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1.
J Ocul Pharmacol Ther ; 40(4): 215-221, 2024 May.
Article in English | MEDLINE | ID: mdl-38597912

ABSTRACT

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.


Subject(s)
Anesthetics, Local , Cornea , Procaine , Propoxycaine , Tetracaine , Humans , Male , Female , Tetracaine/administration & dosage , Tetracaine/pharmacology , Adult , Double-Blind Method , Propoxycaine/administration & dosage , Propoxycaine/pharmacology , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Middle Aged , Prospective Studies , Cornea/drug effects , Procaine/administration & dosage , Procaine/pharmacology , Procaine/analogs & derivatives , Procaine/adverse effects , Young Adult , Ophthalmic Solutions/administration & dosage , Pain Measurement/methods
2.
Eur J Anaesthesiol ; 39(7): 602-610, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35695753

ABSTRACT

BACKGROUND: Plain 2-chloroprocaine , a rapid acting amino-ester-type local anaesthetic, is used in short ambulatory procedures under spinal anaesthesia. The ED 95 of 2-chloroprocaine for lower limb surgery has not yet been defined. Moreover, patients' body height could influence the effects of the administered dose. OBJECTIVES: The aim of this study was to determine the ED 95 of plain 2-chloroprocaine based on the height of patients undergoing ambulatory knee arthroscopy under spinal anaesthesia using the continual reassessment statistical method (CRM). DESIGN: Prospective, dose-response, double blind, controlled, bi-center, clinical trial. SETTING: One university teaching hospital in Brussels and one general teaching hospital, Braine l'Alleud, Belgium. Université libre de Bruxelles. PATIENTS: ASA I-III (120 patients) scheduled for day-case knee arthroscopy under spinal anaesthesia. INTERVENTIONS: Patients were divided into three groups of 40, each comprising 10 cohorts of 4 patients, according to their respective heights (Group 1: 150-165 cm, Group 2: 166-180 cm, Group 3: 181-195 cm). Each patient enrolled into one of the 3 groups received an intrathecal dose of plain 2-chloroprocaine determined by the CRM. The starting doses for the first cohorts of four were 40 mg in group 1, 45 mg in group 2 and 50 mg in group 3. The doses for subsequent cohorts were determined by CRM of outcomes in all patients in the previous competed cohorts. Anaesthesia was considered successful when there was a lack of pinprick or cold sensation up to T12, the visual analogue scale score for tourniquet pain was < 2 and no pain during surgery. MAIN OUTCOMES: The primary outcome was the success or failure of the block. Side effects were also recorded. RESULTS: ED 95 of 2-chloroprocaine is 40 mg in group 1, 35 mg in group 2, 45 mg in group 3. Groups were different in terms of height and gender ( P  < 0.05) and similar in terms of body mass index and age ( P  > 0.05). CONCLUSION: The ED95 of intrathecal 2-chloroprocaine for patients undergoing ambulatory knee arthroscopy is between 35 and 45 mg. Height could be a factor involved in the calculation, and patient sex could partly explain the nonlinear relation between height and dose. TRIAL REGISTRY NUMBER: Clinicaltrials.gov NCT03882489.


Subject(s)
Anesthetics, Local , Arthroplasty, Replacement, Knee , Body Height , Procaine , Ambulatory Surgical Procedures , Anesthesia, Spinal , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Arthroplasty, Replacement, Knee/methods , Double-Blind Method , Female , Humans , Male , Procaine/administration & dosage , Procaine/adverse effects , Procaine/analogs & derivatives , Prospective Studies
3.
Bioorg Med Chem Lett ; 60: 128587, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35091071

ABSTRACT

A series of novel procaine derivatives for intravenous anesthesia were prepared and evaluated by physicochemical properties and pharmacodynamic experiments in vivo and in vitro. Systematic optimization of procaine led to the identification of 6f, 6g, 6h, 6o, 6p and 6q with higher TI value and moderate log D. Compared with procaine (TI = 1.65), most procaine derivatives demonstrated better security, among whichcompound 6h (TI = 2.68)was the most notable one and showed fewer adverse events in animals. The result of hNR2B-HEK293 assay indicated that compound 6h suppressed the NMDA receptor 2B subtype channel activity and it showed more than 80% inhibitory effect at the concentration of 500 µM.


