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  • 1.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Costantini, Mauro
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Echevarria, Camila
    Hosp Privado Comunidad Mar Del Plata, Dept Radiol, Buenos Aires, DF, Argentina..
    Pollioto, Sergio
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Abrego, Diego
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Doppler images of intra-pulmonary shunt within atelectasis in anesthetized children2016In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 8, article id 19Article in journal (Refereed)
    Abstract [en]

    Background: Doppler images of pulmonary vessels in pulmonary diseases associated with subpleural consolidations have been described. Color Doppler easily identifies such vessels within consolidations while spectral Doppler analysis allows the differentiation between pulmonary and bronchial arteries. Thus, Doppler helps in diagnosing the nature of consolidations. To our knowledge, Doppler analysis of pulmonary vessels within anesthesia-induced atelectasis has never been described before. The aim of this case series is to demonstrate the ability of lung ultrasound to detect the shunting of blood within atelectatic lung areas in anesthetized children.

    Findings: Three anesthetized and mechanically ventilated children were scanned in the supine position using a high-resolution linear probe of 6-12 MHz. Once subpleural consolidations were detected in the most dependent posterior lung regions, the probe was rotated such that its long axis followed the intercostal space. In this oblique position, color Doppler mapping was performed to detect blood flow within the consolidation. Thereafter, pulsed waved spectral Doppler was applied in the previously identified vessels during a short expiratory pause, which prevented interferences from respiratory motion. Different flow patterns were identified which corresponded to both, pulmonary and bronchial vessels. Finally, a lung recruitment maneuver was performed which leads to the complete resolution of the aforementioned consolidation thereby confirming the pathophysiological entity of anesthesia-induced atelectasis.

    Conclusions: Lung ultrasound is a non-invasive imaging tool that not only enables the diagnosis of anesthesia-induced atelectasis in pediatric patients but also analysis of shunting blood within this consolidation.

  • 2.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Redistribution Of Regional Lung Perfusion During Mechanical Ventilation With An Open Lung Approach Impacts Pulmonary Vascular Mechanics2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A3751Article in journal (Other academic)
  • 3.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L. V.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lucchetta, Luca
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Amato, Marcelo B. P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed)
    Abstract [en]

    Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

  • 4.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L V
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury2014In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

  • 5.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eduardo, Costa LV
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Widström, Charles
    Maripuu, Enn
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Marcelo, Amato
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.Manuscript (preprint) (Other academic)
  • 6.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Altering the mechanical scenario to decrease the driving pressure2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 342Article in journal (Refereed)
    Abstract [en]

    Ventilator settings resulting in decreased driving pressure (ΔP) are positively associated with survival. How to further foster the potential beneficial mediator effect of a reduced ΔP? One possibility is promoting the active modification of the lung's "mechanical scenario" by means of lung recruitment and positive end-expiratory pressure selection. By taking into account the individual distribution of the threshold-opening airway pressures to achieve maximal recruitment, a redistribution of the tidal volume from overdistended to newly recruited lung occurs. The resulting more homogeneous distribution of transpulmonary pressures may induce a relief of overdistension in the upper regions. The gain in lung compliance after a successful recruitment rescales the size of the functional lung, potentially allowing for a further reduction in ΔP.

  • 7.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Costa, Eduardo L. V.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Comment on Borges et al. "Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse" Reply2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 12, p. 2128-2128Article in journal (Refereed)
  • 8.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H
    Tusman, Gerardo
    Melo, Alexandre
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Park, Marcelo
    Costa, Eduardo L V
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Regional Lung Perfusion estimated by Electrical Impedance Tomography in a piglet model of lung collapse2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 1, p. 225-236Article in journal (Refereed)
    Abstract [en]

    The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology which provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT) based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6 %, with a standard deviation of 2.9 %. This method outperformed the estimates of lung perfusion based on impedance-pulsatility. In conclusion, we describe a novel method based on Electrical Impedance Tomography for estimating regional lung perfusion at the bedside. In both, healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this paper has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

  • 9.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Romero, Carolina
    Consorci Hosp Gen Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar De Plata, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Canet, Jaume
    Hosp Badalona Germans Trias & Pujol, Anesthesiol & Crit Care, Badalona, Spain..
    Dosda, Rosa
    Hosp Clin Univ Valencia, Dept Radiol, Valencia, Spain..
    Valls, Paola
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Villena, Abigail
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Serralta, Ferran
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Jurado, Ana
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Carrizo, Juan
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Navarro, Jose
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Parrilla, Cristina
    Hosp Clin Univ Valencia, Dept Radiol, Valencia, Spain..
    Romero, Jose E.
    Univ Politecn Valencia, ITACA Inst, Grp IBIME, Valencia, Spain..
    Pozo, Natividad
    INCLIVA Clin Res Inst, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Villar, Jesus
    Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.;Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain..
    Belda, Francisco Javier
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 5, article id e015560Article in journal (Refereed)
    Abstract [en]

    Objective To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO(2)) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. Design Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. Setting Postanaesthetic care unit in a tertiary hospital in Spain. Participants Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. Intervention The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO(2) was >= 96% and negative when SpO(2) was >= 97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. Main outcome measures The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. Results The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). Conclusion The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis.

  • 10. Ferrando, Carlos
    et al.
    Soro, Marina
    Canet, Jaume
    Carmen Unzueta, Ma
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Librero, Julian
    Peiro, Salvador
    Llombart, Alicia
    Delgado, Carlos
    Leon, Irene
    Rovira, Lucas
    Ramasco, Fernando
    Granell, Manuel
    Aldecoa, Cesar
    Diaz, Oscar
    Balust, Jaume
    Garutti, Ignacio
    de la Matta, Manuel
    Pensado, Alberto
    Gonzalez, Rafael
    Eugenia Duran, Ma
    Gallego, Lucia
    Garcia del Valle, Santiago
    Redondo, Francisco J.
    Diaz, Pedro
    Pestana, David
    Rodriguez, Aurelio
    Aguirre, Javier
    Garcia, Jose M.
    Garcia, Javier
    Espinosa, Elena
    Charco, Pedro
    Navarro, Jose
    Rodriguez, Clara
    Tusman, Gerardo
    Javier Belda, Francisco
    Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial2015In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 16, article id 193Article in journal (Refereed)
    Abstract [en]

    Background: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. Methods: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra-and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra-and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. Discussion: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications.

  • 11.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Unzueta, Carmen
    Hosp Santa Creu & Sant Pau, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Canet, Jaume
    Hosp Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Librero, Julian
    Navarrabiomed Fdn Miguel Servet, Red Invest Serv Salud Enfermedades Cron REDISSEC, Pamplona, Spain..
    Peiro, Salvador
    Ctr Super Invest Salud Publ CSISP FISABIO, Red Invest Serv Salud Enfermedades Cron REDISSEC, Valencia, Spain..
    Pozo, Natividad
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Delgado, Carlos
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Ibanez, Maite
    Hosp Villajoyosa, Dept Anesthesiol, Villajoyosa, Spain..
    Aldecoa, Cesar
    Hosp Villajoyosa, Dept Anesthesiol & Crit Care, Villajoyosa, Spain..
    Garutti, Ignacio
    Hosp Gen Gregorio Maranon, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Pestana, David
    Hosp Ramon & Cajal, Anesthesiol & Crit Care, Madrid, Spain..
    Rodriguez, Aurelio
    Hosp Dr Negrin, Anesthesiol & Crit Care, Gran Canaria, Spain..
    Garcia del Valle, Santiago
    Hosp Fdn Alcorcon, Anesthesiol & Crit Care, Alcorcon, Spain..
    Diaz-Cambronero, Oscar
    Hosp La Fe, Anesthesiol & Crit Care, Valencia, Spain..
    Balust, Jaume
    Hosp Clin Barcelona, Anesthesiol & Crit Care, Barcelona, Spain..
    Javier Redondo, Francisco
    Hosp Gen, Anesthesiol & Crit Care, Ciudad Real, Spain..
    De La Matta, Manuel
    Hosp Virgen del Rocio, Anesthesiol & Crit Care, Seville, Spain..
    Gallego, Lucia
    Hosp Miguel Servet, Anesthesiol & Crit Care, Zaragoza, Spain..
    Granell, Manuel
    Hosp Gen Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Martinez, Pascual
    Hosp Albacete, Anesthesiol & Crit Care, Albacete, Spain..
    Perez, Ana
    Hosp Elche, Anesthesiol & Crit Care, Elche, Spain..
    Leal, Sonsoles
    Hosp Povisa, Anesthesiol & Crit Care, Vigo, Spain..
    Alday, Kike
    Hosp La Princesa, Anesthesiol & Crit Care, Madrid, Spain..
    Garcia, Pablo
    Hosp 12 Octubre, Anesthesiol & Crit Care, Madrid, Spain..
    Monedero, Pablo
    Clin Univ Navarra, Anesthesiol & Crit Care, Pamplona, Spain..
    Gonzalez, Rafael
    Hosp Univ Leon, Anesthesiol & Crit Care, Leon, Spain..
    Mazzinari, Guido
    Hosp Manises, Anesthesiol & Crit Care, Manises, Spain..
    Aguilar, Gerardo
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Villar, Jesus
    Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.;Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Gran Canaria, Spain.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada..
    Javier Belda, Francisco
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Rationale and study design for an individualised perioperative open-lung ventilatory strategy with a high versus conventional inspiratory oxygen fraction (iPROVE-O2) and its effects on surgical site infection: study protocol for a randomised controlled trial2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 7, article id e016765Article in journal (Refereed)
    Abstract [en]

