RESUMO
Inadequate control of postoperative pain after orthopedic procedures may trigger complications that increase morbidity. Multimodal analgesia is used to manage pain effectively after surgical procedures and reduce the need for rescue analgesia. Intravenous (IV) acetaminophen (OFIRMEV; Cadence Pharmaceuticals, Inc.), an analgesic that has been studied and used in the multimodal management of acute pain after major orthopedic procedures, combines the safety seen with oral and rectal formulations with a preferred route of administration. Two double-blind, randomized, placebo-controlled clinical trials were conducted (total 130 patients) to determine the efficacy and safety of single-dose IV acetaminophen in patients following total hip arthroplasty. Although both studies were stopped prematurely, overlap in patient populations, study design, and methodologies in the single-dose phase of these studies allowed for analysis of their results to be presented concurrently. Both trials demonstrated IV acetaminophen having greater efficacy than placebo in terms of primary endpoints [pain intensity differences from T0.5 to T3 (P < 0.05 in both studies)]. The use of IV acetaminophen also reduced the need for rescue opioid consumption, with patients receiving IV acetaminophen consuming, on average, less than half the amount of rescue medication as those receiving placebo. IV acetaminophen was effective in treating moderate-to-severe pain after total hip arthroplasty and reduced the need for rescue opioid consumption.
Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Artroplastia de Quadril/métodos , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Medição da DorRESUMO
A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.
Assuntos
Analgesia , Bupivacaína , Humanos , Masculino , Bupivacaína/efeitos adversos , Anestésicos Locais/efeitos adversos , Injeções Subcutâneas , Área Sob a Curva , Preparações de Ação RetardadaRESUMO
The objective of this study was to develop a population pharmacokinetic-pharmacodynamic model of subcutaneously administered bupivacaine in a novel extended-release microparticle formulation for postoperative pain management. Bupivacaine was administered subcutaneously in the lower leg to 28 healthy male subjects in doses from 150 to 600 mg in a phase 1 randomized, placebo-controlled, double-blind, dose-ascending study with two different microparticle formulations, LIQ865A and LIQ865B. Warmth detection threshold was used as a surrogate pharmacodynamic endpoint. Population pharmacokinetic-pharmacodynamic models were fitted to plasma concentration-effect-time data using non-linear mixed-effects modelling. The pharmacokinetics were best described by a two-compartment model with biphasic absorption as two parallel absorption processes: a fast, zero-order process and a slower, first-order process with two transit compartments. The slow absorption process was found to be dose-dependent and rate-limiting for elimination at higher doses. Apparent bupivacaine clearance and the transit rate constant describing the slow absorption process both appeared to decrease with increasing doses following a power function with a shared covariate effect. The pharmacokinetic-pharmacodynamic relationship between plasma concentrations and effect was best described by a linear function. This model gives new insight into the pharmacokinetics and pharmacodynamics of microparticle formulations of bupivacaine and the biphasic absorption seen for several local anaesthetics.
Assuntos
Bupivacaína , Modelos Biológicos , Humanos , Masculino , Bupivacaína/farmacologia , Método Duplo-CegoRESUMO
BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).
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Antivirais , Tratamento Farmacológico da COVID-19 , Humanos , Masculino , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/administração & dosagem , Adulto , COVID-19/virologia , SARS-CoV-2 , Idoso , Resultado do Tratamento , Compostos OrgânicosRESUMO
BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Inibidores de Protease de Coronavírus , SARS-CoV-2 , Animais , Humanos , Camundongos , Antivirais/farmacologia , Antivirais/uso terapêutico , Catepsina L/antagonistas & inibidores , COVID-19/prevenção & controle , Modelos Animais de Doenças , Camundongos Transgênicos , Inibidores de Protease de Coronavírus/química , Inibidores de Protease de Coronavírus/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Tratamento Farmacológico da COVID-19/métodosRESUMO
As the number of patients aged 65 years and older increases, joint replacement has become a frequent procedure after progressive osteoarthritis or fractures. Although hip and knee arthroplasty has become a relatively commonplace procedure in this age-group, the advanced age in patients undergoing these procedures often is associated with comorbidities and potential complications that can present challenges and limit analgesic choices. This subset analysis is designed to determine the efficacy and safety of intravenous (IV) acetaminophen in the elderly subpopulation from 3 placebo-controlled studies conducted to document the safety and efficacy of IV acetaminophen. A total of 231 patients were enrolled in the 3 trials, and of these, a total of 107 patients (46%) were aged 65 years or older. Across the studies, safety and efficacy were well documented in the elderly subpopulation and were comparable with the subpopulation younger than 65 years. A review of the literature similarly demonstrates the efficacy and safety of IV acetaminophen used for postoperative analgesia after joint replacement.
Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Artroplastia de Substituição , Infusões Intravenosas , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/uso terapêutico , Feminino , Humanos , Masculino , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND AND METHODS: From the time that Sinatra et al. (Anesthesiology. 2005;102:822) was published to FDA apaproval of intravenous (IV) acetaminophen, an expanded analysis of the original raw study data became necessary for the regulatory submission. The following analyses were conducted: (1) sum of pain intensity differences over 24 hours (SPID24) using currently accepted imputation methods to account for both missing data and the effects of rescue; (2) efficacy results after the first 6 hours; (3) effects of gender, race/ethnicity, age, weight, surgical site, ASA Class, and serotonin antagonists; and (4) a stepwise regression analysis of why adverse events of nausea and vomiting were numerically (although not statistically) higher in the IV acetaminophen group compared with placebo. RESULTS: Sum of pain intensity differences over 24 hours using a 0- to 100-mm visual analog scale was statistically significantly (P < 0.001) in favor of IV acetaminophen (n = 49) compared with placebo (n = 52). Time to rescue was found to be 3.9 and 2.1 hours, respectively, for total hip and knee arthroplasty compared with 0.8 hours for the placebo group. Rescue medication consumption, requests, and actual administration were all significantly lower in the IV acetaminophen group compared with placebo for each dosing interval, except in the 6- to 12-hours interval where a numerical trend was observed. Analysis of various subset variables demonstrated similar efficacy for each variable. A stepwise regression analysis demonstrated that AE reports of nausea and vomiting were most likely due to prerandomization events, particularly opioid consumption and presence of nausea prior to randomization. CONCLUSION: Repeated-dose 24-hours end points were found to be as robust as previously published results. IV acetaminophen efficacy and safety appeared to be unaffected by specific subset variables.âª
Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Procedimentos Ortopédicos/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/efeitos adversos , Adulto , Idoso , Analgésicos não Narcóticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/classificação , Dor Pós-Operatória/fisiopatologia , Placebos , Estudos Prospectivos , Método Simples-CegoRESUMO
BACKGROUND: This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen. METHODS: Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV(®) ; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol(®) 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall(®) 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg. Acetaminophen plasma and CSF levels were obtained at T0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 6 hours. RESULTS: IV acetaminophen showed earlier and higher plasma and CSF levels compared with PO or PR administration. CSF bioavailability over 6 hours (AUC(0-6)) for IV, PO, and PR 1 g was 24.9, 14.2, and 10.3 µg·h/mL, respectively. No treatment-related adverse events were reported. One subject was replaced because of premature failure of his lumbar spinal catheter. The mean CSF level in the IV group was similar to plasma from 3 to 4 hours and higher from 4 hours on. Absorption phase, variability in plasma, and CSF were greater in PO and PR groups than variability with IV administration. CONCLUSIONS: These results demonstrate that earlier and greater CSF penetration occurs as a result of the earlier and higher plasma peak with IV administration compared with PO or PR.
Assuntos
Acetaminofen/administração & dosagem , Administração Oral , Administração Retal , Analgésicos não Narcóticos , Infusões Intravenosas , Acetaminofen/sangue , Acetaminofen/líquido cefalorraquidiano , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/sangue , Analgésicos não Narcóticos/líquido cefalorraquidiano , Área Sob a Curva , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Humanos , Masculino , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: This study's objective was to systematically review the literature to assess analgesic outcomes of intravenous (IV) acetaminophen for acute postoperative pain in adults. METHODS: We searched Medline and the Cochrane library (January 1, 2000 to January 17, 2010, date of last search) for prospective, randomized, controlled trials (RCTs) of IV acetaminophen vs. either an active comparator or placebo. RESULTS: Sixteen articles from 9 countries published between 2005 and 2010 met inclusion criteria and had a total of 1,464 patients. Median sample size=54 patients (range 25 to 165) and median follow-up=1 day (range 1 hour to 7 days). Four of the 16 articles had 3 arms in the study. One article had 4 arms. As a result, 22 study comparisons were analyzed: IV acetaminophen to an active comparator (n=8 studies) and IV acetaminophen to placebo (n=14 studies). The RCTs were of high methodological quality with Jadad median score=5. In 7 of 8 active comparator studies (IV parecoxib [n=3 studies], IV metamizol [n=4], oral ibuprofen [n=1]), IV acetaminophen had similar analgesic outcomes as the active comparator. Twelve of the 14 placebo studies found that IV acetaminophen patients had improved analgesia. Ten of those 14 studies reported less opioid consumption, a lower percentage of patients rescuing, or a longer time to first rescue with IV acetaminophen. Formal meta-analysis pooling was not performed because the studies had different primary end points, and the IV acetaminophen dosing regimens varied in dose, and duration and timing. CONCLUSION: In aggregate, these data indicate that IV acetaminophen is an effective analgesic across a variety of surgical procedures.
Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Anestesia Intravenosa/métodos , Bases de Dados Factuais/estatística & dados numéricos , HumanosRESUMO
BACKGROUND: Intravenous (IV) acetaminophen provides rapid and effective analgesia in the postoperative and inpatient settings. The utility and efficacy of acetaminophen is well established; however, due to chronic excessive dosing of over-the-counter acetaminophen products and prescription opioid combination products resulting in the potential for hepatic toxicity, concerns remain about acetaminophen safety. In order to evaluate the safety of IV acetaminophen 1,000mg q6h or 650mg q4h with repeated dosing for 5 days, a randomized, open-label study assessed the safety and tolerability of repeated doses used to treat acute pain or fever in 213 adult inpatients was conducted. METHODS: Subjects were randomized (3:3:1) to receive IV acetaminophen (1,000mg q6h or 650mg q4h) or standard-of-care treatment for pain or fever. Safety was assessed according to spontaneous reports of adverse events (AEs) and clinically meaningful changes from baseline laboratory parameters. RESULTS: Overall, IV acetaminophen was shown to be safe and well tolerated in adult inpatients when given as repeated doses for up to 5 days. Owing to the comorbidities in the study population, the frequency of AEs reported was high. However, the majority of treatment-emergent adverse events (TEAEs) were unrelated to treatment, and only 8% of the study population withdrew because of TEAEs. No major hepatic issues associated with IV acetaminophen warranted concern, and most hepatic events were likely related to underlying medical conditions or recent trauma/surgery. CONCLUSIONS: Consistent with the tolerability and safety results, both treatment groups (1,000mg q6h and 650mg q4h) demonstrated statistically significantly better ratings for the Subject Global Evaluations for the level of satisfaction with side effects related to study treatments as compared with the control group. The findings from this trial support the use of IV acetaminophen as a safe therapy in adult patients.
Assuntos
Acetaminofen , Analgésicos não Narcóticos , Febre/tratamento farmacológico , Dor/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/uso terapêutico , Humanos , Injeções Intravenosas , Estudos Prospectivos , Resultado do TratamentoRESUMO
This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.
Assuntos
Dor Aguda/dietoterapia , Analgésicos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Medição da Dor/normas , Projetos de Pesquisa , Ensaios Clínicos como Assunto/normas , Humanos , Projetos de Pesquisa/normasRESUMO
OBJECTIVE: To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. METHODS: Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia, governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. CONCLUSIONS: There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy.
Assuntos
Ensaios Clínicos como Assunto/métodos , Diretrizes para o Planejamento em Saúde , Manejo da Dor , Doença Crônica , Ensaios Clínicos como Assunto/normas , Emoções/fisiologia , Humanos , Dor/fisiopatologia , Dor/psicologia , Qualidade de Vida/psicologia , Resultado do TratamentoRESUMO
Botulinum toxin is approved for the treatment of muscle overactivity associated with several disorders, such as dystonias. However, control of muscle spasm often results in pain relief as well. Effective relief of pain associated with myofascial pain syndrome provides a model for the use of botulinum toxin to relieve pain associated with other types of soft-tissue syndromes, such as fibromyalgia. Although the mechanisms that trigger the pain in these syndromes vary, recent data suggest that a central neuroplastic mechanism may contribute to many complex pain syndromes. Botulinum toxin therapy may be particularly useful in soft-tissue syndromes that are refractory to traditional treatment with physical therapy, electrical muscle stimulation, and other approaches. Although not used as first-line therapy for pain relief, botulinum toxin may decrease pain long enough for patients to resume more conservative therapy. A primary benefit of treatment with botulinum toxin is its long duration of action. Several studies have demonstrated the efficacy of botulinum toxin types A and B in treating several neuropathic pain disorders. Proper patient selection, injection technique, and dosing are critical to obtaining the best outcomes in managing pain with botulinum toxin. Additional study is needed to better characterize its use for the treatment of pain.
