Risk factors for onset of delirium after neck of femur fracture surgery: a prospective observational study

Tahir, Mohd Faizal Mat; Malik, Shahbaz S.; Ahmed, Usman; Kozdryk, Jakub; Naqvi, Syeda; Malik, Arshi

doi:10.1051/sicotj/2018018

Cited by 20 publications

(35 citation statements)

References 22 publications

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“…Although dementia status is a major risk factor for delirium (Davis et al, 2015), the changes in lactate and LGR observed are not explained by existing dementia. The data are consistent with previously demonstrated associations between delirium and increased CSF lactate (Caplan et al, 2010) and hypoxia (Tahir et al, 2018).…”

Section: Acute Cognitive Dysfunction and Deliriumsupporting

confidence: 92%

Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium

et al. 2020

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Systemic infection triggers a spectrum of metabolic and behavioral changes, collectively termed sickness behavior, which while adaptive, can affect mood and cognition. In vulnerable individuals, acute illness can also produce profound, maladaptive, cognitive dysfunction including delirium, but our understanding of delirium pathophysiology remains limited. Here, we used bacterial lipopolysaccharide (LPS) in female C57BL/6J mice and acute hip fracture in humans to address whether disrupted energy metabolism contributes to inflammation-induced behavioral and cognitive changes. LPS (250 mg/kg) induced hypoglycemia, which was mimicked by interleukin (IL)-1b (25 mg/kg) but not prevented in IL-1RI 2/2 mice, nor by IL-1 receptor antagonist (IL-1RA; 10 mg/kg). LPS suppression of locomotor activity correlated with blood glucose concentrations, was mitigated by exogenous glucose (2 g/kg), and was exacerbated by 2-deoxyglucose (2-DG) glycolytic inhibition, despite preventing IL-1b synthesis. Using the ME7 model of chronic neurodegeneration in female mice, to examine vulnerability of the diseased brain to acute stressors, we showed that LPS (100 mg/kg) produced acute cognitive dysfunction, selectively in those animals. These acute cognitive impairments were mimicked by insulin (11.5 IU/kg) and mitigated by glucose, demonstrating that acutely reduced glucose metabolism impairs cognition selectively in the vulnerable brain. To test whether these acute changes might predict altered carbohydrate metabolism during delirium, we assessed glycolytic metabolite levels in CSF in humans during inflammatory trauma-induced delirium. Hip fracture patients showed elevated CSF lactate and pyruvate during delirium, consistent with acutely altered brain energy metabolism. Collectively, the data suggest that disruption of energy metabolism drives behavioral and cognitive consequences of acute systemic inflammation.

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Section: Acute Cognitive Dysfunction and Deliriumsupporting

confidence: 92%

Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium

et al. 2020

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“…S3). The data are consistent with previously reported increases in CSF lactate in patients with delirium (43) and with the observation that hypoxia is a risk factor for developing delirium (88,89). Taken collectively, there are several reasons to now focus attention on energy metabolism in delirium.…”

Section: Acute Cognitive Dysfunction and Deliriumsupporting

confidence: 91%

Acute inflammation alters energy metabolism in mice and humans: Role in sickness-induced hypoactivity, impaired cognition and delirium

Kealy

Murray

et al. 2019

Preprint

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Systemic infection can result in a spectrum of metabolic and behavioral changes, termed sickness behavior, an organismal reprioritization that suppresses activity, conserves energy, and maximizes the probability of recovery. In vulnerable individuals, acute sickness can include profound acute cognitive impairments including delirium. The molecular mechanisms driving the acute suppression of activity and the acute cognitive deficits arising remain unclear. Here, we hypothesized that disruption of energy metabolism during acute inflammation is a significant contributor to behavioral changes after bacterial endotoxin in mice, and to delirium after inflammatory trauma. LPS (250 µg/kg) and IL-1b (25 µg/kg) markedly decreased blood glucose in c57BL6J mice. LPS-induced decreases in glucose still occurred in IL-1R1 -/mice and in animals treated with IL-1RA (100 µg/kg). Locomotor activity correlated with blood glucose concentration and treatment with glucose (2 g/kg) prevented the suppression of spontaneous activity. Inhibition of glycolysis using 2-deoxyglucose completely suppressed locomotor activity despite preventing IL-1b synthesis. Selectively in ME7 animals with chronic hippocampal and thalamic synaptic loss, LPS (100 µg/kg) produced robust cognitive dysfunction and this could be mimicked with insulin and significantly mitigated with glucose treatment, demonstrating that reduced glucose levels are a major driver cognitive impairment in the vulnerable brain. Analysis of glycolytic metabolites in human CSF from hip fracture patients showed that there is also a significant alteration of brain energy metabolism (elevated lactate and pyruvate) during delirium. Collectively the data suggest that behavioral impacts of acute systemic inflammation are strongly influenced by disruption of energy metabolism. Introduction:Systemic infection can result in a spectrum of metabolic and behavioral changes, termed sickness behavior, which includes fever, lethargy, loss of appetite, anhedonia, and impairments in cognitive function (1). Sickness behavior is an evolutionarily conserved response to illness and is thought to represent a reprioritization by the organism to conserve energy and maximize the probability of recovery (2). Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS), can induce sickness behavior in humans (3, 4) and rodents (1, 5) and although peripheral LPS does not readily cross the blood-brain barrier (6) it significantly increases systemic and central pro-inflammatory cytokines including interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-a) (1,7,8) and can alter resting state networks (9) and local field potential (10, 11). Therefore information about the inflammatory status of the periphery is communicated to the brain and this occurs by multiple routes: i) direct neural activation of the brainstem and hypothalamus via sensory afferents such as the vagus nerve; ii) activation of macrophages of the circumventricular organs that lack a patent BBB, leading to sec...

