Our study showed an average of 2.5 weeks of wound healing following extravasation regardless of the causative agent. The duration of healing seems to be related to the wound extent. We reported no adverse reactions, and scar formation was not seen. The medical staff and nurses were satisfied as the care of the wound was easy. Infection following the dressings were not reported. We implemented the AM in two premature neonates that the result was acceptable. Extravasations in preterm are due to more extended requirements for intravenous therapy and fragile vessels. The cause in term neonates is more due to the rapid and vigorous limb movements during hunger, agitation, or handling by the mother, that displaces the catheter and tears the vessel.
In both cases, the fluid leaks into the soft tissue. Based on the fluid that escapes the wall, they are divided into infiltrates and vesicant fluid. In infiltration fluids as normal saline, exert mechanical forces on blood supply, lymphatic drainage, and subdermal plexus. The result is occlusion of blood vessels that causes ischemia and finally necrosis [25]. The amount of accumulated fluid shows the extension of injury. Vasoconstriction and ischemia are induced by vasopressors such as dopamine and dobutamine that cause necrosis [26]. Hyperosmolar fluids as hypertonic glucose result in cell shrinking by shifting water from the cell to the interstitial tissue [27]. The injury mechanism of vesicant fluids is both mechanical pressure and cell death. They lead to chemical burning of the skin. Drugs with a PH out of the normal range of blood cause cell damage. Phenytoin and vancomycin are examples of this mechanism [21]. Extravasation of total parenteral fluids, calcium gluconate, can cause necrosis. Tissue injury maybe not be recognized until 48 to 72 hours after the leak. Besides, newborns cannot react to the first stages of injury, so some cases are identified when necrosis is established [28]. There are specific treatments for each mentioned above extravasation mechanism. Hyaluronidase is better administered within the first two hours after extravasation in five separate sites [29].
Phentolamine is the antidote to vasoactive drugs such as dopamine and dobutamine and should be administered within 12 hours after injury. Administration in neonates should be followed with close monitoring due to complications such as tachycardia, hypotension. Nitroglycerin ointment dilates arteries and venous, increases capillary blood flow, and reverses ischemia and necrosis. The mentioned methods show that, when necrosis is established, these methods are useless, and besides timing of recognizing the injury may be delayed in neonates [30]. The immunocompromised state of the neonate demands rapid healing. Acute wound healing consists of four stages: hemostasis, inflammation, proliferation, and tissue remodeling. AM is the inner layer of the placenta that has many biologic and immunologic properties and can induce healing by several mechanisms.AM induces anti-inflammatory, antifibrotic, and antimicrobial properties [31]. These mechanisms are induced by transforming growth factor-beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGFs) [32]. Amniotic membrane's mesenchymal stem cells and epithelial cells contain a variety of mediators such as epidermal growth factor (EGF), keratinocyte growth factor (KGF), primary fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) [33], which leads to cell proliferation, epithelization, inhibition of fibrosis, inflammation and bacterial infection [34]. Researchers have shown class I and class I b antigens in epithelial cells, mesenchymal cells, and fibroblasts.
In contrast, others have concluded that amniotic epithelial and mesenchymal cells reduce the secretion of HLA class A, B, DR molecules, CD-40, CD-80, and CD-86 stimulatory molecules. So, they do not produce immune responses, which is why there have been no reports of immunogenic reactions due to amniotic membrane use in 100 years [35]. FGF-b is a pro-angiogenic factor and plays an essential role in forming fibroblast proliferating granulitic tissue [1]. The presence of platelet growth factor (PDGF) and vascular endothelial-derived growth factor (VEGF) in the amniotic membrane suggests a pro-angiogenic role in the hemostasis phase of wound healing [36]. The use of amniotic membrane on the wound showed many beneficial effects on wound management such as analgesic, anti-scar, preventative effect on dehydration, and excessive fluid loss [37].
The TGF- β family is responsible for synthesizing and depositing extracellular matrix (ECM) proteins and regulating and transporting fibroblasts into myofibroblasts [38]. Mesenchymal stem cells (MSCs) can inhibit TGF-β and cause overproduction of fibrosis and scarring [39]. Amniotic epithelial cells contain interleukin-10 (IL-10), promoting the expression of Th1 cytokine cells, MHC class II complexes. IL-10 also increases B-cell survival, proliferation, and antibody production and has been shown to inhibit the production of anti-inflammatory cytokines such as INF-γ, IL-2, IL-3, tumor necrosis factor (TNF-α). Other anti-inflammatory agents such as IL-1 receptor antagonists and tissue metalloproteinase-1, 2, 3, 4 (TIMP) inhibitors have also been found in amniotic cells [40]. Amniotic epithelial cells express intercellular adhesion molecule-1 (ICAM-1) by inflammatory protein cytokines such as tumor necrosis factor (TNF-a) and IL-1b. ICAM-1 increase the uptake and adhesion of leukocytes [41].
Limitations of the study: To date, we could not find AM application in neonatal Extravasation in the literature; with limited cases, we started our work, and we were beware of unwanted complications.