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1.
J Surg Res ; 245: 107-114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415931

RESUMO

BACKGROUND: To help control opioid overprescription, we conducted a large institutional, 3-site initiative to provide discharge prescribing guidelines for different procedures. Our aim is to refine institutional guidelines for parathyroidectomy. METHODS: Patients undergoing parathyroidectomy completed a 28-question survey about opioid consumption. Discharge opioid prescription amounts were converted into morphine milligram equivalents (MMEs) and reported as median and interquartile range (IQR). Consumption was dichotomized into top quartile MME users (Q4) versus standard users (Q1, Q3). Univariate analysis compared opioid consumption. RESULTS: A total of 91 patients were included; 90% were opioid-naive. While the median prescribed was 75 (IQR 75, 150) MME, the median consumed was 0 (IQR 0, 20). Top users reported higher pain scores [median (IQR): 2 (2, 4)] compared to standard users [1 (0, 3), P = 0.01]. However, there was no difference in opioid consumption between unilateral neck exploration, bilateral exploration, or thyroidectomy and parathyroidectomy, P = 0.11. There was no difference in opioid consumption by age, sex, or BMI (all P > 0.05). Of those receiving a prescription, 94.6% had left-over opioids at the time of survey, resulting in 82% of prescribed opioids being unused. CONCLUSIONS: Over half of patients undergoing parathyroidectomy did not consume any opioid, and very few needed more than 2 d of opioid. Moreover, most patients did not dispose the unused opioids, which put these pills at risk of diversion and misuse. Surgical approach did not change consumption, illustrating that these guidelines are applicable to thyroidectomy given the similarity between techniques. We recommend prescribing nonopioid analgesics for patients undergoing parathyroidectomy.


Assuntos
Analgésicos não Entorpecentes/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Paratireoidectomia/efeitos adversos , Padrões de Prática Médica/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /prevenção & controle , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Guias de Prática Clínica como Assunto , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Estudos Retrospectivos , Tireoidectomia/efeitos adversos
2.
Plast Reconstr Surg ; 144(4): 991-999, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568318

RESUMO

With the growing opioid epidemic, plastic surgeons are being encouraged to transition away from reliance on postoperative opioids. However, many plastic surgeons hesitate to use nonopioid analgesics such as nonsteroidal antiinflammatory drugs and local anesthetic blocks because of concerns about their safety, particularly bleeding. The goal of this systematic review is to assess the validity of risks associated with nonopioid analgesic alternatives. A comprehensive literature search of the PubMed and MEDLINE databases was conducted regarding the safety of opioid alternatives in plastic surgery. Inclusion and exclusion criteria yielded 34 relevant articles. A systematic review was performed because of the variation between study indications, interventions, and complications. Thirty-four articles were reviewed that analyzed the safety of ibuprofen, ketorolac, celecoxib, intravenous acetaminophen, ketamine, gabapentin, liposomal bupivacaine, and local and continuous nerve blocks after plastic surgery procedures. There were no articles that showed statistically significant bleeding associated with ibuprofen, celecoxib, or ketorolac. Similarly, acetaminophen administered intravenously, ketamine, gabapentin, and liposomal bupivacaine did not have any significant increased risk of adverse events. Nerve and infusion blocks have a low risk of pneumothorax. Limitations of this study include small sample sizes, different dosing and control groups, and more than one medication being studied. Larger studies of nonopioid analgesics would therefore be valuable and may strengthen the conclusions of this review. As a preliminary investigation, this review showed that several opioid alternatives have a potential role in postoperative analgesia. Plastic surgeons have the responsibility to lead the reduction of postoperative opioid use by further developing multimodal analgesia.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Procedimentos Cirúrgicos Reconstrutivos , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos Opioides/uso terapêutico , Humanos , Medição de Risco
3.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600996

RESUMO

Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Substâncias Protetoras/farmacologia , Animais , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Espécies Reativas de Oxigênio/metabolismo
4.
Sci Total Environ ; 691: 1059-1064, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466187

