Transfusion-related acute lung injury in the critically ill: prospective nested case-control study.

RATIONALE: Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. OBJECTIVES: To compare patient and transfusion risk factors between patients who do and do not develop ALI. METHODS: In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis. MEASUREMENTS AND MAIN RESULTS: Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37-18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32-17.86) and anti-HLA class II antibodies (OR, 3.08; 95% CI, 1.15-8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI. CONCLUSIONS: Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.

Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study.

BACKGROUND: Using the recent Consensus Panel recommendations, we sought to describe the incidence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in critically ill patients. STUDY DESIGN AND METHODS: Consecutive patients at four intensive care units (ICUs) who did not require respiratory support at the time of transfusion were identified with custom electronic surveillance system that prospectively tracks the time of transfusion and onset of respiratory support. Respiratory failure was defined as the onset of noninvasive or invasive ventilator support within 6 hours of transfusion. Experts blinded to specific transfusion factors categorized the cases of pulmonary edema as permeability edema (suspected or possible TRALI) or hydrostatic edema (TACO) according to predefined algorithm. In a nested case-control design, transfusion variables and lung injury risk factors were compared between the TRALI cases and controls matched by age, sex, and admission diagnosis. RESULTS: There were 8902 units transfused in 1351 patients of whom 94 required new respiratory support within 6 hours of transfusion. Among 49 patients with confirmed acute pulmonary edema, experts identified 7 cases with suspected TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and fluid balance in a stepwise conditional logistic regression analysis, patients who developed acute lung injury (suspected or possible TRALI) received larger amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each liter infused; p = 0.023). CONCLUSION: In the ICU, pulmonary edema frequently occurs after blood transfusion. The association between infusion of plasma and the development of suspected or possible TRALI may have important implications with regards to etiology and prevention of this syndrome.

B-type natriuretic peptide in the assessment of acute lung injury and cardiogenic pulmonary edema.

OBJECTIVE: The role of plasma B-type natriuretic peptide (BNP) in critically ill patients with acute pulmonary edema is controversial. We postulated that a low BNP level would exclude cardiac dysfunction as the principal cause of pulmonary edema and therefore help in the diagnosis of acute lung injury. DESIGN: A retrospective derivation cohort was followed by a prospective validation cohort of consecutive patients with acute pulmonary edema admitted to three intensive care units. BNP was measured within 24 hrs from onset. Critical care experts blinded to BNP results integrated clinical data with the course of disease and response to therapy and served as the reference standard. SETTING: Three intensive care units at the tertiary center. PATIENTS: Consecutive critically ill patients with acute pulmonary edema. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In a derivation cohort of 84 patients, a BNP threshold of

Evidence-based red cell transfusion in the critically ill: quality improvement using computerized physician order entry.

OBJECTIVE: The implementation of evidence-based practice poses a significant challenge in the intensive care unit. In this quality improvement intervention we assessed the effect of an institutional protocol and computerized decision support for red cell transfusion in the critically ill. DESIGN: We compared processes of care and outcomes during the two 3-month periods before and after the introduction of a multidisciplinary quality improvement intervention. SETTING: Multidisciplinary intensive care units--medical, surgical, and mixed--in a tertiary academic center. PATIENTS: Consecutive critically ill patients with anemia (hemoglobin of <10 g/dL). INTERVENTION: Using the computerized provider order entry, we developed an evidence-based decision algorithm for red cell transfusion in adult intensive care units. MEASUREMENTS AND MAIN RESULTS: We collected information on demographics, diagnosis, severity of illness, transfusion complications, and laboratory values. The main outcome measures were number of transfusions, proportion of patients who were transfused outside evidence-based indications, transfusion complications, and adjusted hospital mortality. The mean number of red cell transfusions per intensive care unit admission decreased from 1.08 +/- 2.3 units before to 0.86 +/- 2.3 units after the protocol (p<.001). We observed a marked decrease in the percentage of patients receiving inappropriate transfusions (17.7% vs. 4.5%, p< .001). The rate of transfusion complications was also lower in the period after the protocol (6.1% vs. 2.7%, p = .015). In the multivariate analysis, protocol introduction was associated with decreased likelihood of red cell transfusion (odds ratio, 0.43; 95% confidence interval, 0.30 to 0.62). Adjusted hospital mortality did not differ before and after protocol implementation (odds ratio, 1.12; 95% confidence interval, 0.69 to 1.8). CONCLUSIONS: The implementation of an institutional protocol and decision support through a computerized provider order entry effectively decreased inappropriate red cell transfusions.

