Investigation of the role of infusate properties related to midline catheter failure in an ovine model.

PURPOSE: Infusate osmolarity, pH, and cytotoxicity were investigated as risk factors for midline catheter failure. METHODS: An experimental, randomized, controlled, blinded trial was conducted using an ovine model. Two 10-cm, 18-gauge single-lumen midline catheters were inserted into the cephalic veins of sheep. The animals were divided into 6 study arms and were administered solutions of vancomycin 4 mg/mL (a low-cytotoxicity infusate) or 10 mg/mL (a high-cytotoxicity infusate), doxycycline 1 mg/mL (an acidic infusate), or acyclovir 3.5 mg/mL (an alkaline infusate) and 0.9% sodium chloride injection; or 1 of 2 premixed Clinimix (amino acids in dextrose; Baxter International) products with respective osmolarities of 675 mOsm/L (a low-osmolarity infusate) and 930 mOsm/L (a mid-osmolarity infusate). Contralateral legs were infused with 0.9% sodium chloride injection for control purposes. Catheter failure was evaluated by assessment of adverse clinical symptoms (swelling, pain, leakage, and occlusion). A quantitative vessel injury score (VIS) was calculated by grading 4 histopathological features: inflammation, mural thrombus, necrosis, and perivascular reaction. RESULTS: Among 20 sheep included in the study, the overall catheter failure rate was 95% for test catheters (median time to failure, 7.5 days; range, 3-14 days), while 60% of the control catheters failed before or concurrently (median time to failure, 7 days; range, 4.5-14 days). Four of the 6 study arms (all but the Clinimix 675-mOsm/L and acyclovir 3.5-mg/mL arms) demonstrated an increase in mean VIS of ≥77% in test vs control legs (P ≤ 0.034). Both pain and swelling occurred at higher rates in test vs control legs: 65% vs 10% and 70% vs 50%, respectively. The mean difference in rates of occlusive pericatheter mural thrombus between the test and control arms was statistically significant for the vancomycin 10-mg/mL (P = 0.0476), Clinimix 930-mOsm/L (P = 0.0406), and doxycycline 1-mg/mL (P = 0.032) arms. CONCLUSION: Administration of infusates of varied pH, osmolarity, and cytotoxicity via midline catheter resulted in severe vascular injury and premature catheter failure; therefore, the tested infusates should not be infused via midline catheters.

Pathological Safety Assessment in Preclinical Neurothrombectomy Studies.

The design, production, and preclinical testing of neurothrombectomy devices is in a burgeoning phase as the demand escalates for safe and reliable treatment options following neurovascular stroke. Currently, there is a paucity of published data describing the development of iatrogenic vascular lesions occurring secondary to neurothrombectomy procedures. In an effort to test new devices, demonstrate device safety, satisfy regulatory requirements, and develop an understanding of the potential for associated vascular pathology, investigators are establishing appropriate methodology in suitable animal models. Significant challenges exist in identifying a single animal species that can be consistently utilized in all phases of device development. These aforementioned challenges are underscored by the intricacies of neurovascular pathology, thrombovascular interactions, and vascular responses to injury.

Chlorhexidine-coated peripherally inserted central catheters reduce fibroblastic sleeve formation in an in vivo ovine model.

PURPOSE:: This study compared an antimicrobial and anti-thrombogenic peripherally inserted central catheter treated with a chlorhexidine-based technology, a peripherally inserted central catheter with bulk distributed fluoro-oligomers, and a poly 2-methoxyethyl acrylate-based peripherally inserted central catheter to an untreated peripherally inserted central catheter (control) in an ovine model at 14 and 30 days post-implant. METHODS:: One of four types of peripherally inserted central catheters was surgically implanted into the left jugular vein of each of 18 sheep for 14 or 30 days. Blood analysis consisted of complete blood counts, serum chemistries, and coagulation (fibrinogen, prothrombin time, and partial thromboplastin time) profiles. Sheep were sacrificed to examine the vein and thorax. Histological analysis was performed on serial catheter sections using standard microscopy on hematoxylin and eosin-stained tissues. RESULTS:: All catheters developed fibroblastic sleeves at both 14 and 30 days. The chlorhexidine-peripherally inserted central catheter showed a 64% lower mean fibroblastic sleeve weight and a 66% shorter mean fibroblastic sleeve length compared to the untreated control at 14 days. By 30 days, compared to untreated control, the chlorhexidine-peripherally inserted central catheter showed 81% lower mean fibroblastic sleeve weight with 75% shorter mean fibroblastic sleeve length, the fluoro-oligomer-peripherally inserted central catheter showed 54% lower mean sheath weight with 40% shorter mean fibroblastic sleeve length, and the poly 2-methoxyethyl acrylate-peripherally inserted central catheter had 41% lower mean fibroblastic sleeve weight with 57% lower fibroblastic sleeve length. CONCLUSION:: Among the three anti-thrombogenic peripherally inserted central catheter technologies, the chlorhexidine-peripherally inserted central catheter had the smallest fibroblastic sleeves, followed by the fluoro-oligomer-peripherally inserted central catheter, poly 2-methoxyethyl acrylate-peripherally inserted central catheter, and control peripherally inserted central catheter.

