Related Articles

AIM

To investigate the incidence of oculocardiac reflex (OCR) with two anesthetic regimens and its prevention using topical anesthetics in a rabbit model, and to explore the effect of topical anesthetics on corneal healing.

METHODS

Forty-eight clinically healthy adult New Zealand white rabbits of either sex were divided into two groups (Group A and B) and anesthetized with either ketamine (Group A, n =24) or propofol (Group B, n =24). he incidence of OCR was recorded in each group with a variety of ocular manipulation with or without the use of topical anesthetics (40g/L lignocaine, 5g/L proparacain, 5g/L bupivacaine). Corneal toxicity and healing following the use of each topical anesthetic was assessed one day after surgery and up to 7 days postoperatively by clinical examination of the eye, histopathology and collagen staining and transmission electron microscopy.

RESULTS

No incidence of OCR was recorded with ocular manipulation under ketamine anesthesia, whereas significant reduction in heart rate (P<0.01) was recorded under propofol anesthesia. Topical anesthetics could successfully prevent the OCR without affecting the corneal healing.

CONCLUSION

Topical anesthetics may be recommended for prevention of OCR without any local adverse effect.

The goal of the research was to compare the effectiveness of vibration with that of a topical anesthetic in reducing the pain of local anesthetic injections. Injections were given adjacent to maxillary premolars in four locations in 61 patients. Before injection, sites received either placebo or topical anesthetic with or without vibration. Patients rated the injection pain on a five-point scale. The topical anesthetic caused a statistically significant decrease in pain values; however, the amount of decrease was of questionable clinical significance.

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OBJECTIVE: To consider topical anesthetic options available to primary care physicians, indications for their use, and efficacy and safety of these agents as supported by the literature. QUALITY OF EVIDENCE: Five randomized controlled trials were retrieved that compared various topical anesthetics as well as topical anesthetics versus infiltrative anesthesia. MAIN FINDINGS: A combination of lidocaine, epinephrine, and tetracaine (LET) is currently the topical anesthetic of choice for repair of simple lacerations involving the faces and scalps of children. A promising new topical preparation is bupivacaine and epinephrine, but its efficacy must be studied in larger populations before widespread use can be advocated. Using EMLA (eutectic mixture of local anesthetics) for repair of extremity lacerations requires further study and cannot yet be recommended. Continued use of topical tetracaine, adrenaline, and cocaine (TAC) is not supported in the literature, because of its greater expense, its status as a restricted narcotic, its potential for toxicity, and better availability of an equally efficacious alternative, LET. CONCLUSIONS: Children's simple facial and scalp lacerations can be safely repaired using topical LET gel. Physicians must adhere to recommendations to avoid mucous membrane contact and ensure appropriate dosing with these agents. Bupivacaine-epinephrine topical preparation is a promising analgesic agent that warrants further study.

This investigation evaluated the use and efficacy of prilocaine HCl (4% plain Citanest) for minimizing pain associated with the intraoral administration of local anesthesia. Clinical anecdotes support the hypothesis that prilocaine without a vasoconstrictor reduces pain during injection. To determine relative injection discomfort, use of 4% plain prilocaine was compared with use of 2% lidocaine with 1:100,000 epinephrine and 2% mepivacaine with 1:20,000 levonordefrin. Prior to routine endodontic procedures, 150 adult patients received 0.3 to 1.8 mL of local anesthetic via the same gauge needle without the use of a topical local anesthetic. Injection methods included buccal infiltration, labial infiltration, palatal infiltration, and inferior alveolar nerve block. Following each injection, patients were asked to describe the level of discomfort by scoring on a visual analog scale of 1 to 10, where 1 = painless and 10 = severe pain. Analyses via 2-way analysis of variance revealed no interaction between anesthetic and site of injection. However, there were statistically significant differences among the injection sites. Post hoc analysis revealed that prilocaine was associated with significantly less pain perception when compared to mepivacaine and lidocaine. These results suggest that differences in initial pain perception during transmucosal injection may be a function of the local anesthetic use, and prilocaine can produce less discomfort than the others tested.