Assessing responses of the macula in patients with macular holes using a new system measuring localized visual acuity and the mfERG.

PURPOSE: To evaluate acuity and multifocal electroretinogram (mfERG) responses from the macula in affected and unaffected fellow eyes of patients with macular holes. METHODS: We tested 10 eyes with macular hole and 10 fellow eyes from 11 patients. We measured local visual acuity thresholds at 27 discrete locations within 21 degrees diameter using the Functional Fundus Imaging System (FFIS), a psychophysical system that measures visual acuity as a function of visual field location, and local ERG responses within 45 degrees diameter using the mfERG. RESULTS: In the affected eyes, the mean FFIS visual acuity thresholds were significantly elevated within the central 21 degrees diameter area, compared to a group of control eyes. No significant differences were found between the acuities of the fellow eyes compared to those of the control group. The amplitudes of the first positive peak of the mfERG were reduced in the central 7.8 degrees in affected eyes. In the central 2 degrees , 4 out of 10 affected eyes showed non-measurable ERG signals. The remaining six eyes showed significantly reduced mean amplitudes, but not delayed implicit times, when compared to the control group. For the fellow eyes, the mean amplitudes of the mfERG and implicit times did not differ from the means of the control eyes. CONCLUSIONS: Both local psychophysical and electrophysiological testing demonstrated retinal dysfunction extending beyond the site of the macular holes in some patients (three of the patients had central mfERG amplitudes falling within the normal range).

Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy.

OBJECTIVE: Although restrictive red cell transfusion practice has become a standard of care in the critically ill, data on the use of fresh frozen plasma (FFP) are limited. We hypothesized that the practice of FFP transfusion in the medical intensive care unit is variable and that liberal use may not be associated with improved outcome. DESIGN: Retrospective cohort study. SETTING: A 24-bed medical intensive care unit in a tertiary referral center. PATIENTS: All patients admitted to a medical intensive care unit during a 5-month period who had abnormal coagulation defined as international normalized ratio (INR) of > or = 1.5-times normal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected data on demographics, severity of illness as measured by Acute Physiology and Chronic Health Evaluation (APACHE) III scores, INR, bleeding episodes, and transfusion complications. We identified 115 patients with coagulopathy (INR of > or = 1.5) but without active bleeding. A total of 44 patients (38.3%) received FFP transfusion. INR was corrected in 16 of 44 patients (36%) who received transfusion. Median dose of FFP was 17 mL/kg in patients who had INR corrected vs. 10 mL/kg in those who did not (p = .018). There was no difference in age, sex, APACHE III scores, liver disease, Coumadin treatment, or INR level between those who did and did not receive FFP. Invasive procedures (68.2% vs. 40.8%, p = .004) and history of recent gastrointestinal bleeding (41% vs. 7%, p < .001) were more frequent in the group with transfusion. Although there was no difference in new bleeding episodes (6.8% in transfused vs. 2.8% in nontransfused group, p = .369), new onset acute lung injury was more frequent in the transfused group (18% vs. 4%, p = .021). Adjusted for severity of illness, hospital mortality and intensive care unit length of stay among survivors were not different between the two groups. CONCLUSION: The risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable. Randomized controlled trials evaluating restrictive vs. liberal FFP transfusion strategies are warranted.

Long-haul air travel before major surgery: a prescription for thromboembolism?

