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ABSTRACT: To investigate whether acute hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe systemic sepsis-induced lung and systemic organ injury resulting from cecal ligation and puncture. Acute hypercapnic acidosis protects against lung injury after both nonseptic and early pneumonia-induced lung injury. In contrast, prolonged hypercapnia worsens pneumonia-induced lung injury. The effects of hypercapnia and acidosis in the setting of systemic sepsis remain to be determined.
Prospective randomized animal study.
University research laboratory.
Adult male Sprague-Dawley rats.
In the early systemic sepsis series, post induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (Fico2 = 0.00, n = 12) or hypercapnic acidosis (Fico2 = 0.05, n = 12). Cecal ligation and puncture were performed and the animals were ventilated for 3 hrs. In the prolonged systemic sepsis series, rats were anesthetized, cecal ligation and puncture were performed, and the animals were allowed to recover. The animals were then randomized to housing under conditions of environmental normocapnia (Fico2 = 0.00, n = 20) or hypercapnia (Fico2 = 0.08, n = 20). After 96 hrs, the animals were reanesthetized, and the severity of lung and hemodynamic injury was assessed.
In early systemic sepsis, hypercapnic acidosis attenuated the development and severity of hypotension, and reduced lactate accumulation and the decrement in central venous oxyhemoglobin levels, compared with normocapnia. Hypercapnic acidosis reduced bronchoalveolar lavage neutrophil infiltration, and lung wet/dry weight ratios. In prolonged systemic sepsis, hypercapnic acidosis reduced histologic indices of lung injury. There was no evidence that hypercapnia worsened prolonged systemic sepsis-induced lung injury. Hypercapnic acidosis did not alter lung or systemic bacterial loads in early or prolonged systemic sepsis.
Hypercapnic acidosis exerts beneficial effects in early and prolonged cecal ligation and puncture-induced polymicrobial systemic sepsis.
Critical care medicine 07/2009; 37(8):2412-20. · 6.37 Impact Factor
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ABSTRACT: Hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. The effects of hypercapnic acidosis in the setting of established pulmonary sepsis are not known. The authors investigated whether hypercapnic acidosis -- induced by adding carbon dioxide to inspired gas -- would be beneficial or deleterious in established Escherichia coli pneumonia in an in vivo model, in the presence and absence of antibiotic therapy.
Adult male Sprague-Dawley rats were anesthetized and ventilated. In the first set of experiments, rats were anesthetized, E. coli (5-6.4 x 10(9)/ml colony-forming units) was instilled intratracheally, and the animals were allowed to recover. After 6 h, during which time a severe pneumonia developed, they were reanesthetized and randomly assigned to normocapnia (fraction of inspired carbon dioxide [Fico(2)] = 0.00, n = 10) or hypercapnic acidosis (Fico(2) = 0.05, n = 10). The second set of experiments was performed in a manner identical to that of series 1, but all rats (n = 10 per group) were given intravenous ceftriaxone (30 mg/kg) at randomization. All animals received normocapnia or hypercapnic acidosis for 6 h, and the severity of lung injury was assessed.
In the absence of antibiotic therapy, hypercapnic acidosis reduced the pneumonia-induced increase in peak airway pressure and the decrease in static lung compliance compared with control conditions. In the presence of antibiotic therapy, which substantially reduced lung bacterial counts, hypercapnic acidosis significantly attenuated the extent of pneumonia-induced histologic injury.
Hypercapnic acidosis reduced the magnitude of the lung injury induced by established E. coli pneumonia.
Anesthesiology 12/2008; 109(5):837-48. · 5.36 Impact Factor
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ABSTRACT: Deliberate induction of hypercapnic acidosis protects against lung injury after nonseptic lung injury. In contrast, concerns exist regarding the effects of hypercapnic acidosis in the setting of severe pulmonary sepsis. The potential for the effects of hypercapnic acidosis to be neutrophil-mediated remains to be determined. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe acute lung injury induced by pulmonary Escherichia coli instillation and the role of neutrophils in mediating this effect.
Prospective randomized animal study.
University Research Laboratory.
Adult male Sprague-Dawley rats.
