Continuous Transversus Abdominis Plane Block for Primary Open Inguinal Hernia Repair: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Patients undergoing open inguinal hernia repair may experience moderate to severe postoperative pain. We assessed opioid consumption in subjects who received a continuous transversus abdominis plane block in addition to standard multimodal analgesia. DESIGN: Randomized, double-blind, placebo-controlled. SETTING: Tertiary academic medical center. SUBJECTS: Adult patients undergoing open inguinal hernia repair at Virginia Mason Medical Center. A total of 90 patients were enrolled. METHODS: Subjects presenting for surgery were randomized to receive either a continuous transversus abdominis plane block or a subcutaneous sham block. The primary outcome was opioid consumption within the first 48 hours after surgery. Secondary outcomes included pain scores, activities assessment scores, and opioid-related adverse events. Multimodal analgesia utilized in both groups included acetaminophen, nonsteroidal anti-inflammatory drugs, and surgical local anesthetic infiltration. RESULTS: Eighty-two subjects, 42 from the block group and 40 from the sham group, completed the study, per protocol. The intention-to-treat analysis demonstrated no difference in 48-hour postoperative oxycodone equivalent consumption between the block and sham groups (27.8 mg ± 26.8 vs 32 mg ± 39.2, difference -4.4 mg, P = 0.55). There was a statistically significant reduction in pain scores at 24 hours in the block group. There were no other differences in secondary outcomes. CONCLUSIONS: Continuous transversus abdominis plane blocks provide modest improvements in pain after open inguinal hernia repair but fail to significantly reduce opioid consumption or improve functional activity levels in the setting of multimodal analgesia use.

Comparison of Continuous Proximal Versus Distal Adductor Canal Blocks for Total Knee Arthroplasty: A Randomized, Double-Blind, Noninferiority Trial.

BACKGROUND AND OBJECTIVES: Adductor canal blocks (ACBs) are associated with improved analgesia, preserved quadriceps strength, and decreased length of hospitalization after total knee arthroplasty (TKA). However, controversy remains regarding the ideal location of a continuous block within the adductor canal, and it remains unclear whether similar clinical benefits are obtained irrespective of block location. In this randomized, double-blind, noninferiority study, we hypothesized that a continuous proximal ACB provides postoperative analgesia that is no worse than a continuous distal ACB. METHODS: Subjects presenting for unilateral TKA were randomized in a 1:1 ratio to either a continuous proximal or distal ACB group. The primary outcome of this noninferiority study was opioid consumption within the first 24 hours following surgery. Secondary outcomes included quadriceps strength, pain scores, distance ambulated, and patient satisfaction. RESULTS: Seventy-three subjects, 36 from the proximal group and 37 from the distal group, completed the study per protocol. The intention-to-treat analysis demonstrated a cumulative mean intravenous morphine equivalent consumption difference between the proximal and distal groups of -7.2 mg (95% confidence interval, -14.8 to 0.4; P < 0.001), demonstrating noninferiority of the proximal approach. The per-protocol analysis yielded similar results: -6.2 mg (95% confidence interval, -14.1 to 1.6; P < 0.001). No secondary outcomes showed statistically significant differences between the proximal and distal groups. CONCLUSIONS: This study demonstrates that a continuous proximal ACB offers noninferior postoperative analgesia compared with a distal continuous ACB in the first 24 hours after TKA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02701114).

Successful Continuous Adductor Canal Block Placement in a Patient With Absent Sartorius Muscle: A Case Report.

We report a novel case of a patient who presented for elective total knee arthroplasty and had distorted adductor canal anatomy due to previous sartorius rotational flap surgery. Despite the lack of a sartorius muscle on the intended operative limb, we describe the successful placement of a continuous adductor canal block. This case is a clinically relevant example that highlights the importance of the vastoadductor membrane as the anatomical anteromedial boundary for the adductor canal, and that it remains intact even after sartorius muscle flap surgery.

A Novel Approach to Brachial Plexus Catheter Management: A Brachial Plexus Test Dose for Phrenic Nerve Paralysis and Patient-Controlled, Demand-Only Dosing for a Patient With Extreme Obesity.

A 53-year-old woman with extreme obesity (body mass index = 82 kg/m) presented for an open reduction and internal fixation of the proximal humerus. This report describes the novel management of her continuous brachial plexus catheter in the setting of her comorbidities. Phrenic nerve paralysis from brachial plexus blocks can cause clinically significant dyspnea in obese patients. Brachial plexus catheters can be used effectively for these patients with some modification to routine management. We detail our use of a short-acting chloroprocaine test dose for phrenic paralysis and demand-only dosing to provide effective analgesia while avoiding respiratory complications associated with these blocks.

Expression of human carcinoembryonic antigen-related cell adhesion molecule 6 and alveolar progenitor cells in normal and injured lungs of transgenic mice.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is expressed in the epithelium of various primate tissues, including lung airway and alveoli. In human lung, CEACAM6 is developmentally and hormonally regulated, protects surfactant function, has anti-apoptotic activity and is dysregulated in cancers. We hypothesized that alveolar CEACAM6 expression increases in lung injury and promotes cell proliferation during repair. Studies were performed in CEABAC transgenic mice-containing human CEACAM genes. The level of CEACAM6 in adult CEABAC lung was comparable to that in human infants; expression occurred in epithelium of airways and of some alveoli but rarely co-localized with markers of type I or type II cells. Ten days after bleomycin instillation, both the number of CEACAM6(+) cells and immunostaining intensity were elevated in injured lung areas, and there was increased co-localization with type I and II cell markers. To specifically address type II cells, we crossed CEABAC mice with animals expressing EGFP driven by the SP-C promoter. After bleomycin injury, partially flattened, elongated epithelial cells were observed that expressed type I cell markers and were primarily either EGFP(+) or CEACAM6(+). In cell cycle studies, mitosis was greater in CEACAM6(+) non-type II cells versus CEACAM6(+)/EGFP(+) cells. CEACAM6 epithelial expression was also increased after hyperoxic exposure and LPS instillation, suggesting a generalized response to acute lung injuries. We conclude that CEACAM6 expression is comparable in human lung and the CEABAC mouse. CEACAM6 in this model appears to be a marker of a progenitor cell population that contributes to alveolar epithelial cell replenishment after lung injury.

