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Dexmedetomidine attenuates one-lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta-analysis.

ABSTRACT: One-lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti-inflammatory effects in lung tissues in pre-clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine's anti-inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta-analysis investigated the anti-inflammatory property of dexmedetomidine perioperatively [T1 (30-min OLV), T2 (90-min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine's intraoperative administration resulted in a significant reduction in serum concentration of interleukin-6, tumor necrosis factor-α and other inflammatory cytokines perioperatively. By calculating specific I² index, significant heterogeneity was observed on all occasions, with I² index ranging from 95% to 99%. For IL-6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%-0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.

SUBMITTER: Bai YX

PROVIDER: S-EPMC8453530 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:STUDY OBJECTIVE:To evaluate the effects of dexmedetomidine on hypoxic pulmonary vasoconstriction (HPV) and oxygenation during one-lung ventilation (OLV) in adults undergoing thoracic surgery. DESIGN:Prospective, randomized, double-blinded trial. SETTING:Tertiary care, University-based hospital. PATIENTS:Nineteen adult patients undergoing thoracic surgery requiring OLV. INTERVENTIONS:During inhalational anesthesia with desflurane, patients were randomized to receive either dexmedetomidine (bolus dose of 0.3 ?g/kg followed by an infusion of 0.3 ?g/kg/hr) or saline placebo. MEASUREMENTS:Three arterial blood gas samples (ABG) were obtained to evaluate the effects of dexmedetomidine on oxygenation. Secondary outcomes included differences in hemodynamic parameters (heart rate and mean arterial pressure), end-tidal desflurane concentration required to maintain the bispectral index (BIS) at 40-60, supplemental fentanyl to maintain hemodynamic stability, and phenylephrine to keep the mean arterial pressure (MAP) within 10% of baseline values. MAIN RESULTS:Oxygenation during OLV did not change following the administration of dexmedetomidine (PaO2/FiO2 ratio of 188 ± 115 in dexmedetomidine patients versus 135 ± 70 mmHg in placebo patients). There were no differences in hemodynamic variables or depth of anaesthesia between the two groups. With the administration of dexmedetomidine, there was a decrease in the expired concentration of desflurane required to maintain the BIS at 40-60 when compared with the control group (4.5 ± 0.8% versus 5.1 ± 0.8%). In patients receiving dexmedetomidine, fentanyl requirements were decreased when compared to placebo (2.7 ?g/kg/patient versus 3.1 ?g/kg/patient). However, more patients receiving dexmedetomidine required phenylephrine to maintain hemodynamic stability (6 of 9 patients versus 3 of 10 patients) and the total dose of phenylephrine was greater in patients receiving dexmedetomidine when compared with placebo 10.3 ?g/kg/patient versus 1.1 ?g/kg/patient). CONCLUSION:Dexmedetomidine does not adversely affect oxygenation during OLV in adults undergoing thoracic surgical procedures. The improvement in oxygenation in the dexmedetomidine patients may be related to a decrease in the requirements for inhalational anaesthetic agents thereby limiting its effects on HPV.

Project description:BackgroundDexmedetomidine (Dex), a selective a2-adrenergic receptor agonist, has been previously reported to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. However, the therapeutic effects of nebulized Dex on pulmonary shunt and lung mechanics during OLV have not been evaluated. Here we determine whether nebulized dexmedetomidine improved pulmonary shunt and lung mechanics in patients undergoing elective thoracic surgery in a prospective randomized controlled clinical trial.MethodsOne hundred and twenty-eight patients undergoing elective thoracoscopic surgery were included in this study and randomly divided into four groups: 0.9% saline (Placebo group), 0.5 µg/kg (Dex0.5 group), 1 µg/kg (Dex1 group) and 2 µg/kg (Dex2group) dexmedetomidine. After bronchial intubation, patients received different nebulized doses of dexmedetomidine (0.5 µg/kg, 1 µg/kg and 2 µg/kg) or 0.9% saline placebo during two-lung ventilation(TLV). OLV was initiated 15 min after bronchial intubation. Anesthesia was maintained with intravenous infusion of cisatracurium and propofol. Bispectral Index values were maintained within 40-50 by adjusting the infusion of propofol in all groups. Arterial blood gas samples and central venous blood gas samples were taken as follows: 15 min after bronchial intubation during two-lung ventilation (TLV15), after 30 and 60 min of OLV (OLV30and OLV60, respectively) and 15 min after reinstitution of TLV (ReTLV). Dynamic compliance was also calculated at TLV15, OLV30, OLV60 and ReTLV.ResultsDex decreased the requirement of propofol in a dose-dependent manner(P = 0.000). Heart rate (HR) and mean arterial pressure (MAP) displayed no significant difference among groups (P = 0.397 and 0.863). Compared with the placebo group, Dex administered between 0.5 and 2 µg/kg increased partial pressure of oxygen (PaO2) significantly at OLV30 and OLV60(P = 0.000); however, Dex administered between 1 and 2 µg/kg decreased pulmonary shunt fraction (Qs/Qt) at OLV30 and OLV60(P = 0.000). Compared with the placebo group, there were significant increases with dynamic compliance (Cdyn) after OLV in Dex0.5, Dex1 and Dex2group(P = 0.000). Conclusions. Nebulized dexmedetomidine improved oxygenation not only by decreasing pulmonary shunt but also by improving lung compliance during OLV, which may be effective in managing OLV.

