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.

In situ sono-rheometric assessment of procaine-loaded calcium pectinate hydrogel for enhanced drug releasing under ultrasound stimulation.

Ultrasound (US) triggered alterations in the viscoelastic behavior of the procaine-loaded ionically gelatinized pectin hydrogel matrix, and drug release was observed using a sono-device rheometer. The gel softened immediately upon activation of the ultrasound operated at 43 kHz and remained in a softened state throughout the irradiation. Upon cessation of ultrasound, the gel promptly reverted to its original hardness. This cycle of softening was consistently observed in ionically crosslinked pectin hydrogels, resulting in the promotion of procaine release, particularly with higher US power and lower calcium concentration. As the amount of loaded procaine increased, the gel weakened due to ion exchange with the calcium crosslinker and procaine. The most substantial release efficiency, reaching 82 % with a concentration of 32 µg/ml, was achieved when the hydrogels contained 0.03 % procaine within the gelatinized hydrogel medicine at a calcium concentration of 0.9 M, representing a six-fold increase compared to that without US. Notably, US exposure affected the 3D porous structure and degradation rate, leading to hydrogel collapse and facilitating medicine release. Additionally, the procaine-loaded pectin hydrogels with 0.9 M calcium exhibited improved fibroblast cell viability, indicating non-toxicity compared to those hydrogels prepared at a higher Ca2+ concentration of 2.4 M.

Highly Efficient Loading of Procaine on Water-Soluble Carbon Dots toward Long-Acting Anesthesia.

Safe and efficient local anesthetic delivery carriers are crucial for long-term anesthesia and analgesics in clinical treatment. But currently, most of the local anesthetic carriers still have some disadvantages such as low drug-loading capacity, drug leakage, and potential side effects. Here, we report red-emissive carbon dots (Cys-CDs) synthesized by choosing cysteine and citric acid as precursors, which contain a large and intact sp2-domain with rich hydrophilic groups around the edge. The special structure of Cys-CDs is conducive to the efficient loading of procaine (PrC) via strong π-π stacking interactions. Based on the strong noncovalent interactions between them, the PrC loaded on Cys-CDs achieved slow release in vitro and had a long-lasting nerve blocking effect in vivo, which is 4-fold more than that of free PrC. More importantly, PrC/Cys-CDs do not cause any toxicity and inflammation during treatment owing to slow release of PrC and good water solubility of Cys-CDs, thus demonstrating the potential clinical application of CDs in long-lasting analgesia.

Stellate ganglion block with procaine in breast cancer survivors with hot flashes and sleep disturbances undergoing Endocrine Therapy.

Breast cancer survivors under endocrine therapy (ET) suffer from side effects such as hot flashes and sleep disturbance accompanied by poor quality of life. Many quit ET early and reduce their survival rate. Guidelines recommend gabapentin next to yoga or acupuncture. The role of side effects related to compliance with ET over years require new and effective therapies. Stellate ganglion block (SGB) has shown evidence of safety and efficacy and was found to be more effective than pregabalin without side effects. However, practical guidelines for the long-term use of SGB are still missing. We primarily used procaine instead of bupivacaine presuming effectiveness paired with lower toxic risks. Twenty-nine breast cancer survivors with severe hot flashes and sleep disturbance under ET received SGB with Procaine. Diaries recorded hot flashes and sleep quality scores up to week 24. All patients took part and none refused SGB. Each Patient received one SGB every 4 weeks without any side effects observed. Weekly scores were reduced from baseline by -33.6% (P < .01) (hot flashes) and -22.3% (P < .01) (sleep disturbances) after 4, and by -58.8% (P < .01) (hot flashes) and -50.8% (P < .01) (sleep disturbances) after twenty-for weeks. A wavelike reduction indicated a limited effect of a single SGB during continuous ET. We showed, that procaine in SGB is as effective as bupivacaine with lower risks and costs. High significant reductions in hot flashes and sleep disturbances after 1 and 6 months were found. We conclude that breast cancer survivors need individual treatment with SGB due to her personal impact. Hence, SGB should find its way to guidelines and daily routines as a valuable method for treating side effects in breast cancer survivors undergoing ET.