    Introduction Surgical site infection (SSI) is a serious postoperative complication that increases morbidity and healthcare costs. SSIs tend to increase as the partial pressure of tissue oxygen decreases: previous trials have focused on trying to reduce them by comparing high versus conventional inspiratory oxygen fractions (FIO 2) in the perioperative period but did not use a protocolised ventilatory strategy. The open-lung ventilatory approach restores functional lung volume and improves gas exchange, and therefore it may increase the partial pressure of tissue oxygen for a given FIO 2. The trial presented here aims to compare the efficacy of high versus conventional FIO 2 in reducing the overall incidence of SSIs in patients by implementing a protocolised and individualised global approach to perioperative open-lung ventilation. Methods and analysis This is a comparative, prospective, multicentre, randomised and controlled two-arm trial that will include 756 patients scheduled for abdominal surgery. The patients will be randomised into two groups: (1) a high FIO 2 group (80% oxygen; FIO 2 of 0.80) and (2) a conventional FIO 2 group (30% oxygen; FIO 2 of 0.30). Each group will be assessed intra-and postoperatively. The primary outcome is the appearance of postoperative SSI complications. Secondary outcomes are the appearance of systemic and pulmonary complications. Ethics and dissemination The iPROVE-O2 trial has been approved by the Ethics Review Board at the reference centre (the Hospital Clinico Universitario in Valencia). Informed consent will be obtained from all patients before their participation. If the approach using high FIO 2 during individualised open-lung ventilation decreases SSIs, use of this method will become standard practice for patients scheduled for future abdominal surgery. Publication of the results is anticipated in early 2019.

  • 12.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Soro, Marina
    Unzueta, Carmen
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Canet, Jaume
    Hosp Univ Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Librero, Julian
    REDISSEC, Navarrabiomed Fdn Miguel Servet, Pamplona, Spain..
    Pozo, Natividad
    Hosp Clin Univ Valencia, INCLIVA Clin Res Inst, Valencia, Spain..
    Peiro, Salvador
    REDISSEC, CSISP FISABIO, Valencia, Spain..
    Llombart, Alicia
    Hosp Univ Politecn Fe, IISLAFE Clin Res Inst, Valencia, Spain..
    Leon, Irene
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain..
    India, Inmaculada
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Aldecoa, Cesar
    Hosp Univ Rio Hortega, Dept Anesthesiol & Crit Care, Valladolid, Spain..
    Diaz-Cambronero, Oscar
    Hosp Univ Politecn Fe, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Pestana, David
    Hosp Univ Ramon & Cajal, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Redondo, Francisco J.
    Hosp Gen Univ Ciudad Real, Dept Anesthesiol & Crit Care, Ciudad Real, Spain..
    Garutti, Ignacio
    Hosp Gen Univ Gregorio Maranon, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Balust, Jaume
    Hosp Clin & Prov Univ, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia, Jose I.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Hosp Univ Politecn Fe, Dept Anesthesiol & Crit Care, Valencia, Spain.;Hosp Fdn Alcorcon, Dept Anesthesiol & Crit Care, Alcorcon, Spain.;Hosp Univ Puerta Hierro, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Ibanez, Maite
    Hosp Marina Baixa Vila Joiosa, Dept Anesthesiol, Alicante, Spain..
    Granell, Manuel
    Hosp Gen Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Rodriguez, Aurelio
    Hosp Univ Doctor Negrin, Dept Anesthesiol, Las Palmas Gran Canaria, Spain..
    Gallego, Lucia
    Hosp Univ Miguel Servet, Dept Anesthesiol & Crit Care, Zaragoza, Spain..
    de la Matta, Manuel
    Hosp Univ Virgen Rocio, Dept Anesthesiol & Crit Care, Seville, Spain..
    Gonzalez, Rafael
    Hosp Univ Leon, Dept Anesthesiol, Leon, Spain..
    Brunelli, Andrea
    Hosp Univ Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Garcia, Javier
    Rovira, Lucas
    Hosp Manises, Dept Anesthesiol, Valencia, Spain..
    Barrios, Francisco
    Hosp Principe Asturias Madrid, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Torres, Vicente
    Hosp Son Espases, Dept Anesthesiol & Crit Care, Palma de Mallorca, Spain..
    Hernandez, Samuel
    Hosp NS Candelaria, Dept Anesthesiol, Santa Cruz de Tenerife, Spain..
    Gracia, Estefania
    Gine, Marta
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia, Maria
    Hosp Univ Rio Hortega, Dept Anesthesiol & Crit Care, Valladolid, Spain..
    Garcia, Nuria
    Miguel, Lisset
    Sanchez, Sergio
    Pineiro, Patricia
    Pujol, Roger
    Hosp Clin & Prov Univ, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia-del-Valle, Santiago
    Hosp Fdn Alcorcon, Dept Anesthesiol & Crit Care, Alcorcon, Spain..
    Valdivia, Jose
    Hosp Marina Baixa Vila Joiosa, Dept Anesthesiol, Alicante, Spain..
    Hernandez, Maria J.
    Hosp Gen Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Padron, Oto
    Hosp Univ Doctor Negrin, Dept Anesthesiol, Las Palmas Gran Canaria, Spain..
    Colas, Ana
    Hosp Univ Miguel Servet, Dept Anesthesiol & Crit Care, Zaragoza, Spain..
    Puig, Jaume
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain..
    Azparren, Gonzalo
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Villar, Jesus
    Hosp Univ Doctor Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain..
    Belda, Javier
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Univ Valencia, Dept Surg, Valencia, Spain..
    Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial2018In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 6, no 3, p. 193-203Article in journal (Refereed)
    Abstract [en]

    Background The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. Methods We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m(2). Patients were randomly assigned (1: 1: 1: 1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O-2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. Findings Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0.89 [95% CI 0.74-1.07; p=0.25]), OLA-CPAP (111 [47%] of 238, 0.91 [0.76-1.09; p=0.35]), or STD-CPAP groups (118 [48%] of 244, 0.95 [0.80-1.14; p=0.65]) when compared with patients in the STD-O-2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. Interpretation In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation.

  • 13. Ferrando, Carlos
    et al.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gutierrez, Andrea
    Tusman, Gerardo
    Carbonell, Jose
    Garcia, Marisa
    Piqueras, Laura
    Compan, Desamparados
    Flores, Susanie
    Soro, Marina
    Llombart, Alicia
    Javier Belda, Francisco
    Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, article id 9Article in journal (Refereed)
    Abstract [en]

    Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

  • 14.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, GIBER Enfermedades Resp, Madrid, Spain.
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Leon, Irene
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Romero, Esther
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gracia, Estefania
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Mugarra, Ana
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Arocas, Blanca
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Pozo, Natividad
    Hosp Clin Univ, INCLIVA Clin Res Inst, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Belda, Francisco J.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177399Article in journal (Refereed)
    Abstract [en]

    Background: Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia.