RESUMO

Self-medication during pregnancy continues to be an issue in developing countries due to poor medical education. The most commonly used drugs are analgesics, mainly acetaminophen (paracetamol, APAP) and, to a lesser extent, ketoprofen (KPF). The aim of the study was to establish whether there are consequences of accidental use of these two drugs during early embryogenesis. The experimental study was performed on 30 pregnant white mice, divided into three groups: a first group to which APAP was administered, a second group to which KPF was administered, and group 3 as a control group. At delivery, the baby mice were examined, and after their first parturition, they were taken into study and examined according to the established protocol. Macroscopic and microscopic examinations of the liver and kidney were performed; liver and renal changes were recorded. Regarding the fertility, the number of fetuses born to mothers that were administered APAP and KPF corresponded to the normal values recorded in this species. Microscopic changes that were found in the kidney were as follows: APAP group - necrosis of the urinary tube, vascular congestions and vascular disorders; KPF group - ectasia, especially in the medullary cavity. Microscopic hepatic changes showed in the APAP group - vascular congestions, vascular disorders and hemosiderin deposits in the Kupffer cells; in the KPF group were found - discrete vascular disorders consisting in sinusoidal capillary ectasia and vascular congestions, as well as the presence of lymphocyte conglomerates. The aforementioned lesions indicate hepatic and renal distress with variable degrees of severity, but they appear to be reversible (the longer the time from the maximum effect of the drug the lower its toxicity).


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Animais , Doença Hepática Induzida por Substâncias e Drogas , Feminino , Rim , Fígado/efeitos dos fármacos , Camundongos , Necrose , Gravidez
5.
Trials ; 20(1): 399, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272502

RESUMO

BACKGROUND: The morbidity of knee arthritis is increasing among aged people and total knee arthroplasty has been its mainstream treatment to date. Postoperative rehabilitation is an important part of the procedure. However, the intense pain during the functional exercise involved has always been a challenge for both patients and health care professionals. The aim of this study is to test the analgesic effect of a mixture of nitrous oxide/oxygeb (1:1) inhalation for patients who are doing functional exercise 1 month after total knee arthroplasty. METHODS/DESIGN: This double-blind, randomized, placebo-controlled study will be implemented in the Rehabilitation Department in the General Hospital of Ningxia Medical University. Patients aged between 50 and 75 years who underwent a primary unilateral total knee arthroplasty are eligible for inclusion. The key exclusion criteria include: epilepsy, pulmonary embolism, intestinal obstruction, aerothorax. The treatment group (A) will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesics), and the control group (B) will receive oxygen plus conventional treatment (no analgesics). Patients, physicians, therapists, and data collectors are all blind to the experiment. Assessments will be taken immediately after functional exercise begins (T0), 5 min (T1) after functional exercise begins, and 5 min after functional exercise has finished (T2). Patients will be randomly allocated between a treatment group (A) and a control group (B) in a ratio of 1:1. Primary outcome, including pain severity in the procedure, will be taken for each group. Secondary outcomes include blood pressure, heart rate, oxygen saturation, side effects, knee joint range of motion, Knee Society Score (KSS), rescue analgesia need, and satisfaction from both therapists and patients. DISCUSSION: This study will focus on exploring a fast and efficient analgesic for patients who are doing functional exercise after total knee arthroplasty. Our previous studies suggested that the prefixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burn-dressing pain and breakthrough cancer pain. The results of this study should provide a more in-depth insight into the effects of this analgesic method. If this treatment proves successful, it could be implemented widely for patients doing functional exercise in the rehabilitation department. TRIAL REGISTRATION: ChiCTR-INR-17012891 . Registered on 6 October 2017.


Assuntos
Analgésicos não Entorpecentes/administração & dosagem , Artralgia/prevenção & controle , Artrite/cirurgia , Artroplastia do Joelho/reabilitação , Terapia por Exercício , Articulação do Joelho/cirurgia , Óxido Nitroso/administração & dosagem , Oxigenoterapia , Dor Pós-Operatória/prevenção & controle , Idoso , Analgésicos não Entorpecentes/efeitos adversos , Artralgia/diagnóstico , Artralgia/etiologia , Artralgia/fisiopatologia , Artrite/diagnóstico , Artrite/fisiopatologia , Artroplastia do Joelho/efeitos adversos , China , Método Duplo-Cego , Terapia por Exercício/efeitos adversos , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/efeitos adversos , Oxigenoterapia/efeitos adversos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
6.
Expert Opin Drug Metab Toxicol ; 15(8): 659-669, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31293190