Subject(s)
Drug Design , Procaine/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Anesthesia, Intravenous , Animals , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Molecular Structure , Procaine/administration & dosage , Procaine/chemistry , Rats , Receptors, N-Methyl-D-Aspartate/metabolism , Structure-Activity Relationship , Tissue Distribution
4.
Anesth Analg ; 134(3): 624-632, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34153006

ABSTRACT

BACKGROUND: Cervical cerclage is a short ambulatory procedure. For spinal anesthesia, local anesthetic agents with rapid postoperative resolution are desired. We hypothesized that in combination with fentanyl, intrathecal 2-chloroprocaine would produce earlier resolution of motor block, resulting in shorter time to meet recovery room discharge criteria than hyperbaric bupivacaine. METHODS: Women undergoing cervical cerclage with spinal anesthesia were randomized to receive intrathecal 2-chloroprocaine 3% 50 mg or hyperbaric bupivacaine 0.75% 9 mg, both with fentanyl 15 µg. Doses were empirically selected. The onset and resolution of sensory and motor blockade and time to achieve recovery room discharge criteria were monitored. On postoperative day 1, patients rated their satisfaction with the anesthetic and reported on transient neurologic symptoms (TNS), back pain, or headache. The primary outcome was time from spinal injection to motor block resolution. The main secondary outcomes included times from spinal injection to (i) T12 dermatomal level, (ii) sensory block resolution, and (iii) ability to ambulate and void. RESULTS: Forty-three women were enrolled and randomized to either the chloroprocaine (N = 23) or bupivacaine group (N = 20). The mean (standard deviation [SD]) duration of surgery was 35.3 (11.4) minutes. There was no difference between groups for time to motor block resolution-the median [interquartile range] time for the bupivacaine group (N = 17) was 112 [97-143] minutes versus 109 [88-148] minutes in the chloroprocaine group (N = 22), P = .66, but there was a significant difference in median time to sensory block resolution: 143 [116-162] minutes in the chloroprocaine group versus 198 [152-263] minutes in the bupivacaine group, P = .002. The recovery room discharge criteria, which at our institution include the ability to ambulate unassisted and void urine, were met 76 (95% CI, 33-145) minutes earlier in the chloroprocaine group, P < .0005. One complete block failure occurred with hyperbaric bupivacaine and 2 subjects in each group received treatment for intraoperative discomfort. No patients reported TNS. CONCLUSIONS: Intrathecal 2-chloropocaine 3% provided similarly effective surgical anesthesia for cerclage placement. Although no difference in time to motor block resolution between groups was observed, the time to sensory block resolution and time to meet recovery room discharge criteria were both significantly shorter among patients who received chloroprocaine than patients who received bupivacaine. Future studies are needed to identify and compare equipotent doses of chloroprocaine and bupivacaine to confirm the superiority of chloroprocaine for this ambulatory obstetric procedure.


Subject(s)
Anesthesia, Spinal/methods , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Cerclage, Cervical/methods , Gynecologic Surgical Procedures/methods , Procaine/analogs & derivatives , Adult , Ambulatory Surgical Procedures , Double-Blind Method , Female , Humans , Injections, Spinal , Middle Aged , Nerve Block , Postoperative Complications/epidemiology , Pregnancy , Procaine/administration & dosage , Prospective Studies
5.
Neurotoxicology ; 88: 155-167, 2022 01.
Article in English | MEDLINE | ID: mdl-34801587

ABSTRACT

Spinally-administered local anesthetics provide effective perioperative anesthesia and/or analgesia for children of all ages. New preparations and drugs require preclinical safety testing in developmental models. We evaluated age-dependent efficacy and safety following 1 % preservative-free 2-chloroprocaine (2-CP) in juvenile Sprague-Dawley rats. Percutaneous lumbar intrathecal 2-CP was administered at postnatal day (P)7, 14 or 21. Mechanical withdrawal threshold pre- and post-injection evaluated the degree and duration of sensory block, compared to intrathecal saline and naive controls. Tissue analyses one- or seven-days following injection included histopathology of spinal cord, cauda equina and brain sections, and quantification of neuronal apoptosis and glial reactivity in lumbar spinal cord. Following intrathecal 2-CP or saline at P7, outcomes assessed between P30 and P72 included: spinal reflex sensitivity (hindlimb thermal latency, mechanical threshold); social approach (novel rat versus object); locomotor activity and anxiety (open field with brightly-lit center); exploratory behavior (rearings, holepoking); sensorimotor gating (acoustic startle, prepulse inhibition); and learning (Morris Water Maze). Maximum tolerated doses of intrathecal 2-CP varied with age (1.0 µL/g at P7, 0.75 µL/g at P14, 0.5 µL/g at P21) and produced motor and sensory block for 10-15 min. Tissue analyses found no significant differences across intrathecal 2-CP, saline or naïve groups. Adult behavioral measures showed expected sex-dependent differences, that did not differ between 2-CP and saline groups. Single maximum tolerated in vivo doses of intrathecal 2-CP produced reversible spinal anesthesia in juvenile rodents without detectable evidence of developmental neurotoxicity. Current results cannot be extrapolated to repeated dosing or prolonged infusion.


