Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block.

BACKGROUND: Although pain management after total knee arthroplasty (TKA) affects rehabilitation, length of stay, and functional outcomes, pain management for patients undergoing TKA has yet to be standardized. Femoral nerve blocks (FNBs) are commonly used as an adjunct; however, these can result in transient quadriceps weakness and have been associated with in-hospital falls. Periarticular infiltration of liposomal bupivacaine has been recently introduced as a long-acting analgesic that can be administered without affecting motor function. QUESTIONS/PURPOSES: (1) Does periarticular liposomal bupivacaine compared with FNB result in improved pain control as measured by pain scores and narcotic consumption? (2) How do liposomal bupivacaine and FNB compare in terms of gait and stairclimbing milestones and the proportion of patients who experienced a fall in the hospital? METHODS: Between September 2013 and October 2014, a retrospective analysis was conducted involving 24 surgeons who performed a total of 1373 unilateral, primary TKAs. From September 2013 to April 2014, the routine approach to TKA pain management pathway consisted of preoperative administration of oral analgesics, intraoperative anesthesia (preferred spinal or general), an ultrasound-guided FNB, intraoperative analgesic cocktail injection, patient-controlled analgesia, and oral and IV narcotics for pain as needed. A total of 583 patients were included in this study group. Starting May 2014, FNBs were discouraged and there was department-wide adoption of liposomal bupivacaine. Liposomal bupivacaine became routinely used in all patients undergoing TKA with no other changes made to the multimodal analgesia protocol at that time, and 527 patients in this study group were compared with the FNB cohort. Chart review on a total of 1110 patients was conducted by a research assistant who was not participating in patient care. During the inpatient stay, pain scores during 8-hour intervals, narcotic use, and physical therapy milestones were compared. RESULTS: With the numbers available, we detected no clinically important difference in pain scores throughout the hospital stay; however, patients treated with liposomal bupivacaine consumed very slightly less narcotics overall (96 ± 62 versus 84 ± 73 eq mg of morphine; [95% confidence interval, 11-13 mg]; p = 0.004) through postoperative Day 2 of inpatient hospitalization. Seventy-seven percent (406 of 527) of patients receiving liposomal bupivacaine achieved their gait milestones of clearing 100 feet of ambulation versus 60% (349 of 583) of patients receiving FNB (p < 0.001) before discharge. Likewise, 94% (497 of 527) of patients receiving liposomal bupivacaine completed stairs compared with 73% (427 of 583) of patients receiving FNB (p < 0.001). Patients who received liposomal bupivacaine were less likely to experience a fall during the hospital stay than were patients treated with FNB (3 of 527 [0.6%] versus 12 of 583 [2%]; p = 0.03). CONCLUSIONS: In the absence of strong data supporting FNB over liposomal bupivacaine, we have modified our TKA pain management protocols by adopting liposomal bupivacaine in lieu of FNBs, facilitating rapid rehabilitation while providing adequate pain control. LEVEL OF EVIDENCE: Level III, therapeutic study.

Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to unity.

Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where outcomes for obese patients are better than for their thinner counterparts --- and given the tag "obesity paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of centuries before the public health advances of the 20th century. We conclude with speculation on how understanding the biological elements that protect obese patients with infections or injuries might be applied advantageously to thin patients with the same medical challenges.

Liposomal Bupivacaine as an Adjunct to Postoperative Pain Control in Total Hip Arthroplasty.

BACKGROUND: Although pain management affects rehabilitation, length of stay, and functional outcome, an optimized pain management protocol has yet to be standardized. Opioids are the primary agent used to control acute postoperative pain; however, they are associated with a wide range of side effects. Liposomal bupivacaine (LB), a long-acting analgesic agent administered intraoperatively, has been introduced as a new modality to control pain for up to 72 hours after operation without affecting motor function. METHODS: Six hundred eighty-six primary total hip arthroplasty (THA) patients, who received the standard THA pain management protocol, were compared to a cohort of 586 primary THA patients, who were treated with an additional intraoperative injection of LB. All other pain management parameters and standard of care were identical. Statistical significance was set at P ≤ .05. RESULTS: Although patient-reported pain scores were statistically similar, the LB cohort demonstrated a significant decrease in total narcotic use (P < .001), specifically up to postoperative day 2 (P = .016). Physical therapy milestones were significantly achieved to a greater degree (P < .001) in the LB cohort. Operation time and hospital cost were unaffected (P = .072 and .811, respectively); however, the LB cohort exhibited a decrease in length of stay by 0.31 days (P < .001) and improvement in discharge disposition to home (P = .017). CONCLUSION: LB is a valuable adjunct to our THA pain management protocol, as we strive to achieve improved patient outcomes, reductions in length of stay, and enhanced quality of THA care.

