bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchodilators in critical illness
Authors: Dhand Rajiv , McCormack Michael
Published: April 2016

Inhaled beta-agonists and anticholinergic agents, as well as systemically administered methylxanthines, are frequently employed to achieve bronchodilation in critically-ill patients. Inhaled agents are given by pressurized metered dose inhaler (pMDI), nebulizer, or dry powder inhaler. In ventilator-supported patients, aerosolized agents are generally only administered by pMDI or nebulizer. The ventilator circuit, artificial airway, and circuit humidity complicate the delivery of aerosolized agents, and there is a wide variability in drug delivery efficiency with various bench models of mechanical ventilation. Aerosolized drug by pMDI is affected by the use of spacer devices, synchronization of pMDI actuation and ventilator breath delivery, and appropriate priming of the pMDI device. The efficiency of aerosolized drug delivery by jet nebulization is also affected by device placement in the circuit, as well as by a number of other factors. Several investigators have demonstrated comparable efficiency of aerosol delivery with mechanically-ventilated and ambulatory patients when careful attention is given to the technique of administration. Appropriate administration of aerosolized bronchodilators in patients receiving invasive or non-invasive positive pressure ventilation produces significant therapeutic effects.
Vasopressors in critical illness
Authors: De Backer Daniel , Biston Patrick
Published: April 2016

Vasopressors are used in various shock states to correct hypotension, aiming at restoring or improving organ and tissue perfusion. Vasopressor therapy may be associated with excessive vasoconstriction, but also metabolic and other side-effects. Hence, the ideal target for arterial pressure remains undetermined. Adrenergic agents remain the most commonly used vasopressor agents. Adrenergic agents increase arterial pressure through stimulation of alpha-adrenergic receptors. The effects of the different adrenergic agents differ mostly due to variable associated beta-adrenergic effects. Epinephrine and norepinephrine are strong and equipotent vasopressor agents. Their impact on outcome is as yet unanswered, but there is no sign that epinephrine might be associated with better outcomes. Accordingly, norepinephrine is the adrenergic agent of choice, especially in patients with cardiogenic shock. Vasopressin is a non-adrenergic vasopressor acting via V1 receptor stimulation, with weak vasopressor effects in normal conditions, but markedly increased vascular tone in shock states, especially in septic shock. Splanchnic vasoconstriction may occur. Arginine vasopressin at low doses appears to be a promising alternative to adrenergic agents, but its exact place is not yet well defined.
Inotropic agents in critical illness
Authors: Fayssoil Abdallah , Annane Djillali
Published: April 2016

Inotropes are drugs commonly used in the intensive care unit. This class of agents includes a broad variety of molecules that improve cardiac index by increasing intracellular concentrations of cyclic AMP, or sensitivity to intracellular calcium, or by inhibiting the sodium/potassium pump. The main inotropic agents available are digoxin, catecholamines, and non-catecholergic drugs, e.g. phosphodiesterase inhibitors and levosimendan. In practice, dobutamine, a beta1 and beta2 agonist, is the inotrope of choice in patients with acute heart failure, or in patients with severe sepsis and evidence for left ventricle dysfunction. Levosimendan may be an alternative choice in patients with severe heart failure, particularly for those previously treated with beta-blockers. The main serious adverse events related to any inotrope are life-threatening arrhythmias.
Pulmonary vasodilators in critical illness
Authors: Chousterman Benjamin , Payen Didier
Published: April 2016

Pulmonary vasodilators (PV) are commonly used in the intensive care unit (ICU) to treat pulmonary hypertension and/or hypoxaemia. The choice of drug is based on its pharmacokinetic and pharmacodynamic properties. The inhaled route of administration is preferred to treat hypoxaemia as it improves the ventilation/perfusion ratio. Systemic administration of PVs can lead to a decrease of mean arterial pressure and a worsening of hypoxaemia. Despite their beneficial effects, PVs have not shown improvement in mortality in acute respiratory distress syndrome patients. Rebound of hypoxaemia and/or pulmonary arterial hypertension should be prevented during PV treatment discontinuation with a slow de-escalation protocol. This chapter reviews the use of the main PV available for use in the ICU.
Hormone therapies in critical illness
Authors: Cooper Mark S.
Published: April 2016

A range of hormonal manipulations have been proposed as adjunctive therapy during critical care. These therapies might be used to treat a pre-existing or acquired hormonal disorder. Additionally, hormonal manipulation has been suggested to alter the long-term outcome of critical illness, even in patients without structural abnormalities of endocrine glands. Currently, the effectiveness of these anabolic therapies has not been established and they might be harmful in some patient groups. Recently, it has been recognized that many critically-ill patients have low levels of vitamin D and this is associated with an adverse outcome. It is still unclear whether replacement of vitamin D will be effective in improving outcome. This chapter will also highlight the importance of recognizing and addressing hormonal deficiency in patients with known pituitary disease and with traumatic brain injury (TBI). TBI is associated with a high prevalence of acute and long-term pituitary dysfunction. The management of the rare, but important thyroid disorders requiring critical care, thyroid storm, and myxoedema coma, will also be discussed.
Artificial ventilation in cardiopulmonary resuscitation
Authors: Soar Jasmeet , Nolan Jerry P.
Published: April 2016

