Luca Brazzi

A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients

Background Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal levels may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. Methods A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). Results The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P<0.001). Mortality was 48.4, ...

Prone position in acute respiratory distress syndrome

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. According to the available data, the authors conclude that: 1) oxygenation improves in ∼70–80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.

Positive end-expiratory pressure.

Purpose of review In the last 2 years, several reports have dealt with recruitment/positive end-expiratory pressure (PEEP) selection. Most of them confirm previous results and few add new information. Recent findings It has been definitely confirmed that opening pressures are different throughout the acute respiratory distress syndrome lung parenchyma, ranging from 5–10 up to 30–40 cmH2O. The highest opening pressures are required to open the most dependent lung regions. It has been found that in 2 s, most of the recruitable lung regions may be open when a proper pressure is applied. The best way to assess recruitment is computed tomography scanning, whereas lung mechanics are a reasonable bedside surrogate. Impedance tomography has been increasingly tested, whereas gas exchange is the less reliable indicator of recruitment. A large outcome study showed that higher PEEP might provide survival benefit in a subgroup of more severe patients as compared with lower PEEP. To set PEEP in each individual patient, the use of the expiratory limb of the pressure–volume curve has been suggested. Setting PEEP according to transpulmonary pressure has a robust physiological background, although it requires confirmatory study. Summary Indiscriminate application of recruitment maneuver in unselected acute respiratory distress syndrome population does not provide benefits. However, in the most severe patients, recruitment maneuver has to be considered and higher PEEP applied. To individualize PEEP, the expiratory phase has to be considered, and the esophageal pressure measurement to compute the transpulmonary pressure should be progressively introduced in clinical practice.

The relationship between labour cost per patient and the size of intensive care units: a multicentre prospective study

ObjectiveWe examined the relationship between major ICU characteristics and labour cost per patient.DesignFour-week prospective data collection, in which the hours spent by each physician and nurse on both in-ICU and extra-ICU activities were collected.SettingEighty Italian adult ICUs.Measurements and resultsThe cost of the time actually spent by ICU staff on ICU patients (labour cost) was computed for each participating unit, by applying to the average annual salaries the proportions of in-ICU activity working time for physicians and nurses. Multiple regression analysis was used to identify ICU characteristics that predict labour costs per patient. Labour cost per patient was positively correlated with ICU mortality and patients average length of stay (slopes =0.67, p =0.048 and 0.09, p <0.0001, respectively). Labour cost per patient decreases almost linearly as the number of beds increases up to about eight, and it remains nearly constant above about twelve beds. The number of patients admitted per physician (not per nurse) increases with the number of beds (Spearman correlation coefficient =0.567, p <0.0001).ConclusionsOur findings suggest that ICUs with less than about 12 beds are not cost-effective.

Computed tomography in adult respiratory distress syndrome: what has it taught us?

Computed tomography (CT) has played an important role in improving our knowledge of the pathophysiology of the adult respiratory distress syndrome (ARDS), and in determining the morphological and functional relationships of different manoeuvres commonly used in the therapeutic management of this syndrome (changes in body position, application of positive end-expiratory pressure (PEEP) and mechanical ventilation). During the early phase of the disease, the ARDS lung is characterized by a homogenous alteration of the vascular permeability. Thus, oedema accumulates evenly in all lung regions with a nongravitational distribution (homogenous lung). The increased lung weight, due to increased oedema, causes a collapse of the lung regions along the vertical axis, through the transmission of hydrostatic forces (compression atelectasis). Thus, the lesions appear mainly in the dependent lung regions (dishomogeneous lung). During inspiration, at plateau pressure, the pulmonary units reopen and, if the PEEP applied is adequate, they stay open during the following expiration. Adequate PEEP is equal to or higher than the hydrostatic forces compressing that unit. Prone position is another manoeuvre which allows previously collapsed lung regions to reopen and, conversely, compresses previously aerated regions, reversing the distribution of gravitational forces. During late ARDS, there is less compression atelectasis and the lung undergoes structural changes, due to the reduced amount of oedema. This is usually associated with CO2 retention and the development of emphysema-like lesions. In conclusion, computed tomography is not only a research tool, but a useful technique which allows a better understanding of the progressive change in strategy needed to ventilate the adult respiratory distress syndrome lung at different stages of the disease.

