Garth H. Utter

How valid is the ICD-9-CM based AHRQ patient safety indicator for postoperative venous thromboembolism?

Background:Hospital administrative data are being used to identify patients with postoperative venous thromboembolism (VTE), either pulmonary embolism (PE) or deep-vein thrombosis (DVT). However, few studies have evaluated the accuracy of these ICD-9-CM codes across multiple hospitals. Methods and Materials:The Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator (PSI)-12 was used to identify cases with postoperative VTE in 80 hospitals that volunteered for either an AHRQ or University HealthSystem Consortium (UHC) validation project. Trained abstractors using a standardized tool and guidelines retrospectively verified all coded VTE events. Results:In the combined samples, the positive predictive value of the set of prespecified VTE codes for any acute VTE at any time during the hospitalization was 451 of 573 = 79% (95% CI: 75%–82%). However, the positive predictive value for acute lower extremity DVT or PE diagnosed after an operation was 209 of 452 = 44% (95% CI: 37%–51%) in the UHC sample and 58 of 121 = 48% (95% CI: 42–67%) in the AHRQ sample. Fourteen percent of all cases had an acute upper extremity DVT, 6% had superficial vein thrombosis and 21% had no acute VTE, however, 61% of the latter had a documented prior/chronic VTE. In the UHC cohort, the sensitivity for any acute VTE was 95.5% (95% CI: 86.4%–100%); the specificity was 99.5% (95% CI: 99.4%–99.7%). Conclusion:Current PSI 12 criteria do not accurately identify patients with acute postoperative lower extremity DVT or PE. Modification of the ICD-9-CM codes and implementation of “present on admission” flags should improve the predictive value for clinically important VTE events.

Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial.

Objective:We sought to compare resuscitation with 0.9% NaCl versus Plasma-Lyte A, a calcium-free balanced crystalloid solution, hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury. Background:Sodium chloride (0.9%) (0.9% NaCl), though often used for resuscitation of trauma patients, may exacerbate the metabolic acidosis that occurs with injury, and this acidosis may have detrimental clinical effects. Methods:We conducted a randomized, double-blind, parallel-group trial (NCT01270854) of adult trauma patients requiring blood transfusion, intubation, or operation within 60 minutes of arrival at the University of California Davis Medical Center. Based on a computer-generated, blocked sequence, subjects received either 0.9% NaCl or Plasma-Lyte A for resuscitation during the first 24 hours after injury. The primary outcome was mean change in base excess from 0 to 24 hours. Secondary outcomes included 24-hour arterial pH, serum electrolytes, fluid balance, resource utilization, and in-hospital mortality. Results:Of 46 evaluable subjects (among 65 randomized), 43% had penetrating injuries, injury severity score was 23 ± 16, 20% had admission systolic blood pressure less than 90 mm Hg, and 78% required an operation within 60 minutes of arrival. The baseline pH was 7.27 ± 0.11 and base excess −5.9 ± 5.0 mmol/L. The mean improvement in base excess from 0 to 24 hours was significantly greater with Plasma-Lyte A than with 0.9% NaCl {7.5 ± 4.7 vs 4.4 ± 3.9 mmol/L; difference: 3.1 [95% confidence interval (CI): 0.5–5.6]}. At 24 hours, arterial pH was greater [7.41 ± 0.06 vs 7.37 ± 0.07; difference: 0.05 (95% CI: 0.01–0.09)] and serum chloride was lower [104 ± 4 vs 111 ± 8 mEq/L; difference: −7 (95% CI: −10 to −3)] with Plasma-Lyte A than with 0.9% NaCl. Volumes of study fluid administered, 24-hour urine output, measures of resource utilization, and mortality did not significantly differ between the 2 arms. Conclusions:Compared with 0.9% NaCl, resuscitation of trauma patients with Plasma-Lyte A resulted in improved acid-base status and less hyperchloremia at 24 hours postinjury. Further studies are warranted to evaluate whether resuscitation with Plasma-Lyte A improves clinical outcomes. Randomized controlled trial, level I. (ClinicalTrials.gov Record UCDIRB-200917793.)

High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury

BACKGROUND: Long‐term white blood cell (WBC) microchimerism (MC), of at least 2 years, has been reported in trauma patients receiving fresh nonleukoreduced (non‐LR) blood. It is unknown, however, whether this occurs with LR blood products that are nearly devoid of WBCs. Twenty‐seven patients transfused with LR and non‐LR blood products were studied after severe traumatic injury. A secondary aim was to explore donor‐recipient mixed lymphocyte reactivity in vitro.

Positive predictive value of the AHRQ accidental puncture or laceration patient safety indicator.

