Preoperative Drug Monitoring in Management of Patients with Hip Fracture on Treatment with Direct Oral Anticoagulants.

Purpose: Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture. Patients and Methods: A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL. Results and conclusions: TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A (p<0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; p=0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia). Conclusion: DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines.

Management and 1-Year Outcome in Elderly Patients with Hip Fracture Surgery Receiving Anticoagulation (Warfarin or DOAc) or P2Y12 Antiplatelet Agents.

(1) Background: Little prospective data exist regarding the perioperative management and long-term prognosis of elderly patients receiving treatment with antithrombotic drugs and undergoing urgent surgery for a hip fracture. (2) Methods: The study included patients who required hip surgery and were receiving warfarin, DOAc or P2Y12 antiplatelet agents at the moment of trauma. Ongoing antithrombotic treatment was managed according to existing recommendations. The endpoints of the study were the time to surgery, perioperative bleeding, the need for transfusion and, finally, mortality, major cardiovascular events and re-hospitalization at 6 and 12 months. (3) Results: The study included a total of 138 patients. The mean age was 86 years; 75.4% were female. Eighty-two received DOAc, thirty-six received warfarin and twenty received P2Y12 inhibitors. The controls were 283 age- and sex-matched patients who did not receive antithrombotic treatment. A total of 38% of patients receiving warfarin underwent surgery <48 h, 52% receiving DOAc, 55% receiving P2Y12 inhibitors and, finally, 82% in the control group. Perioperative bleeding and the need for transfusion were not different between the four groups. Mortality at 6 months was higher in patients receiving warfarin and P2Y12 inhibitors (30% and 25%) in comparison to DOAc and the control group (11.6% and 10% p < 0.0001). Similarly, the other endpoints were more frequent in patients receiving warfarin and P2Y12 inhibitors. The trend was maintained for 12 months. No significant differences in mortality were found between early (<48 h) and late (>48 h) surgery independent of the type of treatment. (4) Conclusions: Our study confirmed that anticoagulants delay surgery in patients with hip fractures; however, intervention > 48 h is not associated with a poorer prognosis. This finding is relevant as it underlines that, in patients at high risk of postoperative cardiovascular complications, the careful management of anticoagulation before surgery may compensate for the delay of surgery with a very low in-hospital mortality rate (<1%). One-year survival was significantly lower in patients receiving warfarin, probably related to their worse risk profile at the moment of trauma survival.

Hip Fracture Surgery in Severe Aortic Stenosis: A Study of Factors Affecting Mortality.

Background: In elderly patients with hip fracture, the prevalence of severe aortic stenosis (valve area <1 cm2) is close to 5%. Few studies have evaluated the prognostic role of aortic stenosis in hip fracture surgery and none has considered the effects of the postoperative setting (intensive care unit vs general ward) on clinical outcome. Purpose: The aim of the present study was to evaluate the factors affecting mortality in patients with severe aortic stenosis undergoing surgery for hip fracture. We also evaluated whether postoperative monitoring in the intensive care unit may affect the prognosis in comparison to return to the general ward after surgery. Patients and Methods: All 2274 patients referred for hip fracture to our tertiary teaching hospital between January 1 2015 and December 31 2019 were screened for the presence of severe aortic stenosis, defined by an aortic valve area <1.0 cm2. Results: The study included 66 patients (27 males, 39 females) with a mean±SD age of 85±7 years. The average time between trauma and surgery was 2.6±3 days. The mean aortic valve area was 0.74±0.15 cm2. Seven patients died during hospitalization (10.4%). Diabetes, having two or more comorbidities, a low degree of autonomy, heart failure, history of coronary artery disease, atrial fibrillation, postoperative delirium and pulmonary hypertension were associated with poorer outcome. In logistic multivariate analysis, the number of diseases and values of pulmonary artery pressure were the only independent factors related to mortality. In hospital mortality (12 and 9%, respectively) and complication rates were not statistically different between patients referred to the intensive care unit for postoperative monitoring and patients returned to the general ward after surgery. Conclusion: In patients undergoing hip fracture surgery, severe aortic stenosis is associated with high hospital mortality, and two or more comorbidities and pulmonary hypertension are associated with a worse prognosis. The postoperative setting (intensive care unit or general ward) does not affect outcome.

Independent, Differential Effects of Delirium on Disability and Mortality Risk After Hip Fracture.