CT scan in ARDS: Clinical and physiopathological insights

C T scan of the lungs of patients with Acute Respiratory Failure (ARF) is increasingly being used despite logistic diiliculties of transporting severely ill patients to the C T scan facilities. To our knowledge, Rommelsheim et al. ( 1 I first reported on C T scan images of the lungs of Adult Respiratory Distress Syndrome (ARDS) patients. In 1986, two reports appeared dealing with ARDS lungs studied by C T scan (2, 3). We would like, i n this review, to focus on the C T scan morphology of ARDS lungs, emphasizing the effects of Positive End Expiratory Pressure (PEEP) and of body position changes. Moreover, we will describe the quantitative approach to the C T scan images we have used to estimate lung weight and regional distribution of gases and tissue in normal and in ARDS lungs. O n the basis of thuse data we will propose a model of evolution from normal to full-blown ARDS lung.

Resuscitation from hemorrhagic shock: Experimental model comparing normal saline, dextran, and hypertonic saline solutions

ObjectiveTo compare the effectiveness of normal saline, dextran, hypertonic, and hypertonic-hyperoncotic solutions in hemorrhagic shock. DesignLaboratory investigation. SettingUniversity hospital, Emergency Surgery and Intensive Care staff. SubjectsThirty-two large white female pigs. InterventionsRoutine care included: anesthesia and sedation (ketamine 10 mg/kg, droperidol 0.25 mg/kg, diazepam 0.7 mg/kg, fentanyl 0.006 mg/kg, 2% enflurane, 20% nitrous oxide, pancuronium bromide 0.13 mg/kg); volume-controlled ventilation (Paco2 35–40 torr; 4.7–5.4 kPa); cannulation of right carotid artery and pulmonary artery. Three flow probes (subdiaphragmatic aorta, superior mesenteric artery, right renal artery) and regional venous catheters (superior mesenteric vein, right renal vein) were positioned. Animals were bled to 45 mm Hg for 1 hr and resuscitated with four different fluids and blood to normal aortic blood flow and hemoglobin. Measurements and Main ResultsMean arterial pressure and blood flow through abdominal aorta (&OV0312;aor), mesenteric artery (&OV0312;mes), and renal artery (&OV0312;ren) were continuously monitored. Cardiac output, systemic and regional oxygen delivery (&U1E0A;o2, &U1E0A;o2mes, &U1E0A;o2ren), and consumption (&OV0312;o2, &OV0312;o2mes, &OV0312;o2ren) were recorded every 30 mins. Baseline &OV0312;aor was restored with different amounts of fluids in the four groups: normal saline (91.35 ± 22.18 mL/kg); dextran (16.24 ± 4.42 mL/kg); hypertonic (13.70 ± 1.44 mL/kg); and hypertonic-hyperoncotic (9.11 ± 1.20 mL/kg). The amount of sodium load was less using dextran and hypertonic-hyperoncotic and sodium levels were only transiently increased after hypertonic infusion. Mean arterial pressure and cardiac output were normalized in all groups. Animals resuscitated with normal saline and dextran showed increased pulmonary artery pressures. &U1E0A;o2 was significantly higher after hypertonic-hyperoncotic infusion, because of reduced hemodilution. Hypertonic and hypertonic-hyperoncotic normalized &OV0312;mes, &U1E0A;o2mes, &OV0312;o2mes, &OV0312;ren, and &U1E0A;o2ren, whereas normal saline and dextran did not achieve this result. At the end of the experiment, hypertonic-hyperoncotic maintained mean arterial pressure, cardiac output, and &U1E0A;o2 until the end of observation in contrast to normal saline, dextran, and hypertonic. ConclusionsResuscitation with a small volume of hypertonic-hyperoncotic solution allows systemic and splanchnic hemodynamic and oxygen transport recovery, without an increase in pulmonary artery pressure. It only transiently increased sodium concentration.

