Franco Laghi

An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: an international consensus conference in intensive care medicine.

OBJECTIVES To address the issues of Prevention and Management of Acute Renal Failure in the ICU Patient, using the format of an International Consensus Conference. METHODS AND QUESTIONS Five main questions formulated by scientific advisors were addressed by experts during a 2-day symposium and a Jury summarized the available evidence: (1) Identification and definition of acute kidney insufficiency (AKI), this terminology being selected by the Jury; (2) Prevention of AKI during routine ICU Care; (3) Prevention in specific diseases, including liver failure, lung Injury, cardiac surgery, tumor lysis syndrome, rhabdomyolysis and elevated intraabdominal pressure; (4) Management of AKI, including nutrition, anticoagulation, and dialysate composition; (5) Impact of renal replacement therapy on mortality and recovery. RESULTS AND CONCLUSIONS The Jury recommended the use of newly described definitions. AKI significantly contributes to the morbidity and mortality of critically ill patients, and adequate volume repletion is of major importance for its prevention, though correction of fluid deficit will not always prevent renal failure. Fluid resuscitation with crystalloids is effective and safe, and hyperoncotic solutions are not recommended because of their renal risk. Renal replacement therapy is a life-sustaining intervention that can provide a bridge to renal recovery; no method has proven to be superior, but careful management is essential for improving outcome.

Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives

PurposeEsophageal pressure (Pes) is a minimally invasive advanced respiratory monitoring method with the potential to guide management of ventilation support and enhance specific diagnoses in acute respiratory failure patients. To date, the use of Pes in the clinical setting is limited, and it is often seen as a research tool only.MethodsThis is a review of the relevant technical, physiological and clinical details that support the clinical utility of Pes.ResultsAfter appropriately positioning of the esophageal balloon, Pes monitoring allows titration of controlled and assisted mechanical ventilation to achieve personalized protective settings and the desired level of patient effort from the acute phase through to weaning. Moreover, Pes monitoring permits accurate measurement of transmural vascular pressure and intrinsic positive end-expiratory pressure and facilitates detection of patient–ventilator asynchrony, thereby supporting specific diagnoses and interventions. Finally, some Pes-derived measures may also be obtained by monitoring electrical activity of the diaphragm.ConclusionsPes monitoring provides unique bedside measures for a better understanding of the pathophysiology of acute respiratory failure patients. Including Pes monitoring in the intensivist’s clinical armamentarium may enhance treatment to improve clinical outcomes.

Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity.

Purpose Ultrasound measurements of diaphragm thickness (Tdi) and thickening (TFdi) may be useful to monitor diaphragm activity and detect diaphragm atrophy in mechanically ventilated patients. We aimed to establish the reproducibility of measurements in ventilated patients and determine whether passive inflation by the ventilator might cause thickening apart from inspiratory effort.

Role of the respiratory muscles in acute respiratory failure of COPD: lessons from weaning failure

It is problematic to withhold therapy in a patient with chronic obstructive pulmonary disease (COPD) who presents with acute respiratory failure so that detailed physiological measurements can be obtained. Accordingly, most information on respiratory muscle activity in patients experiencing acute respiratory failure has been acquired by studying patients who fail a trial of weaning after a period of mechanical ventilation. Such patients experience marked increases in inspiratory muscle load consequent to increases in resistance, elastance, and intrinsic positive end-expiratory pressure. Inspiratory muscle strength is reduced secondary to hyperinflation and possibly direct muscle damage and the release of inflammatory mediators. Most patients recruit both their sternomastoid and expiratory muscles, even though airflow limitation prevents the expiratory muscles from lowering lung volume. Even when acute hypercapnia is present, patients do not exhibit respiratory center depression; indeed, voluntary activation of the diaphragm, in absolute terms, is greater in hypercapnic patients than in normocapnic patients. Instead, the major mechanism of acute hypercapnia is the development of rapid shallow breathing. Despite the marked increase in mechanical load and decreased force-generating capacity of the inspiratory muscles, patients do not develop long-lasting muscle fatigue, at least over the period of a failed weaning trial. Although the disease originates within the lung parenchyma, much of the distress faced by patients with COPD, especially during acute respiratory failure, is caused by the burdens imposed on the respiratory muscles.