When cardiac arrest occurs, cardiopulmonary resuscitation (CPR) should be started with chest compressions first. The use of ventilations is determined by the training of rescuers, their ability and willingness to provide rescue breaths, patient characteristics, and the underlying cause of the cardiac arrest. Trained rescuers should give two ventilations after every 30 compressions, or once the airway is secured with a tracheal tube, ventilate the patient at 10 breaths/min without any pause in chest compressions. Rescuers who are unable or unwilling to provide effective ventilation, while awaiting expert help should use compression-only CPR. Ventilations are needed for the treatment of cardiac arrest in children, when arrest is from a primary respiratory cause, or during a prolonged cardiac arrest. Choice of ventilation technique depends on rescuer skills and the airway used. Effective oxygenation and ventilation can be maintained during CPR with a tidal volume of approximately 500 mL given over an inspiratory time of 1 second. Rescuers should give supplemental oxygen in as high a concentration as possible during CPR in order to rapidly correct tissue hypoxia. Once restoration of a spontaneous circulation has been achieved the inspired oxygen should be adjusted to maintain oxygen saturation between 94 and 98%.
Therapeutic strategies in managing cardiac arrest
Authors: Field John
Published: April 2016

Emergency and critical care specialists are important interdisciplinary physicians who often impact on the long-term survival of patients sustaining cardiac arrest, as well as immediate outcomes. These specialists are often at the crossroads of survival for patients achieving return of spontaneous circulation, and it is important to appreciate that out-of-hospital and in-hospital cardiac arrest patients represent different pathophysiological subgroups with respect to aetiology and pathophysiology. Important time-dependent triage and therapy are crucial, and efforts to identify and treat pathophysiological triggers share priority with the initiation of hypothermia protocols and other targeted interventions, such as coronary angiography and percutaneous coronary intervention. Updated basic life support (BLS) and advanced life support (ACLS) protocols emphasize the importance of high quality chest compressions as central to achieving return of spontaneous circulation and emphasize that airway interventions should not detract from this objective. No specific ACLS intervention including intubation, vasopressor therapy or use of anti-arrhythmic agents has been found to improve outcome. The goal of both BLS and ACLS protocols is the achievement of return of spontaneous circulation, the prevention of re-arrest and the initiation of immediate post-resuscitation interventions associated with improved outcome. These include targeted temperature management (induced hypothermia) and coronary angiography for appropriate patients and ‘bundled’ critical care for all recognizing that the post-arrest state is a systemic inflammatory condition requiring multidisciplinary care beyond hypothermia and cardiovascular support.
Post-cardiac arrest arrhythmias
Authors: Jumean Marwan F. , Link Mark S.
Published: April 2016

Our understanding of arrhythmias following resuscitated cardiac arrest has evolved over the past two decades to entail complex pathophysiological processes including, in part, ischaemia and ischaemia-reperfusion injury. Electrical instability after the return of spontaneous circulation (ROSC) is common, ranging from atrial fibrillation to recurrent ventricular tachycardia and fibrillation. Electrical instability following out-of-hospital cardiac arrest is most commonly due to myocardial ischaemia and post-arrest myocardial dysfunction. However, electrolyte disturbances, elevated catecholamine levels, the frequent use of vasopressors and inotropes, and underlying structural heart disease or channelopathies also contribute in the acute setting. Limited data exists that specifically address the management of arrhythmias in the immediate post-arrest period. In addition to treating any potential reversible cause, the management in the haemodynamically-stable patient includes beta-blockers, class I (lignocaine and procainamide) and III anti-arrhythmic agents (amiodarone). Defibrillation is often needed for recurrent ventricular arrhythmias.
Choice of resuscitation fluid
Authors: Myburgh John , Hammond Naomi E.
Published: April 2016

Fluid resuscitation is a ubiquitous intervention in critically-ill patients. There is wide variation in practice and emerging evidence that the choice of resuscitation fluid may affect outcome in selected patient populations. It is likely that beneficial or adverse effects relate not only to the physicochemical properties of the fluid but also to the volume (dose) and rate of administration. Interstitial oedema is a common side-effect associated with all fluids and its development is associated with organ dysfunction. Crystalloids should be first-choice resuscitation fluids for almost all patients, with evidence that balanced salt solutions confer any benefit over saline being limited to observational data. Consideration of serum sodium (or osmolality), pH, renal function and coagulation status may affect selection of a specific crystalloid solution. On the balance of evidence, colloids do not confer any clinical advantage over crystalloids and they should be used with caution, if at all. Albumin is contraindicated for the resuscitation of patients with severe traumatic brain injury. Hydroxyethyl starch is associated with increased risk of death and acute kidney injury in critically-ill patients, particularly those with severe sepsis and septic shock. Current evidence does not support the use of other semi-synthetic colloids for resuscitation.
Therapeutic goals of fluid resuscitation
Authors: Staitieh Bashar S. , Martin Greg S.
Published: April 2016

Optimizing tissue perfusion by administering intravenous fluids presents a special challenge to the intensive care unit (ICU) clinician. Recent studies have drastically altered how we assess a patient’s fluid responsiveness, particularly with regard to upstream surrogates of tissue perfusion. Central venous pressure and pulmonary capillary wedge pressure have been found to be inaccurate markers of fluid responsiveness and have given way to methods such as cardiac output as assessed by echocardiography and the various forms of arterial waveform analysis. These newer techniques, such as stroke volume variation, systolic pressure variation, and pulse pressure variation, have been found to better delineate which patients will respond to a fluid challenge with an increase in cardiac output, and which will not. In addition, traditional methods of assessing the consequences of excessive fluid administration, such as pulmonary oedema and the non-anion gap acidosis of saline administration, have given way to more sophisticated measurements of extravascular lung water, now available at the bedside. Downstream markers of tissue perfusion, such as base deficit, central venous oxygen saturations, and lactic acid, continue to be useful in particular clinical settings, but are all relatively non-specific markers, and are therefore difficult to use as resuscitation targets for ICU patients in general. Finally, recent data on septic shock and ARDS have demonstrated the importance of conservative fluid strategies, while data in surgical populations have emphasized the need for judicious fluid administration and attention to the balance of blood products used in resuscitation efforts.
Blood gas analysis in the critically ill
Authors: Joynt Gavin M. , Choi Gordon Y. S.
Published: April 2016

Arterial blood gases allow the assessment of patient oxygenation, ventilation, and acid-base status. Blood gas machines directly measure pH, and the partial pressures of carbon dioxide (PaCO2) and oxygen (PaO2) dissolved in arterial blood. Oxygenation is assessed by measuring PaO2 and arterial blood oxygen saturation (SaO2) in the context of the inspired oxygen and haemoglobin concentration, and the oxyhaemoglobin dissociation curve. Causes of arterial hypoxaemia may often be elucidated by determining the alveolar–arterial oxygen gradient. Ventilation is assessed by measuring the PaCO2 in the context of systemic acid-base balance. A rise in PaCO2 indicates alveolar hypoventilation, while a decrease indicates alveolar hyperventilation. Given the requirement to maintain a normal pH, functioning homeostatic mechanisms result in metabolic acidosis, triggering a compensatory hyperventilation, while metabolic alkalosis triggers a compensatory reduction in ventilation. Similarly, when primary alveolar hypoventilation generates a respiratory acidosis, it results in a compensatory increase in serum bicarbonate that is achieved in part by kidney bicarbonate retention. In the same way, respiratory alkalosis induces kidney bicarbonate loss. Acid-base assessment requires the integration of clinical findings and a systematic interpretation of arterial blood gas parameters. In clinical use, traditional acid-base interpretation rules based on the bicarbonate buffer system or standard base excess estimations and the interpretation of the anion gap, are substantially equivalent to the physicochemical method of Stewart, and are generally easier to use at the bedside. The Stewart method may have advantages in accurately explaining certain physiological and pathological acid base problems.
The difficult intubation in the ICU
Authors: Frass Michael
Published: April 2016

Airway management in the intensive care unit differs from conventional controlled settings such as general anaesthesia in the operating room (OR). Due to adequate patient preparation and positioning in the OR, endotracheal intubation is usually easy to perform. However, in the intensive care setting, endotracheal intubation is often difficult or impossible because patients are not prepared and intubation is immediately necessary without sufficient time for putting together technical and pharmaceutical equipment. As an alternative, non-invasive alternate airway management may be performed. Besides non-invasive ventilation via mask or helmet, the use of Combitube®, EasyTubeTM, and different types of laryngeal mask airway are described, in order to alleviate decision-making in emergency situations such as difficult intubation, vomiting and bleeding patients, small interincisor distance, etc.
The surgical airway in the ICU
Authors: Groves Danja S. , Durbin Charles G.
Published: April 2016

Tracheostomy is the most commonly performed (elective) surgical procedure in critically-ill patients. Compared with translaryngeal intubation, tracheostomy improves patient comfort, and leads to shorter length of intensive care unit and hospital stay. It relieves upper airway obstruction, protects the larynx and upper airway from damage, allows access to the lower airway for secretion removal, and provides a stable airway for patients requiring prolonged mechanical ventilation or oxygenation support. Timing of tracheostomy remains controversial and should be individualized; however, early tracheostomy (within 7 days) seems to be beneficial in certain patient populations (head injury, medically critically ill). The evolution of percutaneous techniques are rapidly reducing need for surgical tracheostomy and bedside techniques are safe and efficient, allowing timely tracheostomy with low morbidity. Cricothyrotomy is an emergency surgical airway used to save a life when all attempts at securing a patent airway fail and arrest is eminent. Techniques, timing, risks, benefits, as well as contraindications of the surgical airway in critically-ill patients are discussed in this chapter.
Hypoxaemia in the critically ill
Authors: Leaver Susannah , Evans Timothy
Published: April 2016