Subject(s)
Neurotoxicity Syndromes/etiology , Procaine/analogs & derivatives , Animals , Caspase 3/metabolism , Cauda Equina/anatomy & histology , Cauda Equina/drug effects , Female , Injections, Spinal , Male , Morris Water Maze Test/drug effects , Motor Activity/drug effects , Procaine/administration & dosage , Procaine/toxicity , Rats , Rats, Sprague-Dawley , Sensory Gating/drug effects
6.
BMC Cardiovasc Disord ; 21(1): 604, 2021 12 18.
Article in English | MEDLINE | ID: mdl-34922443

ABSTRACT

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.


Subject(s)
Cardiac Surgical Procedures , Electrolytes/administration & dosage , Heart Arrest, Induced , Heart Valve Diseases/surgery , Heart Valves/surgery , Lidocaine/administration & dosage , Magnesium Sulfate/administration & dosage , Mannitol/administration & dosage , Potassium Chloride/administration & dosage , Sodium Bicarbonate/administration & dosage , Solutions/administration & dosage , Adolescent , Adult , Aged , Cardiac Surgical Procedures/adverse effects , Electrolytes/adverse effects , Female , Glucose/administration & dosage , Glucose/adverse effects , Heart Arrest, Induced/adverse effects , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Heart Valves/diagnostic imaging , Heart Valves/physiopathology , Humans , Lidocaine/adverse effects , Magnesium Sulfate/adverse effects , Male , Mannitol/adverse effects , Middle Aged , Operative Time , Postoperative Complications/etiology , Potassium Chloride/adverse effects , Procaine/administration & dosage , Procaine/adverse effects , Recovery of Function , Retrospective Studies , Sodium Bicarbonate/adverse effects , Solutions/adverse effects , Time Factors , Treatment Outcome , Young Adult
7.
Sci Rep ; 11(1): 10035, 2021 05 11.
Article in English | MEDLINE | ID: mdl-33976374

ABSTRACT

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI - 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155-170] min for chloroprocaine versus 380 [209-450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile.Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria-BASG).


Subject(s)
Anesthetics, Local/administration & dosage , Nerve Block , Procaine/analogs & derivatives , Ropivacaine/administration & dosage , Adult , Aged , Aged, 80 and over , Axilla , Double-Blind Method , Female , Humans , Male , Middle Aged , Procaine/administration & dosage , Prospective Studies , Ultrasonography, Interventional , Young Adult
8.
Acta Vet Scand ; 63(1): 1, 2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33407757

ABSTRACT

BACKGROUND: Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the "Danish quality scheme"; a voluntary initiative taken by the Danish pig industry. The approved procedure for local anaesthesia in Denmark is a three-step injection method with procaine. A comparison of lidocaine and procaine with the same concentration and injection methods of local anaesthetics has not previously been studied. The purpose of this study was to investigate the effect of two injection methods and two local anaesthetics on piglets' avoidance behaviour (vocalisation and resistance movements) as well as the time spent on the procedures. The study included 203 male piglets that were randomly assigned to one of five treatments: 1. CONTROL: Sham-handling without injection of local anaesthesia, 2. Pro3: Procaine injection using a three-step method, 3. Pro2: Procaine injection using a two-step method, 4. Lid3: Lidocaine injection using a three-step method, 5. Lid2: Lidocaine injection using a two-step method. During injection of local anaesthesia and castration, vocalisation was measured using a decibel meter and resistance movements were registrated by video recordings. RESULTS: During castration, piglets treated with local anaesthesia showed significantly reduced vocalisation and resistance movements and time spent on castration was also significantly reduced compared to the control group. During injection of the local anaesthesia, the piglets had significantly increased vocalisation and resistance movements compared to the control group. Piglets injected with lidocaine had a significantly reduced resistance movement score and a tendency to reduced vocalisation compared to piglets injected with procaine. No differences in avoidance behaviour were found between the injection methods. CONCLUSIONS: The use of local anaesthesia, irrespective of the method and local anaesthetic, was effective in reducing vocalisation and resistance movements during surgery as well as the time spent on castration.


