RESUMEN
PURPOSE: Frailty is characterized by fragility and decline in physical, mental, and social activities; it is commonly observed in older adults. No studies have reported frailty status changes between the preoperative and postoperative periods, including mental and cognitive factors. Therefore, this study investigated frailty factors, including mental and cognitive functions, that change after non-cardiac surgery in older adults. METHODS: Patients aged ≥ 75 years who underwent non-cardiac surgery were surveyed using five tools (Eastern Cooperative Oncology Group-Performance Status (PS); handgrip strengths; Japan-Cardiovascular Health Study index (J-CHS index); Mini-Mental State Examination (MMSE); and Geriatric Depression Scale) for comprehensive evaluation of perioperative functions. The results before surgery, at discharge, and during follow-up at the outpatient clinic were compared. RESULTS: Fifty-three patients with a median age of 80 (IQR, 77-84) years were evaluated. MMSE scores did not change during the perioperative period. The PS and J-CHS index worsened significantly at discharge and did not improve at the outpatient clinic follow-up. The dominant handgrip strength decreased after surgery (p < 0.001) but improved during follow-up. Additionally, nondominant handgrip strength decreased after surgery (p < 0.001) but did not recover as much as the dominant handgrip strength during follow-up (p = 0.015). CONCLUSION: Changes in physical frailty and mental and cognitive functions were not identical perioperatively in older adult patients undergoing non-cardiac surgery. Physical frailty did not improve 1 month after surgery, mental function recovered early, and cognitive function did not decline. This study may be important for frailty prevention in older adult patients.
Asunto(s)
Fragilidad , Anciano , Humanos , Anciano de 80 o más Años , Fragilidad/complicaciones , Anciano Frágil/psicología , Fuerza de la Mano , Cognición , Encuestas y Cuestionarios , Evaluación Geriátrica/métodosRESUMEN
BACKGROUND: When an obturator nerve block (ONB) is performed, the conventional landmark method or ultrasound-guided method is used. The major complications of this block are hematoma, but there are very few reports of its complications. We encountered massive bleeding and a huge hematoma after ONB. Case Presentation. A 95-year-old female underwent transurethral resection of the bladder tumor. Induction of anesthesia was accomplished via spinal anesthesia and right ONB using the landmark method. Postoperatively, subcutaneous bleeding was detected in the lower right interior thigh. Concentrated red cell transfusion was conducted to address the anemia. There was no subsequent expansion of the hematoma. It resolved on postoperative day (POD) 53. The hematoma was deemed to be inadvertently introduced due to an obturator artery puncture during the obturator nerve block. CONCLUSIONS: Close attention is necessary to avoid advancing the needle too deep into the obturator during obturator nerve block.
RESUMEN
A 78-year-old woman complained of numbness, tingling, and pain in the left leg 6 months after greater saphenous vein stripping. Ultrasonography identified a mass adjacent to the saphenous nerve at the scar. Ultrasound-guided hydrodissection separated the mass from the nerve. The pain disappeared after hydrodissection, and the patient remained pain free for 3 days. The visual analog pain scale decreased from 80 (before treatment) to 60 three days later. The hydrodissection was repeated weekly for a total of 8 times, and the pain completely resolved 4 months later. Ultrasound-guided hydrodissection is effective to treat nerve entrapment after lower extremity varicose vein stripping.
