Rapid cooling anesthesia device effective for achieving LA for intravitreal injection: JAMA

Factors which influence the choice of anesthesia by retina specialists include patient satisfaction, procedure workflow and efficiency, and cost. An alternative method of anesthesia that is well tolerated by patients and has a rapid onset of action may improve both the patient experience as well as clinical workflow.

Using low temperatures as a form of anesthesia for medical applications has been investigated in many settings, and is commonly used as anesthesia for injection of dermal fillers. Mechanisms for anesthesia using low temperature include decreased nerve conduction which inhibits the firing of pain receptors, and release of endorphins. Here, authors define the term "cooling anesthesia" as the focal application of temperatures slightly below freezing (usually between −10 and −20 degrees Celsius) as a method of local anesthesia. This temperature is much higher than temperatures that have been shown to cause tissue damage to the eye, such as from cryotherapy.

To extend this work, a clinical grade next-generation handheld cooling device was developed. In this study, Chao et al reported results from a first in human study using this cooling device to evaluate the safety and feasibility of providing local anesthesia for IVT.

First in human, open-label study of 43 subjects assessed at three different doses: −10°C for 20 seconds (group 1), −15°C for 15 seconds (group 2), and −15°C for 20 seconds (group 3). Main outcome measures were safety and pain of injection using a numeric rating scale (NRS).

Cooling anesthesia did not result in any serious ocular adverse events. One grade 1 adverse event was a vasovagal response during cooling administration which resolved immediately after cooling. Mean NRS scores at the time of injection for each group ranged from 2.5 to 4.3 There was a statistically significant difference between pain scores of the 3 groups at injection in aggregate but not in pairwise comparisons (P value = 0.047). There was a statistically significant decrease in pain from injection to 5 minutes post injection in all groups (P value = 0.00008, 0.003, 0.0005 for groups 1, 2, 3, respectively) as well as from 5 minutes to 24–48 hours (P value = 0.00001, 0.018, and 0.0545 for groups 1, 2, 3, respectively).

In this first in human clinical study, the safety of a clinical grade precision cooling device was evaluated across multiple treatment regimens. Cooling anesthesia during IVT offers potential advantages over current methods of anesthesia, including rapid onset of action and a nonpharmacologic approach. The current study consisted of subjects who had received multiple prior IVTs, all with subconjunctival lidocaine as their previous anesthetic. Multiple studies on cryotherapy on human eyes suggest that the cooling temperatures used in the current study do not cause damage to the eye.

The results of the current study indicate that the device was well tolerated with no serious adverse events or serious ocular adverse events. No signs of conjunctival scarring or thinning with this single administration were observed. One grade 1 adverse event occurred among 43 cooling administrations, a transient vasovagal response that resolved without intervention. Various physiological responses, such as the oculocardiac reflex which can result in bradycardia have been observed with intravitreal injections which potentially could lead to a vasovagal response. Authors believed that this adverse event is related to the cooling anesthesia, as this response began during cooling administration.

A single drop of 0.5% proparacaine was applied before cooling anesthesia application. While proparacaine rapidly anesthetizes the ocular surface, the cooling device simultaneously cools the eye surface including the sclera within 10 seconds, providing rapid and sufficient anesthetic effect for IVT. Thus, one potential benefit of the cooling device is that cooling anesthesia can be applied immediately after instillation of the topical anesthetic, allowing one to perform IVT immediately after examination, which may have benefits for patients and physicians.

"In summary, the cooling anesthesia used in the current study was safe and well tolerated for patients receiving IVT as standard of care management for their retinal disease. The specific properties of cooling anesthesia, particularly its rapid onset of action, may offer unique benefits for the patient experience. Further investigation is needed to understand the long-term effects of repeated cooling anesthesia use, and its effectiveness compared to current standard of care anesthetics."

Source: Chao et al; Clinical Ophthalmology 2021:15 4659–4666

https://doi.org/10.2147/OPTH.S336653