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Drug Candidates for Anesthesia and Analgesia

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 42720

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Special Issue Editors

Dr. Tuomas Lilius

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Guest Editor

1. INDIVIDRUG Research Program and Department of Pharmacology, Faculty of Medicine, University of Helsinki, FI-00290 Helsinki, Finland
2. Department of Emergency Medicine and Services, Helsinki University Hospital and University of Helsinki, FI-00290 Helsinki, Finland
3. Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 København, Denmark
Interests: novel opioids; ketamine; pharmacodynamics

Prof. Dr. Teijo Saari

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Co-Guest Editor

Department of Anaesthesiology and Intensive Care, University of Turku and Turku University Hospital, Turku, Finland
Interests: pain therapy; opioids; pharmacometrics

Special Issue Information

Dear Colleagues,

Most currently used analgesics act either by decreasing the excitability of peripheral nociceptors or through the inhibition of nociceptive signaling in the central nervous system (CNS). Almost all analgesics acting at the CNS level have anxiolytic properties, and a major problem related to their use is the development of dependency. The lack of efficacy, the adverse effects, and the opioid epidemic in the United States have created an urgent need for the development of novel, safer, and more effective analgesics. There are several novel targets under investigation, but even with our advanced understanding of pain pathophysiology, only a few new analgesics with a new mechanism of action have emerged so far during the 21st century. In addition to the discovery of novel analgesic targets, there is also a need for individualized tailoring and repurposing of the currently used analgesics in drug delivery aspects, as well as identifying patient groups benefiting most from therapy.

New innovations in drug development and delivery contribute to continued improvement in anesthesia. Recent and evolving drug innovations are primarily focused on modifying the chemical structures of existing drugs or drug classes with the intent to improve their pharmacodynamic, pharmacokinetic, and adverse effect profiles. Alongside drug development, innovations in intravenous infusion delivery systems and pharmacometric modeling have fostered the development of target-controlled infusion regimens. The goal is to develop a closed-loop system wherein the measured output(s) is/are used by a controller to determine a new input to the control system where the output is determined by the pharmacodynamic input(s). All these innovations will promote more precise and safer patient care, but there is an urgent need for large clinical trials to provide more evidence to ensure patient safety prior to widespread clinical implementation.

The journal Pharmaceuticals warmly invites both reviews and original articles on anesthetic and analgesic drug discovery. This Special Issue includes clinical, translational, and preclinical manuscripts dealing with the development of novel candidates for anesthesia and analgesia, as well as repurposing old drugs for these indications.

Prof. Dr. Tuomas Lilius
Prof. Dr. Teijo Saari
Guest Editors

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Keywords

analgesic
anesthetic
drug discovery
repurposing

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Published Papers (12 papers)

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Research

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19 pages, 7111 KiB

Open AccessArticle

Andrographolide Relieves Post-Operative Wound Pain but Affects Local Angiogenesis

by Yi-Lo Lin, Jiunn-Wang Liao, Shunching Wang, Badrinathan Sridharan, Hsin-Ju Lee, Ai Li, Kai-Ming Chang, Ching-Yang Wu, Siendong Huang, Kai-Ting Chang, Dinesh Chandra Agrawal, Ching-Jung Chen and Meng-Jen Lee

Pharmaceuticals 2022, 15(12), 1586; https://doi.org/10.3390/ph15121586 - 19 Dec 2022