RESUMO

Introduction: Although the hepatotoxicity of acetaminophen is a well-known problem, the search for reliable biomarker of toxicity is still a current issue as clinical tools are missing to assess patients intoxicated following chronic use, sequential ingestion, use of modified release formulations or in case of delayed arrival to hospital. The need for new specific and robust biomarkers for acetaminophen toxicity has prompted many studies exploring the use of blood levels of acetaminophen derivatives, mitochondrial damage markers, liver cell apoptosis and/or necrosis markers and circulating microRNAs. Areas covered: In this review, we present a concise overview of the most promising biomarkers currently under evaluation including descriptions of their properties with respect to exposure type, APAP specificity, and potential clinical application. In addition, we illustrate the power of new technologies for biomarker research and describe their current application to the field of acetaminophen-induced hepatotoxicity. Expert opinion: Recently the use of extracellular vesicles isolation in combination with omics techniques has opened a new perspective to the field of biomarker research. However, the potential of those new technologies for the prediction and monitoring of hepatic diseases and acetaminophen toxicity has not yet been fully taken into consideration.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Acetaminofen/administração & dosagem , Acetaminofen/farmacocinética , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Humanos , MicroRNAs/metabolismo , Mitocôndrias/patologia , Projetos de Pesquisa
7.
Curr Opin Anaesthesiol ; 32(5): 592-599, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306155

RESUMO

PURPOSE OF REVIEW: To explore the data for and against the use of the various components of multimodal analgesia in cranial neurosurgery. RECENT FINDINGS: Postcraniotomy pain is a challenging clinical problem in that analgesia must be accomplished without affecting neurologic function (i.e. 'losing the neurologic exam'). The traditional approach with low-dose opioids is often insufficient and can cause well recognized side effects. Newer multimodal analgesic approaches have proven beneficial in a variety of other surgical patient populations. The combined use of multiple nonopioid analgesics offers the promise of improved pain control and reduced opioid administration, while preserving the clinical neurologic exam. Specifically, acetaminophen and gabapentinoids should be considered for craniotomy patients, both preoperatively and postoperatively. The gabapentinoids have the added benefit of reduced nausea. Scalp blocks have moderate quality evidence supporting their use over incisional infiltration alone, with analgesia that extends into the postoperative period. Intraoperative dexmedetomidine reduces postoperative opioid requirements with the added benefit of reduced postcraniotomy hypertension. Methocarbamol, NSAIDs [both nonspecific cyclooxygenase (COX) 1 and 2 inhibitors and specific COX-2 inhibitors], ketamine, and intravenous lidocaine require further data regarding safety and efficacy in craniotomy patients. SUMMARY: Opioids are the mainstay for treating acute postcraniotomy pain but should be minimized. The evidence to support a multimodal approach is growing; neuroanesthesiologists and neurosurgeons should seek to incorporate multimodal analgesia into the perioperative care of craniotomy patients. Preoperative and postoperative gabapentin and acetaminophen, intraoperative dexmedetomidine, and scalp blocks over incisional infiltration have the most data for benefit, with good safety profiles. Further research is needed to define the safety, efficacy, and dosing parameters for NSAIDs including COX-2 inhibitors, methocarbamol, ketamine, and intravenous lidocaine in cranial neurosurgery.


Assuntos
Analgesia/métodos , Craniotomia/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Equipe de Assistência ao Paciente/organização & administração , Analgesia/efeitos adversos , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestesiologistas/organização & administração , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Medicina Baseada em Evidências/métodos , Humanos , Bloqueio Nervoso/métodos , Neurocirurgiões/organização & administração , Manejo da Dor/efeitos adversos , Dor Pós-Operatória/etiologia , Segurança do Paciente , Assistência Perioperatória/métodos , Resultado do Tratamento
8.
BJOG ; 126(13): 1560-1567, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31310697

RESUMO

OBJECTIVE: Risk of fetotoxicity after paracetamol exposure in the third trimester. DESIGN: Observational cohort study and retrospective case assessment. SETTING: Germany, 2008-2017. POPULATION: Pregnant women exposed to paracetamol. METHODS: Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. MAIN OUTCOME MEASURES: The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. RESULTS: In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. CONCLUSIONS: Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. TWEETABLE ABSTRACT: Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Permeabilidade do Canal Arterial/induzido quimicamente , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Acetaminofen/efeitos adversos , Adulto , Analgésicos não Entorpecentes/efeitos adversos , Permeabilidade do Canal Arterial/embriologia , Feminino , Humanos , Recém-Nascido , Rim/anormalidades , Rim/embriologia , Nefropatias/embriologia , Gravidez , Terceiro Trimestre da Gravidez , Estudos Retrospectivos , Medição de Risco
10.
Drugs Aging ; 36(Suppl 1): 7-14, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073920

