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 transport in adult respiratory distress syndrome and other acute circulatory problems: relationship of oxygen delivery and oxygen consumption

OBJECTIVE: To evaluate the evidence that oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). DATA SOURCES: Studies published since 1972 with their relevant bibliographies and computerized search of MEDLINE. STUDY SELECTION: All clinical papers reporting the relationship of: VO2 to DO2 in the adult respiratory distress syndrome (ARDS), sepsis, other critically ill patients, and normal individuals; cardiac output determined by measured VO2 to calculated VO2 from the arterial-mixed venous oxygen difference; blood lactate to DO2; and selected basic science studies. DATA EXTRACTION: Study quality was assessed and all pertinent data were summarized. RESULTS OF DATA EXTRACTION: Normal individuals display physiologic dependence of VO2 at very low levels of DO2 (330 mL/min.m2). Pathologic dependence of VO2 on DO2 entails two concepts: a) VO2 varies directly with DO2 over a wide range of DO2 and b) of particular import, tissue oxygen extraction is compromised. This pathologic supply dependence was initially identified in patients with ARDS; subsequently, it has been demonstrated in patients with sepsis and in a variety of other critically ill individuals. There are substantial, but not uniform, data documenting this dependence of VO2 on DO2 in ARDS. In some studies, this relationship correlates best with increased lactate concentrations. However, increased blood lactate concentrations do not accurately track other evidence of tissue hypoxia. Some researchers have attributed the finding of this supply dependency to artifact, when VO2 is determined by the arterial-mixed venous oxygen difference. However, when these methods are compared, the correlation is excellent. Others have raised the concern that appreciable changes in VO2, even over short periods of time, may result in physiologic increases in DO2. However, when "control" groups have been contemporaneously compared with patients with ARDS using the same methodology, they have not shown supply dependency. Interwoven throughout the studies reviewed is overwhelming and uniform evidence that both mixed venous oxygen tension (PVO2) and mixed venous oxygen content (CVO2) correlate poorly with cardiac output, DO2, or VO2. The inconsistencies in identifying pathologic DO2 dependency may well reflect the unknown variables that exist in patients with ARDS, perhaps better labeled, multiple organ system failure. CONCLUSIONS: Pathologic dependence of VO2 on DO2, especially the inability to increase tissue oxygen extraction, is present in most patients with ARDS and many other critically ill individuals. PVO2 and CVO2 are both unreliable indicators of cardiac output, DO2, or VO2.     

高频振动通气在急性呼吸窘迫综合征治疗中的作用

目的　评估高频振动通气 (high frequencypercussiveventilation ,HFPV)在成人ARDS治疗中的有效性和安全性 ,探索ARDS治疗的新途径。方法　临床观察 93例ICU条件下使用HFPV的ARDS病人 ,对常规通气 (conventionalventilation ,CV)和HFPV下的PaO2 /FiO2 、PaCO2 、DO2 、VO2 、Qs/Qt、PEEP/CPAP、PAWP等氧代谢、血流动力学指标和呼吸参数的变化进行统计分析。结果　 93例病人中 ,存活 6 6例 ,死亡2 7例 ,死亡率为 2 9 0 % (除外 7例未死于ICU者 ,实际死亡率为 2 1 5 % )。使用HFPV前后PaO2 /FiO2 、PaC O2 、DO2 、VO2 、Qs/Qt的变化为 (77 6± 2 0 0 )和 (2 0 8 7± 70 8)、 (471 2± 114 7)和 (6 0 1 3± 14 0 9)、(10 7 6± 34 3)和 (14 6 4± 2 3 3)、 (35 7± 2 0 5 )和 (2 4 5± 6 5 ) (P <0 0 5 )。X ray胸片双肺阴影减轻或消失 ,同时可看到病人鼻腔口腔有不等量的混浊液体从呼吸道溢出。结论　HFPV在ARDS治疗中是有效和安全的。临床应用HFPV能明显改善氧代谢 ,提高PaO2 /FIO2 。早期应用和合理化管理能明显降低ARDS的病死率     

Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.     

