Abstract:
BACKGROUND:Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. METHODS:Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy. WT mice received several dosing regimens of morphine. Obese mice (30 g) received one 80 mg/kg bolus of morphine. Blood was collected at fixed times after morphine injection for quantification of plasma morphine and morphine 3-glucuronide (M3G) levels. PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2). PK parameters were compared between mouse groups by the use of 1-way analysis of variance, with P values less than .05 considered significant. RESULTS:DIO compared with WT mice had significantly decreased morphine metabolism with lower M3G-to-morphine ratio (mean difference [MD]: -4.9; 95% confidence interval [CI]: -8.8 to -0.9) as well as a decreased Cl/F (MD: -4.0; 95% CI: -8.9 to -0.03) Ob/ob compared with WT mice had a large increase in morphine exposure with a greater AUC150 (MD: 980.4; 95% CI: 630.1-1330.6), CMAX (MD: 6.8; 95% CI: 2.7-10.9), and longer T1/2 (MD: 23.1; 95% CI: 10.5-35.6), as well as a decreased Cl/F (MD: -7.0; 95% CI: -11.6 to -2.7). Several PK parameters were significantly greater in ob/ob compared with DIO mice, including AUC150 (MD: 636.4; 95% CI: 207.4-1065.4), CMAX (MD: 5.3; 95% CI: 3.2-10.3), and T1/2 (MD: 18.3; 95% CI: 2.8-33.7). When leptin was replaced in ob/ob mice, PK parameters began to approach DIO and WT levels. LR compared with ob/ob mice had significant decreases in AUC150 (MD: -779.9; 95% CI: -1229.8 to -330), CMAX (MD: -6.1; 95% CI: -11.4 to -0.9), and T1/2 (MD: -19; 95% CI: -35.1 to -2.8). Metabolism increased with LR, with LR mice having a greater M3G-to-morphine ratio compared with DIO (MD: 5.3; 95% CI: 0.3-10.4). CONCLUSIONS:Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.
journal_name
Anesth Analgjournal_title
Anesthesia and analgesiaauthors
Dalesio NM,Hendrix CW,McMichael DH,Thompson CB,Lee CK,Pho H,Arias RS,Lynn RR,Galinkin J,Yaster M,Brown RH,Schwartz ARdoi
10.1213/ANE.0000000000001578subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1611-1617issue
6eissn
0003-2999issn
1526-7598journal_volume
123pub_type
杂志文章abstract:UNLABELLED:As the surgical population ages, the number of patients presenting with coronary artery disease and age-related loss of pulmonary recoil will increase. Although their influence on gas exchange in this population remains unknown, sevoflurane and isoflurane are used for an increasing variety of surgical proced...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200205000-00009
更新日期:2002-05-01 00:00:00
abstract::The swallowing reflex is depressed by anesthetics. During recovery from anesthesia the rapid return of laryngeal and upper airway reflexes is important to protect the lower airway from aspiration. This study measures the recovery of the swallowing reflex after propofol anesthesia. Fifteen patients undergoing a colonos...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/00000539-199411000-00007
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:Patients with chronic pain frequently suffer affective disorders, particularly anxiety and depression. Although clinical research on the relationship between pain and depressive symptoms has been done, it is not clear whether pain causes depression or depression exaggerates pain. To investigate the relation ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/01.ane.0000261514.19946.66
更新日期:2007-06-01 00:00:00
abstract::The number of anesthesiology residents pursuing critical care medicine (CCM) fellowship training has been decreasing in recent years. A significant number of training positions remain unfilled each year. Possible causes of this decline were evaluated by surveying residents regarding their attitudes toward practice and...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/00000539-199309000-00002
更新日期:1993-09-01 00:00:00
abstract:BACKGROUND:Although bone cancer-related pain is one of the most disruptive symptoms in patients with advanced cancer, patients are often refractory to pharmacological treatments; thus, more effective treatments for bone cancer pain are needed. We evaluated the analgesic efficacy of and interaction between intrathecal G...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e318227824e
更新日期:2011-10-01 00:00:00
abstract:IMPLICATIONS:Postoperative management of sedation and analgesia in pediatric cardiac patients presents many challenges. This case report describes a child who experienced dramatic clinical improvement with the postoperative use of caudal morphine and clonidine after conventional therapy had failed. ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200301000-00019
更新日期:2003-01-01 00:00:00
abstract:IMPLICATIONS:Chronic hiccups may be a serious therapeutic problem. Pharmacological treatment with increasing dosages of baclofen, carbamazepine, or gabapentin is not always successful. In this paper, the use of general anesthesia with positive-pressure ventilation and muscle relaxation for the termination of chronic hi...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200208000-00050
更新日期:2002-08-01 00:00:00
abstract::Atelectasis is common after cardiac surgery and may result in impaired gas exchange. Continuous positive airway pressure (CPAP) is often used to prevent or treat postoperative atelectasis. We hypothesized that noninvasive pressure support ventilation (NIPSV) by increasing tidal volume could improve the evolution of at...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1213/01.ANE.0000130621.11024.97
更新日期:2004-10-01 00:00:00
abstract::In the 1930s and 1940s, photo cells permitted German, English, and American physiologists to construct ear oximeters with red and infrared light, requiring calibration. In 1940 Squire recognized that changes of red and infrared light transmission caused by pneumatic tissue compression permitted saturation to be comput...
