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Chronic Critical Illness: the Price of Survival

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Chronic Critical Illness: the Price of Survival View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia DOI: 10.1111/eci.12547 REVIEW Chronic critical illness: the price of survival Alessandro Marchioni, Riccardo Fantini, Federico Antenora, Enrico Clini and Leonardo Fabbri Respiratory Disease Clinic Department of Oncology, Haematology and Respiratory Disease, University of Modena and Reggio Emilia, Modena, Italy ABSTRACT Background The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients. Materials & Methods No absolute definition of the disease is currently available, although most patients are characterized by the need for prolonged mechanical ventilation. Mortality rates are still high even after dismissal from intensive care unit (ICU) and transfer to specialized rehabilitation care settings. Results In recent years, some studies have tried to clarify the pathophysiological characteristics underlying chronic critical illness (CCI), a disease that is also characterized by severe endocrine and inflammatory impair- ments, partly accounting for the almost constant set of symptoms. Discussion Currently, no specific treatment is available. However, a strategic early therapeutic approach on ICU admission might try to prevent the progress of the acute disease towards chronic critical illness. Keywords chronic critical illness, mechanical ventilation, systemic inflammation, wasting syndrome. Eur J Clin Invest 2015 Clinical case overview What is the patient’s prognosis? Will he recover functional autonomy? A 60-year-old man was admitted to ICU for acute respiratory failure secondary to ARDS. The patient underwent Intensive care units (ICUs) were devised to artificially maintain mechanical ventilation via endotracheal tube with protective vital functions that were previously impaired due to an acute strategy, and started antibiotics and steroids intravenously. condition, while the patient is recovering from the disease [1,2]. Chest CT scan showed diffuse bilateral ground glass with Their set of treatments is quite commonly applied to a popu- atelectasis in dorsal areas. After 10 days of treatment, due to lation presenting with an increasingly advanced average age the persistence of severe respiratory failure, a tracheostomy and with multimorbidities [3,4]. Although significantly was performed. The patient’s clinical conditions and gas achieving a reduction in mortality rates, ICUs also led to a exchange improved in the following days, but an evolution growth in the number of patients who overcome the acute stage towards lung fibrosis was radiographically detected. Thirty of the disease, but who become dependent for a long time on days after admission, the patient presented with severe techniques supporting one or more vital functions, therefore muscle wasting, while weaning from mechanical ventilation becoming ‘chronically critically ill’. was difficult due to the onset of severe alveolar hypoventi- lation during spontaneous breathing trial. Blood tests showed Definition and epidemiology hyperglycaemia requiring insulin administration at high The definition of ‘chronically critically ill patient’ was coined doses. Furthermore, the patient experienced periods of by Girard and Raffin in 1985, in an article describing a set of delirium, treated with sedatives and antipsychotics, forcing patients who remained dependent on vital support treat- the patient to prolonged immobility. After 40 days of hospi- ments after an acute critical disease requiring admission to talization in ICU, the patient was transferred to a weaning ICU [5]. centre. European Journal of Clinical Investigation 1 A. MARCHIONI ET AL. www.ejci-online.com Due to the clinical difficulty in identifying the progression from the acute phase of the disease to its becoming chronically critical, an absolute definition of chronic critical illness is cur- rently unavailable. However, as prolonged mechanical venti- lation is required by the vast majority of the affected patients, this feature is a primary indicator for the definition of chronic critical illness [6].‘Prolonged mechanical ventilation’ has been defined as the need for ventilatory support for more than 21 consecutive days for at least 6 h per day [7]. Another element for the identification of these patients is the need to perform tracheotomy at ICU, when the patient requires prolonged mechanical ventilation and on the basis of a clinical judgment regarding patient stability. However, these defini- tions are limited, take into account the need for prolonged mechanical ventilation and fail to cover the entire spectrum of conditions that fall into this syndrome. Epidemiologically, chronic critical illness has become a rele- Figure 1 Clinical features of chronic critical illness vant emerging issue: some studies report that up to 5–10% of patients admitted to ICU require prolonged mechanical venti- lation, with 100 000 patients assessed in the US only [8]. old age, comorbidities and type of disease, while the most fre- Around 30–50% of chronically critically ill patients can be dis- quent acute conditions involved are sepsis and ARDS (acute charged from ICU or other acute care settings without venti- respiratory distress syndrome), both characterized by an latory support, although comorbidities, weak functional immune response triggering a significant systemic inflamma- compensation and common infectious complications are the tion [14]. The progress from acute disease to chronic critical main factors affecting prognosis [9,10]. One-year mortality is illness leads to significant changes in endocrine response, assessed to be around 48–68%, and some studies report that partly accounting for the clinical syndrome present in such only 10% of chronically critically ill patients achieve functional patients (Fig. 2). Systemic inflammation and endocrine autonomy and live at their home at 1 year after the onset of the derangement are related with malnutrition, brain dysfunction acute condition requiring admission to ICU [11–13]. and muscle weakness. Clinical features Systemic inflammation Chronic critical illness can also be defined as a persistent sys- Although the main marker in patients with chronic critical ill- temic inflammation triggered by an initial insult. The progress ness is respiratory failure requiring prolonged mechanical from an acute condition into chronic critical illness may be ventilation, other clinical features are always present and out- favoured by two factors: (i) inflammation insult severity during line a specific clinical syndrome (Fig. 1). Endocrine alterations acute phase and (ii) missed resolution of inflammation. For and prolonged inflammation cause myopathy, neuropathy and example, ARDS patients present with a significant increase in changes in body composition including loss of lean body mass. TNF-a, IL-1b, IL-6 and IL-8 plasma levels. Neurological changes often occur such as coma or delirium Patients presenting with higher inflammation levels at dis- extending over a long period. These patients present with dif- ease onset and persistent blood cytokine increase during its ferent levels of nutritional deficiency, while prolonged immo- course show worse prognosis and higher incidence of multiple bility and enhanced susceptibility to infections are extremely organ failure [15]. This group of patients, whose survival common. depends on life support techniques, requires prolonged Physiopathological mechanisms mechanical ventilation and therefore faces an increased risk of developing chronic critical illness. Old age, as a risk factor, is Currently, no explanation is available on the reason why associated with the chronic increase in the levels of some among patients with similar severity and requiring intensive inflammatory markers, such as IL-6, TNF, IL-1 receptor antag- treatment some experience a rapid recovery of vital functions onist and CPR, on which an acute condition may trigger and while others become chronically critically ill. Moreover, there amplify an inflammatory response [16]. are no biomarkers that can assist in predicting the development The process leading to the resolution of inflammation is of this condition. Risk factors for chronic critical illness include not a passive mechanism, as it involves a complex biological 2 ª 2015 Stichting European Society for Clinical Investigation Journal Foundation CHRONIC CRITICAL ILLNESS Figure 2 Pathophysiology of progression from acute disease to chronic critical illness. The acute disease is characterized by the presence of a significant inflammatory response and the activation of the hypothalamic–pituitary axis, with the purpose of delaying the anabolism and increase the catabolism to make available the energy substrates. The resolution of the inflammatory process results in healing and restoration of normal neuroendocrine activity. If inflammation fails to resolve, the persistent disease leads to the development of an exhaustion of the neuroendocrine response with the appearance of chronic critical illness. programme requiring the function of specific mediators and increases host susceptibility to infections, thus promoting the cells. The main
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