In series 1, after induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (FICO2 0.00, n = 12) or hypercapnic acidosis (FICO2 0.05, n = 12). E. coli (0.5-3.0 x 10(15) colony-forming units) was instilled intratracheally and the animals were ventilated for 6 hrs to allow a severe acute lung injury to evolve. In series 2, animals were randomized to neutrophil depletion or nondepletion before bacterial instillation, in a three-group design: normocapnia alone (Normo + polymorphonuclear neutrophils [PMN], n = 9), normocapnia with neutrophil depletion (Normo - PMN, n = 9), or hypercapnic acidosis with neutrophil depletion (hypercapnic acidosis - PMN, n = 9). After intratracheal E. coli administration these animals were also ventilated for 6 hrs.
Hypercapnic acidosis protected against evolving pneumonia-induced acute lung injury, attenuating the increase in airway pressure, and the decrement in lung compliance and arterial PO2. However, hypercapnic acidosis did not reduce histologic injury. Hypercapnic acidosis also protected against evolving pneumonia-induced acute lung injury in the presence of neutrophil depletion, reducing both physiologic and histologic indices of lung injury.
Hypercapnic acidosis reduces indices of intratracheal E. coli induced lung injury by a mechanism that seems to be neutrophil-independent.
Critical care medicine 11/2008; 36(12):3135-44. · 6.37 Impact Factor
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ABSTRACT: The Airtraq laryngoscope is a novel intubation device that may possess advantages over conventional direct laryngoscopes for use by personnel that are infrequently required to perform tracheal intubation. We conducted a prospective study in 20 medical residents with little prior airway management experience. After brief didactic instruction, each participant took turns performing laryngoscopy and intubation using the Macintosh (Welch Allyn, Welch Allyn, NY) and Airtraq (Prodol Ltd. Vizcaya, Spain) devices, in 3 laryngoscopy scenarios in a Laerdal Intubation Trainer (Laerdal, Stavanger, Norway) and 1 scenario in a Laerdal SimMan manikin (Laerdal, Kent, UK). They then performed tracheal intubation of the normal airway a second time to characterize the learning curve. In all scenarios tested, the Airtraq decreased the duration of intubation attempts, reduced the number of optimization maneuvers required, and reduced the potential for dental trauma. The residents found the Airtraq easier to use in all scenarios compared with the Macintosh laryngoscope. The Airtraq may constitute a superior device for use by personnel infrequently required to perform tracheal intubation.
American Journal of Emergency Medicine 12/2006; 24(7):769-74. · 1.98 Impact Factor
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ABSTRACT: Current protective lung ventilation strategies commonly involve hypercapnia. This approach has resulted in an increase in the clinical acceptability of elevated carbon dioxide tension, with hypoventilation and hypercapnia 'permitted' in order to avoid the deleterious effects of high lung stretch. Advances in our understanding of the biology of hypercapnia have prompted consideration of the potential for hypercapnia to play an active role in the pathogenesis of inflammation and tissue injury. In fact, hypercapnia may protect against lung and systemic organ injury independently of ventilator strategy. However, there are no clinical data evaluating the direct effects of hypercapnia per se in acute lung injury. This article reviews the current clinical status of permissive hypercapnia, discusses insights gained to date from basic scientific studies of hypercapnia and acidosis, identifies key unresolved concerns regarding hypercapnia, and considers the potential clinical implications for the management of patients with acute lung injury.
Critical care (London, England) 03/2005; 9(1):51-9. · 4.61 Impact Factor
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ABSTRACT: 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.
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.
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.
Current Opinion in Critical Care 03/2005; 11(1):56-62. · 2.51 Impact Factor
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ABSTRACT: Hypercapnia has traditionally been avoided in paediatric critical illness; indeed, traditional approaches advocated hypocapnia in a number of disease states. However, recent advances in understanding of the role of excessive tidal stretch has prompted clinicians to avoid high tidal volumes or plateau pressures, and to tolerate the resulting ‘permissive’ hypercapnia. Advances in understanding of the biology of hypercapnia have led to consideration of an active role for hypercapnia in the pathogenesis of inflammation and tissue injury. Newer data suggest that elevated CO2 may be protective, but in some experimental situations can cause harm. This review assesses the role of ventilatory strategies involving permissive hypercapnia in the management of neonates and children with acute severe respiratory failure. The physiological effects of hypercapnia on the lung and systemic organs are discussed, and evidence from laboratory models of lung and systemic organ injury is considered, demonstrating the potential for hypercapnia to modulate the injury process. The role of permissive hypercapnia in various clinical settings relevant to neonatal and paediatric practice, and the risks and benefits of hypercapnia in specific clinical situations are also considered.
Paediatrics and Child Health.