RESUMO

Osteoarthritis (OA) is a major cause of pain and physical disability in adults, and an increasingly common disease given its associations with aging and a growing obese/overweight population. Paracetamol is widely recommended for analgesia at an early stage in the management of OA, and, although frequently prescribed, evidence suggests the efficacy of paracetamol for OA pain is low. Furthermore, there have been recent concerns over the safety profile of paracetamol, with reports of gastrointestinal, cardiovascular, hepatic and renal adverse events. This narrative review summarizes recent literature on the benefits and harms of paracetamol for OA pain. Data on long-term paracetamol safety are derived largely from observational evidence, and are difficult to interpret given the potential biases of such data. Nonetheless, a considerable degree of toxicity is associated with paracetamol use among the general population, especially at the upper end of standard analgesic doses. Paracetamol is linked to liver function abnormalities and there is evidence for liver failure associated with non-intentional paracetamol overdose. Safety data for paracetamol use in the older population (aged >65 years) are sparse; however, there is some evidence that frail elderly people may have impaired paracetamol clearance. Given that the analgesic benefit of paracetamol in OA joint pain is uncertain and potential safety issues have been raised, more careful consideration of its use is required.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Artralgia/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Idoso , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Humanos , Manejo da Dor/métodos
11.
J Int Med Res ; 47(6): 2562-2570, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079512

RESUMO

OBJECTIVE: This study was designed to evaluate the neurotoxicity of dexmedetomidine combined with ropivacaine for continuous femoral nerve block in rabbits. METHODS: Thirty New Zealand rabbits were randomly divided into 5 groups of 6 rabbits each and received a continuous femoral nerve block with saline; 0.25% ropivacaine; or 1, 2, or 3 µg/mL of dexmedetomidine added to 0.25% ropivacaine (Groups A-E, respectively). Sensory and motor function was assessed after the nerve block. The rabbits were anesthetized and killed after 48 hours of a continuous femoral nerve block, and the femoral nerves were removed for light and electron microscopy analyses. RESULTS: The behavior scores were highest in Group A at 2 and 6 hours after injection. The scores were higher in Groups B and C than in Groups D and E at these same time points. All groups showed normal pathological tissues in the femoral nerves under optical microscopy. Under electron microscopy, histological abnormalities were observed only in Group E; none of the other groups exhibited pathological abnormalities. Quantitative analysis of the myelin sheath area revealed no significant difference in the axonal area, total area of the myelin sheath, or ratio of the total axonal area to the total area of the myelin sheath in all groups. CONCLUSION: The lowest doses of dexmedetomidine (1 and 2 µg/mL) combined with 0.25% ropivacaine for continuous femoral nerve block resulted in no neurotoxic lesions, but the higher dose (3 µg/mL) resulted in neurotoxic lesions in this rabbit experimental model.


Assuntos
Analgésicos não Entorpecentes/efeitos adversos , Anestésicos Locais/efeitos adversos , Dexmedetomidina/efeitos adversos , Nervo Femoral/efeitos dos fármacos , Bloqueio Nervoso/métodos , Síndromes Neurotóxicas/patologia , Ropivacaina/efeitos adversos , Analgésicos não Entorpecentes/administração & dosagem , Anestésicos Locais/administração & dosagem , Animais , Dexmedetomidina/administração & dosagem , Relação Dose-Resposta a Droga , Síndromes Neurotóxicas/etiologia , Coelhos , Ropivacaina/administração & dosagem
12.
Paediatr Drugs ; 21(2): 113-121, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31025304

