The efficacy of continuous-flow cryo and cyclic compression therapy after hip fracture surgery on postoperative pain: design of a prospective, open-label, parallel, multicenter, randomized controlled, clinical trial.

BACKGROUND: The number of hip fractures and resulting post-surgical outcome are a major public health concern and the incidence is expected to increase significantly. The acute recovery phase after hip fracture surgery in elder patients is often complicated by severe pain, high morphine consumption, perioperative blood loss with subsequent transfusion and delirium. Postoperative continuous-flow cryocompression therapy is suggested to minimize these complications and to attenuate the inflammatory reaction that the traumatic fracture and subsequent surgical trauma encompass. Based on a pilot study in patients undergoing total hip arthroplasty for osteoarthritis, it is anticipated that patients treated with continuous-flow cryocompression therapy will have less pain, less morphine consumption and lower decrease of postoperative hemoglobin levels. These factors are associated with a shorter hospital stay and better long-term (functional) outcome. METHODS/DESIGN: One hundred and sixty patients with an intra or extracapsular hip fracture scheduled for internal fixation (intramedullary hip nail, dynamic hip screw or cannulated screws) or prosthesis surgery (total hip or hemiarthroplasty) will be included in this prospective, open-label, parallel, multicenter, randomized controlled, clinical superiority trial. Patients will be allocated to two treatment arms: group 'A' will be treated with continuous-flow cryocompression therapy and compared to group 'B' that will receive standard care. Routine use of drains and/or compressive bandages is allowed in both groups. The primary objective of this study is to compare acute pain the first 72 h postoperative, measured with numeric rating scale for pain. Secondary objectives are: (non-) morphine analgesic use; adjusted postoperative hemoglobin level; transfusion incidence; incidence, duration and severity of delirium and use of psychotropic medication; length of stay; location and duration of rehabilitation; functional outcome; short-term patient-reported health outcome; general and cryotherapy related complications and feasibility. DISCUSSION: This is the first randomized controlled trial that will assess the analgesic efficiacy of continuous-flow cryocompression therapy in the acute recovery phase after hip fracture surgery. TRIAL REGISTRATION: www.trialregister.nl, NTR4152 (23(rd) of August 2013).

Continuous-flow cryocompression therapy penetrates to bone level in hip fracture patients in a numerical simulation.

BACKGROUND: The aim of this study was to define deep tissue temperature during cryotherapy in postoperative hip fracture patients, by using measured skin temperature as input parameter for a simple numerical model. Second, an association was investigated between pain and tissue temperature distribution, to assess cryotherapy-induced analgesia of soft tissue-derived pain. METHODS: Data from 35 participants in an ongoing trial was used. In three subjects who consented on optional measurements, skin temperature was measured in 3 days during and after cryotherapy. A simple numerical model was developed to calculate tissue temperature distribution during cryotherapy. RESULTS: Inter and intrasubject skin temperature displayed high variation: trochanter 11-27 °C, mid-femur 11-24 °C, distal femur 10-16 °C. Predicted temperatures decreased to 20 °C at 1 cm, 26 °C at 2 cm, and 30 °C at 3 cm tissue depth. Smallest soft tissue layer was measured at the trochanter; 42% had less than 30 mm and 21% had less than 20 mm. Numeric rating scale pain varied (mean = 2.14; SD = 1.92), and no association was found between pain and decrease in temperature (r = 0.064; p = 0.204). CONCLUSIONS: Cryotherapy was predicted to reduce temperature up to 3 cm; in cachectic patients, this reaches the bone, where it might have implications for bone tissue healing when treated for a prolonged period of time. Cryotherapy-induced analgesia is likely to originate from skin analgesia rather than analgesia of muscle or bone-derived pain.

Hypothermia reduces VEGF-165 expression, but not osteogenic differentiation of human adipose stem cells under hypoxia.

Cryotherapy is successfully used in the clinic to reduce pain and inflammation after musculoskeletal damage, and might prevent secondary tissue damage under the prevalent hypoxic conditions. Whether cryotherapy reduces mesenchymal stem cell (MSC) number and differentiation under hypoxic conditions, causing impaired callus formation is unknown. We aimed to determine whether hypothermia modulates proliferation, apoptosis, nitric oxide production, VEGF gene and protein expression, and osteogenic/chondrogenic differentiation of human MSCs under hypoxia. Human adipose MSCs were cultured under hypoxia (37°C, 1% O2), hypothermia and hypoxia (30°C, 1% O2), or control conditions (37°C, 20% O2). Total DNA, protein, nitric oxide production, alkaline phosphatase activity, gene expression, and VEGF protein concentration were measured up to day 8. Hypoxia enhanced KI67 expression at day 4. The combination of hypothermia and hypoxia further enhanced KI67 gene expression compared to hypoxia alone, but was unable to prevent the 1.2-fold reduction in DNA amount caused by hypoxia at day 4. Addition of hypothermia to hypoxic cells did not alter the effect of hypoxia alone on BAX-to-BCL-2 ratio, alkaline phosphatase activity, gene expression of SOX9, COL1, or osteocalcin, or nitric oxide production. Hypothermia decreased the stimulating effect of hypoxia on VEGF-165 gene expression by 6-fold at day 4 and by 2-fold at day 8. Hypothermia also decreased VEGF protein expression under hypoxia by 2.9-fold at day 8. In conclusion, hypothermia decreased VEGF-165 gene and protein expression, but did not affect differentiation, or apoptosis of MSCs cultured under hypoxia. These in vitro results implicate that hypothermia treatment in vivo, applied to alleviate pain and inflammation, is not likely to harm early stages of callus formation.

