Gregory A. Wilson

Transfusion related acute lung injury: incidence and risk factors

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Predictors of survival following Cardiac arrest in patients undergoing noncardiac surgery: A study of 518,294 patients at a tertiary referral center

Background The authors determined the incidence of cardiac arrest and predictors of survival following perioperative cardiac arrest in a large population of patients at a tertiary referral center. Methods Medical records of patients who experienced cardiac arrest in the perioperative period surrounding noncardiac surgery between January 1, 1990, and December 31, 2000, were reviewed. Logistic regression identified characteristics associated with immediate (≥ 1 h) and hospital survival, with P ≤ 0.01 considered statistically significant. Results Cardiac arrest occurred in 223 of 518,294 anesthetics (4.3 per 10,000) during the study period. Frequency of arrest for patients receiving general anesthesia decreased over time (7.8 per 10,000 during 1990–1992; 3.2 per 10,000 during 1998–2000). The frequency of arrest during regional anesthesia (1.5 per 10,000) and monitored anesthesia care (0.7 per 10,000) remained consistent. Immediate survival after arrest was 46.6%, and hospital survival was 34.5%. Twenty-four patients (0.5 per 10,000) had cardiac arrest related primarily to anesthesia. From multivariate analysis, patients who experienced arrest due to bleeding were less likely to survive hospitalization (P = 0.001). Survival was also lower for patients who experienced arrest during nonstandard working hours (P = 0.006) and for patients who had protracted hypotension before arrest (P < 0.001). Conclusions The overall frequency of arrest for patients receiving anesthesia decreased during the study period. Most arrests were not due to anesthesia-related causes, and most patients experiencing anesthesia-related arrest survived to hospital discharge. Although many factors determining survival may not be amenable to modification, the fact that arrests during nonregular working hours had worse outcomes may indicate that the availability of human resources influences survival.

Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status A Randomized Clinical Trial

RATIONALE Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. OBJECTIVES To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. METHODS This is a double-blind, randomized, clinical trial comparing fresh (≤5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (ΔPa(O(2))/Fi(O(2))). Secondary outcomes include changes in immune and coagulation status. MEASUREMENTS AND MAIN RESULTS Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ΔPa(O(2))/Fi(O(2)) (difference between the mean ΔPa(O(2))/Fi(O(2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status. CONCLUSIONS In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).

Derivation and Validation of Automated Electronic Search Strategies to Extract Charlson Comorbidities From Electronic Medical Records

OBJECTIVE To develop and validate automated electronic note search strategies (automated digital algorithm) to identify Charlson comorbidities. PATIENTS AND METHODS The automated digital algorithm was built by a series of programmatic queries applied to an institutional electronic medical record database. The automated digital algorithm was derived from secondary analysis of an observational cohort study of 1447 patients admitted to the intensive care unit from January 1 through December 31, 2006, and validated in an independent cohort of 240 patients. The sensitivity, specificity, and positive and negative predictive values of the automated digital algorithm and International Classification of Diseases, Ninth Revision (ICD-9) codes were compared with comprehensive medical record review (reference standard) for the Charlson comorbidities. RESULTS In the derivation cohort, the automated digital algorithm achieved a median sensitivity of 100% (range, 99%-100%) and a median specificity of 99.7% (range, 99%-100%). In the validation cohort, the sensitivity of the automated digital algorithm ranged from 91% to 100%, and the specificity ranged from 98% to 100%. The sensitivity of the ICD-9 codes ranged from 8% for dementia to 100% for leukemia, whereas specificity ranged from 86% for congestive heart failure to 100% for leukemia, dementia, and AIDS. CONCLUSION Our results suggest that search strategies that use automated electronic search strategies to extract Charlson comorbidities from the clinical notes contained within the electronic medical record are feasible and reliable. Automated digital algorithm outperformed ICD-9 codes in all the Charlson variables except leukemia, with greater sensitivity, specificity, and positive and negative predictive values.

Characterizing the Epidemiology of Perioperative Transfusion-associated Circulatory Overload

Background:Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related fatalities, but its incidence and associated patient and transfusion characteristics are poorly understood. To inform surgical transfusion practice and to begin mitigating perioperative TACO, the authors aimed to define its epidemiology. Methods:In this retrospective cohort study, the medical records of adult patients undergoing noncardiac surgery with general anesthesia during 2004 or 2011 and receiving intraoperative transfusions were screened using an electronic algorithm for identification of TACO. Those patients who were screened as high probability for TACO underwent rigorous manual review. Univariate and multivariate analyses evaluated associations between patient and transfusion characteristics with TACO rates in a before-and-after study design. Results:A total of 2,162 and 1,908 patients met study criteria for 2004 and 2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus 3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% [98 of 2,023]) and women (3.8% [78 of 2,047]) (P = 0.09). Overall, vascular (12.1% [60 of 497]), transplant (8.8% [17 of 193]), and thoracic surgeries (7.2% [10 of 138]) carried the highest TACO rates. Obstetric and gynecologic patients had the lowest rate (1.4% [4 of 295]). The incidence of TACO increased with volume transfused, advancing age, and total intraoperative fluid balance (all P < 0.001). Conclusions:The incidence of perioperative TACO is similar to previous estimates in nonsurgical populations. There was a reduction in TACO rate between 2004 and 2011, with incidence patterns remaining comparable in subgroup analyses. Future efforts exploring risk factors for TACO may guide preventive or therapeutic interventions, helping to further mitigate this transfusion complication.

