L. D H Wood

Absence of supply dependence of oxygen consumption in patients with septic shock

We tested whether oxygen consumption (VO2) was dependent on oxygen delivery (QO2) in 10 patients with septic shock when QO2 was changed by the use of the inotropic agent, dobutamine. The mean acute physiology and chronic health evaluation (APACHE) II score of the patients was 27.3 +/- 8.1 with a mean blood pressure on entry of 66.8 +/- 12.4 mm Hg, and all had been volume resuscitated to a pulmonary artery occlusion pressure of greater than 10 mm Hg. We measured VO2 by analysis of respiratory gases (VO2G) while calculating VO2 by the Fick equation (VO2F) at three different O2 deliveries. When the dobutamine infusion rate was increased from 2.5 +/- 4.0 to 12.3 +/- 6.0 micrograms/kg/min, thermodilution cardiac output increased from 7.7 +/- 2.6 to 10.1 +/- 2.7 L/min (P < .01). Accordingly, dobutamine increased QO2 from 13.5 +/- 3.8 to 18.2 +/- 4.3 mL/min per kg (increase of 36.4% +/- 19.7%; P < .01), but VO2G did not increase (3.2 +/- 0.5 to 3.2 +/- 0.6 mL/min per kg). During these same interventions, the VO2F tended to increase (2.9 +/- 0.7 to 3.4 +/- 0.8 mL/min per kg, P < .06), presumably a spurious correlation because of measurement errors shared by the calculation of VO2F and QO2. Neither lactic acidosis nor acute respiratory distress syndrome (ARDS) conferred supply dependence of VO2G, but the presence of ARDS was predictive of death in this cohort. It is concluded that VO2 is independent of QO2 in patients with septic shock and lactic acidosis. These data confirm that maximizing QO2 beyond values achieved by initial fluid and vasoactive drug resuscitation of septic shock does not improve tissue oxygenation as determined by respiratory gas measurement of VO2.

Management of the Clitically Ill Asthmatic Patient

Status asthmaticus is a life-threatening condition characterized by rapid or inexorable progression of airflow obstruction that may lead to respiratory failure. It must be distinguished from other causes of dyspnea with signs of airflow limitation, and therapy must then be directed at relief of bronchospasm and airway inflammation, with use of multiple pharmacologic agents. Patients require moment-to-moment assessment until airway disease reverses. During this early portion of their course, intubation and mechanical ventilation may be required. Successful management on the ventilator requires an understanding of underlying abnormalities of lung mechanics and the interaction of the lungs and circulation.

The Effect of Nitroprusside on Pulmonary Edema, Oxygen Exchange, and Blood Flow in Hydrochloric Acid Aspiration

In canine pulmonary capillary leak induced by intravenous oleic acid, reducing pulmonary wedge pressure (Ppw) reduces pulmonary edema, venous admixture (Qva/Qt), and cardiac output (Qt). The authors tested the possibility that in another canine model of pulmonary capillary leak, that induced by endobronchial instillation of hydrochloric acid, nitroprusside would reduce Ppw and edema without reducing Qt or oxygen delivery (QO2). In 18 dogs, the authors measured extravascular lung water (EVLW) by thermal-dye dilution and the hemodynamic and gas exchange variables before and at intervals (1,1.5,3, and 5 h) after .1 N HCI bronchial infusion. By 1 h, HCI increased EVLW from 175 to 250 ml and Qva/Qt from 11 to 21%. Immediately after the 1-h measurements, the dogs were divided into three equal groups: six controls (C) were maintained with a Ppw of 12 mmHg, while plasmapheresis (P) or nitroprusside (NP) reduced Ppw to 5 mmHg for the next 4 h. EVLW continued to increase to 548 ml in C, but did not increase further in P and NP. Weights of lungs excised at 5 h confirmed that P and NP reduced edema by 50% in 4 h. In C, Qva/Qt increased, but there was no reduction in Qt or QO2. In contrast, plasmapheresis reduced Qva/Qt, Qt, and QO2. With nitroprusside, Qt and QO2 were maintained despite reduced Ppw at 1.5 and 3 h, and Qva/Qt did not decrease as in Group P. We conclude that plasmapheresis-induced reduction in Ppw reduces the pulmonary capillary leak and venous admixture following acid aspiration, but this has the potentially adverse effect of reducing cardiac output and oxygen delivery. Nitroprusside decreases Ppw and edema by a similar amount, but maintains Qt and QO2.