Hypoxaemia is a reduction in the partial pressure of oxygen in the blood below 8 kPa/60 mmHg. Hypoxaemia results from one, or several, or a combination of causes. Calculating the alveolar–arterial gradient can help to delineate the cause. Acute respiratory failure manifests in a number of ways, the most sensitive indicator being an increased respiratory rate. Diagnosis is dependent on a comprehensive history, examination in combination with appropriate blood tests, and imaging. Hypoxaemia is the final common pathway of a number of conditions and the exact cause may not be immediately apparent. Despite this, the same management principles apply. A trial of non-invasive ventilation can be used to support patients during respiratory failure who do not require immediate endotracheal intubation. However, it is recommended that this is instituted for a preset trial period (e.g. 1–2 hours) in an HDU/ICU setting where facilities for definitive airway management are available. Invasive ventilation aims to facilitate treatment of the underlying condition whilst minimizing side effects through lung protective ventilatory strategies.
Physiology of positive-pressure ventilation
Authors: Hedenstierna Göran , Rothen Hans Ulrich
Published: April 2016

During positive pressure ventilation the lung volume is reduced because of loss of respiratory muscle tone. This promotes airway closure that occurs in dependent lung regions. Gas absorption behind the closed airway results sooner or later in atelectasis depending on the inspired oxygen concentration. The elevated airway and alveolar pressures squeeze blood flow down the lung so that a ventilation/perfusion mismatch ensues with more ventilation going to the upper lung regions and more perfusion going to the lower, dependent lung. Positive pressure ventilation may impede the return of venous blood to the thorax and right heart. This raises venous pressure, causing an increase in systemic capillary pressure with increased capillary leakage and possible oedema formation in peripheral organs. Steps that can be taken to counter the negative effects of mechanical ventilation include an increase in lung volume by recruitment of collapsed lung and an appropriate positive end-expiratory pressure, to keep aerated lung open and to prevent cyclic airway closure. Maintaining normo- or hypervolaemia to make the pulmonary circulation less vulnerable to increased airway and alveolar pressures, and preserving or mimicking spontaneous breaths, in addition to the mechanical breaths, since they may improve matching of ventilation and blood flow, may increase venous return and decrease systemic organ oedema formation (however, risk of respiratory muscle fatigue, and even overexpansion of lung if uncontrolled).
Non-invasive positive-pressure ventilation
Authors: Spoletini Giulia , Hill Nicholas S.
Published: April 2016

Non-invasive ventilation (NIV) has been increasingly used over the past decades to avoid endotracheal intubation (ETI) in critical care settings. In selected patients with acute respiratory failure, NIV improves the overall clinical status more rapidly than standard oxygen therapy, avoids ETI and its complications, reduces length of hospital stay, and improves survival. NIV is primarily indicated in respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema and associated with immunocompromised states. Weaker evidence supports its use in other forms of acute hypercapnic and hypoxaemic respiratory failure. Candidates for NIV should be carefully selected taking into consideration the risk factors for NIV failure. Patients on NIV who are unstable or have risk factors for NIV failure should be monitored in an intensive or intermediate care units by experienced personnel to avoid delay when intubation is needed. Stable NIV patients can be monitored on regular wards.
Design and function of mechanical ventilators
Authors: Chatburn Robert L. , Mireles-Cabodevila Eduardo
Published: April 2016

This chapter presents a new approach to understanding the design and function of mechanical ventilators. Mechanical ventilators have become so complex that a practical classification system or taxonomy is required to compare and contrast treatment options. This chapter describes the 10 fundamental maxims from which we construct a taxonomy to describe each mode of mechanical ventilation. This method provides a framework for the comparison of published studies of mechanical ventilation, gives consistency in education and clinical practice. It also allows comparisons between different ventilator manufacturers and, most importantly, it provides a framework to match modes to specific patient needs.
Respiratory support with positive end-expiratory pressure
Authors: Martin-Loeches Ignacio , Artigas Antonio
Published: April 2016

Positive-end-expiratory pressure (PEEP) is the pressure present in the airway (alveolar pressure) above atmospheric pressure that exists at the end of expiration. The term PEEP is defined in two particular settings. Extrinsic PEEP (applied by ventilator) and intrinsic PEEP (PEEP caused by non-complete exhalation causing progressive air trapping). Applied (extrinsic) PEEP—is usually one of the first ventilator settings chosen when mechanical ventilation (MV) is initiated. Applying PEEP increases alveolar pressure and volume. The increased lung volume increases the surface area by reopening and stabilizing collapsed or unstable alveoli. PEEP therapy can be effective when used in patients with a diffuse lung disease with a decrease in functional residual capacity. Lung protection ventilation is an established strategy of management to reduce and avoid ventilator-induced lung injury and mortality. Levels of PEEP have been traditionally used from 5 to 12 cmH2O; however, higher levels of PEEP have also been proposed and updated in order to keep alveoli open, without the cyclical opening and closing of lung units (atelectrauma). The ideal level of PEEP is that which prevents derecruitment of the majority of alveoli, while causing minimal overdistension; however, it should be individualized and higher PEEP might be used in the more severe end of the spectrum of patients with improved survival. A survival benefit for higher levels of PEEP has not been yet reported for any patient under MV, but a higher PaO2/FiO2 ratio seems to be better in the higher PEEP group.
Pressure support ventilation
Authors: Aguirre-Bermeo Hérnan , Mancebo Jordi
Published: April 2016