Subject(s)
Anesthetics, Local/administration & dosage , Castration/veterinary , Lidocaine/administration & dosage , Procaine/administration & dosage , Animals , Animals, Newborn , Industry , Male , Meat , Pain Measurement/veterinary , Swine , Treatment Outcome
9.
PLoS One ; 15(11): e0241567, 2020.
Article in English | MEDLINE | ID: mdl-33151993

ABSTRACT

The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride treatment in healthy rats. A randomized, blinded, crossover study was conducted on 20 healthy adult Wistar rats, following complete physical and ophthalmological examination. Baseline corneal touch threshold (CTT) was determined in the central corneal area of both eyes with a Cochet-Bonnet aesthesiometer, in mm filament length. Oxybuprocaine was randomly applied to one eye and 0.9% sterile sodium chloride solution was instilled into the contralateral eye. Subsequent CTT measurements were performed in both eyes 5 minutes after topical application and at 5-minute intervals thereafter for 75-minutes in the anesthetized eye. Following a 2-week washout period, this protocol was repeated with ropivacaine. Quantitative data were summarized as mean ± standard deviation, median and inter-quartile range (Q1-Q3). Repeated measures data were analyzed over time and between treatments using Friedman test and Wilcoxon signed-rank test with Bonferroni adjustment (p < 0.05). Baseline CTT values were 60 mm in all eyes. With oxybuprocaine, CTT values decreased significantly for 65 minutes (0-55 mm; p = 0.002) when compared with baseline; the maximal anesthetic effect (no blink response at 5 mm filament length) was maintained for up to 15 minutes (p < 0.0001). With ropivacaine, CTT values were significantly lower than baseline for 30 minutes (0-55 mm; p = 0.002), with a maximal anesthetic effect recorded at 5 minutes in 18 eyes (p < 0.0001). Oxybuprocaine induced a significantly lower CTT than ropivacaine (p = 0.002) from 10 to 65 minutes following topical application. Both anesthetic agents induced significant corneal anesthesia; however, oxybuprocaine provided a greater and longer anesthetic effect, making it more suitable for potentially painful ophthalmologic procedures.


Subject(s)
Cornea/drug effects , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacology , Procaine/analogs & derivatives , Ropivacaine/administration & dosage , Ropivacaine/pharmacology , Administration, Topical , Animals , Female , Male , Procaine/administration & dosage , Procaine/pharmacology , Rats, Wistar , Sensory Thresholds/drug effects
10.
BMJ Case Rep ; 13(9)2020 Sep 07.
Article in English | MEDLINE | ID: mdl-32900720

ABSTRACT

Ensuring respiratory stability with early tracheal extubation and adequate pain control is challenging in premature neonates after thoracotomy. Continuous erector spinae plane (ESP) block, a relatively new truncal nerve block, has the potential to provide analgesia for thoracic surgeries while reducing opioid use. However, there have been only a few reports utilising this technique in infants, and none in preterm neonates. We present the perioperative pain management of a preterm neonate requiring thoracotomy. Epidural analgesia was deemed contraindicated due to coexisting coagulopathy; therefore, an ESP catheter was placed. The patient was extubated at the end of the surgery and had excellent pain control with rectal acetaminophen, chloroprocaine infusion via the ESP catheter and with minimal opioid requirement. Continuous ESP block may be safe and effective for postoperative pain management in coagulopathic premature neonates. Chloroprocaine is an effective local anaesthetic in the erector spinae compartment, which has not been previously reported.


Subject(s)
Anesthetics, Local/administration & dosage , Catheterization , Nerve Block , Pain, Postoperative/drug therapy , Paraspinal Muscles , Procaine/analogs & derivatives , Thoracotomy , Female , Humans , Infant, Newborn , Infant, Premature , Nerve Block/methods , Procaine/administration & dosage
11.
Korean J Anesthesiol ; 73(5): 417-424, 2020 10.
Article in English | MEDLINE | ID: mdl-32842722

