The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
John G. Laffey - One of the best experts on this subject based on the ideXlab platform.
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Permissive Hypercapnia: what to remember.
Current Opinion in Anesthesiology, 2015Co-Authors: Maya Contreras, Claire Masterson, John G. LaffeyAbstract:PURPOSE OF REVIEW: Hypercapnia is a central component of diverse respiratory disorders, while 'permissive Hypercapnia' is frequently used in ventilatory strategies for patients with severe respiratory failure. This review will present data from recent studies relating to Hypercapnia, focusing on issues that are of importance to anesthesiologists caring for the surgical and/or critically ill patient. RECENT FINDINGS: Protective ventilatory strategies involving permissive Hypercapnia are widely used in patients with severe respiratory failure, particularly in acute respiratory distress syndrome, status asthmaticus, chronic obstructive pulmonary disease and neonatal respiratory failure. The physiologic effects of Hypercapnia are increasingly well understood, and important recent insights have emerged regarding the cellular and molecular mechanisms of action of Hypercapnia and acidosis. Acute hypercapnic acidosis is protective in multiple models of nonseptic lung injury. These effects are mediated in part through inhibition of the NF-κB pathway. Hypercapnia-mediated NF-κB inhibition may also explain several deleterious effects, including delayed epithelial wound healing and decreased bacterial killing, which has been demonstrated to cause worse lung injury in prolonged untreated pneumonia models. SUMMARY: The mechanisms of action of Hypercapnia and acidosis continue to be elucidated, and this knowledge is central to determining the safety and therapeutic utility of Hypercapnia in protective lung ventilatory strategies.
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Acidosis in the critically ill - balancing risks and benefits to optimize outcome
Critical Care, 2014Co-Authors: Gerard F Curley, John G. LaffeyAbstract:Acidosis is associated with poor outcome in critical illness. However, acidosis - both hypercapnic and metabolic - has direct effects that can limit tissue injury induced by many causes. There is also a clear potential for off-target harm with acute exposure (for example, raised intracranial pressure, pulmonary hypertension), and with exposure for prolonged periods (for example, increased risk of infection) or at high doses. Ongoing comprehensive determination of molecular, cellular and physiologic impact across a range of representative pathologies will allow us to understand better the risks and benefits of Hypercapnia and acidosis during critical illness.
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Hypercapnia: Permissive, Therapeutic, or Not at All?
Intensive Care Medicine, 2008Co-Authors: Patrick Hassett, Maya Contreras, John G. LaffeyAbstract:In the past, Hypercapnia and its concomitant hypercapnic acidosis, have been considered to be adverse, and were strictly avoided in the critically ill. Support for this approach derived from concerns regarding the link between Hypercapnia and/or acidosis and adverse outcome in diverse clinical contexts, including cardiac arrest, sepsis, and neonatal asphyxia [1]. However, accumulating evidence from experimental and clinical studies demonstrates the potential for mechanical ventilation to directly injure the lungs — a phenomenon termed ‘ventilator-induced lung injury (VILI)’ — and has mandated a rethink of our approaches to Hypercapnia.
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Permissive Hypercapnia: role in protective lung ventilatory strategies.
