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Permissive Hypercapnia: Role in Protective Lung Ventilatory Strategies

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Permissive Hypercapnia: Role in Protective Lung Ventilatory Strategies Permissive hypercapnia: role in protective lung ventilatory strategies Martina Ni Chonghailea,b, Brendan Higginsa and John G. Laffeya,b Purpose of review Supported by grants from the Health Research Board, Ireland, the Irish Lung Hypercapnia is a central component of current protective Foundation, the Yamanouchi European Foundation, and The Association of Anaesthetists of Great Britain and Ireland (J.G.L.) and an Abbott Scholarship ventilatory strategies. This review aims to present and awarded by the College of Anaesthetists, Ireland (M.N.C.). interpret data from recent clinical and experimental studies relating to hypercapnia and its role in protective ventilatory Correspondence to John G. Laffey, Department of Anaesthesia, Clinical Sciences Institute, National University of Ireland, Galway, Ireland strategies. Tel: 353 91 544608; fax: 353 91 544908; e-mail: [email protected] Recent findings Current Opinion in Critical Care 2005, 11:56–62 Increasing clinical evidence supports the use of permissive hypercapnia, particularly in acute lung injury/acute Abbreviations respiratory distress syndrome, status asthmaticus, and ALI acute lung injury ARDS acute respiratory distress syndrome neonatal respiratory failure. However, there are no clinical NF-kB nuclear factor kappa beta data examining the contribution of hypercapnia per se to PEEP positive end-expiratory pressure TGI tracheal gas insufflation protective ventilatory strategies. Recent experimental VILI ventilator-induced lung injury studies provide further support for the concept of therapeutic hypercapnia, whereby deliberately elevated ª 2005 Lippincott Williams & Wilkins. PaCO2 may attenuate lung and systemic organ injury. CO2 1070-5295 administration attenuates experimental acute lung injury because of adverse ventilatory strategies, mesenteric Introduction ischemia reperfusion, and pulmonary endotoxin instillation. Mechanical ventilatory strategies that use high tidal vol- Hypercapnic acidosis attenuates key effectors of the umes and transpulmonary pressures directly injure the inflammatory response and reduces lung neutrophil lung, a phenomenon termed ventilator-induced lung infiltration. At the genomic level, hypercapnic acidosis injury (VILI). Developments in our understanding of the attenuates the activation of nuclear factor-kB, a key pathogenesis of VILI, and clinical outcome data, have in- regulator of the expression of multiple genes involved in the creased the use of low lung stretch ventilatory strategies inflammatory response. The physiologic effects of that reduce mechanical trauma and the associated inflam- hypercapnia, both beneficial and potentially deleterious, are matory effects [1,2]. These strategies generally necessi- increasingly well understood. In addition, reports suggest tate hypoventilation and tolerance of hypercapnia to that humans can tolerate extreme levels of hypercapnia for realize the benefits of low lung stretch. This has resulted relatively prolonged periods without adverse effects. in a shift in clinical paradigms regarding hypercapnia— Summary from strict avoidance to acceptance, and a realization that The potential for hypercapnia to contribute to the beneficial even moderate to marked degrees of hypercapnia are well effects of protective lung ventilatory strategies is clear from tolerated. Paralleling this paradigm shift, several investiga- experimental studies. However, the optimal ventilatory tors have demonstrated the potential for induced hypercap- strategy and the precise contribution of hypercapnia to this nic acidosis to directly attenuate experimental acute lung strategy remain unclear. A clearer understanding of its injury. These findings raise the possibility that hypercapnia effects and mechanisms of action is central to determining may have an active role in the pathogenesis of inflammation the safety and therapeutic utility of hypercapnia in and tissue injury. The effects of hypercapnia in acute lung protective lung ventilatory strategies. injury states may be independent of, and distinct from, the demonstrated benefits of reduced lung stretch. Keywords hypercapnia, acidosis, mechanical ventilation, acute lung This paper reviews the current clinical status of permis- injury, acute respiratory distress syndrome sive hypercapnia, discusses the insights gained to date from basic scientific studies of hypercapnia and acidosis, Curr Opin Crit Care 11:56–62. ª 2005 Lippincott Williams & Wilkins. and considers the potential clinical implications of these findings for the management of acute lung injury. Exper- aDepartment of Anaesthesia, Clinical Sciences Institute and National Centre for Biomedical Engineering Sciences, National University of Ireland, Galway, Ireland; imental and clinical studies of special interest, published and bUniversity College Hospital, Galway, Ireland within the annual period of review, have been highlighted. 