Chloroprocaine 3% Gel as a Novel Ocular Topical Anesthetic: Results from a Multicenter, Randomized Clinical Trial in Patients Undergoing Cataract Surgery.

Purpose: To compare the efficacy and safety of a novel ophthalmic anesthetic, chloroprocaine 3% gel to tetracaine 0.5% eye drops in patients undergoing cataract surgery with phacoemulsification. Methods: This was a prospective, randomized, multicenter, active-controlled, masked-observer, parallel group competitive equivalence study. The study comprised 338 patients having routine cataract extraction by clear corneal phacoemulsification, randomized to receive 3 drops of chloroprocaine gel (n = 166) or tetracaine eye drops (n = 172) before surgery. The primary objective of the study was to assess the equivalence of chloroprocaine gel to tetracaine eye drops as proportion of patients with successful ocular surface anesthesia, without any supplementation just before intraocular lens implantation. Safety measurements were pain, irritation, burning, stinging, photophobia, and foreign body sensation, graded by the patient and objective ocular signs. Results: Equivalence was demonstrated, with a somewhat higher success rate of chloroprocaine gel: 152/166 (92.0%) chloroprocaine versus 153/172 (90.5%) tetracaine patients achieved ocular surface anesthesia with no supplementation. Difference in proportions was 1.5% confidence interval [95% CI: (-3.6 to 6.6)] and 90% CI fell within (-10 to 10). Mean onset of anesthesia was 1.35 ± 0.87 min for chloroprocaine and 1.57 ± 1.85 for tetracaine (P = 0.083). Mean duration of anesthesia was 21.57 ± 12.26 min for chloroprocaine and 22.04 ± 12.58 for tetracaine (P = 0.574). No treatment emergent adverse events related to chloroprocaine were reported and no relevant findings related to local tolerance or vital signs were observed in both arms. Conclusions: Results obtained from the present cataract study demonstrated that chloroprocaine 3% ophthalmic gel is safe and effective, representing a valid alternative in ocular topical anesthesia. Clinical Trial Registration number: NCT04685538.

Treatment of catecholaminergic polymorphic ventricular tachycardia in mice using novel RyR2-modifying drugs.

RATIONALE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal arrhythmic disorder caused by mutations in the type-2 ryanodine receptor (RyR2). Mutant RyR2 cause abnormal Ca2+ leak from the sarcoplasmic reticulum (SR), which is associated with the development of arrhythmias. OBJECTIVE: To determine whether derivatives of tetracaine, a local anesthetic drug with known RyR2 inhibiting action, could prevent CPVT induction by suppression of RyR2-mediated SR Ca2+ leak. METHODS AND RESULTS: Confocal microscopy was used to assess the effects of tetracaine and 9 derivatives (EL1-EL9) on spontaneous Ca2+ sparks in ventricular myocytes isolated from RyR2-R176Q/+ mice with CPVT. Whereas each derivative suppressed the Ca2+ spark frequency, derivative EL9 was most effective at the screening dose of 500nmol/L. At this high dose, the Ca2+ transient amplitude was not affected in myocytes from WT or R176Q/+ mice. The IC50 of EL9 was determined to be 13nmol/L, which is about 400× time lower than known RyR2 stabilizer K201. EL9 prevented the induction of ventricular tachycardia observed in placebo-treated R176Q/+ mice, without affecting heart rate or cardiac contractility. CONCLUSIONS: Tetracaine derivatives represent a novel class of RyR2 stabilizing drugs that could be used for the treatment of the potentially fatal disorder catecholaminergic polymorphic ventricular tachycardia.

Does the use of topical lidocaine, epinephrine, and tetracaine solution provide sufficient anesthesia for laceration repair?

OBJECTIVE: To determine: 1) the effectiveness of lidocaine, epinephrine, and tetracaine (LET) solution in eliminating or reducing the pain experienced in suturing superficial lacerations in adult patients; and 2) the effectiveness of LET in reducing the pain of local anesthetic injection. METHODS: A prospective, randomized, double-blind study in which 60 adult patients with superficial lacerations were entered was conducted in the ED of a community-based teaching hospital affiliated with the University of Toronto. Following application of the LET or placebo (sterile water) solution to the laceration, a visual analog pain scale was recorded by the patient upon needle probing of the wound margin. If probing was painless, the laceration was repaired using LET alone. If injection of local anesthetic was required, an additional pain scale was elicited to quantify the attenuation of the pain of injection by the prior application of LET. RESULTS: Pain scale values on needle probing were significantly reduced in the LET group vs the placebo group (medians of 4.0 vs 5.0 cm, respectively; p < 0.05). Only 13 of the 30 patients in the LET group required additional anesthetic, while all 30 patients in the placebo group requested local anesthetic. Pain scale values on injection of local anesthetic were not significantly different between the LET and placebo groups (medians of 3.5 vs 5.0 cm, respectively; p = 0.09), although there was a trend for lower pain scale values for those patients who received LET. No adverse effects were noted after the application of either LET or placebo solution. Follow-up was achieved for 54 of 60 patients with only 1 complication (a wound infection) reported in the LET group. CONCLUSIONS: Significantly fewer patients require an injectable anesthetic when LET is applied. Those who do require an injection may experience less discomfort. These advantages should be balanced against the 20 to 30 minutes necessary for the LET to take effect.