Pressure support ventilation (PSV) is one of the most common ventilatory modalities used in intensive care units. PSV is an assisted, pressure-limited, and flow-cycled ventilatory mode. The ventilator provides assistance when the patient makes a breathing effort, and when inspiratory flow reaches a certain threshold level, cycling to exhalation occurs. PSV unloads respiratory muscle effort, while allowing the patient to retain control over the respiratory rate and tidal volume. Withdrawal from mechanical ventilation should be performed with a gradual reduction of levels of support until extubation. Asynchronies can be present during PSV and are typically associated with high levels of support. A closed-loop modality, which adjusts support levels to keep the patient in a ‘comfort zone’, has been designed to assist in the withdrawal of mechanical ventilation. It performs at least as well as experienced medical staff and could be useful in specific groups of patients.
High-frequency ventilation and oscillation
Authors: Cuartero Mireia , Ferguson Niall D.
Published: April 2016

High-frequency oscillatory ventilation (HFOV) is a key member of the family of modes called high-frequency ventilation and achieves adequate alveolar ventilation despite using very low tidal volumes, often below the dead space volume, at frequencies significantly above normal physiological values. It has been proposed as a potential protective ventilatory strategy, delivering minimal alveolar tidal stretch, while also providing continuous lung recruitment. HFOV has been successfully used in neonatal and paediatric intensive care units over the last 25 years. Since the late 1990s adults with acute respiratory distress syndrome have been treated using HFOV. In adults, several observational studies have shown improved oxygenation in patients with refractory hypoxaemia when HFOV was used as rescue therapy. Several small older trials had also suggested a mortality benefit with HFOV, but two recent randomized control trials in adults with ARDS have shed new light on this area. These trials not show benefit, and in one of them a suggestion of harm was seen with increased mortality for HFOV compared with protective conventional mechanical ventilation strategies (tidal volume target 6 mL/kg with higher positive end-expiratory pressure). While these findings do not necessarily apply to patients with severe hypoxaemia failing conventional ventilation, they increase uncertainty about the role of HFOV even in these patients.
Prone positioning in the ICU
Authors: Taccone Paolo , Chiumello Davide
Published: April 2016

Prone positioning (also known as ‘proning’, ‘prone manoeuvre’ or ‘prone ventilation’) refers to mechanical ventilation with patients positioned in prone position in contrast of standard supine (flat or semi-recumbent) position. The use of the prone positioning was proposed over 30 years ago as a means to improve arterial oxygenation in patients with acute respiratory distress syndrome (ARDS). Since then, extensive physiological research has been conducted to explore the possible mechanisms underlying the observed improvement in gas exchange, which involve changes in the distribution of both ventilation and pulmonary blood flow. Furthermore, it has been shown that, independently of gas exchange, prone positioning may reduce the harm of mechanical ventilation, which is known to adversely impact patient survival. In this chapter we will summarize the physiological effect of prone positioning, as well as the clinical evidences supporting its use to reduce mortality in patients with ARDS.
Failure to ventilate in critical illness
Authors: Fanelli Vito , Ranieri V. Marco
Published: April 2016

Mechanical ventilation is an efficacious therapy to respiratory failure because it improves gas exchange and rests respiratory muscles. During controlled mechanical ventilation, a patient’s inspiratory muscles are resting and the ventilator delivers a preset tidal volume through the generation of inspiratory flow, overcoming resistive and elastic thresholds of the respiratory system. During assisted ventilation, the same goal is reached through an interplay between the patient’s inspiratory muscles and ventilator. Every perturbation of this interaction causes patient ventilator asynchrony and exposes to the risk of failure to ventilate. Patient–ventilator asynchrony may occur at each stage of assisted breath Signs of patient’s discomfort, the use of accessory muscles, tachycardia, hypertension, and assessment of flow and airway pressure traces displayed on modern ventilators, helps to detect asynchronies. Prompt recognition and intervention to improve patient–ventilator interaction may expedite liberation from mechanical ventilation, and reduce intensive care unit and length of hospital stay.
Assessment and technique of weaning
Authors: Tobin Martin J.
Published: April 2016

