Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery—a pilot study

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E2 (PGE2) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs(O–24h)] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2–7%). Individual CSF lag times with respect to (50%) peak plasma concentration were ≤2 h in all but one case (median: 1 h). PGE2 production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE2 production at the presumed site of action

Celecoxib does not appear to affect prosthesis fixation in total knee replacement: A randomized study using radiostereometry in 50 patients

Background and purpose After joint replacement, a repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration—and with time, loosening. Cox-2 inhibitors are widely used as postoperative analgesics, and have adverse effects on bone healing. This could tamper prosthesis fixation. We investigated whether celecoxib, a selective Cox-2 inhibitor, increases prosthesis migration in total knee replacement (TKR)

Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction.</p> <p>Methods</p> <p>One hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle.</p> <p>Results</p> <p>Among 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups.</p> <p>Conclusions</p> <p>Etoricoxib is more effective than celecoxib and placebo for using as preemptive analgesia for acute postoperative pain control in patients underwent arthroscopic anterior cruciate ligament reconstruction.</p> <p>Trial registration number</p> <p>NCT01017380</p

Development of a Management Algorithm for Post-operative Pain (MAPP) after total knee and total hip replacement: study rationale and design.

BACKGROUND: Evidence from clinical practice and the extant literature suggests that post-operative pain assessment and treatment is often suboptimal. Poor pain management is likely to persist until pain management practices become consistent with guidelines developed from the best available scientific evidence. This work will address the priority in healthcare of improving the quality of pain management by standardising evidence-based care processes through the incorporation of an algorithm derived from best evidence into clinical practice. In this paper, the methodology for the creation and implementation of such an algorithm that will focus, in the first instance, on patients who have undergone total hip or knee replacement is described. METHODS: In partnership with clinicians, and based on best available evidence, the aim of the Management Algorithm for Post-operative Pain (MAPP) project is to develop, implement, and evaluate an algorithm designed to support pain management decision-making for patients after orthopaedic surgery. The algorithm will provide guidance for the prescription and administration of multimodal analgesics in the post-operative period, and the treatment of breakthrough pain. The MAPP project is a multisite study with one coordinating hospital and two supporting (rollout) hospitals. The design of this project is a pre-implementation-post-implementation evaluation and will be conducted over three phases. The Promoting Action on Research Implementation in Health Services (PARiHS) framework will be used to guide implementation. Outcome measurements will be taken 10 weeks post-implementation of the MAPP. The primary outcomes are: proportion of patients prescribed multimodal analgesics in accordance with the MAPP; and proportion of patients with moderate to severe pain intensity at rest. These data will be compared to the pre-implementation analgesic prescribing practices and pain outcome measures. A secondary outcome, the efficacy of the MAPP, will be measured by comparing pain intensity scores of patients where the MAPP guidelines were or were not followed. DISCUSSION: The outcomes of this study have relevance for nursing and medical professionals as well as informing health service evaluation. In establishing a framework for the sustainable implementation and evaluation of a standardised approach to post-operative pain management, the findings have implications for clinicians and patients within multiple surgical contexts

Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

Peer reviewe

A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle

The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight0.262 =0.95 + 0.022 × girth which has an R2 value of 0.98 and 95 % prediction intervals that fall within the ±20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting