Wilson, Gregory

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. Design: An observational case-control study. Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. Conclusions: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

BACKGROUNDIt is increasingly recognized that recipient risk factors play a prominent role in possible transfusion‐related acute lung injury (pTRALI) and transfusion‐associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI.STUDY DESIGN AND METHODSWe performed a post hoc analysis of a case‐control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI.RESULTSWe found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated BNP levels relative to those of controls and TRALI. The following variables were useful in distinguishing cases of pTRALI and TACO from TRALI: age more than 70 years, BNP levels more than 1000 pg/mL, 24‐hour fluid balance of more than 3 L, and a lower number of transfused blood components. Using the above variables, our logistic model had a 91% negative predictive value in the differential diagnosis of TRALI.CONCLUSIONSModels incorporating readily available clinical and biomarker data can be used to differentiate transfusion‐related respiratory complications. Additional studies examining recipient risk factors and the likelihood of TRALI may be useful in decision making regarding donor white blood cell antibody testing.

BACKGROUNDPlatelet (PLT) transfusion before interventional radiology procedures is commonly performed in patients with thrombocytopenia. However, it is unclear if PLT transfusion is associated with reduced bleeding complications.STUDY DESIGN AND METHODSThis is a retrospective cohort study of adults undergoing interventional radiology procedures between January 1, 2009, and December 31, 2013. Baseline characteristics, coagulation variables, transfusion requirements, and procedural details were evaluated. Propensity‐matched analyses were used to assess relationships between PLT transfusions and the outcomes of interest, including a primary outcome of periprocedural red blood cell (RBC) transfusion during the procedure or within the first 24 hours after procedure.RESULTSA total of 18,204 participants met inclusion criteria, and 2060 (11.3%) had a PLT count of not more than 100 × 109/L before their procedure. Of these, 203 patients (9.9) received preprocedural PLTs. There was no significant difference in RBC requirements between those receiving or not receiving preprocedural PLTs in propensity‐matched analysis (odds ratio [OR], 1.45; 95% confidence interval [CI], 0.95‐2.21; p = 0.085). PLT transfusion was associated with increased rates of intensive care unit admission (OR [95% CI], 1.57 [1.07‐2.32]; p = 0.022).CONCLUSIONIn patients with thrombocytopenia undergoing interventional radiology procedures, preprocedural PLT transfusion was not associated with reduced periprocedural RBC requirements. These findings suggest that prophylactic PLT transfusions are not warranted in nonbleeding patients with preprocedural PLT counts exceeding 50 × 109/L. Future clinical trials are needed to further define relationships between prophylactic PLT administration and bleeding complications, especially at more severe levels of thrombocytopenia or in the presence of PLT dysfunction.

BACKGROUND: Subjects with severe hypoxemic respiratory failure have shown a high mortality in previous studies. METHODS: All adult ICU patients requiring mechanical ventilation from 2005 to 2010 at Mayo Clinic were screened for severe hypoxemia (Murray lung injury score of ≥ 3). Extracorporeal membrane oxygenation, prone positioning, high-frequency oscillatory ventilation (HFOV), and inhaled vasodilators were considered as rescue strategies. A propensity-based scoring was created for the indication or predilection to use each strategy. A model was created to evaluate the association of each rescue strategy with hospital mortality. RESULTS: Among 1,032 subjects with severe hypoxemia, 239 subjects received some form of rescue strategy (59 received a combination of therapies, and 180 received individual therapies). Inhaled vasodilators were the most common, followed by HFOV. Rescue strategies were used in younger subjects with severe oxygenation deficits. Subjects receiving rescue strategies had higher mortality and longer ICU stays. None of the strategies individually or in combination showed a significant association with hospital mortality after adjusting covariates by propensity scoring. Adjusted Odds ratios and respective 95% CI were as follows: HFOV 0.67 (0.35–1.27), extracorporeal membrane oxygenation 0.63 (0.18–1.92), prone position 1.07 (0.49–2.28), and inhaled vasodilators 1.17 (0.78–1.77). CONCLUSIONS: In this retrospective comparative effectiveness study, there was no association of rescue strategies with hospital mortality in subjects with severe hypoxemia.