Several studies suggest that most patients weaned successfully could have tolerated the weaning attempts had they been initiated a day or so earlier. Such data emphasize the need for the early use of screening tests. A screening test should have a high sensitivity. The ratio of respiratory frequency to tidal volume has been evaluated in more than 25 studies and its average sensitivity is 0.89. Weaning involves undertaking three diagnostic tests in sequence, measuring predictors, a weaning trial, and a trial of extubation. Of the techniques used for a weaning trial, intermittent mandatory ventilation has been repeatedly shown to be inferior to the use of T-tube trials or pressure support. Six randomized trials have evaluated the usefulness of protocols in the management of weaning. Three revealed no benefit—two had major methodological problems, leaving only one supporting the use of protocols.
Weaning failure in critical illness
Authors: Carlucci Annalisa , Navalesi Paolo
Published: April 2016

Weaning failure has been defined as failure to discontinue mechanical ventilation, as assessed by the spontaneous breathing trial, or need for re-intubation after extubation, so-called extubation failure. Both events represent major clinical and economic burdens, and are associated with high morbidity and mortality. The most important mechanism leading to discontinuation failure is an unfavourable balance between respiratory muscle capacity and the load they must face. Beyond specific diseases leading to loss of muscle force-generating capacity, other factors may impair respiratory muscle function, including prolonged mechanical ventilation, sedation, and ICU-acquired neuromuscular dysfunction, potentially consequent to multiple factors. The load depends on the mechanical properties of the respiratory system. An increased load is consequent to any condition leading to increased resistance, reduced compliance, and/or occurrence of intrinsic positive-end-expiratory pressure. Noteworthy, the load can significantly increase throughout the spontaneous breathing trial. Cardiac, cerebral, and neuropsychiatric disorders are also causes of discontinuation failure. Extubation failure may depend, on the one hand, on a deteriorated force-load balance occurring after removal of the endotracheal tube and, on the other hand, on specific problems. Careful patient evaluation, avoidance and treatment of all the potential determinants of failure are crucial to achieve successful discontinuation and extubation.
Extracorporeal respiratory and cardiac support techniques in the ICU
Authors: Westrope Claire , Peek Giles
Published: April 2016

Extra corporeal life support (ECLS) is an essential tool for the modern intensivist and surgeon. The addition of extracorporeal therapy should be considered in all cases when pathology is potentially reversible and conventional therapy is clearly failing. ECLS is a general term to describe prolonged, but temporary support of heart and lung function using mechanical devices, which has developed as an extension of cardiopulmonary bypass techniques used in the operating theatre. Use in adult severe respiratory and cardiac failure is increasing following significant advances in ECLS techniques learnt from paediatric and neonatal experiences, and successful use of extra corporeal membrane oxygenation in the 2009 and 2001 H1N1 (swine flu) outbreaks. This chapter describes the techniques required for providing successful ECLS in adult respiratory and cardiac failure.
Treating respiratory failure with extracorporeal support in the ICU
Authors: Bellani Giacomo , Pesenti Antonio
Published: April 2016

During extracorporeal support or extracorporeal membrane oxygenation (ECMO) blood is diverted from the patient to an artificial lung for gas exchange, then returned into the patient’s circulation once arterialized. While a low-blood-flow bypass can remove comparatively high amounts of CO2, oxygenation is limited by venous haemoglobin saturation and requires high flows. Several technical improvements led to a profound change in the safety and applicability of ECMO in recent years, even permitting the transfer of patients undergoing ECMO. ECMO has been proposed as salvage therapy for the most severe acute respiratory distress syndrome patients—warranting viable levels of oxygenation. In 2009, the ‘CESAR’ trial provided formal evidence in favour of ECMO application in adults with ARDS. An important indication for the early use of ECMO in ARDS came from the outbreaks of H1N1 influenza, when several countries set up networks aimed at coordinating the application of ECMO. Recent reports suggest the use of ECMO in less severe patients with the purpose of removing CO2, decreasing the need for ventilation and ventilator-induced lung injury,
Therapeutic strategy in acute respiratory distress syndrome
Authors: Summers Charlotte , Bellingan Geoffrey
Published: April 2016

Acute respiratory distress syndrome (ARDS) is a pathological syndrome characterized by arterial hypoxaemia and bilateral pulmonary infiltrates. Until recently, the diagnosis of ARDS was made in accordance with the American–European Consensus Conference criteria established in 1994, although an updated ‘Berlin’ definition was produced in 2012. It is important to remember that ARDS is not a single disease, but rather a constellation of conditions with similar pathophysiology, and thus there may not be one unifying clinical treatment. The mainstay of ARDS management is the identification and treatment of the predisposing condition, surveillance for the presence of intercurrent infection, and supportive care, including lung-protective ventilation, and even prone ventilation in more severe cases. Fluid restriction, after patients are appropriately resuscitated, is probably of benefit. Despite many clinical trials, there are currently no licensed pharmacological therapies for ARDS, however a number of novel agents are under development.
Pathophysiology and therapeutic strategy of respiratory alkalosis
Authors: Langer Thomas , Caironi Pietro
Published: April 2016

