The management of corneal abrasions has largely excluded dispensing topical local anesthetics for home use due to concern for corneal toxicity. We have reviewed and critically appraised the available ...literature evidence regarding the use of topical anesthetics in patients with simple corneal abrasions. Using sequential Delphi review, we have developed these clinical guidelines. Herein are evidentiary summaries and consensus recommendations for 8 specific relevant questions. Our key observation is that for only simple corneal abrasions, as diagnosed and treated in accordance with the full protocol described herein, it appears safe to prescribe or otherwise provide a commercial topical anesthetic (ie, proparacaine, tetracaine, oxybuprocaine) for use up to every 30 minutes as needed during the first 24 hours after presentation, as long as no more than 1.5 to 2 mL total (an expected 24-hour supply) is dispensed and any remainder is discarded after 24 hours. Importantly, although published findings suggest absent harm for short courses, more rigorous studies with a greater cumulative sample size and ophthalmologic follow-up are needed.
Background: The administration of amide-type local anesthetics to cartilaginous tissues has revealed potential chondrotoxicity.
Purpose: This study evaluated whether administration of single doses of ...1% lidocaine, 0.25% bupivacaine, and 0.5% ropivacaine resulted in decreased chondrocyte viability or cartilage matrix degradation in vitro.
Study Design: Controlled laboratory study.
Methods: Monolayer human chondrocytes and intact cartilage samples were cultured for 1 week in media. Each drug was delivered in a custom bioreactor over its clinical duration of action. A Live/Dead Viability/Cytotoxicity Assay was used to determine the ratio of dead to live cells for monolayer chondrocyte cultures compared with controls. Damage to the cartilage extracellular matrix (ECM) in en bloc cartilage samples was evaluated by analysis of DNA, glycosaminoglycan (GAG), and collagen content.
Results: Chondrocytes treated for 3 hours with a single dose of 1% lidocaine exhibited significantly more cell death (7.9%) compared with control media (2.9%; P < .001). No significant difference in cell death was observed in chondrocytes treated for 6 hours with 0.25% bupivacaine (2.7%) versus controls (2.8%; P = .856) or cells treated for 12 hours in 0.5% ropivacaine (2.9%) versus controls (2.4%; P = .084). There was no significant difference in GAG expression (P = .627) or DNA-normalized GAG expression (P = .065) between the intact cartilage treatment groups; however, the DNA-normalized GAG expression was markedly lower in cartilage cultures treated with 1% lidocaine (3.36 ± 1.15) compared with those in control media (7.61 ± 3.83).
Conclusion: The results of this in vitro study indicate that a single-dose administration of 1% lidocaine resulted in a significant decrease in chondrocyte viability when compared with control cultures.
Clinical Relevance: Single-dose injections of 1% lidocaine may be significantly chondrotoxic, and further investigation regarding in vivo chondrotoxicity appears warranted.
The dural puncture epidural (DPE) technique is a modification of the combined spinal epidural (CSE) technique, where a dural perforation is created from a spinal needle but intrathecal medication ...administration is withheld. The DPE technique has been shown to improve caudal spread of analgesia compared with epidural (EPL) technique without the side effects observed with the CSE technique. We hypothesized that the onset of labor analgesia would follow this order: CSE > DPE > EPL techniques.
A total of 120 parturients in early labor were randomly assigned to EPL, DPE, or CSE groups. Initial dosing for EPL and DPE consisted of epidural 20 mL of 0.125% bupivacaine plus fentanyl 2 μg/mL over 5 minutes, and for CSE, intrathecal 0.25% bupivacaine 1.7 mg and fentanyl 17 μg. Upon block completion, a blinded coinvestigator assessed the outcomes. Two blinded obstetricians retrospectively interpreted uterine contractions and fetal heart rate tracings 1 hour before and after the neuraxial technique. The primary outcome was time to numeric pain rating scale (NPRS) ≤ 1 analyzed by using Kaplan-Meier curves and Cox proportional hazard model. Secondary outcomes included block quality, maternal adverse effects, uterine contraction patterns, and fetal outcomes analyzed by using the χ test with Yates continuity correction.
There was no significant difference in the time to NPRS ≤ 1 between DPE and EPL (hazard ratio 1.4; 95% confidence interval CI 0.83-2.4, P = .21). DPE achieved NPRS ≤ 1 significantly slower than CSE (hazard ratio 0.36; 95% CI 0.22-0.59, P = .0001). The median times (interquartile range) to NPRS ≤ 1 were 2 (0.5-6) minutes for CSE, 11 (4-120) minutes for DPE, and 18 (10-120) minutes for EPL. Compared with EPL, DPE had significantly greater incidence of bilateral S2 blockade at 10 minutes (risk ratio RR 2.13; 95% CI 1.39-3.28; P < .001), 20 minutes (RR 1.60; 95% CI 1.26-2.03; P < .001), and 30 minutes (RR 1.18; 95% CI 1.01-1.30; P < .034), a lower incidence of asymmetric block after 30 minutes (RR 0.19; 95% CI 0.07-0.51; P < .001) and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; P = .011). Compared with CSE, DPE had a significantly lower incidence of pruritus (RR 0.15; 95% CI 0.06-0.38; P < .001), hypotension (RR 0.38; 95% CI 0.15-0.98; P = .032), combined uterine tachysystole and hypertonus (RR 0.22; 95% CI 0.08-0.60; P < .001), and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; p = .011).