ABSTRACT

BACKGROUND: Multiple comparative studies report that adductor canal blocks provide similar pain relief to femoral nerve blocks following total knee arthroplasty. However, adductor canal blockade fails to anesthetize several important femoral nerve branches that contribute to knee innervation. We sought to clarify this anatomic discrepancy by performing both blocks in sequence, using patients as their own controls. We hypothesized that patients would experience additional pain relief following a superimposed femoral nerve block, demonstrating that these techniques are not equivalent. METHODS: Sixteen patients received continuous adductor canal block before undergoing knee arthroplasty under general anesthesia. In the recovery room, patients reported their pain score on a numeric scale of 0-10. Once a patient reached a score of five or greater, he/she was randomized to receive an additional femoral nerve block using 2% chloroprocaine or saline sham, and pain scores recorded every 5 min for 30 min. Patients received opioid rescue as needed. Anesthesiologists performing and assessing block efficacy were blinded to group allocation. RESULTS: Patients randomized to chloroprocaine versus saline reported significantly improved median pain scores 30 min after the femoral block (2.0 vs. 5.5, P = 0.0001). Patients receiving chloroprocaine also required significantly fewer morphine equivalents during the 30 min post-femoral block (1.0 vs. 4.5 mg, P = 0.03). CONCLUSIONS: Adductor canal block is a useful technique for postoperative pain following total knee arthroplasty, but it does not provide equivalent analgesic efficacy to femoral nerve block. Future studies comparing efficacy between various block sites along the thigh are warranted.


Subject(s)
Analgesia/methods , Arthroplasty, Replacement, Knee/adverse effects , Autonomic Nerve Block/methods , Femoral Nerve/drug effects , Pain Measurement/methods , Pain, Postoperative/prevention & control , Aged , Analgesia/trends , Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee/trends , Autonomic Nerve Block/trends , Double-Blind Method , Female , Femoral Nerve/physiology , Humans , Male , Middle Aged , Pain Measurement/drug effects , Pain, Postoperative/etiology , Procaine/administration & dosage , Procaine/analogs & derivatives , Prospective Studies , Thigh/innervation , Thigh/physiology
12.
Mol Pharm ; 17(10): 3952-3965, 2020 10 05.
Article in English | MEDLINE | ID: mdl-32845650

ABSTRACT

Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the anticonvulsant phenytoin sodium can promote reepithelization of corneal ulcers as it was repurposed for skin wound healing. Herein, our aim is to develop novel crown ether-based nanovesicles "Crownsomes" of phenytoin sodium for ocular delivery with minimal drug-induced irritation and enhanced efficacy owing to "host-guest" properties of crown ethers. Crownsomes were successfully fabricated using span-60 and 18-crown-6 and their size, morphology, polydispersity index, ζ potential, drug loading efficiency, conductivity, and drug release were characterized. Crownsomes exhibited favorable properties such as formation of spherical nanovesicles of 280 ± 18 nm and -26.10 ± 1.21 mV surface charges. Crownsomes depicted a high entrapment efficiency (77 ± 5%) with enhanced and controlled-release pattern of phenytoin sodium. The optimum crownsomes formulation ameliorated ex vivo corneal drug permeability (1.78-fold than drug suspension) through the corneal calcium extraction ability of 18-crown-6. In vivo study was conducted utilizing an alkali-induced corneal injury rabbit model. Clinical and histopathological examination confirmed that crownsomes exhibited better biocompatibility and minimal irritation due to complex formation and drug shielding. Further, they enhanced corneal healing, indicating their effectiveness as a novel drug delivery system for ocular diseases.


Subject(s)
Corneal Ulcer/drug therapy , Crown Ethers/chemistry , Drug Carriers/chemistry , Phenytoin/administration & dosage , Wound Healing/drug effects , Administration, Ophthalmic , Animals , Cornea/drug effects , Cornea/pathology , Corneal Ulcer/chemically induced , Corneal Ulcer/pathology , Disease Models, Animal , Drug Liberation , Drug Repositioning , Humans , Nanoparticles/chemistry , Ophthalmic Solutions , Particle Size , Permeability , Phenytoin/adverse effects , Phenytoin/pharmacokinetics , Procaine/administration & dosage , Procaine/analogs & derivatives , Procaine/toxicity , Rabbits
14.
Brain Res Bull ; 162: 180-190, 2020 09.
Article in English | MEDLINE | ID: mdl-32540420

ABSTRACT

Previously obtained data suggests that noradrenaline (NE) released from the efferent locus coeruleus (LC) endings in hippocampal formation (HPC) may serve as an important modulating signal involved in the pharmacological mechanisms responsible for the production of type 2 theta rhythm in rats. Hence, two distinct hypotheses were tested in the present study: 1/ if the decrease in HPC level of NE is correlated with the desynchronization of HPC field potential, then the inhibition of LC would be expected to abolish HPC type 2 theta rhythm; 2/ if the increase in HPC NE level is correlated with synchronization of HPC field potential, then the stimulation of LC would be expected to produce type 2 theta. The experiments were performed using an experimental model of HPC type 2 theta rhythm recorded in urethanized rats. It was demonstrated that electrical stimulation of LC produced type 2 theta rhythm whereas procaine injection into LC, in contrast, reversibly abolished type 2 theta. The possible relation of type 2 theta rhythm with some disturbances of Alzheimer disease are addressed.


