When administering an intradermal injection you should insert the needle at a?

8.3.2.4 Intradermal Injection

Intradermal injections are delivered into the outer layers of the dermis, underneath the upper skin layer (the epidermis). This procedure requires that the animal remain very still; anesthesia is often needed so that animals are sufficiently restrained.

Most intradermal injections are aqueous-based compounds that are physiologically buffered to have a neutral pH. If the solution is not buffered, tissue necrosis can occur at the injection site. The dose range per injection site is 50–100 μL. Injections exceeding this range can cause tissue necrosis at the injection site or leakage of the compound out of the site due to pressure. The needle size range is typically 25–30 gauge.

The injection site is prepared by clipping the hair at the injection site. The skin is stretched taut between the technician's thumb and index finger, providing stability to the skin when positioning the needle. The needle is placed, bevel up, on the skin and is gently inserted into the skin between the epidermis and the dermis layers. The needle is advanced just beyond the bevel and the substance is injected slowly. A small bleb or blister will form in the skin, indicating that the needle was properly placed. When removing the needle, allow the skin to stretch over the bleb to prevent loss of the injected material. Blotting or wiping the area should be avoided as that can cause the compound to leak from the injection sites.

Intradermal and subcutaneous injection

Intradermal or subcutaneous injection avoids the barrier presented by the stratum corneum, and entry into the general circulation is limited mainly by the rate of blood flow to the site of injection. However, these sites generally only allow the administration of small volumes of drugs and tend to be used mostly for local effects, such as local anaesthesia, or to deliberately limit the rate of drug absorption (e.g. insulin; see Chapter 40). Subdermal implants are increasingly used for long-term hormonal contraception; the implants are flexible polymer rods or tubes inserted under the skin of the upper arm that slowly release the hormone for up to 3 years, with contraception being reversible by removal of the implant (see Chapter 45).

Intradermal Vaccine

Intradermal administration of vaccines has been suggested as a solution to improve vaccine immunogenicity. Intradermal administration results in antigen presentation by dendritic cells in the skin, which may improve the antigen presentation process. In healthy adults, intradermal vaccines have allowed for lower doses of vaccine antigens than in intramuscular vaccines with similar immunogenicity outcomes.97 A metaanalysis of RCTs comparing the immunogenicity and safety of intradermal influenza vaccines with intramuscular vaccines in immunocompromised patients (including SOT recipients, persons with cancer and HIV, those treated with TNF-α inhibitors, and HSCT patients) demonstrated that intradermal vaccines were safe and showed similar vaccine immunogenicity as intramuscular vaccines, with lower doses of antigen being used in intradermal vaccines.98 However, a solution for immunocompromised patient in terms of influenza prevention would not merely match the immunogenicity of intramuscular influenza vaccines, but rather would result in increased vaccine immunogenicity. One RCT among lung transplant recipients did compare immunogenicity outcomes in SOT recipients receiving standard-dose intramuscular TIV versus high-dose intradermal TIV. This study did not report any higher immunogenicity outcomes for the intradermal vaccine.99 Based on immunogenicity data from this study, intradermal influenza vaccination is unlikely to be the solution for influenza vaccine prevention in the SOT population, although it appears to be a safe and acceptable alternative to intramuscular vaccine. A solution for influenza prevention in immunocompromised adults would also result in increased influenza vaccine efficacy and effectiveness, which have yet to be studied with intradermal influenza vaccines in many subgroups of this diverse population. A QIV (Fluzone Intradermal Quadrivalent; Sanofi Pasteur) is currently an FDA-approved vaccine and listed as an option for influenza vaccine by ACIP for the 2017–18 influenza season.75 ACIP has not preferentially recommended one influenza vaccine formulation over another for persons in whom each influenza vaccine is licensed. Fluzone Intradermal Quadrivalent influenza vaccine is recommended for adults aged 18–64 years.75

EPR and LPR in the skin

Intradermal injection of allergen induces a characteristic ‘triple response’ characterized by an almost immediate reddening of the skin (histamine-mediated arteriolar vasodilatation) at the site of allergen injection, which is followed within 5–10 minutes by the development of an area of oedema, or wheal (histamine-mediated increased permeability) (Fig. 1.32). The third component of the triple response is an area of erythema, or flare, around the wheal. This is initiated by the stimulation of histamine receptors on afferent non-myelinated nerves, which results in the release of neuropeptides with consequent vasodilatation and skin erythema. Histamine-induced nerve stimulation also results in itch. The size of the flare is again dose dependent and may measure several centimetres across. The wheal-and-flare generally resolves within about 30 minutes. However, in up to 50% of subjects challenged intradermally with a high dose of allergen the immediate reaction evolves into a late phase reaction characterized by an indurated erythematous inflammatory reaction. The latter reaches a peak at about 6–8 hours and often persists for 24 hours. The reduction in the size of the LPR to intradermal allergen challenge correlates well with the clinical response to subcutaneous allergen immunotherapy in patients with allergic rhinitis.

Description of technique

Intradermal injections can be administered at a variety of accessible sites, but the skin of the abdomen or back is often used. The area in which the injections will be administered should be shaved with a small animal clipper to allow good visualization during and after dosing. Doses can be administered using a small hypodermic needle attached to a graduated tuberculin syringe. Needle diameter should be limited to 27 gauge or smaller, and 30 gauge is preferable. The use of a needle with an intradermal bevel is not necessary. Prior to dosing, the same procedures for test article preparation and analysis of formulations, weighing of mice, and calculation of doses should be followed as recommended for IP dosing. The dose is drawn into the syringe and air bubbles are expelled. The mouse is held in one hand, and the needle is inserted into the skin at a shallow angle with the bevel of the needle up to avoid penetration into the subcutaneous space. With practice, the toxicologist can feel the needle penetrate into the subcutaneous space, if that happens by accident, and can relocate the needle prior to injection. A properly administered intradermal dose will appear as a small bleb on the surface of the skin. A dose administered into the subcutaneous space will not appear as a bleb, as the dose will be distributed over a larger area.