Michele Umbrello

Diaphragm ultrasound as indicator of respiratory effort in critically ill patients undergoing assisted mechanical ventilation: a pilot clinical study

IntroductionPressure-support ventilation, is widely used in critically ill patients; however, the relative contribution of patient’s effort during assisted breathing is difficult to measure in clinical conditions. Aim of the present study was to evaluate the performance of ultrasonographic indices of diaphragm contractile activity (respiratory excursion and thickening) in comparison to traditional indices of inspiratory muscle effort during assisted mechanical ventilation.MethodConsecutive patients admitted to the ICU after major elective surgery who met criteria for a spontaneous breathing trial with pressure support ventilation were enrolled. Patients with airflow obstruction or after thoracic/gastric/esophageal surgery were excluded. Variable levels of inspiratory muscle effort were achieved by delivery of different levels of ventilatory assistance by random application of pressure support (0, 5 and 15 cmH2O). The right hemidiaphragm was evaluated by B- and M-mode ultrasonography to record respiratory excursion and thickening. Airway, gastric and oesophageal pressures, and airflow were recorded to calculate indices of respiratory effort (diaphragm and esophageal pressure–time product).Results25 patients were enrolled. With increasing levels of pressure support, parallel reductions were found between diaphragm thickening and both diaphragm and esophageal pressure–time product (respectively, R = 0.701, p < 0.001 and R = 0.801, p < 0.001) during tidal breathing. No correlation was found between either diaphragm or esophageal pressure–time product and diaphragm excursion (respectively, R = −0.081, p = 0.506 and R = 0.003, p = 0.981), nor was diaphragm excursion correlated to diaphragm thickening (R = 0.093, p = 0.450) during tidal breathing.ConclusionsIn patients undergoing in assisted mechanical ventilation, diaphragm thickening is a reliable indicator of respiratory effort, whereas diaphragm excursion should not be used to quantitatively assess diaphragm contractile activity.

Pharmacokinetics of orally administered melatonin in critically ill patients

Abstract:  Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high‐risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio‐immuno‐assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half‐absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half‐elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers.

Current Concepts of ARDS: A Narrative Review

Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of pulmonary edema of non-cardiogenic origin, along with bilateral pulmonary infiltrates and reduction in respiratory system compliance. The hallmark of the syndrome is refractory hypoxemia. Despite its first description dates back in the late 1970s, a new definition has recently been proposed. However, the definition remains based on clinical characteristic. In the present review, the diagnostic workup and the pathophysiology of the syndrome will be presented. Therapeutic approaches to ARDS, including lung protective ventilation, prone positioning, neuromuscular blockade, inhaled vasodilators, corticosteroids and recruitment manoeuvres will be reviewed. We will underline how a holistic framework of respiratory and hemodynamic support should be provided to patients with ARDS, aiming to ensure adequate gas exchange by promoting lung recruitment while minimizing the risk of ventilator-induced lung injury. To do so, lung recruitability should be considered, as well as the avoidance of lung overstress by monitoring transpulmonary pressure or airway driving pressure. In the most severe cases, neuromuscular blockade, prone positioning, and extra-corporeal life support (alone or in combination) should be taken into account.

Tolerance of enteral feeding: from quantity to quality of gastric residual volume?

Dear Sir: Nutritional support is essen-tial in the management of critically illpatients; enteral nutrition is preferredto parenteral [1], because the lattermay favour immune compromise andinfections, is more costly, and leads toadverse outcome in some subsets ofpatients. Moreover, many studies haveshown that this evidence is even morepronounced with the use of early ent-eral nutrition [2].The major concerns with its use arethe potential development of upperdigestive intolerance (UDI, i.e. thepresence of gastric residual volumes,GRV, of 150–500 ml in two consec-utive measurements, or[500 ml, orvomiting) [3] and the risk of aspira-tion of gastric content andpneumonia. Recently, some authorshave demonstrated that GRVs arepoor markers of gastric aspiration inenterally fed, critically ill patients [4],downsizing their role in the develop-ment of aspiration pneumonia.To the best of our knowledge thereare no reports on the role that thepresence of air in the stomach mayplay in the development of aspiration.The objective of our study was to testthe association between UDI, thepresence of air, and the developmentof pneumonia in enterally fed, criti-cally ill patients.We enrolled all adult patientsthe last year, received enteral nutri-tion and stayed more than four days.Admission and main outcome data forthe 78 patients are shown in Table 1.During ICU stay 43 (55.1%) receivedvasoactives, 44 (56.4%) opioids, and17 (21.8%) prokinetics. Ventilatorysupport was provided for 78.6% days,and CPAP for 9.9% days; 11.6% dayswere on spontaneous ventilation.Sedation was endovenous in 4.1%days, totally enteral [5] on 78.1%days, and mixed enteral/parenteral on17.8% days; as a result mean RASSscore was -0.85 ± 1.43 (52.1% dayswere on RASS 0). Patients were in asemi-recumbent position (mean headinclination 35.6 ± 8.9 ). Energysupply was, on average,17.8 ± 6.7 kcal/kg per day; time tostart of nutrition from admission was6 [4–16] h, and we took 72[46–100] h to reach full support.A total of 2695 GRV measure-ments were performed (every fourhours, or every two hours in presenceof GRV or air). On 339 occasionsGRV was found (on average158 ± 117 ml); 226 times there wasair (mean volume: 140 ± 110 ml).UDI was developed by 11 patients,whereas 15 patients were defined as‘‘aerophagic’’ ([2 consecutive find-ings of at least 150 ml of air).Developing of pneumonia during ICUstay was not associated with UDI(P = 0.782), but occurred signifi-cantly more frequently in aerophagicpatients (odds-ratio 4.0 ± 2.7,P = 0.041). The presence of air wasnot associated with UDI (P = 0.132).Consistent with the literature, ourstudy reconfirms the poor value ofUDI as a risk factor for the develop-ment of aspiration pneumonia, andsuggests a potential role for thepresence of air in the stomach. Thisfinding has a physiopathologicalrationale, because air tends to locatein the upper parts, thus in critically ill,semi-recumbent patients it may con-centrate against the loweroesophageal sphincter, facilitatingreflux of gastric content. Furtherstudies are needed to better elucidatethis relationship, and to find thedeterminants of air presence.