Subject(s)
Anesthetics, Local/administration & dosage , Hippocampus/physiology , Locus Coeruleus/physiology , Procaine/administration & dosage , Theta Rhythm/physiology , Animals , Electric Stimulation/methods , Hippocampus/drug effects , Infusions, Intraventricular , Locus Coeruleus/drug effects , Male , Rats , Rats, Wistar , Theta Rhythm/drug effects
15.
Biosci Rep ; 40(5)2020 05 29.
Article in English | MEDLINE | ID: mdl-32129456

ABSTRACT

AIM: The present study aims to evaluate protective effects of a novel histidine-tryptophan-ketoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. METHODS: Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4°C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs-Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. RESULTS: The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia-reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. CONCLUSION: HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.


Subject(s)
Intestine, Small/drug effects , Organ Preservation Solutions/administration & dosage , Organ Preservation/methods , Reperfusion Injury/prevention & control , Animals , Cold Ischemia/adverse effects , Cold Ischemia/methods , Disease Models, Animal , Glucose/administration & dosage , Glucose/chemistry , Humans , Intestinal Mucosa/blood supply , Intestinal Mucosa/drug effects , Intestinal Mucosa/transplantation , Intestinal Mucosa/ultrastructure , Intestine, Small/blood supply , Intestine, Small/transplantation , Intestine, Small/ultrastructure , Male , Mannitol/administration & dosage , Mannitol/chemistry , Microscopy, Electron, Transmission , Organ Preservation Solutions/chemistry , Perfusion/methods , Potassium Chloride/administration & dosage , Potassium Chloride/chemistry , Procaine/administration & dosage , Procaine/chemistry , Rats , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Tromethamine/administration & dosage , Warm Ischemia/adverse effects , Warm Ischemia/methods
16.
J Thorac Cardiovasc Surg ; 159(5): 1857-1863.e1, 2020 05.
Article in English | MEDLINE | ID: mdl-31204129

ABSTRACT

OBJECTIVE: The present prospective noninferiority randomized trial was designed to demonstrate the safety and efficacy of a single dose of Custodiol histidine-tryptophan-ketoglutarate compared with repetitive cold-blood cardioplegia. METHODS: From October 2012 to May 2014, 110 patients were randomly assigned to 1 of 2 groups: Group 1 (55 patients) received repetitive cold-blood cardioplegia, and group 2 (55 patients) received single-dose Custodiol histidine-tryptophan-ketoglutarate. Isolated aortic valve replacement, isolated mitral valve replacement, and multivalve procedures represented the most frequent operations, with 39 cases (71%) in group 1 and 49 cases (89%) in group 2. There was no difference in cardiopulmonary bypass time (102 ± 26 minutes vs 99 ± 19 minutes, P = .70) or aortic crossclamp time (77 ± 19 minutes vs 74 ± 17 minutes, P = .33). All patients underwent preoperative electrocardiogram and determination of creatine kinase-MB, troponin I, left ventricular ejection fraction, and regional wall motion. Postoperative cardiac biomarkers were checked at 7, 24, and 48 hours, and an echocardiogram was obtained to check for left ventricular function abnormalities. RESULTS: There was no difference in cardiac biomarkers release between the 2 groups at baseline and 7, 24, and 48 hours postoperatively (creatine kinase, P = .18, troponin P = .23). Left ventricular function was similar between groups preoperatively and at 24 hours after surgery. No death or myocardial infarction was observed in either group. There were no differences in intensive care unit length of stay, incidence of atrial fibrillation, use of inotropes or vasopressors support, time of intubation, or creatinine levels. CONCLUSIONS: A single dose of Custodiol histidine-tryptophan-ketoglutarate cardioplegia is not inferior to repeated cold-blood cardioplegia during elective cardiac surgery.