Asunto(s)
Extremidad Inferior/irrigación sanguínea , Dolor Postoperatorio/terapia , Várices/cirugía , Anciano , Femenino , Humanos , Dimensión del Dolor , Resultado del Tratamiento , Ultrasonografía Intervencional/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
The short-axis out-of-plane approach (SAX-OOP) is commonly used in ultrasound-guided internal jugular vein catheterization. However, this approach has a risk of posterior vein wall injuries. The authors hypothesized that a shallow angle of approach may reduce the rate of posterior wall injuries compared with the conventional steep angle approach. The present study aimed to evaluate whether a difference in the angle of approach of the needle affects the rate of posterior wall injuries. The present study was a randomized crossover-controlled trial involving 40 medical residents, conducted in the clinical training center at a hospital with a residency program. The primary outcome measure was the rate of posterior vessel wall injuries. Subjects received a didactic lecture during which the instructors taught three SAX-OOP techniques including the conventional free-hand method (procedure C), a needle navigation system (procedure N), and a shallow puncture angle using a guidance system (procedure S). Participants were trained in these approaches under supervision and each technique tested in a simulation environment. Thirty-four of 40 residents had no previous experience with central venous catheterization and were included in the final analysis. The rate of posterior vessel wall injuries in procedure S (9%) was significantly lower than using the other approaches (procedure C, 53%; procedure N, 41%). In conclusion, a shallow angle of approach using the SAX-OOP technique resulted in significantly fewer posterior vein wall injuries in central venous catheterization compared with steep angle techniques.
Asunto(s)
Cateterismo Venoso Central/métodos , Venas Yugulares/lesiones , Humanos , Estudios Prospectivos , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: On a pharmacologic basis, levobupivacaine is expected to last longer than ropivacaine. However, most reports of these anesthetics for brachial plexus block do not suggest a difference in analgesic effect. The aim of this study is to compare the postoperative analgesic effects of levobupivacaine and ropivacaine when used for treating ultrasound-guided brachial plexus block. METHODS: A total of 62 patients undergoing orthopedic surgery procedures were prospectively enrolled and randomized to receive levobupivacaine (groupâL, Nâ=â31) or ropivacaine (group R, Nâ=â31). The duration of analgesia, offset time of motor block, need for rescue analgesics, and sleep disturbance on the night of surgery were recorded. Pain score was recorded on the day of surgery, and on postoperative days 1 and 2. RESULTS: There was no difference in the time interval until the first request for pain medication comparing the two groups (groupâL: 15.6 [11.4, 16.8] hours; group R: 12.5 [9.4, 16.0] hours, Pâ=â0.32). There was no difference in the duration of motor block (groupâL: 12.2 [7.6, 14.4] hours; group R: 9.4 [7.9, 13.2] hours, Pâ=â0.44), pain score (Pâ=â0.92), need for rescue analgesics (groupâL: 55%; group R: 65%, Pâ=â0.6), or rate of sleep disturbance (groupâL: 61%, group R: 58%, Pâ=â1.0) on comparing the two groups. CONCLUSIONS: There was no difference in postoperative analgesia comparing levobupivacaine and ropivacaine when used for brachial plexus block.
Asunto(s)
Amidas/uso terapéutico , Anestésicos Locales/uso terapéutico , Bloqueo del Plexo Braquial/métodos , Bupivacaína/análogos & derivados , Procedimientos Ortopédicos/métodos , Dolor Postoperatorio/prevención & control , Anciano , Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Bupivacaína/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Levobupivacaína , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ropivacaína , Factores de Tiempo , Ultrasonografía IntervencionalRESUMEN
A 13-month-old infant weighing 8.3 kg with a height of 72.3 cm visited our hospital for surgical resection of facial vascular malformation detected at birth. Because we anticipated the patient would have difficult airway management and massive perioperative bleeding, we postponed surgery to discuss the appropriate timing and general anesthesia approach with anesthesiologists at other institutions, while explaining the risk of general anesthesia and bleeding to the parents. When the patient was 21 months old and 10 kg, he started bleeding while undressing, when his lips touched his clothes. Because the cricothyroid membrane puncture kit (QuickTrach Child™ (VBM Medizintechnik GmbH, Sulz am Neckar, Germany)) can be used on infants weighing over 10 kg, we decided to give him general anesthesia. The infant was successfully intubated by Airwayscope™ and the lesion was surgically removed in accordance with the preoperative plan. The procedure took 65 min and created 8 g of bleeding. The infant had no postoperative bleeding or respiratory complications. There is no data on the timing of safe anesthesia management in infants with difficult airway management. Thus, taking the time to discuss the case with surgeons, other anesthesiologists, and the parents can be helpful.
