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BMC Pediatrics Jun 2023To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
PURPOSE
To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
METHODS
Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders. Multivariate logistic regression analysis was performed to identify factors leading to life-threatening reaction (i.e. continuous seizures or cardiorespiratory arrest).
RESULTS
Among 512 cases retrieved, 64 LAST cases were included (neonates 11%, infants 30%, children 36%, adolescents 23%) mainly involving lidocaine (47%), lidocaine + prilocaine (22%) and ropivacaine (14%). Toxicity profiles were neurological (58%), cardiac (11%) or mixed (20%) and 7 patients (11%) developed methemoglobinemia. LAST was life-threatening for 23 patients (36%) and 2 patients died. Doses were above recommendations in 26 patients (41%) and were not different between life-threatening and non-life-threatening cases. The context of use (general and orthopedic surgery, p = 0.006) and the type of LA agent (lidocaine, p = 0.016) were independently associated with a life-threatening outcome.
CONCLUSION
In this national retrospective analysis, LAST in children appear to be a rare event. Neurological and cardiac signs were the most frequently reported reactions. LAST in children can be life-threatening, even at therapeutic doses. Although a fatal outcome may anecdotally occur, the vast majority of patients recovered after appropriate medical care.
Topics: Infant; Infant, Newborn; Adolescent; Humans; Child; Anesthetics, Local; Pharmacovigilance; Retrospective Studies; Lidocaine; Ropivacaine; Lidocaine, Prilocaine Drug Combination
PubMed: 37355586
DOI: 10.1186/s12887-023-04126-7 -
Atherosclerosis Nov 2023To understand pathophysiological mechanisms underlying migraine as a cardiovascular risk factor, we studied neuropeptide action and endothelial function as measures of...
BACKGROUND AND AIMS
To understand pathophysiological mechanisms underlying migraine as a cardiovascular risk factor, we studied neuropeptide action and endothelial function as measures of peripheral microvascular function in middle-aged women with or without migraine.
METHODS
We included women with the endocrine disorder polycystic ovary syndrome (PCOS), a population with supposed elevated cardiovascular risk, with and without comorbid migraine. In 26 women without and 23 women with migraine in the interictal phase (mean age 50.8 ± 2.9 years) local thermal hyperemia (LTH) of the skin of the volar forearm was measured cross-sectionally under control conditions, after inhibition of neuropeptide release by 5% lidocaine/prilocaine (EMLA) cream application, and after inhibition of nitric oxide formation by iontophoresis of NG-monomethyl-l-arginine (L-NMMA). Hereafter, changes in the natural logarithm of the reactive hyperemia index (lnRHI) and augmentation index (AI) during reperfusion after occlusion-derived ischemia were measured.
RESULTS
While mean values under control conditions and L-NMMA conditions were similar, migraine patients had a significantly higher mean area of the curve (AUC) of the total LTH response after EMLA application than those without (86.7 ± 26.5% versus 67.9 ± 24.2%; p = 0.014). This was also reflected by a higher median AUC of the plateau phase under similar conditions in women with migraine compared to those without (83.2% (IQR[73.2-109.5]) versus 73.2% (IQR[54.3-92.0]); p = 0.039). Mean changes in lnRHI and AI scores were similar in both groups.
CONCLUSIONS
In PCOS patients with migraine, neuropeptide action was lower compared with those without migraine. While larger studies are warranted, these findings provide a potential mechanism supporting previous findings that migraine may be independent from traditional risk factors, including atherosclerosis.
Topics: Middle Aged; Humans; Female; omega-N-Methylarginine; Polycystic Ovary Syndrome; Vasodilation; Risk Factors; Migraine Disorders
PubMed: 37400308
DOI: 10.1016/j.atherosclerosis.2023.06.078 -
Journal of Anesthesia, Analgesia and... Oct 2023Spinal anesthesia is considered safe and reliable for most surgical procedures involving the lower part of the body, but its use in the ambulatory setting requires drugs...
Spinal anesthesia is considered safe and reliable for most surgical procedures involving the lower part of the body, but its use in the ambulatory setting requires drugs with rapid onset and regression of the motor and sensory block-like prilocaine.The purpose of this study is to retrospectively analyze data from 3291 procedures recorded in our institutional database, to better define the safety profile of spinal prilocaine and the incidence of complications and side effects.All clinical data, prospectively collected from 2011 to 2019 in an Italian tertiary hospital, of patients treated with spinal anesthesia performed with 40 mg of hyperbaric 2% prilocaine, according to our internal protocol of day surgery, were analyzed.Surgical procedures included saphenectomy (28.5%, n = 937), knee arthroscopy (26.8%, n = 882), proctologic surgery (15.16%, n = 499), and inguinal canal surgery (14.9%, n = 491).Anesthesia-related complication was represented by urinary retention (1.09%, n = 36), lipotimia (0.75%, n = 25), and postoperative nausea (0.33%, n = 11); arrhythmic events were uncommon (0.18%, n = 6). One case of persistent hypotension and 2 cases of persistent hypertension were reported.Persistent motor or sensory block (lasting more than 5 h) was experienced by 7 patients. One patient (0.03%), who underwent knee arthroscopy, experienced pelvic pain lasting for 6 h, compatible with a transient neurological symptom.Proctologic surgery was a factor associated with unplanned admission due to anesthesia-related complications (OR = 4.9; 95% CI: 2-14%).The number of complications related to the method was low as well as the need for hospitalization. This drug is valid and safe for the most performed day surgery procedures; however, further trials are needed to investigate the incidence of complications in the days following the procedure.