    Methods: Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml.kg(-1)) and standard PEEP of 5 cmH(2)O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography.

    Results: OL-PEEP was found at 8 +/- 2 cmH(2)O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035).

    Conclusions: Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery.

  • 15. Garcia-Fernandez, Javier
    et al.
    Canfran, Susana
    Gomez de Segura, Ignacio A.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Aguado, Delia
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Pressure safety range of barotrauma with lung recruitment manoeuvres: A randomised experimental study in a healthy animal model2013In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 30, no 9, p. 567-574Article in journal (Refereed)
    Abstract [en]

    CONTEXT

    Recruitment manoeuvres aim at reversing atelectasis during general anaesthesia but are associated with potential risks such as barotrauma.

    OBJECTIVE

    To explore the range of pressures that can be used safely to fully recruit the lung without causing barotrauma in an ex-vivo healthy lung rabbit model.

    DESIGN

    Prospective, randomised, experimental study.

    SETTING

    Experimental Unit, La Paz University Hospital, Madrid, Spain.ANIMALSFourteen healthy young New Zealand rabbits of 12 weeks of age.

    INTERVENTIONS

    Animals were euthanised, the thorax and both pleural spaces were opened and the animals were allocated randomly into one of two groups submitted to two distinct recruitment manoeuvre strategies: PEEP-20 group, in which positive end-expiratory pressure (PEEP) was increased in 5-cmH(2)O steps from 0 to 20cmH(2)O and PEEP-50 group, in which PEEP was increased in 5-cmH(2)O steps from 0 to 50cmH(2)O. In both groups, a driving pressure of 15cmH(2)O was maintained until maximal PEEP and its corresponding maximal inspiratory pressures (MIPs) were reached. From there on, driving pressure was progressively increased in 5-cmH(2)O steps until detectable barotrauma occurred. Two macroscopic conditions were defined: anatomically open lung and barotrauma.

    MAIN OUTCOME MEASURES

    We measured open lung and barotrauma MIP, PEEP and driving pressure obtained using each strategy. A pressure safety range, defined as the difference between barotrauma MIP and anatomically open lung MIP, was also determined in both groups.RESULTSOpen lung MIP was similar in both groups: 23.63.8 and 23.3 +/- 4.1cmH(2)O in the PEEP-50 and PEEP-20 groups, respectively (P=0.91). However, barotrauma MIP in the PEEP-50 group was higher (65.7 +/- 3.4cmH(2)O) than in the PEEP-20 group (56.7 +/- 5 0.2cmH(2)O) (P=0.003) resulting in a safety range of pressures of respectively 33.3 +/- 8.7 and 42.1 +/- 3.9cmH(2)O (P=0.035).

    CONCLUSION

    In this ex-vivo model, we found a substantial difference between recruitment and barotrauma pressures using both recruitment strategies. However, a higher margin of safety was obtained when a higher PEEP and lower driving pressure strategy was used for recruiting the lung.

  • 16.
    Gogniat, Emiliano
    et al.
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Ducrey, Marcela
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Dianti, Jose
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Madorno, Matias
    Inst Tecnol Buenos Aires ITBA, Buenos Aires, DF, Argentina.
    Roux, Nicolas
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Midley, Alejandro
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Raffo, Julio
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Giannasi, Sergio
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    San Roman, Eduardo
    Hosp Italiano Buenos Aires, Dept Intens Care Med, Buenos Aires, DF, Argentina.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBERES, Madrid, Spain;Hosp Univ & Politecn La Fe, Serv Med Intens, Valencia, Spain.
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina.
    Dead space analysis at different levels of positive end-expiratory pressure in acute respiratory distress syndrome patients2018In: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 45, p. 231-238Article in journal (Refereed)
    Abstract [en]

    Purpose: To analyze the effects of positive end-expiratory pressure (PEEP) on Bohr's dead space (VDBohr/VT) in patients with acute respiratory distress syndrome (ARDS).

    Material and methods: Fourteen ARDS patients under lung protective ventilation settingswere submitted to 4 different levels of PEEP (0, 6, 10, 16 cmH(2)O). Respiratory mechanics, hemodynamics and volumetric capnography were recorded at each protocol step.

    Results: Two groups of patients responded differently to PEEP when comparing baseline with 16-PEEP: those in which driving pressure increased > 15% (Delta P.(15%), n = 7, p = .016) and those in which the change was <= 15% (Delta P-<= 15%, n = 7, p = .700). VDBohr/VT was higher in Delta P-<= 15% than in Delta P-<= 15% patients at baseline ventilation [0.58 (0.49-0.60) vs 0.46 (0.43-0.46) p = .018], at 0-PEEP [0.50 (0.47-0.54) vs 0.41 (0.40-0.43) p = .012], at 6-PEEP [0.55 (0.49-0.57) vs 0.44 (0.42-0.45) p = .008], at 10-PEEP [0.59 (0.51-0.59) vs 0.45 (0.44-0.46) p = .006] and at 16-PEEP [0.61 (0.56-0.65) vs 0.47 (0.45-0.48) p =. 001]. We found a good correlation between Delta P and VDBohr/VT only in the Delta P.(15%) group (r = 0.74, p < .001).

    Conclusions: Increases in PEEP result in higher VDBohr/VT only when associated with an increase in driving pressure.

  • 17.
    Hällsjö Sander, Caroline
    et al.
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sigmundsson, Thorir
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Hallbäck, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Maquet Crit Care AB, Solna, Sweden..
    Oldner, Anders
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björne, Hakan
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow2017In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, no 4, p. 717-725Article in journal (Refereed)
    Abstract [en]

    In a previous study a new capnodynamic method for estimation of effective pulmonary blood flow (COEPBF) presented a good trending ability but a poor agreement with a reference cardiac output (CO) measurement at high levels of PEEP. In this study we aimed at evaluating the agreement and trending ability of a modified COEPBF algorithm that uses expiratory instead of inspiratory holds during CO and ventilatory manipulations. COEPBF was evaluated in a porcine model at different PEEP levels, tidal volumes and CO manipulations (N = 8). An ultrasonic flow probe placed around the pulmonary trunk was used for CO measurement. We tested the COEPBF algorithm using a modified breathing pattern that introduces cyclic end-expiratory time pauses. The subsequent changes in mean alveolar fraction of carbon dioxide were integrated into a capnodynamic equation and effective pulmonary blood flow, i.e. non-shunted CO, was calculated continuously breath by breath. The overall agreement between COEPBF and the reference method during all interventions was good with bias (limits of agreement) 0.05 (-1.1 to 1.2) L/min and percentage error of 36 %. The overall trending ability as assessed by the four-quadrant and the polar plot methodology was high with a concordance rate of 93 and 94 % respectively. The mean polar angle was 0.4 (95 % CI -3.7 to 4.5)A degrees. A ventilatory pattern recurrently introducing end-expiratory pauses maintains a good agreement between COEPBF and the reference CO method while preserving its trending ability during CO and ventilatory alterations.

  • 18.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Kerstin M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

    METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

    RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

    CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

  • 19.
    Jalde, Francesca Campoccia
    et al.
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Jalde, Fredrik
    Maquet Crit Care, Solna, Sweden.
    Wallin, Mats K. E. B.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden;Maquet Crit Care, Solna, Sweden.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Hosp Univ & Politecn, Dept Intens Care Med, Valencia, Spain;Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Radell, Peter J.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Nelson, David
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Eksborg, Staffan
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Sackey, Peter V.
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 129, no 4, p. 769-777Article in journal (Refereed)
    Abstract [en]

    Background: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. Methods: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. Results: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. Conclusions: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

  • 20. Karagiannidis, C.
    et al.
    Kampe, K. Aufm
    Sipmann, F. Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Görna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Windisch, W.
    Mueller, T.
    Pathophysiology and technical Prerequisites of veno-venous extracorporal C0(2) Elimination(ECCO2R) to the treatment of difficult respiratory Acidosis2015In: MEDIZINISCHE KLINIK-INTENSIVMEDIZIN UND NOTFALLMEDIZIN, ISSN 2193-6218, Vol. 110, no 4, p. 311-311Article in journal (Other academic)
  • 21. Karagiannidis, Christian
    et al.
    Kampe, Kristin Aufm
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Windisch, Wolfram
    Mueller, Thomas
    Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 3, p. R124-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO2R in terms of cannula size, blood and sweep gas flow.