RESUMEN
A 38-year-old man with pancreatic cancer was scheduled to undergo pancreaticoduodenectomy. He had an unremarkable past medical history. After inducing general anesthesia, a left radial arterial catheter was successfully placed at first attempt. A wrist splint was used to obtain good arterial pulse waveforms. After the operation, he was transferred to the intensive care unit. The radial artery catheter was removed on the fourth postoperative day. He experienced numbness and a tingling sensation in the left thumb, the second and third fingers, and the lateral half of the fourth finger. He was diagnosed with carpal tunnel syndrome. Diagnostic imaging revealed a swollen median nerve, but no hematoma or injury. Some studies have suggested that excessive extension of the wrist may cause neuropathy. We recommend that patients' wrists not be over-extended, even if good arterial waveforms cannot be obtained.
RESUMEN
BACKGROUND: Dexamethasone added to local anesthetic for brachial plexus block improves postoperative pain after arthroscopic rotator cuff repair, as compared with the use of local anesthetic alone. Dexamethasone is present in non-particulate form in local anesthetic solution, while betamethasone is partially present in particulate form. The particulate betamethasone gradually decays and is expected to cause its longer-lasting effect. This study investigated the postoperative analgesic effect of betamethasone added to ropivacaine for brachial plexus block in patients who underwent arthroscopic rotator cuff repair. METHODS: This was a prospective, randomized, triple-blind study of 44 patients undergoing arthroscopic rotator cuff repair surgery. Ultrasound-guided interscalene brachial plexus block, involving 20 mL of 0.375 % ropivacaine (group R) or 19 mL of 0.375 % ropivacaine with 4 mg (1 mL) of betamethasone (group BR), was administered and surgery was performed under general anesthesia. After surgery, the pain score was recorded at 12 h after surgery, and on the first, second, and seventh postoperative day. Analgesia duration, offset time of motor block, frequency of rescue analgesic administration, postoperative nausea/vomiting, and sleep disturbance during the night after surgery were recorded. The numerical values were expressed as median [interquartile range]. P values < 0.05 were considered statistically significant. RESULTS: The duration of analgesia was significantly prolonged in group BR (group BR: 19.1 h [16.6, 20.9 h], group R: 13.3 h [11.6, 16.5 h], p < 0.001). The pain scores at 12 h after surgery and on the first and seventh day after surgery were significantly lower in group BR than in group R. The duration of motor block was significantly prolonged in group BR. The frequency of rescue analgesic administration and the sleep disturbance rate were significantly lower in group BR. There was no difference in postoperative nausea/vomiting between the two groups. CONCLUSIONS: Betamethasone added to local anesthetic in interscalene brachial plexus block improved postoperative pain after arthroscopic rotator cuff repair, and betamethasone prolonged the duration of analgesia by almost 6 h. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trials Registration System ( UMIN000012899 ).
Asunto(s)
Amidas/administración & dosificación , Artroscopía/métodos , Betametasona/administración & dosificación , Bloqueo del Plexo Braquial/métodos , Dolor Postoperatorio/prevención & control , Anciano , Analgésicos/administración & dosificación , Anestesia General/métodos , Anestésicos Locales/administración & dosificación , Método Doble Ciego , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ropivacaína , Manguito de los Rotadores/cirugía , Factores de Tiempo , Ultrasonografía Intervencional/métodosRESUMEN
INTRODUCTION: Atherosclerosis has a complex etiology that leads to arterial obstruction and often results in inadequate perfusion of the distal limbs. Patients with atherosclerosis can have severe complications of this condition, with widespread systemic manifestations, and the operations undertaken are often challenging for anesthesiologists. CASE REPORT: A 79-year-old woman with chronic heart failure and respiratory dysfunction presented with bilateral gangrene of the distal lower extremities with obstruction of the left common iliac artery due to atherosclerosis. Femoral-femoral bypass graft and bilateral foot amputations were planned. Spinal anesthesia failed due to severe scoliosis and deformed vertebrae. General anesthesia was induced after performing multiple nerve blocks including quadratus lumborum, sciatic nerve, femoral nerve, lateral femoral cutaneous nerve, and obturator nerve blocks. However, general anesthesia was abandoned because of deterioration in systemic perfusion. The surgery was completed; the patient remained comfortable and awake without the need for further analgesics. CONCLUSION: Quadratus lumborum block may be a useful anesthetic technique to perform femoral-femoral bypass.
