Current Respiratory Medicine Reviews - Volume 6, Issue 4, 2010

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Mechanical ventilation is an integral component in the management of patients with acute respiratory failure. The role of neuromuscular junction blocking agents (NMBA) in facilitating mechanical ventilation in intensive care remains controversial. NMBA have been variously advocated to decrease oxygen consumption through reduction of the work of breathing, ablation of shivering and reduction of metabolic rates, as well as to increase oxygen delivery through improved ventilation. Additional attributed benefits include the reduced potential for barotrauma, enhanced ventilatorpatient synchrony, and an ability to reduce the inspired fraction of oxygen. Despite all of these putative benefits, there remains scant high-grade evidence to guide rationale use of NMBA in the critically ill patient. Many Clinical Practice Guidelines recommend that NMBA be avoided due to the associated risk of prolonged neuromuscular weakness. Other adverse effects associated with NMBA use include the consequences of undetected circuit disconnection, reduced neurological signs, risk of awareness and recall in inadequately sedated patients, increased post-traumatic stress disorder, and reduction in supported spontaneous breathing and coughing. Optimal paralysis depth remains empiric and is often poorly controlled or monitored in intensive care. Nonetheless prudent NMBA does not appear to prolong ventilation. Refractory hypoxemia almost invariably leads to the use of NMBA. Intriguingly, systematic use of NMBA for 48 hours appears to have beneficial long-term effects in patients with severe ARDS. Rather than simply targeting short term gain in oxygenation and lung mechanics, this benefit may justify a 2-day period of NMBA use in severe ARDS.

Whatever the aetiology and whatever the severity, the active management of respiratory failure habitually results in the administration of supplemental oxygen therapy. This review re-examines aspects of the optimization of such therapy. The oft-cited and well described risks of oxygen toxicity are revisited. Although no universal absolutes can be stipulated, the safe use of oxygen therapy is explored with particular reference to optimal oxygen targets. Specific attention is directed to the balance between the tolerable lower limits of systemic oxygenation and the putatively safe limits for titration of supplemental inspired oxygen fraction. Additional consideration is given to the emerging concept of permissive hypoxaemia. The attractiveness of this notion, and its potential role when the adverse effects of pursuing increased oxygenation combine to outweigh any benefit, has been enhanced by recent experiences with severe hypoxic respiratory failure arising from pandemic influenza viruses. Significant shortcomings remain in the existing definitions and descriptors of dysoxia, as well as the available technology for monitoring oxygenation. In clinical practice, oxygen displays a relatively narrow therapeutic index, and requires a careful balance of its benefits and risks. A detailed understanding of this ubiquitous therapy is obligatory in the optimal care of the critically ill.

Ventilator associated pneumonia (VAP) increases mortality and hospital length of stay, In addition, increased costs can be directly linked to the development of VAP in the critically ill. Significant variability exists in the incidence of VAP, which is not entirely accounted for by the variation in case-mix between intensive care units. Controversy exists regarding the need for bronchoscopic or other invasive diagnostic techniques compared to clinically based diagnosis. VAP occurs as a result of airway colonisation with pathogenic bacteria, aspiration into the distal airways and the progression of tracheobronchitis to pneumonia. Preventive measures involve strategies to prevent aspiration, limit the duration of mechanical ventilation and reduce the potential for contamination by ventilation equipment. Pharmacological prophylaxis and infection control procedures aim to reduce airway bacterial colonization. The introduction of protocolised strategies to reduce VAP with performance monitoring has shown efficacy in reducing this complication of mechanical ventilation.

Pulmonary infections are very common in critically ill patients and are the source of significant morbidity and mortality. Early and appropriate antibiotic therapy is essential to maximise the likelihood of clinical success and decrease the development of antibiotic resistance from sub-optimal antibiotic concentrations. However, the altered physiology of critically ill patients can have significant effects on antibiotic concentrations at the site of infection. Antibiotics such as ??- lactams, aminoglycosides and glycopeptides may occasionally have elevated lung concentrations in some forms of acute lung injury, although not often within lung parenchyma, and certainly have decreased concentrations in patients with chronic lung injury (e.g., cystic fibrosis patients). For these antibiotics, high doses in the first 24-48 hours of treatment may be required to maximise penetration into the lung. Other antibiotics including fluoroquinolones, macrolides, tigecycline and linezolid will typically penetrate the lungs extensively and therefore will not require specific doses for critically ill patients with pulmonary infections. The purpose of this review article is to focus on the pharmacokinetic and pharmacodynamic principles of antibiotics in critically ill patients, with particular emphasis on optimising therapy for pulmonary infections.

Background: Non-invasive ventilation (NIV) has now become an integral part of ventilatory support in the Intensive Care Unit (ICU). There has been much research carried out looking at the pathophysiology of various conditions as well as attempts to define the clinical effects of NIV in various conditions. This article discusses some of the conditions for which NIV has been used in the intensive care setting. It examines some of the underlying pathophysiology as well as clinical research into the effectiveness of NIV for these conditions. Some of the practical issues in the application of NIV are also discussed. Discussion: NIV is indicated as the treatment of choice in respiratory failure due to pulmonary oedema and exacerbations of COPD. There is also significant evidence for its use in the management of pulmonary infection in immunocompromised patients and in managing respiratory failure in patients who cannot be invasively ventilated. The use of NIV in asthma and acute lung injury have been well reported but remain experimental at this stage. Consideration of the underlying pathophysiology helps to explain the reasons why NIV is more useful in some of these conditions and can also be used to guide effective use for an individual patient. Conclusion: The choice of mode of respiratory support, interface and equipment settings will be tailored to the individual patients needs based on clinical experience. In the acute care setting the success of NIV therapies is dependent on patient selections and good nursing care by the clinical team.