AbstractAbstract In a series of 57,787 patients receiving arterial cannulation, 21 patients were identified as having experienced vascular complications or nerve injuries, resulting in a very low complication rate of 3.4/10,000. The rate of complications differed significantly (P < 0.001) across the three most common catheter sizes (2.7/10,000 for 20 gauge, 17.2/10,000 for 18 gauge, and 9.4/10,000 for 5 French). Given the low frequency of complications observed, the current study does not have sufficient statistical power to make definitive conclusions regarding the risk factors (listed in the appendix). Background Prior research has provided inconsistent data regarding the risk factors associated with complications from arterial cannulation. The goal of this study was to clearly define the incidence and risks factors associated with arterial cannulation complications. Methods After obtaining institutional review board approval, all patients requiring arterial line placement with documentation were included in this retrospective study between January 1, 2006, and December 31, 2012. Leveraging two robust data warehouses, the Perioperative DataMart and the Mayo Clinic Life Silences System, the authors cross-matched arterial line cannulation with a documented vascular consult, neurologic consult, infection, or return to surgery within 30 days in order to identify the initial patient population. Results A total of 62,626 arterial lines were placed in 57,787 patients, and 90.1% of the catheters placed were 20-gauge catheters. The radial artery was cannulated in 94.5% of patients. A total of 21 patients were identified as having experienced vascular complications or nerve injuries, resulting in a complication rate of 3.4 per 10,000 (95% CI, 2.1 to 5.1). Cardiac surgery had the largest number of catheters placed (n = 15,419) with 12 complications (complication rate = 7.8 per 10,000; 95% CI, 4.0 to 13.6). The rate of complications differed significantly (P < 0.001) across the three most common catheter sizes (2.7 per 10,000 [95% CI, 1.5 to 4.4] for 20 gauge, 17.2 per 10,000 [95% CI, 4.7 to 43.9] for 18 gauge, and 9.4 per 10,000 [95% CI, 1.1 to 34.1] for 5 French). Conclusion In a large retrospective study, the authors document a very low rate of complications with arterial line placement.

BACKGROUNDPerioperative hemorrhage impacts patient outcomes and health care resource utilization, yet the risks of transfusion therapies are significant. In patients with preoperative thrombocytopenia, the effects of prophylactic preoperative platelet (PLT) transfusion on perioperative bleeding complications remain uncertain.STUDY DESIGN AND METHODSThis is a retrospective cohort study of noncardiac surgical patients between January 1, 2008, and December 31, 2011. Propensity‐adjusted analyses were used to evaluate associations between preoperative thrombocytopenia, preoperative PLT transfusion, and the outcomes of interest, with a primary outcome of perioperative red blood cell (RBC) transfusion.RESULTSA total of 13,978 study participants were included; 860 (6.2%) had a PLT count of not more than 100 × 109/L with 71 (8.3%) receiving PLTs preoperatively. Administration of PLTs was associated with higher rates of perioperative RBC transfusion (66.2% vs. 49.1%, p = 0.0065); however, in propensity‐adjusted analysis there was no significant difference between groups (odds ratio [OR] [95% confidence interval {95% CI}], 1.68 [0.95‐2.99]; p = 0.0764]. Patients receiving PLTs had higher rates of intensive care unit (ICU) admission (OR [95% CI], 1.95 [1.10‐3.46]; p = 0.0224) and longer hospital lengths of stay (estimate [95% bootstrap CI], 7.2 [0.8‐13.9] days; p = 0.0006) in propensity‐adjusted analyses.CONCLUSIONPreoperative PLT transfusion did not attenuate RBC requirements in patients with thrombocytopenia undergoing noncardiac surgery. Moreover, preoperative PLT transfusion was associated with increased ICU admission rates and hospital duration. These findings suggest that more conservative management of preoperative thrombocytopenia may be warranted.

BACKGROUND 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. STUDY DESIGN AND METHODS In a nested case‐control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte‐macrophage–colony‐stimulating factor, interleukin (IL)‐6, IL‐8, IL‐10, and tumor necrosis factor‐α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS Before and after transfusion, IL‐6 and IL‐8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL‐10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion‐related respiratory complications such as TRALI and TACO.

Abstract 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.

Abstract 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.