Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome

Objective To determine if oxygen consumption (VO₂) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO₂) rather than O₂ demand.Design Prospective study.Setting Intensive care unit of a tertiary referral center.Patients 12 patients with ARDS and sepsis syndrome.Interventions Routine intensive care unit monitoring including pulmonary and radial artery catheters.Measurements Dobutamine was used to increase cardiac output, thereby directly varying TO₂ under conditions of constant O₂ demand. After baseine measurements of TO₂ and VO₂, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 g/kg/min and measurements of TO₂ and VO₂ were repreated after 30 min at each dose.Results Dobutamine increased TO₂ in 8 of the 12 patients, by 29% at 5 g/kg/min and by 45% (net) at 10 g/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO₂ by 15% at 5 g/kg/min, but did not further increase VO₂ at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO₂ or VO₂ to dobutamine.Conclusions In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutatmine can increase both TO₂ and VO₂. Achievement of a TO₂-independent level of VO₂ could not be convincingly demonstrated in any individual patient. The response of TO₂ and VO₂ to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study.     

Oxygen delivery-consumption relationship in adult respiratory distress syndrome patients: The effects of sepsis

The oxygen consumption-delivery relationship (VO2/ O₂) was studied in 15 sedated paralyzed patients with the adult respiratory distress syndrome (ARDS) due to multiple trauma and in whom sepsis was absent. Different levels (0 to 15 cm H2O) of positive end-expiratory pressure (PEEP) were applied. Oxygen delivery was calculated from cardiac index (thermodilution technique) and arterial oxygen content measurements. Oxygen consumption was calculated using Fick's equation. Regression lines were obtained for each patient. Oxygen supply dependency was defined as a significant (P < .05) relationship between changes in O2 and O₂ with PEEP. Results were compared with those obtained in 18 ARDS patients in whom ARDS was due to sepsis. In nonseptic ARDS patients no significant relationship between changes in VO2 and O₂ with PEEP was found within the experimental range of O₂ on zero end-expiratory pressure (ZEEP) (347 to 845 mL/min/m²). None of these patients had multiple organ system failure (MOSF), and 73% survived. In ARDS patients in whom sepsis was present, supply dependency was present only when O₂ on ZEEP ranged between 330 and 640 mL/min/m². All these patients developed MOSF and died. When O₂ on ZEEP ranged between 686 and 951 mL/min/m² in septic ARDS patients, the supply dependency phenomenon was absent and only three patients developed MOSF and died (70% survivors). In almost all patients PEEP reduced O₂ and therefore worsened OZ balance by either increasing OZ extraction ratio and approaching the critical threshold for supply dependency or dismissing O₂ from the range of non-supply dependency.     

Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome

We asked whether increasing systemic oxygen delivery by blood transfusion could identify pathologic dependence of oxygen consumption on oxygen delivery in patients who have adult respiratory distress syndrome (ARDS) with and without increased concentrations of plasma lactate. Twenty-four ARDS patients were divided into normal (n = 11, lactate ≤ 1.8 mmol/L) and increased (n = 13, lactate > 1.8 mmol/L) plasma lactate groups. After transfusion of two units of packed red blood cells, oxygen delivery index increased significantly in both the normal and increased plasma lactate groups. In the increased plasma lactate group, this was associated with a significant increase in oxygen consumption index and an unchanged oxygen extraction ratio. In contrast, in the normal plasma lactate group, oxygen consumption index did not change from the baseline value and the oxygen extraction ratio decreased significantly. We conclude that increasing systemic oxygen delivery by blood transfusion identifies pathologic dependence of oxygen consumption on oxygen delivery in patients who have ARDS and increased concentrations of plasma lactate.     

Oxygen delivery-dependent oxygen consumption in acute respiratory failure

OBJECTIVE: To investigate whether oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in adult respiratory distress syndrome (ARDS) and non-ARDS acute respiratory failure. DESIGN: Intervention study of a consecutive sample of patients admitted to the ICU with the diagnosis of acute respiratory failure. SETTING: Tertiary care center. PATIENTS: Thirteen consecutive patients with a diagnosis of ARDS and 11 with a diagnosis of respiratory failure not due to ARDS. Patients were monitored with an oximetric pulmonary artery catheter and mechanically ventilated. INTERVENTIONS: DO2 was decreased by the application of positive end-expiratory pressure (PEEP) (20 cm H2O), and subsequently increased by an iv infusion of dobutamine (10 micrograms/kg.min). RESULTS: After the application of PEEP, DO2 decreased significantly in both groups. However, VO2 decreased significantly (p less than .01) only in the ARDS group. When dobutamine was infused, DO2 increased significantly (p less than .01) in both groups, but VO2 increased only in ARDS patients. DO2 correlated significantly with VO2 both in ARDS (r2 = .81, p less than .01) and in non-ARDS (r2 = .38, p less than .05) patients. The correlation coefficient was significantly higher for ARDS than for non-ARDS patients. Comparing the slopes of the regression lines, a stronger dependency of VO2 on DO2 was found in ARDS than in non-ARDS respiratory failure (p less than .001). The oxygen extraction ratio correlated with DO2 in non-ARDS patients (r2 = .49, p less than .05), but not in ARDS patients. CONCLUSIONS: VO2 is dependent on DO2 over a wide range of DO2 values in acute respiratory failure. This dependency phenomenon is much stronger in ARDS than in respiratory failure due to other causes. Due to the abnormal dependency of VO2 on DO2, changes in the oxygenation status may not be reflected by changes in mixed venous oxygen saturation in ARDS.     

