RESUMEN
Background: Few studies have evaluated opioid consumption after various inpatient surgical procedures. Objectives: To describe opioid prescription patterns and to characterize patient-reported use of opioids after surgery. Methods: This single-centre prospective observational study was conducted between February and October 2021 at the Jewish General Hospital in Montréal, Quebec. Patients 18 years of age or older who underwent a surgical procedure, were hospitalized for 24 hours or longer after the procedure, and had an opioid prescription at the time of discharge were included. Data were collected for the quantity of opioids prescribed, as documented in hospital records, and the quantity consumed, as reported by participants. Various potential predictors of opioid consumption were explored, and data were also collected on patients' use of non-opioid coanalgesia, scores on the Numeric Rating Scale for pain, opioid renewal requests, and proper opioid disposal during the 30-day follow-up period. Results: A total of 150 participants completed the study. The median dose prescribed was 10 opioid pills (75.0 morphine milligram equivalents). By the end of the follow-up period, a median of 1 pill (7.5 morphine milligram equivalents) had been consumed from the total amount in the discharge prescription. Overall, 66 participants (44.0%) did not consume any of the opioids prescribed at discharge. Of the total number of pills prescribed, 58.2% (1193/2050) were unused, and 7.0% (5/71) of participants with unused pills disposed of them properly. Conclusions: Following discharge from hospital, postoperative patients consumed a median proportion of only 10% of prescribed opioid pills. More than half of all prescribed pills were unused. Protocols implementing specific prescribing strategies warrant further investigation to evaluate their potential impact on opioid prescription and consumption.
Contexte: Peu d'études ont évalué la consommation d'opioïdes après diverses interventions chirurgicales en milieu hospitalier. Objectifs: Décrire les schémas de prescription d'opioïdes et caractériser leur utilisation déclarée par les patients après une intervention chirurgicale. Méthodologie: Cette étude observationnelle prospective monocentrique a été menée entre février et octobre 2021 à l'Hôpital général juif de Montréal, au Québec. Les patients d'au moins 18 ans ayant subi une intervention chirurgicale, ayant été hospitalisés pendant au moins 24 heures après l'intervention et qui avaient une prescription d'opioïdes au moment de leur congé ont été inclus dans l'étude. Des données ont été recueillies sur la quantité d'opioïdes prescrite, telle que documentée dans les dossiers de l'hôpital, et sur la quantité consommée, telle que déclarée par les participants. Divers prédicteurs potentiels de la consommation d'opioïdes ont été étudiés et des données ont aussi été recueillies, sur une période de suivi de 30 jours, sur l'utilisation de coanalgésie non opioïde par les patients, leurs scores sur l'échelle d'évaluation numérique de la douleur, les demandes de renouvellement d'opioïdes et l'élimination appropriée de ces dernières. Résultats: Au total, 150 participants ont complété l'étude. La dose médiane prescrite était de 10 comprimés d'opioïdes (75,0 équivalents en milligrammes de morphine). À la fin de la période de suivi, une moyenne de 1 comprimé (7,5 équivalents en milligrammes de morphine) avait été consommée sur la quantité totale indiquée dans l'ordonnance remise au moment du congé. Dans l'ensemble, 66 participants (44,0 %) n'ont consommé aucun des opioïdes prescrits au moment du congé. Sur le nombre total de comprimés prescrits, 58,2 % (1193/2050) n'ont pas été utilisés et 7,0 % (5/71) des participants ayant des comprimés inutilisés s'en sont débarrassés correctement. Conclusions: Suite au congé de l'hôpital, les patients postopératoires ne consommaient qu'une proportion médiane de 10 % des comprimés d'opioïde prescrits. Plus de la moitié de tous les comprimés prescrits n'ont pas été utilisés. Les protocoles mettant en oeuvre des stratégies de prescription spécifiques justifient des recherches plus approfondies pour évaluer leur incidence potentielle sur la prescription et la consommation d'opioïdes.
RESUMEN
Extended thromboprophylaxis with oral anticoagulation can reduce the risk of symptomatic venous thromboembolism (VTE) in high-risk patients. We sought to estimate the proportion of medically ill patients in the United States who might qualify for extended thromboprophylaxis according to the criteria used in the Medically-Ill Patient Assessment of Rivaroxaban versus Placebo in Reducing Post-Discharge Venous ThromboEmbolism Risk (MARINER) trial. We analyzed 2014 National Inpatient Sample (NIS) data that provide a 20% weighted annual sample of all discharges from US acute-care hospitals. Hospitalizations for acute medically ill patients were identified as those with a primary discharge diagnosis code for heart or respiratory failure, ischemic stroke, infection, or inflammatory diseases. Patients were excluded if they were <40 years old, admitted for surgery or trauma, had a length of stay <3- or >35-days, or were contraindicated to nonvitamin K antagonist oral anticoagulants. The modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE)-VTE score was used to stratify patients' risk for postdischarge VTE, with a score of 2 to 3 suggesting patients were at moderate- and ≥4 as high-risk. Of the 35 358 810 hospitalizations in the 2014 NIS, 1 849 535 were medically ill patients admitted for heart failure (10.1%), respiratory failure (12.2%), ischemic stroke (8.8%), infection (58.5%), or inflammatory diseases (10.4%). The modified IMPROVE-VTE score classified 1 186 475 (64.1%) of these hospitalizations as occurring in moderate-risk and 407 095 (22.0%) in high-risk patients. This real-world study suggests a substantial proportion of acute medically ill patients might benefit from extended thromboprophylaxis using the modified IMPROVE-VTE score and clinical elements of the MARINER trial.