Current Opinion in Critical Care, 2005Co-Authors: Martina Ni Chonghaile, Brendan D. Higgins, John G. LaffeyAbstract:Purpose of review Hypercapnia is a central component of current protective ventilatory strategies. This review aims to present and interpret data from recent clinical and experimental studies relating to Hypercapnia and its role in protective ventilatory strategies. Recent findings Increasing clinical evidence supports the use of permissive Hypercapnia, particularly in acute lung injury/acute respiratory distress syndrome, status asthmaticus, and neonatal respiratory failure. However, there are no clinical data examining the contribution of Hypercapnia per se to protective ventilatory strategies. Recent experimental studies provide further support for the concept of therapeutic Hypercapnia, whereby deliberately elevated PaCO2 may attenuate lung and systemic organ injury. CO2 administration attenuates experimental acute lung injury because of adverse ventilatory strategies, mesenteric ischemia reperfusion, and pulmonary endotoxin instillation. Hypercapnic acidosis attenuates key effectors of the inflammatory response and reduces lung neutrophil infiltration. At the genomic level, hypercapnic acidosis attenuates the activation of nuclear factor-kappaB, a key regulator of the expression of multiple genes involved in the inflammatory response. The physiologic effects of Hypercapnia, both beneficial and potentially deleterious, are increasingly well understood. In addition, reports suggest that humans can tolerate extreme levels of Hypercapnia for relatively prolonged periods without adverse effects. Summary The potential for Hypercapnia to contribute to the beneficial effects of protective lung ventilatory strategies is clear from experimental studies. However, the optimal ventilatory strategy and the precise contribution of Hypercapnia to this strategy remain unclear. A clearer understanding of its effects and mechanisms of action is central to determining the safety and therapeutic utility of Hypercapnia in protective lung ventilatory strategies.
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Permissive Hypercapnia — role in protective lung ventilatory strategies
Intensive Care Medicine, 2004Co-Authors: John G. Laffey, Donall O’croinin, Paul Mcloughlin, Brian P. KavanaghAbstract:‘Permissive Hypercapnia’ is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of Hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for Hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First , we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second , we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO_2, in the absence of protective ventilation, is beneficial or deleterious. Fourth , we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for Hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO_2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of Hypercapnia. At present, protective ventilatory strategies that involve Hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that Hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of Hypercapnia in ARDS.
Brian P. Kavanagh - One of the best experts on this subject based on the ideXlab platform.
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Permissive Hypercapnia — role in protective lung ventilatory strategies
Intensive Care Medicine, 2004Co-Authors: John G. Laffey, Donall O’croinin, Paul Mcloughlin, Brian P. KavanaghAbstract:‘Permissive Hypercapnia’ is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of Hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for Hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First , we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second , we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO_2, in the absence of protective ventilation, is beneficial or deleterious. Fourth , we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for Hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO_2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of Hypercapnia. At present, protective ventilatory strategies that involve Hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that Hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of Hypercapnia in ARDS.
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permissive Hypercapnia role in protective lung ventilatory strategies
Intensive Care Medicine, 2004Co-Authors: John G. Laffey, Paul Mcloughlin, Donall Ocroinin, Brian P. KavanaghAbstract:‘Permissive Hypercapnia’ is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of Hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for Hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO2, in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for Hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of Hypercapnia. At present, protective ventilatory strategies that involve Hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that Hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of Hypercapnia in ARDS.
Kevin J Shoemaker - One of the best experts on this subject based on the ideXlab platform.
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impact of age on cerebrovascular dilation versus reactivity to Hypercapnia
Journal of Cerebral Blood Flow and Metabolism, 2017Co-Authors: Nicole S Coverdale, Mark B Badrov, Kevin J ShoemakerAbstract:This study quantified the effect of age on cerebrovascular reactivity and cerebrovascular conductance while accounting for differences in grey matter volume in younger (YA: n = 12; 24 ± 4 years, six females) and older adults (OA: n = 10; 66 ± 7 years; five females). Cerebral blood flow velocity (CBFV; transcranial Doppler) in the middle cerebral artery (MCA), MCA cross-sectional area (CSA), intracranial volumes (magnetic resonance imaging), and mean arterial pressure (MAP; Finometer), were measured under normocapnic and hypercapnic (6% carbon dioxide) conditions. Cerebral blood flow (CBF) was quantified from CBFV and MCA CSA and normalized to grey matter volume. Grey matter volume was 719 ± 98 mL in YA and 622 ± 50 mL in OA (P = 0.009). Cerebrovascular reactivity (%ΔCBF/ΔPETCO2) was not different between YA and OA. In contrast, cerebrovascular conductance (CBF/MAP) in response to Hypercapnia was reduced in OA (P = 0.02). Of note, MAP increased more with Hypercapnia in OA compared with YA. Therefore, the c...