Objective: To introduce the reader to the topic of lung ultrasound. The considerable value of lung ultrasound has recently gained attention and it is rapidly becoming a vital point of care investigation in patients with dyspnoea or haemodynamic instability. Although normal lung tissue is not directly visualized by ultrasound, the presence of various artifacts enables the clinician to diagnose several pathologic entities. The intercostal spaces form an ultrasound window and the hyperechoic parietal pleura present between any two ribs is the major source of diagnostic artifacts. Sliding of the visceral against parietal pleura identifies lung inflation in the scanned area and the respective proportions of air and fluid in the lung tissue determine the way parietal pleural reverberation artifacts are reflected and displayed. Lung consolidation resembles other parenchymal organs such as liver not only on gross pathological examination but also is similarly reflected by ultrasound. Pleural effusion is diagnosed above the diaphragm usually as a hypoechoic space and the volume of fluid present can be estimated. Other advantages of lung ultrasound include bedside availability, dynamic nature, simplicity and the absence of radiation exposure.

This review addresses the current state of Lung Protective Ventilation and PEEP settings in critical ill patients, especially with Acute Respiratory Distress Syndrome (ARDS). Mechanisms of mediator and cytokine activation are described and results from clinical studies on mechanical ventilation are compared with results obtained in experimental studies. Furthermore, several ventilation strategies, particularly the Open Lung Maneuver, are discussed highlighting their role in the prevention of VALI. Finally, the Open Lung Maneuver is described through an example of an illustrative case.

Respiratory injury in burns occurs as a result of thermal, chemical or systemic inflammatory effects. Inhalation injury occurs in up to 40% of patients admitted to hospital following burns. Three stages in the evolution of inhalation injury are described. The early phase (first 48 hours) is associated with pulmonary edema, acute respiratory distress syndrome, airway obstruction, and carbon monoxide and cyanide toxicity. During the middle phase (days to weeks), pneumonia and venous thromboembolism may develop. Late sequelae (months to years post burn injury), while uncommon, include reactive airways dysfunction syndrome, bronchiolitis obliterans and tracheal stenosis. Specific interventions early in the management of inhalation injury are necessary to prevent worsening the injury and minimizing late sequelae.

Analogous to the “triad of anaesthesia” (hypnosis, analgesia and muscle relaxation), analgesia, prevention or control of delirium, and sedation form the ‘triad’ of intensive care pharmacotherapy to facilitate tolerable mechanical ventilation in the critically ill. As in the triad of anaesthesia, agents used primarily for one of these three purposes have additional effects on the other two. In intensive care practice, sedation should therefore not be considered in isolation, but as part of an integrated strategy aimed at minimising patient distress, maximising the efficiency of mechanical ventilation, and facilitating extubation as soon as possible. This review begins by discussing the pharmacology of the agents primarily targeting each component of the ‘triad of intensive care’ , followed by a review of recent research into how these agents should be optimally combined and administered to achieve the best possible patient outcomes.

From a laboratory perspective, conventional respiratory viral tests (antigen detection by immunofluorescence and viral culture) are assumed to be less sensitive than nucleic acid amplification tests (NATs). We systematically reviewed the literature to estimate the diagnostic accuracy of conventional tests compared to NATs as the reference standard, when studied in the pediatric inpatient setting. We searched Medline, Embase, and bibliographies of relevant articles for studies that compared conventional respiratory viral tests to NATs. Descriptions of methodology were appraised using the QUADAS criteria. Thirty-three publications (10297 patients) were included. Viral diagnostic approaches varied considerably. The majority of studies reported less than 70% of QUADAS items. Important flaws comprised a lack of clear criteria for patient selection and the absence of blinding. Study results could not be pooled due to heterogeneity. The sensitivity of conventional tests varied between 0.00 and 1.00, whereas the specificity was mostly higher than 0.90. In conclusion, the sensitivity of conventional tests varied considerably between studies, compared to NATs as the reference standard. Because clinical studies used a large variety of viral test approaches, the anticipated inferiority of conventional viral tests could not be confirmed. International standards are needed to assure efficient viral diagnosis and patient management.

Non-small cell lung cancer [NSCLC] is a major cause of cancer related deaths in the world. In a significant proportion of NSCLC cases, the Epidermal Growth Factor Receptor [EGFR] is over-expressed prompting the development of anti-EGFR therapies. Clinical studies of EGFR tyrosine kinase inhibitors [TKIs] demonstrated an overall response rate of 10% in NSCLC with higher response rates in females, never smokers, adenocarcinoma histology and East Asians. Mutations in exons 18-21 of the EGFR gene appear to be the most important molecular predictors of response to TKIs with response rates of >60% reported in most studies. Consequently screening NSCLC patients for tumours harbouring EGFR mutations will assist in selecting patients for TKI therapy. The gold standard for detecting EGFR mutations has been direct DNA sequencing however the sensitivity of this molecular technique is limited by the amount of tumour DNA is time and resource consuming. Recently several highly sensitive techniques have been developed to detect EGFR mutant DNA in different biological samples. In this review we aim to provide an overview of the clinical relevance of screening for EGFR mutations in NSCLC and recent molecular tests that have been developed for this purpose to allow the reader to critically evaluate the various methodologies that are available.