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Anticoagulantes/administración & dosificación , Isquemia Encefálica/prevención & control , Tiempo de Internación , Sistema de Registros , Rivaroxabán/administración & dosificación , Accidente Cerebrovascular/prevención & control , Tromboembolia Venosa/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The vasopressin analogue desmopressin (desamino-d-arginine8 vasopressin, dDAVP, 1) is a potent vasopressin 2 (V2) receptor (V2R) agonist approved in many countries for the treatment of diabetes insipidus, primary nocturnal enuresis, nocturia, and coagulation disorders. Since 1 is primarily excreted via the kidneys, an age-related decline in kidney function leads to slower elimination, prolonged antidiuresis, and hyponatremia. In search of novel, potent, selective, and short-acting peptidic V2R agonists, we synthesized a series of C-terminally truncated analogues of [Val4]dDAVP, 2, modified in positions 2, 3, and 7 and/or at the disulfide bridge. The peptides were evaluated for in vitro potency at the human V2 receptor, selectivity versus the related receptors (human vasopressin 1a receptor, human vasopressin 1b receptor, and human oxytocin receptor), and pharmacokinetic profiles in rodents and other higher species. The truncated analogues show excellent potency at the V2R, increased systemic clearance, and shorter half-life in rats. Two compounds 19 (c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-Agm) and 38 (c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-d-Arg-NEt2) have been selected for clinical development for nocturia.
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Fármacos Antidiuréticos/síntesis química , Fármacos Antidiuréticos/farmacología , Receptores de Vasopresinas/agonistas , Animales , Fármacos Antidiuréticos/farmacocinética , Desamino Arginina Vasopresina/análogos & derivados , Desamino Arginina Vasopresina/síntesis química , Desamino Arginina Vasopresina/farmacología , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Descubrimiento de Drogas , Semivida , Humanos , Nocturia/tratamiento farmacológico , Ratas , Receptores de Oxitocina/efectos de los fármacos , Fármacos Renales/síntesis química , Fármacos Renales/farmacología , Relación Estructura-ActividadRESUMEN
Mothers of preterm babies frequently have difficulty establishing or maintaining lactation, thought to be due to interference with the milk ejection reflex. Administration of exogenous oxytocin can produce alveolar contraction and adequate breast emptying resulting in establishment of successful lactation. The natural hormone oxytocin is not receptor-selective and may cause hyponatremia via V2 receptor mediated antidiuresis. We have designed a series of potent oxytocin analogues containing N-alkylglycines in position 7 with excellent selectivity versus the related V1a, V1b, and V2 vasopressin receptors and short half-life: agonists 31 ([2-ThiMeGly(7)]dOT), 47 (carba-6-[Phe(2),BuGly(7)]dOT), 55 (carba-6-[3-MeBzlGly(7)]dOT), and 57 (carba-1-[4-FBzlGly(7)]dOT) have EC50 values at hOTR < 0.1 nM, selectivity ratios versus related human vasopressin receptors of >2000, IC50 at hV1aR > 500 nM, and total clearance in rats in the range of 60-80 mL min(-1) kg(-1). Compound 57 (FE 202767) is currently in clinical development for the treatment of preterm mothers requiring lactation support.
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Oligopéptidos/química , Oxitocina/análogos & derivados , Oxitocina/química , Péptidos Cíclicos/química , Receptores de Oxitocina/agonistas , Animales , Células CHO , Cricetulus , Genes Reporteros , Humanos , Masculino , Oligopéptidos/farmacocinética , Oligopéptidos/farmacología , Oxitocina/farmacocinética , Oxitocina/farmacología , Péptidos Cíclicos/farmacocinética , Péptidos Cíclicos/farmacología , Ratas Sprague-Dawley , Receptores de Oxitocina/genética , Receptores de Vasopresinas/agonistas , Receptores de Vasopresinas/genética , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
FE 202158, ([Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]vasopressin, where Hgn is homoglutamine and iPr is isopropyl), a peptidic analog of the vasoconstrictor hormone [Arg(8)]vasopressin (AVP), was designed to be a potent, selective, and short-acting vasopressin type 1a receptor (V(1a)R) agonist. In functional reporter gene assays, FE 202158 was a potent and selective human V(1a)R agonist [EC(50) = 2.4 nM; selectivity ratio of 1:142:1107:440 versus human vasopressin type 1b receptor, vasopressin type 2 receptor (V(2)R), and oxytocin receptor, respectively] contrasting with AVP's lack of selectivity, especially versus the V(2)R (selectivity ratio of 1:18:0.2:92; human V(1a)R EC(50) = 0.24 nM). This activity and selectivity profile was confirmed in radioligand binding assays. FE 202158 was a potent vasoconstrictor in the isolated rat common iliac artery ex vivo (EC(50) = 3.6 nM versus 0.8 nM for AVP) and reduced rat ear skin blood flow after intravenous infusion in vivo (ED(50) = 4.0 versus 3.4 pmol/kg/min for AVP). The duration of its vasopressor effect by intravenous bolus in rats was as short as AVP at submaximally effective doses. FE 202158 had no V(2)R-mediated antidiuretic activity in rats by intravenous infusion at its ED(50) for reduction of ear skin blood flow, in contrast with the pronounced antidiuretic effect of AVP. Thus, FE 202158 seems suitable for treatment of conditions where V(1a)R activity is desirable but V(2)R activity is potentially deleterious, such as vasodilatory hypotension in septic shock. In addition to the desirable selectivity profile, its short-acting nature should allow dose titration with rapid onset and offset of action to optimize vasoconstriction efficacy and safety.