Viewed by 2231

Abstract

Andrographolide (Andro), the major constituent of Andrographis paniculata Nees (Acanthaceae), is was known to reduces inflammatory reaction. In the current study, the ability of Andro to reduce pain sensation in a rat post-operative wound model was explored. The hind paws of 18 Sprague-Dawley rats (SD) bearing post-operative wounds received the following three treatments: Saline, Andro via direct injection into the paw (Andro-injected) and Tablet containing Andro + poly (lactic-co-glycolic acid) (PLGA) (Andro-tablet). Von Frey tests assessed mechanical allodynia at 1, 3, 5 h and 1-, 2-, 3-, 4-, and 5-days post-operation. Behavioral analyses were performed to measure reaction threshold and reaction frequencies. Immunoreactivity of p-ERK and GluR1 was examined in the dorsal horn of the spinal cord. Histopathological and immunostaining studies were conducted on paw epidermis to observe the gross morphology and angiogenesis. The threshold for inducing allodynia increased and the reaction frequency reduced in the Andro-injected group compared to the saline-group, at 3 h post-surgery and the effect lasted between 3–4 days. The threshold for inducing pain and reaction frequency for the Andro-tablet group did not differ from the saline-treated group. The levels of p-ERK and GluR1 in the dorsal horn were reduced after Andro treatment. No significant difference in wound healing index was observed between saline and Andro-injected groups, but CD-31 staining showed less angiogenesis in the Andro-injected group. Andro significantly reduced mechanical allodynia compared to saline treatment, both in shorter and longer time frames. Furthermore, Andro influenced the expression of p-ERK and GluR1 in the dorsal horn, and the angiogenesis process in the wound healing area. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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11 pages, 575 KiB

Open AccessArticle

Analgesic and Anesthetic Efficacy of Rocuronium/Sugammadex in Otorhinolaryngologic Surgery: A Propensity Score-Matched Analysis

by En-Bo Wu, Chao-Ting Hung, Sheng-Dean Luo, Shao-Chun Wu, Tsung-Yang Lee, Jo-Chi Chin, Peng-Neng Tsai and Johnson Chia-Shen Yang

Pharmaceuticals 2022, 15(7), 894; https://doi.org/10.3390/ph15070894 - 19 Jul 2022

Cited by 2 | Viewed by 2638

Abstract

The use of rocuronium/sugammadex in otorhinolaryngologic surgery improves intubation conditions and surgical rating scales. This study primarily aimed to evaluate the effect of the combination of rocuronium and sugammadex on intraoperative anesthetic consumption. The secondary outcomes were the intraoperative and postoperative morphine milligram equivalent (MME) consumption, duration of intraoperative hypertension, extubation time, incidence of delayed extubation and postoperative nausea and vomiting, pain score, and length of stay. A total of 2848 patients underwent otorhinolaryngologic surgery at a tertiary medical center in southern Taiwan. After applying the exclusion criteria, 2648 of these cases were included, with 167 and 2481 in the rocuronium/sugammadex and cisatracurium/neostigmine groups, respectively. To reduce potential bias, 119 patients in each group were matched by propensity scores for sex, age, body weight, and type of surgery. We found that the rocuronium/sugammadex group was associated with significant preservation of the intraoperative sevoflurane and MME consumption, with reductions of 14.2% (p = 0.009) and 11.8% (p = 0.035), respectively. The use of the combination of rocuronium and sugammadex also significantly increased the dose of intraoperative labetalol (p = 0.002), although there was no significant difference in intraoperative hypertensive events between both groups. In conclusion, our results may encourage the use of the combination of rocuronium and sugammadex as part of volatile-sparing and opioid-sparing anesthesia in otorhinolaryngologic surgery. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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13 pages, 2283 KiB

Open AccessArticle

[6]-Shogaol Attenuates Oxaliplatin-Induced Allodynia through Serotonergic Receptors and GABA in the Spinal Cord in Mice

by Suyong Kim, Juan Gang, Ji-Hwan Lee, Hyejin Yang, Chunhoo Cheon, Seong-Gyu Ko, Hyunsu Bae and Woojin Kim

Pharmaceuticals 2022, 15(6), 726; https://doi.org/10.3390/ph15060726 - 8 Jun 2022