Subject(s)
Cardioplegic Solutions/administration & dosage , Heart Arrest, Induced/methods , Heart/physiology , Aged , Cardioplegic Solutions/adverse effects , Cardioplegic Solutions/therapeutic use , Creatine Kinase, MB Form/blood , Female , Glucose/administration & dosage , Glucose/adverse effects , Glucose/therapeutic use , Hemodynamics/physiology , Humans , Length of Stay , Male , Mannitol/administration & dosage , Mannitol/adverse effects , Mannitol/therapeutic use , Middle Aged , Postoperative Complications , Potassium Chloride/administration & dosage , Potassium Chloride/adverse effects , Potassium Chloride/therapeutic use , Procaine/administration & dosage , Procaine/adverse effects , Procaine/therapeutic use , Prospective Studies , Troponin I/blood
17.
Ann Vasc Surg ; 63: 459.e5-459.e8, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31622767

ABSTRACT

CASE REPORT: We report an unusual case of a 65-year-old male patient with horseshoe kidney, who underwent a successful open repair for an abdominal aortic aneurysm (AAA). The accessory renal arteries were perfused with histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol®; Dr. Franz-Kohler Chemie GmbH, Bensheim, Germany) during the vascular reconstruction. There were no creatinine and estimated glomerular filtration rate (eGFR) modifications in the postoperative time. In the literature, only two cases of Custodiol solution for kidney protection during aortic surgery are reported. To the best of our knowledge, this is the first case of Custodiol perfusion for horseshoe kidney protection. DISCUSSION: The concomitant presence of horseshoe kidney and an AAA requires a specific preoperative planning. This is necessary to define the appropriate surgical procedure and strategy. The onset of acute kidney injury is an aspect that must always be taken into consideration during aortic surgery, even more in the case we are reporting. Indeed, despite the complexity of the kidney anatomy, the use of Custodiol solution allowed a proper maintenance of the perioperative renal function, as shown by the postoperative levels of creatinine and eGFR. CONCLUSIONS: Preoperative planning and organ preservation are crucial in AAA open repair, especially in the presence of congenital anomalies such as horseshoe kidney.


Subject(s)
Acute Kidney Injury/prevention & control , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation , Fused Kidney/complications , Perfusion , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Aged , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/physiopathology , Blood Vessel Prosthesis Implantation/adverse effects , Fused Kidney/diagnosis , Fused Kidney/physiopathology , Glucose/administration & dosage , Humans , Male , Mannitol/administration & dosage , Potassium Chloride/administration & dosage , Procaine/administration & dosage , Renal Circulation , Risk Factors , Treatment Outcome
18.
J Orthop Surg (Hong Kong) ; 27(3): 2309499019865534, 2019.
Article in English | MEDLINE | ID: mdl-31370751

ABSTRACT

This study aimed to compare clinical efficacy and safety of chloroprocaine and lidocaine in epidural anesthesia for outpatient knee arthroscopy. Eighty patients undergoing knee arthroscopy were randomly allocated to receive 3% 2-chloroprocaine (group C, n = 40) or 2% lidocaine (group L, n = 40) for epidural block. Latency to anesthesia onset, highest block level, time to achieve peak effect, time to complete sensory and motor block regression, vital signs including respiration and hemodynamics, and complications during follow-up were recorded. No significant differences were found in the latency to anesthesia onset and peak effect, duration of anesthesia efficacy, and the time for recovery of sensory function between the two groups. However, the latency to maximal block of pain sensation and the time needed to recover motor function were significantly shorter in group C than in group L (p < 0.05). No adverse effects or neurologic complications were found in both groups. In conclusion, epidural chloroprocaine elicits rapid anesthetic effects, fast sensor and motor block, and faster recovery of motor function compared to lidocaine. These characteristics make chloroprocaine better than lidocaine as the choice of epidural anesthesia in short clinical operations such as knee arthroscopy.


Subject(s)
Ambulatory Surgical Procedures/methods , Anesthesia, Epidural/methods , Arthroscopy/methods , Knee Joint/surgery , Lidocaine/administration & dosage , Outpatients , Procaine/analogs & derivatives , Adult , Anesthetics, Local/administration & dosage , Double-Blind Method , Female , Humans , Male , Procaine/administration & dosage , Prospective Studies , Time Factors
19.
Prog Urol ; 29(8-9): 402-407, 2019.
Article in French | MEDLINE | ID: mdl-31266700

