Treatment of a Neonatal Peripheral Intravenous Infiltration/Extravasation (PIVIE) Injury With Hyaluronidase: A Case Report

Highlights Abstract Introduction: Intravenous therapy-related injury, its prevention, and treatment are ubiquitous topics of interest among neonatal clinicians and practitioners. This is due to the economic costs, reputational censure, and patents’ wellbeing concerns coupled with the possibility of potentially avoidable serious and life-long harm occurring in this vulnerable patient population. Case description: A term infant receiving a hypertonic dextrose infusion for the management of hypoglycemia developed a fulminating extravasation shortly after commencement of the infusion. This complication developed without notification of infusion pump pressure changes pertaining to a change in blood vessel compliance or early warning of infiltration by the optical sensor site monitoring technology (ivWatch®) in use. The injury was extensive and treated with a hyaluronidase/saline mix subcutaneously injected into the extravasation site using established techniques. Over a period of 2 weeks, the initially deep wound healed successfully without further incident, and the infant was discharged home without evident cosmetic scarring or functional effects. Conclusion: This article reports on a case of a term baby who postroutine insertion of a peripherally intravenous catheter showed an extreme reaction to extravasation of the administered intravenous fluids. We discuss the condition, our successful management with hyaluronidase, and the need to remain observationally vigilant of intravenous infusions despite the advances in infusion monitoring technology.

Efficacy of hypertonic dextrose injection (prolotherapy) in temporomandibular joint dysfunction: a systematic review and meta-analysis

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by “Cochrane risk of bias 2” tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: − 0.76; 95% CI − 1.19 to − 0.32, I2 = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections.Protocol registration at PROSPERO: CRD42020214305.

Hypertonic Dextrose Stimulates Chondrogenic Cells to Deposit Collagen and Proliferate

Objective Hypertonic dextrose (HD) injections (prolotherapy) for osteoarthritis are reported to reduce pain. Cartilage regeneration is hypothesized as a mechanism. This in vitro study identifies an HD concentration that stimulates chondrogenic cells to increase metabolic activity and assesses whether this concentration affects collagen deposition and proliferation. Design ATDC5 chondrogenic cells were cultured in normoglycemic DMEM/F12 medium, treated with concentrations of HD (4-400 mM), and assessed with PrestoBlue. Advanced light microscopy was used to conduct live imaging of collagen deposition through second harmonic generation microscopy (SHG) and proliferation via 2-photon excitation microscopy. Proliferation was additionally assessed with hemocytometer counts. Results A linear regression model found that, relative to the 4 mM baseline control, cells treated with 200 mM had a higher mean absorbance ( P = 0.023) and cells treated with 250 mM were trending toward a higher mean absorbance ( P = 0.076). Polynomial regression interpolated 240 mM as producing the highest average absorbance. Hemocytometer counts validated 250 mM as stimulating proliferation compared with the 4 mM control ( P < 0.01). A concentration of 250 mM HD led to an increase in collagen deposition compared with that observed in control ( P < 0.05). This HD concentration also led to increases in proliferation of ATDC5 cells relative to that of control ( P < 0.001). Conclusions A 250 mM HD solution appears to be associated with increased metabolic activity of chondrocytes, increased collagen deposition, and increased chondrocyte proliferation. These results support clinical prolotherapy research suggesting that intra-articular HD joint injections reduce knee pain. Further study of HD and cellular processes is warranted.

Adding Ozone to Dextrose and Somatropin for Intra-Articular Knee Prolotherapy: A Randomized Single-Blinded Controlled Trial

Background: Prolotherapy, as an alternative therapy, has emerged as an effective treatment for chronic musculoskeletal injury, including knee osteoarthritis (OA). Several studies have mention ozone as a potential treatment for these diseases, which is based on analgesic, anti-inflammatory, and anti-oxidant. Objectives: The current study aimed to investigate the effect of adding ozone gas to hypertonic dextrose and somatropin for knee prolotherapy in patients with knee OA. For this purpose, pain, knee stiffness, and physical activity are measured. Methods: Sixty patients with chronic knee OA were randomly assigned into two groups of DS and DSO. The DS group received intra-articular hypertonic dextrose (10 ml) plus 4 IU somatropin (4 IU), and the DSO group received 10 ml ozone 25 mcg plus intervention in the DS group. This procedure was performed three times (first, third, and fifth weeks). WOMAC score was examined during the third, fifth, and sixteenth weeks. Results: The mean WOMAC score of the DS group was decreased significantly (P < 0.001) sixteen weeks after providing the intervention (before 64.9 ± 10.6, vs. after 49.2 ± 9.0). A similar decrease (P < 0.001) was observed in the DSO group (before 64.1 ± 11.3, vs. after 41.3 ± 8.0). The decrease of the WOMAC score in the third and sixteenth weeks after providing the intervention was significant in the DSO group compared to the DS group (P < 0.005). Conclusions: For patients with knee OA, prolotherapy with ozone plus hypertonic dextrose and somatropin was more effective in sedating the pain and improving the stiffness and function of the knee than dextrose and somatropin alone.

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array

BACKGROUND/AIMOsteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers.METHODSOA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients’ knee-joint synovial fluid. The WOMAC Index and minimum joint space width prior to receiving the intra-articular injection and at 2-week intervals were compared.RESULTS12 patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between the high-glucose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. These findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which accompanying with the improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width.