Cited by 8 | Viewed by 2718

Abstract

Although oxaliplatin is a well-known anti-cancer agent used for the treatment of colorectal cancer, treated patients often experience acute cold and mechanical allodynia as side effects. Unfortunately, no optimal treatment has been developed yet. In this study, [6]-shogaol (10 mg/kg, i.p.), which is one of the major bioactive components of Zingiber officinale roscoe (Z. officinale), significantly alleviated allodynia induced by oxaliplatin (6 mg/kg, i.p.) injection. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. The analgesic effect of [6]-shogaol was blocked by the intrathecal injection of 5-HT1A, 5-HT3, and GABAB receptor antagonists, NAN-190 (1 μg), MDL-72222 (15 μg), and CGP 55845 (10 μg), respectively. Furthermore, oxaliplatin injection lowered the GABA concentration in the superficial laminae of the spinal dorsal horn, whereas [6]-shogaol injection significantly elevated it. The GAD (glutamic acid decarboxylase) 65 concentration also increased after [6]-shogaol administration. However, pre-treatment of NAN-190 completely inhibited the increased GABA induced by [6]-shogaol in the spinal dorsal horn, whereas MDL-72222 partially blocked the effect. Altogether, these results suggest that [6]-shogaol could attenuate oxaliplatin-induced cold and mechanical allodynia through 5-HT_1A and 5-HT₃ receptor antagonists located in the GABAergic neurons in the spinal dorsal horn in mice. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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11 pages, 1787 KiB

Open AccessArticle

Rapid Absorption of Naloxone from Eye Drops

by Johanna Tuunainen, Lasse Saloranta, Jouko Levijoki, Jenni Lindstedt, Jenni Lehtisalo, Sari Pappinen, Meri Ramela, Sami Virtanen and Heikki Joensuu

Pharmaceuticals 2022, 15(5), 532; https://doi.org/10.3390/ph15050532 - 25 Apr 2022

Viewed by 3146

Abstract

Naloxone as emergency treatment for opioid overdosing can be administered via several routes. However, the available administration methods are invasive or may be associated with incomplete or slow naloxone absorption. We evaluated pharmacokinetics and local tolerance of naloxone ocular drops in healthy beagle dogs. Naloxone administration as eye drops produced fast absorption with time to maximum plasma concentration (t_max) achieved in 14 to 28 min, high plasma exposure (C_max 10.3 ng/mL to 12.7 ng/mL), and good bioavailability (41% to 56%). No signs of ocular irritability were observed in the scored ocular tolerability parameters, and the reactions of dogs suggesting immediate ocular discomfort after the dosing were sporadic and short lasting. Slight and transient increase in the intraocular pressure and transient decrease in the tear production were recorded. The results suggest that eye drops may provide a fast and an effective non-invasive route for naloxone administration to reverse opioid overdosing, and clinical studies in the human are warranted. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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13 pages, 582 KiB

Open AccessArticle

Adverse Events during Vitreoretinal Surgery under Adequacy of Anesthesia Guidance—Risk Factor Analysis

by Michał Jan Stasiowski, Aleksandra Pluta, Anita Lyssek-Boroń, Seweryn Król, Lech Krawczyk, Ewa Niewiadomska, Jakub Żak, Magdalena Kawka, Dariusz Dobrowolski, Beniamin Oskar Grabarek, Izabela Szumera, Michael Janusz Koss, Anna Missir, Robert Rejdak and Przemysław Jałowiecki

Pharmaceuticals 2022, 15(2), 237; https://doi.org/10.3390/ph15020237 - 16 Feb 2022

Cited by 4 | Viewed by 2779

Abstract

Vitreoretinal surgeries require the administration of general anesthesia (GA) in selected groups of patients. The administration of intraoperative rescue narcotic analgesia (IRNA) during GA poses the risk of postoperative nausea and vomiting (PONV). The surgical pleth index (SPI), a crucial component of the adequacy of anesthesia (AoA) guidance of GA, optimizes the intraoperative titration of IRNA. The current analysis evaluated the risk factors for the occurrence of PONV and the oculo-cardiac reflex (OCR) in patients undergoing pars plana vitrectomy (PPV) under AoA guidance. In total, 175 patients undergoing PPV were randomly allocated to receive either GA with SPI-guided IRNA administration using fentanyl alone or in addition to different preoperative analgesia techniques. Any incidence of PONV or OCR was recorded. Obesity, overweight, smoking status, motion sickness, postoperative intolerable pain perception, female gender, fluid challenge and arterial hypertension did not correlate with an increased incidence of PONV or OCR under AoA guidance. Diabetes mellitus, regardless of insulin dependence, was found to correlate with the increased incidence of PONV. The AoA regimen including SPI guidance of IRNA presumably created similar conditions for individual subjects, so no risk factors of the occurrence of PONV or OCR were found, except for diabetes mellitus. We recommend using AoA guidance for GA administration to reduce OCR and PONV rates. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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12 pages, 269 KiB

