authors included not having a standard definition of acute mountain sickness amongst all studies, inclusion of studies where participants were already at 4000 m elevation (therefore risking partial pre-acclimatization), a mean altitude amongst the studies included (3800–5000 m) higher than that where symptoms of acute mountain sickness can already be seen, the inability to generalize study conclusions to those treated below 3800 m, and that only two studies met criteria to be included in the 750-mg dosing group. [Kathlynn M. Dominguez, MD Denver Health Medical Center, Denver, CO] Comment: This study helps to establish that a lower effective dose of acetazolamide at 250 mg daily vs. the prior published 750 mg daily can be used to prevent acute mountain illness in ascent to high altitude. This lower dosing will minimize the unpleasant side effects experienced in taking higher doses. , THE ASSOCIATION OF EARLY TRANSFUSION WITH ACUTE LUNG INJURY IN PATIENTS WITH SEVERE INJURY. Holena DN, Netzer G, Localio R. J Trauma Acute Care Surg 2012;73:825–31. Injury from major trauma remains a significant source of morbidity and mortality worldwide. Lifesaving therapies such as early blood transfusion after traumatic injury have enabled survival or improved morbidity. As a result of the increased use of early blood transfusion after traumatic injury, the
The Journal of Emergency Medicine incidence of adverse effects resulting from such early transfusion has also increased, including an increase in the incidence of post-transfusion acute lung injury (ALI). Prior studies demonstrated an overall risk for development of ALI after transfusion in the first 24–48 h of hospitalization, yet did not assess if the association varied with exact time of transfusion after traumatic injury. The current study aimed to better delineate this relationship. A prospective cohort study was conducted at the Hospital of the University of Pennsylvania (Level I trauma center) from June 28,1999 to November 20, 2002 and again from October 1, 2005 to April 30, 2010 using data from the adult respiratory distress syndrome (ARDS) I and II studies. All patients older than 13 years with critical illness and severe trauma (Injury Severity Score [ISS] > 16) that presented to the Emergency Department (ED) and were subsequently admitted to a surgical Intensive Care Unit (ICU) were studied. Exclusion criteria were also established. All patients were followed for the first 5 days after ICU admission after acute trauma for the development of ALI. Blood gas, laboratory, and ventilator data were collected and subjects were determined to have ALI as defined by the American-European Consensus Conference by two independent physician investigators trained in standardized chest radiograph interpretation. Physician interpreters were blinded to knowledge of transfusion and other clinical variables. Logistic regression models were used to test the association of recent blood transfusion with the development of ALI while adjusting for potential baseline confounding factors, and were also used to analyze the relationship between transfusion product ratios (blood to fresh frozen plasma [FFP] to platelets) and development of ALI in instances of mass-transfusion protocols. Discreet time failure model statistical modeling and analyses were used to derive an odds ratio for developing ALI on any given day after initial transfusion. There were 602 patients who met eligibility criteria and for whom transfusion data were available included in the analysis. Demographics included a median age of 33 years, a mostly male cohort (77%), and patients who were equally black and white. Patients in the ALI group were more likely to be older (median age 38 [interquartile range (IQR) 23–50 years] vs. 33 years [IQR 23–47]), were more likely to have a blunt mechanism of injury (73% vs. 66%), were more likely to be severely injured (median ISS 25 [IQR 20–29] vs. 22 [IQR 18–27]), and were more likely to have a greater degree of physiologic derangement (Acute Physiology and Chronic Health Evaluation [APACHE] III median score, 65 [IQR 52–77] vs. 58 [IQR 48–71]). APACHE III
575 score, ISS, pulmonary contusion, and blood products delivered at resuscitation were associated with development of ALI. ISS of < 28 was not found to be significantly associated with development of ALI, whereas ISS of 28 or higher was found to contribute significantly to the development of ALI (odds ratio 1.2 per 5 ISS points; 95% confidence interval 1.01– 1.60). Patients who developed ALI received > 6 U of packed red blood cells (PRBC) more often than patients who did not develop ALI (20% vs. 7%); the number of FFP transfusion units were greater in those who developed ALI than those who did not (50% vs. 33%). Ratios of FFP/PRBC were not significantly different between those who did and did not develop ALI and were not themselves associated with the development of ALI. The current study also found a significant interaction between blood transfusion and time, implying that the effect of transfusion on ALI risk was modified by day of transfusion (c24 = 819.70, p < 0.0001). This effect was found to be driven by the amount of PRBC delivered during the first 24 h. Specifically, with each additional unit of PRBC given at resuscitation during the initial 24 h, the odds of subsequent ALI development increased by 7%. PRBC transfusion beyond the first 24 h after ED admission was not consistently associated with subsequent ALI development. In conclusion, the authors stated that in patients who sustained severe trauma, early transfusion of PRBC, especially in the first 24 h after injury, was associated with an increased risk of development of ALI. The authors determined the strengths of the study to be their rigorous definition of ALI and being the first study to use a discreet time failure model methodology to prospectively look at the time-dependent relationship between transfusion and risk of ALI. Limitations discussed included the observational nature of the study, which therefore prevented conclusion of a causal relationship between early PRBC transfusion and development of ALI. [Kathlynn M. Dominguez, MD Denver Health Medical Center, Denver, CO] Comment: The above study demonstrated a correlation between early (within the first 24 h) blood transfusion and the subsequent development of ALI. It also found the larger early transfusions to be associated with increased risk of development of ALI. Yet, any potential practice shift toward less aggressive blood transfusion after severe trauma must be balanced with the risk of withholding transfusion in the acutely hemorrhaging and severely injured trauma patient.