| 1. |
- Hedenstierna, Göran, 1941-, et al.
(author)
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Nitric oxide dosed in short bursts at high concentrations may protect against Covid 19.
- 2020
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In: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 103, s. 1-3
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Journal article (peer-reviewed)abstract
- It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.
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| 2. |
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| 3. |
- Akaberi, Dario, 1989-, et al.
(author)
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Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
- 2020
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In: Redox Biology. - : Elsevier. - 2213-2317. ; 37
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Journal article (peer-reviewed)abstract
- The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.
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| 4. |
- Akca, Ozan, et al.
(author)
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WHO Needs High FIO2?
- 2017
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In: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION. - : AVES. - 2149-0937. ; 45:4, s. 181-192
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Journal article (peer-reviewed)abstract
- World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations
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| 5. |
- Auckburally, Adam, et al.
(author)
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Effects of pulsed inhaled nitric oxide delivery on the distribution of pulmonary perfusion in spontaneously breathing and mechanically ventilated anesthetized ponies
- 2022
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In: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645 .- 1943-5681. ; 83, s. 171-179
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Journal article (peer-reviewed)abstract
- OBJECTIVETo measure changes in pulmonary perfusion during pulsed inhaled nitric oxide (PiNO) delivery in anesthetized, spontaneously breathing and mechanically ventilated ponies positioned in dorsal recumbency.ANIMALS6 adult ponies.PROCEDURESPonies were anesthetized, positioned in dorsal recumbency in a CT gantry, and allowed to breathe spontaneously. Pulmonary artery, right atrial, and facial artery catheters were placed. Analysis time points were baseline, after 30 minutes of PiNO, and 30 minutes after discontinuation of PiNO. At each time point, iodinated contrast medium was injected, and CT angiography was used to measure pulmonary perfusion. Thermodilution was used to measure cardiac output, and arterial and mixed venous blood samples were collected simultaneously and analyzed. Analyses were repeated while ponies were mechanically ventilated.RESULTSDuring PiNO delivery, perfusion to aerated lung regions increased, perfusion to atelectatic lung regions decreased, arterial partial pressure of oxygen increased, and venous admixture and the alveolar-arterial difference in partial pressure of oxygen decreased. Changes in regional perfusion during PiNO delivery were more pronounced when ponies were spontaneously breathing than when they were mechanically ventilated.CLINICAL RELEVANCEIn anesthetized, dorsally recumbent ponies, PiNO delivery resulted in redistribution of pulmonary perfusion from dependent, atelectatic lung regions to nondependent aerated lung regions, leading to improvements in oxygenation. PiNO may offer a treatment option for impaired oxygenation induced by recumbency.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Baumgardner, James E., et al.
(author)
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Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics
- 2021
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In: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 135:6, s. 1042-1054
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Journal article (peer-reviewed)abstract
- Background: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (V-A/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane.Methods: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung V-A/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different V-A/Q conditions: normal, low, and high.Results: The mathematical model predicts that the global V-A/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three V-A/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure P-art/P-mv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant.Conclusions: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The V-A/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower V-A/Q ratios.
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| 11. |
- Bergmann, Astrid, et al.
(author)
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Data on the effects of remote ischemic preconditioning in the lungs after one-lung ventilation
- 2018
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In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 21, s. 441-448
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Journal article (peer-reviewed)abstract
- This article contains data on experimental endpoints of a randomized controlled animal trial. Fourteen healthy piglets underwent mechanical ventilation including injurious one-lung ventilation (OLV), seven of them experienced four cycles of remote ischemic preconditioning (RIP) on one hind limb immediately before OLV, seven of them did not receive RIP and served as controls, in a randomized manner. The two major endpoints were (1) pulmonary damage assessed with the diffuse alveolar damage (DAD) score and (2) the inflammatory response assessed by cytokine concentrations in serum and in bronchoalveolar lavage fluids (BAL). The cytokine levels in the homogenized lung tissue samples are presented in the original article. Further interpretation and discussion of these data can be found in Bergmann et al. (in press).
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| 12. |
- Bergmann, Astrid, et al.
