The mornings after-periarticular liposomal bupivacaine infiltration does not improve analgesic outcomes beyond 24 hours following total knee arthroplasty: a systematic review and meta-analysis.

Periarticular local infiltration analgesia (LIA) is integral to multimodal analgesia following total knee arthroplasty (TKA); however, the duration of analgesia using traditional long-acting local anesthetics is often insufficient. LIA with slow-release liposomal bupivacaine may provide extended analgesia, but evidence of efficacy beyond the first 24 hours is conflicting. This meta-analysis compares the effects of periarticular liposomal and plain bupivacaine LIA on day 2 analgesic outcomes post-TKA. Trials comparing liposomal and plain bupivacaine LIA for TKA were sought. The two coprimary outcomes were (1) cumulative oral morphine equivalent consumption and (2) difference in area under the curve (AUC) of pooled rest pain scores on day 2 (24-48 hours) post-TKA. We also evaluated pain and analgesic consumption on day 3 (48-72 hours), functional recovery, length of hospital stay, patient satisfaction; and opioid-related side effects. Data were pooled using random-effects modeling. Seventeen trials (1836 patients) were analyzed. Comparing liposomal versus plain bupivacaine LIA for TKA failed to detect differences in morphine consumption and pain AUC on day 2 postoperatively, with mean differences of 0.54 mg (95% CI -5.09 to 6.18) and 0.08 cm/hour (95% CI -0.19 to 0.35), respectively (high-quality evidence). Secondary outcome analysis did not uncover any additional analgesic, functional or safety advantages to liposomal bupivacaine on postoperative day 2 or 3. Results indicate that liposomal and plain bupivacaine LIAs are not different for extended postoperative analgesic outcomes, including pain control, opioid consumption, as well as functional and safety outcomes on days 2 and 3 post-TKA. High-quality evidence does not support using liposomal bupivacaine LIA for TKA.

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.