PubMed: 37864260
DOI: 10.1186/s44158-023-00122-6 -
BMC Pharmacology & Toxicology Oct 2023EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers.
BACKGROUND
EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers.
MATERIALS AND METHODS
The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study.
RESULTS
After applied 15 g of the cream for 4 h to a 100 cm area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated.
CONCLUSION
The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study.
CLINICAL TRIAL REGISTRATION
CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.
Topics: Humans; Lidocaine, Prilocaine Drug Combination; East Asian People; Healthy Volunteers; Drug Combinations; Anesthetics, Local; Prilocaine; Lidocaine; Erythema
PubMed: 37828535
DOI: 10.1186/s40360-023-00690-x -
European Journal of Pharmaceutical... Jun 2024Using accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical...
Cutaneous Pharmacokinetics-Based Bioequivalence: A Clinical Dermal Open Flow Microperfusion Verification Study Using Lidocaine and Prilocaine Combination Topical Products.
BACKGROUND
Using accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical generic products. A clinical dermal open flow microperfusion (dOFM) study has previously demonstrated the BE of topical drug products containing a hydrophilic drug. However, the utility of dOFM to evaluate the topical BE of drug products containing moderately lipophilic drugs, more representative of most topical drugs, has not yet been established.
OBJECTIVE
To evaluate the ability of a clinical dOFM study to assess BE of topical products containing two moderately lipophilic drugs that have only minor differences in chemical and physical properties.
METHODS
The study included 20 healthy subjects. Four application sites on each thigh were treated with fixed dose lidocaine/prilocaine combination products, and dermal drug concentrations were monitored with two dOFM probes per application site for 12 hours. A reference cream was compared to itself and to an approved generic cream (both serving as positive controls for BE), and to a gel (negative control). BE was established based on AUC and C using the scaled-average-BE approach. Systemic exposure of both drugs was assessed throughout the study.
RESULTS
BE was successfully demonstrated for the positive controls, and not for the negative control, for both drugs. The systemic exposure of both drugs was negligible.
CONCLUSIONS
dOFM accurately demonstrated BE between bioequivalent topical creams, sensitively discriminated between different formulations and differentiated the cutaneous PK of both study drugs, even though they differ only slightly in chemical and physical properties. These results support the utility of dOFM as a cutaneous PK BE approach for topical lipophilic drugs, including lidocaine and prilocaine.
PubMed: 38857708
DOI: 10.1016/j.ejps.2024.106827 -
International Journal of Pharmaceutics Feb 2024It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Ts) of amorphous drugs and drug excipient systems. However, previous...
It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Ts) of amorphous drugs and drug excipient systems. However, previous studies suggest that water, as an anti-plasticizer, can increase the Ts of co-amorphous systems of prilocaine (PRL) and lidocaine (LID). In order to investigate the intermolecular interactions between water and co-amorphous PRL-LID systems, Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were conducted. Water was found to bind with the carbonyl groups of PRL and LID molecularly evenly in the hydrated co-amorphous PRL-LID systems. Quantum chemical simulations visually confirmed the interactions between water and co-amorphous PRL-LID systems. Furthermore, the physical stability of hydrated co-amorphous PRL-LID systems was improved due to the anti-plasticizing effect of water, compared with the anhydrous samples. The preference of water to interact with the carbonyl groups of PRL and LID as binding sites could be associated with the anti-plasticizing effect of water on the co-amorphous PRL-LID systems.
