Alveolar-arterial Oxygen Difference Research Articles

Can new pulmonary gas exchange parameters contribute to evaluation of pulmonary congestion in left-sided heart failure?

Assessment of pulmonary congestion in left-sided heart failure is necessary for guiding anticongestive therapy. Clinical examination and chest x-ray are semiquantitative methods with poor diagnostic accuracy and reproducibility. To establish reference values, describe reproducibility, and investigate the diagnostic and monitoring properties in relation to pulmonary congestion of new pulmonary gas exchange parameters describing ventilation/perfusion mismatch (variable fraction of ventilation [fA2] or the drop in oxygen pressure from the mixed alveolar air of the two ventilated compartments to the nonshunted end-capillary blood [DeltaPO(2)]) and pulmonary shunt. Sixty healthy volunteers and 69 patients requiring an acute chest x-ray in a cardiac care unit were included. The gas exchange parameters were estimated by analyzing standard bedside respiratory and circulatory measurements obtained during short-term exposure to different levels of inspired oxygen. Nine patients were classified as having pulmonary congestion using a reference diagnosis and were followed during 30 days of anticongestive therapy. Diagnostic and monitoring properties were compared with chest x-ray, N-terminal probrain natriuretic peptide (NT-proBNP), spirometry values, arterial oxygen tension, alveolar-arterial oxygen difference and venous admixture. The 95% reference intervals for healthy subjects were narrow (ie, fA2 [0.75 to 0.90], DeltaPO(2) [0.0 kPa to 0.5 kPa] and pulmonary shunt [0.0% to 8.2%]). Reproducibility was relatively good with small within subject coefficients of variation (ie, fA2 [0.05], DeltaPO(2) [0.4 kPa] and pulmonary shunt [2.0%]). fA2, DeltaPO(2) and NT-proBNP had significantly better diagnostic properties, with high sensitivities (100%) but low specificities (30% to 40%). During successful anticongestive therapy, fA2, DeltaPO(2), NT-proBNP and spirometry values showed significant improvements. The gas exchange parameter for ventilation/perfusion mismatch but not pulmonary shunt can have a possible role in rejecting the diagnosis of pulmonary congestion and in monitoring anticongestive therapy.

Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest

The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest. We obtained samples of arterial blood from 10 climbers during their ascent to and descent from the summit of Mount Everest. The partial pressures of arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)), pH, and hemoglobin and lactate concentrations were measured. The arterial oxygen saturation (SaO(2)), bicarbonate concentration, base excess, and alveolar-arterial oxygen difference were calculated. PaO(2) fell with increasing altitude, whereas SaO(2) was relatively stable. The hemoglobin concentration increased such that the oxygen content of arterial blood was maintained at or above sea-level values until the climbers reached an elevation of 7100 m (23,294 ft). In four samples taken at 8400 m (27,559 ft)--at which altitude the barometric pressure was 272 mm Hg (36.3 kPa)--the mean PaO(2) in subjects breathing ambient air was 24.6 mm Hg (3.28 kPa), with a range of 19.1 to 29.5 mm Hg (2.55 to 3.93 kPa). The mean PaCO(2) was 13.3 mm Hg (1.77 kPa), with a range of 10.3 to 15.7 mm Hg (1.37 to 2.09 kPa). At 8400 m, the mean arterial oxygen content was 26% lower than it was at 7100 m (145.8 ml per liter as compared with 197.1 ml per liter). The mean calculated alveolar-arterial oxygen difference was 5.4 mm Hg (0.72 kPa). The elevated alveolar-arterial oxygen difference that is seen in subjects who are in conditions of extreme hypoxia may represent a degree of subclinical high-altitude pulmonary edema or a functional limitation in pulmonary diffusion.

Effect of Body Mass Index on Perioperative Complications in Thoracic Surgery

Obesity is perceived as a risk factor in general thoracic surgery. We conducted a single-center retrospective evaluation of perioperative complications in 822 patients who underwent thoracic surgery between 2000 and 2005. According to body mass index, 82 were underweight (< 18.5 kg m(-2)), 568 were normal (18.5-24.9 kg m(-2)), 155 were overweight (25.0-29.9 kg m(-2)), and 17 were obese (>or=30 kg m(-2)). A significant increase in preoperative comorbidity (hypertension and ischemic heart disease) was observed with increasing body mass index. There was no significant difference in operation time or length of stay in the operating room, but extubation time was significantly different among the 4 groups. Of the intraoperative complications, alveolar-arterial oxygen difference increased significantly with increasing obesity, and hypoxia was least common in the normal group. Postoperatively, there was more pulmonary leakage in the underweight group and less pneumonia in the normal group. Both the underweight and the obese are at increased risk of perioperative complications and need to be carefully observed and managed intraoperatively and postoperatively.