Postoperative continuous-flow cryocompression therapy in the acute recovery phase of hip fracture surgery-A randomized controlled clinical trial.

BACKGROUND: The acute recovery phase after hip fracture surgery is often complicated by severe pain, postoperative blood loss with subsequent transfusion, and delirium. Prevalent comorbidity in hip fracture patients limit the use of opioid-based analgesic therapies, yielding a high risk for inferior pain treatment. Postoperative cryotherapy is suggested to provide an analgesic effect, and to reduce postoperative blood loss. In this prospective, open-label, parallel, multicentre, randomized controlled, clinical trial, we aimed to determine the efficacy of continuous-flow cryocompression therapy (CFCT) in the acute recovery phase after hip fracture surgery. METHODS: Patients with an intra or extracapsular hip fracture scheduled for surgery were included. Subjects were allocated to receive postoperative CFCT or usual care. The primary endpoint was numeric rating scale (NRS) pain the first 72 postoperative hours. Secondly, analgesic use; postoperative haemoglobin change and transfusion incidence; functional outcome; length of stay; delirium incidence; location of rehabilitation; patient-reported health outcome; complications and feasibility were assessed. RESULTS: Sixty-one subjects in the control group, and 64 subjects in the CFCT group were analysed. Within the CFCT group, post treatment NRS pain declined 0.31 (p=0.07) at 24h, 0.28 (p=0.07) at 48h, and 0.47 (p=0.002) at 72h relative to pre treatment NRS pain. Sensitivity analysis at 72h showed that NRS pain was 0.92 lower in the CFCT group when compared to the control group (1.50 vs. 2.42; p=0.03). Postoperative analgesic use was comparable between groups. Between postoperative day one and three haemoglobin declined 0.29mmol/l in the CFCT group and 0.51mmol/l in controls (p=0.06), and transfusion incidence was comparable. The timed up and go test and length of stay were also comparable between both groups. Complications, amongst delirium and cryotherapy-related adverse events were not statistically significantly different. Discharge locations did not differ between groups. At outpatient follow-up subjects did not differ in patient-reported health outcome scores. Subjects rated CFCT satisfaction with an average of 7.1 out of 10 points. CONCLUSIONS: No evidence was recorded to suggest that CFCT has an added value in the acute recovery phase after hip fracture surgery. If patients complete the CFCT treatment schedule, a mild analgesic effect is observed at 72h.

Cryocompression therapy after elective arthroplasty of the hip.

Pneumatic compression and cryotherapy have been successfully being employed in the management of acute tissue damage. The Game Ready System (GRS) combines cyclic compression and cryotherapy. No randomised controlled trial has been performed on the effects of combined cyclic compression and cryotherapy in total hip arthroplasty (THA). We observed postoperative pain, morphine usage, blood loss, wound discharge, patient and medical staff satisfaction, together with the feasibility of a cryocompression machine, total hospital admission time, infection rate, deep vein thrombosis, and short-term prosthesis related problems in this context. Thirty patients, mean age 68 yrs (range 31-83 yrs) undergoing elective hip arthroplasty for end-stage osteoarthritis were included. Control patients (n = 15) received a tricot compression bandage alone, and patients studied received a tricot compression bandage plus intermittent cryocompression therapy 15 times for 30 minutes. Haemoglobin levels on postoperative day (POD) 1 dropped 2.34 mmol/L in the control group and 1,87 mmol/L in the intervention group (p = 0,027). At POD 3 haemoglobin levels were reduced by 2,63 and 2,16 respectively (p = 0,646). A trend occurred towards lower morphine usage, shorter hospital admission time and less wound discharge in the study group. No difference was found in postoperative pain scores. One event of deep venous thrombosis occurred in the control group. Intermittent cryocompression therefore appears to reduce postoperative blood loss. A trend towards less analgesic use, shorter hospital stay, less wound discharge and less pain at 6 weeks postoperatively was also observed.