Chloroprocaine antagonizes progression of breast cancer by regulating LINC00494/miR-3619-5p/MED19 axis.

Breast cancer, as the most prevalent female malignancy, leads the cancer-related death in women worldwide. Local anesthetic chloroprocaine exhibits antitumor potential, but its specific functions and underlying molecular mechanisms in breast cancer remain unclear. Here, we demonstrated chloroprocaine significantly inhibited proliferation, invasion and induced apoptosis of breast cancer cells in vitro. Tumor growth and pulmonary metastasis were also suppressed in BABL/c nude mice model with chloroprocaine treatment. LINC00494 was identified as one of the most downregulated long noncoding RNAs in chloroprocaine-treated breast cancer cells by high-throughput sequencing. Futhermore, high level of LINC00494 was positively associated with poor outcome of breast cancer patients. LINC00494 acted as a "miRNAs sponge" to compete with MED19 for the biding of miR-3619-5p, led to the upregulation of MED19. LINC00494/miR-3619-5p/MED19 axis participated in chloroprocaine-mediated inhibition of proliferation, invasion and promotion of apoptosis of breast cancer cells. Consequently, our finding suggested local anesthetic chloroprocaine attenuated breast cancer aggressiveness through LINC00494-mediated signaling pathway, which detailly revealed the clinical value of chloroprocaine during breast cancer treatment.

Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study.

BACKGROUND: We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome. METHODS: Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417). CONCLUSION: IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.

Use of chloroprocaine in orthopedic day surgery: a brief report in a cohort of patients undergoing knee arthroscopy.

OBJECTIVE: Spinal anesthesia with local anesthetics is a viable alternative to general anesthesia in orthopedic surgery, and it is currently considered the standard of care for knee arthroscopy. The use of chloroprocaine may offer several potential advantages over other local anesthetics, including, above all, its rapid onset and short duration of action. The aim of the present retrospective study is to evaluate the post-surgical outcomes of patients who underwent knee arthroscopy using spinal anesthesia with chloroprocaine in an outpatient orthopedic setting. PATIENTS AND METHODS: Data from patients who underwent elective knee arthroscopy between January 2022 and December 2022 were collected for the present study. Spinal anesthesia with chloroprocaine 10 mg/mL was administered in the designated subarachnoid space (L3-L4 in the majority of patients). A dosage of 40 mg was used to obtain a satisfactory sensory and motor block. RESULTS: A total number of 302 patients met the inclusion criteria. No complications were reported during surgery in the present series of patients. None of the patients required bladder catheterization. In 84% of cases, the PADSS (Post-Anesthetic Discharge Scoring System) score at discharge was 10, whereas in 16% of cases, the PADSS score was 9. The mean time from anesthesia induction to first urination was 75±9.4 minutes, while the mean time from the anesthesia induction to the discharge from the hospital was 152±18.5 minutes. CONCLUSIONS: Spinal chloroprocaine for knee arthroscopy demonstrated a short motor block duration, resulting in a fast time to discharge. These limited data show that chloroprocaine may be safely and effectively applied in outpatient knee arthroscopy procedures. However, more studies, possibly with a randomized design, are required to confirm these findings.

The Influence of the Nature of the Polymer Incorporating the Same A3B Multifunctional Porphyrin on the Optical or Electrical Capacity to Recognize Procaine.

The multifunctionality of an A3B mixed-substituted porphyrin, namely 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (5-COOH-3MPP), was proven due to its capacity to detect procaine by different methods, depending on the polymer matrix in which it is incorporated. The hybrid nanomaterial containing k-carrageenan and AuNPs (5-COOH-3MPP-k-carrageenan-AuNPs) was able to optically detect procaine in the concentration range from 5.76 × 10-6 M to 2.75 × 10-7 M, with a limit of detection (LOD) of 1.33 × 10-7 M. This method for the detection of procaine gave complementary results to the potentiometric one, which uses 5-COOH-3MPP as an electroactive material incorporated in a polyvinylchloride (PVC) membrane plasticized with o-NPOE. The detected concentration range by this ion-selective membrane electrode is wider (enlarged in the field of higher concentrations from 10-2 to 10-6 M), linearly dependent with a 53.88 mV/decade slope, possesses a detection limit of 7 × 10-7 M, a response time of 60 s, and has a certified stability for a working period of six weeks.