RESUMO

BACKGROUND: The ductus arteriosus (DA) is situated between the aortic arch and the pulmonary artery in fetal circulation, and its closure is one of the most important changes required for the transition to extrauterine life. Prolonged duration of patent DA (PDA) impairs hemodynamics and contributes both to morbidity associated with prematurity and to mortality. Therefore, when best to initiate treatment and what drug to use as first-line treatment to close the ductus is important. OBJECTIVE: The aim of this study was to compare the efficacy and side effects of the oral forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug to be selected in the medical treatment of PDA. METHODS: This observational, retrospective cohort study was conducted in infants born at ≤ 28 weeks' gestation and admitted to our Neonatal Intensive Care Unit (Manisa Merkezefendi State Hospital, Manisa, Turkey) between February 2015 and April 2018. Included infants were born at ≤ 28 weeks' gestation, had PDA-related clinical findings and hemodynamically significant PDA on echocardiography, and received oral ibuprofen or oral paracetamol therapy as the closure treatment. RESULTS: The most common clinical findings for the diagnosis of PDA were hyperdynamic circulation, tachycardia, and increased oxygen requirement. In total, 43 of the 51 (84.3%) premature infants in the ibuprofen group and 32 of the 36 (88.8%) in the paracetamol group achieved PDA closure after the first treatment cycle. There was no statistically significant difference between the two groups in terms of respiratory morbidity, renal and liver function, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, length of hospital stay, and mortality. CONCLUSIONS: Our results indicate that oral paracetamol was as effective as oral ibuprofen in the medical treatment of PDA. In addition, both drugs were considered well-tolerated in terms of effects on kidney, liver, and intestinal functions. Our results demonstrate that oral paracetamol can be used effectively and safely as the first-line treatment of PDA.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Permeabilidade do Canal Arterial/tratamento farmacológico , Ibuprofeno/administração & dosagem , Recém-Nascido Prematuro , Acetaminofen/efeitos adversos , Administração Oral , Analgésicos não Entorpecentes/efeitos adversos , Permeabilidade do Canal Arterial/diagnóstico , Idade Gestacional , Hemodinâmica , Humanos , Ibuprofeno/efeitos adversos , Recém-Nascido de Baixo Peso , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Retrospectivos , Resultado do Tratamento
13.
Rom J Intern Med ; 57(1): 69-71, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954974

RESUMO

There are few case reports of cases of carotid and aortic dissection related to the ergotamine abuse, but the cases that affect the coronary arteries is a very rare coronary. We present a patient of a 48-year-old female with an ST-segment elevation myocardial infarction attributable to chronic ergotamine use. The coronary angiography showed dissection of right coronary artery proximal.


Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Analgésicos não Entorpecentes/efeitos adversos , Ergotamina/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/induzido quimicamente , Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
14.
Clin Perinatol ; 46(2): 203-213, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010556

RESUMO

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Congênitas/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/prevenção & controle , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/uso terapêutico , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Asma/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Antagonistas de Leucotrienos/efeitos adversos , Antagonistas de Leucotrienos/uso terapêutico , Troca Materno-Fetal , Metimazol/uso terapêutico , Êmese Gravídica/tratamento farmacológico , Ondansetron/uso terapêutico , Gravidez , Propiltiouracila/uso terapêutico , Teratogênios
15.
J Clin Psychopharmacol ; 39(3): 226-237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939592

RESUMO

PURPOSE/BACKGROUND: N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonists are potential agents for the treatment of several central nervous system disorders including major depressive disorder. Racemic methadone, L-methadone, and D-methadone all bind the NMDAR with an affinity similar to that of established NMDAR antagonists, whereas only L-methadone and racemic methadone bind to opioid receptors with high affinity. Therefore, D-methadone is expected to have no clinically significant opioid effects at therapeutic doses mediated by its NMDAR antagonism. METHODS: We conducted 2 phase 1, double-blind, randomized, placebo-controlled, single- and multiple-ascending-dose studies to investigate the safety and tolerability of oral D-methadone and to characterize its pharmacokinetic profile in healthy opioid-naive volunteers. RESULTS: D-Methadone exhibits linear pharmacokinetics with dose proportionality for most single-dose and multiple-dose parameters. Single doses up to 150 mg and daily doses up to 75 mg for 10 days were well tolerated with mostly mild treatment-emergent adverse events and no severe or serious adverse events. Dose-related somnolence and nausea occurred and were mostly present at the higher dose level. There was no evidence of respiratory depression, dissociative and psychotomimetic effects, or withdrawal signs and symptoms upon abrupt discontinuation. An overall dose-response effect was observed, with higher doses resulting in larger QTcF (QT interval corrected using Fridericia formula) changes from baseline, but none of the changes were considered clinically significant by the investigators. Mild, dose-dependent pupillary constriction of brief duration occurred particularly at the 60-mg dose or above in the single-ascending-dose study and at the dose of 75 mg in the multiple-ascending-dose study. No detectable conversion of D-methadone to L-methadone occurred in vivo. CONCLUSIONS: These results support the safety and continued clinical development of D-methadone as an NMDAR antagonist for the treatment of depression and other central nervous system disorders.