OBJECTIVES: To assess the independent effect of delirium on mortality and disability after 1 year of follow-up, in consecutive older patients with hip fracture hospitalized for surgical repair. DESIGN: This is a prospective observational study. SETTING AND PARTICIPANTS: Patients aged older than 65 years consecutively admitted for hip fracture to the Trauma and Orthopedics Centre of a third-level hospital, between March and October 2014. METHODS: Patients were evaluated by a multidisciplinary team. A comprehensive geriatric assessment was performed on admission. Delirium was assessed before and after surgical repair according to the Confusion Assessment Method. Mortality and disability status were collected at 3 months and 1 year after hospital discharge. RESULTS: Of 411 patients with hip fracture, 387 (mean age 82 years, female 72%) were enrolled. Delirium was assessed in 50% of the enrolled population. Patients with delirium were older, frequently affected by dementia, severe prefracture disability, history of falls, and polypharmacy. One-year mortality was 19% in all populations, and higher in patients with delirium, although delirium did not show an independent association with mortality, in multivariable analysis. Conversely, delirium was identified as an independent prognostic factor of long-term disability (B-1.605, SE 0.211, P < .001). CONCLUSION AND IMPLICATIONS: This study identifies delirium as an independent long-term disability generator, regardless of associated clinical conditions and premorbid cognitive and functional status. This emphasises the importance of delirium prevention through a multidisciplinary approach and the potential role of systematic treatment of risk factors in reducing functional decline, even in subjects with preexistent disability and dementia. Moreover, these data call for research on rehabilitation interventions specifically targeted to these complex patients, with the aim of identifying approaches effective in reducing long-term disability. Conversely, a high level of clinical alertness is required in patients with delirium, as an appropriate treatment of acute diseases should reduce their high mortality risk.

Underlying hemodynamic differences are associated with responses to tilt testing.

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01-1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11-1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17-1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38-1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result.

Management of ongoing direct anticoagulant treatment in patients with hip fracture.

Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p < 0.0001) and treatment within 48 h was 47% vs. 80% in control group (p < 0.0001). The adherence to guidelines' suggested time from last drug intake to surgery was 46%. Neither anticipation nor delay in surgery did result in increased mortality, length of stay or complication rates with the exception of larger perioperative blood loss (Hb levels < 8 g/dl) in DOACs patients (34% vs 9% p < 0.0001). Present results suggest that time to surgery is significantly longer in DOAC patients in comparison to controls and adherence to guidelines still limited.

Postoperative atrial fibrillation is related to a worse outcome in patients undergoing surgery for hip fracture.

Few information exist about incidence and prognostic significance of postoperative atrial fibrillation (POAF) in patients undergoing hip fracture surgery. In the period comprised between January 2012 and December 2016, we evaluated 3129 patients referred for hip fracture. At hospital admission 277 were in permanent atrial fibrillation and were excluded from the study. POAF was defined as symptomatic or asymptomatic AF of duration > 10 min occurring during hospitalization after hip surgery. In-hospital and 1-year outcomes of POAF patients were compared to that of an age- and sex-matched hip fracture control group. Survival rates were estimated by Kaplan-Meier curves and differences between groups compared by log-rank test. One hundred and four patients (mean age 83.7 years, men 27%) developed POAF (3.6%). Time of onset after surgery was on average 2 days after surgery. Eight POAF patients died during hospitalization. 81.7% were discharged in sinus rhythm. Patients with POAF had a longer time to surgery (3.8 ± 3.3 vs. 2.4 ± 1.6 days, p = 0.0007) and length of hospital stay (19.7 ± 10.4 vs. 14.4 ± 5.1 days p < 0.0001) in comparison to control group. Eight patients had AF recurrence during follow-up. 1-year mortality was significantly higher in POAF group in comparison to control group (39.3. vs 20.9%, p < 0.001). Postoperative atrial fibrillation in patients undergoing hip fracture surgery is associated with a longer length of hospital stay in comparison to patients who maintain stable sinus rhythm. Moreover, these patients had a significant higher mortality at 1-year follow-up.

Perioperative Myocardial Infarction/Myocardial Injury Is Associated with High Hospital Mortality in Elderly Patients Undergoing Hip Fracture Surgery.