Asunto(s)
Amputación Quirúrgica , Arteria Femoral/cirugía , Bloqueo Nervioso/métodos , Injerto Vascular , Músculos Abdominales , Anciano , Anestesia General/efectos adversos , Femenino , Nervio Femoral , Pie/cirugía , Humanos , Nervio ObturadorRESUMEN
PURPOSE: Chronic pain after cesarean section (CS) is a serious concern, as it can result in functional disability. We evaluated the prevalence of chronic pain after CS prospectively at a single institution in Japan. We also analyzed perioperative risk factors associated with chronic pain using logistic regression analyses with a backward-stepwise procedure. MATERIALS AND METHODS: Patients who underwent elective or emergency CS between May 2012 and May 2014 were recruited. Maternal demographics as well as details of surgery and anesthesia were recorded. An anesthesiologist visited the patients on postoperative day (POD) 1 and 2, and assessed their pain with the Prince Henry Pain Scale. To evaluate the prevalence of chronic pain, we contacted patients by sending a questionnaire 3 months post-CS. RESULTS: Among 225 patients who questionnaires, 69 (30.7%) of patients complained of persistent pain, although no patient required pain medication. Multivariate analyses identified lighter weight (p = 0.011) and non-intrathecal administration of morphine (p = 0.023) as determinant factors associated with persistent pain at 3 months. The adjusted odds ratio of intrathecal administration of morphine to reduce persistent pain was 0.424, suggesting that intrathecal administration of morphine could decrease chronic pain by 50%. In addition, 51.6% of patients had abnormal wound sensation, suggesting the development of neuropathic pain. Also, 6% of patients with abnormal wound sensation required medication, yet no patients with persistent pain required medication. CONCLUSION: Although no effect on acute pain was observed, intrathecal administration of morphine significantly decreased chronic pain after CS.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Cesárea/efectos adversos , Dolor Crónico/prevención & control , Morfina/uso terapéutico , Dolor Postoperatorio/prevención & control , Adulto , Anestesia Raquidea/métodos , Cesárea/rehabilitación , Dolor Crónico/diagnóstico , Dolor Crónico/etiología , Dolor Crónico/fisiopatología , Femenino , Humanos , Inyecciones Espinales , Modelos Logísticos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/fisiopatología , Embarazo , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
The perioperative management of pulmonary hypertension in a patient with Eisenmenger syndrome, the most advanced form of associated pulmonary artery hypertension (PAH), who required a sigmoidectomy is presented. The treatment for pulmonary hypertension was switched from oral sildenafil to intravenous epoprostenol to avoid the unexpected discontinuation of vasodilation during the perioperative period. The scheduled perioperative conversion should be considered for patients with severe PAH undergoing major abdominal surgery to ensure the stabilization of pulmonary and systemic hemodynamics.
