We prospectively evaluated the effects of dobutamine on gastric mucosal perfusion and hepatocytic clearance in patients with septic shock. After resuscitation with volume expansion and norepinephrine (12 patients) as needed, 14 hemodynamically stable patients (median age: 60 yr, median SAPS II score: 47) were given an infusion of 7.5 microg/kg/min dobutamine for 1 h. Gastric mucosal perfusion and hepatocytic clearance were assessed with tonometry and indocyanine green (ICG) elimination, respectively. All measurements were made before dobutamine infusion, after 1 h of dobutamine infusion, and 1 h after the infusion ended. Cardiac output (thermodilution technique) increased with dobutamine from a baseline median level of 4.0 L/min/m(2) (range: 1.7 to 7.4 L/min/m(2)) to 5.0 L/min/m(2) (range: 3.5 to 8.9 L/min/m(2)) (p = 0.004) and returned to baseline levels after dobutamine infusion ended. The gastric-arterial PCO(2) difference decreased from a baseline median level of 13 mm Hg (range: 5 to 54 mm Hg) to 7 mm Hg (range: 5 to 48 mm Hg) (p = 0.005). ICG elimination was low in all patients at baseline (median plasma disappearance rate: 12.2%; range: 7.6 to 16.2%) and did not change significantly during or after dobutamine infusion. In summary, dobutamine increases gastric mucosal perfusion but does not alter hepatocytic clearance in patients with septic shock. The absence of a beneficial effect of dobutamine on hepatocytic clearance may be related to profound alterations in hepatocellular metabolism during septic shock.

To identify the potential impact of novel therapeutic approaches, we studied the early predictive factors of survival at the onset of acute respiratory distress syndrome (ARDS) in a 24-bed medical ICU of an academic tertiary care hospital. Over a 48-mo period, a total of 3,511 adult patients were admitted and 259 mechanically ventilated patients met ARDS criteria, as defined by American-European consensus conference, i.e., bilateral pulmonary infiltrates and PaO2/FIO2 lower than 200 without left atrial hypertension. These patients were randomly included in a developmental sample (177 patients) and a validation sample (82 patients). Demographic variables, hemodynamic and respiratory parameters, underlying diseases, as well as several severity scores (SAPS, SAPS-II, OSF) and Lung Injury Score (LIS) were collected. These variables were compared between survivors and nonsurvivors and entered into a stepwise logistic regression model to evaluate their independent prognostic roles. The overall mortality rate was 65%. SAPS-II, the severity of the underlying medical conditions, the oxygenation index (mean airway pressure x FIO2 x 100/PaO2), the length of mechanical ventilation prior to ARDS, the mechanism of lung injury, cirrhosis, and occurrence of right ventricular dysfunction were independently associated with an elevated risk of death. Model calibration was very good in the developmental and validation samples (p = 0.84 and p = 0.72, respectively), as was model discrimination (area under the ROC curves of 0.95 and 0.92, respectively). Thus, the prognosis of ARDS seems to be related to the triggering risk factor, the severity of the respiratory illness, and the occurrence of a right ventricle dysfunction, after adjustment for a general severity score.

Purpose: The aim of this study was to evaluate the reliability of a new continuous cardiac output (CCO) monitoring device (Qvue/OptiQ system; Abbott Critical Care Systems, Mountain View, CA) based on the pulsed warm thermodilution technique in critically ill medical patients.Methods: Nineteen patients with cardiogenic or septic shock were included in the study. Pairs of CCO and intermittent bolus cardiac output (ICO) were noted at least every 6 hours for determination of bias, precision, and limits of agreement. Simultaneously, blood samples were collected, and arterial-venous oxygen content difference (C[a-V]O-2) was determined. A multiple stepwise logistic regression was used to identify situations associated with a CCO-ICO difference exceeded 20%. A multiple linear regression was performed to analyze the respective accuracy of CCO and ICO to predict the variations of C[a-v]O-2.Results: A total of 203 pairs of cardiac output measurements was obtained, The bias was 0.12 L/min (1.2% of pairs mean) and the precision 1.0 L/min (13%). The 95% limits of agreement were between -1.7 L/min (-25%) and 1.9 L/min (+26%), Low blood temperatures and heart rates above 120 beats/min were significantly associated with a ICO-CCO difference higher than 20%. In a multiple linear regression, CCO was significantly correlated with C[a-v]O-2, an independent reflection of the patient's cardiac output; by contrast, ICO did not.Conclusion: These results suggest that ICO and CCO measurement by the Qvue/OptiQ system are interchangeable, except for temperature or heart rate extreme values. Copyright (C) 1998 by W.B. Saunders Company.