Open AccessArticle

The Safety Profile of General and Local Anaesthetic Agents: Data Collected during 20 Years of Spontaneous Reporting Activities in the Campania Region (Southern Italy)

by Francesca Gargano, Cristina Scavone, Gabriella di Mauro, Alberto Della Corte, Alice Zoccoli, Francesco Rossi, Giovanni Francesco Nicoletti and Annalisa Capuano

Pharmaceuticals 2021, 14(12), 1261; https://doi.org/10.3390/ph14121261 - 3 Dec 2021

Cited by 3 | Viewed by 2742

Abstract

Background: General and local anaesthetics are widely used during surgery. These drugs have peculiar safety profiles, being commonly associated with mild and reversible local adverse drug reactions (ADRs), but also with more severe and systemic ADRs, including respiratory and cardiovascular depression and anaphylaxis. Methods and Objectives: We carried out a descriptive analysis of Individual Case Safety Reports (ICSRs) sent to the Campania Regional Centre of Pharmacovigilance (Southern Italy) from 2001 to 2021 that reported general or local anaesthetics as suspected drugs, with the aim of describing their overall characteristics, focussing on the ADRs’ seriousness and distribution by System Organ Class (SOC) and Preferred Term (PT). Results: A total of 110 ICSRs documenting general or local anaesthetics were sent to the Italian pharmacovigilance database during 20 years of spontaneous reporting activities in the Campania region. ADRs mainly occurred in patients with a median age of 48 years and in a slightly higher percentage of men. ADRs were more commonly classified as not serious and had a favourable outcome. In terms of ADRs’ distribution by SOC and PT, both general and local anaesthetics were associated with general and cutaneous disorders, with common ADRs that included lack of efficacy, rash, and erythema. In addition, general anaesthetics were associated with the occurrence of respiratory ADRs, while local anaesthetics were associated with the occurrence of nervous ADRs. Conclusion: Even though a limited number of ICSRs documenting anaesthetics-induced ADRs were retrieved from the Italian spontaneous reporting database in the Campania region, we believe that the continuous monitoring of these drugs is highly recommended, especially among the frail population. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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15 pages, 950 KiB

Open AccessReview

Epidural Oxycodone for Acute Pain

by Panu Piirainen, Hannu Kokki and Merja Kokki

Pharmaceuticals 2022, 15(5), 643; https://doi.org/10.3390/ph15050643 - 23 May 2022

Cited by 1 | Viewed by 4979

Abstract

Epidural analgesia is commonly used in labour analgesia and in postoperative pain after major surgery. It is highly effective in severe acute pain, has minimal effects on foetus and newborn, may reduce postoperative complications, and enhance patient satisfaction. In epidural analgesia, low concentrations of local anaesthetics are combined with opioids. Two opioids, morphine and sufentanil, have been approved for epidural use, but there is an interest in evaluating other opioids as well. Oxycodone is one of the most commonly used opioids in acute pain management. However, data on its use in epidural analgesia are sparse. In this narrative review, we describe the preclinical and clinical data on epidural oxycodone. Early data from the 1990s suggested that the epidural administration of oxycodone may not offer any meaningful benefits over intravenous administration, but more recent clinical data show that oxycodone has advantageous pharmacokinetics after epidural administration and that epidural administration is more efficacious than intravenous administration. Further studies are needed on the safety and efficacy of continuous epidural oxycodone administration and its use in epidural admixture. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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22 pages, 35397 KiB