    METHODS:

    ECCO2R with a 0.98 m2 surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter).

    RESULTS:

    Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO2-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute, which did not result in the normalization of pH.

    CONCLUSIONS:

    Veno-venous ECCO2R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO2R in this setting.

  • 22.
    Longo, Silvina
    et al.
    Hosp Privado Univ Cordoba, Dept Anesthesia, Cordoba, Argentina..
    Siri, Juan
    Acosta, Cecilia
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    Palencia, Alberto
    Hosp Privado Univ Cordoba, Dept Cardiovasc Surg, Cordoba, Argentina..
    Echegaray, Arturo
    Chiotti, Ivan
    Hosp Privado Univ Cordoba, Dept Intens Care, Cordoba, Argentina..
    Parisi, Andres
    Ricci, Lila
    Univ Nacl Mar del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Buenos Aires, Argentina..
    Natal, Marcela
    Univ Nacl Mar del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Buenos Aires, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. CIBERES, Madrid, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    Lung recruitment improves right ventricular performance after cardiopulmonary bypass A randomised controlled trial2017In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, no 2, p. 66-74Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Atelectasis after cardiopulmonary bypass (CPB) can affect right ventricular (RV) performance by increasing its outflow impedance. OBJECTIVE The aim of this study was to determine whether a lung recruitment manoeuvre improves RV function by re-aerating the lung after CPB. DESIGN Randomised controlled study. SETTING Single-institution study, community hospital, Cordoba, Argentina. PATIENTS Forty anaesthetised patients with New York Heart Association class I or II, preoperative left ventricular ejection fraction at least 50% and Euroscore 6 or less scheduled for cardiac surgery with CPB. INTERVENTIONS Patients were assigned to receive either standard ventilation with 6 cmH(2)O of positive end-expiratory pressure (PEEP; group C, n = 20) or standard ventilation with a recruitment manoeuvre and 10 cmH(2)O of PEEP after surgery (group RM, n = 20). RV function, left ventricular cardiac index (CI) and lung aeration were assessed by transoesophageal echocardiography (TOE) before, at the end of surgery and 30 min after surgery. MAIN OUTCOME MEASURES RV function parameters and atelectasis assessed by TOE. RESULTS Haemodynamic data and atelectasis were similar between groups before surgery. At the end of surgery, CI had decreased from 2.9 +/- 1.1 to 2.6 +/- 0.9 l min(-1) m(-2) in group C (P = 0.24) and from 2.8 +/- 1.0 to 2.6 +/- 0.8 l min(-1) m +/- 2 in group RM (P = 0.32). TOE-derived RV function parameters confirmed a mild decrease in RV performance in 95% of patients, without significant differences between groups (multivariate Hotelling t-test P = 0.16). Atelectasis was present in 18 patients in group C and 19 patients in group RM (P = 0.88). After surgery, CI decreased further from 2.6 to 2.4 l min(-)1 m(-2) in group C (P = 0.17) but increased from 2.6 to 3.7 l min(-1) m(-2) in group RM (P<0.001). TOE-derived RV function parameters improved only in group RM (Hotelling t-test P<0.001). Atelectasis was present in 100% of patients in group C but only in 10% of those in group RM (P<0.001). CONCLUSION Atelectasis after CPB impairs RV function but this can be resolved by lung recruitment using 10 cm H2O of PEEP.

  • 23.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bruhn, A
    Cao, Xiaofang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Feinstein, R
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 1, p. 79-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium.

    METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated.

    RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.

    CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

  • 24.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Departament de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spai.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Pulmonary Divison, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
    Feinstein, Ricardo
    The Swedish National Veterinary Institute, Sweden.
    Jalkanen, Sirpa
    MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Roivainen, Anne
    Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Turku Center for Disease Modelling, University of Turku, Furku, Finland.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome2016In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 1, p. 18-31Article in journal (Refereed)
    Abstract [en]

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.

  • 25.
    Retamal Montes, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Cardiopulm Dept, Pulm Div, Heart Inst Incor, Sao Paulo, Brazil.
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Feinstein, Ricardo
    Natl Vet Inst, Dept Pathol & Wildlife Dis, Uppsala, Sweden.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 8, p. 1131-1141Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy.

    METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated.

    RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups.

    CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.

  • 26.
    Retamal Montes, Jamie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bruhn, A.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Open Lung Approach Impedes Pulmonary Edema Accumulation Secondary To High Respiratory Rate In An Experimental Model Of Acute Lung Injury2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191Article in journal (Other academic)
  • 27. Sakr, Y
    et al.
    Payen, D
    Reinhart, K
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Zavala, E
    Bewley, J
    Marx, G
    Vincent, J-L
    Effects of hydroxyethyl starch administration on renal function in critically ill patients2007In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 98, no 2, p. 216-224Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The influence of hydroxyethyl starch (HES) solutions on renal function is controversial. We investigated the effect of HES administration on renal function in critically ill patients enrolled in a large multicentre observational European study. METHODS: All adult patients admitted to the 198 participating intensive care units (ICUs) during a 15-day period were enrolled. Prospectively collected data included daily fluid administration, urine output, sequential organ failure assessment (SOFA) score, serum creatinine levels, and the need for renal replacement therapy (RRT) during the ICU stay. RESULTS: Of 3147 patients, 1075 (34%) received HES. Patients who received HES were older [mean (SD): 62 (SD 17) vs 60 (18) years, P = 0.022], more likely to be surgical admissions, had a higher incidence of haematological malignancy and heart failure, higher SAPS II [40.0 (17.0) vs 34.7 (16.9), P < 0.001] and SOFA [6.2 (3.7) vs 5.0 (3.9), P < 0.001] scores, and less likely to be receiving RRT (2 vs 4%, P < 0.001) than those who did not receive HES. The renal SOFA score increased significantly over the ICU stay independent of the type of fluid administered. Although more patients who received HES needed RRT than non-HES patients (11 vs 9%, P = 0.006), HES administration was not associated with an increased risk for subsequent RRT in a multivariable analysis [odds ratio (OR): 0.417, 95% confidence interval (CI): 0.05-3.27, P = 0.406]. Sepsis (OR: 2.03, 95% CI: 1.37-3.02, P < 0.001), cardiovascular failure (OR: 6.88, 95% CI: 4.49-10.56, P < 0.001), haematological cancer (OR: 2.83, 95% CI: 1.28-6.25, P = 0.01), and baseline renal SOFA scores > 1 (P < 0.01 for renal SOFA 2, 3, and 4 with renal SOFA = 0 as a reference) were all associated with a higher need for RRT. CONCLUSIONS: In this observational study, haematological cancer, the presence of sepsis, cardiovascular failure, and baseline renal function as assessed by the SOFA score were independent risk factors for the subsequent need for RRT in the ICU. The administration of HES had no influence on renal function or the need for RRT in the ICU.