ABSTRACT

INTRODUCTION: Spinal anesthesia in outpatient urology is controversial (longer hospital stay, risk of urinary retention). The main goal was to evaluate outpatient spinal anesthesia and to compare 2 local anesthetics secondarily. MATERIAL: Monocentric retrospective study including all patients undergoing surgery in urological ambulatory surgery under spinal anesthesia between December 2011 and May 2015, split into two groups according to the local anesthetic used: bupivacaine (BP) and chloroprocaine (CP). Quantitative variables were compared by Student's t-test, qualitative variables by χ2 test. RESULTS: Seventy-one (95%) out of the 75 patients included have been discharged the same day. Discharge was impossible in these cases: patient alone at home (1), bladder clot (1), JJ intolerance (1), delayed micturition (1). The mean duration of the procedure was 27±19min, the SSPI's was 55±31min, the stay's was 360±91min. A total of 45 patients (60%) received BP and 30 (40%) received CP. The mean residence time in SSPI was significantly reduced in the CP group (47±24min vs. 61±34min, P=0.04). One patient experienced urination delay in the BP group with no significant difference. No significant difference for the other criteria studied despite the mean age, which is higher in the CP group (P=0.02). CONCLUSION: Spinal anesthesia is adapted to ambulatory urology, and does not increase the risk of urinary retention, especially with CP that would decrease the length of stay in SSPI compared to BP. LEVEL OF EVIDENCE: 4.


Subject(s)
Anesthesia, Spinal/methods , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Procaine/analogs & derivatives , Urologic Surgical Procedures/methods , Adult , Aged , Ambulatory Surgical Procedures/methods , Anesthesia, Spinal/adverse effects , Anesthetics, Local/adverse effects , Bupivacaine/adverse effects , Female , Humans , Length of Stay , Male , Middle Aged , Procaine/administration & dosage , Procaine/adverse effects , Retrospective Studies , Urinary Retention/epidemiology , Urinary Retention/etiology
20.
Article in German | MEDLINE | ID: mdl-31212342

ABSTRACT

OBJECTIVE: Comparison of the effectiveness of local anaesthesia (LA) in piglet castration with the combination of scrotal and inguinal application of procaine 2 % and lidocaine 5 % to the intratesticular application of lidocaine 1 % using following parameters: adrenaline (A), noradrenaline (NA), defensive movements and coordinated movement patterns. MATERIAL AND METHODS: In 2 substudies 232 male suckling piglets (3-6 days of age) were randomly allocated to study groups. In groups L5 and group P2 lidocaine 5 % and procaine 2 % was applied inguinally and scrotally, respectively, while piglets of groups H (handling) and K (castration without local anaesthesia) were only fixated as for an injection. In group L1 lidocaine 1 % was injected intratesticularly. After 30 min piglets were were castrated, whereas animals of group H were again only fixated. In substudy 1 (n = 112) blood samples were taken to determine the concentration of catecholamines after castration. During injection and castration defensive movements were judged. In substudy 2 (n = 120) piglets completed a chute to document the individual stress level. RESULTS: Groups H and L1 demonstrated significantly less defensive movements during fixation for injection/injection compared to the other study groups (p ≤ 0.05). After the injection piglets of group P2 had significantly more difficulties in the chute and needed > 50 % more time to complete the course. In all study groups defensive movements during castration were the highest at the moment of severing the spermal cord. Group K obtained the highest possible rating of 8 and differed significantly from the other groups as well as when cutting the skin (p ≤ 0.05). Both the concentration of A and NA significantly rose in all groups. The increase in A and NA was significantly higher in group 2, as well as the increase in NA in group K, both in comparison to the other study groups (p ≤ 0.05). CONCLUSION: None of the applied techniques for local anaesthesia achieved a complete elimination of pain during castration of suckling piglets. The behaviour analysis indicated an altogether higher distress for P2. After castration, this injection led to a neuroendocrine pain reaction that was comparable to or higher than that of group K. In both lidocaine groups (L1, L5) the pain reaction after castration tended to be lower. These results provide approaches to apply longer acting LA with a higher analgesic potency in an appropriate dosage and with an appropriate method of application.


Subject(s)
Anesthetics, Local , Lidocaine , Orchiectomy , Pain , Procaine , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Anesthetics, Local/therapeutic use , Animals , Animals, Suckling , Behavior, Animal/drug effects , Catecholamines/blood , Injections/adverse effects , Lidocaine/administration & dosage , Lidocaine/pharmacology , Lidocaine/therapeutic use , Male , Orchiectomy/adverse effects , Orchiectomy/veterinary , Pain/drug therapy , Pain/etiology , Pain/veterinary , Procaine/administration & dosage , Procaine/pharmacology , Procaine/therapeutic use , Stress, Physiological/drug effects , Swine
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