The integration of radiosurgery for the treatment of patients with metastatic spine diseases.

Significant evidence emerging in the spinal oncology literature recommends radiosurgery as a primary modality of treatment of spinal metastasis. Improvements in the methods of delivering radiation have increased the ability to provide a higher and more exacting dose of radiation to a tumor bed than previously. Using treatment-planning software, radiation is contoured around a specific lesion with the intent of administering a tumoricidal dose. Combined with a minimally invasive, tumor-load reducing surgery, this advanced form of radiation therapy can provide better local control of the tumor compared with conventional external beam radiation.

Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive.

Tumors of mesenchymal and epithelial origin produce IGF-2, which activates pathways in the tumors. In a minority of patients, the tumors (hepatomas, fibromas, and fibrosarcomas are the most common among many) release into the circulation enough IGF-2-related peptides to mimic the fasting hypoglycemia characteristic of patients with insulin-producing islet-cell tumors. Rarely, markedly elevated IGF-2 levels produce somatic changes suggestive of acromegaly. Typically, the elevated IGF-2 levels are associated with suppressed plasma levels of insulin, IGF-1, and GH. Complicating the pathophysiology are the IGF binding proteins (IGFBPs) that can bind IGF-2 and IGF-1, modifying hormone metabolism and action. IGFBP concentrations are often altered in the presence of these tumors. At the cellular level, the 3 hormone-related ligands, IGF-2, IGF-1, and insulin, all bind to 4 (or more) types of IGF-1 receptor (IGF-1R) and insulin receptor (IR). Each receptor has its own characteristic affinity for each ligand, a tyrosine kinase, and overlapping profiles of action in the target cells. The IGF-2R, in addition to binding mannose-6-phosphate-containing proteins, provides an IGF-2 degradation pathway. Recent evidence suggests IGF-2R involvement also in signal transduction. Surgery, the treatment of choice, can produce a cure. For patients not cured by surgery, multiple therapies exist, for the tumor and for hypoglycemia. Potential future therapeutic approaches are sketched. From 1910 to 1930, hypoglycemia, insulin, insulinomas, and non-islet-cell tumors were recognized. The latter third of the century witnessed the emergence of the immunoassay for insulin; the IGFs, their binding proteins, and assays to measure them; and receptors for the insulin-related peptides as well as the intracellular pathways beyond the receptor. In closing, we replace non-islet-cell tumor hypoglycemia, an outdated and misleading label, with IGF-2-oma, self-explanatory and consistent with names of other hormone-secreting tumors.

Energy, evolution, and human diseases: an overview.

In the symposium entitled "Transcriptional controls of energy sensing," the authors presented recent advances on 1) AMP kinase, an intracellular energy sensor; 2) PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α), a transcriptional co-activator that has powerful effects on mitochondria; 3) methylation and demethylation in response to metabolic fluctuations; and 4) FGF21 (fibroblast growth factor 21) as an emerging hormone-like intercellular metabolic coordinator. This introduction places these advances within a broad overview of energy sensing and energy balance, with a focus on human evolution and disease. Four key elements of human biology are analyzed: 1) elevated body temperature; 2) complex prolonged reproductive pathways; 3) emergence of 4 large, well-defined fat depots, each with its own functional role; and 4) an immune system that is often up-regulated by nutrition-related signals, independent of the actual presence of a pathogen. We propose that an overactive immune system, including the "metabolic syndrome," was adopted evolutionarily in the distant past to help hold out against unconquerable infections such as tuberculosis, malaria, and trypanosomiasis. This immune activation is advantageous in the absence of other disease management methods, especially under conditions in which life expectancy is short. The inflammation has become a major agent of pathology in wealthy populations in whom the pathogens are a minor threat and life expectancy is long. The "Conclusions" section sketches cautiously how understanding the molecules involved in energy sensing and energy balance may lead to specific therapies for obesity and diabetes and for their complications.