  • 28. Sander, C. Hallsjo
    et al.
    Hallbaeck, M.
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Wallin, M.
    Oldner, A.
    Bjorne, H.
    A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 8, p. 1022-1031Article in journal (Refereed)
    Abstract [en]

    BackgroundWe have evaluated a new method for continuous monitoring of effective pulmonary blood flow (COEPBF), i.e. cardiac output (CO) minus intra-pulmonary shunt, during mechanical ventilation. The method has shown good trending ability during severe hemodynamic challenges in a porcine model with intact lungs. In this study, we further evaluate the COEPBF method in a model of lung lavage. MethodsCO(EPBF) was compared to a reference method for CO during hemodynamic and PEEP alterations, 5 and 12cmH(2)O, before and after repeated lung lavages in 10 anaesthetised pigs. Bland-Altman, four-quadrant and polar plot methodologies were used to determine agreement and trending ability. ResultsAfter lung lavage at PEEP 5cmH(2)O, the ratio of arterial oxygen partial pressure related to inspired fraction of oxygen significantly decreased. The mean difference (limits of agreement) between methods changed from 0.2 (-1.1 to 1.5) to -0.9 (-3.6 to 1.9)l/min and percentage error increased from 34% to 70%. Trending ability remained good according to the four-quadrant plot (concordance rate 94%), whereas mean angular bias increased from 4 degrees to -16 degrees when using the polar plot methodology. ConclusionBoth agreement and precision of COEPBF were impaired in relation to CO when the shunt fraction was increased after lavage at PEEP 5cmH(2)O. However, trending ability remained good as assessed by the four-quadrant plot, whereas the mean polar angle, calculated by the polar plot, was wide.

  • 29.
    Sander, Caroline Hällsjö
    et al.
    Karolinska Univ Hosp, Dept Anesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Lönnqvist, Per-Arne
    Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Paediat Anesthesia & Intens Care, Stockholm, Sweden..
    Hallbäck, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Carlos III, CIBERES, CIBER Enfermedades Resp, Madrid, Spain..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Maquet Crit Care AB, Solna, Sweden..
    Oldner, Anders
    Karolinska Univ Hosp, Dept Anesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björne, Håkan
    Karolinska Univ Hosp, Dept Anesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Capnodynamic assessment of effective lung volume during cardiac output manipulations in a porcine model2016In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 30, no 6, p. 761-769Article in journal (Refereed)
    Abstract [en]

    A capnodynamic calculation of effective pulmonary blood flow includes a lung volume factor (ELV) that has to be estimated to solve the mathematical equation. In previous studies ELV correlated to reference methods for functional residual capacity (FRC). The aim was to evaluate the stability of ELV during significant manipulations of cardiac output (CO) and assess the agreement for absolute values and trending capacity during PEEP changes at different lung conditions. Ten pigs were included. Alterations of alveolar carbon dioxide were induced by cyclic reoccurring inspiratory holds. The Sulphur hexafluoride technique for FRC measurements was used as reference. Cardiac output was altered by preload reduction and inotropic stimulation at PEEP 5 and 12 cmH(2)O both in normal lung conditions and after repeated lung lavages. ELV at baseline PEEP 5 was [mean (SD)], 810 (163) mL and decreased to 400 (42) mL after lavage. ELV was not significantly affected by CO alterations within the same PEEP level. In relation to FRC the overall bias (limits of agreement) was -35 (-271 to 201) mL, and percentage error 36 %. A small difference between ELV and FRC was seen at PEEP 5 cmH(2)O before lavage and at PEEP 12 cmH(2)O after lavage. ELV trending capability between PEEP steps, showed a concordance rate of 100 %. ELV was closely related to FRC and remained stable during significant changes in CO. The trending capability was excellent both before and after surfactant depletion.

  • 30.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. CIBER Enfermedades Resp CIBERES, Madrid, Spain.; CNIC, Ctr Nacl Invest Cardiovasc Carlos 3, Madrid, Spain.
    Gomez-Peñalver, Eva
    Hosp Gen Villalba, Intens Care Unit, Villalba, Spain.
    Monge-Garcia, M Ignacio
    Hosp SAS, Intens Care Unit, Jerez de la Frontera, Spain.
    Retamal, Jaime
    Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Sao Paulo, Heart Inst InCor, Hosp Clin, Div Pulm, Sao Paulo, Brazil.
    Tusman, Gerardo
    Department of Anesthesia, Hospital Privado de Comunidad, Mar del Plata, Argentina.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain..
    Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 11, p. e1157-e1164Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome.

    DESIGN: Experimental study.

    SETTING: University animal research laboratory.

    SUBJECTS: Twelve pigs (30.8 ± 2.5 kg).

    INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected.

    MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005).

    CONCLUSIONS: In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  • 31.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Monge-Garcia, M Ignacio
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Tusman, Gerardo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 3, p. e298-e305Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome.

    DESIGN: Experimental study.

    SETTING: Animal research laboratory.

    SUBJECTS: Ten pigs, 35 ± 5.2 kg.

    INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves.

    MEASUREMENTS AND MAIN RESULTS: After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p < 0.001), vascular compliance decreased (from 2.76 ± 0.86 to 1.48 ± 0.32 mL/mm Hg; p = 0.003), and reflected waves arrived earlier (0.23 ± 0.07 vs 0.14 ± 0.05, arbitrary unit; p = 0.002) compared with baseline. Comparing the three positive end-expiratory pressure levels, open lung approach resulted in the lowest: 1) Z0 (297 ± 83 vs 378 ± 79 dyn.s.cm, p = 0.033, and vs 450 ± 119 dyn.s.cm, p = 0.002); 2) effective arterial elastance (0.37 ± 0.08 vs 0.50 ± 0.15 mm Hg/mL, p = 0.04, and vs 0.61 ± 0.12 mm Hg/mL, p < 0.001), and 3) reflection coefficient (0.35 ± 0.17 vs 0.48 ± 0.10, p = 0.024, and vs 0.53 ± 0.19, p = 0.005), comparisons with hyperinflation and collapse, respectively.

    CONCLUSIONS: In this experimental setting, positive end-expiratory pressure consistent with the open lung approach resulted in the best pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressure settings.

  • 32.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Monge-Garcia, I
    Gomez Peñalver, E
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, L
    Retamal, Jaime
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Tusman, G
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    ARDS Decreases Pulmonary Artery Compliance in a Porcine Model2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 93, article id A7917Article in journal (Refereed)
    Abstract [en]

    Rationale: Importance of pulmonary hemodynamic disarrangements in ARDS has been remarked recently. In this study we describe the effect of ARDS on pulmonary artery compliance and the related effect on pulmonary hemodynamics. In this way we highlight the importance of pulsatile hemodynamic evaluation beyond the classic evaluation based only on resistance.

    Methods: 17 anesthetized and muscle relaxed pigs were monitored with a transonic flow probe and high fidelity micro-tip pressure sensor placed in the pulmonary artery through a small thoracotomy. An experimental model of ARDS was induced in these animals by means of lung saline lavages followed by two hours of injurious mechanical ventilation. Pulmonary artery compliance was measured as the stroke volume divided by the pulse pressure. Waveform analysis of pulmonary artery pressure and flow signal was applied to calculate the following variables: first harmonic impedance magnitude (inversely related with arterial compliance), characteristic impedance, wave reflections (which are affected by arterial compliance) magnitude and peak and foot arrival time (normalized to cardiac period). These variables are related to the pulmonary vessels efficiency to transmit pressure and flow produced by the right ventricle. In addition, pulmonary vascular resistance was evaluated as usual. Variables were evaluated before (Baseline) and after (ARDS) development of the model.

    Results: Comparing with Baseline, ARDS provoked a decrease in pulmonary artery compliance (3.03±0.99 vs 1.53±0.41 ml/mmHg, p<0.001), and in the wave reflections arrival time of foot (0.18±0.09 vs 0.11±0.05, p<0.001) and peak (0.50±0.12 vs 0.39±0.10, p< 0.001) and an increase in the impedance magnitude of the first harmonic (80±29 vs 145±38 dyn.s.cm-5, p<0.001) and in the pulmonary vascular resistance (230±79 vs 504±129 dyn.s.cm-5, p<0.001). Characteristic impedance and wave reflections magnitude showed no differences.