Redox status of cytochrome a,a3: a noninvasive indicator of dysoxia in regional hypoxic or ischemic hypoxia

OBJECTIVE: Multiwavelength near infrared (NIR) spectrophotometry can monitor the redox state of cytochrome a,a3 (cyt a,a3) in vivo. Because cyt a,a3 is the most immediate reductant of oxygen, this technique has been proposed to evaluate tissue oxygenation. The purpose of this study was to examine the relationship between cyt a,a3 oxidation level as an indicator of dysoxia and oxygen uptake (VO2) when oxygen delivery (DO2) was progressively lowered in an in situ vascularly isolated hindlimb. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Fourteen pigs. INTERVENTIONS: Measurement of critical values for both VO2 and cyt a,a3 oxidation during ischemic and hypoxic hypoxia. MEASUREMENTS AND MAIN RESULTS: The right hindlimb of anesthetized, paralyzed, and ventilated pigs was subjected to progressive ischemic or hypoxic hypoxia for 100 mins by ten stepwise decreases in DO2. In ischemic hypoxia (n = 7), arterial inflow (Q) from a pump-membrane oxygenator system was lowered from 50 to 0 mL/min, with PaO2 maintained at 100 mm Hg. In hypoxic hypoxia (n = 6), PaO2 was lowered from 100 mm Hg to 0 mm Hg. Hindlimb DO2 was calculated as the product of Q and arterial oxygen content, and VO2 as the product of Q and arteriovenous difference. The cyt a,a3 oxidation level was measured every 10 secs with a four-wavelength spectrophotometer. These parameters were measured 9 mins after each change of DO2. Critical values for both VO2 and cyt a,a3 oxidation level as a function of DO2 were determined in each animal by dual linear regression analysis. In ischemic and hypoxic hypoxia, a strong correlation was found between cyt a,a3 oxidation level and VO2 in both ischemic and hypoxic hypoxia (r2 =.90 and .87, respectively). Hindlimb vascular resistance increased in ischemic hypoxia and decreased in hypoxic hypoxia when DO2 reached critical DO2. CONCLUSIONS: From these results, we concluded that monitoring the cyt a,a3 redox state by NIR spectrophotometry is, in this experimental setting, a sensitive indicator of dysoxia during regional hypoxic or ischemic hypoxia.     

Blood transfusion and oxygen consumption in surgical sepsis

OBJECTIVE: To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption (VO2) in response to increasing oxygen delivery (DO2) after blood transfusion in surgical sepsis. DESIGN: Prospective study. SETTING: Tertiary care, trauma center. PATIENTS: Twenty-one patients, postsurgical or posttrauma, judged septic by defined criteria. INTERVENTIONS: Serum lactic acid concentrations, DO2, and VO2 were measured before and after transfusion therapy. MEASUREMENTS AND MAIN RESULTS: Overall, the DO2 increased from 532 +/- 146 to 634 +/- 225 (SD) mL/min.m2 (p less than .001), and the VO2 increased from 145 +/- 39 to 160 +/- 56 mL/min.m2 (p = .02). These changes occurred with an Hgb increase from 9.3 +/- 1.1 to 10.7 +/- 1.5 g/dL (p less than .001). The patients were grouped by their pretransfusion serum lactic acid values. In those patients with normal (less than 1.6 mmol/dL) serum lactic acid (n = 10), DO2 increased from 560 +/- 113 to 676 +/- 178 mL/min.m2 (p less than .02), and VO2 increased from 150 +/- 25 to 183 +/- 46 mL/min.m2 (p less than .02). However, in the increased serum lactic acid group (n = 17), VO2 was not significantly changed after transfusion (143 +/- 46 to 146 +/- 58 mL/min.m2) despite increased DO2 (515 +/- 163 to 609 +/- 251 mL/min.m2, p less than .01). CONCLUSIONS: Blood transfusion can be used to augment DO2 and VO2 in septic surgical patients. Increased serum lactic acid values do not predict patients who will respond. The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent VO2. Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in VO2 with increasing DO2.     

Cell metabolism in patients undergoing major valvular heart surgery: relationship with intra and postoperative hemodynamics, oxygen transport, and oxygen utilization patterns