Open AccessReview

Biased, Bitopic, Opioid–Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction

by Robert Root-Bernstein

Pharmaceuticals 2022, 15(2), 214; https://doi.org/10.3390/ph15020214 - 10 Feb 2022

Cited by 10 | Viewed by 4718

Abstract

This paper proposes the design of combination opioid–adrenergic tethered compounds to enhance efficacy and specificity, lower dosage, increase duration of activity, decrease side effects, and reduce risk of developing tolerance and/or addiction. Combinations of adrenergic and opioid drugs are sometimes used to improve analgesia, decrease opioid doses required to achieve analgesia, and to prolong the duration of analgesia. Recent mechanistic research suggests that these enhanced functions result from an allosteric adrenergic binding site on opioid receptors and, conversely, an allosteric opioid binding site on adrenergic receptors. Dual occupancy of the receptors maintains the receptors in their high affinity, most active states; drops the concentration of ligand required for full activity; and prevents downregulation and internalization of the receptors, thus inhibiting tolerance to the drugs. Activation of both opioid and adrenergic receptors also enhances heterodimerization of the receptors, additionally improving each drug’s efficacy. Tethering adrenergic drugs to opioids could produce new drug candidates with highly desirable features. Constraints—such as the locations of the opioid binding sites on adrenergic receptors and adrenergic binding sites on opioid receptors, length of tethers that must govern the design of such novel compounds, and types of tethers—are described and examples of possible structures provided. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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33 pages, 1672 KiB

Open AccessReview

Mechanistic Insight into the Effects of Curcumin on Neuroinflammation-Driven Chronic Pain

by Hasriadi, Peththa Wadu Dasuni Wasana, Opa Vajragupta, Pornchai Rojsitthisak and Pasarapa Towiwat

Pharmaceuticals 2021, 14(8), 777; https://doi.org/10.3390/ph14080777 - 7 Aug 2021

Cited by 23 | Viewed by 6349

Abstract

Chronic pain is a persistent and unremitting condition that has immense effects on patients’ quality of life. Studies have shown that neuroinflammation is associated with the induction and progression of chronic pain. The activation of microglia and astrocytes is the major hallmark of spinal neuroinflammation leading to neuronal excitability in the projection neurons. Excessive activation of microglia and astrocytes is one of the major contributing factors to the exacerbation of pain. However, the current chronic pain treatments, mainly by targeting the neuronal cells, remain ineffective and unable to meet the patients’ needs. Curcumin, a natural plant product found in the Curcuma genus, improves chronic pain by diminishing the release of inflammatory mediators from the spinal glia. This review details the role of curcumin in microglia and astrocytes both in vitro and in vivo and how it improves pain. We also describe the mechanism of curcumin by highlighting the major glia-mediated cascades in pain. Moreover, the role of curcumin on inflammasome and epigenetic regulation is discussed. Furthermore, we discuss the strategies used to improve the efficacy of curcumin. This review illustrates that curcumin modulating microglia and astrocytes could assure the treatment of chronic pain by suppressing spinal neuroinflammation. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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12 pages, 473 KiB

Open AccessCase Report

Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study

by Reino Pöyhiä, Teija Nieminen, Ville W. T. Tuompo and Hannu Parikka

Pharmaceuticals 2022, 15(11), 1372; https://doi.org/10.3390/ph15111372 - 8 Nov 2022