Levosimendan for Hemodynamic Support after Cardiac Surgery

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta‐analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double‐blind, placebo‐controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30‐day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30‐day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], ‐5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, ‐2 hours; 95% CI, ‐5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, ‐12 hours; 95% CI, ‐21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, ‐1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low‐dose levosimendan in addition to standard care did not result in lower 30‐day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.)

Respiratory mechanics and bronchodilator responsiveness in patients with the adult respiratory distress syndrome.

ObjectiveTo study the effects of salbutamol (a selective β2-adrenergic receptor agonist) on respiratory mechanics in patients with the adult respiratory distress syndrome (ARDS). DesignProspective study. SettingICU in a university hospital. PatientsSeven mechanically ventilated, paralyzed ARDS patients. Main Outcome MeasurementsMeasurements of respiratory system compliance, maximum, and minimum inspiratory resistance (by the end-inspiratory occlusion method during constant flow inflation) were performed at 0, 5, 10 cm H2O positive end-expiratory pressure, both before and at least 30 mins after the start of a continuous iv infusion of salbutamol (15 μg/min). Minimum inspiratory resistance represents the ohmic air flow resistance, while maximum inspiratory resistance includes minimum inspiratory resistance plus the effective additional resistance due to stress adaptation and to time constant inhomogeneities. Air flow was measured at the airway connector and tracheal pressure near the central end of the artificial airway. ResultsMaximum inspiratory resistance, minimum inspiratory resistance, and additional resistance were higher than the values reported for normal anesthetized subjects. On average, salbutamol caused a decrease in maximum and minimum inspiratory resistances (from 6.48 ± 2.56 to 4.67 ± 1.74 and from 4.06 ± 2.12 to 2.07 ± 0.95 cm H2O/L/sec, respectively). Positive end-expiratory pressure increased additional resistance, whereas it decreased minimum inspiratory resistance. No interaction was found between positive end-expiratory pressure and salbutamol. Respiratory system compliance was not significantly affected by salbutamol nor positive end-expiratory pressure. ConclusionsIn ARDS patients, salbutamol decreases the abnormally high airway resistance by reducing minimum resistance, but has effect on the effective additional resistance. (Crit Care Med 1993: 21:78–83)

Mesenteric and Renal Oxygen Transport during Hemorrhage and Reperfusion: Evaluation of Optimal Goals for Resuscitation

BACKGROUND Changes in flow to the gut and the kidney during hemorrhage and resuscitation contribute to organ dysfunction and outcome. We evaluated regional and splanchnic oxygen (O2) flow distribution and calculated oxygen supply distribution during hemorrhage and reperfusion and compared them with global measures. METHODS Seven anesthetized pigs were instrumented to evaluate global hemodynamics, visceral blood flow, and oxygen transport. Tonometric pH probes were positioned in the stomach and jejunum. Animals were bled to 45 mm Hg for 1 hour. Crystalloids and blood were infused during the following 2 hours to normalize blood pressure, heart rate, urine output, and hemo- globin. RESULTS During hemorrhage, mesenteric flow and O2 consumption were significantly decreased, whereas systemic consumption remained normal. Renal flow was reduced, but renal O2 consumption remained normal. After resuscitation, despite normal hemodynamics, neither systemic, mesenteric, nor renal O2 delivery returned to baseline. Lactate remained significantly increased. Arterial pH, base excess, and gastric and jejunal pH were all decreased. CONCLUSION During hemorrhage, the gut is more prone than other regions to O2 consumption supply dependency. After resuscitation, standard clinical parameters do not detect residual O2 debt. Lactate, arterial pH, base excess, and intramucosal gut pH are all markers of residual tissue hypoperfusion.