Asunto(s)
Complejo de Eisenmenger/tratamiento farmacológico , Epoprostenol/uso terapéutico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Administración Oral , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Colectomía/métodos , Complejo de Eisenmenger/complicaciones , Complejo de Eisenmenger/fisiopatología , Epoprostenol/administración & dosificación , Hipertensión Pulmonar Primaria Familiar , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Atención Perioperativa/métodos , Piperazinas/administración & dosificación , Purinas/administración & dosificación , Purinas/uso terapéutico , Neoplasias del Colon Sigmoide/cirugía , Citrato de Sildenafil , Sulfonas/administración & dosificación , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéuticoRESUMEN
A 61-year-old woman with pulmonary lymphangioleiomyomatosis was scheduled for video-assisted thoracoscopic surgery for partial resection of the lung. The patient had micrognathism and a recent history of difficult airway management [difficult mask ventilation and intubation (Cormak grade III)]. On induction, mask ventilation was accomplished with the use of nasal airway. We initially inserted Airtraq laryngoscope and gained a view of Cormak grade III. Therefore, a 32 Fr left-sided Blue Line endobroncheal tube was nasotracheally intubated using a fiberscope (3.1-mm diameter). Nasotracheal intubation with a 32F Blue Line endobroncheal tube can be a choice for patients with difficult airway when one lung ventilation is required.
Asunto(s)
Intubación Intratraqueal/métodos , Micrognatismo/complicaciones , Femenino , Humanos , Intubación Intratraqueal/instrumentación , Neoplasias Pulmonares/cirugía , Linfangioleiomiomatosis/cirugía , Persona de Mediana Edad , Neumonectomía , Cirugía Torácica Asistida por VideoRESUMEN
OBJECTIVE AND DESIGN: The aim was to investigate the signaling mechanisms and regulation of bradykinin (BK)-induced inflammation in rat knee joint. MATERIALS AND METHODS: Knee joints of anesthetized rats were perfused with BK (0.1-1.0 microM), and synovial plasma extravasation (PE) was evaluated by spectrophotometrical measurement of Evans Blue leakage. To examine the signaling pathway, B1 antagonist [des-Arg10]-HOE140 (0.1-1.0 microM) and B2 antagonist HOE140 (0.05-1.0 microM), calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 (0.5-1.0 microM), prostaglandin E2 antagonist AH-6809 (0.1-1.0 microM), and histamine H1 antagonist mepyramine (0.1-1.0 microM) were used. Nociceptin (0.0001-1.0 microM) and antagonist J-113397 were tested for modulation of BK-induced PE. The analyses were compared side-by-side with 5-hydroxytryptamine-induced PE. RESULTS: BK perfusion dose-dependently induced PE, which was blocked by HOE140, CGRP8-37, AH-6809, and mepyramine. It was also inhibited by nociceptin, which could be reversed by antagonist J-113397. In contrast, 5-hydroxytryptamine-induced PE was biphasically regulated by nociceptin and was not antagonized by CGRP8-37. CONCLUSIONS: BK-induced PE is mediated by B2 receptors and may involve CGRP, prostaglandin, and histamine pathways. BK-induced PE is inhibited by nociceptin through the activation of ORL1 receptors. There are differences between BK- and 5-hydroxytryptamine-induced inflammation in signaling and modulation.
Asunto(s)
Bradiquinina/metabolismo , Articulación de la Rodilla/metabolismo , Péptidos Opioides/metabolismo , Plasma/metabolismo , Receptor de Bradiquinina B1/metabolismo , Receptor de Bradiquinina B2/metabolismo , Animales , Antagonistas del Receptor de Bradiquinina B1 , Antagonistas del Receptor de Bradiquinina B2 , Péptido Relacionado con Gen de Calcitonina/metabolismo , Colorantes/metabolismo , Dinoprostona/antagonistas & inhibidores , Dinoprostona/metabolismo , Azul de Evans/metabolismo , Histamina/metabolismo , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Transducción de Señal/fisiología , NociceptinaRESUMEN