Respiratory alkalosis is a condition characterized by low partial pressure of carbon dioxide and an associated elevation in arterial pH caused by an imbalance between CO2 production and removal, in favour of the latter. Conditions that cause increased alveolar ventilation, without having a reduction in pH as input stimulus, will cause hypocapnia associated with a variable degree of alkalosis. The major effect of hypocapnia is the increase in pH (alkalosis) and the consequent shift of electrolytes that occurs in relation to it. As a general law, in plasma, anions will increase, while cations will decrease. The acute reduction in ionized calcium, due to the change in extracellular pH, may cause neuromuscular symptoms ranging from paraesthesias, to tetany and seizures. The effect on urine is an increase in urinary strong ion difference/urinary anion gap and a consequent increase in urinary pH. Finally, acute hypocapnic alkalosis causes a constriction of cerebral arteries that can lead to a reduction of cerebral blood flow. The clinical approach to respiratory alkalosis is usually directed toward the diagnosis and treatment of the underlying clinical disorder.
Pathophysiology of pneumonia
Authors: Rello Jordi , Borgatta Bárbara
Published: April 2016

Airway colonization, ventilator-associated tracheobronchitis (VAT), and hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) are three manifestations having the presence of micro-organisms in airways in common. Newer definitions have to consider worsening of oxygenation, in addition to purulent respiratory secretions, chest-X rays opacities, and biomarkers of inflammation. Bacteria are the main causes of HAP/VAP. During hospitalization there’s a shift of airway’s colonizing flora from core organisms to enteric and non-fermentative ones. Macro- and micro-aspiration is the most important source of pneumonia. Endotracheal tube secretion leakage is an important source, serving biofilm as a reservoir. Exogenous colonization is infrequent, but it may contribute to cross-infection with resistant species. Prevention of VAP can be achieved by implementing multidisciplinary care bundles focusing on oral/hand hygiene and control of sedation. Pneumonia develops when micro-organisms overwhelm host defences, resulting in a multifocal process. Risk and severity of pneumonia is determined by bacterial burden, organism virulence and host defences. Innate and adaptive immune responses are altered, decreasing clearing of pathogens. Some deficits of the complement pathway in intubated patients are associated with increased risk for VAP and higher mortality. Micro-arrays have demonstrated specific different immunological signatures for VAP and VAT. Early antibiotic therapy is associated with a decrease in early HAP/VAP incidence, but selects for MDR organisms. Attributable mortality is lower than 10%, but HAP/VAP prolongs length of stay, and dramatically increase costs and use of health care resources.
Diagnosis and management of nosocomial pneumonia
Authors: Chastre Jean
Published: April 2016

Quantitative culture techniques, performed before the introduction of new antibiotics, enable physicians to identify most patients who need immediate treatment for nosocomial pneumonia, and help select optimal therapy in a safe, well-tolerated manner. These techniques avoid resorting to broad-spectrum coverage of all patients with a clinical suspicion of infection, and may minimize the emergence of resistant micro-organisms in the intensive care unit. However, the full impact of this decision tree on patient outcome remains controversial. Antimicrobial therapy of patients with nosocomial pneumonia is a two-stage process. The first stage involves administering broad-spectrum antibiotics at doses maximizing bacterial killing as soon as possible to avoid inadequate treatment in patients with true bacterial pneumonia. The second stage focuses on trying to achieve this objective without overusing or abusing antibiotics. This will need the combination of a number of different steps, including commitment to focused and narrow treatment once the aetiological agents are known, switching to monotherapy after day 3, and shortening duration of therapy to 7–8 days in most patients, as dictated by the patient’s clinical response and microbiological information.
Diagnosis and management of atypical pneumonia
Authors: Langer Martin , Carretto Edoardo
Published: April 2016

‘Atypical pneumonia’ is an old, but successful term, which covers respiratory infections caused by different micro-organisms, causing similar clinical symptoms, and characterized by similar antimicrobial sensitivity/resistance. Out of specific epidemic contexts, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumonia are the micro-organisms involved, L. pneumophila being by far the most frequently involved in severe community-acquired ‘atypical’ pneumonia. It is important to suspect ‘atypical’ pneumonia on the basis of clinical presentation and the correlated extrapulmonary symptoms. Knowledge of symptoms leads to suspicion and, consequently, to timely and adequate empiric treatment and proper diagnostic work-up. Standard microbiological diagnosis is based on urinary antigen test for L. pneumophila and on serology for the other pathogens. A culture should be performed if legionellosis is suspected. NATs techniques could be the future diagnostic tests. Close collaboration with the microbiologist will improve the diagnosis.
Chest physiotherapy and tracheobronchial suction in the ICU
Authors: Li Bassi Gianluigi , Marti J. D.
Published: April 2016