Topics: Prilocaine; Lidocaine; Transition Temperature; Temperature; Water; Spectroscopy, Fourier Transform Infrared; Drug Stability; Calorimetry, Differential Scanning; Solubility
PubMed: 38220121
DOI: 10.1016/j.ijpharm.2024.123807 -
Cureus Mar 2024Intrauterine devices (IUDs) are considered a reliable contraceptive option for women, but they can come with side effects. There is a disconnect in standard guidelines... (Review)
Review
Intrauterine devices (IUDs) are considered a reliable contraceptive option for women, but they can come with side effects. There is a disconnect in standard guidelines for IUD insertion within and without the U.S. The objective of this review was to address a gap in the literature regarding official procedures for pain management during IUD implantation. This scoping review was initiated using keywords to extract relevant articles from multiple databases: U.S. National Library of Medicine National Institutes of Health (PubMed), MEDLINE (Ovid), and Excerpta Medica dataBASE (EMBASE, Ovid). Initially, 457 articles were identified and after a rigorous screening and selection process, 37 articles were chosen to be further assessed to ascertain if they met the study's inclusion criteria. Those 37 articles were further evaluated fully to check for relevancy. From that process, 19 articles were chosen for the review, and all passed quality assessment evaluations using the JB Appraisal Tools. To best address the research question, the data from the 19 articles were divided into three categories: 1) circumstantial factors, 2) non-pharmacological methods, and 3) pharmacological methods. Circumstantially, women with previous vaginal deliveries experienced the lowest pain during the procedure, and nulligravid (never pregnant) women experienced the most pain. Lower pain scores were reported by lactating women compared to non-lactating. Black women experienced the most anticipated pain compared to other races. Regarding non-pharmacological methods, different insertion techniques, tools, and the use of a cold compress were found to not affect the level of pain during IUD insertion. Lastly, it was shown that pharmacological methods such as lidocaine gel, lidocaine paracervical block, and lidocaine combined with either diclofenac or prilocaine decreased pain scores at different time stamps of the procedure. Also, oral ketorolac and a vaginal combination of misoprostol and dinoprostone helped reduce pain. Findings from this scoping review revealed a lack of uniformity across practices when performing IUD insertions, possibly due to differences in procedures across circumstantial factors, non-pharmacological methods, and pharmacological methods. More research is needed to investigate the intricacies of pain with IUD insertion. Moving forward, especially following a potential increase in the use of IUDs after the reversal of Roe v. Wade, establishing this gap may lead to a more refined standardized protocol to mitigate pain with IUD insertions.
PubMed: 38586685
DOI: 10.7759/cureus.55785 -
Dental Research Journal 2023Although most of the metabolism of local anesthetics (LAs) takes place in the liver, no study has investigated the effect of these anesthetics on the kidney function of...
BACKGROUND
Although most of the metabolism of local anesthetics (LAs) takes place in the liver, no study has investigated the effect of these anesthetics on the kidney function of single-kidney humans or animals. The present study was conducted to examine the effect of LAs on renal function in single-kidney rats.
MATERIALS AND METHODS
The present experimental animal study with two control groups was done in an animal laboratory. Forty-two rats were randomly assigned to seven groups of six rats, including two control groups and five experimental groups. The experimental groups underwent intraperitoneal anesthesia with 2% lidocaine, 2% lidocaine with 1:80,000 epinephrine, 4% articaine, 3% prilocaine with 0.03 IU Felypressin, and 3% mepivacaine, respectively. Unilateral nephrectomy was done. After 24 h, the rats' blood urea nitrogen (BUN), serum creatinine (Cr), and blood specific gravity (BSG) were measured. A standard dose of anesthetics was injected into the peritoneum for 4 days afterward. Then, these indices were measured again 24 h after the last injection. Data were analyzed using IBM SPSS (version 21.0). One-way analysis of variance, Tukey's honestly significant difference , and paired -tests were used for statistical analysis. < 0.05 was considered statistically significant.
RESULTS
The results indicated significant differences among groups in the rats' BUN and serum Cr 24 h after nephrectomy ( < 0.05). However, there were no significant differences in BUN, BSG, and Cr among groups after the interventions.
CONCLUSION
LAs did not affect renal function in single-kidney rats. Therefore, dentists can use the anesthetics in single-kidney people.
PubMed: 38020254
DOI: No ID Found -
Sultan Qaboos University Medical Journal Feb 2024This review aimed to assess the effectiveness of the eutectic mixture of local anaesthetics (EMLA) cream in the management of arteriovenous fistula (AVF) needle... (Review)
Review
This review aimed to assess the effectiveness of the eutectic mixture of local anaesthetics (EMLA) cream in the management of arteriovenous fistula (AVF) needle insertion pain in adult patients undergoing haemodialysis (HD) compared with other alternative interventions. The main search was conducted in November 2020 and updated in December 2021. In the search strategy, keywords and synonyms were used and multiple databases were searched with no date limitation to ensure a comprehensive search that would yield all studies relevant to the review and minimise location bias. A total of 209 studies were found in this search and filtered. After filtering through these studies, only five studies were finally included in the review. EMLA-cream was found to be effective in reducing AVF needle insertion pain among adult patients undergoing HD. Despite EMLA cream's effectiveness in reducing HD needle insertion pain and its fewer side effects, the findings of the included studies should be interpreted with caution, as there are some limitations, and further research is required.
Topics: Adult; Humans; Lidocaine, Prilocaine Drug Combination; Anesthetics, Local; Renal Dialysis; Arteriovenous Fistula; Emollients; Pain
PubMed: 38434453
DOI: 10.18295/squmj.10.2023.058