Oxygen delivery-consumption relationship in septic adult respiratory distress syndrome patients: The effects of positive end-expiratory pressure

The oxygen consumption/ delivery relationship (VO2/602) was studied in 18 sedated, paralyzed, septic adult respiratory distress syndrome patients. Different levels (0 to 15 cm H2O) of positive end-expiratory pressure (PEEP) were applied. DO₂ was calculated from cardiac index (thermodilution technique) and arterial oxygen content measurements. VO₂ was calculated using Fick's equation. Regression lines were obtained for each patient. The following results were obtained. First, patients with DO₂ at zero end-expiratory pressure ≤ 640 mL/min/m² showed a highly significant relationship between changes in DO₂ and VO₂ with PEEP (supply dependency). In all these patients PEEP decreased DO₂ by reducing cardiac index without significant changes in arterial oxygen saturation. All these patients developed multiple organ system failure and died. Second, changes in DO₂ and VO₂ with PEEP were not correlated in patients with a DO₂ on zero end-expiratory pressure ≥ 686 mL/min/m² (nonsupply dependency). As PEEP was applied, changes in DO₂ were compensated by changes in oxygen extraction ratio such as to keep VO₂ constant. On average, DO₂ decreased with PEEP, while oxygen extraction ratio and arterial-mixed venous oxygen difference increased as PEEP was applied. Only three of these patients developed multiple organ system failure and died (70% survivors).     

Hemodynamic and oxygen transport effects of prostaglandin E1 in patients with adult respiratory distress syndrome

The hemodynamic and oxygen transport effects of prostaglandin E1 (PGE1, Prostin -VR), in increasing doses from 1 to 30 ng/kg X min were evaluated in 5 severely ill surgical patients with adult respiratory distress syndrome (ARDS). This agent produced marked reductions in pulmonary arterial and venous pressures, and increases in cardiac output and oxygen transport. Improvement in PaO2 occurred several hours after these effects. The data indicate that this agent may be a useful adjunctive therapy for ARDS.     

Extracorporeal membrane oxygenation in adult acute respiratory distress syndrome

The role of extracorporeal membrane oxygenation (ECMO) in supporting adult refractory respiratory failure continues to evolve. Technical advances and the clinical challenges of H1N1 associated severe ARDS have spurred a resurgence of interest in ECMO. Published systematic review and pooled analyses point out the limitations of available studies, however, a growing body of evidence suggest potential for benefit. Referral to a specialized center with ECMO experience should be considered early after the initiation of high-level ventilator support in adult patients with severe ARDS.     

High-frequency oscillatory ventilation in adult acute respiratory distress syndrome

Objective This study examined whether ARDS patients in whom predefined ventilator settings fail to maintain oxygenation and CO₂ removal can be safely transitioned to high-frequency oscillatory ventilation (HFOV), and whether HFOV use is efficacious.Design and setting Prospective observational study in the 14-bed intensive care unit of a university hospital.Patients and participants 42 patients with ARDS (APACHE II score 28 (IQR 24–37) and ventilation time prior HFOV 3.0 days (0.7–9.1).Measurements and results Gas exchange parameters and ventilator data were recorded before and during HFOV treatment (–12 h, –6 h, baseline, 10 min, 1 h, 6 h, 12 h, 24 h). Primary endpoints included: (a) P_aO₂/FIO₂ ratio 24 h after start of HFOV treatment or the last point of measurement if HFOV ended within the first 24 h; (b) HFOV-related complications. Post hoc analysis assessed the relationship between outcome and the response to HFOV, and between outcome and time of mechanical ventilation prior to HFOV. At baseline the median P_aO₂/FIO₂ ratio was 95 (IQR 62–129); after 24 h of HFOV the P_aO₂/FIO₂ ratio had increased significantly to 165 (88–225); only one patient developed a unilateral pneumothorax. Of the 42 patients 18 (43%) had died by day 30. Subset analyses showed a significantly higher 30-day mortality rate in patients with at least 3 days of mechanical ventilation prior to HFOV (64%) and in patients without oxygenation improvement after 24 h on HFOV (71%).Conclusions HFOV is an effective and safe method to ventilate ARDS patients. Failure to improve oxygenation within 24 h of HFOV is associated with high mortality.An editorial regarding this article can be found in the same issue     