The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model

Cardiopulmonary bypass may cause acute lung injury and can seriously affect postoperative outcome, especially in younger patients. A synthesized neutrophil elastase inhibitor, sivelestat sodium, may be most effective when used during cardiopulmonary bypass. After anesthesia induction, sivelestat (2 mg/kg/h) was given to the SS group (n=7), and 0.9% saline solution to the placebo group (n=7). Piglets were placed on hypothermic cardiopulmonary bypass and subjected to myocardial ischemia (2 h) induced by cold crystalloid cardioplegia. At 24 h after surgery, PaO(2)/FiO(2) ratio and alveolar-arterial oxygen difference were significantly better in the SS group (379.1+/-93.9 mmHg and 250.5+/-89.3 mmHg) than the placebo group (232.4+/-105.3 mmHg, and 378.3+/-90.8 mmHg, P<0.05). Interleukin-8 level in the epithelial lining fluid was above the lowest standard in 6 out of 7 (4.5, 12.9, 24.6, 27.7, 37.7, and 159.8; mean=44.5+/-57.6 g/l) in the placebo group, and in 2 out of 7 (36.1 and 67.8 g/l) in the SS group (P<0.05). The median histological score of acute lung injury in the harvested lung was 3 (2-5) in the placebo group and 1 (1-5) in the SS group (P<0.05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model.

High Frequency Oscillatory Ventilation in Children: Experience of a Medical Center in Taiwan

Data about the effectiveness of high frequency oscillatory ventilation (HFOV) in children with respiratory failure are limited. This study investigated the efficacy and prognostic factors of this treatment. Children between 2 months and 18 years of age who received HFOV between January 2000 and September 2006 in a tertiary care center were enrolled in this retrospective study. Thirty-six HFOV treatments were given to 33 patients (twice in one patient and three times in another patient) at a mean age of 5.4 +/- 5.0 years. HFOV was used as a rescue after conventional mechanical ventilation (CMV) for 4.4 +/- 4.2 days. The mean duration of HFOV was 7.6 +/- 7.9 days. The most common indication for HFOV was oxygenation failure, which was due to pneumonia with acute respiratory distress syndrome in 15 (45.5%), severe lobar pneumonia in nine (27.3%), pulmonary hemorrhage in eight (24.2%) and pneumothorax in one (3%). PaCO2 was significantly improved 4 hours after HFOV and the PaO2/FiO2 ratio increased significantly 12 hours later. The oxygenation index and alveolar-arterial oxygen difference P(A-a)O2, however, did not change markedly. Four (12%) patients needed further extracorporeal life support and two of these survived. The overall survival rate was 45.5%. Patients with heavier body weight (p less than 0.05) and of the male gender (p less than 0.05) had a higher risk of mortality. As a relatively late rescue therapy after failure of CMV, HFOV may improve PaCO2 and PaO2/FiO2 in children with respiratory failure. However, it carries an increased mortality rate in patients with heavier body weight and male gender.

Acute Respiratory Distress Syndrome in Obstetric Patients

Objective: to define the specific features of the course of acute respiratory distress syndrome (ARDS) in puer-peras with a complicated postpartum period. Subjects and methods. Sixty-seven puerperas with ARDS were examined. Group 1 included 27 puerperas with postpartum ARDS; Group 2 comprised 10 puerperas who had been treated in an intensive care and died; Group 3 consisted of nonobstetric patients with ARDS of various genesis (a control group). Results. In obstetric patients, the baseline oxygenation index was significantly lower than that in the control group. However, Group 1 patients showed a rapid increase in PaO2/FiO2 on days 3—4 of treatment. In the control group, the changes occurred later — on days 5—6. The baseline alveolar-arterial oxygen difference was significantly higher in the obstetric patients than that in the controls. In Group 1, AaDpO2 drastically decreased on days 3—4, which took place in parallel with an increase in the oxygenation index. At the beginning of the study, pulmonary shunting was high in the group of survivors, deceased, and controls. In Group 1, the shunting decreased on days 3—4 whereas in the control group this index normalized later — only by days 6—7. In Group 1, compliance remained lower throughout the observation, but on day 7 there was a significant difference in this index between the deceased, survivors, and controls. Conclusion. Thus, more severe baseline pulmonary gas exchange abnormalities are observed in obstetric patients than in general surgical and traumatological patients; the oxygenation index, alveolar-arterial oxygen difference, and pulmonary shunting index more rapidly change in patients with severe obstetric disease in its favorable course than in general surgical and traumatological patients; throughout the observation, thoracopulmonary compliance was less in obstetric patients than in the controls. Key words: acute respiratory distress syndrome, puerperium.

