Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial.

BACKGROUND: Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy. METHODS: In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032. FINDINGS: Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median duration of follow-up was 3·1 years (IQR 2·4-4·1 years), during which 841 (42%) patients died. Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 1·09 [95% CI 0·95-1·25]; p=0·21). INTERPRETATION: Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high-risk group of elderly patients with underlying cardiovascular disease or risk factors. The underlying causes of death did not differ between the trial groups. These findings do not support hypotheses that blood transfusion leads to long-term immunosuppression that is severe enough to affect long-term mortality rate by more than 20-25% or cause of death. FUNDING: National Heart, Lung, and Blood Institute.

Delirium outcomes in a randomized trial of blood transfusion thresholds in hospitalized older adults with hip fracture.

OBJECTIVES: To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery. DESIGN: Ancillary study to a randomized clinical trial. SETTING: Thirteen hospitals in the United States and Canada. PARTICIPANTS: One hundred thirty-nine individuals hospitalized with hip fracture aged 50 and older (mean age 81.5 ± 9.1) with cardiovascular disease or risk factors and hemoglobin concentrations of less than 10 g/dL within 3 days of surgery recruited in an ancillary study of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair. INTERVENTION: Individuals in the liberal treatment group received one unit of packed red blood cells and as much blood as needed to maintain hemoglobin concentrations at greater than 10 g/dL; those in the restrictive treatment group received transfusions if they developed symptoms of anemia or their hemoglobin fell below 8 g/dL. MEASUREMENTS: Delirium assessments were performed before randomization and up to three times after randomization. The primary outcome was severity of delirium according to the Memorial Delirium Assessment Scale (MDAS). The secondary outcome was the presence or absence of delirium defined according to the Confusion Assessment Method (CAM). RESULTS: The liberal group received a median two units of blood and the restrictive group zero units of blood. Hemoglobin concentration on Day 1 after randomization was 1.4 g/dL higher in the liberal group. Treatment groups did not differ significantly at any time point or over time on MDAS delirium severity (P = .28) or CAM delirium presence (P = .83). CONCLUSION: Blood transfusion to maintain hemoglobin concentrations greater than 10 g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10 g/dL.

Liberal or restrictive transfusion in high-risk patients after hip surgery.

BACKGROUND: The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. METHODS: We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. RESULTS: A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. CONCLUSIONS: A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

General anesthesia occurs frequently in elderly patients during propofol-based sedation and spinal anesthesia.

STUDY OBJECTIVE: To test the hypothesis that sedation in elderly patients is often electrophysiologically equivalent to general anesthesia (GA). DESIGN: Prospective, observational study. SETTING: Operating room of a university medical center. PATIENTS: 40 elderly patients (>or=65 yrs of age) undergoing hip fracture repair with spinal anesthesia and propofol-based sedation. INTERVENTIONS: In the routine practice group (RP; n = 15), propofol sedation was administered per the usual routine of the anesthesiologist. In the targeted sedation group (TS; n = 25), sedation was titrated to an observer's assessment of alertness/sedation (OAA/S) score of 4 (ie, lethargic in response to name called) to 5 (ie, awake and alert). MEASUREMENTS: Both patient groups underwent processed electroencephalographic monitoring using bispectral index (BIS) intraoperatively. BIS levels were compared between groups to determine amount of surgical time spent in GA (BIS

Eight-year follow-up on the effect of a hip fracture service on patient care and outcome.

The purpose of this study was to evaluate the 8-year effect of a hip fracture service on time to surgery; duration of surgery; length of stay in acute care, intensive care, and rehabilitation unit; and incidence of postoperative complications and in-hospital mortality. The study group consisted of 50 female patients 65 years of age or older who were treated for hip fractures in 1999 and 50 case-, age-, and American Society of Anesthesiologists score-matched female patients treated in 2006. Group differences were compared via the Student paired t test and χ² analysis (statistical significance, p ≤ .05). The 2006 group had a significantly shorter mean surgical time than did the 1999 group, but time to surgery did not change. The 2006 group showed improvements (but not statistically significant ones) in length of stay in acute care, intensive care, and rehabilitation unit, and in the incidence of complications and in-hospital mortality.

Recovery room delirium predicts postoperative delirium after hip-fracture repair.