(author)
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Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers
- 2020
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In: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 271
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Journal article (peer-reviewed)abstract
- Purpose: Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol.Results: 60 min after RIP capillary pO(2) decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO(2), variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups.Conclusion: Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.
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| 13. |
- Bergmann, Astrid, et al.
(author)
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Effect of remote ischemic preconditioning on exhaled nitric oxide concentration in piglets during and after one-lung ventilation
- 2020
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In: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 276
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Journal article (peer-reviewed)abstract
- BACKGROUND: Remote ischemic preconditioning (RIP) may protect target organs from ischemia - reperfusion injury, however, little is known on pulmonary effects of RIP prior to, immediately after and several hours after one-lung ventilation (OLV). The present randomized, controlled, animal experiment was undertaken to analyze these issues.METHODS: After animal ethics committee approval, twelve piglets (26 ± 2 kg) were anesthetized and randomly assigned to a control (n = 6) or to a RIP group (n = 6). For RIP, arterial perfusion of a hind limb was suspended by an inflated blood pressure cuff (200 mmHg for 5 min) and deflated for another 5 min, this was repeated four times. After intubation, mechanical ventilation (MV) was kept constant with tidal volume 10 ml/kg, inspired oxygen fraction (FIO2) 0.40, and positive end-expiratory pressure (PEEP) 5cmH2O. FIO2 was increased to 1 after RIP in the RIP group and after the sham procedure in the control group, respectively, for the time of OLV. OLV was established by left-sided bronchial blockade. After OLV, TLV was re-established until the end of the protocol. Exhaled nitric oxide (NO) was measured by ozon chemiluminiscense and ventilatory and hemodynamic variables were assessed according to the protocol.RESULTS: Hemodynamic and respiratory data were similar in both groups. Arterial pO2 was higher in the RIP group after two hours of OLV. In the control group, exhaled NO decreased during OLV and remained at low levels for the rest of the protocol. In the RIP group, exhaled NO decreased as well during OLV but returned to baseline levels when TLV was re-established.CONCLUSIONS: RIP has no effects on hemodynamic and respiratory variables in juvenile, healthy piglets. RIP improves the oxygenation after OLV and prevents the decline of exhaled NO after OLV.
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| 14. |
- Bergmann, Astrid, et al.
(author)
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Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury
- 2019
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In: Respiratory Physiology & Neurobiology. - : Elsevier. - 1569-9048 .- 1878-1519. ; 259, s. 111-118
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Journal article (peer-reviewed)abstract
- BACKGROUND: One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV.METHODS: Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score.RESULTS: Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP.CONCLUSIONS: OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.
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| 15. |
- Bergmann, Astrid, 1972-
(author)
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Remote Ischemic Preconditioning and its Effects on the Respiratory System
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Mechanical ventilation in itself can lead to pulmonary damage, and one-lung ventilation (OLV), necessary for thoracic surgery, accentuates this injury. Remote ischemic preconditioning (RIP) is a potential tool to reduce lung injury after mechanical ventilation, including OLV. However, current data on pulmonary RIP-effects are contradictory. Therefore, the overall purpose of this Ph.D. project was to assess the effects of RIP on the respiratory system. In Study I, in healthy spontaneously breathing volunteers, oxygenation was impaired early after RIP, which was possibly induced by transient ventilation-perfusion inequality. Studies II, III, and IV were performed in a porcine OLV model. In Study II, we found that RIP possibly enhances alveolar injury, but attenuates the immune response. In Study III, we confirmed that an immune response to RIP takes place, which shows a different time pattern in each cytokine, depending on the site of measurement as well. In Study IV, we studied the porcine model for eight hours and found that RIP improved oxygenation after two hours of OLV and impeded the decline of exhaled nitric oxide (NO) during and after OLV. These findings indicate that RIP mitigates hypoxic pulmonary vasoconstriction (HPV).In summary, RIP has a complex effect on the respiratory system, which partly explains the previous contradictory findings.
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| 16. |
- Bergquist, Maria, et al.
(author)
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Altered adrenal and gonadal steroids biosynthesis in patients with burn injury
- 2016
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In: Clinical Mass Spectrometry. - : Elsevier BV. - 2213-8005 .- 2376-9998. ; 1, s. 19-26
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Journal article (peer-reviewed)abstract
- Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury.Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry.Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OH-pregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury.Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis driven study.