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Introduction

Corneal damage associated with abuse of topical anesthetics is a rare clinic entity. Topical anesthetic abuse is one of the causes of ring keratitis. Ring keratitis is easily overlooked because it can mimic acanthamoeba keratitis or other infectious keratitis. The outcome is often poor, leading to persistent epithelial defects, corneal scarring, and perforations.

Case presentation

We report the clinical presentation, diagnosis, and treatment of a 65-year-old Caucasian man, who worked as a health care worker, with bilateral toxic keratopathy caused by topical anesthetic abuse. Nonpreserved amniotic membrane transplantation was performed for both eyes of the patient.

Conclusion

It is important to identify and treat patients who abuse topical anesthetics before permanent vision loss ensues. Nonpreserved amniotic membrane transplantation may be useful in relieving pain and improving corneal surface in anesthetic agent abusers.

Background

Historically, children have been undertreated for their pain, and they continue to undergo painful cutaneous procedures without analgesics. A new topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR Pharma, Windsor, Ont.), has become available. It has pharmacologic properties that are superior to other topical anesthetics, including an onset of action of only 30 minutes. We sought to determine the success rate of cannulation, analgesic effectiveness, procedure duration and rate of adverse skin reactions when liposomal lidocaine is used before intravenous cannulation of children.

Methods

In this double-blind randomized controlled trial, children aged 1 month to 17 years received liposomal lidocaine or placebo before cannulation. Success on first cannulation attempt was recorded, and, among children 5 years and older, pain was evaluated before and after the attempt by the child, parents and research assistant using a validated measure (Faces Pain Scale-Revised). For children younger than 5 years, pain was evaluated by the parents and research assistant only. The total duration of the procedure and adverse skin reactions were also recorded.

Results

Baseline characteristics did not differ (p > 0.05) between children who received liposomal lidocaine (n = 69) and those who received placebo (n = 73). Cannulation on the first attempt was achieved in 74% of children who received liposomal lidocaine compared with 55% of those who received placebo (p = 0.03). Among children 5 years of age and older (n = 67), lower mean pain scores during cannulation were reported by those receiving liposomal lidocaine (p = 0.01). Similarly, lower mean pain scores during cannulation were reported by the parents and research assistant for all children who received liposomal lidocaine than for all those who received placebo (p < 0.001). The mean total procedure duration was shorter with liposomal lidocaine (6.7 v. 8.5 minutes; p = 0.04). The incidence of transient dermal changes was 23% in both groups (p = 1.0).

Conclusions

Use of liposomal lidocaine was associated with a higher intravenous cannulation success rate, less pain, shorter total procedure time and minor dermal changes among children undergoing cannulation. Its routine use for painful cutaneous procedures should be considered whenever feasible.

A local anesthetic-impregnated mucosal adhesive patch (DentiPatch) was compared with topical anesthetic (Hurricaine Dry Handle Swab) for gingival anesthesia before rubber dam clamp placement in children. Twenty-eight children needing sealants on their posterior teeth were enrolled in this study. Topical anesthesia was provided using either the mucoadhesive patch (20% lidocaine) or topical anesthetic (20% benzocaine). Subjects were randomized using a split mouth model. Either the patch or topical anesthetic was applied to the gingiva for 5 minutes or 1 minute, respectively. Subjects used a visual analog scale to describe their pain during the procedure. Linear regression and mixed linear models were used for data analysis. The visual analog scale results (pain scores) showed no significant difference between treatments. The mean per-child patch-sticking fraction was 29.7%. Patch adherence to oral mucosa increased with age in girls (P = .0045), but not in boys. The DentiPatch is as effective as, although not superior to, the Hurricaine Dry Handle Swab for gingival anesthesia before rubber dam clamp placement in children. These study results would not support the use of the DentiPatch for gingival anesthesia in children because of poor adherence to oral mucosa and the extra time necessary to apply and retain the device.

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This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery.

