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1.
Emerg Med Clin North Am ; 39(3): 677-687, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215409

RESUMO

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.


Assuntos
Drogas Desenhadas/efeitos adversos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Canabinoides/efeitos adversos , Drogas Desenhadas/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Loperamida/administração & dosagem , Loperamida/efeitos adversos , Mitragyna/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Fenetilaminas/efeitos adversos
2.
Medicine (Baltimore) ; 100(27): e26527, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232187

RESUMO

ABSTRACT: Interscalene block (ISB) is commonly performed for regional anesthesia in shoulder surgery. Ultrasound-guided ISB enables visualization of the local anesthetic spread and a reduction in local anesthetic volume. However, little is known about the appropriate local anesthetic dose for surgical anesthesia without sedation or general anesthesia. The purpose of our study was to evaluate the appropriate local anesthetic volume by comparing intraoperative analgesics and hemodynamic changes in ISB in arthroscopic shoulder surgery.Overall, 1007 patients were divided into groups 1, 2, and 3 according to the following volume of local anesthetics: 10-19, 20-29, and 30-40 mL, respectively. The use of intraoperative analgesics and sedatives, and the reduction in intraoperative maximum blood pressure and heart rate were compared through retrospective analysis.Fentanyl was used in 55.6% of patients in group 1, which was significantly higher than in those groups 2 and 3 (22.3% and 30.7%, respectively); furthermore, it was also higher than those in groups 2 and 3 in dose-specific comparisons (P < .05). The percent of the maximum reduction in intraoperative systolic blood pressure and heart rate in group 3 was significantly higher than those in groups 1 and 2. Ephedrine administration was lower in group 2 than that in other groups (P < .05). The incidence of hypotensive bradycardic events was lowest (9.1%) at the local anesthetic volume of 24 mL as revealed by the quadratic regression analysis (R2 = 0.313, P = .003).Decreasing the local anesthetic volume to less than 20 mL for ultrasound-guided ISB as the sole anesthesia increases the opioid consumption during shoulder arthroscopic surgery. Local anesthetics >30 mL or increased opioid consumption with <20 mL of local anesthetics could increase the risk of cardiovascular instability intraoperatively. Our findings indicate that 24 mL of local anesthetic could be used to lower the incidence of hypotensive bradycardic events.


Assuntos
Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Artroscopia/métodos , Bloqueio do Plexo Braquial/métodos , Artropatias/cirurgia , Dor Pós-Operatória/prevenção & controle , Articulação do Ombro/cirurgia , Anestesia Local , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia de Intervenção
3.
Bone Joint J ; 103-B(7 Supple B): 103-110, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34192916

RESUMO

AIMS: Due to the opioid epidemic in the USA, our service progressively decreased the number of opioid tablets prescribed at discharge after primary hip (THA) and knee (TKA) arthroplasty. The goal of this study was to analyze the effect on total morphine milligram equivalents (MMEs) prescribed and post-discharge opioid repeat prescriptions. METHODS: We retrospectively reviewed 19,428 patients undergoing a primary THA or TKA between 1 February 2016 and 31 December 2019. Two reductions in the number of opioid tablets prescribed at discharge were implemented over this time; as such, we analyzed three periods (P1, P2, and P3) with different routine discharge MME (750, 520, and 320 MMEs, respectively). We investigated 90-day refill rates, refill MMEs, and whether discharge MMEs were associated with represcribing in a multivariate model. RESULTS: A discharge prescription of < 400 MMEs was not a risk factor for opioid represcribing in the entire population (p = 0.772) or in opioid-naïve patients alone (p = 0.272). Procedure type was the most significant risk factor for narcotic represcribing, with unilateral TKA (hazard ratio (HR) = 5.62), bilateral TKA (HR = 6.32), and bilateral unicompartmental knee arthroplasty (UKA) (HR = 5.29) (all p < 0.001) being the highest risk for refills. For these three procedures, there was approximately a 5% to 6% increase in refills from P1 to P3 (p < 0.001); however, there was no significant increase in refill rates after any hip arthroplasty procedures. Total MMEs prescribed were significantly reduced from P1 to P3 (p < 0.001), leading to the equivalent of nearly 500,000 fewer oxycodone 5 mg tablets prescribed. CONCLUSION: Decreasing opioids prescribed at discharge led to a statistically significant reduction in total MMEs prescribed. While the represcribing rate did not increase for any hip arthroplasty procedure, the overall refill rates increased by about 5% for most knee arthroplasty procedures. As such, we are now probably prescribing an appropriate amount of opioids at discharge for knee arthroplasty procedure, but further reductions may be possible for hip arthroplasty procedures. Cite this article: Bone Joint J 2021;103-B(7 Supple B):103-110.