Narrative Review: Ventilator-Induced Respiratory Muscle Weakness

Clinicians have long been aware that substantial lung injury results when mechanical ventilation imposes too much stress on the pulmonary parenchyma. Evidence is accruing that substantial injury may also result when the ventilator imposes too little stress on the respiratory muscles. Through adjustment of ventilator settings and administration of pharmacotherapy, the respiratory muscles may be rendered almost (or completely) inactive. Research in animals has shown that diaphragmatic inactivity produces severe injury and atrophy of muscle fibers. Human data have recently revealed that 18 to 69 hours of complete diaphragmatic inactivity associated with mechanical ventilation decreased the cross-sectional areas of diaphragmatic fibers by half or more. The atrophic injury seems to result from increased oxidative stress leading to activation of protein-degradation pathways. Scientific understanding of ventilator-induced respiratory muscle injury has not reached the stage where meaningful controlled trials can be done, and thus, it is not possible to give concrete recommendations for patient management. In the meantime, clinicians are advised to select ventilator settings that avoid both excessive patient effort and excessive respiratory muscle rest. The contour of the airway pressure waveform on a ventilator screen provides the most practical indication of patient effort, and clinicians are advised to pay close attention to the waveform as they titrate ventilator settings. Research on ventilator-induced respiratory muscle injury is in its infancy and portends to be an exciting area to follow.

Ventilator-induced respiratory muscle weakness

The most common reason to institute mechanical ventilation is to decrease patient distress resulting from an increase in work of breathing (1). In this situation, the ventilator is functioning as an additional set of muscles, and so decreases the load placed on the patient’s own respiratory muscles. The second major indication for mechanical ventilation is to improve oxygenation, as, for example, in patients with the acute respiratory distress syndrome (ARDS) (1). A ventilator improves oxygenation by increasing tidal volume and end-expiratory lung volume, and by better matching of ventilation and perfusion within the lung parenchyma (2). While the oxygen-enhancing action of the ventilator is not directed at the respiratory muscles per se, patients with impaired oxygenation are commonly treated with antibiotics (3), corticosteroids (4), sedatives (5) and neuromuscular agents (6), all of which can weaken respiratory muscles. Every patient who survives an episode of acute respiratory failure faces a major challenge at the point of ventilator discontinuation. The main reason that patients fail weaning attempts is because their work of breathing is high consequent to abnormal lung mechanics (increased resistance, decreased compliance) and their respiratory muscles are unable to cope with the increased load (7). From the above account, it is evident that performance of the respiratory muscles is a dominant consideration at the points when mechanical ventilation is first instituted and when it is being withdrawn. A major concern of critical care physicians is the growing awareness that mechanical ventilation can harm the lung. From the earliest days of intensive care, it has been recognized that use of high airway pressure can rupture the lung parenchyma, causing a pneumothorax. In 1974, Webb and Tierney demonstrated that mechanical ventilation can cause hemorrhagic and edematous lesions independent of barotrauma (8). This seminal observation was extended by other animal experiments and the alveolar injury has been shown to result from the use of high tidal volumes; the injury has been named volutrauma or ventilator-induced lung injury (9). Studies in animals were followed by studies in patients, which culminated in randomized controlled trials that have shown that use of high tidal volume leads to increased mortality in patients with ARDS. Just as mechanical ventilation can damage the lung parenchyma, investigators have postulated that the ventilator can damage the respiratory muscles (10). The fear is that mechanical ventilation lowers demands on a patient’s respiratory muscles to such an extent that they become inactive, resulting in injury and atrophy at a structural level. In contrast to research on ventilator-induced lung injury, scientific understanding of ventilator-induced respiratory muscle injury has not reached the stage where it is possible to undertake meaningful randomized controlled trials and thus it is not possible to render concrete recommendations for patient management. Nevertheless, the accruing biological and pathophysiological research on the effect of mechanical ventilation on the respiratory muscles is leading many experts to change their approach to ventilator management.

Can ventilation-feedback training augment exercise tolerance in patients with chronic obstructive pulmonary disease?

RATIONALE Exercise-induced dynamic hyperinflation contributes to decreased exercise tolerance in chronic obstructive pulmonary disease (COPD). It is unknown whether respiratory retraining (ventilation-feedback [VF] training) can affect exercise-induced dynamic hyperinflation and increase exercise tolerance. OBJECTIVES To determine whether patients with COPD would achieve longer exercise duration if randomized to a combination of exercise training plus VF training than either form of training on its own. METHODS A total of 64 patients randomized to 1 of 3 groups: VF plus exercise (n = 22), exercise alone (n = 20), and VF alone (n = 22). MEASUREMENTS AND MAIN RESULTS Exercise duration before and after 36 training sessions and exercise-induced dynamic hyperinflation and respiratory pattern before and after training were measured. In the 49 patients who completed training, duration of constant work-rate exercise was 40.0 (+/- 20.4) minutes (mean +/- SD) with VF plus exercise, 31.5 (+/- 17.3) minutes with exercise alone, and 16.1 (+/- 19.3) minutes with VF alone. Exercise duration was longer in VF plus exercise than in VF alone (P < 0.0001), but did not reach predetermined statistical significance when VF plus exercise was compared with exercise alone (P = 0.022) (because of multiple comparisons, P </= 0.0167 was used for statistical significance). After training, exercise-induced dynamic hyperinflation, measured at isotime, in VF plus exercise was less than in exercise alone (P = 0.014 for between-group changes) and less than in VF alone (P = 0.019 for between-group changes). After training, expiratory time was longer in VF plus exercise training (P < 0.001), and it was not significantly changed in the other two groups. CONCLUSIONS The combination of VF plus exercise training decreases exercise-induced dynamic hyperinflation and increases exercise duration more than VF alone. An additive effect to exercise training from VF was not demonstrated by predetermined statistical criteria.

