Delirium in Elderly Patients With Trauma of the Hip

Study Overview
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Brief Summary
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A broken hip occurs frequently in elderly patients and is often very painful. Side effects of inadequately treated pain as well as the traditional drugs (administered through intravenous catheter) used to treat pain are, among others, a confusional state, called delirium. When pain medication is administered locally, only around the hip joint, pain might be treated more effectively and these side effects could be prevented. This is called a nerve block. The current study evaluates the use of a continuous nerve block throughout the complete hospital admission with a catheter around the hip joint versus the use of traditionally used pain medication administered though an intravenous catheter in elderly patients with a broken hip. Half of all patients will receive the nerve block while in the emergency department and the other half will receive pain medication through the intravenous access.

Detailed Description
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BACKGROUND Hip fractures occur frequently and are usually very painful. Pain itself is an indicator for increased risk of complications. A significant complication is delirium, occurring in up to 25% of all elderly patients with hip fractures. For a large proportion, triggers for development of delirium reaches back to the preoperative phase, where polypharmacy (including opioid use) and inadequately treated pain are major risk factors. Delirium is associated with negative health consequences, increased hospital stay, falls, higher mortality, decreased physical and cognitive function, re-hospitalization, increased risk of dementia and increased societal costs. Therefore, pain should be optimally treated as soon as possible, however the elderly patient poses a challenge in good pain treatment, because of physiological age-related changes, different drug effects, distribution, metabolism and elimination. Opioids frequently lead to respiratory depression, hypotension, nausea/vomiting and sedation in this vulnerable patient group. As a consequence, these drugs are often under dosed and pain treated insufficiently. Besides, drugs as opioids and NSAIDs have been associated with an increased delirium risk. A nerve block could alleviate these clinical issues. An example of a nerve block frequently utilized in the Emergency Department (ED) is a Fascia Iliaca Compartment Block (FICB), in which local anesthetics are injected underneath the pelvic iliac fascia in order to block femoral, obturator and lateral cutaneous nerves to provide anesthesia of hip, thigh and knee. Case-series and historically controlled cohort studies show a single-shot FICB is a rapid, safe and easy procedure providing excellent analgesia, decreased opioid need and little risk of complications. Delirium as outcome was reported in one RCT; a decreased delirium incidence after using repetitive, blind, single-shot FICBs (not in the acute setting) with pethidine (with increased intrinsic risk of developing delirium) as comparison. In order to prevent the need for repetitive insertions, leaving a catheter would create a route in order to provide continuous analgesia with local anesthetics. Two case series describe this continuous FICB in hip fractures and reported good pain control and decreased length of hospital stay without any infectious complications. No comparison studies have been done with a continuous FICB. The objective of the current study is to investigate whether the use of a continuous FICB, started early (in the ED) and continued throughout the complete clinical course of a hip fracture, will decrease occurrence of delirium in elderly patients with hip fractures. METHODS This study is designed as a prospective, open, multi-center, randomized interventional trial. Patients will be allocated to continuous FICB or care as usual (according to national guidelines) in a 1:1 ratio and followed up until three months after hospital discharge. SAMPLE SIZE AND DATA ANALYSIS The primary outcome (occurrence of delirium) is expected to be distributed normally. Although evidence to prevent delirium is scarce, an absolute reduction of 13% incidence has been reported previously after an intervention. The estimated delirium incidence according to literature is 25%. The hypothesis is that by using a continuous FICB administered very early in the clinical course in the ED, the incidence can be decreased from 25 to 12%. Superiority of the FICB versus usual care will be tested using the Chi Square Test. In order to detect a clinically relevant between-group-difference of 13% decrease in incidence, a significance level of 0.05 and 80% power will be used. For this analysis, each group will have 154 patients. When accounting for 10% loss to follow-up after three months, a total study population of 340 will be needed. The primary analysis will be based on the intention to treat principle. Per protocol analysis will be performed to check robustness of results. Baseline characteristics will be presented using descriptive statistics. Ordinal data will be analyzed using Chi Square Test or Fisher exact test. Continuous data will be assessed by a Student's t-test if normally distributed or Mann Whitney U test if otherwise. Missing data will be corrected by multiple imputation. An economic evaluation will be performed focusing on possible gained benefits of pain management with a continuous FICB compared to care as usual and the related health care costs. The economic evaluation will be performed from a societal perspective with a time horizon of three months and capturing the value of all resources utilized. The economic evaluation will be set up as a Cost-Effectiveness Analysis (CEA). Besides a CEA, a Budget Impact Analysis (BIA) will be performed according to the ISPOR Task Force principles.