The problem of glass breakage in the local anesthetic cartridge system was evaluated under laboratory conditions with a mechanical testing machine. The anticipated breakage of the glass did not occur with any frequency, as the rubber stopper produced more uniform failures of the system. The glass cartridge appeared to be quite reliable and resistant to breakage.

Local anesthetics have been used for many years to provide patients temporary freedom from pain. Local anesthetic solutions are in wide use in both dentistry and medicine and are the most frequently used drugs in dentistry. Various estimates place the number of injections at approximately one half million daily or 125 million injections per year.

These drugs and the armamentarium necessary to administer them have proven to be safe and reliable. Only rarely are there reports of sensitivity to the anesthetic solution or breakage of needles.. Sterility of the solutions has not been a problem as they are carefully processed and evaluated at the factory. Although there are sporadic reports of loss of sterility, this has been attributed to the reuse of the anesthetic cartridges on more than one patient. Monheim states “The success of the cartridge system in dentistry has been due to the sincerity, honesty, and high standards of the manufacturers in giving the profession a near-perfect product.” However, on occassion a glass cartridge will break or shatter when inserting the harpoon into the rubber stopper or even during injection. Cooley et al reported on eye injuries occurring in the dental office, one of which was due to glass from a local anesthetic cartridge that exploded and propelled particles into the patient's eye. Forrest evaluated syringes, needles, and cartridges and reported that one brand (made in Britain) fractured more often than any other, but that the fracture rate was too low to be of any consequence.

It is apparent that glass cartridges will fracture or burst from time to time. This study evaluates the cartridge system with carefully controlled laboratory procedures. The cartridges were tested under various pressures and conditions in an attempt to determine the causes of failure and when such failure may be anticipated.

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One century after the clinical introduction of cocaine, local anesthesia remains the most important method of pain control in dentistry. Many local anesthetics have been marketed since 1884, and it is likely that attempts to produce drugs that enhance anesthetic efficacy, reduce systemic and local toxicity, and increase nociceptive selectivity, will continue. In addition, new methods of drug administration have been and will be developed to achieve these goals. Of fundamental importance to such improvements are investigations into the pharmacology of drugs with local anesthetic activity and anatomical and physiologic studies pertaining to the reasons why local anesthetics sometimes fail to achieve desired results. This paper reviews recent advances in our understanding of these drugs and their clinical use.

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Background

Topical anesthesia is a safe and cost-effective method considered as the first-choice in many procedures. Due to the physiological characteristics of eye, most of the local anesthetics cannot efficiently penetrate through the conjunctiva deep to tenon. The aim of this pilot study was to find a new form of lidocaine to give a sufficient level of anesthesia.

Methods:

Lidocaine Cyclodextrin complex ophthalmic drop was produced and its pharmacological properties were studied [tested] in standard temperature and pressure. 30 patients (18 males, 12 females) with the mean age of 30.68±8.02 years enrolled in this clinical trial. All the patients were fully informed and signed the ethics committee consent forms. The patients were given tetracaine drop as the anesthetic: 3 drops separated 2 minute apart 10 min before the intervention. If we achieved a sufficient level of anesthesia, the procedure was done after. If the patient could not tolerate the procedure, the method was changed to lidocaine drop (administered after wash-out period like the first drop).The last option was conventional injection method if the patient could not tolerate the procedure with the second method either.We used this type of anesthesia for conventional procedures such as forced duction test, symblepharon, pterygium, and disport injection into extra-ocular muscles. All the procedures were done by one surgeon in a university hospital. We used a 0 to 10 visual analogue scale for pain and two 0 to 4 patient and physician satisfaction scales designed for this study.

Results

The mean pain score was 7.53±0.90 in group 1 and 3.03±1.83 in group 2 (P=0.00). Patient and surgeon satisfaction in group 1 were 1.33±0.48 and 1.40±0.56 respectively; while 3.23±1.00 and 3.56±0.77 for group 2 (P=0.00). Tetracaine drop could not induce sufficient anesthesia for none of the patients. Cyclodextrin based lidocaine drop was successful except For two patients for whom we changed the anesthesia to Sub-conjunctival injection method.