Ultrasonographic Assessment of Diaphragm Function in Critically Ill Subjects

The majority of patients admitted to the ICU require mechanical ventilation as a part of their process of care. However, mechanical ventilation itself or the underlying disease can lead to dysfunction of the diaphragm, a condition that may contribute to the failure of weaning from mechanical ventilation. However, extended time on the ventilator increases health-care costs and greatly increases patient morbidity and mortality. Nevertheless, symptoms and signs of muscle disease in a bedridden (or bed rest-only) ICU patient are often difficult to assess because of concomitant confounding factors. Conventional assessment of diaphragm function lacks specific, noninvasive, time-saving, and easily performed bedside tools or requires patient cooperation. Recently, the use of ultrasound has raised great interest as a simple, noninvasive method of quantification of diaphragm contractile activity. In this review, we discuss the physiology and the relevant pathophysiology of diaphragm function, and we summarize the recent findings concerning the evaluation of its (dys)function in critically ill patients, with a special focus on the role of ultrasounds. We describe how to assess diaphragm excursion and diaphragm thickening during breathing and the meaning of these measurements under spontaneous or mechanical ventilation as well as the reference values in health and disease. The spread of ultrasonographic assessment of diaphragm function may possibly result in timely identification of patients with diaphragm dysfunction and to a potential improvement in the assessment of recovery from diaphragm weakness.

Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial

BackgroundA relevant innovation about sedation of long-term Intensive Care Unit (ICU) patients is the ‘conscious target’: patients should be awake even during the critical phases of illness. Enteral sedative administration is nowadays unusual, even though the gastrointestinal tract works soon after ICU admission. The enteral approach cannot produce deep sedation; however, it is as adequate as the intravenous one, if the target is to keep patients awake and adapted to the environment, and has fewer side effects and lower costs.Methods/DesignA randomized, controlled, multicenter, single-blind trial comparing enteral and intravenous sedative treatments has been done in 12 Italian ICUs. The main objective was to achieve and maintain the desired sedation level: observed RASS = target RASS ± 1. Three hundred high-risk patients were planned to be randomly assigned to receive either intravenous propofol/midazolam or enteral melatonin/hydroxyzine/lorazepam. Group assignment occurred through online minimization process, in order to balance variables potentially influencing the outcomes (age, sex, SAPS II, type of admission, kidney failure, chronic obstructive pulmonary disease, sepsis) between groups. Once per shift, the staff recorded neurological monitoring using validated tools. Three flowcharts for pain, sedation, and delirium have been proposed; they have been designed to treat potentially correctable factors first, and, only once excluded, to administer neuroactive drugs. The study lasted from January 24 to December 31, 2012. A total of 348 patients have been randomized, through a centralized website, using a specific software expressly designed for this study. The created network of ICUs included a mix of both university and non-university hospitals, with different experience in managing enteral sedation. A dedicated free-access website was also created, in both Italian and English, for continuous education of ICU staff through CME courses.DiscussionThis ‘educational research’ project aims both to compare two sedative strategies and to highlight the need for a profound cultural change, improving outcomes by keeping critically-ill patients awake.Trial registration numberClinicaltrials.gov #NCT01360346