Official Title
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A Multicenter Randomized Controlled Trial in Elderly Patients With Hip Fractures Comparing Continuous Fascia Iliaca Compartment Block to Systemic Opioids and Its Effect on Delirium Occurrence

Conditions
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Hip Fractures, Anesthesia

Intervention / Treatment
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* Drug: Bupivacaine
* Drug: Acetaminophen
* Drug: Diclofenac
* Drug: Ibuprofen
* Drug: Naproxen
* Drug: Dipyrone
* Drug: Fentanyl
* Drug: Morphine
* Drug: Levobupivacaine
* Drug: Ropivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients aged ≥ 55 years with a radiographically confirmed hip fracture Exclusion Criteria: multiple injuries (polytrauma patients) previous adverse reaction or known allergy to local anaesthetics or opioids or paracetamol skin infection in proximity of injection site delirious state at presentation in the ED

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous FICB with local anesthetics<br>With ultrasound guidance, a Fascia Iliaca Compartment Block will be administered and a catheter left in the compartment underneath the iliac fascia. This catheter will remain in place until two days after surgery. Initial pain treatment in the Emergency Department will be with 40 mL bupivacaine 0.25% or equipotent dosages of levobupivacaine or ropivacaine. Thereafter, until removal of the catheter, pain is treated by titrating local anesthetics according to pain scores. | Drug: Bupivacaine<br>* Local anesthetic: amide group ATC code N01BB01<br>* Other names: Marcaine;Drug: Levobupivacaine<br>* Local anesthetic: amide group ATC code N01BB10<br>* Other names: Chirocaine;Drug: Ropivacaine<br>* Local anesthetic: amide group ATC code N01BB09<br>* Other names: Naropin;|
| Active Comparator: Traditional care with systemic analgesia<br>Traditional care (usual care) will be on the discretion of the treating physician or hospital protocols and will comprise of systemic opioids such as fentanyl or morphine. Usually, these opioids are combined with several other drugs, such as: paracetamol, NSAIDs (diclofenac or ibuprofen or naproxen) or dipyrone. (Inter)national guidelines advice morphine as first line agent in elderly patients with hip fractures, as longer acting analgesics are usually required. | Drug: Acetaminophen<br>* Analgesic drug: Acetanilide derivate with analgetic and antipyretic properties ATC code N02BE01<br>* Other names: Paracetamol;Drug: Diclofenac<br>* Non-Steroidal Anti-Inflammatory Drug: Acetic acid derivative ATC code M01AB05 Usual dosage is 50 mg t.i.d. orally or 75 mg b.i.d. intramuscularly. In the Netherlands, intravenous administration is not used.<br>Drug: Ibuprofen<br>* Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE01 Usual dosage is 400 mg t.i.d. or q.i.d. orally.<br>Drug: Naproxen<br>* Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE02 Usual dosage is initially 500 mg orally, followed by 250 mg b.i.d. or t.i.d.<br>Drug: Dipyrone<br>* Analgesic drug: Pyrazolone derivate with analgetic, antipyretic and antiphlogistic properties ATC N02BB02 Usual dosage is 1000 mg t.i.d. or q.i.d. orally and intravenously<br>* Other names: Metamizole, Novalgin;Drug: Fentanyl<br>* Opioids: Phenylpiperidine derivative. Short-acting opioid. ATC code N02AB03 Usual dosage is 1 ug/kg intravenously and titrated guided by pain scores and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.<br>Drug: Morphine<br>* Opioids: Natural opium alkaloid. Longer-acting opioid. ATC code N02AA01 Usual dosage is 0.1 mg intravenously and titrated guided by pain and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of delirium | Diagnosis will be based on DSM-IV criteria. During hospital admission screening is actively. After discharge, information is gathered by contacting patients and family members, general practitioners or nursing facilities | three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of delirium | duration is defined as the total number of days with delirium. | three months | 
| severity of delirium | severity is defined as percentage of patients with delirium duration > 2 days. | three months | 
| NRS pain scores | NRS pain scores during complete hospital stay, NRS pain scores will be recorded in the Emergency Department before the intervention as well as after the intervention at 30-minutes time intervals (this is according standard protocol in case opioids are administered). During hospital stay, during each nursing shift, a minimum of one NRS pain score is documented. | from hospital admission until 48 hours after surgery | 
| need for additional analgesia | need for rescue analgesia will be documented during complete Emergency Department and hospital stay. | hospital admission until 48 hours after surgery | 
| patient satisfaction | satisfaction of patients and health care staff regarding efficacy of pain treatment and method of pain treatment is recorded in the Emergency Department and daily during hospital admission (5-point Likert scales and reference questions). | from hospital admission until 48 hours after surgery | 
| length of hospital stay | defined as total consecutive days admitted in the hospital. | from hospital admission until discharge; an average of 9 days | 
| ICU admission | binary endpoint, whether patient is admitted to the ICU at any moment during hospital stay. | from hospital admission until discharge; an average of 9 days | 
| ICU length of stay | defined as total days admitted to the ICU department. | from hospital admission until discharge; an average of 9 days | 
| hospital re-admission rate | a re-admission occurs when a patient is admitted to the hospital within three months after initial discharge (from hip fracture related admission). | three months | 
| medical complications | all events regarding infections, renal- or pulmonary function and cardiovascular events will be accounted for. | three months | 
| surgical complications | defined as dislocations and fractures. | three months | 
| mortality | all cause in-hospital-mortality and mortality after hospital discharge. | three months | 
| activities of daily living | 15-item modified Katz Index of Activities of Daily Living at three months after discharge. Baseline will be 2 weeks before presentation. | three months | 
| generic quality of life | generic HRQol (Euroqol - EQ-5D-5L) at three months after discharge. Baseline will be 2 weeks before presentation. | three months | 
| Oxford hip score | Oxford Hip Score after 3 months. | three months | 
| cognitive function with Mini Mental State Examination | Mini Mental State Examination at inclusion in the study, at hospital discharge and at three months after discharge. | three months | 
| cost effectiveness analysis | primary focus on direct medical costs, direct non-medical costs, indirect costs and productivity loss. | three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nerve block, Analgesia