Age decreases endothelial progenitor cell recruitment through decreases in hypoxia-inducible factor 1alpha stabilization during ischemia.

BACKGROUND: Advanced age is known to impair neovascularization. Because endothelial progenitor cells (EPCs) participate in this process, we examined the effects of aging on EPC recruitment and vascular incorporation. METHODS AND RESULTS: Murine neovascularization was examined by use of an ischemic flap model, which demonstrated aged mice (19 to 24 months) had decreased EPC mobilization (percent mobilized 1.4+/-0.2% versus 0.4+/-0.1%, P<0.005) that resulted in impaired gross tissue survival compared with young mice (2 to 6 months). This decrease correlated with diminished tissue perfusion (P<0.005) and decreased CD31+ vascular density (P<0.005). Gender-mismatched bone marrow transplantation demonstrated significantly fewer chimeric vessels in aged mice (P<0.05), which confirmed a deficit in bone marrow-mediated vasculogenesis. Age had no effect on total EPC number in mice or humans. Reciprocal bone marrow transplantations confirmed that impaired neovascularization resulted from defects in the response of aged tissue to hypoxia and not from intrinsic defects in EPC function. We demonstrate that aging decreased hypoxia-inducible factor 1alpha stabilization in ischemic tissues because of increased prolyl hydroxylase-mediated hydroxylation (P<0.05) and proteasomal degradation. This resulted in a diminished hypoxia response, including decreased stromal cell-derived factor 1 (P<0.005) and vascular endothelial growth factor (P<0.0004). This effect can be reversed with the iron chelator deferoxamine, which results in hypoxia-inducible factor 1alpha stabilization and increased tissue survival. CONCLUSIONS: Aging impairs EPC trafficking to sites of ischemia through a failure of aged tissues to normally activate the hypoxia-inducible factor 1alpha-mediated hypoxia response.

Uniaxial mechanical strain: an in vitro correlate to distraction osteogenesis.

BACKGROUND: Distraction osteogenesis is a valuable clinical tool; however the molecular mechanisms governing successful distraction remain unknown. We have used a uniaxial in vitro strain device to simulate the uniaxial mechanical environment of the interfragmentary distraction gap. MATERIALS AND METHODS: Using the Flexcell system, normal human osteoblasts were subjected to different levels of cyclical uniaxial mechanical strain. Cellular morphology, proliferation, migration, and the expression of angiogenic (vascular endothelial growth factor [VEGF] and fibroblast growth factor-2 [FGF-2]) and osteogenic (osteonectin, osteopontin, and osteocalcin) proteins and extracellular matrix molecules (collagen IalphaII) were analyzed in response to uniaxial cyclic strain. RESULTS: Osteoblasts exposed to strain assumed a fusiform spindle-shaped morphology aligning parallel to the axis of uniaxial strain and osteoblasts exposed to strain or conditioned media had a 3-fold increase in proliferation. Osteoblast migration was maximal (5-fold) in response to 9% strain. Angiogenic cytokine, VEGF, and FGF-2, increased 32-fold and 2.6-fold (P < 0.05), respectively. Osteoblasts expressed greater amounts of osteonectin, osteopontin, and osteocalcin (2.1-fold, 1.8-fold, 1.5-fold respectively, P < 0.01) at lower levels of strain (3%). Bone morphogenic protein-2 production increased maximally at 9% strain (1.6-fold, P < 0.01). Collagen I expression increased 13-, 66-, and 153-fold in response to 3, 6, and 9% strain, respectively. CONCLUSIONS: Uniaxial cyclic strain using the Flexcell device under appropriate strain parameters provides a novel in vitro model that induces osteoblast cellular and molecular expression patterns that simulate patterns observed in the in vivo distraction gap.

Mechanical strain alters gene expression in an in vitro model of hypertrophic scarring.

Fibroblasts represent a highly mechanoresponsive cell type known to play key roles in normal and pathologic processes such as wound healing, joint contracture, and hypertrophic scarring. In this study, we used a novel fibroblast-populated collagen lattice (FPCL) isometric tension model, allowing us to apply graded biaxial loads to dermal fibroblasts in a 3-dimensional matrix. Cell morphology demonstrated dose-dependent transition from round cells lacking stress fibers in nonloaded lattices to a broad, elongated morphology with prominent actin stress fibers in 800-mg-loaded lattices. Using quantitative real-time RT-PCR, a dose dependent induction of both collagen-1 and collagen-3 mRNA up to 2.8- and 3-fold, respectively, as well as a 2.5-fold induction of MMP-1 (collagenase) over unloaded FPCLs was observed. Quantitative expression of the proapoptotic gene Bax was down-regulated over 4-fold in mechanically strained FPCLs. These results suggest that mechanical strain up-regulates matrix remodeling genes and down-regulates normal cellular apoptosis, resulting in more cells, each of which produces more matrix. This "double burden" may underlie the pathophysiology of hypertrophic scars and other fibrotic processes in vivo.