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| 17. |
- Bluth, Thomas, et al.
(author)
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Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients : A Randomized Clinical Trial.
- 2019
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 321:23, s. 2292-2305
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Journal article (peer-reviewed)abstract
- Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.
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| 18. |
- Bluth, T., et al.
(author)
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Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE) : study protocol for a randomized controlled trial
- 2017
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18
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Journal article (peer-reviewed)abstract
- Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients.Methods/design: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index >= 35 kg/m(2) scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH(2)O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH(2)O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint.Discussion: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs.
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| 19. |
- Borges, Joao Batista, et al.
(author)
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Real-time effects of PEEP and tidal volume on regional ventilation and perfusion in experimental lung injury
- 2020
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In: Intensive Care Medicine Experimental. - : SPRINGEROPEN. - 2197-425X. ; 8:1
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Journal article (peer-reviewed)abstract
- Background Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V-T) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V-T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH(2)O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V-T) was used, with a three-way mixed analysis of variance (ANOVA). Results Two-way interactions between PEEP and group, and V-T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V-T in the injured group than in the control group. A two-way interaction between PEEP and V-T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions Large PEEP and V-T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.
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| 20. |
- Broche, Ludovic, et al.
(author)
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Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
- 2017
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:4, s. 687-694
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Journal article (peer-reviewed)abstract
- Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.
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| 21. |
- Broche, Ludovic, et al.
(author)
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Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung
- 2019
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In: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 47:9, s. E774-E781
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Journal article (peer-reviewed)abstract
- Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.Design: Laboratory animal investigation.Setting: European synchrotron radiation facility.Subjects: Six New-Zealand White rabbits.Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.
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| 22. |
- Bulte, Carolien S. E., et al.
(author)
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The effects of preoperative moderate to severe anaemia on length of hospital stay : A propensity score-matched analysis in non-cardiac surgery patients
- 2021
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In: European Journal of Anaesthesiology. - : Wolters Kluwer. - 0265-0215 .- 1365-2346. ; 38:6, s. 571-581
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Journal article (peer-reviewed)abstract
- BACKGROUND Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively.OBJECTIVES The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay.DESIGN Post hoc analysis of the international observational prospective ‘Local ASsessment of VEntilatory management during General Anaesthesia for Surgery’ (LAS VEGAS) study.PATIENTS AND SETTING The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl−1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria.MAIN OUTCOME MEASURES The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs).RESULTS Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis.CONCLUSIONS In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality.
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| 23. |
- Crockett, D. C., et al.
(author)
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Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model
- 2019
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In: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 122:2, s. 277-285
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Journal article (peer-reviewed)abstract
- Background: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O-2 (FiO(2)) of 0.7 and a tidal volume of 10 ml kg(-1) Protocolised changes in pressure-and volume-controlled modes, inspiratory: expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. Results: During tidal ventilation, the expiratory lung collapse increased when I: E <1 [mean (standard deviation) lung collapse = .7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [ 2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.
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| 24. |
- Crockett, Douglas C., et al.
(author)
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Validating the inspired sinewave technique to measure the volume of the 'baby lung' in a porcine lung-injury model
- 2020
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In: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:3, s. 345-353
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Journal article (peer-reviewed)abstract
- Background: Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. Methods: Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (Delta ELV) between PEEP levels for each method (Delta ELVIST, Delta ELVSF6, and Delta ELVCT). Results: The coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r(2)=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r(2)=0.87 and 0.92, respectively). ELVIST had a mean bias of -12 to 13% (95% limits=+/- 17 - 25%) compared with ELVSF6 and ELVCT. Delta ELVIST was concordant with Delta ELVSF6 and Delta ELVCT in 98-100% of measurements, and had a mean bias of -73 to -77 ml (95% limits=+/- 128 - 186 ml) compared with Delta ELVSF6 and -1 ml (95% limits +/- 333 ml) compared with Delta ELVCT. Conclusions: IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.
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| 25. |
- Cronin, John N, et al.
(author)
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Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury
- 2019
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In: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 7:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified.METHODS: Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images.RESULTS: Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75-0.94) with agreement between CT density distributions (r 0.89-0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology.CONCLUSIONS: Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.
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