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Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass.

ABSTRACT: Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared with a conventional total intravenous anesthesia (TIVA) group of 11 patients (4 females and 7 males). The endpoints used to assess inflammatory and biochemical responses to mini-CPB were plasma interleukin (IL)-1, IL-6, IL-10, interferon (INF)-?, tumor necrosis factor (TNF)-?, C-reactive protein, creatine phosphokinase, creatine phosphokinase-MB, cardiac troponin I, cortisol, and glucose levels. These variables were determined before anesthesia, 90 min after beginning CPB, 5 h after beginning CPB, and 24 h after the end of surgery. Endpoints of oxidative stress, including thiobarbituric acid reactive species and delta-aminolevulinate dehydratase activity in erythrocytes were also determined. DEX+TIVA use was associated with a significant reduction in IL-1, IL-6, TNF-?, and INF-? (P<0.0001) levels compared with TIVA (two-way ANOVA). In contrast, the surgery-induced increase in thiobarbituric acid reactive species was higher in the DEX+TIVA group than in the TIVA group (P<0.01; two-way ANOVA). Delta-aminolevulinate dehydratase activity was decreased after CPB (P<0.001), but there was no difference between the two groups. DEX as an adjuvant in anesthesia reduced circulating IL-1, IL-6, TNF-?, and INF-? levels after mini-CPB. These findings indicate an interesting anti-inflammatory effect of DEX, which should be studied in different types of surgical interventions.

SUBMITTER: Bulow NM

PROVIDER: S-EPMC4792505 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass.

Bulow N M H NM Colpo E E Pereira R P RP Correa E F M EF Waczuk E P EP Duarte M F MF Rocha J B T JB

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 20160223 4

Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared ...[more]

PMID: 26909786

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Project description:BackgroundPreventing myocardial ischemia-reperfusion injury in on-pump cardiac surgeries remains an enormous challenge. Sevoflurane postconditioning has been effective at overcoming this challenge by modulating inflammatory mediators and ameliorating antioxidative stress. Dexmedetomidine (DEX) is a commonly used medication for cardiac patients with organ-protective properties that lead to positive outcomes. Whether DEX also has cardiac-protective properties and the associated mechanism in sevoflurane postconditioning-based valve replacement surgeries are unknown.ObjectiveThis study was conducted to observe the effect of DEX administration before cardiopulmonary bypass (CPB) on myocardial injury, oxidative stress, and inflammatory response indicators in the peripheral blood.MethodsTwenty-eight eligible cardiac patients who underwent valve replacement surgery with standard sevoflurane postconditioning were included in the study. The patients were randomly divided into a DEX group and a non-DEX group according to whether DEX (0.5-µg/kg overload dose for 10 minutes and a 0.5-μg/kg/h maintenance dose) or saline was administered from induction to the beginning of CPB. The primary outcome was the cardiac troponin I concentration (cTnI) in the blood 24 hours after CPB. The levels of malondialdehyde (MDA), superoxide dismutase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) were also measured.ResultsThe mean cTnI at 24 hours after CPB was clearly decreased in the DEX group compared with that in the non-DEX group (4.16 ± 1.58 vs. 6.90 ± 3.73, P < 0.05). TNF-α levels were lower in the DEX group after CPB (T1-T5), with a significant difference found at 1-6 hours after CPB (1 hour, 19.03 vs. 28.09; 6 hours, 20.74 vs. 30.94, P < 0.05). The IL-6 and IL-8 concentrations in the DEX group were dramatically increased at 6 hours after CPB (P < 0.05). The MDA content and superoxide dismutase activity were comparable between the 2 groups. A lower proportion of anemia cases were noted after CPB in the DEX group than in the non-DEX group (non-DEX, 10% vs. DEX, 5%, P < 0.05).ConclusionsIn valve replacement surgery with sevoflurane postconditioning, pre-CPB administration of DEX can reduce the cTnI level at 24 hours after CPB and brings synergic benefits of the inflammatory response.

Project description:BackgroundDexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB. We hypothesized that CL would decrease, and V would increase during CPB compared to pre- or post-CPB states.MethodsOpen-label, single-center, opportunistic pharmacokinetics (PK) and safety study of dexmedetomidine in patients ≤36 months of age administered dexmedetomidine per standard of care via continuous infusion. We analyzed dexmedetomidine PK data using standard nonlinear mixed effects modeling with NONMEM software. We compared model-estimated PK parameters to those from historical patients receiving dexmedetomidine before anesthesia for urologic, lower abdominal, or plastic surgery; after low-risk cardiac or craniofacial surgery; or during bronchoscopy or nuclear magnetic resonance imaging. We investigated the influence of CPB-related factors on PK estimates and used the final model to simulate dosing recommendations, targeting a plasma concentration previously associated with safety and efficacy (0.6 ng/mL). We used the Wilcoxon rank sum test to evaluate differences in dexmedetomidine exposure between infants with hypotension or bradycardia and those who did not develop these adverse events.ResultsWe collected 213 dexmedetomidine plasma samples from 18 patients. Patients had a median (range) age of 3.3 months (0.1-34.0 months) and underwent CPB for 161 minutes (63-394 minutes). We estimated a CL of 13.4 L/h/70 kg (95% confidence interval, 2.6-24.2 L/h/70 kg) during CPB, compared to 42.1 L/h/70 kg (95% confidence interval, 38.7-45.8 L/h/70 kg) in the historical patients. No specific CPB-related factor had a statistically significant effect on PK. A loading dose of 0.7 µg/kg over 10 minutes before CPB, followed by maintenance infusions through CPB of 0.2 or 0.25 µg/kg/h in infants with postmenstrual ages of 42 or 92 weeks, respectively, maintained targeted concentrations. We identified no association between dexmedetomidine exposure and selected adverse events (P = .13).ConclusionsCPB is associated with lower CL during CPB in infants and young children compared to those not undergoing CPB. Further study should more closely investigate CPB-related factors that may influence CL.

Project description:Essentials Heparin-protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post-operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin-initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB.SummaryBackground Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin-protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin-protamine balance was assessed with calibrated automated thrombography, thrombin-initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti-FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti-FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long-established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.

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Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass.

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Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass.

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