Assuntos
Analgésicos não Entorpecentes/administração & dosagem , Metadona/administração & dosagem , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Metadona/efeitos adversos , Metadona/farmacocinética , Pessoa de Meia-Idade , Adulto Jovem
16.
Medicina (Kaunas) ; 55(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939851

RESUMO

Background and objectives: The combination of non-steroidal anti-inflammatory drugs and paracetamol is widely used for pediatric postoperative pain management, although the evidence of superiority of a combination over either drug alone is insufficient. We aimed to find out if intravenous (i.v.) paracetamol in a dose of 60 mg kg-1 24 h-¹, given in addition to i.v. ketoprofen (4.5 mg kg-1 24 h-¹), improves analgesia, physical recovery, and satisfaction with postoperative well-being in children and adolescents following moderate and major general surgery. Materials and Methods: Fifty-four patients were randomized to receive either i.v. paracetamol or normal saline as a placebo in adjunct to i.v. ketoprofen. For rescue analgesia in patients after moderate surgery, i.v. tramadol (2 mg kg-¹ up two doses in 24 h), and for children after major surgery, i.v. morphine-patient-controlled analgesia (PCA) were available. The main outcome measure was the amount of opioid consumed during the first 24 h after surgery. Pain level at 1 and over 24 h, time until the resumption of normal oral fluid intake, spontaneous urination after surgery, and satisfaction with postoperative well-being were also assessed. Results: Fifty-one patients (26 in the placebo group and 25 in the paracetamol group) were studied. There was no difference in required rescue tramadol doses (n = 11 in each group) or 24-h morphine consumption (mean difference (95% CI): 0.06 (⁻0.17; 0.29) or pain scores between placebo and paracetamol groups. In patients given morphine-PCA, time to normal fluid intake was faster in the paracetamol than the placebo subgroup: median difference (95% CI): 7.5 (1.3; 13.7) h, p = 0.02. Parental satisfaction score was higher in the paracetamol than the placebo group (mean difference: ⁻1.3 (⁻2.5; ⁻0.06), p = 0.04). Conclusions: There were no obvious benefits to opioid requirement or analgesia of adding regular intravenous paracetamol to intravenous ketoprofen in used doses. However, intravenous paracetamol may contribute to faster recovery of normal functions and higher satisfaction with postoperative well-being.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Cetoprofeno/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/efeitos adversos , Administração Intravenosa , Adolescente , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Satisfação do Paciente , Estatísticas não Paramétricas , Tramadol/administração & dosagem , Tramadol/uso terapêutico , Resultado do Tratamento
17.
Drug Des Devel Ther ; 13: 965-974, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988599

RESUMO

Objective: The meta-analysis was conducted to assess the effectiveness and safety of intravenous administration of dexmedetomidine for cesarean section under general anesthesia, as well as neonatal outcomes. Materials and methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials and the China National Knowledge Infrastructure database for relevant randomized controlled trials (RCTs) about the application of intravenous dexmedetomidine under general anesthesia for cesarean section. RevMan 5.3 was used to conduct the meta-analysis of the outcomes of interest. Results: Eight RCTs involved 376 participants were included in this study. The meta-analysis showed that the mean blood pressure at the time of intubation (weighted mean difference [WMD]: -15.67, 95% CI: -21.21, -10.13, P<0.00001), skin incision (WMD: -12.83, 95% CI -20.53, -5.14, P=0.001), and delivery (WMD: -11.65, 95% CI -17.18, -6.13, P<0.0001) in dexmedetomidine group were significantly lower than that in the control group. The heart rate (HR) at the time of intubation (WMD: -31.41, 95% CI -35.01, -27.81, P<0.00001), skin incision (WMD: -22.32, 95% CI -34.55, -10.10, P=0.0003), and delivery (WMD: -19.07, 95% CI -22.09, -16.04, P<0.00001) were also lower than that in control group. For neonatal parameters, no differences existed in umbilical blood gases at delivery, and Apgar scores at 1 minute (WMD: -0.12, 95% CI -0.37, 0.12, P=0.33) and 5 minutes (WMD: -0.17, 95% CI -0.13, 0.46, P=0.27) among two groups. Conclusion: Intravenous administration of dexmedetomidine could efficiently attenuate the maternal cardiovascular response during cesarean section, without affecting Apgar score of the neonate.