Assuntos
Toxinas Botulínicas/uso terapêutico , Fibromialgia/tratamento farmacológico , Síndromes da Dor Miofascial/tratamento farmacológico , Dor/tratamento farmacológico , Toxinas Botulínicas/metabolismo , Relação Dose-Resposta a Droga , Fibromialgia/complicações , Humanos , Injeções Intramusculares , Dor/etiologiaRESUMO
BTs are a useful treatment in refractory MPS and have shown promise in various superficial neuropathic pain syndromes. Presumably BTs work by breaking the spasm/pain cycle, giving the patient a "window of opportunity" for traditional conservative measures to have a greater beneficial impact, but several studies suggest that a direct antinociceptive effect distinct from any reduction in muscle spasm may be at play. The major benefit of BTs compared with standard therapies is duration of response. BTs cannot be considered a "first line" treatment for any pain application; however, in refractory cases in which nothing else has helped, BTs may offer the patient and physician a chance for improvement and perhaps even cure.
Assuntos
Analgésicos/uso terapêutico , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Síndromes da Dor Miofascial/tratamento farmacológico , Analgésicos/administração & dosagem , Animais , Antidiscinéticos/administração & dosagem , Toxinas Botulínicas/administração & dosagem , Humanos , Síndromes da Dor Miofascial/diagnósticoRESUMO
CONTEXT: Facet arthropathy is a common cause of spine-related pain. Typically resulting from spondylosis, trauma, including surgical trauma or post surgical stress is also a significant cause. Radiofrequency thermocoagulation or neurolysis may be an effective modality providing long-term improvement. OBJECTIVES: To evaluate the success rates for radiofrequency neurolysis for facet arthropathy in a large retrospective case series in a single pain practice setting. DESIGN: A retrospective case series involving chart reviews and patient follow-up visits or telephone contacts of radiofrequency neurolytic procedures performed for facet arthropathy over a 4-year period. SETTING: Private practice pain clinic with academic affiliation in Tulsa, OK. PARTICIPANTS: One hundred forty eight patients with confirmed facet arthropathy refractory to conservative measures underwent 230 radiofrequency neurolysis procedures and were followed for a minimum of 1 year post procedure. For cervical facet procedures: 63 patients (106 procedures); age range F: 27-84 years old; M: 33-65 years old. For lumbar facet procedures: 85 patients (124 facet procedures); age range F: 19-81 years old; M: 20-77 years old. MAIN OUTCOME MEASURES: After the radiofrequency procedure, patients were followed with periodic visits or telephone contacts. Outcome measures were McGill short form pain questionnaire, VAS pain scores, muscle spasm scores, tenderness, range of motion and patient subjective global responses. RESULTS: Subjective patient responses were graded as follows: excellent:greater than 70% improvement, good: 50% to 70% improvement, fair: 30% to 49%, and poor: less than 30%. One hundred six radiofrequency procedures were performed in the 63 cervical cases and 124 in the 85 lumbar cases with those patients who had good to excellent responses undergoing repeat procedures. Of the patients with cervical facet radiofrequency procedures, 38 (37%), 51 (48%), 4 (3%) and 13 (12%) had excellent, good, fair or poor responses, respectively. Of the lumbar facet radiofrequency cases, 37 (30%), 52 (41%), 13 (10%) and 22 (19%) had excellent, good, fair or poor responses, respectively. Excellent responders noted an average duration of 10.8 months (range 3-34 months before dropping below 70% improvement level) for cervical cases and 7.9 months (range 3-20) for lumbar. Good responders noted an average duration of 6.5 months (range 3-22 months before dropping below 50% improvement level) for cervical and 6.8 months (range 3-48) for lumbar radiofrequency procedures. No significant side effects were experienced (short-term neuritis was seen in 2 patients who had cervical and 1 who had lumbar RFTC, but resolved in each case after a few weeks). CONCLUSIONS: In summary, 85% of cervical and 71% of lumbar RFTC cases had at least a 50% improvement in symptoms for extended periods. RFTC of median branches for facet arthropathy is a safe and efficacious modality with the potential for long-term benefit.