Conclusion

Our newly manufactured cyclodextrin based lidocaine eye drop could successfully induce sufficient anesthesia for 28 of 30 patients. Further studies with larger sample sizes are now being designed to find more clinical evidence about this method.

The objective of this study was to determine the effect of time on the clinical efficacy of topical anesthetic in reducing pain from needle insertion alone as well as injection of anesthetic. This was a randomized, double-blind, placebo-controlled, split-mouth, clinical trial which enrolled 90 subjects, equally divided into 3 groups based upon time (2, 5, or 10 minutes) of topical anesthetic (5% lidocaine) application. Each group was further subdivided into 2: needle insertion only in the palate or needle insertion with deposition of anesthetic (0.5 mL 3% mepivacaine plain). Each subject received drug on one side and placebo on the other. Subjects recorded pain on a 100-mm visual analog scale (VAS). The results showed that for needle insertion only, 5% lidocaine reduced pain as determined by a significant difference in mean VAS after 2 minutes (20.1 mm, P < .002), 5 minutes (15.7 mm, P < .022), and 10 minutes (13.7 mm, P < .04), as analyzed by paired t tests. For needle insertion plus injection of local anesthetic, a significant difference in mean VAS was noted only after 10 minutes (14.9 mm, P < .031), yet pain scores for both topical anesthetic and placebo were elevated at this time point resulting in no reduction in actual pain. Time of application did not result in a significant difference in effect for either needle insertion only or needle insertion plus injection of local anesthetic, as analyzed by 1-way analysis of variance (ANOVA). In conclusion, topical anesthetic reduces pain of needle insertion if left on palatal mucosa for 2, 5, or 10 minutes, but has no clinical pain relief for anesthetic injection.

Background:

The Infobutton Manager (IM) is an application that provides clinical users with context-specfic links to health information resources. Usage of the first version (IM-1) suggested that the user interface was suboptimal.

Methods:

We conducted a laboratory-based observational study of IM-1 use, applied standard user interface design techniques to address observed problems, developed a new version (IM-2), conducted a second observational study and analyzed log files of the actual use of IM-1 and IM-2.

Results:

Modifications to the IM resulted in a reduction of “perusal time” (time between evocation of the IM and selecting a topic) from 11.13 to 5.92 seconds. However, evaluation of 14 months of usage logs did not show an appreciable effect on the perusal time or the rate at which users selected a topic once the IM was evoked.

Conclusions:

Laboratory analysis of the IM guided redesign that led to improved performance in the laboratory, but did not address factors that are influencing use.

Background

Post-herpetic neuralgia (PHN) is a common type of neuropathic pain that can severely affect quality of life. NGX-4010, a capsaicin 8% dermal patch, is a localized treatment that can provide patients with significant pain relief for up to 3 months following a single 60-minute application. The NGX-4010 application can be associated with application-site pain and in previous clinical trials pretreatment with a topical 4% lidocaine anesthetic was used to enhance tolerability. The aim of the current investigation was to evaluate tolerability of NGX-4010 after pretreatment with lidocaine 2.5%/prilocaine 2.5% anesthetic cream.

Methods

Twenty-four patients with PHN were pretreated with lidocaine 2.5%/prilocaine 2.5% cream for 60 minutes before receiving a single 60-minute application of NGX-4010. Tolerability was assessed by measuring patch application duration, the proportion of patients completing over 90% of the intended treatment duration, application site-related pain using the Numeric Pain Rating Scale (NPRS), and analgesic medication use to relieve such pain. Safety was assessed by monitoring adverse events (AEs) and dermal irritation using dermal assessment scores.

Results

The mean treatment duration of NGX-4010 was 60.2 minutes and all patients completed over 90% of the intended patch application duration. Pain during application was transient. A maximum mean change in NPRS score of +3.0 was observed at 55 minutes post-patch application; pain scores gradually declined to near pre-anesthetic levels (+0.71) within 85 minutes of patch removal. Half of the patients received analgesic medication on the day of treatment; by Day 7, no patients required medication. The most common AEs were application site-related pain, erythema, edema, and pruritus. All patients experienced mild dermal irritation 5 minutes after patch removal, which subsequently decreased; at Day 7, no irritation was evident. The maximum recorded dermal assessment score was 2.