Endocrinological derangements in COPD

Chronic obstructive pulmonary disease (COPD) is no longer considered to affect only the lungs and airways but also the rest of the body. The systemic manifestations of COPD include a number of endocrine disorders, such as those involving the pituitary, the thyroid, the gonads, the adrenals and the pancreas. The mechanisms by which COPD alters endocrine function are incompletely understood but likely involve hypoxaemia, hypercapnia, systemic inflammation and glucocorticoid administration. Altered endocrine function can worsen the clinical manifestations of COPD through several mechanisms, including decreased protein anabolism, increased protein catabolism, nonenzymatic glycosylation and activation of the rennin–angiotensin–aldosterone system. Systemic effects of endocrine disorders include abnormalities in control of breathing, decreases in respiratory and limb-muscle mass and function, worsening of respiratory mechanics, impairment of cardiac function and disorders of fluid balance. Research on endocrine manifestations of COPD embraces techniques of molecular biology, integrative physiology and controlled clinical trials. A sound understanding of the various disorders of endocrine function associated with COPD is prudent for every physician who practices pulmonary medicine.

Can diaphragmatic contractility be assessed by airway twitch pressure in mechanically ventilated patients

Background: In critically ill patients inspiratory muscle function may be assessed by measurements of maximal inspiratory airway pressure and the response of twitch transdiaphragmatic pressure (Pdi tw) to bilateral phrenic nerve stimulation. The first is limited by its total dependence on patient cooperation. Although the second approach is independent of patient volition, it is impractical because it requires oesophageal and gastric balloons. Because airway pressure is easily and non-invasively recorded in patients with artificial airways, we hypothesised that twitch airway pressure (Paw tw) reliably predicts Pdi tw and twitch oesophageal pressure (Poes tw) in mechanically ventilated patients. Methods: Thirteen mechanically ventilated patients recovering from an episode of acute respiratory failure received phrenic nerve stimulation at end exhalation. The rapid occlusion technique was used to record respiratory system mechanics. Results: Stimulations were well tolerated. Mean (SE) Paw tw at end exhalation was –8.2 (1.2) cm H2O and Poes tw and Pdi tw were –7.3 (1.1) and 10.4 (1.8) cm H2O, respectively. Stimulations produced a good correlation between Paw tw and Pdi tw (p<0.001), although the limits of agreement were wide. The results were similar for Poes tw. No relationship was found between the Paw tw/Poes tw ratio and respiratory system compliance or airway resistance. Paw tw reproducibility was excellent (mean coefficient of variation 6%, range 3–9%). Conclusions: Despite a good correlation between Paw tw and Poes tw, Paw tw did not reliably predict Poes tw or Pdi tw in mechanically ventilated patients. Nevertheless, the excellent reproducibility of Paw tw suggests that it may be a useful means of monitoring inspiratory muscle contractility in the routine care of mechanically ventilated patients.

Low vitamin D levels are associated with increased rejection and infections after lung transplantation

BACKGROUND The prevalence of vitamin D deficiency in lung disease is greater than in the general population. Vitamin D deficiency may negatively affect immune and lung function. Accordingly, we hypothesized that lung transplant recipients with vitamin D deficiency are more susceptible to rejection and infections after transplantation. METHODS Transplant outcomes were reviewed in a retrospective cohort of 102 lung transplant recipients who had 25-hydroxyvitamin D [25(OH)D] levels drawn during the near-transplant period (100 days pre- or post-transplant). RESULTS In the near-transplant period, 80% of recipients were 25(OH)D-deficient and 20% were not 25(OH)D-deficient. Episodes of acute cellular rejection in the deficient group were more frequent than in the non-deficient group [mean 1.27 (0.99 to 1.55) vs 0.52 (0.12 to 0.93), p = 0.006]. The rejection rate in the deficient group was more than double that of the the non-deficient group [IRR 2.43 (1.30 to 4.52), p = 0.005]. Infectious episodes were also more frequent in the deficient group than in the non-deficient group [mean 4.01 (3.24 to 4.79) vs 2.71 (1.47 to 3.96), p = 0.04]. The mortality rate of recipients who remained 25(OH)D-deficient 1 year after transplant was almost 5-fold higher than in recipients who were not 25(OH)D-deficient [IRR 4.79 (1.06 to 21.63), p = 0.04]. CONCLUSIONS Low serum 25(OH)D levels in lung transplant recipients were associated with increased incidence of acute rejection and infection. The mortality of recipients who remained deficient 1 year post-transplant was higher than that of recipients who maintained normal vitamin D levels at 1 year post-transplant.