1. Geriatrics Journal Club Yee Chuan Ang, MD Geriatric Medicine Fellow PGY-4 Boston University School of Medicine

2. Mrs. K.M. 78-year-old Caucasian female admitted to the hospital for surgical repair of her right hip fracture after a fall. 78-year-old Caucasian female admitted to the hospital for surgical repair of her right hip fracture after a fall.

3. Mrs. K.M. Past Medical History Past Medical History –Mild Alzheimer’s dementia –Chronic iron deficiency anemia ( baseline 10- 11g/dL) –Hypertension –hypercholesterolemia –Knee osteoarthritis –Vitamin D deficiency –GERD Home medications Home medications –Ferrous sulfate 325mg daily –Lisinopril 20mg daily –Amlodipine 10mg daily –Pravastatin 40mg daily –Acetaminophen 650mg PRN –Cholecalciferol 1000IU daily –Pantoprazole 20mg daily

4. Mrs. K.M. Baseline functional status Baseline functional status –Walked with a cane, required assistance in the shower –Partially IADLs dependent ( required assistance for grocery, house chores, finances)

5. Hospital Course A day prior to hip surgery, Mrs. KM had a Hgb level of 10.6g/dL. A day prior to hip surgery, Mrs. KM had a Hgb level of 10.6g/dL. She received one unit of blood transfusion during the operation, post- op Hgb level was 8.2 g/dL. She received one unit of blood transfusion during the operation, post- op Hgb level was 8.2 g/dL.

6. Hospital Course She developed delirium on post-op day 1. No blood transfusion received. She developed delirium on post-op day 1. No blood transfusion received.

7. Clinical question 78-year-old lady with history of chronic anemia, and cardiovascular risk factors, who had a Hgb level of 8.2g/dL after hip surgery, does blood transfusion improve delirium symptoms in the hospital? 78-year-old lady with history of chronic anemia, and cardiovascular risk factors, who had a Hgb level of 8.2g/dL after hip surgery, does blood transfusion improve delirium symptoms in the hospital?

8. Background Delirium is common in individual with hip fracture ( 35-62%). Delirium is common in individual with hip fracture ( 35-62%). Frequently have anemia ( ~75%), with post-operative hemoglobin concentrations of less than 10g/dL. 1 Frequently have anemia ( ~75%), with post-operative hemoglobin concentrations of less than 10g/dL. 1 Studies have shown association between postoperative Hgb < 10 and subsequent incidence of delirium. 2 Studies have shown association between postoperative Hgb < 10 and subsequent incidence of delirium. 2 1.Carson JL, et al. Anemia and postoperative rehabilitation.Can J Anesth 2004;50:S60–S64. 2.Marcantonio ER, et al. The association of intraoperative factors with the development of postoperative delirium. Am J Med 1998;105:380–384.

9. Background Transfusion was one component of two multifactorial geriatric consultation interventions shown to reduce delirium, but it is unknown whether transfusions contributed to the improved outcome. 1,2 1. Marcantonio ER, et al. Reducing delirium after hip fracture: A randomized trial. J Am Geriatr Soc 2001;49:516–522. 2. Lundstrom M, et al. Postoperative delirium in old patients with femoral neck fracture: A randomized intervention study.Aging Clin Exp Res 2007;19:178–186.

10. Article

11. Objective To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery

12. Study Design Ancillary study to a randomized, multicenter clinical trial ( FOCUS) Ancillary study to a randomized, multicenter clinical trial ( FOCUS)Setting Thirteen hospitals in the United States and Canada from April 2008 to Feb 2009. Thirteen hospitals in the United States and Canada from April 2008 to Feb 2009.

13. FOCUS The Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) to test whether a higher blood transfusion threshold improved functional status, and reduced morbidity and mortality. Carson JL, et al. Liberal or restrictive transfusion inhigh-risk patients after hip surgery. N Engl J Med 2011;365:2453–2462

14. Inclusion criteria Aged 50 and older, were undergoing surgical repair of hip fracture Aged 50 and older, were undergoing surgical repair of hip fracture Hgb <10g/dL within 3 days after surgery Hgb <10g/dL within 3 days after surgery Had clinical evidence of cardiovascular disease or risk factors Had clinical evidence of cardiovascular disease or risk factors

15. Exclusion criteria Unable to walk without human assistance before hip fracture Unable to walk without human assistance before hip fracture Had multiple traumas Had multiple traumas Had pathological hip fracture Had pathological hip fracture Had acute MI 30 days prior to randomization Had acute MI 30 days prior to randomization Had symptoms associated with anemia, or were actively bleeding at the time of randomization Had symptoms associated with anemia, or were actively bleeding at the time of randomization Non-English speaking Non-English speaking

16. Methods Liberal group: received one unit of PRBC and as much blood as needed to maintain Hgb of greater than 10g/dL Liberal group: received one unit of PRBC and as much blood as needed to maintain Hgb of greater than 10g/dL Restrictive group: transfused if developed symptoms of anemia or if Hgb < 8g/dL Restrictive group: transfused if developed symptoms of anemia or if Hgb < 8g/dL Subjects with dementia were transfused if Hgb <8g/dL Subjects with dementia were transfused if Hgb <8g/dL

17. Methods Delirium assessment performed before randomization, and multiple times within 5 days after randomization or up to hospital discharge. Delirium assessment performed before randomization, and multiple times within 5 days after randomization or up to hospital discharge. Post-surgical assessments were performed at least 12 hours after surgery Post-surgical assessments were performed at least 12 hours after surgery

18. Primary outcome Memorial Delirium Assessment Scale( MDAS) Memorial Delirium Assessment Scale( MDAS) –10-item scale to rates the severity of delirium – score from 0 to 30 ( 30 is most severe) –Predicts the long-term outcomes of delirium

19. MDAS

20. Secondary outcome Confusion Assessment Method Diagnostic Algorithm ( CAM) Confusion Assessment Method Diagnostic Algorithm ( CAM) –Four-item algorithm

21. Statistical Analysis Previous work has found a clinically meaningful difference of 2.5 points on the MDAS. Previous work has found a clinically meaningful difference of 2.5 points on the MDAS. 80% power to detect a difference of 2.5 MDAS points. 80% power to detect a difference of 2.5 MDAS points. Baseline differences in sex, history of dementia, use of sedative hypnotics and antidepressants, were adjusted for. Baseline differences in sex, history of dementia, use of sedative hypnotics and antidepressants, were adjusted for.

23. Baseline Characteristic

31. Result

32. Result

35. Discussion

36. Limitations Three full days of postrandomization assessments were not available for many subjects, which could limit the power for many of these comparisons Three full days of postrandomization assessments were not available for many subjects, which could limit the power for many of these comparisons Delirium evaluators were not blind to treatment Delirium evaluators were not blind to treatment Sample size was relatively small Sample size was relatively small

37. Conclusions Blood transfusion to maintain Hgb greater than 10g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10g/dL. Blood transfusion to maintain Hgb greater than 10g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10g/dL.

38. Thank you! Thank you!