Conclusion

NGX-4010 was well tolerated following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with PHN. The tolerability of the patch application appeared comparable with that seen in other studies that used 4% lidocaine cream as the pretreatment anesthetic. This study is registered at http://www.clinicaltrials.gov as number NCT00916942.

Propolis possesses various biological activities such as antibacterial, antifungal, anti-inflammatory, anesthetic and antioxidant properties. A topically applied product based on Brazilian green propolis was developed for the treatment of burns. For such substance to be used more safely in future clinical applications, the present study evaluated the mutagenic potential of topical formulations supplemented with green propolis extract (1.2, 2.4 and 3.6%) based on the analysis of chromosomal aberrations and of micronuclei. In the in vitro studies, 3-h pulse (G1 phase of the cell cycle) and continuous (20 h) treatments were performed. In the in vivo assessment, the animals were injured on the back and then submitted to acute (24 h), subacute (7 days) and subchronic (30 days) treatments consisting of daily dermal applications of gels containing different concentrations of propolis. Similar frequencies of chromosomal aberrations were observed for cultures submitted to 3-h pulse and continuous treatment with gels containing different propolis concentrations and cultures not submitted to any treatment. However, in the continuous treatment cultures treated with the 3.6% propolis gel presented significantly lower mitotic indices than the negative control. No statistically significant differences in the frequencies of micronuclei were observed between animals treated with gels containing different concentrations of propolis and the negative control for the three treatment times. Under the present conditions, topical formulations containing different concentrations of green propolis used for the treatment of burns showed no mutagenic effect in either test system, but 3.6% propolis gel was found to be cytotoxic in the in vitro test.

Purpose

Tear film composition depends on water and ion transport across ocular surface epithelia and on fluid secretion by lacrimal glands. The purpose of this study was to establish in situ fluorescence methods to measure tear film ionic concentrations and pH in mice and to determine whether tear film composition is sensitive to deficiency of the major ocular surface aquaporin water channels.

Methods

Tear film ionic concentrations and pH were measured in anesthetized mice by ratio imaging fluorescence microscopy after topical application of ion/pH-sensing, dual-wavelength fluorescent indicators. [Na+], [K+], and [Cl−] were measured with membrane-impermeant indicators developed by our laboratory, and pH was measured with bis(carboxyethyl)-carboxyfluorescein fluorescence-conjugated dextran. Measurements were performed on wild-type mice and on knockout mice lacking aquaporins AQP1, AQP3, and AQP5.

Results

In wild-type mice, tear film [Na+] was 139 ± 8 mM, [K+] was 48 ± 1 mM, [Cl−] was 127 ± 4 mM, and pH was 7.59 ± 0.2 (SE; n = 5–8). pH did not differ significantly in the AQP knockout mice. [Na+] was increased by approximately twofold in AQP5 null mice (230 ± 20 mM) and was greatly reduced after exposure of the ocular surface to a humidified atmosphere. [K+] was mildly reduced in AQP1 null mice.

Conclusions

These results establish an in situ optical methodology to measure tear film [Na+], [K+], [Cl−], and pH in living mice, without the need for fluid sampling. Tear film hypertonicity in AQP5 deficiency is likely caused by reduced transcorneal water secretion in response to evaporative water loss.

Wellness and pre-anesthetic screening of blood and urine of geriatric companion animals are routinely recommended. In addition, there are occasional references to the use of imaging in clinically normal geriatric patients. However, the utility of wellness testing is not known, and there is limited information regarding the value of pre-anesthetic testing. Wellness testing, including complete blood cell count, biochemical profile, urinalysis, and abdominal ultrasound, was performed on 53 clinically normal, mature golden retriever dogs. Laboratory analysis revealed abnormalities in 54.7% (29/53) of the dogs. Abdominal ultrasound screening demonstrated abnormalities in 64.2% (34/53) of the dogs. As only a small number of dogs had follow-up diagnostic testing available, the significance of these abnormalities is unknown. Further study involving a larger cohort of animals and analysis of follow-up data is necessary to determine the utility of laboratory and imaging studies in clinically normal geriatric patients.