    Conclusions: In this porcine model, ARDS provoked a decrease in pulmonary artery compliance. This effect was followed by a deterioration of pulmonary vascular efficiency. Our findings can be relevant for the pathophysiology of right ventricle failure during ARDS. This abstract is funded by: European Society of Intensive Care Medicine (ESICM), Basic Science Award 2012, the Swedish Heart and Lung foundation and the Swedish Research Council (K2015-99X-22731-01-4)

  • 33.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Monge-Garcia, M.
    Hosp SAS, Jerez de la Frontera, Spain..
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gomez-Penalver, E.
    Hosp Gen Villalba, Villalba, Spain..
    Retamal, J.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Pulmonary Vascular Efficiency Worsening And Cardiac Energy Wasting During Early Stages Of Experimental Acute Respiratory Distress Syndrome2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, no D27, article id A7698Article in journal (Other academic)
  • 34.
    Sigmundsson, Thorir Svavar
    et al.
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Öhman, Tomas
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Hallbäck, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Redondo, Eider
    Hosp Navarra, Dept Intens Care Med, Pamplona, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Maquet Crit Care AB, Solna, Sweden..
    Oldner, Anders
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sander, Caroline Hällsjö
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björne, Håkan
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Performance of a capnodynamic method estimating effective pulmonary blood flow during transient and sustained hypercapnia2018In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 32, no 2, p. 311-319Article in journal (Refereed)
    Abstract [en]

    The capnodynamic method is a minimally invasive method continuously calculating effective pulmonary blood flow (COEPBF), equivalent to cardiac output when intra pulmonary shunt flow is low. The capnodynamic equation joined with a ventilator pattern containing cyclic reoccurring expiratory holds, provides breath to breath hemodynamic monitoring in the anesthetized patient. Its performance however, might be affected by changes in the mixed venous content of carbon dioxide (CvCO2). The aim of the current study was to evaluate COEPBF during rapid measurable changes in mixed venous carbon dioxide partial pressure (PvCO2) following ischemia-reperfusion and during sustained hypercapnia in a porcine model. Sixteen pigs were submitted to either ischemia-reperfusion (n = 8) after the release of an aortic balloon inflated during 30 min or to prolonged hypercapnia (n = 8) induced by adding an instrumental dead space. Reference cardiac output (CO) was measured by an ultrasonic flow probe placed around the pulmonary artery trunk (COTS). Hemodynamic measurements were obtained at baseline, end of ischemia and during the first 5 min of reperfusion as well as during prolonged hypercapnia at high and low CO states. Ischemia-reperfusion resulted in large changes in PvCO2, hemodynamics and lactate. Bias (limits of agreement) was 0.7 (-0.4 to 1.8) L/min with a mean error of 28% at baseline. COEPBF was impaired during reperfusion but agreement was restored within 5 min. During prolonged hypercapnia, agreement remained good during changes in CO. The mean polar angle was -4.19A degrees (-8.8A degrees to 0.42A degrees). Capnodynamic COEPBF is affected but recovers rapidly after transient large changes in PvCO2 and preserves good agreement and trending ability during states of prolonged hypercapnia at different levels of CO.

  • 35.
    Suarez Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Ciber Enfermedades Resp CIBERES Inst Invest Carlo, Madrid, Spain.;Univ Hosp La Fe, Dept Intens Care, Valencia, Spain..
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Ciber Enfermedades Resp CIBERES Inst Invest Carlo, Madrid, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies2018In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 6, no 2, article id 27Article, review/survey (Refereed)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) is the most severe form of acute respiratory failure characterized by diffuse alveolar and endothelial damage. The severe pathophysiological changes in lung parenchyma and pulmonary circulation together with the effects of positive pressure ventilation profoundly affect heart lung interactions in ARDS. The term pulmonary vascular dysfunction (PVD) refers to the specific involvement of the vascular compartment in ARDS and is expressed clinically by an increase in pulmonary arterial (PA) pressure and pulmonary vascular resistance both affecting right ventricular (RV) afterload. When severe, PVD can lead to RV failure which is associated to an increased mortality. The effect of PVD on RV function is not only a consequence of increased pulmonary vascular resistance as afterload is a much more complex phenomenon that includes all factors that oppose efficient ventricular ejection. Impaired pulmonary vascular mechanics including increased arterial elastance and augmented wave-reflection phenomena are commonly seen in ARDS and can additionally affect RV afterload. The use of selective pulmonary vasodilators and lung protective mechanical ventilation strategies are therapeutic interventions that can ameliorate PVD. Prone positioning and the open lung approach (OLA) are especially attractive strategies to improve PVD due to their effects on increasing functional lung volume. In this review we will describe some pathophysiological aspects of heart-lung interactions during the ventilatory support of ARDS, its clinical assessment and discuss therapeutic interventions to prevent the occurrence and progression of PVD and RV failure.

  • 36.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    New modes of assisted mechanical ventilation2014In: Medicina Intensiva, ISSN 0210-5691, E-ISSN 1578-6749, Vol. 38, no 4, p. 249-260Article in journal (Refereed)
    Abstract [en]

    Recent major advances in mechanical ventilation have resulted in new exciting modes of assisted ventilation. Compared to traditional ventilation modes such as assisted-controlled ventilation or pressure support ventilation, these new modes offer a number of physiological advantages derived from the improved patient control over the ventilator. By implementing advanced closed-loop control systems and using information on lung mechanics, respiratory muscle function and respiratory drive, these modes are specifically designed to improve patient-ventilator synchrony and reduce the work of breathing. Depending on their specific operational characteristics, these modes can assist spontaneous breathing efforts synchronically in time and magnitude, adapt to changing patient demands, implement automated weaning protocols, and introduce a more physiological variability in the breathing pattern. Clinicians have now the possibility to individualize and optimize ventilatory assistance during the complex transition from fully controlled to spontaneous assisted ventilation. The growing evidence of the physiological and clinical benefits of these new modes is favoring their progressive introduction into clinical practice. Future clinical trials should improve our understanding of these modes and help determine whether the claimed benefits result in better outcomes. (C) 2013 Elsevier Espana, S.L. and SEMICYUC. All rights reserved.

  • 37.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bohm, Stephan H.
    Tusman, Gerardo
    Volumetric capnography: the time has come2014In: Current Opinion in Critical Care, ISSN 1070-5295, E-ISSN 1531-7072, Vol. 20, no 3, p. 333-339Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review This review article summarizes the recent advances in electrical impedance tomography (EIT) related to cardiopulmonary imaging and monitoring on the background of the 30-year development of this technology. Recent findings EIT is expected to become a bedside tool for monitoring and guiding ventilator therapy. In this context, several studies applied EIT to determine spatial ventilation distribution during different ventilation modes and settings. EIT was increasingly combined with other signals, such as airway pressure, enabling the assessment of regional respiratory system mechanics. EIT was for the first time used prospectively to define ventilator settings in an experimental and a clinical study. Increased neonatal and paediatric use of EIT was noted. Only few studies focused on cardiac function and lung perfusion. Advanced radiological imaging techniques were applied to assess EIT performance in detecting regional lung ventilation. New approaches to improve the quality of thoracic EIT images were proposed. EIT is not routinely used in a clinical setting, but the interest in EIT is evident. The major task for EIT research is to provide the clinicians with guidelines how to conduct, analyse and interpret EIT examinations and combine them with other medical techniques so as to meaningfully impact the clinical decision-making.

  • 38.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    How We Stretch the Lung Matters2013In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 41, no 4, p. 1153-1155Article in journal (Other academic)
  • 39.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Santos, A.
    Peces-Barba, G.
    Bohm, S. H.
    Gracia, J. L.
    Calderón, P.
    Tusman, G.
    Pulmonary artery pulsatility is the main cause of cardiogenic oscillations2013In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 27, no 1, p. 47-53Article in journal (Refereed)
    Abstract [en]

    The genesis of cardiogenic oscillations, i.e. The small waves in airway pressure (COSpaw) and flow (COSflow) signals recorded at the airway opening is under debate. We hypothesized that these waves are originated from cyclic changes in pulmonary artery (PA) pressure and flow but not from the physical transmission of heartbeats onto the lungs. The aim of this study was to test this hypothesis. In 10 anesthetized pigs, COS were evaluated during expiratory breath-holds at baseline with intact chest and during open chest conditions at: (1) close contact between heart and lungs; (2) no heart-lungs contact by lifting the heart apex outside the thoracic cavity; (3) PA clamping at the main trunk during 10 s; and (4) during manual massage after cardiac arrest maintaining the heart apex outside the thorax, with and without PA clamping. Baseline COSpaw and COSflow amplitude were 0.70 ± 0.08 cmH2O and 0.51 ± 0.06 L/min, respectively. Both COS amplitude decreased during open chest conditions in step 1 and 2 (p &lt; 0.05). However, COSpaw and COSflow amplitude did not depend on whether the heart was in contact or isolated from the surrounding lung parenchyma. COSpaw and COSflow disappeared when pulmonary blood flow was stopped after clamping PA in all animals. Manual heart massages reproduced COS but they disappeared when PA was clamped during this maneuver. The transmission of PA pulsatilty across the lungs generates COSpaw and COSflow measured at the airway opening. This information has potential applications for respiratory monitoring.