Ozone and procaine increase secretion of platelet-derived factors in platelet-rich plasma.

Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes. Two interesting candidates are ozone, administered at low doses as gaseous oxygen-ozone mixtures, and procaine. In the present study, we investigated the effects induced on platelets by the in vitro treatment of PRP with ozone or procaine, or both. We combined transmission electron microscopy to obtain information on platelet modifications and bioanalytical assays to quantify the secreted factors. The results demonstrate that, although platelets were already activated by the procedure to prepare PRP, both ozone and procaine induced differential morpho-functional modifications in platelets resulting in an increased release of factors. In detail, ozone induced an increase in surface protrusions and open canalicular system dilation suggestive of a marked α-granule release, while procaine caused a decrease in surface protrusions and open canalicular system dilation but a remarkable increase in microvesicle release suggestive of high secretory activity. Consistently, nine of the thirteen platelet-derived factors analysed in the PRP serum significantly increased after treatment with ozone and/or procaine. Therefore, ozone and procaine proved to have a remarkable stimulating potential without causing any damage to platelets, probably because they act through physiological, although different, secretory pathways.

The Local Anaesthetic Procaine Prodrugs ProcCluster® and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro.

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster® and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Effect of Femoral Nerve Block with Different Concentrations of Chloroprocaine on Early Postoperative Rehabilitation Training After Total Knee Arthroplasty.

BACKGROUND Patients experience severe pain in early postoperative rehabilitation after total knee arthroplasty (TKA). This study aimed to compare the effect of femoral nerve block with different concentrations of chloroprocaine on postoperative rehabilitation in patients with TKA. MATERIAL AND METHODS Ninety patients who only received unilateral TKA were randomly and equally divided into C1 (1% chloroprocaine 0.2 ml/kg), C2 (2% chloroprocaine 0.2 ml/kg), or NS (0.9% sodium chloride solution 0.2 ml/kg) groups. The patients received rehabilitation 3 times a day on days 3-6 after surgery, and femoral nerve block was performed with corresponding solution 10 min before each training session. We recorded the maximum knee flexion angles (MKFA) and maximum knee extension angles (MKEA) during active exercise on day 7 after surgery, as well as the incidence of MKFA ³100°, American knee society (AKS) scores, and postoperative rehabilitation satisfaction. Adverse effects after administration in each group were also recorded. RESULTS Compared with group NS, patients in group C1 and C2 had larger MKFA during active exercise on day 7 after TKA, and had better rehabilitation satisfaction (P<0.05). MKEA, the incidence of MKFA ≥100°, and AKS scores showed no significant differences in the 3 groups. There were more patients with decline of muscle strength in group C2 (P<0.05), and no other adverse reactions were recorded. CONCLUSIONS Chloroprocaine for femoral nerve block can be safely used in rehabilitation after TKA and to improve the knee flexion angle in the early postoperative period. Because they may have fewer adverse effects, 1% chloroprocaine 0.2 ml/kg may be preferred.

Electrocatalytic barium-oxide decorated MWCNT amperometric sensor for the quantification of anesthetic drug Procaine.