The efficiency of a topical anesthetic occluded with Orahesive Oral Bandage was investigated. Experimental pain was provoked by needle insertions into two palatal test areas in 20 healthy subjects. Pain, estimated on a 100-mm visual analogue scale (VAS), decreased significantly from 23.5 mm to 10.5 mm at the greater palatine foramen and from 51.5 mm to 35.0 mm at the incisive foramen after application of a eutectic mixture of local anesthetics (EMLA). No significant change in pain perception was obtained after placebo application. The EMLA cream and the Orahesive Oral Bandages were well accepted by the subjects, as only two out of 20 subjects experienced slight gagging reflexes and only three considered the taste unpleasant. No other adverse reactions were observed. Occlusion of topical anesthetics seems to be a useful technique for achieving superficial mucosal anesthesia.

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Articaine, a new local anesthetic and the first substance of the amide type with a thiophene ring, has been studied to evaluate its effects on intrapulpal blood pressure (IPP) and mandibular and femoral pressures (MAP, FAP) after injections in the posterior mental foramen (PMF). Eight mongrel dogs of either sex, 9-12 months of age weighing from 15-25 kg were anesthetized. The PMF and the middle foramen were uncovered to expose the vascular-nerve bundle. The mandibular artery was dissected, cannulated, and filled with a heparinized normal saline solution. A 27-gauge needle was placed into the PMF for the injections of the local anesthetic. Into the ipsilateral canine, a cannula hermetically sealed and filled with heparinized saline solution was inserted. All hemodynamic measurements (IPP, MAP, FAP) were recorded with a precalibrated polygraph. The results obtained allow us to conclude that articaine 4% with epinephrine 1:100,000 injected in the PMF (0.3 ml), produces a drop of the intrapulpal blood pressure due to a strong vasoconstriction, whereas this effect is less pronounced at the MAP level and almost inexistent in the FAP.

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Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura. It negatively impacts tissue injury during stroke, cerebral contusion and intracranial hemorrhage. Susceptibility to CSD has been assessed in several experimental animal models in vivo, such as after topical KCl application or cathodal stimulation. Various combinations of anesthetics and ambient conditions have been used by different laboratories making comparisons problematic and differences in data difficult to reconcile. We systematically studied CSD susceptibility comparing commonly used experimental anesthetics (isoflurane, α-chloralose, urethane) with or without N2O or normobaric hyperoxia (100% O2 inhalation). The frequency of evoked CSDs, and their propagation speed, duration, and amplitude were recorded during 2 hour topical KCl (1M) application. We found that N2O reduced CSD frequency when combined with isoflurane or urethane, but not α-chloralose; N2O also decreased CSD propagation speed and duration. Urethane anesthesia was associated with the highest CSD frequency that was comparable to pentobarbital. Inhalation of 100% O2 did not alter CSD frequency, propagation speed or duration in combination with any of the anesthetics tested. Our data show anesthetic modulation of CSD susceptibility in an experimental model of human disease, underscoring the importance of proper study design for hypothesis testing as well as for comparing results between studies.

Background

The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.

Methods

This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4® [Ferndale Laboratories Inc, Ferndale, MI], Topicaine® Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL]) for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included “pain now” Numeric Pain Rating Scale (NPRS) scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs), clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for “average pain for the past 24 hours” from baseline to weeks 2 through 12.

Results

Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate, and could be adequately managed by local cooling or short-acting oral opioid analgesics. Although slightly more patients used medication for treatment-related discomfort following pretreatment with Topicaine compared with L.M.X.4 or Betacaine, there were no statistical differences between the topical anesthetics. Neuropathic pain reduction from baseline to weeks 2 through 12 was approximately 30% and was similar among the topical anesthetics; the proportion of responders ranged from 45% to 50%.

Conclusion

Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated; no significant differences in the parameters measured were noted between the pretreatment groups.

Background

Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.

Methods

Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution.