Assuntos
Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/farmacologia , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Cesárea , Dexmedetomidina/efeitos adversos , Dexmedetomidina/farmacologia , Analgésicos não Entorpecentes/administração & dosagem , Raquianestesia , Anestésicos Intravenosos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Cardiovasculares , Dexmedetomidina/administração & dosagem , Humanos , Injeções Intravenosas , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Am J Epidemiol ; 188(4): 768-775, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30923825

RESUMO

Frequent maternal use of acetaminophen in pregnancy has been linked to attention-deficit/hyperactivity disorder (ADHD) in children, but concerns regarding uncontrolled confounding remain. In this article, we illustrate use of the negative control exposure (NCE) approach to evaluate uncontrolled confounding bias in observational studies on pregnancy drug safety and explain the causal assumptions behind the method. We conducted an NCE analysis and evaluated the associations between maternal acetaminophen use during different exposure periods and ADHD among 8,856 children born in 1993-2005 to women enrolled in the Nurses' Health Study II cohort. Information on regular maternal acetaminophen use was collected prospectively in biennial questionnaires. A total of 721 children (8.1%) in the cohort had been diagnosed with ADHD as reported by the mothers. Our NCE analysis suggested that only acetaminophen use at the time of pregnancy was associated with childhood ADHD (odds ratio = 1.34, 95% confidence interval: 1.05, 1.72), and the effect estimates for the 2 NCE periods (about 4 years before and 4 years after the pregnancy) were null. Our findings corroborate those of prior reports suggesting that prenatal acetaminophen exposure may influence neurodevelopment. The lack of an association between acetaminophen use in the pre- and postpregnancy exposure periods and ADHD provides assurance that uncontrolled time-invariant factors do not explain this association.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Criança , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
19.
Praxis (Bern 1994) ; 108(4): 283-285, 2019.
Artigo em Alemão | MEDLINE | ID: mdl-30890081

RESUMO

The Sour Patient Abstract. We report the case of a 75-year-old woman presenting with an elevated anion gap metabolic acidosis. The evaluation proved a 5-oxoprolin acidosis due to acetaminophen in therapeutic dose and concomitant risk factors such as malnutrition, chronic alcohol abuse, renal insufficiency, hepatopathy, and female sex. After stopping paracetamol medication and admission of bicarbonate and N-acetylcysteine, there was a rapid improvement in clinical symptoms and blood analysis.


Assuntos
Acidose , Analgésicos não Entorpecentes , Acetaminofen/efeitos adversos , Acetilcisteína , Equilíbrio Ácido-Base , Acidose/induzido quimicamente , Idoso , Analgésicos não Entorpecentes/efeitos adversos , Feminino , Humanos , Ácido Pirrolidonocarboxílico
20.
Br J Anaesth ; 122(5): 587-604, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30916011

RESUMO

Nitrous oxide (N2O) is one of the oldest drugs still in use in medicine. Despite its superior pharmacokinetic properties, controversy remains over its continued use in clinical practice, reflecting in part significant improvements in the pharmacology of other anaesthetic agents and developing awareness of its shortcomings. This narrative review describes current knowledge regarding the clinical use of N2O based on a systematic and critical analysis of the available scientific literature. The pharmacological properties of N2O are reviewed in detail along with current evidence for the indications and contraindications of this drug in specific settings, both in perioperative care and in procedural sedation. Novel potential applications for N2O for the prevention or treatment of chronic pain and depression are also discussed. In view of the available evidence, we recommend that the supply of N2O in hospitals be maintained while encouraging its economic delivery using modern low flow delivery systems. Future research into its potential novel applications in prevention or treatment of chronic conditions should be pursued to better identify its role place in the developing era of precision medicine.


Assuntos
Anestésicos Inalatórios/farmacologia , Óxido Nitroso/farmacologia , Analgesia Obstétrica/métodos , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/farmacologia , Analgésicos não Entorpecentes/uso terapêutico , Anestesia Dentária/métodos , Anestésicos Inalatórios/efeitos adversos , Antidepressivos/uso terapêutico , Dor Crônica/prevenção & controle , Sedação Consciente/métodos , Contraindicações de Medicamentos , Transtorno Depressivo Maior/tratamento farmacológico , Medicina Baseada em Evidências/métodos , Humanos , Óxido Nitroso/efeitos adversos , Óxido Nitroso/uso terapêutico
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