Measurement of hydrogen peroxide in plasma and blood

Measurement of the oxygen metabolite hydrogen peroxide (H2O2) in biological fluids such as plasma could be of interest because it might indicate participation of toxic oxygen species in tissue injury. Recently several reports claimed to measure H2O2 using spectrophotometric and high pressure liquid chromatographic (HPLC) techniques that utilize oxidation of a substrate to a product by a peroxidase. In such a system it is crucial to perform two control experiments to verify whether the measured substance is H2O2. The specificity of the assay for H2O2 should be checked with catalase, and the degradation of H2O2 or inhibition of the assay system by the sample should be checked by determining the recovery of exogenously added H2O2. We performed both types of controls for HPLC and spectrophotometric determinations of H2O2 in plasma and blood. Our results indicate that contrary to previous reports in the literature the measured substance(s) in plasma or blood is not H2O2. Moreover, quantitative measurements of H2O2 in plasma or blood by HPLC was unreliable due to the irreversible binding of H2O2 to the column surface.

Constant Flow Ventilation in Anesthetized Patients: Efficacy and Safety

Constant flow ventilation (CFV) maintains normal gas exchange in apneic dogs and has potential clinical application during thoracic surgery or pulmonary edema. We compared CFV and intermittent positive pressure ventilation (IPPV) in five healthy, anesthetized, (fentanyl, diazepam, and nitrous oxide) and paralyzed patients undergoing nonthoracic operations. Constant flow ventilation was delivered at a total flow of 0.9–1.6 L·kg 1·min−1 (nitrous oxide-oxygen of 1:1) into two tubes of 2.5–3.5 mm inner diameter attached to each side of an 8–9 mm inner diameter orotracheal tube (OTT). Under brochoscopic guidance, the CFV-OTT was advanced to position each ventilating tube at a mainstem bronchial orifice. Gas exhausted through the OTT lumen. If intrathoracic pressure exceeded a preset limit, a solenoid valve automatically interrupted gas flow to the patient to prevent barotraumas. Compared to IPPV, during CFV for up to 30 min average PaCO2 increased to 69.2 ± 14.5 from 35.9 ± 2.9 mil Hg, reflecting a calculated alveolar ventilation (VA) of 46 ± 22% of the eucapnic level. We suggest that a technique combining CFV at lower flow rates with IPPV may prom clinically useful by allowing decreased tidal volume and inspiratory pressure while maintaining normal VA.

The Pathophysiology and Treatment of Canine Kerosene Pulmonary Injury: Effects of Plasmapheresis and Positive End-Expiratory Pressure