The regulators of G protein signaling (RGS) are a family of proteins with conserved RGS domains and play essential roles in regulating G protein-mediated signal transduction and physiological events. GAIP/RGS19 (G alpha interacting protein, also classified as RGS19), a member of the RGS family, has been shown to negatively regulate the signaling of many G protein-coupled receptors, including the opioid receptors. Two GAIP/RGS19 mRNA variants, resulted from an alternative splicing of exon 2 of the GAIP/RGS19 gene, were identified in multiple mouse tissues. One of the transcripts consists of a complete set of exons and encodes a full-length GAIP/RGS19 protein, and the other does not have exon 2 and therefore encodes an N-terminal 22 residue truncated short GAIP/RGS19 protein. When co-expressed with either the opioid-receptor-like (ORL1) receptor or one of the mu, delta, and kappa opioid receptors, by transfecting dual-expression plasmids into COS-7 cells, the full-length GAIP/RGS19 was more effective than the N-terminally truncated variant and was more selective in regulating the ORL1 receptor signaling than in regulating the mu, delta, and kappa opioid receptors, as measured by the effectiveness to increase the agonist-stimulated GTPase activity and to reverse the agonist-induced inhibition of cyclic AMP accumulation. In the same assays, the N-terminally truncated GAIP/RGS19 did not distinguish ORL1 from the mu, delta, and kappa opioid receptors. In contrast, co-expression of RGS4 with either ORL1 or opioid receptors showed the selectivity of RGS4 for regulating opioid receptors was mu > kappa > delta > ORL1, an order completely different from that of GAIP/RGS19. The results suggest that GAIP/RGS19 prefers regulating ORL1 receptor signaling over other opioid receptors, and that the N-terminal domain of GAIP/RGS19 plays a crucial role in its receptor preference.
Asunto(s)
Empalme Alternativo , Proteínas RGS/fisiología , Receptores Opioides/metabolismo , Transducción de Señal , Animales , Células COS , Chlorocebus aethiops , AMP Cíclico/metabolismo , Guanosina Trifosfato/metabolismo , Ratones , Estructura Terciaria de Proteína , Proteínas RGS/genética , ARN Mensajero/análisis , Receptores Opioides/genética , Transfección , Receptor de NociceptinaRESUMEN
Regulators of G protein signaling (RGS) proteins are GTPase-activating proteins which act as modulators of G-protein-coupled receptors. RGS9 has two alternative splicing variants. RGS9-1 is expressed in the retina. RGS9-2 is expressed in the brain, especially abundant in the striatum. It is believed to be an essential regulatory component of dopamine and opioid signaling. In this study, we compared the expression of RGS9 proteins in the nervous system of different age groups of rats employing immunocytochemistry. In both 3-week- and 1-year-old rats, RGS9 is expressed abundantly in caudate-putamen, nucleus accumbens, and olfactory tubercle. It is also expressed abundantly in the ventral horn of the spinal cord and the dorsal root ganglion (DRG) cells. Quantitative analysis showed that the intensities of RGS9 expression in 1-year-old rats are higher than those in the 3-week-old rats in caudate-putamen, nucleus accumbens, olfactory tubercle, periaqueductal gray, and gray matter of the spinal cord. In contrast, in thalamic nuclei and locus coeruleus, the intensities of RGS9 immunostaining in 3-week-old rats are higher than in 1-year-old rats. In DRG cells, there is no significant difference between the two age groups. These data suggest that RGS9 is differentially expressed with age. Such differential expression may play an important role in neuronal differentiation and development as well as in neuronal function, such as dopamine and opioid signaling.