The relationships between cell metabolism and both hemodynamics and oxygen transport/utilization (VO2/DO2) pattern were evaluated intra and postoperatively in eight patients undergoing major valvular heart surgery with the aid of moderately hypothermic cardiopulmonary bypass (CPB). Quadriceps femoris specimens were obtained by the needle biopsy technique for muscle ATP, ADP, AMP, phosphocreatine (PCr), creatine and lactate determination at anesthesia induction, after CPB, as well as in the ICU 18 h after surgery. Moreover, hemodynamic variables, oxygen transport and utilization indices, and plasma lactate were measured at the same intervals and throughout the CPB period. After CPB, muscle ATP and PCr contents were reduced (p less than .05) as compared to those of both pre-CPB patients and healthy control subjects; muscle and plasma lactate levels were increased (p less than .05). Mean VO2 and DO2 values measured during CPB significantly decreased (p less than .05), but VO2 reduction was proportionally greater than that of DO2 (-62% vs. -41%). No correlation was found between VO2 and DO2 at that time, but a significant relationship (p less than .05) was found at the end of CPB. A further decrease in muscle ATP and PCr levels was measured in the ICU, as muscle and plasma lactate levels were still elevated. At that time, VO2 and DO2 were not significantly different from pre-CPB values, but were significantly (p less than .05) correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Experience with phenylephrine as a component of the pharmacologic support of septic shock

OBJECTIVE: To evaluate the use of the selective alpha 1-adrenergic receptor agonist phenylephrine in the hemodynamic support of patients with septic shock. DESIGN: Retrospective analysis of clinical use of phenylephrine. SETTING: Surgical ICU in a university hospital. PATIENTS: Thirteen patients with septic shock (diagnosed by defined criteria) requiring pharmacologic support for the treatment of hypotension. INTERVENTIONS AND MAIN RESULTS: All patients underwent invasive hemodynamic monitoring followed by volume resuscitation and inotropic support to reverse flow-dependent oxygen consumption and lactic acidosis. Patients with persistent hypotension (mean arterial pressure [MAP] less than 65 mm Hg) and vasodilation (systemic vascular resistance index [SVRI] less than 1500 dyne.sec/cm5.m2 received phenylephrine at iv infusion rates of 0.5 to 9 micrograms/kg.min to maintain MAP greater than 70 mm Hg. MAP, SVRI, left ventricular stroke work index, and stroke volume index were significantly (p less than .05) increased after phenylephrine administration and at the time of highest oxygen consumption (VO2). Cardiac index was unchanged initially but increased at the time of highest VO2 (p less than .05). Pulmonary artery occlusion pressure and heart rate were unchanged. Average baseline VO2 increased from 145 to 200 mL/min.m2 and oxygen delivery (DO2) increased from 447 to 597 mL/min.m2 during phenylephrine treatment (p less than .05). Blood lactate concentrations decreased and urine output increased significantly (p less than .05), while serum creatinine concentrations remained unchanged during phenylephrine therapy. CONCLUSIONS: Treatment with phenylephrine was associated with beneficial hemodynamic effects when used to maintain perfusion, while increasing DO2 and VO2 in patients with septic shock.     

End-tidal CO2 pressure determinants during hemorrhagic shock

OBJECTIVES: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. DESIGN AND SETTING: Prospective, observational study in a research laboratory at a university center. SUBJECTS AND INTERVENTIONS: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. MEASUREMENTS AND RESULTS: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/ DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r2 = 0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r2 = 0.77). Critical DO2 for PETCO2 and VO2 was 8.0 +/- 3.3 and 6.3 +/- 2.5 ml x min(-1) kg(-1), respectively (NS). CONCLUSIONS: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency.     

Ventilation/perfusion indices do not correlate with the difference between oxygen consumption measured by the Fick principle and metabolic monitoring systems in critically ill patients.

OBJECTIVE: To determine whether the difference between oxygen consumption (VO2) measured by metabolic gas monitoring systems and by the Fick principle is related to venous admixture, deadspace/tidal volume ratio, or alveolar-arterial oxygen tension gradient in critically ill patients. DESIGN: A prospective study. SETTING: An 11-bed general ICU in a 900-bed teaching hospital. PATIENTS: Twenty critically ill patients admitted to the ICU who required mechanical ventilation, right heart catheterization, and arterial and mixed venous gas measurements for normal clinical management. RESULTS: Thirty-three recordings were analyzed. The mean VO2 measured by the metabolic gas monitoring system was 308 +/- 63.9 (SD) mL/min and was significantly greater than the mean VO2 measured by the Fick principle of 284 +/- 72.0 mL/min. The difference between the two measurements of 24.3 +/- 47.6 mL/min correlated poorly with venous admixture (r2 = .0009), dead-space/tidal volume ratio (r2 = .0064) and alveolar-arterial oxygen tension gradient (r2 = .017). CONCLUSIONS: If the difference in VO2 measured by metabolic gas monitoring systems and the Fick principle is due to intrapulmonary VO2 then in critically ill patients the ventilation/perfusion indices of venous admixture, deadspace/tidal volume ratio and alveolar-arterial oxygen tension gradient correlate poorly with intrapulmonary VO2.     