Novel indications for the Boussignac CPAP valve

Sir:The use of standard devices to provide continuous positive airway pressure (CPAP) outside the intensive care unit (ICU) environment may be awkward in the absence of adequate facilities. Therefore, simplified respirators and transportable CPAP systems are employed. However, these devices are still bulky, due to the presence of ventilatory circuits and separate additional machines. Recently, an innovative device has been proposed: the Boussignac CPAP valve [1] (Vygon, Ecouen, France) (Fig. 1). The valve is a small plastic tube (5.5 cm long, 1.3 cm internal diameter) that has to be attached to a face mask. The oxygen flow, connected to four micro-channels present in the wall of the valve, is accelerated, resulting in a PEEP level ranging from 2.5 to 10 cmH2O according to gas flow. Its efficacy during bronchoscopy in hypoxaemic patients [2] and in the treatment of acute cardiogenic pulmonary oedema, both in emergency departments [3, 4] and in extra-hospital settings [5], is reported. We believe that the Boussignac CPAP system, owing to its low weight, simplicity and small size, represents an optimal solution in a variety of clinical situations. Three illustrative cases are presented. A 50-year-old, morbidly obese (BMI 40.2) man was admitted to the emergency room due to a thoracic trauma. He presented with mild dyspnoea and tachypnoea (respiratory rate, RR 36 min–1). He underwent a lung CT scan, but, owing to the additional effect of obesity, supine positioning resulted in a rapidly progressive dyspnoea and SpO2 of 84%. With the application of the Boussignac CPAP valve, the SpO2 increased to 97% and eupnoea was maintained throughout the procedure. At the end of the investigation, which showed minor lung contusion, the patient was transferred to the ward. An 85-year-old woman was admitted to a medical ward due to heart failure, acute-on-chronic renal failure, and confusional state. Her co-morbidities and general condition made an aggressive respiratory strategy inappropriate. Due to poor peripheral vascular access, a central venous line was requested to provide medical treatment. Supine position was not tolerated (RR> 38 min–1, SpO2 84% in O2 10 l/min within 1 min). Therefore, a Boussignac CPAP valve was applied during the procedure, resulting in improved oxygenation parameters (SpO2 > 93% and RR< 30/min).

Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients

In this study, the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit (ICU) patients, since their blood levels are decreased. Sixty-four patients were enrolled in the study. From the evening of the 3rd ICU day, patients were randomized to receive oral melatonin (3 mg, group M) or placebo (group P) twice daily, at 20:00 and 24:00, until discharged. Blood was taken (at 00:00 and 14:00), on the 3rd ICU day to assess basal nocturnal melatonin values, and then during the treatment period on the 4th and 8th ICU days. Melatonin, total antioxidant capacity, and oxidative stress were evaluated in serum. Melatonin circadian rhythm before treatment was similar in the two groups, with a partial preservation of the cycle. Four hours from the 1st administration (4th ICU day, 00:00), melatonin levels increased to 2514 (982.3; 7148) pg·mL−1 in group M vs. 20.3 (14.7; 62.3) pg·mL−1 in group P (p < 0.001). After five treatment days (8th ICU day), melatonin absorption showed a repetitive trend in group M, while in group P nocturnal secretion (00:00) was impaired: 20 (11.5; 34.5) pg·mL−1 vs. 33.8 (25.0; 62.2) on the 3rd day (p = 0.029). Immediately from the beginning of treatment, the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00; a significant correlation was found between total antioxidant capacity and blood melatonin values (ρ = 0.328; p < 0.001). The proposed enteral administration protocol was adequate, even in the early phase, to enhance melatonin blood levels and to protect the patients from oxidative stress. The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients.

Evaluation of the performance of a new OptiScanner™ 5000 system for an intermittent glucose monitoring

BACKGROUND Mid-infrared spectral technology has shown a high degree of promise in detecting glucose in plasma. OptiScan Biomedical has developed a glucose monitor based on mid-infrared spectroscopy that withdraws blood samples and measures plasma glucose. The objective of this study was to evaluate the accuracy and performance of the OptiScanner™ 5000 system on different pools of blood. METHODS This study was performed to validate the blood glucose measurements obtained with the OptiScanner™ 5000 by comparing them to Central Laboratory glucose measurements (VITROS® 5600 Integrated System) as a comparative method across a broad range of glucose values over a three day period to obtain 80-90 paired measurements. RESULTS A total of 81 paired measurements, distributed between 33 and 320mg/100mL of glucose, were performed. The aggregate data points were within International Organization for Standardization standards, with 100% of the glucose values within ±15%. CONCLUSIONS The current study suggests that a mid-IR fixed-wavelength system (OptiScanner) can measure glucose accurately across a wide range of glucose values in plasma of ICU patients.

Systemic Capillary Leak Syndrome: Is Methylene Blue the Silver Bullet?

Background. Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by unexplained, recurrent episodes of transient, abrupt increase in endothelial permeability, leading to severe hypotension, generalized edema, and hemoconcentration. Case Report. We report the case of a patient suffering from systemic capillary leak syndrome and present a possible interpretation of the pathophysiology of this condition. Besides the classical triad of hypotension, edema, and hemoconcentration, we recorded increased levels of methemoglobin, an index of NO overproduction. We present a possible interpretation of the pathophysiology of this condition based on the fast and complete reversal of symptoms after methylene blue administration (which opposes NO-induced effects) and speculate that increased NO levels could be implicated in the pathophysiology of the capillary leak phase. Why should an emergency physician be aware of this? The safety of this treatment and its fluid- and cathecolamine-sparing effect deserve consideration and further research.