Hydrocarbon aspiration is a relatively common cause of pulmonary injury in the pediatric age group. We evaluated the pathophysiology of kerosene aspiration in 18 anesthetized dogs during the first hour after injury and then compared the effects of treatments by plasmapheresis (n = 6) and positive end-expiratory pressure (PEEP) of 10 cm H2O (n = 6) with the results obtained in untreated control dogs (n = 6) over the next four hours. A group of uninjured control dogs (n = 3) confirmed that surgical preparation and saline sham injury did not cause acute lung injury like that due to kerosene. The untreated control dogs with a stable pulmonary capillary wedge pressure (Ppw) of 10 torr received 0.5 mL/kg of intratracheal kerosene. Although Ppw was maintained at 10 torr for five hours post-injury in these dogs, there was a wide range of lung edema (wet lung weight to body weight ratios from 16.4 to 61.1 g/kg; median of 41.4 g/kg). Between one and five hours, extravascular thermal volume (ETV) increased by 19.1 mL/kg, associated with a median increase in venous admixture (Ova/ Qt) of 28.5% and a median reduction in lung compliance of 12.7 mL/cm H2O. Another group of dogs was similarly injured, but underwent batch plasmapheresis one hour after injury to reduce Ppw to a target value of 5 torr for the remainder of the protocol. Plasmapheresis was associated with a smaller change in ETV (0.8 mL/kg, P < .05 compared with injured animals, Kruskall-Wallis). Gravimetric analysis of edema from lungs excised at five hours confirmed the in vivo findings that reduced Ppw was associated with a lower median wet weight to body weight ratio (20.5 g/kg) than in the untreated group (P < .06, Kruskall-Wallis). Similarly, progressive increases in Qva/Qt (2.6%, P < .06) and decreases in lung compliance (3.7 mL/cm H2O, P < .05) were prevented by plasmapheresis. A third group of dogs with transmural Ppw maintained at 10 torr underwent identical injury but were treated from one hour with 10 cm H2O PEEP. In this group, Qva/Qt was also stabilized (median decrease of 2.5%): but edema formation continued (median ETV increase of 28.5 mL/kg). Cardiac output and oxygen delivery were adequately maintained in both treatment groups so that oxygen consumption was not reduced. We conclude that kerosene aspiration caused pulmonary vascular leaks of varied severity and that plasmapheresis reduced pulmonary edema and its adverse effects on gas exchange and lung mechanics in this model. PEEP also reduced Qva/Qt, but did not reduce edema or lung stiffness and so necessitated the use of higher inflation pressures. Because plasmapheresis did not adversely affect systemic oxygen delivery and consumption, this canine study supports a therapeutic approach to early hydrocarbon pneumonitis of seeking the lowest vascular volume or Ppw associated with an adequate cardiac output and oxygen transport.

Artificial Ventilation of a Canine Model of Bronchopleural Fistula

The authors studied the abnormalities of gas exchange and lung mechanics in a canine model of bronchopleural fistula during intermittent positive pressure ventilation (IPPV) and high-frequency oscillatory ventilation (HFOV). The left lower lobe bronchus was opened to atmosphere and it was determined that end expired volume was best maintained at frequencies of 45–50 breaths/min. during IPPV. Comparing alternating periods of IPPV and HFOV in six dogs (Group 1) at matched airway opening pressure (Pao), we found that PaO2 decreased significantly to 68 ± 14 mmHg and 69 ± 24 mmHg, respectively, on opening the fistula. In a second group of six dogs (Group 2), when Pao was increased by additional bias flow into the ventilatory circuit during both IPPV and HFOV, PaO2 increased significantly to 89 ± 12 mmHg and 87 ± 8 mmHg, respectively. Repeating Group 2 studies after induction of oleic acid lowpressure pulmonary edema demonstrated that conventional IPPV was associated with large intrapulmonary shunts. HFOV, however, maintained gas exchange at near baseline values. For both Group 1 and Group 2, the calculated gas flow through the fistula was significantly less at all levels of airway pressure during HFOV. The authors conclude that HFOV offers advantages over conventional IPPV in the maintenance of oxygenation and in the reduction of gas leak through the fistula.

Volume Recruitment and Oxygenation in Pulmonary Edema: A Comparison Between HFOV and CMV

PURPOSE In acute lung injury, edema floods alveoli decreasing mean lung volume (MLV) and increasing pulmonary venous admixture (Ova/Qt). We reasoned that a ventilatory strategy that uses large tidal volumes (VT) might recruit volume differently than a strategy that uses very small VT (high-frequency oscillatory ventilation, HFOV) which may require an inflation maneuver to total lung capacity (TLC) for full recruitment. MATERIALS AND METHODS We studied six dogs with pulmonary edema induced by oleic acid injury and compared HFOV with conventional mechanical ventilation (CMV). Increasing mean airway opening pressure (Pao) from 6 to 14 cm H2O raised MLV from 932+/-162 to 1,550+/-210 mL and from 872+/-145 to 1,242+/-192 mL during CMV and HFOV, respectively, whereas Qva/Qt decreased from 24.1+/-8.5 to 9.3+/-4.3% and from 42.2+/-6.8 to 30.4+/-9.3%. We repeated our measurements at a Pao of 14 cm H2O after an inflation maneuver to TLC. RESULTS Intlation to TLC recruited additional lung volume and decreased Qva/Qt further only during HFOV. After an inflation to TLC, we observed a rapid isobaric volume loss from the deflation limb of the pressure-volume curve during both CMV and HFOV. CONCLUSIONS We conclude that after oleic acid injury in dogs pressure-volume hysteresis has two components: a recruitable portion associated with gas exchange improvement and a nonrecruitable portion. At the level of PEEP used in this study (8.5 cm H2O), full lung recruitment during HFOV required inflation to TLC, whereas during CMV it was accomplished by the relatively large VT.