Assuntos
Analgésicos Opioides/administração & dosagem , Artroplastia de Quadril , Artroplastia do Joelho , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Alta do Paciente , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 100(22): e25884, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087830

RESUMO

BACKGROUND: Currently, no meta-analysis exists elucidate the analgesic effect of adding IPACK block to our current multimodal analgesia regimen after total knee replacement (TKR). The purpose of this study is to systematically review the level I evidence in the literature to ascertain whether IPACK block can bring additional analgesic benefits to existing multimodal analgesia regimens. METHODS: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Only level I randomized controlled trials (RCTs) were included in our study. The primary outcome was the pain scores with rest and activity. Secondary outcomes included cumulative opioid consumption, cumulative distance ambulated, and length of stay (LOS). RESULTS: Five RCTs with a total of 467 patients were included. The most important finding in our study was that although IPACK block supplementation improved pain scores at 12 hours with rest or activity after surgery, no such benefit was observed at subsequent time points during the postoperative period. Interestingly, IPACK supplementation did not reduce opioid consumption, especially in the first 24 hours after surgery. Furthermore, other postoperative outcomes, including cumulative distance ambulated and LOS, were also not improved by the addition of an IPACK. CONCLUSIONS: The addition of an IPACK block to multimodal analgesia regiments does not reduce the postoperative opioid consumption nor improve functional performance. However, it may be an appropriate method to improve immediate analgesic effects after TKR.


Assuntos
Analgesia/métodos , Artroplastia do Joelho/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Analgésicos Opioides/administração & dosagem , Índice de Massa Corporal , Terapia Combinada , Deambulação Precoce , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Zoo Wildl Med ; 52(2): 715-720, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130416

RESUMO

Fifty-three free-ranging moose (Alces americanus) cows were darted from a helicopter with 3-4 ml of a premix combination of butorphanol (27.3 mg/ml), azaperone (9.1 mg/ml), and medetomidine (10.9 mg/ml; BAM), equivalent to estimated dosages of: butorphanol 0.26 ± 0.08 (mean ± SD) mg/kg, azaperone 0.09 ± 0.03 mg/kg, and medetomidine 0.11 ± 0.03 mg/kg. After a mean chase time (from sighting to darting) of 6.1 ± 5.5 min, the mean induction time (from darting to recumbency) was 8.3 ± 2.6 min. This combination provided a safe and reliable sedation for minor procedures that lasted 30-60 min. Heart rate (50.4 ± 7.0 beats/min), respiratory rate (21.3 ± 11.1 breaths/minute), ETCO2 via nasal canula (43.2 ± 7.0 mmHg), and rectal temperature (38.5°C ± 0.7°C) mostly remained at expected values for wild cervid and bovid species anesthetized with this drug combination. SpO2 (90.0% ± 3.7%) was suggestive of moderate hypoxemia despite intranasal oxygen supplementation (1 L per 100 kg/min). The recovery time to standing was 6.7 ± 3.8 min after reversal with IM naltrexone (3 mg/mg butorphanol) and atipamezole (5 mg/mg medetomidine). Despite a larger volume to inject, this protocol offers an alternative to highly potent opioids, and should be considered for practical or staff safety reasons. On the basis of the results of this study, the use of 4 ml of BAM is considered a safe and effective protocol for immobilization of cow moose under comparable settings.