Procaine hydrochloride (P.HCl) is one of the earliest and most well-established local anesthetic drugs used in medicine. Though it is employed frequently for effective clinical nerve blocks during surgeries, its immoderate administration has often shown reports of systemic toxicity. To prevent such repercussions, developing a sensor for the drug is crucial to enable real-time monitoring of the drug and assist in quality control procedures during its industrial preparations. Thus, in this work, we have fabricated a simple yet highly selective and sensitive amperometric sensor for P.HCl detection based on a Barium-oxide multi-wall carbon nanotube-modified carbon paste electrode (BaO-MWCNT/CPE). Herein, we have adopted a novel approach devoid of sophisticated procedures and pretreatments for rapidly determining P.HCl. Furthermore, experimental conditions, including supporting electrolytes, pH, and scan rate, were optimized to achieve a well-defined P.HCl anodic peak current at 631 mV, which is lower than the previously reported peak potentials, indicating an advantage of reduced overpotential. Besides, a striking 66-fold rise in current responsiveness to P.HCl was achieved upon modification with BaO-MWCNT. Such an intense signal enhancement upon electrode modification compared to bare CPE was due to the strong electrocatalytic feature of BaO-MWCNT, which was verified using surface morphology studies with scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Additionally, the charge transfer kinetics analyzed via electrochemical impedance spectroscopy (EIS) justified the enhancement of electrocatalytic activity upon electrode modification. The developed sensor exhibited a remarkable analytical performance over a wide linear dynamic range of 2.0-100.0 µM with a detection limit of 0.14 µM. Moreover, a significant merit of this sensor is its excellent selectivity towards P.HCl even in the presence of various common interferants. Finally, the versatility of the sensor was further validated by implementing it for the trace analysis of urine and blood serum real samples.

Quality by design paradigm for optimization of green stability indicating HPLC method for concomitant determination of fluorescein and benoxinate.

A green, robust and fast stability indicating chromatographic method has been developed for concomitant analysis of fluorescein sodium and benoxinate hydrochloride in the presence of their degradation products within four minutes. Two different designs including fractional factorial and Box-Behnken designs were implemented for screening and optimization steps, respectively. The optimum chromatographic analysis was achieved using a mixture of isopropanol and 20 mM potassium dihydrogen phosphate solution (pH 3.0) in the ratio 27:73 as mobile phase. The flow rate was 1.5 mL/min and column oven temperature was 40 °C. Chromatographic analysis was performed on Eclipse plus C18 (100 mm × 4.6 mm × 3.5 µm) column with DAD detector set at 220 nm. A linear response was acquired over the range of 2.5-60 µg/mL and 1-50 µg/mL for benoxinate and fluorescein respectively. Stress degradation studies were executed under acidic, basic, and oxidative stress conditions. The method was implemented for quantitation of cited drugs in ophthalmic solution with mean percent recovery ± SD of 99.21 ± 0.74 and 99.88 ± 0.58 for benoxinate and fluorescein respectively. The proposed method is more rapid and eco-friendly compared to the reported chromatographic methods for determination of cited drugs.

High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats.

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 µM limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (±10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.

Application of quality-by-design for adopting an environmentally green fluorogenic determination of benoxinate hydrochloride in eye drops and artificial aqueous humour.

Herein, a sensitive and selective spectrofluorimetric method has been developed for the determination of the ocular local anesthetic benoxinate hydrochloride (BEN-HCl) in eye drops and artificial aqueous humour. The proposed method is based on the interaction of fluorescamine with the primary amino group of BEN-HCl at room temperature. Following the excitation of the reaction product at 393 nm, the emitted relative fluorescence intensity (RFI) was measured at 483 nm. The key experimental parameters were carefully examined and optimized by adopting an analytical quality-by-design approach. The method used a two-level full factorial design (24 FFD) to obtain the optimum RFI of the reaction product. The calibration curve was linear at the range of 0.10-1.0 µg/mL of BEN-HCl with sensitivity down to 0.015 µg/mL. The method was applied for analyzing the BEN-HCl eye drops and could also assess its spiked levels in artificial aqueous humour with high % recoveries (98.74-101.37%) and low SD values (≤ 1.11). To investigate the green profile of the proposed method, a greenness assessment was performed with the aid of the Analytical Eco-Scale Assessment (ESA) and GAPI. The developed method obtained a very high ESA rating score in addition to being sensitive, affordable, and environmentally sustainable. The proposed method was validated according to ICH guidelines.

Local anaesthetic procaine derivatives protect rat against diabetic nephropathy via inhibition of DPP-4, inflammation and oxidative stress.