Natascha Sommer - One of the best experts on this subject based on the ideXlab platform.
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effects of Hypercapnia and no synthase inhibition in sustained hypoxic pulmonary vasoconstriction
Respiratory Research, 2012Co-Authors: Farzaneh Ketabchi, Bakytbek Egemnazarov, Ralph T Schermuly, Hossein Ardeschir Ghofrani, Werner Seeger, Friedrich Grimminger, Mostafa Shidmoosavi, Gholam Abbas Dehghani, Norbert Weissmann, Natascha SommerAbstract:Background Acute respiratory disorders may lead to sustained alveolar hypoxia with Hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of Hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined.
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effects of Hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction
American Journal of Physiology-lung Cellular and Molecular Physiology, 2009Co-Authors: Farzaneh Ketabchi, Bakytbek Egemnazarov, Ralph T Schermuly, Hossein Ardeschir Ghofrani, Werner Seeger, Friedrich Grimminger, Mostafa Shidmoosavi, Gholam Abbas Dehghani, Norbert Weissmann, Natascha SommerAbstract:Acute respiratory disorders and permissive hypercapnic strategy may lead to alveolar hypoxia and hypercapnic acidosis. However, the effects of Hypercapnia with or without acidosis on hypoxic pulmon...
Hergen Buscher - One of the best experts on this subject based on the ideXlab platform.
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association of Hypercapnia and hypercapnic acidosis with clinical outcomes in mechanically ventilated patients with cerebral injury
JAMA Neurology, 2018Co-Authors: Ravindranath Tiruvoipati, David Pilcher, Hergen Buscher, John Botha, Robert Simister, Michael BaileyAbstract:Importance Clinical studies investigating the effects of Hypercapnia and hypercapnic acidosis in acute cerebral injury are limited. The studies performed so far have mainly focused on the outcomes in relation to the changes in partial pressure of carbon dioxide and pH in isolation and have not evaluated the effects of partial pressure of carbon dioxide and pH in conjunction. Objective To review the association of compensated Hypercapnia and hypercapnic acidosis during the first 24 hours of intensive care unit admission on hospital mortality in adult mechanically ventilated patients with cerebral injury. Design, Setting, and Participants Multicenter, binational retrospective review of patients with cerebral injury (traumatic brain injury, cardiac arrest, and stroke) admitted to 167 intensive care units in Australia and New Zealand between January 2000 and December 2015. Patients were classified into 3 groups based on combination of arterial pH and arterial carbon dioxide (normocapnia and normal pH, compensated Hypercapnia, and hypercapnic acidosis) during the first 24 hours of intensive care unit stay. Main Outcomes and Measures Hospital mortality. Results A total of 30 742 patients (mean age, 55 years; 21 827 men [71%]) were included. Unadjusted hospital mortality rates were highest in patients with hypercapnic acidosis. Multivariable logistic regression analysis and Cox proportional hazards analysis in 3 diagnostic categories showed increased odds of hospital mortality (cardiac arrest odds ratio [OR], 1.51; 95% CI, 1.34-1.71; stroke OR, 1.43; 95% CI, 1.27-1.6; and traumatic brain injury OR, 1.22; 95% CI, 1.06-1.42; P Conclusions and Relevance Hypercapnic acidosis was associated with increased risk of hospital mortality in patients with cerebral injury. Hypercapnia, when compensated to normal pH during the first 24 hours of intensive care unit admission, may not be harmful in mechanically ventilated patients with cerebral injury.
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effects of Hypercapnia and hypercapnic acidosis on hospital mortality in mechanically ventilated patients
Critical Care Medicine, 2017Co-Authors: Ravindranath Tiruvoipati, David Pilcher, Hergen Buscher, John Botha, Michael BaileyAbstract:Objectives:Lung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause Hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of Hypercapnia and hypercapnic