Assuntos
Azaperona/farmacologia , Butorfanol/farmacologia , Cervos , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestesia/veterinária , Animais , Animais Selvagens , Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Medetomidina/administração & dosagem
7.
Br J Anaesth ; 127(1): 75-84, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34147159

RESUMO

BACKGROUND: Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied. METHODS: Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database. RESULTS: On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways. CONCLUSIONS: Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Analgésicos Opioides/efeitos adversos , Genômica/tendências , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/mortalidade , Idoso , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Cuidados Intraoperatórios/efeitos adversos , Cuidados Intraoperatórios/tendências , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências
8.
AAPS PharmSciTech ; 22(5): 186, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145510

RESUMO

The aim of this study was to investigate the effect of various parameters on the stability of butorphanol tartrate injection and to screen the optimal packaging material. The effect of the headspace oxygen levels, ampoule color, manufacturer, and size on the stability of butorphanol tartrate formulation were evaluated. The headspace oxygen levels controlled by nitrogen purging were found to be particularly effective in improving stability of the butorphanol formulation, especially below 2%. Although it is a photolabile drug, butorphanol tartrate was getting degraded at much higher extent in amber color ampoules in comparison to clear ampoules. The degradation by oxidation was found to be a free radical-mediated process catalyzed by the presence of iron ions leached from the amber ampoules. The ampoule manufacturers also had a significant effect on the stability of butorphanol. Two-milliliter ampoules provided a better stability of the butorphanol tartrate injection than 1mL ampoules as 2-mL ampoules had the lower headspace oxygen level at the same level of oxygen content. The oxidation mechanism of the butorphanol tartrate injection was investigated under various conditions, which include iron powder spiking, removal of excipients, exposure to oxygen/nitrogen, exposure to stainless steel and at different pH. Iron powder spiking, presence of citric acid, exposure to oxygen, exposure to stainless steel, and high pH accelerated the oxidative degradation. The effect of oxygen, iron ion and citric acid is in agreement with a metal-catalyzed oxidation mechanism called Udenfriend reaction. Based on the formulation test results, limiting headspace oxygen level, ampoule color, manufacturer, size, controlling iron ion contamination, and pH are recommended for formulation development. In conclusion, it can be suggested that this study can lead to a better understanding of the degradation mechanism of butorphanol tartrate; hence, it would contribute to the development of butorphanol tartrate injection with improved stability. Virous packaging materials have different effects on the stability of butorphanol tartrate injection, and the leached iron of packaging ampoules and stainless steel can trigger Udenfriend reaction with butorphanol tartrate and citric acid (CA), which lead to the oxydative degradation of butorphanol tartrate injection.


Assuntos
Analgésicos Opioides/química , Butorfanol/química , Contaminação de Medicamentos/prevenção & controle , Embalagem de Medicamentos/normas , Ferro/análise , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/metabolismo , Butorfanol/administração & dosagem , Butorfanol/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Embalagem de Medicamentos/métodos , Estabilidade de Medicamentos , Injeções Subcutâneas , Ferro/metabolismo , Oxirredução
9.
J Zoo Wildl Med ; 52(2): 453-459, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130387

RESUMO

Przewalski's horses (Equus ferus przewalskii) are an endangered equid species. Anesthesia administered by remote delivery is often needed to provide medical care. Behavioral and physiologic parameters were prospectively compared in 14 horses (8 females and 6 males, 3-18 yr) after a single-dart or staged two-dart anesthesia induction protocol with intramuscular medetomidine (0.06 mg/kg), butorphanol (0.05 mg/kg), thiafentanil (0.02 mg/kg), and ketamine (1 mg/kg). Seven horses were randomly assigned to receive all drugs in a single dart, and the other seven to receive medetomidine and butorphanol 10 min prior to thiafentanil and ketamine in a second dart. Induction and recovery quality were scored on a scale from 1 to 5 (worst to best), and video recordings were assessed for frequency of specific behaviors. Need for supplemental propofol was recorded. Median induction score was significantly better (P = 0.01) after two darts (4/5) compared to a single dart (3/5). Degree of muscle fasciculation (undesirable) during induction was significantly lower (P= 0.006) with the two-dart protocol. During the transition to recumbency, 71% versus 14% of horses transitioned headfirst (undesirable) after a single dart versus two darts, respectively (P= 0.07). Supplemental propofol administration was necessary in 43% of horses after two darts and in 100% of horses after a single dart (P= 0.10) to facilitate intubation and reach a working depth of anesthesia. Physiologic and recovery parameters were not significantly different between groups. Improved induction quality was observed clinically using a staged two-dart versus a single-dart protocol and should be considered when anesthetizing captive Przewalski's horses using this drug combination.