56 Permissive hypercapnia Chonghaile et al. 57 Permissive hypercapnia: clinical spectrum on its therapeutic potential in ALI/ARDS, its use was first described in patients with status asthmaticus. Permissive Acute lung injury and acute respiratory hypercapnia continues to play a central role in the venti- distress syndrome latory management of acute severe asthma. Dhuper et al. Mechanical ventilation potentiates and may even cause [9], in a study of the factors contributing to the need for lung damage, and it worsens the outcome in patients with tracheal intubation and mechanical ventilation in asthma, ALI and ARDS [3•,4]. The potential for protective lung ven- report a low incidence of barotrauma and no mortality with tilatory strategies, with varying degrees of permissive hy- a ventilation strategy involving permissive hypercapnia percapnia, to improve survival in patients with ALI/ARDS (peak airway pressures maintained <50 cm H O irrespec- is increasingly clear [3•,4–6]. The direct contribution of 2 tive of the PaCO level). Gupta et al. [10] analyzed the hypercapnia per se to these protective effects in the clin- 2 factors contributing to outcome in patients with acute se- ical context has not been determined. However, the po- vere asthma admitted to 128 intensive care units in Eng- tential for hypercapnia to directly protect against the land, Wales, and Northern Ireland participating in the effects of high stretch mechanical ventilation has recently ICNARC (Intensive Care National Audit and Research received strong support in a preliminary communica- Center) case-mix database. An analysis of PaCO levels tion. Kregenow et al. [7] examined mortality as a function 2 in all patients receiving ventilation within 24 hours of ad- of permissive hypercapnia on the day of enrollment of mission showed that these patients were treated with patients to the ARDSnet tidal volume study [6]. Using a ventilatory strategy that resulted in significant hypercap- multivariate logistic regression analysis, and controlling nia (mean highest PaCO of 8.2 KPa) [10]. for other comorbidities and severity of lung injury, they 2 reported that permissive hypercapnia reduced mortality Neonatal respiratory failure in patients randomized to the higher tidal volume [7]. The benefits of permissive hypercapnia in neonatal respi- However permissive hypercapnia did not affect outcome ratory failure are well recognized [11]. In fact, the clearest in patients randomized to the lower tidal volume. evidence for the use of permissive hypercapnia is in infants with neonatal respiratory distress syndrome, in Of concern, there is clear evidence that many clinicians do which a randomized controlled clinical trial of preterm not use protective ventilatory strategies in patients with infants demonstrated a clear benefit with permissive hyper- ALI/ARDS, despite convincing outcome data supporting capnia [12]. Kamper et al. [13•] conducted a prospective their use [5,6]. Rubenfeld et al. [8•] attempted to identify multicenter study of the respiratory treatment of neonates barriers to the implementation of protective ventilatory of extremely low gestational age (gestational age <28 strategies. Experienced nurses and respiratory therapists, weeks) and birthweight (birthweight <1000 g) admitted based at hospitals that participated in the ARDS Network to neonatal intensive care units across Denmark in 1994 trial, were surveyed. Identified barriers to the institution through 1995. They reported that a ventilatory support of protective ventilatory strategies included an unwilling- strategy based on permissive hypercapnia with the early ness by physicians to relinquish control of ventilator to use of nasal continuous positive airway pressure, with sur- a set protocol, delays in the diagnosis of ARDS/ALI, and factant therapy and mechanical ventilation reserved for the presence of conditions that were considered by the failure of nasal continuous positive airway pressure, was physicians to be contraindications to a protective lung as effective as strategies involving early mechanical venti- strategy. Barriers to the continuation of lung protective lation and seemed to significantly reduce the incidence of ventilation included concerns about patient comfort and chronic lung disease [13•]. concerns relating to the potential for hypercapnia, acido- sis, and hypoxemia to exert deleterious effects. The ther- Permissive hypercapnia plays an increasing role in the ven- apeutic benefit of protective strategies did not seem to tilatory treatment of infants with congenital diaphrag- be adequately recognized. This survey has clear limita- matic hernia.
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