Different dosages of dobutamine in septic shock patients: determining oxygen consumption with a metabolic monitor integrated in a ventilator

OBJECTIVE: Oxygen consumption (VO2) obtained from respiratory gases by indirect calorimetry (VO2,IC) with a metabolic monitor integrated in a ventilator were to be compared to VO2 obtained by the Fick principle (VO2,Fick) in septic patients following an increase in oxygen delivery (DO2) induced by positive inotropic support. DESIGN: Prospective clinical study. SETTING: University Hospital, Surgical Intensive Care Unit (ICU). PATIENTS: Thirty patients suffering from sepsis. INTERVENTIONS: DO2 was increased by dobutamine infusion, starting with an initial dosage of 5 microg x kg x min, increased to a maximum of 10 microg x kg x min. MEASUREMENTS AND MAIN RESULTS: Dobutamine infusion induced a dosage-related increase in DO2 (from 577 +/- 192 to 752 +/- 202 ml x min x m2, p < 0.01), which was associated with a statistically significant increase in VO2,IC (from 173 +/- 30 to 188 +/- 28 ml x min x m2, p < 0.01) and in VO2,Fick (from 140 +/- 25 to 156 +/- 24 ml x min x m2, p < 0.01). The comparison between VO2,IC and VO2,Fick revealed differences (bias and precision--33 +/- 32 ml x min x m2). CONCLUSIONS: With a metabolic monitor integrated in a ventilator it was possible to carry out continuous monitoring of calorimetric data under clinical conditions. In contrast to previous studies using indirect calorimetry, this study showed a moderate correlation between VO2 and DO2 in septic patients using either method. The clinical relevance of this finding requires further investigation. Different factors (e. g. injectant temperature, pulmonary VO2) produced substantial differences between VO2,IC and VO2,Fick as previously shown.     

Intensive care unit length of stay: Benchmarking based on Acute Physiology and Chronic Health Evaluation (APACHE) IV

OBJECTIVE: To revise and update the Acute Physiology and Chronic Health Evaluation (APACHE) model for predicting intensive care unit (ICU) length of stay. DESIGN: Observational cohort study. SETTING: One hundred and four ICUs in 45 U.S. hospitals. PATIENTS: Patients included 131,618 consecutive ICU admissions during 2002 and 2003, of which 116,209 met inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The APACHE IV model for predicting ICU length of stay was developed using ICU day 1 patient data and a multivariate linear regression procedure to estimate the precise ICU stay for randomly selected patients who comprised 60% of the database. New variables were added to the previous APACHE III model, and advanced statistical modeling techniques were used. Accuracy was assessed by comparing mean observed and mean predicted ICU stay for the excluded 40% of patients. Aggregate mean observed ICU stay was 3.86 days and mean predicted 3.78 days (p < .001), a difference of 1.9 hrs. For 108 (93%) of 116 diagnoses, there was no significant difference between mean observed and mean predicted ICU stay. The model accounted for 21.5% of the variation in ICU stay across individual patients and 62% across ICUs. Correspondence between mean observed and mean predicted length of stay was reduced for patients with a short (< or =1.7 days) or long (> or =9.4 days) ICU stay and a low (<20%) or high (>80%) risk of death on ICU day 1. CONCLUSIONS: The APACHE IV model provides clinically useful ICU length of stay predictions for critically ill patient groups, but its accuracy and utility are limited for individual patients. APACHE IV benchmarks for ICU stay are useful for assessing the efficiency of unit throughput and support examination of structural, managerial, and patient factors that affect ICU stay.     