Project description:OBJECTIVE:Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS:Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS:Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. CONCLUSIONS:Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

Project description:Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly with high mortality; however, there is no effective treatment, and the specific mechanism is not well understood. The antiaging protein klotho (KL) has multiple functions and exerts significant influences on various pathophysiological processes. This work evaluated the impact of KL on PQ-induced ALI and investigated its underlying mechanisms. As for in vivo research, C57BL/6 mice were treated with PQ (30?mg/kg) intraperitoneal (IP) injection to create a toxicity model of ALI (PQ group). The mice were divided into control group, KL group, PQ group, and PQ+KL group. For in vitro experiment, A549 cells were incubated with or without KL and then treated in the presence or absence of PQ for 24?h. In vivo result indicated that KL reduced the mortality, reduced IL-1? and IL-6 in the bronchoalveolar lavage fluid (BALF), attenuated ALI, and decreased apoptosis in situ. In vitro result revealed that KL significantly improved cell viability, reduced the levels of IL-1? and IL-6 in culture supernatants, suppressed cell apoptosis, inhibited caspase-3 activation, and enhanced mitochondrial membrane potential (??m) after PQ treatment. Besides, KL effectively abated reactive oxygen species (ROS) production, improved GSH content, and lowered lipid peroxidation in PQ-exposed A549 cells. Further experiments indicated that phosphorylated JNK and P38 MAPK was increased after PQ treatment; however, KL pretreatment could significantly lower the phosphorylation of P38 MAPK. Suppression of P38 MAPK improved cell viability, alleviated inflammatory response, and reduced apoptosis-related signals; however, it had no obvious effect on the production of ROS. Treatment with N-acetylcysteine (NAC), a classic ROS scavenger, could suppress ROS production and P38 MAPK activation. These findings suggested that KL could alleviate PQ-caused ALI via inhibiting ROS/P38 MAPK signaling-regulated inflammatory responses and mitochondria-dependent apoptosis.

Project description:Introduction: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 mL/kg) tidal volume (VT) ventilation with open lung positive end-expiratory pressure set according to the minimal static elastance of the respiratory system (LVT/OLPEEP), attenuate the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 mL/kg) VT and low PEEP ventilation (HVT/LPEEP). Methods: Twenty-eight adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LVT/OLPEEP; 2) NBD with HVT/LPEEP; 3) brain damage (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analysed. Whole genome analysis was performed using Affimetrix gene chips and confirmatory real-time PCR. Results: In NBD, both LVT/OLPEEP and HVT/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time PCR. In BD, LVT/OLPEEP, compared to HVT/LPEEP, reduced lung damage according to histology, genome analysis and real-time PCR with decreased interleukin (IL-6), cytokine-induced neutrophil chemoattractant (CINC)-1 and angiopoietin-4 expressions. LVT/OLPEEP compared to HVT/LPEEP improved overall survival. Conclusions: In BD, LVT/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HVT/LPEEP. LVT/OLPEEP might represent a suitable ventilatory strategy in massive brain damage. 24 Wistar rats - lung samples, 4 groups, 1. non-braindamaged/braindead high tidal volume ventilation, 2. non-braindamaged/braindead best PEEP ventilation, 3. Braindamaged/braindead high tidal volume ventilation, 4. Braindamaged/braindead best PEEP ventilation

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Dexmedetomidine attenuates one-lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta-analysis.

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