Severity of acute lung injury (ALI) can widely vary amongst patients, ranging from mild-to-moderate to the acute respiratory distress syndrome (ARDS) [1, 2]. An abnormal inflammatory response with acute microvascular lung injury causes permeability edema and pulmonary arterial hypertension (PAH). This acute increase in pulmonary artery pressure is usually progressive and results from several mechanisms including increased vascular tone, extrinsic compression, hypoxic pulmonary vasoconstriction (HPV) and vascular microthrombi [3], Clinical studies have demonstrated elevated pulmonary vascular resistance (PVR) persisting after correction of arterial hypoxemia [4]. The presence of PAH has been identified as a poor prognostic factor in patients with ARDS, but the relationship between PAH and outcome is still not well understood [5, 6]. It is plausible that increased mortality observed in the subset of patients with PAH could be related to the effects of pulmonary hypertension on pulmonary edema formation and right ventricular (RV) performance [3, 7]. We found abnormal RV performance, reflected by an increased right atrial pressure/pulmonary artery occlusive pressure ratio, was an early predictive factor of mortality in a multivariate analysis of patients with severe ARDS [8]. However, RV failure, defined as the in-ability to maintain adequate stroke volume, is rare in ALI/ARDS, in which RV output is usually conserved by the Frank-Starling mechanism [9–13]. RV failure occurs only when PAH is acute and severe, or when associated diseases alter RV contractile state.

OBJECTIVE The Sometec Dynemo-3000 system allows the permanent measurement of descending aorta diameter by an echographic (A-scan) device and the blood flow velocity by a pulse Doppler velocimeter. The Dynemo-3000 then furnishes a new hemodynamic parameter, i.e., descending aortic blood flow (ABF), which is a fraction of the cardiac output (CO). We evaluate the ability of this system to measure the aortic diameter and to accurately detect ABF changes. DESIGN A case study prospective trial. SETTING A 24-bed medical intensive care unit of a 1,100-bed university hospital. PATIENTS Twenty critically ill patients fully sedated, mechanically ventilated, and monitored by a pulmonary artery catheter. INTERVENTIONS CO values determined by conventional thermodilution method (TD-CO) and ABF were recorded during the study, which included two initial baseline periods, a dobutamine infusion (5 microg/kg/min) interval of 30 mins, and a third baseline period. To assess the accuracy of A-scan, aortic diameter was measured by transesophageal echocardiography. The difference between echocardiography and A-scan was used to determine bias and precision for aortic diameter measurements. TD-CO and ABF variations were analyzed using Kruskal-Wallis and Wilcoxon tests. Association between TD-CO and ABF values was determined by calculating the linear correlation coefficient. The ability of ABF to detect a TD-CO >6.0 L/min and its variations >13% was analyzed by determination of sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. MEASUREMENTS AND MAIN RESULTS Aortic diameter measurements by A-scan and bidimensional methods were 23.0+/-2.8 mm (SD) and 24.2+/-2.7 mm, respectively. Bias and precision were 1.1 mm and 1.4 mm (95% confidence interval: -1.9 to 3.7), respectively. During the course of dobutamine infusion, we observed a significant increase of TD-CO mean value from 6.65+/-1.53 L/min to 9.30+/-2.5 L/min (p=.0008), and a parallel and significant increase in ABF mean value from 4.34+/-1.18 L/min to 5.70+/-1.63 L/min (p= .0029). Absolute TD-CO and ABF values had a correlation coefficient of 0.80. For detection of an increased TD-CO, PPV and NPV were 87% and 86%, respectively. For detection of TD-CO changes >13%, PPV and NPV were 80% and 94%, respectively. CONCLUSIONS The Dynemo-3000 system is able to display the real aortic diameter, which is one of the most important components of this noninvasive ultrasonic technique. When compared with TD-CO, the ABF determination provided by this ultrasonic device constitutes a reliable noninvasive tool for estimating CO and tracking its changes.

The purpose of this study was to investigate circulating polymorphonuclear leucocyte (PMNL) oxidative metabolism and lipid peroxidation in patients with adult respiratory distress syndrome (ARDS) who were treated with low- frequency, positive-pressure ventilation with extracorporeal carbon dioxide removal.

Several risk factors for deep sternal wound infection after sternotomy remain unclear. To assess and compare risk factors among units, a prospective study included 1830 patients in 10 units during a 4-month period: 960 underwent coronary artery bypass grafting and 870 underwent other procedures. According to the Centers for Disease Control and Prevention definitions, 2.3% of patients (42/1830) acquired a deep sternal wound infection. Independent risk factors for deep sternal wound infection were obesity, coronary artery bypass grafting, reoperation, and postoperative inotropic support. Independent risk factors after coronary artery bypass grafting were obesity, bilateral internal thoracic artery grafting, reoperation, and postoperative inotropic support. In all five of the units usually performing bilateral internal thoracic artery graftings, this procedure was associated with high risk of deep sternal wound infection. Duration of operation was a major risk factor in comparison of the unit with the highest risk of deep sternal wound infection with the other nine units; this suggests that parameters related to the perioperative period were involved. Multicenter surveillance is useful to determine reliable risk factors for deep sternal wound infection, to define a high-risk population before operation, and to assess unit-specific risk factors.