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“…Perioperative delirium affects approximately one-third of patients with hip fractures 4 and has been associated with longer inpatient stays and higher 1-year mortality rates. 5 Hip fracture patients with prediagnosed dementia have been shown to be significantly more likely to develop delirium postoperatively. 5 Thus, in 2012, the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines stated that one should "Assess patient's risk of delirium or dementia by actively looking for cognitive impairment when patients first present with hip fracture and perform regular reassessment."…”

Section: Introductionmentioning

confidence: 99%

“…5 Hip fracture patients with prediagnosed dementia have been shown to be significantly more likely to develop delirium postoperatively. 5 Thus, in 2012, the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines stated that one should "Assess patient's risk of delirium or dementia by actively looking for cognitive impairment when patients first present with hip fracture and perform regular reassessment." 6 More recently, the British Orthopaedic Association extended their guidelines beyond hip fractures, stating that all elderly or frail orthopedic trauma patients should routinely be assessed using a validated delirium assessment tool such as the 4AT.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Odor et al compared the impact of regional anesthesia on preand postoperative AMTS, 15 and Tahir et al used the AMTS on admission to assess baseline cognitive function when screening for postoperative delirium. 5 Thus, it has been suggested that, due to its brevity and sensitivity, the AMTS is a very useful screening test for elderly trauma patients to assess for impaired cognition of any cause. 16 Research has shown that while many orthopedic junior doctors are aware of the importance of the use of the AMTS, only a small proportion (approximately 10%) can identify all 10 questions involved.…”

Section: Introductionmentioning

confidence: 99%

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Improving Identification of Cognitive Impairment in Fragility Fracture Patients: Impact of Educational Guidelines on Current Practice

Kennedy¹,

Mohandas²,

Anderson³

et al. 2020

Geriatr Orthop Surg Rehabil

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Introduction: Cognitive impairment can hinder a fracture patient’s capacity to consent to surgery and negatively impact their postoperative recovery and rehabilitation. National guidelines recommend screening for cognitive impairment upon admission, and the Abbreviated Mental Test Score (AMTS) is a commonly used tool for this. This project aimed to assess current practice regarding documentation of AMTS among frail fracture patients upon admission and to improve AMTS documentation following a simple intervention. Methods: Baseline data were obtained by inpatient chart review throughout November to December 2018 in a district general hospital with emergency fracture services. All patients admitted with a fragility hip fracture and patients over 65 years with any fracture were included. National guidelines and baseline results were then distributed among junior doctors. Following an intervention, further data were collected throughout January to February 2019. Results: Preintervention, 40 suitable patients (mean age: 82 years) were identified; 9 (22.0%) of whom had an AMTS recorded upon admission. Among the hip fracture subgroup (n = 25), 7 (26.9%) had an AMTS recorded. Postintervention, 39 patients (mean age: 80 years) were identified; 15 (38.5%) of whom had an AMTS recorded. Among the hip fracture subgroup (n = 30), 11 (36.7%) had an AMTS recorded. Statistical analysis demonstrated a significant improvement in AMTS documentation both among the overall cohort ( P = .001) and hip fracture patients ( P = .019). No significant association was found between AMTS documentation and patient age ( P = .566), grade of admitting doctor ( P = .058), or prior cognitive/mental health disorder ( P = .256). Discussion: A small yet significant improvement in AMTS documentation among elderly/hip fracture patients was observed following distribution of educational material. Further work should explore the effect of cognitive impairment on outcomes related to orthopedic injuries beyond hip fractures.

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Risk factors for onset of delirium after neck of femur fracture surgery: a prospective observational study

Cited by 20 publications

References 22 publications

Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium

Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium

Acute inflammation alters energy metabolism in mice and humans: Role in sickness-induced hypoactivity, impaired cognition and delirium

Improving Identification of Cognitive Impairment in Fragility Fracture Patients: Impact of Educational Guidelines on Current Practice

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