Asunto(s)
Vías Aferentes/crecimiento & desarrollo , Envejecimiento/metabolismo , Sistema Nervioso/crecimiento & desarrollo , Nociceptores/fisiología , Dolor/metabolismo , Proteínas RGS/metabolismo , Vías Aferentes/metabolismo , Factores de Edad , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Ganglios Espinales/crecimiento & desarrollo , Ganglios Espinales/metabolismo , Inmunohistoquímica , Masculino , Sistema Nervioso/metabolismo , Neuronas Aferentes/metabolismo , Dolor/fisiopatología , Ratas , Ratas Sprague-Dawley , Médula Espinal/crecimiento & desarrollo , Médula Espinal/metabolismo , Transmisión Sináptica/fisiología , Regulación hacia Arriba/fisiologíaRESUMEN
In all age groups, the use of opioids to treat chronic pain conditions has increased, yet the impact of age on opioid tolerance development has not been comprehensively addressed. In this study, we investigated age-related differences in morphine tolerance development in rats. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr were used in the study. Morphine (8 mg/kg) was injected subcutaneously twice each day and its analgesic effect assessed by the change in tail-flick latency using a thermal stimulus 5 min before and 30 min after dosing. Tolerance was defined as a 75% reduction in morphine-induced analgesia compared to Day 1. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr developed tolerance on the 4th, 10th, 14th, and 22nd days of morphine treatment, respectively. Plasma levels of morphine and its metabolites showed that pharmacokinetic differences among the groups did not correlate with the differences in tolerance development. This study demonstrates that morphine tolerance occurs more rapidly in younger rats than older rats and is unlikely to be the result of differences in drug metabolism or clearance. Aging may impact molecular processes involved in tolerance development and provide insight into novel therapeutic targets to delay opioid tolerance development.
Asunto(s)
Envejecimiento/fisiología , Analgésicos Opioides/farmacología , Tolerancia a Medicamentos/fisiología , Morfina/farmacología , Analgésicos Opioides/farmacocinética , Animales , Cromatografía Líquida de Alta Presión , Masculino , Espectrometría de Masas , Morfina/farmacocinética , Derivados de la Morfina/sangre , Dimensión del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacosRESUMEN
Rapid opioid dose escalation, possibly caused by tolerance, has been observed in some patients on daily opioid therapy, although clinically identifiable characteristics of these patients are unknown. In this retrospective chart review of 206 patients, we examined whether the age of the patient was related to opioid escalation. Initial starting doses of long-acting opioids were similar in younger patients (< or =50 yr; 49 +/- 3 mg/d oral morphine-equivalent dose) versus older patients (> or =60 yr; 42 +/- 3 mg/d). Younger patients reached a maximum dose of 452 +/- 63 mg/d over 15.0 +/- 1.3 mo, whereas older patients achieved a maximum dose of 211 +/- 23 mg/d over 14.4 +/- 1.5 mo (P < 0.0001). At the last clinic visit, younger-patient dosing averaged 365 +/- 61 mg/d, with older patients averaging 168 +/- 18 mg/d (P < 0.0001). Only older patients demonstrated a reduction in visual analog scale scores from start of opioid therapy until discharge from the clinic (6.9 +/- 0.3 to 5.6 +/- 0.3; P < 0.01). These clinical data suggest that age is an important variable in opioid dose escalation. Although factors other than opioid tolerance can result in dose escalation, it is possible that older patients may have a reduced rate of tolerance development.
Asunto(s)
Envejecimiento/fisiología , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Dolor/tratamiento farmacológico , Adulto , Anciano , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios RetrospectivosRESUMEN
Neuropeptide nociceptin/orphanin FQ is the endogenous ligand for the opioid-receptor-like receptor 1 (ORL1), mediating essential functions in the central and peripheral nervous systems. The present study was performed to investigate the role of nociceptin and ORL1 receptor in nociception and morphine-induced antinociception in the arcuate nucleus of hypothalamus in rats. Hindpaw withdrawal latencies (HWL) were measured by hot-plate and Randall Selitto tests. The HWL to both thermal and mechanical stimulation decreased significantly after intra-arcuate nucleus injection of nociceptin in a dose-dependent manner. The effect of nociceptin was blocked significantly by subsequent intra-arcuate nucleus administration of [Nphe(1)]nociceptin(1-13)-NH(2), an ORL1 receptor antagonist. Furthermore, an intra-arcuate nucleus injection of nociceptin dramatically attenuated the antinociceptive effect induced by morphine either injected in the same site or applied intraperitoneally. These results suggest that nociceptin in the arcuate nucleus induces a hyperalgesic effect by acting on ORL1 receptors. The present study also demonstrates an interaction between nociceptin and opioids in the arcuate nucleus of the hypothalamus.