Dopamine does not correct oxygen consumption/oxygen delivery relation abnormality during vasomotor shock induced by interleukin-1beta

We previously showed that interleukin 1beta (IL-1beta) induces vasomotor shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. In the present study, we investigated the inotropic effect of dopamine on the VO2/DO2 abnormality induced by IL-1beta. Twelve rabbits were divided into two groups (n = 6, each) and were given 10 microg/kg of IL-1beta or saline (control) intravenously. After baseline measurements were obtained, dopamine was infused continuously at a rate of 20 microg/kg/min throughout the study in both groups. All rabbits were subjected to stepwise cardiac tamponade to reduce the DO2 to <5 mL/min/kg by inflation of a handmade balloon placed into the pericardial sac. The VO2/DO2 relation was then analyzed by the dual-line method. Dopamine failed to correct the IL-1beta-induced decrease in mean arterial pressure to the baseline level. Dopamine significantly increased cardiac index in both groups, resulting in significant increases in DO2 (IL-1beta, 28.5 +/- 6.0 mL/min/kg from baseline 24.1 +/- 3.5 mL/min/kg; control, 27.7 +/- 2.9 mL/min/kg from baseline 22.9 +/- 2.9 mL/min/kg), but did not affect VO2 (IL-1beta, 10.0 +/- 0.5 mL/min/kg from baseline 9.9 +/- 0.7 mL/min/kg; control, 10.2 +/- 0.4 mL/min/kg from baseline 10.2 +/- 0.2 mL/min/kg). The IL-1beta group showed a significantly greater supply-independent line slope than that of controls (IL-1beta, y = 0.14x + 6.3; control, y = 0.06x + 8.6) during stepwise decreases in DO2. These results indicate that continuous infusion of dopamine at 20 microg/kg/min increases DO2 but does not correct the vasomotor disturbance or VO2/DO2 abnormality caused by IL-1beta.     

Gastric-arterial PCO2 gradient does not reflect systemic and splanchnic hemodynamics or oxygen transport after cardiac surgery

Gastric mucosal-arterial PCO2 gradient (P(g-a)CO2) is used to assess splanchnic perfusion and oxygenation. We evaluated whether P(g-a)CO2 reflects whole body (Q) and splanchnic (Qsp) blood flow, oxygen delivery (DO2) and consumption (VO2) after coronary artery by pass graft (CABG) operation. Thirty patients received dobutamine or dopexamine to increase cardiac index, 15 patients enalapril or sodium nitroprusside to lower blood pressure, and 30 patients were controls. We measured Q, Qsp (hepatic vein catheter and indocyanine green), and gastric mucosal PCO2 (nasogastric tonometer) before and after interventions. Multiple linear regression model showed that none of the changes in Q, Qsp, and splanchnic or systemic DO2 and VO2 significantly explained changes in P(g-a)CO2 (deltaP(g-a)CO2). All independent variables together explained only 7% of deltaP(g-a)CO2. Increased splanchnic blood flow (0.65 +/- .19 vs. 0.94 +/- .31 L/min/m2, P < 0.001) and increased splanchnic DO2 (101 +/- 28 vs. 143 +/- 42 mL/min/m2, P < 0.001) during catecholamine infusions were associated with increased P(g-a)CO2 (8 +/- 8 vs. 11 +/- 7 mmHg, P = 0.003). P(g-a)CO2 does not reflect whole body or splanchnic blood flow, DO2 or VO2 after CABG operations. The physiology of P(g-a)CO2 is complex and therefore it is difficult for clinicians to interpret changes in gastric mucosal-arterial PCO2 gradient in individual patients after cardiac surgery.     

Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs.

BACKGROUND AND METHODS: This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each group): control, endotoxin alone (E) 4 mg/kg iv, and endotoxin + dopexamine (E + D) 12 micrograms/kg.min. Data were analyzed between and within groups by split-plot analysis of variance with significance of identified differences tested post hoc by Duncan's multiple range test. Donor RBC and dextran were used after endotoxin to maintain adequate perfusion pressures, with Hct kept near 40%. Blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization. RESULTS: In E group, cardiac output (Qt), mean arterial pressure (MAP), systemic DO2, and oxygen uptake (VO2) decreased despite blood volume expansion. In E + D group with similar volume expansion, dopexamine maintained Qt, systemic DO2, and VO2 near the control levels, although MAP and systemic vascular resistance were reduced. In comparison with control subjects, endotoxin increased critical DO2 in the isolated limb muscles from 4.6 to 7. mL/kg.min and decreased critical oxygen extraction from 81% to 68%. The pressure/flow relationship in the limb became flattened, indicating loss of vascular reactivity. In the E + D group, there was no further change in the pressure/flow curve nor in the critical oxygen extraction level. CONCLUSIONS: Dopexamine provided hemodynamic support for endotoxic dogs, thereby increasing total DO2 and VO2, while not altering oxygen extraction in the muscle.     