Characterizing the epidemiology of postoperative transfusion-related acute lung injury.

Background:Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related death in the United States; however, it remains poorly characterized in surgical populations. To better inform perioperative transfusion practice, and to help mitigate perioperative TRALI, the authors aimed to better define its epidemiology before and after TRALI mitigation strategies were introduced. Methods:This retrospective cohort study examined outcomes of adult patients undergoing noncardiac surgery with general anesthesia who received intraoperative transfusions during 2004 (n = 1,817) and 2011 (n = 1,562). The demographics and clinical characteristics of transfusion recipients, blood transfusion descriptors, and combined TRALI/possible TRALI incidence rates were evaluated. Univariate analyses were used to compare associations between patient characteristics, transfusion details, and TRALI mitigation strategies with TRALI/possible TRALI incidence rates in a before-and-after study design. Results:The incidence of TRALI/possible TRALI was 1.3% (23 of 1,613) in 2004 versus 1.4% (22 of 1,562) in 2011 (P = 0.72), with comparable overall rates in males versus females (1.4% [23 of 1,613] vs. 1.2% [22 of 1,766]) (P = 0.65). Overall, thoracic (3.0% [4 of 133]), vascular (2.7% [10 of 375]), and transplant surgeries (2.2% [4 of 178]) carried the highest rates of TRALI/possible TRALI. Obstetric and gynecologic surgical patients had no TRALI episodes. TRALI/possible TRALI incidence increased with larger volumes of blood product transfused (P < 0.001). Conclusions:Perioperative TRALI/possible TRALI is more common than previously reported and its risk increases with greater volumes of blood component therapies. No significant reduction in the combined incidence of TRALI/possible TRALI occurred between 2004 and 2011, despite the introduction of TRALI mitigation strategies. Future efforts to identify specific risk factors for TRALI/possible TRALI in surgical populations may reduce the burden of this life-threatening complication.

Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*.

Objective:Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases. Design:Prospective case study with controls. Setting:University of California, San Francisco and Mayo Clinic, Rochester. Patients:We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury. Interventions:None. Measurements and Main Results:Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls. Conclusions:In conclusion, transfusion-related acute lung injury produced a condition resembling the systemic inflammatory response syndrome and was associated with substantial in-hospital morbidity and mortality in patients with transfusion-related acute lung injury compared with transfused controls. Patients with possible transfusion-related acute lung injury had even higher in-hospital morbidity and mortality, suggesting that clinical outcomes in this group are mainly influenced by the underlying acute lung injury risk factor(s).

Electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications

BACKGROUND: Transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) are leading causes of transfusion‐related mortality. Notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. We aimed to develop accurate electronic health record–based screening algorithms for improved detection of TRALI/transfused acute lung injury (ALI) and TACO.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions

Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion‐related acute lung injury (TRALI), transfusion‐associated circulatory overload (TACO), and possible TRALI.

Multimodal Analgesic Protocol and Postanesthesia Respiratory Depression During Phase I Recovery After Total Joint Arthroplasty.

Background Multimodal analgesia protocols have shortened hospitalizations after total joint arthroplasty. It is unclear whether individual components of these protocols are associated with respiratory depression during phase I postanesthesia recovery. Objectives To test the hypothesis that sedating analgesics used in a multimodal protocol are associated with an increased rate of phase I postanesthesia respiratory depression. Methods Our Department of Anesthesiology records were searched to identify patients undergoing total joint arthroplasty with a multimodal analgesia protocol, including peripheral nerve blockade, from 2008 through 2012. Patient records were reviewed for episodes of postanesthesia respiratory depression, and potential causative factors were abstracted and analyzed for potential associations. Respiratory depression was defined as apnea, hypopnea, oxyhemoglobin desaturations, or episodes of severe pain despite moderate to profound sedation. Results Of 11,970 patients who underwent joint arthroplasty, 2836 (23.7%; 237 per 1000 cases; 95% confidence interval [95% CI], 214–262) had episodes of respiratory depression. A higher rate of respiratory depression was observed among patients who underwent general anesthesia (312 per 1000 cases; 95% CI, 301–323) than neuraxial anesthesia (144 per 1000 cases; 95% CI, 135–153) (P < 0.001). With both anesthetic techniques, respiratory depression was associated with preoperative use of gabapentin (>300 mg) (P < 0.001 for both anesthesia groups) and sustained-release oxycodone (>10 mg) (P = 0.01 for general anesthesia; P = 0.008 for neuraxial anesthesia). Conclusions Use of medications with long-acting sedative potential was associated with increased risk of respiratory depression during phase I anesthesia recovery. These effects were more pronounced when used in conjunction with general anesthesia than with neuraxial anesthesia.