Results

All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution’s buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution’s osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution’s H+ concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA).

Conclusions

(1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H+]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H+], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.

The efficacy of a topical anesthetic on pain and unpleasantness provoked by scaling of gingival pockets was investigated in 20 patients with mild chronic periodontitis. A eutectic mixture of local anesthetics (EMLA) and a placebo cream, both occluded by Orahesive Oral Bandages, were applied in a balanced, randomized, double-blind, split-mouth design, which enabled within-subject comparison of the anesthetic and the placebo in the upper and the lower jaw. Pretreatment interviews showed that approximately two-thirds of the patients considered gingival scaling to be associated with some degree of pain and unpleasantness. Pain intensity and unpleasantness were evaluated on 100-mm visual analog scales (VAS). Application of EMLA reduced both pain intensity and unpleasantness significantly compared to placebo cream. Median reductions in VAS pain intensity in the upper and lower jaw were 58.9% and 61.9%, and corresponding reductions in VAS unpleasantness were 31.9% and 25.6%, respectively. Generally, the patients accepted the anesthetic procedure well. The residual perception of pain and unpleasantness following topical anesthesia may be dependent on activation of nonanesthetized nociceptive fibers in the tooth pulp. However, the present study clearly demonstrates the efficacy of a topical anesthetic in a clinical situation, which may be recommended as a simple pharmacologic strategy to reduce pain and unpleasantness during scaling procedures.

Objective

To report the incidence of endophthalmitis following intravitreal injection using a standardized procedure.

Methods

Intravitreal injections of preservative-free triamcinolone acetonide or ranibizumab were performed in two Diabetic Retinopathy Clinical Research Network prospective, randomized clinical trials. The standardized procedure for these trials requires topical povidone-iodine, use of a sterile lid speculum and topical anesthetic, but does not require the use of topical antibiotics prior to, on the day of, or after injection.

Results

As of February 23, 2009, 3226 intravitreal injections of ranibizumab and 612 injections of preservative-free triamcinolone have been administered. Topical antibiotics were given on the day of injection in 361(9%), for several days after injection in 813(21%), on the day of injection and after injection in 1388(36%), and neither on the day of injection nor after injection in 1276(33%). Three cases of culture positive endophthalmitis occurred following ranibizumab injections (0.09%) and no cases occurred following triamcinolone injections. In all three endophthalmitis cases, topical antibiotics were given for several days after the injection but not prior to injection.

Conclusions

The results suggest that a low rate of endophthalmitis can be achieved using a protocol that includes topical povidone-iodine, use of a sterile lid speculum and topical anesthetic but does not require topical antibiotics.

Background:

Various studies have assessed patient satisfaction with topical versus peribulbar anesthesia with conflicting results. Aim of study was to determine satisfaction level in same patient who gets topical anesthesia in one eye and peribulbar block in another eye. We propose that evaluation of various indicators of patient satisfaction will enable better selection of cases for topical anesthesia in the future.

Methods:

Eighty patients scheduled for phacoemulsification were enrolled in prospective, randomized, double-blind study. Each patient scheduled twice for one eye under topical anesthesia and other in peribulbar block. Pain, discomfort and pressure during application of local anesthetic, during phacoemulsification and at 2 hours after procedure were assessed on standard scales. Before discharge patient satisfaction level was checked with Iowa satisfaction with anesthesia scale (ISAS). The Student's t-test was used to determine the significance of IOWA score in both groups. P<0.05 was considered significant.

Results:

Feeling of pain, pressure and discomfort scores during administration of topical anesthesia were all significantly lower compared to peribulbar anesthesia (P=0.004, 0.000, 0.002, respectively). In contrast, intraoperative scores were significantly higher in the topical anesthesia group compared to peribulbar anesthesia (P=0.022, 0.000, 0.000, respectively). Patient satisfaction measured with ISAS shows that peribulbar anesthesia with P=0.000 is strongly significant.

Conclusion:

Peribulbar anesthesia provided significantly better patient satisfaction in comparison with topical anesthesia when used for cataract surgery.