Assuntos
Analgésicos Opioides/farmacologia , Anestésicos/farmacologia , Cavalos , Hipnóticos e Sedativos/farmacologia , Analgésicos Opioides/administração & dosagem , Anestésicos/administração & dosagem , Animais , Animais de Zoológico , Esquema de Medicação , Feminino , Hipnóticos e Sedativos/administração & dosagem , Masculino
10.
Med Clin North Am ; 105(4): 699-721, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059246

RESUMO

Chronic pruritus (itch lasting ≥6 weeks) is a bothersome chief complaint that may present in a broad variety of diseases. Most itch-causing diagnoses fit into 1 of 5 categories (inflammatory, secondary to systemic disease, neuropathic, chronic pruritus of undetermined origin, and psychogenic itch) and this broad differential can be narrowed using key findings in the history and physical. In this article, we discuss which key findings are most pertinent for narrowing this differential and guiding further workup and treatment, as well as how to treat many itchy conditions.


Assuntos
Inflamação/complicações , Doenças do Sistema Nervoso Periférico/complicações , Prurido/diagnóstico , Prurido/etiologia , Dermatopatias/patologia , Administração Tópica , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Algoritmos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/uso terapêutico , Doença Crônica , Aconselhamento/métodos , Detergentes/administração & dosagem , Detergentes/uso terapêutico , Diagnóstico Diferencial , Emolientes/administração & dosagem , Emolientes/uso terapêutico , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Neurotransmissores/administração & dosagem , Neurotransmissores/uso terapêutico , Apoio Nutricional/métodos , Prurido/tratamento farmacológico , Terapia de Relaxamento/métodos
11.
Bone Joint J ; 103-B(6 Supple A): 102-107, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34053282

RESUMO

AIMS: Liposomal bupivacaine (LB) as part of a periarticular injection protocol continues to be a highly debated topic in total knee arthroplasty (TKA). We evaluated the effect of discontinuing the use of LB in a periarticular protocol on immediate postoperative pain scores, opioid consumption, and objective functional outcomes. METHODS: On 1 July 2019, we discontinued the use of intraoperative LB as part of a periarticular injection protocol. A consecutive group of patients who received LB as part of the protocol (Protocol 1) and a subsequent group who did not (Protocol 2) were compared. All patients received the same opioid-sparing protocol. Verbal rating scale (VRS) pain scores were collected from our electronic data warehouse and averaged per patient per 12-hour interval. Events relating to the opiate administration were derived as morphine milligram equivalences (MMEs) per patient per 24-hour interval. The Activity Measure for Post-Acute Care (AM-PAC) tool was used to assess the immediate postoperative function. RESULTS: A total of 888 patients received Protocol 1 and while 789 received Protocol 2. The mean age of the patients was significantly higher in those who did not receive LB (66.80 vs 65.57 years, p = 0.006). The sex, BMI, American Society of Anesthesiologists physical status score, race, smoking status, marital status, operating time, length of stay, and discharge disposition were similar in the two groups. Compared with the LB group, discontinuing LB showed no significant difference in postoperative VRS pain scores up to 72 hours (p > 0.05), opioid administration up to 96 hours (p > 0.05), or AM-PAC scores within the first 24 hours (p > 0.05). CONCLUSION: The control of pain after TKA with a multimodal management protocol is not improved by the addition of LB compared with traditional bupivacaine. Cite this article: Bone Joint J 2021;103-B(6 Supple A):102-107.


Assuntos
Anestésicos Locais/administração & dosagem , Artroplastia do Joelho , Bupivacaína/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Injeções Intra-Articulares , Lipossomos , Masculino , Medição da Dor , Recuperação de Função Fisiológica
12.
Curr Opin Psychiatry ; 34(4): 357-362, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33993168