Cardiovascular complications in patients undergoing non-cardiac surgery are associated with longer hospital stays and higher in-hospital mortality. The aim of this study was to assess the incidence of in-hospital myocardial infarction and/or myocardial injury in patients undergoing hip fracture surgery and their association with mortality. Moreover, we evaluated the prognostic value of troponin increase stratified on the basis of peak troponin value. The electronic records of 1970 consecutive hip fracture patients were reviewed. Patients <70 years, those with myocardial infarction <30 days, and those with sepsis or active cancer were excluded from the study. Troponin and ECG were obtained at admission and then at 12, 24, and 48 h after surgery. Echocardiography was made before and within 48 h after surgery. Myocardial injury was defined by peak troponin I levels > 99th percentile. A total of 1854 patients were included. An elevated troponin concentration was observed in 754 (40.7%) patients in the study population. Evidence of myocardial ischemia, fulfilling diagnosis of myocardial infarction, was found in 433 (57%). ECG and echo abnormalities were more frequent in patients with higher troponin values; however, mortality did not differ between patients with and without evidence of ischemia. Peak troponin was between 0.1 and 1 µg/L in 593 (30.3%). A total of 191 (10%) had peak troponin I ≥ 1 µg/L, and 98 died in hospital (5%). Mortality was significantly higher in both groups with troponin increase (HR = 1.37, 95% CI 1.1-1.7, p < 0.001 for peak troponin I between 0.1 and 1 µg/L; HR = 2.28, 95% CI 1.72-3.02, p < 0.0001 for peak troponin ≥1 µg/L) in comparison to patients without myocardial injury. Male gender, history of coronary heart disease, heart failure, and chronic kidney disease were also associated with in-hospital mortality. Myocardial injury/infarction is associated with increased mortality after hip fracture surgery. Elevated troponin values, but not ischemic changes, are related to early worse outcome.

Takotsubo Syndrome: Is this a Common Occurrence in Elderly Females after Hip Fracture?

BACKGROUND: The prevalence of Takotsubo syndrome in hip fracture is not known. METHODS: Hip fracture patients were evaluated in a multidisciplinary unit. Patients with ECG abnormalities and increased troponin I values at the time of hospital admission were included in the study Follow-up was clinical at 30 days and by telephonic interview at one year. RESULTS: Between October 1st 2011 to September 30th 2016, 51 of 1506 patients had preoperative evidence of myocardial damage. Eight, all females, fulfilled the Mayo criteria for Takotsubo syndrome, six had no coronary lesions. Hip surgery was uneventful, and all eight were alive at thirty days, and seven of these were still alive after one year. Forty-three patients had myocardial infarction: mortality at thirty days and one year were 11% and 44% (p<0.0001, Student's t-test; log-rank test). CONCLUSION: At least 15% of patients with hip fracture and preoperative myocardial damage had Takotsubo syndrome. They were all elderly females. Contrary to myocardial infarction, Takotsubo syndrome has a favourable long term prognosis.

Renal function and delirium in older fracture patients: different information from different formulas?

OBJECTIVES: the association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. AIM: to confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) METHODS: patients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. RESULTS: 571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30-60 ml/min/1.73 m2) and delirium remained significant in patients aged 75-84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. CONCLUSIONS: in older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75-84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

The "syncope and dementia" study: a prospective, observational, multicenter study of elderly patients with dementia and episodes of "suspected" transient loss of consciousness.

BACKGROUND AND AIM: Syncope and related falls are one of the main causes and the predominant cause of hospitalization in elderly patients with dementia. However, the diagnostic protocol for syncope is difficult to apply to patients with dementia. Thus, we developed a "simplified" protocol to be used in a prospective, observational, and multicenter study in elderly patients with dementia and transient loss of consciousness suspected for syncope or unexplained falls. Here, we describe the protocol, its feasibility and the characteristics of the patients enrolled in the study. METHODS: Patients aged ≥65 years with a diagnosis of dementia and one or more episodes of transient loss of consciousness during the previous 3 months, subsequently referred to a Geriatric Department in different regions of Italy, from February 2012 to May 2014, were enrolled. A simplified protocol was applied in all patients. Selected patients underwent a second-level evaluation. RESULTS: Three hundred and three patients were enrolled; 52.6% presented with episodes suspected to be syncope, 44.5% for unexplained fall and 2.9% both. Vascular dementia had been previously diagnosed in 53.6% of participants, Alzheimer's disease in 23.5% and mixed forms in 12.6%. Patients presented with high comorbidity (CIRS score = 3.6 ± 2), severe functional impairment, (BADL lost = 3 ± 2), and polypharmacy (6 ± 3 drugs). CONCLUSION: Elderly patients with dementia enrolled for suspected syncope and unexplained falls have high comorbidity and disability. The clinical presentation is often atypical and the presence of unexplained falls is particularly frequent.