UNLABELLED: In this study, we sought to determine the incidence of recovery room delirium in elderly patients having hip-fracture repair under general anesthesia and to discover whether recovery room delirium is associated with continuing postoperative delirium. In this prospective study, patients undergoing hip-fracture repair were anesthetized using a standardized protocol. In addition, postoperative pain management was standardized in both the postoperative anesthesia care unit and in the hospital ward. The presence of delirium was determined using the confusion assessment method (CAM) score. Recovery room delirium was assessed by obtaining a CAM score at 60 min after discontinuation of isoflurane. Postoperative delirium was assessed by obtaining a daily CAM score during the postoperative in-hospital recovery period. Fifty patients consented to the study and 47 patients were included in the analysis (surgery cancelled postinduction n = 1; nonadherence to protocol n = 2). Average patient age was 77 +/- 1 (mean +/- SE) yr (range, 56-98 yr). Seventy-seven percent of the study patients were ASA class III or more. The prevalence of recovery room delirium was 45%. The prevalence of postoperative delirium was 36%. Recovery room delirium predicted postoperative delirium (P < 0.001, Fisher's exact test) with a sensitivity of 100% and a specificity of 85%. Analgesic doses administered in the postoperative anesthesia care unit and ward were similar in patients with or without postoperative delirium. Results of this study show that recovery room delirium is a strong predictor of postoperative delirium. IMPLICATIONS: In patients undergoing hip-fracture repair, recovery room delirium is a strong predictor of postoperative delirium when using a standardized protocol for general anesthesia and postoperative pain management.

Brief postoperative delirium in hip fracture patients affects functional outcome at three months.

UNLABELLED: It is unclear how brief postoperative delirium (DEL) affects functional outcomes. In this study, we sought to determine if patients with brief postoperative DEL (<6-wk duration) have different living situations when compared with non-DEL patients after hip fracture repair. In a prospective study, patients admitted to the geriatric hip fracture service were assessed every postoperative day for the presence of DEL using the confusion assessment method (CAM) score. Patients were reassessed at 6 wk and 3 mo postoperatively for CAM score, current living situation, and activities of daily living. Group comparisons were tested after dividing patients into two groups: DEL (DEL; [+] CAM at any time during the postoperative period while in the hospital); no-DEL (no DEL; [-] CAM throughout the postoperative period while in the hospital). The study included 92 patients of whom 26 (28%) were CAM (+) after surgery. At 6 wk follow-up, n = 81; at 3 mo follow-up, n = 76. Eight patients died during the study. At 6 wk and 3 mo, a larger percentage of DEL patients were not living with a family member (27% versus 8% patients not living with a family member at 3 mo follow-up in DEL and no-DEL, respectively). There was no difference in activities of daily living by 3 mo. We conclude that brief postoperative DEL lasting <6 wk is a determining factor for poor long-term functional outcome after hip fracture repair, because it significantly impacts the ability to live independently. IMPLICATIONS: Brief postoperative delirium lasting <6 wk is a determining factor for poor long-term functional outcome after hip fracture repair, because it significantly impacts the ability to live independently.

Preoperative factors associated with postoperative change in confusion assessment method score in hip fracture patients.

UNLABELLED: Postoperative delirium is a major problem in elderly patients undergoing surgical repair of hip fracture. It is imperative to identify potentially treatable preoperative factors associated with the onset of postoperative delirium to optimize outcome. We sought to determine what preoperative variables are associated with postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. In a prospective, IRB-approved study, patients admitted to the geriatric hip fracture service were examined daily in the hospital for the occurrence of postoperative delirium. All patients with a preoperative diagnosis of dementia or delirium were eliminated. A positive confusion assessment method score ([+]CAM) was used to determine the presence of postoperative delirium during the acute hospital stay. To determine the association between preoperative variables (demographics, laboratory values, and comorbidities) and postoperative (+)CAM scores, chi(2) and logistic regression analysis were performed with calculation for the odds ratios (OR). One-hundred-sixty-eight patients (72% women) were included in the analysis. Twenty-eight percent (n = 47) of patients had a (+)CAM score. Three variables were significant predictors of a (+)CAM score: (a) normal white blood cell count (OR, 2.2), (b) abnormal serum sodium (OR, 2.4); and (c) ASA physical status >II (OR, 11.3). The results suggest that preoperative medical conditions (abnormal serum sodium and ASA physical status >II) and an inability to mount a stress response (normal white blood cell count) may influence the patient's postoperative mental status. In particular, two of the risk factors we identified may be amenable to therapy and are abnormal serum sodium and lack of an increase in white blood cell count during the stress of trauma and surgery. IMPLICATIONS: This prospective study investigated preoperative variables that are predictive of postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. The results suggest that the patient's preoperative medical condition and inability to mount a stress response influence postoperative delirium.