RESUMO

PURPOSE OF REVIEW: Opioid use is prevalent in the United Kingdom and prior to the COVID-19 pandemic it had been recognized that the safety of opioids was an important issue to be monitored by the UK medicines regulatory agency. With the emergence of COVID-19, this requirement has been even greater. This review was undertaken to determine the impact of the pandemic on safety and surveillance of opioids in the United Kingdom. RECENT FINDINGS: During the COVID-19 pandemic, the surveillance of opioids in the United Kingdom continued, although primary research was often conducted with data prior to the pandemic. Of those studies that were conducted while the pandemic was ongoing, access to opioids (or opioid substitution therapy) and the subsequent effect on patient safety was the main theme. SUMMARY: In the United Kingdom, changes in accessibility to the healthcare system and how healthcare providers operated during the COVID-19 pandemic may have had unintended consequences on use and safety of opioids, due to the shift in focus to preventing COVID-19 from overwhelming the healthcare system. The findings from this review support the need to continue surveillance in the United Kingdom, including the impact of the COVID-19 pandemic on opioid utilization and safety.


Assuntos
Analgésicos Opioides/administração & dosagem , COVID-19/prevenção & controle , Uso Indevido de Medicamentos/prevenção & controle , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Analgésicos Opioides/efeitos adversos , Acesso aos Serviços de Saúde , Humanos , Transtornos Relacionados ao Uso de Opioides/terapia , Cuidados Paliativos/métodos , Pandemias , SARS-CoV-2 , Assistência Terminal/métodos , Reino Unido/epidemiologia
13.
Cochrane Database Syst Rev ; 5: CD013263, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998669

RESUMO

BACKGROUND: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE. AUTHORS' CONCLUSIONS: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.


Assuntos
Dor Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Cetorolaco/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Viés , Diclofenaco/administração & dosagem , Humanos , Injeções Intravenosas , Isoxazóis/administração & dosagem , Cetorolaco/efeitos adversos , Pessoa de Meia-Idade , Números Necessários para Tratar , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
14.
Anesth Analg ; 133(1): 233-242, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33939649

RESUMO

BACKGROUND: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. METHODS: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. RESULTS: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. CONCLUSIONS: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.


Assuntos
Analgésicos Opioides/administração & dosagem , Cafeína/administração & dosagem , Cuidados Intraoperatórios/métodos , Laparoscopia/efeitos adversos , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/prevenção & controle , Adulto , Idoso , Estimulantes do Sistema Nervoso Central/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Laparoscopia/tendências , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Resultado do Tratamento
15.
Psychopharmacology (Berl) ; 238(7): 1857-1866, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33988725

RESUMO

RATIONALE: Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans. OBJECTIVE: To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals. METHODS: Participants with recreational opioid use, but without opioid physical dependence, were enrolled as inpatients for ~6 weeks (n = 8). A within-subject, double-blind, randomized, placebo-controlled, crossover design was employed. The pharmacodynamic response to intranasal oxycodone across a range of doses (0 to 30 mg) was examined during two counterbalanced maintenance periods (tradipitant 0 or 85 mg/bid). Oxycodone self-administration was assessed with a modified progressive ratio procedure, and analgesia was assessed with the cold pressor test. RESULTS: Oxycodone produced significant and dose-related increases on a broad array of prototypic opioid measures, including subjective ratings related to abuse liability (e.g., liking) and physiological outcomes (i.e., expired CO2). Oxycodone self-administration increased with increasing dose, as did analgesia. Tradipitant largely did not alter any of these effects of oxycodone, with the exception of producing a reduction in ratings of desire for opioids. CONCLUSIONS: Given that the vast majority of oxycodone effects were unchanged by tradipitant, these data do not provide support for the utility of NK1 antagonists as a potential treatment for opioid use disorder.


Assuntos
Analgésicos Opioides/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Oxicodona/administração & dosagem , Medição da Dor/efeitos dos fármacos , Receptores da Neurocinina-1 , Administração Intranasal , Adolescente , Adulto , Analgesia/métodos , Analgesia/psicologia , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/psicologia , Medição da Dor/métodos , Medição da Dor/psicologia , Reforço Psicológico , Autoadministração , Resultado do Tratamento , Adulto Jovem
16.
Paediatr Drugs ; 23(4): 361-372, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34046854