The acute effects of prostaglandin E1 on the pulmonary circulation and oxygen delivery in patients with the adult respiratory distress syndrome

Prostaglandin E₁ was administered intravenously to 10 patients who had the adult respiratory distress syndrome associated with severe infection in order to investigate its hemodynamic effects. Infusion of PGE₁ significantly decreased the mean pulmonary arterial pressure, mean systemic arterial pressure, pulmonary vascular resistance and systemic vascular resistance, and increased the cardiac index, oxygen delivery and oxygen consumption. No significant difference was noted in the intrapulmonary shunt fraction. These results indicate that administration of PGE₁ improves pulmonary hemodynamics and tissue oxygenation in patients with acute respiratory distress syndrome, by reducing right ventricular afterload and increasing the cardiac index.     

Persistence of supply dependency of oxygen uptake at high levels of delivery in adult respiratory distress syndrome

OBJECTIVE: To identify any plateau in oxygen consumption (VO2) when oxygen delivery (DO2) is increased in patients with the adult respiratory distress syndrome (ARDS). DESIGN: Clinical prospective study; multiple regression analysis was done to assess the relationship between VO2 and DO2 for pooled data and for each individual patient. SETTING: University hospital ICU. PATIENTS: Twenty consecutive patients aged 18 to 78 yrs (mean 43.5) in whom ARDS was present during their ICU stay. INTERVENTIONS: Multiple measurements were obtained in individual patients (mean number of measurements 40, range 20 to 83) and mathematical models were fitted to both pooled and individual patient data. DO2 ranged from 212 to 1550 mL/min.m2 with a maximum of 758 to 1550 mL/min.m2 (mean 1136). Because of the large variations between patients, it was not justifiable to describe a relationship for the pooled data and each case was analyzed individually. MEASUREMENTS AND MAIN RESULTS: We found the optimal regression model to be linear in 13 patients, cubic in four, and either cubic or linear in one. Two patients demonstrated no significant relationship. The relationship for the group was determined from each patient's data and was best described by linear regression. CONCLUSIONS: In no patient was there evidence of a plateau, despite high levels of DO2 being achieved in all patients.     

Roles of the neutrophil and other mediators in adult respiratory distress syndrome

The adult respiratory distress syndrome (ARDS) and transfusion-related acute lung injury (TRALI) are characterized by diffuse, acute lung injury. Most likely, TRALI is a type of ARDS although it is associated with a much lower morbidity and mortality than found with classic ARDS. For years, the pathogenesis of ARDS has been explained by the complement hypothesis in which pulmonary neutrophilic sequestration and degranulation follow complement-mediated neutrophil chemotaxis. A definitive role for the neutrophil in diffuse, acute lung injury, however, has not been established. Although numerous chemoattractants for neutrophils are generated in the lungs and, through degranulation and formation of toxic oxygen free radicals, the neutrophil is fully capable of causing tissue injury, substantial evidence refutes the requirement for neutrophils in diffuse, acute lung injury. Other potential factors in the pathogenesis of ARDS include primary endothelial cell injury, alveolar macrophage activity, and hemostatic disorders.     

Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome

Reactive oxygen species are reactive, partially reduced derivatives of molecular oxygen (O 2 ). Important reactive oxygen species in biologic systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely related species include the hypohalous acids, particularly hypochlorous acid; chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and its protonated form, peroxynitrous acid, are the most significant reactive nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic processes can generate reactive oxygen species and reactive nitrogen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species and reactive nitrogen species are important in the pathogenesis of acute respiratory distress syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species-mediated or reactive nitrogen species-mediated stress with the development of acute respiratory distress syndrome. Despite these data, pharmacologic strategies directed at minimizing reactive oxygen species-mediated or reactive nitrogen species-mediated damage have yet to be successfully introduced into clinical practice. The most extensively studied compound in this regard is N -acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results.     