  • 40.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Boehm, Stephan H.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Tusman, Gerardo
    Corrections of Enghoffs dead space formula for shunt effects still overestimate Bohr's dead space2013In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 189, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Dead space ratio is determined using Enghoffs modification (VDB-E/V-T) of Bohr's formula (V-DBohr/V-T) in which arterial is used as a surrogate of alveolar PCO2. In presence of intrapulmonary shunt Enghoffs approach overestimates dead space. In 40 lung-lavaged pigs we evaluated the Kuwabara's and Niklason's algorithms to correct for shunt effects and hypothesized that corrected VDB-E/V-T should provide similar values as V-DBohr/V-T. We analyzed 396 volumetric capnograms and arterial and mixed-venous blood samples to calculate V-DBohr/V-T and VDB-E/V-T. Thereafter, we corrected the latter for shunt effects using Kuwabara's (K) VDB-E/V-T and Niklason's (N) VDB-E/V-T algorithms. Uncorrected VDB-E/V-T (mean +/- SD of 0.70 +/- 0.10) overestimated V-DBohr/V-T (0.59 +/- 0.12) (p < 0.05), over the entire range of shunts. Mean (K) VDB-E/V-T was significantly higher than V-DBor/V-T (0.67 +/- 0.08, bias 0.085, limits of agreement 0.232 to 0.085; p< 0.05) whereas (N)VDB-E/V-T showed a better correction for shunt effects (0.64 +/- 0.09, bias 0.048, limits of agreement -0.168 to 0.072; p < 0.05). Neither Kuwabara's nor Niklason's algorithms were able to correct EnghofFs dead space formula for shunt effects. 

  • 41.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Mar Del Plata, Buenos Aires.
    Acosta, Cecilia
    Hosp Privado Comunidad Mar Del Plata, Mar Del Plata, Buenos Aires.
    Longo, Silvina
    Hosp Privado Cordoba, Dept Anaesthesia, Cordoba.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBERES, Madrid.
    Reply to: alveolar recruitment manoeuvres after cardiac surgery2018In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 35, no 1, p. 62-63Article in journal (Refereed)
  • 42.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Acosta, Cecilia M.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Boehm, Stephan H.
    Hepa Wash GmbH, Munich, Germany..
    Waldmann, Andreas D.
    Swisstom AG, Landquart, Switzerland..
    Ferrando, Carlos
    Univ Hosp Valencia, Dept Anesthesiol, Valencia, Spain..
    Perez Marquez, Manuel
    FJD, IIS, Dept Intens Care Med, Madrid, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. CIBERES, Madrid, Spain; Department of Critical Care, Hospital La Fe, Valencia, Spain..
    Postural lung recruitment assessed by lung ultrasound in mechanically ventilated children2017In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 9, article id 22Article in journal (Refereed)
    Abstract [en]

    Background: Atelectasis is a common finding in mechanically ventilated children with healthy lungs. This lung collapse cannot be overcome using standard levels of positive end-expiratory pressure (PEEP) and thus for only individualized lung recruitment maneuvers lead to satisfactory therapeutic results. In this short communication, we demonstrate by lung ultrasound images (LUS) the effect of a postural recruitment maneuver (P-RM, i.e., a ventilatory strategy aimed at reaerating atelectasis by changing body position under constant ventilation). Results: Data was collected in the operating room of the Hospital Privado de Comunidad, Mar del Plata, Argentina. Three anesthetized children undergoing mechanical ventilation at constant settings were sequentially subjected to the following two maneuvers: (1) PEEP trial in the supine position PEEP was increased to 10 cmH(2)O for 3 min and then decreased to back to baseline. (2) P-RM patient position was changed from supine to the left and then to the right lateral position for 90 s each before returning to supine. The total P-RM procedure took approximately 3 min. LUS in the supine position showed similar atelectasis before and after the PEEP trial. Contrarily, atelectasis disappeared in the non-dependent lung when patients were placed in the lateral positions. Both lungs remained atelectasis free even after returning to the supine position. Conclusions: We provide LUS images that illustrate the concept and effects of postural recruitment in children. This maneuver has the advantage of achieving recruitment effects without the need to elevate airways pressures.

  • 43.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, RA-4545 Cordoba, Argentina..
    Acosta, Cecilia M.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, RA-4545 Cordoba, Argentina..
    Nicola, Marco
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, RA-4545 Cordoba, Argentina..
    Esperatti, Mariano
    Hosp Privado Comunidad Mar Del Plata, Intens Care Med, Buenos Aires, DF, Argentina..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Real-time images of tidal recruitment using lung ultrasound2015In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 7, article id 19Article in journal (Refereed)
    Abstract [en]

    Background: Ventilator-induced lung injury is a form of mechanical damage leading to a pulmonary inflammatory response related to the use of mechanical ventilation enhanced by the presence of atelectasis. One proposed mechanism of this injury is the repetitive opening and closing of collapsed alveoli and small airways within these atelectatic areas-a phenomenon called tidal recruitment. The presence of tidal recruitment is difficult to detect, even with high-resolution images of the lungs like CT scan. The purpose of this article is to give evidence of tidal recruitment by lung ultrasound. Findings: A standard lung ultrasound inspection detected lung zones of atelectasis in mechanically ventilated patients. With a linear probe placed in the intercostal oblique position. We observed tidal recruitment within atelectasis as an improvement in aeration at the end of inspiration followed by the re-collapse at the end of expiration. This mechanism disappeared after the performance of a lung recruitment maneuver. Conclusions: Lung ultrasound was helpful in detecting the presence of atelectasis and tidal recruitment and in confirming their resolution after a lung recruitment maneuver.

  • 44. Tusman, Gerardo
    et al.
    Boehm, Stephan H.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Dead space during one-lung ventilation2015In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 28, no 1, p. 10-17Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Describe the importance of monitoring dead space during thoracic surgery, specifically during one-lung ventilation. Recent findings The concept of dead space has gained renewed interest among anesthesiologists ever since breath-by-breath measurement by volumetric capnography became available. Monitoring dead space during thoracic surgery assesses the ventilatory deficiencies related to increases in instrumental, airway and/or alveolar dead space, when ventilating patients with positive pressure and double-lumen tubes. Another interesting use of such monitoring is to detect ventilator-induced lung injury due to tidal overdistension. This type of injury threatens the fragile lungs especially during one-lung ventilation and can clinically be recognized as an increase in airway and alveolar dead space above normal values. To date, lung protective ventilation is based on the use of low tidal volumes and airway pressures to decrease overdistension. It has been shown to reduce the incidence of postoperative pulmonary complications after thoracic surgeries. However, such a ventilatory strategy impairs ventilation and induces hypercapnia due to increases in dead space. Therefore, continuous assessment of dead space is helpful in guiding ventilation and avoiding overdistension while maintaining the elimination of CO2 during thoracic surgery sufficiently high. Summary Monitoring dead space helps anesthesiologists monitor the status of the lung and find appropriate ventilatory settings during thoracic surgeries.

  • 45.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina.
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients2017In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 124, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (Spo(2)). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, Spo(2) can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a Spo(2)/Fio(2) diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real-time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals and the analysis of arterial impedance, Which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry.