Plasma endothelin levels are increased during septic shock.

OBJECTIVE: To study whether serially measured plasma concentrations of endothelin (a novel, potent, endogenous vasoconstrictor derived from endothelium and macrophages) relate to the pathophysiology and severity of human septic shock. DESIGN: Prospective analysis. SETTING: Medical ICU of a university hospital. PATIENTS: Six patients with septic shock, studied for 8 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: The initial plasma endothelin concentration was increased (14.2 +/- 5.2 [SD] vs. normal 4.2 +/- 0.7 pg/mL, p less than .05) and correlated with the Acute Physiology and Chronic Health Evaluation II score (r2 = .79, p less than .05). For pooled data, endothelin levels correlated poorly with leukocyte counts (r2 = .13), mean arterial pressure (MAP) (r2 = .16), and administered doses of dopamine (r2 = .26). In multiple regression analyses, plasma endothelin concentrations were predicted by dopamine doses and not by MAP. Plasma endothelin concentrations predicted the decrease in creatinine clearance, independently from MAP. The pooled value for correlations between endothelin levels and creatinine clearance, during the course of disease in individual patients, was statistically significant (r2 = .31). CONCLUSIONS: During septic shock, the release or production of endothelin may increase as a consequence of endothelial injury by activated leukocytes and the infusion of catecholamines, and this mechanism may relate to renal vasoconstriction and to the severity of disease.     

The spontaneous breathing pattern and work of breathing of patients with acute respiratory distress syndrome and acute lung injury

BACKGROUND: The spontaneous breathing pattern and its relationship to compliance, resistance, and work of breathing (WOB) has not been examined in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). Clinically, the ratio of respiratory frequency to tidal volume (f/VT) during spontaneous breathing may reflect adaptation to altered compliance, resistance, and increased WOB. We examined the relationship between f/VT, WOB, and respiratory system mechanics in patients with ARDS/ALI. METHODS: Data from spontaneous breathing trials were collected from 33 patients (20 with ARDS, 13 with ALI) at various points in their disease course. WOB and respiratory system mechanics were measured with a pulmonary mechanics monitor that incorporates Campbell diagram software. Differences between the patients with ARDS and ALI were assessed with 2-sided unpaired t tests. Multivariate linear regression models were constructed to assess the relationship between f/VT and other pulmonary-related variables. RESULTS: Patients with ARDS had significantly lower compliance than those with ALI (24 +/- 6 mL/cm H2O vs 40 +/- 13 mL/cm H2O, respectively, p < 0.001), but this did not translate into significant differences in either WOB (1.70 +/- 0.59 J/L vs 1.43 +/- 0.90 J/L, respectively, p = 0.30) or f/VT (137 +/- 82 vs 107 +/- 49, respectively, p = 0.23). Multivariate linear regression modeling revealed that peak negative esophageal pressure, central respiratory drive, duration of ARDS/ALI, minute ventilation deficit between mechanical ventilation and spontaneous breathing, and female gender were the strongest predictors of f/VT. CONCLUSION: The characteristic rapid shallow breathing pattern in patients with ARDS/ALI occurs in the context of markedly diminished compliance, elevated respiratory drive, and increased WOB. That f/VT had a strong, inverse relationship to peak negative esophageal pressure also may reflect the influence of muscle weakness.     

体外膜肺氧合治疗ARDS期间氧代谢变化与预后的关系

目的探讨体外膜肺氧合（ECMO）治疗重症急性呼吸窘迫综合征（ARDS）期间的氧代谢、乳酸水平的变化与预后的关系。方法回顾性分析17例机械通气效果不佳、应用体外膜肺氧合治疗的急性呼吸窘迫综合征患者,以应用ECMO后30d为观察终点,分为存活组和死亡组,统计分析治疗前后两组患者的氧代谢、血乳酸水平变化,分析各项指标与预后的关系。结果应用体外膜肺氧合后,患者氧代谢情况明显改善,10例患者治愈,7例死亡。两组患者应用ECMO后氧供、氧耗均明显增加,存活组患者的氧摄取率基本维持在正常水平,乳酸水平呈下降趋势。死亡组患者的氧摄取率明显提高,乳酸水平未见明显下降。结论体外膜肺氧合治疗重症急性呼吸窘迫综合征,氧摄取率维持在正常水平、乳酸水平逐渐下降提示预后良好。