Chlorzoxazone in Hip and Knee Arthroplasty
Chlorzoxazone in Hip and Knee Arthroplasty
The purpose of this study is to elucidate whether patients operated with THA and TKA can
 benefit from treatment with chlorzoxazone.
Introduction and rationale Background Modern treatment of pain following surgery based on
 multimodal analgesic strategy where the pain system different points of attack struck with
 different types analgesics. This also tries to reduce the consumption of opioids associated
 with frequent side effects like nausea, vomiting, constipation, difficulty urinating, weather
 stretch problems and Lethargy.

 But in spite of intense research over the last decades, is pain after arthroplastic surgery
 in hip (total hip arthroplasty (THA)) or knee (total knee replacement (TKA)) continue a
 significant clinical problem. It is a current clinical assumption that patients with pain in
 the hip or knee region immediately after TKA or THA have tense muscles, which reinforces pain
 behavior. The mechanism for such muscle tension is not fully understood.

 For many years the investigators have been on Danish orthopedic departments dealt with these
 patients with postoperative pain after major joint prosthesis operations with the muscle
 relaxant chlorzoxazone. On some sections included in the standard chlorzoxazone prescriptions
 for pain after hip and knee replacement.

 chlorzoxazone has for many years been marketed for the treatment of pain in skeletal muscle
 by inhibition of mono- and polysynaptic reflexes in the CNS. The muscle relaxing effect is
 mediated by inhibitory effects on spinal polysynaptic reflexes. In placebo-designed clinical
 studies of chlorzoxazone's beneficial effect on heterogeneous groups of patients with
 spasticity, motor neuron syndromes, as well as muscle pain and spasm of peripheral
 musculoskeletal diseases have not been able to demonstrate no significant analgesic effect;
 chlorzoxazone have also failed to show pain-relieving effect in the treatment of back pain It
 is remarkable that in spite of the widespread use of chlorzoxazone not can be found only one
 study of chlorzoxazone used as adjuvant pain relieving treatment after hip or knee surgery
 (or other orthopaedic treatment). The current clinical practice is therefore made on purely
 empirical basis. The effect must be considered as uncertain, but may in some cases be
 indicated, most often as an adjunct to other therapy, for example analgesics,
 anti-inflammatory agents, physiotherapy or even training. In such cases, regarded
 chlorzoxazone be an alternative to benzodiazepines. There is therefore a need for a
 prospective, randomized, double-blind, placebo-controlled study evaluating the potential
 analgesic effect of chlorzoxazone. In this intervention study is the selected dosage of
 chlorzoxazone set at based on the recommendation of the Danish Medicines Information A / S 7
 (http://pro.medicin.dk/Medicine / Preparations / 638) and Takeda Pharma A / S. The latter
 produces chlorzoxazone. The recommendation is based on our current knowledge of
 chlorzoxazones pharmacodynamic and pharmacokinetic properties. chlorzoxazone given in this
 study as tablet chlorzoxazone, 250 mg, 3 times daily for the first seven postoperative days.
 Adverse reactions to chlorzoxazone are well known. They are relatively few, mostly mild and
 transient. The most frequent adverse events related to chlorzoxazone, fatigue and dizziness
 (about 1-10% of patients) Adverse reactions are to some extent overlapping with the side
 effects that are related to the perioperative opioid treatment. It is therefore possible that
 the frequency of adverse events overall is reduced if chlorzoxazone found to be analgesic
 (and opioid-sparing). Patients will be hospitalized for a minimum of two nights after surgery
 and thus be close observation in the period in which the risk of side effects is greatest. At
 the same time, all patients undergo standardized adverse event registration. If, contrary to
 expectations unexpected or unacceptable side effects medication will promptly be interrupted.
 The study involves a group of patients (THA and TKA), which is an important clinical pain
 problem. All of these patients receive a well-implemented and evidence-based treatment. Thus,
 anesthesia, analgesia and surgical procedure standardized for all patients receiving
 concomitant consequences usual principles of early mobilization 8; 9th The planned
 randomized, double-blind, placebo-controlled design in which all patients receive the same
 and standardized interventions, enabling the best possible evaluation of modality under study
 intervention with chlorzoxazone vs. placebo). The level of pain after surgery as the primary
 endpoint, recorded by means of a well-tested and validated tool (visual analog scale (VAS))
 48 hours after operation. The current study could contribute to a clarification of the
 postoperative analgesic effect of chlorzoxazone immediately after THA and TKA. As secondary
 endpoints, the patients functional level be determined Oxford Hip / Knee Score 7 days after
 surgery. Furthermore, a number of tertiary parameters related to pain, function and side
 effect profile be determined as shown in Table 1. Evidence in this area will be of immediate
 benefit to patients operated with THA and TKA - and maybe for other surgical patients.
Inclusion Criteria:

 -  Planned primary unilateral THA or TKA

 -  Patients (male/female) ≥ 18 år

 -  Patients giving written informed consent and authority.

 -  Patients receiving spinal anaesthesia

 Exclusion Criteria:

 -  Patients with intolerance to trial medications

 -  Rejection of or contraindicated spinal anaesthesia

 -  Patients with rheumatoid arthritis.

 -  Patients with Body Mass Index (BMI) ≥ 35

 -  Patients that do not read or write Danish