journal_title:Anesthesia and analgesia
pub_type: 传,历史文章,杂志文章
doi:10.1213/01.ane.0000269514.31660.09
更新日期:2007-12-01 00:00:00
abstract::In view of the overall experience regarding regional anesthetic techniques to control postoperative pain in infants and children, it is feasible that a similar efficacy and safety profile can be obtained when using such techniques after major orthopedic procedures such as anterior or posterior spinal fusion. I reviewe...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,评审
doi:10.1213/01.ane.0000107938.80562.75
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:Tardiness from scheduled start times is a common source of frustration for both operating room (OR) personnel and patients. Factors that influence tardiness were quantified in a companion paper and have been used to develop interventions that have the potential for reducing tardiness. METHODS:Data from two ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ane.0b013e31819f9fd2
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Hypothermia (HT) reduces neuronal injury after perinatal asphyxia. The anesthetic gas xenon (XE) may enhance this effect. We investigated the sedative and respiratory effects of variable XE concentrations at 37 degrees C normothermia (NT) or 32 degrees C HT after a hypoxic-ischemic (HI) insult to determine t...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ane.0b013e3181618669
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:We studied the effects of isoflurane on hippocampal synaptic transmission and paired-pulse plasticity, under in vivo intact interneuron circuitry. METHODS:Using rats chronically implanted with electrodes, excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA) were measured in the hipp...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/01.ane.0000281433.73260.8d
更新日期:2007-10-01 00:00:00
abstract::The ex utero intrapartum treatment (EXIT) procedure provides time to secure the airway of the fetus while utero-placental circulation supplies the fetus with oxygen. We report the anesthetic management of a fetus with a large neck mass during an EXIT procedure in which the confirmation of correct endotracheal intubati...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/01.ANE.0000175206.91231.77
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Surveys suggest that, consistent with a high smoking prevalence, Chinese smokers in the general population report little interest in quitting. In other cultures, surgery is a powerful teachable moment for smoking cessation, increasing the rate of spontaneous quitting. We determined the perioperative tobacco ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e31828e5cf0
更新日期:2013-06-01 00:00:00
abstract::The effect of the alpha 2-agonist dexmedetomidine on the cerebral blood flow (CBF) and the metabolic rate for oxygen was studied by a sagittal sinus outflow technique in dogs during halothane anesthesia. Dexmedetomidine was given in a dose (10 micrograms/kg) reported to reduce the anesthetic requirement of halothane b...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/00000539-199008000-00003
更新日期:1990-08-01 00:00:00
abstract::In this review, we summarize the clinical implications of residual neuromuscular block. Data suggest that residual neuromuscular block is a common complication in the postanesthesia care unit, with approximately 40% of patients exhibiting a train-of-four ratio <0.9. Volunteer studies have demonstrated that small degre...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,评审
doi:10.1213/ANE.0b013e3181da832d
更新日期:2010-07-01 00:00:00
abstract:UNLABELLED:Sameridine is a new compound with local anesthetic and analgesic properties when injected intrathecally. We studied the anesthetic and analgesic efficacy of three doses of isobaric sameridine (15, 20, and 23 mg) compared with 100 mg of hyperbaric lidocaine for spinal anesthesia in 140 healthy male patients u...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00000539-199904000-00025
更新日期:1999-04-01 00:00:00
abstract:UNLABELLED:We evaluated the blood-sparing effects of intraoperative moderate acute normovolemic hemodilution (ANH) combined with intraoperative tranexamic acid treatment and shed blood reinfusion in patients undergoing off-pump coronary artery bypass (OPCAB). One-hundred consecutive OPCAB patients (baseline hematocrit ...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1213/01.ane.0000113238.35409.fe
