Effect of Early Rehabilitation Using an Active/Passive Cycling Device on Muscle Wasting in the Critically Ill: A Randomised Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Ultrasound assessment of the medial head of gastrocnemius - change in fascicle pennation angle (degrees)
研究概览
简要总结
Muscle wasting is a common consequence of critical illness, and has a profound impact upon the rehabilitation of those who survive admission to critical to care. The investigators intend to assess if the application of 10 sessions over two weeks of passive cycling with electrical stimulation to the lower limbs and abdomen can prevent muscle loss, or at least cause less muscle loss, compared to patients who receive standard daily sessions of physiotherapy. This will be done by comparing the changes in muscle size on ultrasound between the two groups, comparing functional measures at a 3 month follow up, and by performing translational research using tissue samples taken during the study.
详细描述
Patients are mechanically ventilated and sedated with a diagnosis of sepsis (from any source) will be eligible for this study. Provided they meet the inclusion criteria, they will be randomised within 48 hours of admission, to either ten 30 minute sessions of passive cycling with functional electrical stimulation (FES) to the thighs, hamstrings, calves and abdomen over a 14 day period, or to a control group of routine physiotherapy. The trial group will also receive this physiotherapy.
On admission to the study, all patients will receive on day 1:
Ultrasound measurements of:
Rectus femoris cross-sectional area Thickness of rectus femoris and vastus intermedius Thickness, pennation angle and derived fascicle length of vastus lateralis and medial head of gastrocnemius Thickness of rectus abdominis. Thickness of diaphragm
A blood sample taken from an arterial line A urine sample taken from a urinary catheter A muscle biopsy taken from the right vastus lateralis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Ultrasound images will be labelled by their participant number, and not by intervention. Therefore, when image analysis takes place, the investigators will not know whether the images come from somebody who received cycling sessions or the control group.
Tissue samples will be treated in the same way.
In follow up sessions, participants will be asked not to reveal if they can remember whether they cycled or not.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be recruited in the Intensive Care Unit of the Royal Liverpool University Hospital. All patients will be over 18, and have a critical illness that requires mechanical ventilation with an initial period of sedation. This study will focus on patients with a definite or suspected case of sepsis from any source.
- •Sepsis has been recently redefined as: "Life threatening organ-dysfunction caused by dysregulated host response to infection" whilst septic shock has become a subset of sepsis, defined as: "circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality(44).
- •For the purposes of this study, a patient will be regarded as septic if they have evidence of infection-related organ failure (e.g. sepsis-associated coagulopathy, altered mental state, cardiovascular dysfunction, acute kidney injury, and altered liver function) and require invasive mechanical ventilation with either definite or suspected evidence of infection. This is to allow prompt treatment with FES rather than waiting for a positive microbiological result to be obtained.
- •Within the definition of sepsis "from any source" a list of following is illustrative but not exhaustive:
- •Urogenital sepsis (including urosepsis, pyelonephritis, endometritis and chorioamnionitis)
- •Pneumonia (including community acquired, hospital acquired, and aspiration pneumonia. Ventilator associated pneumonia would be excluded.)
- •Neurological infections such as encephalitis and meningitis.
- •Cellulitis, osteomyelitis and infections of soft tissue NOT affecting the lower limb.
- •Surgical infections, including post-operative laparotomy with evidence of peritoneal soiling, and evidence of infection prior to the operation, in patients who require 2 or more organ system support after the operation.
- •Intra-abdominal sepsis, including biliary sepsis, hepatitis, and acute pancreatitis. In the case of acute pancreatitis, evidence of infection is required to fulfil the criteria. Acute pancreatitis with sterile tissue/fluid samples would not be suitable.
排除标准
- •Patients under 18
- •Patients who decline consent
- •Pregnancy
- •Neuromuscular disease
- •Rhabdomyolysis
- •Lower limb trauma
- •Patients unlikely to survive to 96 hours post admission
- •Consent unobtainable within 48 hours of admission
- •Morbid obesity (BMI>40).
- •Presence of a pacemaker or Implantable Cardiac Defibrillator (ICD).
- •Unlikely to be mechanically ventilated for more than 48 hours.