EMLA versus TAC for topical anesthesia of extremity wounds in children.

STUDY OBJECTIVE: To compare the anesthetic efficacy of EMLA (eutectic mixture of local anesthetics) cream with that of TAC (tetracaine, adrenaline, and cocaine) solution for suturing uncomplicated extremity wounds. METHODS: We conducted a prospective, single-blind, randomized trial in a convenience sample of 32 children, ages 5 to 18 years, who required repair of an extremity laceration. Eligible wounds were less than 5 cm long and less than 12 hours old. Lacerations involving digits, deep tissues, or musculature were excluded. Patients receiving medications that predisposed them to methemoglobinemia were also excluded. Lacerations were treated with TAC .1 mL/kg (maximum, 3.0 mL) or EMLA .15 g/kg (maximum, 5.0 g). Anesthesia was assessed every 10 minutes. TAC and EMLA were allowed to remain on the wounds for a maximum of 30 and 60 minutes, respectively. Anesthesia was deemed successful if no supplemental lidocaine was required, as judged by a suturing caregiver who was blinded to the anesthetic used. RESULTS: The two groups were similar with regard to age, sex, wound length and depth, and wound age. EMLA-treated wounds were repaired without supplemental anesthesia more often than TAC-treated wounds: 13 of 16 (85%) versus 7 of 16 (45%, P= .03). More time was required for EMLA to cause anesthesia (55 versus 29 minutes, P<.01). Dehiscence occurred in one wound in each group; no wound infections were observed. CONCLUSION: EMLA appears to be superior to TAC for anesthesia of simple extremity lacerations in that those wounds treated with EMLA required supplemental anesthesia less often. EMLA required approximately 1 hour to cause optimal anesthesia in open wounds. Protocols should be developed to allow efficient use of EMLA for anesthesia of extremity lacerations in the ED.

Effect of percutaneous local anaesthetics on pain reduction during pulse dye laser treatment of portwine stains.

We have used EMLA, 4% amethocaine gel and placebo for facial portwine stains, for a period of 1 h, in a double-blind study. After removal of the preparations from the skin surface, each area was treated with six pulses of the laser, each 5 mm in diameter. Any pain noted immediately after treatment was recorded using both visual analogue (VAS) and verbal rating (VRS) scores. Twenty nine patients completed the study and statistical analysis of the results indicated that both EMLA and 4% amethocaine gel were superior to placebo (P < 0.001). However, when EMLA and 4% amethocaine gel were compared, the amethocaine preparation was significantly better (P < 0.05, VAS; P < 0.005 VRS) than EMLA in reducing pain caused by the laser treatment.

Tetracaine, epinephrine (adrenalin), and cocaine (TAC) versus lidocaine, epinephrine, and tetracaine (LET) for anesthesia of lacerations in children.

STUDY OBJECTIVE: To compare the duration of anesthesia experienced with lidocaine, epinephrine, and tetracaine (LET) solution and that with tetracaine, epinephrine (Adrenalin), and cocaine (TAC) solution during suturing of uncomplicated lacerations on the face or scalp. DESIGN: Double-blind, randomized, controlled trial. SETTING: The emergency department of a university-affiliated private children's hospital. PARTICIPANTS: One hundred seventy-one children with lacerations on the face and scalp requiring suturing. INTERVENTIONS: After standard application of the anesthetic solution, patients were assessed for signs of discomfort before and during laceration repair. Duration of anesthesia during laceration repair was determined on the basis of the length of time after removal of the anesthetic solution to the first sign(s) of discomfort that required additional anesthesia. RESULTS: There was no statistical difference between TAC and LET in adequacy of anesthesia before suturing or in duration of anesthesia during suturing. CONCLUSION: LET is an effective alternative to TAC for topical anesthesia during suturing of uncomplicated lacerations on the face and scalp in children.

Pain management in the child.

The most common complaint motivating patients to seek care in Emergency Departments is pain. The specialty of emergency medicine has an ideal opportunity to practice compassionate, effective analgesic techniques. Children and adults should have pain treated with the same vigor and concern as if we ourselves or our family members were suffering. The technology is currently available for effective compassionate analgesic techniques to be provided to pediatric and adult victims of illness and injury presenting to Emergency Departments for care. Acute pain should be treated with the same priority given to the medical and surgical emergencies. There are many approaches to treating the above case, all allowing the necessary procedures to be done comfortably. If emergency physicians would treat the pain of their patients as they would want it to be treated in themselves or their families, then we will have made great strides as a specialty in mastering the art and science of analgesia.

Failure of tetracaine to reverse spinal cord injury in the cat.

Beginning 30 minutes after acute spinal cord injury, cats were treated by the administration of continuous spinal anesthesia for 8 hours. This was achieved by the intermittent injection of hyperbaric tetracaine into the subarachnoid space at the site of injury via an indwelling catheter. There were no significant differences in functional recovery or histologically assessed tissue preservation between treated cats and concurrently managed control animals. The indwelling subarachnoid catheter used for drug administration was found to have no significant effect on the spinal cord injury.