Systemic oxygen delivery and consumption during acute lung injury in dogs

Abstract When oxygen delivery (QO2 = Qt × CaO2) is reduced in healthy animals, oxygen uptake by tissues (VO2) is maintained by an increase in the O2 extraction ratio ((CaO2 − CvO2)/CaO2) until a critical level of delivery QO2C is reached, below which VO2 becomes dependent on QO2. In patients with adult respiratory distress syndrome (ARDS), VO2 becomes dependent on O2 delivery even at high levels of QO2 implying a systemic O2 extraction defect. To determine whether lung injury, or its management with positive end-expiratory pressure (PEEP) and high inspired oxygen fractions (F1O2), might disrupt O2 extraction by peripheral tissues, we compared the critical O2 delivery and extraction ratio in 30 anesthetized and paralyzed dogs in four groups. One group (n = 7) received oleic acid to produce an acute lung injury (FlO2 = 1.0) and a second group (n = 7) was maintained with PEEP (FlO2 = 1.0) after receiving oleic acid. A third group (n = 8) received no oleic acid (FlO2 = 1.0), and a fourth group received no oleic acid and was ventilated with room air. The critical O2 delivery was determined in each animal as QO2 was lowered in a stepwise manner by controlled blood removal. Neither the critical QO2 nor critical O2 extraction ratios were different (P > .05) among oleic acid, PEEP-treated, or hyperoxic control animals. Similarly, the critical QO2 determined from the point at which arterial lactate began to increase showed no difference among groups. Thus, neither acute lung injury produced with oleic acid nor its treatment with PEEP was associated with a peripheral O2 extraction defect. However, a linear regression across all groups demonstrated a positive correlation between the arterial PO2 and corresponding critical O2 delivery (r =

The pulmonary vascular effects of dopamine, dobutamine, and isoproterenol in unilobar pulmonary edema in dogs

Although catecholamine inotropic drugs are often used to support the circulation of critically ill patients with hypoxemic respiratory failure, their effect on the pulmonary circulation and on gas exchange is incompletely understood. In order to improve our understanding of the effects of these drugs on the pulmonary circulation, we made measurements of total and regional intrapulmonary shunt (Qs/Qt), distribution of pulmonary blood flow, and pulmonary hemodynamics before and after infusions of dopamine (n = 6, 5 micrograms/kg/min), dobutamine (n = 6, 10 micrograms/kg/min), isoproterenol (n = 6, 0.1 micrograms/kg/min), or saline in dogs with unilobar oleic acid-induced pulmonary edema. In addition to permitting determination of the overall hemodynamic and gas exchange effects of these drugs, this preparation allowed measurement of changes in distribution of pulmonary blood flow between normal and edematous lung. In 6 dogs given dobutamine, mean cardiac output (CO) increased by 1 liter/min, while pulmonary arterial pressure (PPA) increased by 2 mm Hg with no change in pulmonary vascular resistance (PVR) or distribution of pulmonary blood flow. There was a 5% increase in mean Qs/Qt which, because of the lack of evidence of pulmonary vasoactivity, was attributed to time or to increased CO. Isoproterenol produced a similar increase in CO, but reduced PPA and PVR indicating pulmonary vasodilator activity. Pulmonary vasodilation was most prominent in edematous lung, resulting in an increase in relative blood flow to the edema lung lobe and a substantial increase in Qs/Qt, exceeding the increase in all other groups. Dopamine, similarly increasing CO, did not change overall PVR but reduced fractional blood flow to the edema lobe by 3.4% of CO. Neither Qs/Qt nor PaO2 changed significantly in this group. The differing effects of these agents on pulmonary hemodynamics, intrapulmonary blood flow distribution, and gas exchange have potentially significant implications affecting the choice of drug used for circulatory support in hypoxemic respiratory failure.