Diabetic nephropathy (DN) is a serious devastating disease. However, the current clinical options to treat DN are not adequate. Thus, in the present study, we intend to develop novel series of procaine-embedded thiazole-pyrazoles as protective agent against DN. The compounds were tested for inhibition of dipeptidyl peptidase (DPP)-4, -8, and - 9 enzyme subtypes, where they selectively and potently inhibit DPP-4 as compared to other subtypes. The top three ranked DPP-4 inhibitors (8i, 8e and 8k) were further screened for inhibitory activity against NF-ĸB transcription. Among these three, compound 8i was identified as the most potent NF-ĸB inhibitor. The pharmacological benefit of compound 8i was further established in streptozotocin-induced diabetic nephropathy in rats. Compound 8i showed marked improvements in blood glucose, ALP, ALT, total protein, serum lipid profile such as total cholesterol, triglyceride, HDL levels and renal functions such as urine volume, urinary protein excretion, serum creatinine, blood urea nitrogen and creatinine clearance as compared to nontreated diabetic control group. It also reduces oxidative stress (MDA, SOD and GPx) and inflammation (TNF-α, IL-1ß and IL-6) in the rats as compared to disease control group rats. This study demonstrated the discovery of procaine-embedded thiazole-pyrazole compounds as a novel class of agent against diabetic nephropathy.

A case of severe trigeminal neuralgia: recovery by means of stellate ganglion block with procaine. Discussion of possible mechanisms of action.

Drug and invasive treatment options for trigeminal neuralgia (TN) are often fraught with problems. Knowledge of the involvement of the autonomic nervous system, especially the sympathetic portion, in the pain process has grown rapidly in recent years. Both nociceptive and neuropathic pain can be maintained by the sympathetic nervous system, known as 'sympathetically maintained pain' (SMP). This current case report describes a patient with refractory TN that was treated with a stellate ganglion block (SGB). After the first SGB, the patient experienced significant pain relief that became long-lasting after repeated application of the SGB. These findings suggest that this patient had a high level of SMP. In patients with a low percentage of SMP, SGB may be less or not successful. A literature search did not find any case reports or studies about patients with refractory idiopathic TN treated with sympathetic blocks using local anaesthetics. From our point of view, it might be useful to test by means of SGB the extent to which an individual has SMP present, and, if that is the case, to perform a short series of SGB, as done in this current patient. Studies are needed to provide further insights.

Crystallization of short-acting and intermediate-acting local anesthetics when mixed with adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: The addition of adjuvants to short-acting local anesthetics (LA) is common practice in clinical routine to speed up block onset and decrease pain on injection. In a previous study, we observed the development of microscopic crystal precipitations after bupivacaine or ropivacaine were mixed with adjuvants; this follow-up study is intended to clarify whether crystallization (A) also occurs in short-acting or intermediate-acting LA-adjuvant mixtures, (B) changes over time, and (C) is associated with the solutions' pH. METHODS: Lidocaine 2%, prilocaine 2%, mepivacaine 2%, procaine 2% and chloroprocaine 2% were individually mixed with clonidine, dexamethasone, dexmedetomidine, epinephrine, fentanyl, morphine or sodium bicarbonate 8.4% in clinically established ratios. For each mixture, we measured initial pH and recorded crystallization patterns at 0, 15, 30 and 60 min using a standardized, semiquantitative light microscopy approach. RESULTS: Lidocaine 2% and mepivacaine 2% plus sodium bicarbonate 8.4%, and mepivacaine 2% plus dexamethasone developed delayed grade 5 crystallization over 1 hour. Prilocaine-based, procaine-based and chloroprocaine-based mixtures showed much less pronounced crystallization, with a maximum of grade 2. Initial pH and grade of crystallization showed weak monotonic relationships at time points t0, t15 and t30 (ρ=-0.17, 0.31 and 0.32, (all p>0.05)) and a moderate relationship time point t60 (ρ=0.57 (p=0.0003)) CONCLUSIONS: Our study revealed high grades of crystallization in lidocaine/mepivacaine-bicarbonate and mepivacaine-dexamethasone mixtures, although these were previously considered safe for local, perineural or neuraxial use. Our findings cast particular doubt on the safety of preparing these formulations for later use.