Evaluation of prognostic indices based on hemodynamic and oxygen transport variables in shock patients with adult respiratory distress syndrome

We tested prospectively 30 hypotensive shock patients using a continuous, on-line, real-time hemodynamic and oxygen transport monitoring system with a previously described predictive index, modified for the clinical conditions in our ICU. Continuous monitoring and display of cardiac output and 20 or more derived variables, together with the predictive index, were a feasible and useful approach. Unlike previously documented series of elective postoperative general surgical patients, our series consisted of patients with multiple trauma, myocardial infarction, sepsis, and other medical emergencies as well as postoperative cardiac and general surgical patients, all of whom had respiratory failure (acute respiratory distress syndrome). In addition to these differences, our patients were invariably admitted to the ICU after the nadir of their hypotensive crisis. To compare the continuous recorded values with previous studies that used intermittent measurements, three comparable time intervals were selected; data at these time intervals and the predictions derived from them were in satisfactory agreement with prior studies. Moreover, therapeutic goals based on the median values of survivors of the present series were similar, but not identical, to prior series despite differences in the clinical mix and the later postresuscitation ICU admissions of our series.     

Effects of rapid permissive hypercapnia on hemodynamics,gas exchange,and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome

Objective To measure the effects of rapid permissive hypercapnia on hemodynamics and gas exchange in patients with acute respiratory distress syndrome (ARDS).Design Prospective study.Setting: 18-bed, medical intensive care unit, university hospital.Patients 11 mechanically ventilated ARDS patients.Intervention Patients were sedated and ventilated in the controlled mode. Hypercapnia was induced over a 30–60 min period by decreasing tidal volume until pH decreased to 7.2 and/or P₅₀ increased by 7.5 mmHg. Settings were then maintained for 2 h.Results Minute ventilation was reduced from 13.5±6.1 to 8.2±4.1l/min (mean±SD), PaCO₂ increased (40.3±6.6 to 59.3±7.2 mmHg), pH decreased (7.40±0.05 to 7.26±0.05), and P₅₀ increased (26.3±2.02 to 31.1±2.2 mmHg) (p<0.05). Systemic vascular resistance decreased (865±454 to 648±265 dyne·s·cm^–5, and cardiac index (CI) increased (4±2.4 to 4.7±2.4 l/min/m²) (p<0.05). Mean systemic arterial pressure was unchanged. Pulmonary vascular resistance was unmodified, and mean pulmonary artery pressure (MPAP) increased (29±5 to 32±6 mmHg,p<0.05). PaO₂ remained unchanged, while saturation decreased (93±3 to 90±3%,p<0.05), requiring an increase in FIO₂ from 0.56 to 0.64 in order to maintain an SaO₂>90%. PvO₂ increased (36.5±5.7 to 43.2±6.1 mmHg,p<0.05), while saturation was unmodified. The arteriovenous O₂ content difference was unaltered. Oxygen transport (DO₂) increased (545±240 to 621±274 ml/min/m²,p<0.05), while the O₂ consumption and extraction ratio did not change significantly. Venous admixture (Q_va/Q_t) increased (26.3±12.3 to 32.8±13.2,p<0.05).Conclusions These data indicate that acute hypercapnia increases DO₂ and O₂ off-loading capacity in ARDS patients with normal plasma lactate, without increasing O₂ extraction. Whether this would be beneficial in patients with elevated lactate levels, indicating tissue hypoxia, remains to be determined. Furthermore, even though hypercapnia was well tolerated, the increase in Q_va/Q_t, CI, and MPAP should prompt caution in patients with severe hypoxemia, as well as in those with depressed cardiac function and/or severe pulmonary hypertension.     

Imaging in acute respiratory distress syndrome

Purpose

Imaging has become increasingly important across medical specialties for diagnostic, monitoring, and investigative purposes in acute respiratory distress syndrome (ARDS).

Methods

This review addresses the use of imaging techniques for the diagnosis and management of ARDS as well as gaining knowledge about its pathogenesis and pathophysiology. The techniques described in this article are computed tomography, positron emission tomography, and two easily accessible imaging techniques available at the bedside—ultrasound and electrical impedance tomography (EIT).

Results

The use of computed tomography has provided new insights into ARDS pathophysiology, demonstrating that ARDS does not homogeneously affect the lung parenchyma and that lung injury severity is widely distributed in the ARDS population. Positron emission tomography is a functional imaging technique whose value resides in adding incremental insights to morphological imaging. It can quantify regional perfusion, ventilation, aeration, lung vascular permeability, edema, and inflammation. Lung ultrasound and EIT are radiation-free, noninvasive tools available at the bedside. Lung ultrasound can provide useful information on ARDS diagnosis when x-rays or CT scan are not available. EIT is a useful tool to monitor lung ventilation and to assess the regional distribution of perfusion.

Conclusions

The future of imaging in critical care will probably develop in two main directions: easily accessible imaging techniques that can be used at the bedside and sophisticated imaging methods that will be used to aid in difficult diagnostic cases or to advance our understanding of the pathogenesis and pathophysiology of an array of critical illnesses.

     

Miliary tuberculosis and adult respiratory distress syndrome

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role.