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

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

Mrs. K. M. n Past Medical History – Mild Alzheimer’s dementia – Chronic iron Mrs. K. M. n Past Medical History – Mild Alzheimer’s dementia – Chronic iron deficiency anemia ( baseline 1011 g/d. L) – Hypertension – hypercholesterolemia – Knee osteoarthritis – Vitamin D deficiency – GERD n Home medications – Ferrous sulfate 325 mg daily – Lisinopril 20 mg daily – Amlodipine 10 mg daily – Pravastatin 40 mg daily – Acetaminophen 650 mg PRN – Cholecalciferol 1000 IU daily – Pantoprazole 20 mg daily

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

Hospital Course n A day prior to hip surgery, Mrs. KM had a Hgb Hospital Course n A day prior to hip surgery, Mrs. KM had a Hgb level of 10. 6 g/d. L. n She received one unit of blood transfusion during the operation, postop Hgb level was 8. 2 g/d. L.

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

Clinical question 78 -year-old lady with history of chronic anemia, and cardiovascular risk factors, Clinical question 78 -year-old lady with history of chronic anemia, and cardiovascular risk factors, who had a Hgb level of 8. 2 g/d. L after hip surgery, does blood transfusion improve delirium symptoms in the hospital?

Background n n n 1. 2. Delirium is common in individual with hip fracture Background n n n 1. 2. Delirium is common in individual with hip fracture ( 35 -62%). Frequently have anemia ( ~75%), with postoperative hemoglobin concentrations of less than 10 g/d. L. 1 Studies have shown association between postoperative Hgb < 10 and subsequent incidence of delirium. 2 Carson JL, et al. Anemia and postoperative rehabilitation. Can J Anesth 2004; 50: S 60–S 64. Marcantonio ER, et al. The association of intraoperative factors with the development of postoperative delirium. Am J Med 1998; 105: 380– 384.

Background n Transfusion was one component of two multifactorial geriatric consultation interventions shown to Background n 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.

Article Article

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

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

FOCUS n n The Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing FOCUS n n 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

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

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

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

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

Primary outcome n Memorial Delirium Assessment Scale( MDAS) – 10 -item scale to rates Primary outcome n 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

MDAS MDAS

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

Statistical Analysis n Previous work has found a clinically meaningful difference of 2. 5 Statistical Analysis n Previous work has found a clinically meaningful difference of 2. 5 points on the MDAS. n 80% power to detect a difference of 2. 5 MDAS points. n Baseline differences in sex, history of dementia, use of sedative hypnotics and antidepressants, were adjusted for.

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

Baseline Characteristic Baseline Characteristic

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Result Result

Result Result

Discussion Discussion

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

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

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