More than a decade ago, the existence of an extremely labile and potent endogenous vasodilator synthesized by the endothelium, termed endothelium-derived relaxing factor (EDRF), was established by Furchgott and Zawadzki [1]. The nature of EDRF since remained elusive until experimental results from several laboratories identified it as the free radical nitric oxide (NO) [2,3]. Because it has a single unpaired electron, NO is also considered to be a free radical [4]. Molecular targets of NO are diverse, including heme proteins, non-heme iron-sulfur enzymes, DNA, and reactive oxygen species such as superoxide anion [5, 6]. Depending on its nature, the target molecule can either be activated (e.g. the heme-protein soluble guanylate cyclase) or inhibited (e.g. the non-heme iron protein ferritin) as a result of reacting with NO. In vascular smooth muscle, the molecular target of NO is the soluble enzyme guanylate cyclase [7]. Stimulation of the latter by NO increases the level of the second messenger cyclic guanosine monophosphate (cGMP) within vascular smooth muscle, thereby causing vasorelaxation [8]. The biochemistry of NO synthesis is remarquably simple, as to the nature of its precursors. The nitrogen atom of NO is derived from the N-guanidino terminal of the amino acid, L-arginine, whereas the oxygen atom is provided by molecular oxygen [7]. NO is synthesized from these two precursors by a newly discovered family of enzymes, the NO synthases (NOS).The complementary DNA for various isoforms of the NOS family have been recently cloned, and their amino acid primary structure sequenced [9]. There are two major subgroups of NOS isoforms, the constitutive and the inducible one. Endothelial NOS are predominantly constitutive, and most certainly play a key role in the modulation of systemic [10] and pulmonary [11] vascular tone.

This study was aimed at providing data for optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). The effects of ventilation with positive end-expiratory pressure (PEEP) titrated to blood gases were studied by thoracic computed tomographic (CT) scans and lung mechanics measurements in eight patients. CT density histograms at end-expiration were used to investigate the effects of PEEP on three differently aerated zones. Static pressure-volume (P-V) curves were used to determine the deflection point above which baro-volotrauma (a combination of barotrauma and volotrauma) may occur. Peak pressures, plateau pressures, and lung volumes measured by Respitrace were compared with the deflection point. CT scan showed that PEEP increased "normally aerated" areas, decreased "nonaerated" areas, and did not change "poorly aerated" zones. No correlations were found between CT scan and either PaO2 or mechanical data. Pressure at the deflection point was lower than the usually recommended 35 to 40 cm H2O for peak pressure in four patients (range, 28 to 32 cm H2O). With regard to plateau pressures, only one patient was ventilated above the deflection point. However, monitoring of volumes showed that these four patients had an end-inspiratory volume above this point. We conclude that mechanical ventilation may be initially adjusted on the basis of blood gas values and then optimized on the basis of lung mechanics to limit the risk of baro-volotrauma.

The mortality of the adult respiratory distress syndrome (ARDS) remains high, but patients who survived the acute phase of the syndrome generally resume productive lives with no serious pulmonary limitations [1–3]. Specific treatments of ARDS should ideally be directed to limit the initial abnormal inflammatory response. However, ARDS therapy is essentially supportive with a central role for mechanical ventilation. Conventional mode of ventilation aimed to obtain “normal” pulmonary function as reflected by arterial blood gases, and some lung injury was accepted as an inevitable consequence [4, 5]. Positive-end expiratory pressure (PEEP) has been early proposed to achieve adequate arterial oxygenation while decreasing FiO2 to limit oxygen toxicity [4, 5]. This type of ventilatory support is frequently associated with high airway pressures and volumes for effective ventilation which, in turn, may worsen the lung injury [7–11]. Optimal ventilation would be the mode achieving adequate gas exchange without increasing the risk of ventilator-induced barotrauma [7, 12]. New strategies have been developed to prevent the lungs exposure to high pressures and to lower minute ventilation [13–15]. All these modes of ventilation introduce a new concept of ventilation which allows “abnormal” respiratory function with hypercapnia [12, 16]. There are no convincing data indicating that any ventilatory mode is superior to others for ARDS patients, both in terms of reduction of morbidity and mortality.

Tracheal gas insufflation (TGI) of pure oxygen combined with mechanical ventilation decreases dead space and increases CO2 clearance. In the present study, TGI was used in six patients with ARDS who met extracorporeal membrane oxygenation criteria and who were severely hypoxemic and hypercapnic despite optimal pressure-controlled ventilation. This open clinical study aimed to investigate the effects of 4 L/min continuous flow of oxygen given via an intratracheal catheter. PaCO2 decreased from 108 +/- 32 to 84 +/- 26 mm Hg (p < 0.05), and no significant change in PaO2 (68 +/- 18 vs 96 +/- 43, p = 0.06). There was no change in airway pressures and hemodynamic variables. A slight increase in end-expiratory and end-inspiratory volumes with TGI possibly occurred, as seen on tracings from respiratory inductive plethysmography (Respitrace). We conclude that TGI improves tolerance of limited pressure ventilation by removing CO2, but it may induce changes in lung volumes that are not detected by ventilator measurements.