The airway lining fluid is a biphasic layer covering the respiratory tract epithelium. It has antimicrobial and immunomodulatory properties, and it is formed by a gel-phase (mucus), and a low-viscosity inner layer (sol-phase) that provides lubrication for ciliary beating. Mucus is continuously cleared from the airways through the ciliated epithelium and via the two-phase gas–liquid flow mechanism (i.e. coughing). Mucus production in healthy subjects is approximately 10–100 mL/day. Whereas, mucociliary clearance rates range between 4 and 20 mm/min. Critically-ill, mechanically-ventilated patients often retain mucus. Several chest physiotherapy techniques are applied to promote mucus clearance in these patients. The role of chest physiotherapy in mechanically-ventilated patients is debated, due to the lack of evidence from well-designed clinical trials. Retained mucus is aspirated through tracheobronchial suctioning. Closed suctioning is beneficial in patients with severe lung failure and at risk of alveolar collapse upon ventilator disconnection.
Toilet bronchoscopy in the ICU
Authors: Li Bassi Gianluigi , Agusti Carles
Published: April 2016

Critically-ill patients retain respiratory secretions. Toilet bronchoscopy is applied to aspirate retained secretions and revert lung atelectasis. Toilet bronchoscopy is particularly indicated when retained secretions are visible during the procedureand air-bronchograms are not present at the chest radiograph. Yet, toilet bronchoscopy should only be applied when other less invasive methods of secretion removal have failed. Ventilatory settings during the intervention, the inspiratory fraction of oxygen should be increased to 100%. In volume control ventilation, the pressure limit alarm needs to be increased; during pressure-controlled ventilation, the set inspiratory pressure should be increased. The external PEEP should be decreased to at least 50% of the baseline values, to prevent barotrauma. The use of sedatives, analgesics, and topical anaesthetics is mandatory to achieve favourable procedural condition. Toilet bronchoscopy is also feasible and safe in critically-ill patients undergoing non-invasive ventilation.
Pathophysiology of pleural cavity disorders
Authors: Chiumello Davide , Mietto Cristina
Published: April 2016

The pleural cavity is normally a virtual space that is essential to guarantee the mechanical coupling between the lung and the chest wall. The volume of pleural liquid is determined by the equilibrium of fluid turnover. The determinants of this balance are the Starling forces, the lymphatic drainage, and the active trans-membrane transport. When fluid or air accumulate inside the pleural cavity, pleural pressure rises to atmospheric level causing the lung to collapse while the chest wall to expand. The displacement is not equally distributed between lung and chest wall, because it depends upon their own compliance. Pneumothorax and pleural effusion are common diseases in critically-ill patients. Pneumothorax is divided in two groups based upon the aetiological mechanism—spontaneous and traumatic. Pleural effusion is classified as transudates or exudates, mainly based on protein content; this classification comprises different pathological mechanisms beneath the two kind of pleural effusion.
Therapeutic approach in haemoptysis
Authors: Blasi Francesco , Tarsia Paolo
Published: April 2016

The aim of diagnostic studies in patients with haemoptysis is two-fold—locate the source of bleeding and identify the underlying cause. A chest X-ray may be informative regarding conditions involving the lung parenchyma, pulmonary vasculature, or the heart, but may be normal in 20–40% of cases. A chest CT scan may allow correct localization of the bleeding site in 65–100% of cases. Contrast-enhanced CT scans allow high resolution angiographic studies that may be useful prior to planning bronchial arterial embolization. Bronchoscopy may allow identification of the site of bleeding, identify the underlying cause, help clear the airways from blood clots favouring gas exchange, and be a means to stop the bleeding. Treatment of haemoptysis varies from outpatient management to intensive care unit admittance. Choice of optimal management depends on the intensity of bleeding, degree of respiratory compromise, and severity of underlying cardiorespiratory status. Important steps in the management of patients with massive haemoptysis include resuscitation, airway protection and patient stabilization as the priority, subsequent localization of the site of bleeding, and specific interventions to stop the bleeding and prevent recurrence. Bronchoscopy may be useful in stopping bleeding through use of cold saline lavage, use of topical vasoconstrictive agents, or temporary endobronchial tamponade with a balloon catheter. The procedure of choice in many cases is selective bronchial artery embolization. With this procedure immediate control of bleeding may be obtained in 70–95% of patients, although recurrence has been reported in 10–30% of cases.
Right ventricular function in the ICU
Authors: Vieillard-Baron Antoine
Published: April 2016

Under normal conditions, the right ventricle (RV) virtually acts as a passive conduit. In critically-ill patients many situations induce uncoupling between the right ventricle and pulmonary circulation, leading to RV systolic dysfunction, then failure. Mechanical ventilation has a major impact by decreasing RV preload, but also significantly increasing RV afterload. RV function should thus always be interpreted and re-evaluated in the light of respiratory mechanics and ventilator settings. RV systolic function is key to the patient’s haemodynamic profile and must be monitored to achieve optimal haemodynamic management. Echocardiography is the best compromise between clinical effectiveness and invasiveness to monitor RV function. A limitation is its inability to monitor haemodynamics continuously. Acute cor pulmonale is defined by the combination of RV dilatation with paradoxical septal motion during systole. In conclusion, RV function monitoring is strongly recommended in many situations encountered in the intensive care unit, such as ARDS, septic shock, and pulmonary embolism. Many devices are available, but echocardiography constitutes the best compromise between accuracy and invasiveness.