Analgesia onset was most rapid with CSE with no difference between DPE and EPL techniques. The DPE technique has improved block quality over the EPL technique with fewer maternal and fetal side effects than the CSE technique for parturients requesting early labor analgesia.
Periarticular injections (PAIs) are becoming a staple component of multimodal joint pathways. Motor-sparing peripheral nerve blocks, such as the infiltration between the popliteal artery and capsule ...of the posterior knee (IPACK) and the adductor canal block (ACB), may augment PAI in multimodal analgesic pathways for knee arthroplasty, but supporting literature remains rare. We hypothesized that the addition of ACB and IPACK to PAI would lower pain on ambulation on postoperative day (POD) 1 compared to PAI alone.
This triple-blinded randomized controlled trial included 86 patients undergoing unilateral total knee arthroplasty. Patients either received (1) a PAI (control group, n = 43) or (2) an IPACK with an ACB and modified PAI (intervention group, n = 43). The primary outcome was pain on ambulation on POD 1. Secondary outcomes included numeric rating scale (NRS) pain scores, patient satisfaction, and opioid consumption.
The intervention group reported significantly lower NRS pain scores on ambulation than the control group on POD 1 (difference in means 95% confidence interval, -3.3 -4.0 to -2.7; P < .001). In addition, NRS pain scores on ambulation on POD 0 (-3.5 -4.3 to -2.7; P < .001) and POD 2 (-1.0 -1.9 to -0.1; P = .033) were significantly lower. Patients in the intervention group were more satisfied, had less opioid consumption (P = .005, postanesthesia care unit, P = .028, POD 0), less intravenous opioids (P < .001), and reduced need for intravenous patient-controlled analgesia (P = .037).
The addition of IPACK and ACB to PAI significantly improves analgesia and reduces opioid consumption after total knee arthroplasty compared to PAI alone. This study strongly supports IPACK and ACB use within a multimodal analgesic pathway.
Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a ...literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.
Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the ...barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo.
Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution.
Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval CI, -1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129-1818 µg/(cm(2)·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468-2157 µg/(cm(2)·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs.
Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.
The prevalence of chronic low back pain and related disability is rapidly increasing as are the myriad treatments, including epidural injections. Even though epidural injections are one of the most ...commonly performed procedures in managing low back and lower extremity pain, starting in 1901 with local anesthetic alone, conflicting recommendations have been provided, despite the extensive literature. Recently Chou et al performed a technology assessment review for Agency for Healthcare Research and Quality (AHRQ) part of which was published in Annals of Internal Medicine showing lack of effectiveness of epidural steroid injections in managing lumbar radiculopathy and spinal stenosis. In contrast, multiple other publications have supported the efficacy and use of epidural injections.
To assess the efficacy of 3 categories of epidural injections for lumbar and spinal stenosis: performed with saline with steroids, local anesthetic alone, or steroids with local anesthetic and separate facts from opinions.
PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed through August 2015.
Randomized trials, either placebo or active control, of epidural injections for lumbar radiculopathy and spinal stenosis.
Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing principles of best evidence synthesis.
Thirty-nine randomized controlled trials met inclusion criteria. There were 9 placebo-controlled trials evaluating epidural corticosteroid injections, either with sodium chloride solution or bupivacaine, compared to placebo injections. There were 12 studies comparing local anesthetic alone to local anesthetic with steroid.
A meta-analysis of 5 studies utilizing sodium chloride or bupivacaine with steroid showed a lack of efficacy.A comparison of lidocaine to lidocaine with steroids in 7 studies showed significant effectiveness from baseline to long-term follow-up periods. Meta-analysis showed a similar effectiveness for pain and function without non-inferiority of lidocaine compared to lidocaine with steroid at 3 months and 12 months.
The review was restricted to the data available with at least 3 months of follow-up, which excluded some studies. The inclusion criteria were restricted to English language studies.
Epidural corticosteroid injections for radiculopathy or spinal stenosis with sodium chloride solution or bupivacaine were shown to be ineffective. Lidocaine alone or lidocaine in conjunction with steroids were significantly effective.
The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic ...nerve blockade without causing nerve damage.
Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.
High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.
The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.
Zusammenfassung
Die Entwicklung von Lokalanästhetika (LA) hat die Durchführung schmerzhafter Eingriffe revolutioniert. Lokalanästhetika wirken auf spannungsabhängige Natriumkanäle an Nervenfasern und ...modulieren die Impulsweiterleitung. Hinsichtlich der chemischen Struktur der Lokalanästhetika lassen sich der Amid- und Estertyp unterscheiden. Die strukturellen Unterschiede der Lokalanästhetika haben Einfluss auf Wirkdauer, Abbauwege und spezifische Nebenwirkungen. Schwerwiegende Nebenwirkungen sind unter anderem die Kardio- und Neurotoxizität. Neben Basismaßnahmen wie der Überwachung und Sicherstellung von Vitalparametern stellt die Lipidinfusion eine Therapieform bei Intoxikation dar. Die neueren Entwicklungen von Lokalanästhetika betreffen vor allem die Reduktion der Toxizität und die Verlängerung der Wirkdauer.
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