OBJECTIVE: To investigate the Incidence of postoperative venous thromboembolism (VTE) in patients who had flown long distances before major surgery. PATIENTS AND METHODS: Using the Mayo Clinic computerized patient database, we Identified patients who had flown more than 5000 km before major surgery (travelers) and had experienced an episode of clinically significant VTE within 28 days after surgery. Individual medical records were reviewed for the diagnosis of VTE, pertinent risk factors, and outcome. We compared the Incidence of VTE in travelers to the incidence of VTE in patients from North America (nontravelers) undergoing similar surgical procedures. RESULTS: Eleven patients met our criteria for long-haul air travel and clinically significant VTE within 28 days after surgery. Compared with nontravelers undergoing similar surgical procedures, long-haul travelers had a higher Incidence of VTE (4.9% vs 0.15%; P < .001). Compared with nontravelers who developed VTE, travelers were younger (P = .006), developed VTE earlier in the postoperative course (P = .01), had higher American Society of Anesthesiologists physical status classification (P = .02), and had higher prevalence of smoking (P = .007). Of the 11 travelers with VTE, 10 were of Middle Eastern origin. CONCLUSION: Prolonged air travel before major surgery significantly increases the risk of perioperative VTE. Such patients should receive more Intensive VTE prophylactic measures during the flight and throughout the perioperative period.

Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.

OBJECTIVE: Although ventilation with small tidal volumes is recommended in patients with established acute lung injury, most others receive highly variable tidal volume aimed in part at normalizing arterial blood gas values. We tested the hypothesis that acute lung injury, which develops after the initiation of mechanical ventilation, is associated with known risk factors for ventilator-induced lung injury such as ventilation with large tidal volume. DESIGN: Retrospective cohort study. SETTING: Four intensive care units in a tertiary referral center. PATIENTS: Patients who received invasive mechanical ventilation for > or = 48 hrs between January and December 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome of interest, acute lung injury, was assessed by independent review of daily digital chest radiographs and arterial blood gases. Ventilator settings, hemodynamics, and acute lung injury risk factors were extracted from the Acute Physiology and Chronic Health Evaluation III database and the patients' medical records. Of 332 patients who did not have acute lung injury from the outset, 80 patients (24%) developed acute lung injury within the first 5 days of mechanical ventilation. When expressed per predicted body weight, women were ventilated with larger tidal volume than men (mean 11.4 vs. 10.4 mL/kg predicted body weight, p <.001) and tended to develop acute lung injury more often (29% vs. 20%, p =.068). In a multivariate analysis, the main risk factors associated with the development of acute lung injury were the use of large tidal volume (odds ratio 1.3 for each mL above 6 mL/kg predicted body weight, p <.001), transfusion of blood products (odds ratio, 3.0; p < 0.001), acidemia (pH < 7.35; odds ratio, 2.0; p =.032) and a history of restrictive lung disease (odds ratio, 3.6; p =.044). CONCLUSIONS: The association between the initial tidal volume and the development of acute lung injury suggests that ventilator-associated lung injury may be an important cause of this syndrome. Height and gender should be considered when setting up the ventilator. Strong consideration should be given to limiting large tidal volume, not only in patients with established acute lung injury but also in patients at risk for acute lung injury.

Acute lung injury after blood transfusion in mechanically ventilated patients.

BACKGROUND: Liberal transfusion strategy increases the risk of acute lung injury (ALI), but specific transfusion-related factors have not been characterized. We tested the hypotheses that storage age and specific type of blood products are associated with increased risk of ALI in mechanically ventilated patients. STUDY DESIGN AND METHODS: From a database of mechanically ventilated patients, we identified those who received blood products during the first 48 hours of intensive care. We extracted information about underlying ALI risk factors as well as the type, amount, and shelf age of administered blood products. Outcome was assessed by an independent, blind review of chest radiographs and clinical findings. RESULTS: Of 181 patients transfused during the first 48 hours of mechanical ventilation, 60 (33%) developed ALI. There was no difference in average duration of red blood cells storage between patients who did and did not develop ALI (median, 18.5 vs. 17.5 days; p = 0.22). In a multivariable logistic regression analysis, important risk factors associated with the development of ALI were thrombocytopenia (odds ratio, 5.9; p = 0.004) and transfusion of fresh frozen plasma (odds ratio, 3.2; p = 0.023). CONCLUSION: Thrombocytopenia and transfusion of fresh frozen plasma, but not storage age of red blood cells, were associated with the development of ALI in this cohort of mechanically ventilated patients.