Comparison of Topical Hemostatic Agents in a Swine Model of Extremity Arterial Hemorrhage: BloodSTOP iX Battle Matrix vs. QuikClot Combat Gauze.

BloodSTOP iX Battle Matrix (BM) and QuikClot Combat Gauze (CG) have both been used to treat traumatic bleeding. The purpose of this study was to examine the efficacy and initial safety of both products in a swine extremity arterial hemorrhage model, which mimics combat injury. Swine (37.13 ± 0.56 kg, NBM = 11, NCG = 9) were anesthetized and splenectomized. We then isolated the femoral arteries and performed a 6 mm arteriotomy. After 45 s of free bleeding, either BM or CG was applied. Fluid resuscitation was provided to maintain a mean arterial pressure of 65 mmHg. Animals were observed for three hours or until death. Fluoroscopic angiography and wound stability challenge tests were performed on survivors. Tissue samples were collected for histologic examination. Stable hemostasis was achieved in 11/11 BM and 5/9 CG subjects, with recovery of mean arterial pressure and animal survival for three hours (p < 0.05, Odds Ratio (OR) = 18.82 (0.85-415.3)). Time to stable hemostasis was shorter for the BM-treated group (4.8 ± 2.5 min vs. 58 ± 20.1 min; Median = 2, Interquartile Range (IQR) = 0 min vs. Median = 60, IQR = 120 min; p < 0.05) and experienced longer total stable hemostasis (175.2 ± 2.5 min vs. 92.4 ± 29.9 min; Median = 178, IQR = 0 min vs. Median = 120, IQR = 178 min; p < 0.05). Post-treatment blood loss was lower with BM (9.5 ± 2.4 mL/kg, Median = 10.52, IQR = 13.63 mL/kg) compared to CG (29.9 ± 9.9 mL/kg, Median = 29.38, IQR = 62.44 mL/kg) (p = 0.2875). Standard BM products weighed less compared to CG (6.9 ± 0.03 g vs. 20.2 ± 0.4 g) (p < 0.05) and absorbed less blood (3.4 ± 0.8 g vs. 41.9 ± 12.3 g) (p < 0.05). Fluoroscopic angiography showed recanalization in 5/11 (BM) and 0/5 (CG) surviving animals (p = 0.07, OR = 9.3 (0.41-208.8)). The wound stability challenge test resulted in wound re-bleeding in 1/11 (BM) and 5/5 (CG) surviving animals (p < 0.05, OR = 0.013 (0.00045-0.375)). Histologic evidence indicated no wound site, distal limb or major organ damage in either group. BM is more effective and portable in treating arterial hemorrhage compared to CG. There was no histologic evidence of further damage in either group.

Mynx vascular closure device achieves reliable closure and hemostasis of percutaneous transfemoral venous access in a porcine vascular model.

AIMS: Vascular closure device (VCD)-based venous closure has been anecdotally reported, but systematic evaluation of the reparative response of the vessel wall to venous closure is lacking. The need to control groin complications, and minimize risks associated with postponed sheath removal under conditions of persistent anticoagulation, has generated interest in the role of VCDs for venous access closure. We sought to characterize the vessel wall response to venous closure, both acutely and in delayed fashion at 30 days using angiography, ultrasound, and histology. METHODS: Ten venous 7 Fr sheaths were deployed in the femoral veins of swine. Bilateral venous access sites were subsequently closed utilizing manual compression (MC; control arm: n = 4) or a closure device utilizing an extravascular polyethylene glycol sealant (MynxGrip treatment arm: n = 6). Acute (post closure), 3-day, and 30-day vascular ultrasound, as well as venography (internal jugular approach) were used to assess outcomes. Gross pathology and histology were obtained at the 30-day endpoint for all femoral venous closure sites. RESULTS: Hemostasis was successfully achieved in all cases without access-site complications. Venography and ultrasound confirmed normal ilio-femoral anatomy and flow at all study time points. Gross pathology and histopathology revealed no evidence of deep vein thrombosis, and no abnormalities were seen in the vena cava, heart, or lungs. Histology at 30 days showed complete healing of the vein wall access site, with a small focus of chronic inflammation and fibrosis in the perivascular adventitial tissue of the access tract. There was no microscopic evidence of the sealant. The tissue tract showed mild discrete inflammation (foamy macrophages, lymphocytes, plasma cells) with microgranulomas centered on residual red cells in both treatment and control groups. CONCLUSIONS: This study characterizes the angiographic, ultrasound, and histopathology outcomes of femoral vein closure, and provides insight into the healing mechanisms following venotomy. The bio-resorptive role of MynxGrip extravascular sealant in achieving effective venous closure and preserved long-term vessel patency without venous thromboembolism is demonstrated.