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In this article we are reporting on the use of fluoroscopy-guided 6% Phenol injections for the ablation of the sacroiliac joints (SIJs), utilizing retrospective review of case reports. We reviewed 10 patients (7 male and 3 female) who have known sacroiliitis proven by fluoroscopically guided sacroiliac joint (SIJ) injection (age ranged from 25 to 78). They all had 2 to 4 weeks of relief after the injections utilizing Bupivacaine 0.5% and 80 mg of depomedrol. They all had repeat fluoroscopy-guided injections of the SIJs with neurolysis of either a unilateral SIJ or bilateral SIJs using 6% Phenol. Phenol 6% with saline 2.5 cc per joint was injected; the needle was cleared with local anesthetic before removing it from the joint. Twenty percent of the patients had a greater than 70% improvement with an average duration of 24 weeks. Sixty percent of the patients had a 50% to 70% improvement with an average duration of 20 weeks. Ten percent had a 20% to 50% improvement with a total duration of 12 1/2 weeks. Ten percent had a less than 20% improvement. With intra-articular injections of phenol for the ablation of the SIJs, we have found a significant improvement in pain relief accompanied by prolonged duration of relief.
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Moderate-to-severe postoperative pain is usually controlled using a multimodal approach, including opioids. Intravenously administered patient-controlled analgesia (IV PCA) with opioids, popular for over 40 years, enables patients to control their level of analgesia and has advantages over a nurse-administered approach, including more satisfied patients and improved pain relief. Unfortunately, IV PCA has drawbacks such as device programming errors, medication prescribing errors, pump malfunction, limitations on patient mobility, IV patency issues, and transmission of infection. Furthermore, the setup of an infusion pump is often complex, time-consuming, and requires witnessed confirmation. Complicating IV PCA is the problem of commonly used compounds, morphine and hydromorphone, having significantly reduced brain/effector-site permeability and active metabolites, both of which create the risk of delayed adverse events. Novel patient-controlled modalities that incorporate rapid effector site-permeating opioids and non-invasive routes of administration offer great promise to enhance both patient and caregiver experiences with postoperative analgesia systems.
Assuntos
Analgésicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Dor Pós-Operatória/tratamento farmacológico , Analgesia/efeitos adversos , Analgesia/métodos , Analgesia Controlada pelo Paciente/efeitos adversos , Analgesia Controlada pelo Paciente/métodos , Analgésicos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Humanos , Dor Pós-Operatória/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?
Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Acetaminofen/efeitos adversos , Adulto , Analgésicos não Narcóticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Rotulagem de Medicamentos , Humanos , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sem Prescrição/efeitos adversos , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVES: The purpose of this study was to assess the safety and dynamics of the onset of antipyretic efficacy of intravenous (IV) acetaminophen versus oral (PO) acetaminophen in the treatment of endotoxin-induced fever. METHODS: This randomized, double-blind, double-dummy, single-dose study was conducted at a single center in the United States in healthy volunteer adult males with an endotoxin-induced fever to assess the antipyretic efficacy and safety of IV acetaminophen 1 g versus PO acetaminophen 1 g over 6 hours. Subjects who achieved a sufficient fever response to a test dose of reference standard endotoxin were randomly assigned to receive either IV acetaminophen and PO placebo (n = 54) or PO acetaminophen and IV placebo (n = 51). The primary efficacy outcome was the weighted sum of temperature differences from baseline at time T0 through T120 minutes. Safety evaluations included adverse event (AE), physical exam, and laboratory assessments. RESULTS: Of 105 subjects receiving study medication, 24 vomited within 2 hours postdose (PO acetaminophen, n = 15; and IV acetaminophen, n = 9) and were excluded from the modified intent-to-treat population that consisted of 36 and 45 subjects treated with PO and IV acetaminophen, respectively. While this was done to not confer an advantage to the IV formulation, a sensitivity analysis including these subjects did not change the overall efficacy results. Statistically significant results favoring IV acetaminophen were observed for the primary endpoint (weighted sum of temperature differences over 120 minutes, p = 0.0039) and also at each time point from T30 to T90 minutes, although the maximum mean observed temperature difference was only 0.3°C. The study drugs were well tolerated. The AE frequency was comparable between the IV and PO groups. CONCLUSIONS: A single dose of IV acetaminophen is as safe and effective in reducing endotoxin-induced fever as PO acetaminophen. IV acetaminophen may be useful where patients are unable to tolerate PO intake or when an earlier onset of action is desirable.