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used for pediatric pain management in the emergency setting and postoperatively. This narrative literature review evaluates pain relief, opioid requirements, and adverse effects associated with NSAID use. A PubMed search was conducted to identify randomized controlled trials evaluating the use of conventional systemic NSAIDs as pain management for children in the perioperative or emergency department (traumatic injury) setting. Trials of cyclooxygenase-2 inhibitors ("coxibs") were excluded. Search results included studies of ibuprofen (n = 12), ketoprofen (n = 5), ketorolac (n = 6), and diclofenac (n = 4). NSAIDs reduced the opioid requirement in 10 of 13 studies in which this outcome was measured. NSAID use did not compromise pain relief; NSAIDs provided improved or similar pain scores compared with opioids (or other control) in 24 of 27 studies. Adverse event frequencies were reported in 26 studies; adverse event frequencies with NSAIDs were lower than with opioids (or other control) in three of 26 studies, similar in 21 of 26 studies, and more frequent in two of 26 studies. Perioperative and emergency department use of NSAIDs may reduce opioid requirements while maintaining pain control, with similar or reduced frequencies of opioid-associated adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Serviço Hospitalar de Emergência , Manejo da Dor/métodos , Dor/tratamento farmacológico , Assistência Perioperatória/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Dor/diagnóstico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico
17.
Lancet Digit Health ; 3(6): e397-e407, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34045004

RESUMO

A need exists to accurately estimate overdose risk and improve understanding of how to deliver treatments and interventions in people with opioid use disorder in a way that reduces such risk. We consider opportunities for predictive analytics and routinely collected administrative data to evaluate how overdose could be reduced among people with opioid use disorder. Specifically, we summarise global trends in opioid use and overdoses; describe the use of big data in research into opioid overdose; consider the potential for predictive modelling, including machine learning, for prevention and monitoring of opioid overdoses; and outline the challenges and risks relating to the use of big data and machine learning in reducing harms that are related to opioid use. Future research for improving the coverage and provision of existing interventions, treatments, and resources for opioid use disorder requires collaboration of multiple agencies. Predictive modelling could transport the concept of stratified medicine to public health through novel methods, such as predictive modelling and emulated trials for evaluating diagnoses and prognoses of opioid use disorder, predicting treatment response, and providing targeted treatment recommendations.


Assuntos
Analgésicos Opioides , Big Data , Overdose de Drogas , Aprendizado de Máquina , Modelos Estatísticos , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/administração & dosagem , Overdose de Drogas/etiologia , Overdose de Drogas/mortalidade , Overdose de Drogas/prevenção & controle , Previsões , Humanos , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides/mortalidade
18.
Pain Res Manag ; 2021: 2542010, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055117

RESUMO

Background: Acute postoperative pain delays recovery and increases morbidity and mortality. Opioid therapy is effective but is accompanied by adverse reactions. Patient-controlled analgesia (PCA) enables self-administration of analgesics. Oral-PCA is a safe and beneficial alternative to intravenous (IV) PCA. We have developed a novel Oral-PCA device, which enables self-administration of solid pills to the patient's mouth. This is a retrospective study comparing the effectiveness and usability of this novel Oral-PCA with those of IV-PCA. Methods: Medical records of patients who received PCA following gynecology and orthopedic surgeries were analyzed. The control cohort (n = 61) received oxycodone by IV-PCA. The test cohort (n = 44) received oxycodone by Oral-PCA via the PCoA Acute device. Outcome measures include the Numeric Rating Scale (NRS) score at rest and movement, side effects, technical difficulties, bolus dose administered, and bolus dose requested. Results: Patient demographics, initial NRS, and PCA duration were comparable between cohorts. NRS reduction in rest and movement was stronger in the Oral-PCA cohort (rest: 1.61 and 2.27, P = 0.077; movement: 2.05 and 2.84, P = 0.039), indicating better pain control and mobility for Oral-PCA. Side effect rates were comparable between cohorts (9% and 11% of patients who experienced side effects, P = 1.000). The rate of technological difficulties was higher in the Oral-PCoA cohort (19.7% and 36.4%, P = 0.056). The mean total bolus dose administered to patients was comparable in both cohorts (18.32 mg and 21.14 mg oxycodone, P = 0.270). However, the mean total boluses requested by patients during lockout intervals were lower in the Oral-PCA cohort (12.8 mg and 6.82 mg oxycodone, P = 0.004), indicating better pain control. Conclusions: Oral-PCA by using PCoA® Acute provides pain control and usability which is noninferior to the IV-PCA, as well as superior to pain reduction in rest and movement. These results, along with the noninvasiveness, medication flexibility, and reduced cost, suggest the potential of Oral-PCA, by using PCoA Acute, to replace IV-PCA for postoperative analgesia.


