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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:BackgroundCardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators.MethodsTwenty pediatric patients undergoing cardiac surgery, CPB and SBUF were prospectively enrolled. Blood samples were collected prior to CPB initiation (Pre-CPB Plasma) and immediately before weaning off CPB (End-CPB Plasma). Ultrafiltrate effluent samples were also collected at the End-CPB time-point (End-CPB Effluent). The concentrations of thirty-nine inflammatory factors were assessed and sieving coefficients were calculated.ResultsA profound increase in inflammatory cytokines and activated complement products were noted in plasma following CBP. Twenty-two inflammatory mediators were detected in the ultrafiltrate effluent. Novel mediators removed by ultrafiltration included cytokines IL1-Ra, IL-2, IL-12, IL-17A, IL-33, TRAIL, GM-CSF, ET-1, and the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2 and CXCL10. Mediator extraction by SBUF was significantly associated with molecular mass < 66 kDa (Chi2 statistic = 18.8, Chi2 with Yates' correction = 16.0, p < 0.0001). There was a moderate negative linear correlation between molecular mass and sieving coefficient (Spearman R = - 0.45 and p = 0.02). Notably, the anti-inflammatory cytokine IL-10 was not efficiently extracted by SBUF.ConclusionsCPB is associated with a burden of circulating inflammatory mediators, and SBUF selectively extracts twenty of these pro-inflammatory factors while preserving the key anti-inflammatory regulator IL-10. Ultrafiltration could potentially function as an immunomodulatory therapy during pediatric cardiac surgery. Trial registration ClinicalTrials.gov, NCT05154864. Registered retrospectively on December 13, 2021. https://clinicaltrials.gov/ct2/show/record/NCT05154864 .

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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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