更新日期:2004-05-01 00:00:00
abstract::As of November 2016, the Florida Department of Health (FDH) and the Centers for Disease Control and Prevention have confirmed more than 4000 travel-related Zika virus (ZIKV) infections in the United States with >700 of those in Florida. There have been 139 cases of locally acquired infection, all occurring in Miami, F...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0000000000002047
更新日期:2017-06-01 00:00:00
abstract:UNLABELLED:Previous reports indicate that cyclosporine increases sleeping time from barbiturate administration, and analgesia from fentanyl administration, suggesting a possible contribution of cyclosporine to anesthesia. Accordingly, we determined whether cyclosporine pretreatment decreases isoflurane MAC (the minimum...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200210000-00025
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND:In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0000000000001976
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:Mounting evidence from animal studies shows that anesthetic exposure in early life leads to apoptosis in the developing nervous system. This loss of neurons has functional consequences in adulthood. Clinical retrospective reviews have suggested that multiple anesthetic exposures in early childhood are associ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e31826d37c5
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The cellular mechanisms underlying the sedative effect of general anesthetics are not completely understood. Accumulating evidence indicates that the ventrolateral preoptic area (VLPO) of the hypothalamus plays a critical role. The VLPO contains 2 major types of neurons, the noradrenalin-inhibited GABAergic ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e318297366e
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol. METHODS:Forty-five prepubertal subjects (children) and 45 postpubertal subjects (adults) were stu...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ane.0b013e318164f388
更新日期:2008-04-01 00:00:00
abstract::Thirty patients undergoing craniotomies were given infusions of fentanyl 1 microgram X kg-1 X hr-1, sufentanil 0.1 microgram X kg-1 X hr-1, or normal saline in a double-blind study of cerebral relaxation. Significantly better relaxation scores were achieved in patients given a narcotic infusion, but there was no diffe...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章
doi:10.1213/00000539-198705000-00007
更新日期:1987-05-01 00:00:00
abstract:BACKGROUND:Whether intraoperative analgesics have an impact on postoperative cancer recurrence is unknown. Some investigations suggest that the opioids could favor relapse and that regional analgesia and nonsteroidal antiinflammatory drugs could improve cancer prognosis. We retrospectively reviewed our series of breast...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e3181d2ad07
更新日期:2010-06-01 00:00:00
abstract::The effects of commercial and crystalline solutions of chloroprocaine (CP) (1.6 X 10(-3)-0.4 X 10(-3)M) and sodium bisulfite (SB) (0.8 X 10(-3)-0.08 X 10(-3)M) were studied on the multiplication of human neuroblastoma cells. These cells were chosen because of putative neurotoxicity associated with CP; cell multiplicat...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Initial, but not subsequent, inhalation of 8% desflurane produces transient sympathetic stimulation. We hypothesized that initial but not subsequent increases should produce pupil dilation, and that N2O, fentanyl, and clonidine, but not esmolol, should blunt the response. In 10 volunteers, we maintained anesthesia wit...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199508000-00028
更新日期:1995-08-01 00:00:00
abstract:BACKGROUND:Inhalation agents are being used in place of intravenous agents to provide sedation in some intensive care units. We performed a systematic review and meta-analysis of prospective randomized controlled trials, which compared the use of volatile agents versus intravenous midazolam or propofol in critical care...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,meta分析,评审
doi:10.1213/ANE.0000000000001634
更新日期:2017-04-01 00:00:00