Cited by 6 | Viewed by 3163

Abstract

Dexmedetomidine (DEX) is a commonly used sedative agent with no or minimal effects on breathing. DEX may also be beneficial in myocardial protection. Since the mechanisms of cardiac effects are not well known, we carried out a descriptive review and examined the effects of DEX on myocardial electrical conduction in a prospective and controlled manner. For the review, clinical studies exploring DEX in myocardial protection published between 2020-2022 were explored. A case study included 11 consecutive patients at a median (range) age of 48 (38–59), scheduled for elective radiofrequency ablation of paroxysmal atrial fibrillation. A bolus dose of DEX 1 µg/kg given in 15 min was followed by a continuous infusion of 0.2–0.7 µg/kg/h. Direct intracardiac electrophysiologic measurements, hemodynamics and oxygenation were measured before and after the DEX bolus. Experimental studies show that DEX protects the heart both via stabilizing cardiac electrophysiology and reducing apoptosis and autophagy after cell injury. The clinical evidence shows that DEX provides cardiac protection during different surgeries. In a clinical study, DEX increased the corrected sinus node recovery time, prolongated the atrioventricular (AV) nodal refractory period and cycle length producing AV nodal Wenckebach retrograde conduction block. DEX has a putative role in organ protection against hypoxic, oxidative and reperfusion injury. DEX slows down the firing of the sinus node and prolongs AV refractoriness. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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16 pages, 2921 KiB

Open AccessSystematic Review

Effects of Short-Acting Opioids on Intraocular Pressure during General Anesthesia: Systematic Review and Network Meta-Analysis

by Jian-You Huang, Ping-Cheng Shih, Chu-Ting Chen, Han-Yu Lin, Yung-Jiun Chien, Meng-Yu Wu, Chih-Hao Chen and Chun-Yu Chang

Pharmaceuticals 2022, 15(8), 989; https://doi.org/10.3390/ph15080989 - 11 Aug 2022

Cited by 3 | Viewed by 2329

Abstract

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 μg kg⁻¹) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, −3.64; confidence interval (CI), −5.47 to −1.81 and after endotracheal intubation (MD, −9.71; CI, −11.91 to −7.51). Remifentanil (1 μg kg⁻¹) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 μg kg⁻¹) should be considered the drug of choice in the circumstances where increased IOP is a great concern. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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14 pages, 1691 KiB

Open AccessSystematic Review

Dexamethasone Increases the Anesthetic Success in Patients with Symptomatic Irreversible Pulpitis: A Meta-Analysis

by Lorenzo Franco-de la Torre, Eduardo Gómez-Sánchez, Nicolás Addiel Serafín-Higuera, Ángel Josabad Alonso-Castro, Sandra López-Verdín, Nelly Molina-Frechero, Vinicio Granados-Soto and Mario Alberto Isiordia-Espinoza

Pharmaceuticals 2022, 15(7), 878; https://doi.org/10.3390/ph15070878 - 16 Jul 2022

Cited by 2 | Viewed by 2936

Abstract

Inferior alveolar nerve block (IANB) has a high failure rate in subjects with symptomatic irreversible pulpitis (SIP). It has been suggested that drugs with anti-inflammatory activity could improve the efficacy of the anesthetic used for IANB. The aim of this study was to assess the effect of dexamethasone on the success of dental anesthesia in patients with SIP. An information search was performed using PubMed and Google Scholar. The risk of bias of the included studies was evaluated with the Cochrane Collaboration’s risk-of-bias tool. The anesthetic success rate, pain intensity (VAS), and adverse effects were extracted. Data were analyzed using the Mantel–Haenszel test and odds ratio or the inverse variance and standardized mean difference. Dexamethasone increased the anesthetic success in comparison with placebo (n = 502; p < 0.001; OR = 2.59; 95% CIs: 1.46 to 4.59). Moreover, patients who were given dexamethasone had lower pain scores at 6 h (n = 302; p < 0.001; MD= −1.43; 95% CIs: −2.28 to −0.58), 12 h (n = 302; p < 0.0001; MD = −1.65; 95% CIs: −2.39 to −0.92), and 24 h (n = 302; p < 0.0008; MD = −1.27; 95% CIs: −2.01 to −0.53) when compared with placebo. In conclusion, the systemic administration of dexamethasone increases the anesthetic success rate and improves pain management in patients with SIP. Full article

(This article belongs to the Special Issue Drug Candidates for Anesthesia and Analgesia)

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