结局指标
主要结局
Ultrasound assessment of the medial head of gastrocnemius - change in fascicle pennation angle (degrees)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of the pennation angle of the muscle fascicles as they insert into the deep aponeuroses of the medial head of gastrocnemius (angles)
Diaphragm thickness assessment by ultrasound - change in end inspiratory thickness (mm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Assessment of thickness at end inspiration (mm)
Ultrasound assessment of rectus femoris - Change in muscle layer thickness (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement on muscle layer thickness of rectus femoris (cm)
Ultrasound assessment of vastus lateralis - change in fascicle pennation angle (degrees)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of the pennation angle of the muscle fascicles as they insert into the deep aponeuroses of the vastus lateralis muscle (degrees)
Ultrasound assessment of the rectus abdominis muscle - change in muscle layer thickness (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of rectus abdominis muscle layer thickness - (cm)
Diaphragm thickness assessment by ultrasound - change in end expiratory thickness (mm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Assessment of thickness at end expiration (mm)
Ultrasound assessment of anterior thigh musculature - Change in muscle layer thickness (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of combined muscle layer thickness of rectus femoris and vastus intermedius (cm)
Ultrasound assessment of vastus lateralis - change in muscle layer thickness (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of the thickness of the vastus lateralis between the superficial and deep aponeuroses (cm)
Ultrasound assessment of rectus femoris - Change in cross sectional area (cm2)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of cross-sectional area of rectus femoris (cm2)
Ultrasound assessment of vastus lateralis - change in fascicle length (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
This is a single measure, derived by trigonometry (the Sine of the pennation angle multiplied by the muscle thickness).
Ultrasound assessment of the medial head of gastrocnemius - change in muscle thickness (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Measurement of the thickness of the medial head of the gastrocnemius between the superficial and deep aponeuroses (cm)
Ultrasound assessment of the medial head of gastrocnemius - change in fascicle length (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
This is single measure which is mathematically derived by trigonometry using the known pennation angle (degrees) and thickness (cm): the Sine of the pennation angle multiplied by the muscle thickness.
Diaphragm thickness assessment by ultrasound - change in thickening fraction (%)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Assessment of thickening fraction, derived mathematically from thicknesses at inspiration and expiration (%)
Ultrasound assessment of change in diaphragmatic excursion (cm)
时间窗: Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.
Assessment of maximal excursion of diaphragm, measured with M-mode ultrasonography (mm)
次要结局
- Follow up testing - Hand grip dynamometry (hand grip strength, Newtons)(At 3 month follow up)
- Follow up testing - Distance achieved in a 6 minute walk test, metres)(At 3 month follow up)
- Measurement of change in blood biomarkers (microRNA analysis for markers of muscle loss, expressed as a percentage fold increase/decrease compared to baseline).(Samples taken on days 1, 5, 10 and 14)
- Measurement of change in urinary biomarkers (microRNA analysis for markers of muscle loss, expressed as a percentage-fold increase/decrease compared to baseline).(Samples taken on days 1, 5, 10 and 14)
- Follow up testing - Psychological assessment - Comparison of total scores obtained from the SF-36 questionnaire (maximum score 100, minimum score zero).(At 3 month follow up)
- Incidence of renal replacement therapy during the trial period(Days 1-14)
- Total dose of noradrenaline given per day(Day 1-14)
- Overall fluid balance (in mls) at the end of each study day(Day 1-14)
- Total Insulin doses (in international units) required per day(Day 1-14)
- Blood glucose concentration (mmol/L)(Day 1-14)
- Safety - number of times an nasogastric tube is dislodged during the cycling sessions(Days 1 - 14 but only on the days where cycling takes place (ten sessions).)
- Measurement of the number of biomarkers expressed from muscle biopsies (microRNA analysis for markers of muscle loss, expressed as the number and type of micro-RNAs expressed within the samples).(Samples taken on day 1 and 14)
- Measurement of muscle fibre cross sectional area from muscle biopsies (mm2)(Samples taken on day 1 and 14)
- Follow up - Lower limb strength assessment - Force generated at maximal contraction for knee extension (Newtons)(At 3 month follow up)
- Follow up testing - Balance assessment - Comparison of changes in center of pressure on a pressure plate.(At 3 month follow up)
- Follow Up - Maximal Inspiratory Pressure monitoring in kilopascals (kPa)(At 3 month follow up)
- Incidence of delirium during the trial period - using the CAM-ICU tool.(Days 1-14)
- Heart rate variability(Days 1 - 14 but only on the days where cycling takes place (ten sessions))
- Safety - number of times an endotracheal/tracheostomy tube is dislodged during the cycling sessions(Days 1 - 14 but only on the days where cycling takes place (ten sessions))
- Safety - number of times an a central or arterial line device is dislodged during the cycling sessions(Days 1 - 14 but only on the days where cycling takes place (ten sessions).)
研究者
Ingeborg Welters
Senior Lecturer, Institute of Aging and Chronic Disease
University of Liverpool