Objective:Patient Safety Indicator (PSI) 15, or “Accidental Puncture or Laceration” (APL), of the US Agency for Healthcare Research and Quality was recently endorsed as a consensus standard for quality of care by the National Quality Forum. We sought to determine the positive predictive value (PPV) of this indicator. Methods:We conducted a retrospective cross-sectional study of hospitalization records that met PSI 15 criteria. We sampled cases from 32 geographically diverse hospitals, including both teaching and nonteaching hospitals, between October 1, 2005 and March 31, 2007. Trained abstractors from each center reviewed randomly sampled medical records, using a standard instrument. We determined the PPV of the indicator and conducted descriptive analyses of the cases. Results:Of the 249 cases that met PSI 15 criteria, 226 (91%; 95% CI: 88%–94%) represented true APL. Fifty-six of the true APL cases (24%) represented injuries that generally would be expected to heal without repair, yielding, from the standpoint of clinical relevance, a PPV of 68% (95% CI: 62%–74%). True positive cases that would typically warrant repair (n=170) were most likely to involve the gastrointestinal tract (30%), bladder (25%), dura (19%), or an important blood vessel (16%). In 97 of the true APL cases (43%), adhesions or other scar tissue were thought to have contributed to the complication. The 23 false-positive cases involved no apparent event other than normal operative conduct (n=7), a complication other than APL (bleeding, infection, dislodgement of a gastrostomy tube, or fracture) (7), an APL present on admission (5), or a disease-related lesion (4). Conclusions:Although PSI 15 is highly predictive of APL from a coding perspective, the indicator is less predictive of APL that could be considered clinically important. A significant proportion of cases represent relatively inconsequential injuries or injuries for which the risk may have been acceptable relative to the goals of the procedure.

Transfusion-associated microchimerism.

Blood transfusion is a newly recognized cause of microchimerism, the stable persistence of a minor population of allogeneic cells. Relatively recent advances in polymerase chain reaction technology have spawned new information about the frequency and aetiology of transfusion‐associated microchimerism (TA‐MC). Although conceptually related to fetal‐maternal microchimerism, TA‐MC is a distinct and separate entity. Evidence of TA‐MC has been strongest among patients with severe traumatic injuries who receive relatively fresh blood products shortly after an episode of massive haemorrhage. The presence of a focal deficit in the cellular immunologic repertoire prior to transfusion that happens to match a blood donors human leucocyte antigen type also appears to be an important predisposing factor. TA‐MC seems to be common (affecting approximately 10% of transfused injured patients), enduring (lasting years to decades) and pronounced (involving up to 5% of circulating leucocytes and multiple immunophenotypic lineages suggestive of haematopoietic engraftment). Further study of this topic may reveal important information regarding potential clinical consequences of TA‐MC, as well as basic haematologic and immunologic processes.

Blood transfusion is associated with donor leukocyte microchimerism in trauma patients.

INTRODUCTION Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients. OBJECTIVE To determine how frequently transfusion after trauma is associated with microchimerism. METHODS We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. RESULTS Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. CONCLUSIONS Transfusion after trauma is associated with over half of recipients having evidence of microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with microchimerism. Because the median time from transfusion to sampling for PCR analysis was not longer in the group without microchimerism, it is unlikely microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.

Enhanced ascertainment of microchimerism with real-time quantitative polymerase chain reaction amplification of insertion-deletion polymorphisms

BACKGROUND: The characterization of microchimerism (MC) by gene amplification has been limited by few allogeneic markers, ascertainment bias, and assay analytic performance. To address this, a panel of 12 MC assays based on insertion‐deletion (InDel) polymorphisms had been optimized.

Leukoreduction of blood transfusions does not diminish transfusion‐associated microchimerism in trauma patients

BACKGROUND: Transfusion of trauma patients can result in long‐term survival of donor white blood cells (WBCs) or “transfusion‐associated microchimerism” (TA‐MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA‐MC.

Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response.

BACKGROUND Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism. METHODS We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. RESULTS Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. CONCLUSIONS Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.

Anemia in the Setting of Traumatic Brain Injury: The Arguments For and Against Liberal Transfusion

Anemia is recognized as a possible cause of secondary injury following traumatic brain injury (TBI). Cogent arguments can be made for both liberal and restrictive blood transfusion practices in this setting. In this narrative review, we summarize available knowledge regarding the risks of anemia and transfusion in patients with TBI. Laboratory studies using animal models and healthy human subjects suggest that anemia below a hemoglobin (Hb) concentration of 7 g/dL results in impaired brain function and below 10 g/dL may be detrimental to recovery from TBI. Clinical studies that have evaluated the association of anemia with clinical outcomes have not consistently demonstrated harm, but they generally have important methodological weaknesses. Alternatively, studies that have analyzed transfusion as a predictor of worse outcome have consistently identified such an association, but these studies may involve residual confounding. What little information exists from randomized trials that have included patients with TBI and evaluated liberal versus restrictive transfusion strategies is inconclusive. Since anemia in the setting of TBI is relatively common and there is considerable variation in transfusion preferences, greater study of this topic - preferably with one or more rigorous, adequately powered, non-inferiority randomized trials - is desirable.