  • 46. Tusman, Gerardo
    et al.
    Gogniat, Emiliano
    Bohm, Stephan H.
    Scandurra, Adriana
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Torroba, Agustin
    Casella, Federico
    Giannasi, Sergio
    San Roman, Eduardo
    Reference values for volumetric capnography-derived non-invasive parameters in healthy individuals2013In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 27, no 3, p. 281-288Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine typical values for non-invasive volumetric capnography (VCap) parameters for healthy volunteers and anesthetized individuals. VCap was obtained by a capnograph connected to the airway opening. We prospectively studied 33 healthy volunteers 32 +/- A 6 years of age weighing 70 +/- A 13 kg at a height of 171 +/- A 11 cm in the supine position. Data from these volunteers were compared with a cohort of similar healthy anesthetized patients ventilated with the following settings: tidal volume (VT) of 6-8 mL/kg, respiratory rate 10-15 bpm, PEEP of 5-6 cmH(2)O and FiO(2) of 0.5. Volunteers showed better clearance of CO2 compared to anesthetized patients as indicated by (median and interquartile range): (1) an increased elimination of CO2 per mL of VT of 0.028 (0.005) in volunteers versus 0.023 (0.003) in anesthetized patients, p < 0.05; (2) a lower normalized slope of phase III of 0.26 (0.17) in volunteers versus 0.39 (0.38) in anesthetized patients, p < 0.05; and (3) a lower Bohr dead space ratio of 0.23 (0.05) in volunteers versus 0.28 (0.05) in anesthetized patients, p < 0.05. This study presents reference values for non-invasive volumetric capnography-derived parameters in healthy individuals. Mechanical ventilation and anesthesia altered these values significantly.

  • 47. Tusman, Gerardo
    et al.
    Groisman, Ivan
    Fiolo, Felipe E.
    Scandurra, Adriana
    Martinez Arca, Jorge
    Krumrick, Gustavo
    Bohm, Stephan H.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Noninvasive Monitoring of Lung Recruitment Maneuvers in Morbidly Obese Patients: The Role of Pulse Oximetry and Volumetric Capnography2014In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 118, no 1, p. 137-144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We conducted this study to determine whether pulse oximetry and volumetric capnography (VCap) can determine the opening and closing pressures of lungs of anesthetized morbidly obese patients. METHODS: Twenty morbidly obese patients undergoing laparoscopic bariatric surgery with capnoperitoneum were studied. A lung recruitment maneuver was performed in pressure control ventilation as follows: (1) During an ascending limb, the lungs' opening pressure was detected. After increasing positive end-expiratory pressure (PEEP) from 8 to 16 cm H2O, fraction of inspired oxygen (Fio(2)) was decreased until pulse oximetric arterial saturation (Spo(2)) was <92%. Thereafter, end-inspiratory pressure was increased in steps of 2 cm H2O, from 36 to a maximum of 50 cm H2O. The opening pressure was attained when Spo(2) exceeded 97%. (2) During a subsequent decreasing limb, the lungs' closing pressure was identified. PEEP was decreased from 22 to 10 cm H2O in steps of 2 cm H2O. The closing pressure was determined as the PEEP value at which respiratory compliance decreased from its maximum value. We continuously recorded lung mechanics, Spo(2), and VCap. RESULTS: The lungs' opening pressures were detected at 44 (4) cm H2O (median and interquartile range) and the closing pressure at 14 (2) cm H2O. Therefore, the level of PEEP that kept the lungs without collapse was found to be 16 (3) cm H2O. Using respiratory compliance as a reference, receiver operating characteristic analysis showed that Spo(2) (area under the curve [AUC] 0.80 [SE 0.07], sensitivity 0.65, and specificity 0.94), the elimination of CO2 per breath (AUC 0.91 [SE 0.05], sensitivity 0.85, and specificity 0.98), and Bohr's dead space (AUC 0.83 [SE 0.06], sensitivity 0.70, and specificity 0.95] were relatively accurate for detecting lung collapse during the decreasing limb of a recruitment maneuver. CONCLUSIONS: Lung recruitment in morbidly obese patients could be effectively monitored by combining noninvasive pulse oximetry and VCap. Spo(2), the elimination of CO2, and Bohr's dead space detected the individual's opening and closing pressures.

  • 48.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Groisman, Ivan
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Maidana, Gustavo A.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Scandurra, Adriana
    Univ Mar del Plata, Sch Engn, Dept Elect, Bioengn Lab, Mar Del Plata, Buenos Aires, Argentina..
    Martinez Arca, Jorge
    Univ Mar del Plata, Sch Engn, Dept Elect, Bioengn Lab, Mar Del Plata, Buenos Aires, Argentina..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Inst Salud Carlos III, CIBERES, CIBER Enfermedades Resp, Madrid, Spain..
    The Sensitivity and Specificity of Pulmonary Carbon Dioxide Elimination for Noninvasive Assessment of Fluid Responsiveness2016In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 122, no 5, p. 1404-1411Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We sought to determine whether the response of pulmonary elimination of CO2 (Vco(2)) to a sudden increase in positive end-expiratory pressure (PEEP) could predict fluid responsiveness and serve as a noninvasive surrogate for cardiac index (CI). METHODS: Fifty-two patients undergoing cardiovascular surgery were included in this study. By using a constant-flow ventilation mode, we performed a PEEP challenge of 1-minute increase in PEEP from 5 to 10 cm H2O. At PEEP of 5 cm H2O, patients were preloaded with 500 mL IV saline solution after which a second PEEP challenge was performed. Patients in whom fluid administration increased CI by >= 15% from the individual baseline value were defined as volume responders. Beat-by-beat CI was derived from arterial pulse contour analysis, and breath-by-breath Vco(2) data were collected during the protocol. The sensitivity and specificity of Vco(2) for detecting the fluid responders according to CI was performed by the receiver operating characteristic curves. RESULTS: Twenty-one of 52 patients were identified as fluid responders (40%). The PEEP maneuver before fluid administration decreased CI from 2.65 +/- 0.34 to 2.21 +/- 0.32 L/min/m(2) (P = 0.0011) and Vco(2) from 150 +/- 23 to 123 +/- 23 mL/min (P = 0.0036) in responders, whereas the changes in CI and Vco(2) were not significant in nonresponders. The PEEP challenge after fluid administration induced no significant changes in CI and Vco(2), in neither responders nor nonresponders. PEEP-induced decreases in CI and Vco(2) before fluid administration were well correlated (r(2) = 0.75, P < 0.0001) but not thereafter. The area under the receiver operating characteristic curves for a PEEP-induced decrease in Delta CI and Delta Vco(2) was 0.99, with a 95% confidence interval from 0.96 to 0.99 for Delta CI and from 0.97 to 0.99 for Delta Vco(2). During the PEEP challenge, a decrease in Vco(2) by 11% predicted fluid responsiveness with a sensitivity of 0.90 (95% confidence interval, 0.87-0.93) and a specificity of 0.95 (95% confidence interval, 0.92-0.98). CONCLUSIONS: PEEP-induced changes in Vco(2) predicted fluid responsiveness with accuracy in patients undergoing cardiac surgery.

  • 49. Tusman, Gerardo
    et al.
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H.
    Rationale of Dead Space Measurement by Volumetric Capnography2012In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 114, no 4, p. 866-874Article in journal (Refereed)
    Abstract [en]

    Dead space is the portion of a tidal volume that does not participate in gas exchange because it does not get in contact with blood flowing through the pulmonary capillaries. It is commonly calculated using volumetric capnography, the plot of expired carbon dioxide (CO2) versus tidal volume, which is an easy bedside assessment of the inefficiency of a particular ventilatory setting. Today, Bohr's original dead space can be calculated in an entirely noninvasive and breath-by-breath manner as the mean alveolar partial pressure of CO2 (PAco(2)) which can now be determined directly from the capnogram. The value derived from Enghoff's modification of Bohr's formula (using Paco(2) instead of PAco(2)) is a global index of the inefficiency of gas exchange rather than a true "dead space" because it is influenced by all causes of ventilation/perfusion mismatching, from real dead space to shunt. Therefore, the results obtained by Bohr's and Enghoff's formulas have different physiological meanings and clinicians must be conscious of such differences when interpreting patient data. In this article, we describe the rationale of dead space measurements by volumetric capnography and discuss its main clinical implications and the misconceptions surrounding it.

  • 50. Tusman, Gerardo
    et al.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H.
    Bohr Dead Space Calculation In Response2012In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 115, no 6, p. 1472-1473Article in journal (Refereed)
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