Assuntos
Administração Intravenosa , Administração Oral , Analgesia Controlada pelo Paciente/instrumentação , Analgésicos Opioides/administração & dosagem , Oxicodona/administração & dosagem , Manejo da Dor/instrumentação , Dor Pós-Operatória/tratamento farmacológico , Administração Intravenosa/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
19.
Int J Surg ; 90: 105962, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33932589

RESUMO

BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, is a potential alternative analgesic to reduce opioid consumption after Pancreaticoduodenectomy (PD). Further, the safety and efficacy of long-term use of parecoxib for patients after PD remain a major concern. MATERIALS AND METHODS: In this single-center, randomized clinical trial, 134 patients undergoing open PD were randomized into the parecoxib group (group P) and control group (group C) at a 1:1 ratio. Besides a routine patient-controlled epidural analgesia (PCEA) until 3 days postoperatively for both groups, patients in group P (n = 68) received parecoxib (40 mg, intravenously, Q 12 h) for the first 5 postoperative days and were encouraged to receive opioid analgesics to control severe pain as needed. Patients in group C (n = 66) received on-demand opioid analgesics (pethidine or morphine) postoperatively. The primary outcomes included the effectiveness of parecoxib in controlling pain (measured using the visual analog scale (VAS)) and reduction of opioid use (measured as accumulated doses). Secondary outcomes included the postoperative recovery process, rate of postoperative complications, and the anti-inflammatory effect of parecoxib. RESULTS: The VAS scores were not significantly different between the two groups. The number of doses of opioids for patients in group P (3.2 ± 0.3 doses) was significantly lower than in group C (8.5 ± 0.4 doses) (p = 0.0007). The incidence of opioid-related side effects was significantly lower in group P than in group C (p = 0.001). There were no significant differences in postoperative complications or readmission rates between the two groups. The postoperative time to first pass flatus, time to first mobilization out of bed, and time of removal of nasogastric tube in group P were significantly shorter than those in group C (P < 0.05). The postoperative serum IL-6 levels of patients in group P were significantly lower than those in group C at each time point (P < 0.05). CONCLUSIONS: Parecoxib effectively controls pain after PD. Prophylactic analgesia using parecoxib for up to 5 days after PD is safe, feasible, and can provide the same optimal pain control as opioids without adverse effects.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Isoxazóis/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Analgesia Controlada pelo Paciente , Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Isoxazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Manejo da Dor , Medição da Dor , Dor Pós-Operatória/etiologia
20.
Medicine (Baltimore) ; 100(15): e25531, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847679

RESUMO

INTRODUCTION: As the adjunctive anesthesia to propofol, both dezocine and fentanyl showed some potential for gastrointestinal endoscopy. This meta-analysis aimed to compare their efficacy and safety. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of dezocine versus fentanyl for the anesthesia of patients undergoing gastrointestinal endoscopy were included. RESULTS: Five RCTs involving 677 patients were included in the meta-analysis. Overall, compared with fentanyl plus propofol for gastrointestinal endoscopy, dezocine plus propofol resulted in the reduction in propofol dose(mean difference [MD] = -11.72; 95% confidence interval [CI] = -22.83 to -0.61; P = .04), awakening time (std. MD = -1.79; 95% CI = -3.31 to -0.27; P = .02) and hypopnea (risk ratio [RR] = 0.16; 95% CI = 0.06-0.41; P = .0002), but had no remarkable effect on induction time (MD = 1.20; 95% CI = -0.98 to 3.39; P = .28), postoperative pain score (MD = -0.38; 95% CI = -1.00 to 0.24; P = .24), nausea or vomiting (RR = 0.45; 95% CI = 0.10-1.98; P = .29). CONCLUSION: Dezocine plus propofol may be better for the anesthesia of gastrointestinal endoscopy than fentanyl plus propofol.


Assuntos
Analgésicos Opioides/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Endoscopia Gastrointestinal/efeitos adversos , Fentanila/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Propofol/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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