The effect of positive pressure ventilatory patterns on post-bypass lung functions

Background: This study aimed at evaluating the effect of application of different patterns of positive ventilatory pressure either during or after cardiopulmonary bypass (CPB) on lung functions. Methods: 30 patients undergoing coronary artery revascularisation under the management of CPB were randomly allocated into 3 groups. Group I (VCM) 10 patients were subjected to manual vital capacity manoeuvre (VCM) before weaning off the CPB. Group II (CPAP) 10 patients were subjected to continuous positive airway pressure (CPAP) of 10 cmH 2 O during CPB. Group III (PEEP) 10 patients were subjected to positive end expiratory pressure (PEEP) of 7 cmH 2 O after weaning off the CPB. Measurements included the PO 2 , PCO 2 , together with derived calculated parameters as the alveolar-arterial oxygen difference [P (A-a) DO2] and shunt fraction, as well as the dynamic lung compliance being recorded directly from the anaesthetic and ventilatory equipments. All readings were taken on closed chest and on FiO 2 of 0.5. Intraoperative anaesthetic and surgical data as well as postoperative extubation time and length of ICU stay were also evaluated. Results: Statistical analysis of ventilatory parameters showed no significant differences for both PO 2 and PCO 2 in between the studied groups. Alveolar-Arterial oxygen difference mean values were comparable in the 3 studied groups. The mean values of intrapulmonary shunt fraction showed a significant difference in relation to the baseline values in Group I (VCM) and Group III (PEEP) at 30 minutes after ICU admission and 4 hours post CPB with estimated P value Group II (CPAP) mean values started to be significant after chest closure with a p value P value > 0.01. Dynamic lung compliance mean values showed no intergroup statistical significance. Conclusion: Maintenance of Ventilatory parameters was achieved in all the positive pressure ventilatory methods applied, either being applied during or after CPB.

Non-invasive positive pressure ventilation improves lung volumes in the obesity hypoventilation syndrome

Our objective was to study the long-term effects of non-invasive positive pressure ventilation (NPPV) on lung function and gas exchange in patients with the obesity hypoventilation syndrome (OHS). Prospective observational study in OHS patients performing NPPV over a period of 24 months. We studied 35 clinically stable OHS patients with a mean body mass index (BMI) 45.9+/-8.8 kg/m(2) and daytime PaCO(2) at room air of 6.92+/-0.48 kPa at baseline. Nocturnal NPPV was initiated with pressure-cycled devices on IPAP 24+/-3 cm H(2)O, EPAP 6+/-2 cm H(2)O and respiratory frequency of 18.8+/-3.7/min. After 12 and 24 months of NPPV hypercapnia was persistently normalized and hypoxemia was markedly improved while no changes in calculated alveolar-arterial oxygen difference occurred. Augmented ventilation was followed by a significant reduction in hemoglobin and hematocrit (P<0.001 each). Daily duration of ventilator use significantly correlated with the decrease in PaCO(2) after 12 months (r = 0.37; P<0.05) and 24 months (r = 0.47; P<0.05). Vital capacity (VC) and expiratory reserve volume (ERV) significantly increased after 12 and 24 months NPPV compared to the baseline values, though BMI was only slightly reduced. The 2-year survival rate was 91% with three patients (9%) discontinuing NPPV during the study period. Long-term domiciliary NPPV normalizes hypercapnia and markedly improves hypoxemia as well as polycythemia in OHS patients. In addition, NPPV leads to a significant reduction in restrictive ventilatory disturbance, predominantly by increasing ERV. Application of high inspiratory pressures and good adherence to therapy are presumed to be the basis for the beneficial effects of NPPV in OHS.

Effect of Positive End‐Expiratory Pressure on Oxygen Delivery During 1‐Lung Ventilation for Thoracoscopy in Normal Dogs

To evaluate the effect of positive end-expiratory pressure (PEEP) on oxygen delivery (DO(2)) with 1-lung ventilation during thoracoscopy in normal anesthetized dogs. Prospective, controlled experimental study. Eight, adult, intact Walker Hound dogs weighing 25.6-29.2 kg. Anesthetized dogs had 1-lung ventilation during an open-chest condition. A Swan-Ganz catheter was used to measure pulmonary hemodynamic variables and to obtain mixed venous blood samples for blood gas analysis. A dorsal pedal catheter was used for measurement of systemic arterial pressure and to obtain arterial blood samples for blood gas analysis. Oxygen delivery was calculated and used to assess the effect of 0, 2.5, and 5 cm H(2)O PEEP during 1-lung ventilation on cardiopulmonary function. Each dog was its own control at 0 cm H(2)O PEEP. A randomized block ANOVA for repeated measures was used to evaluate the effect of the treatment on hemodynamic and pulmonary variables. Use of 5 cm H(2)O PEEP induced a significant augmentation in the arterial partial pressure of oxygen (PaO(2)). Shunt fraction (Q(s)/Q(t)), physiologic dead space (V(D)/V(T)), and the alveolar-arterial oxygen difference (P(A-a)O(2)) decreased significantly after 5 cm H(2)O PEEP, compared with 1-lung ventilation without PEEP. Use of 2.5 cm H(2)O PEEP had no significant effect on cardiopulmonary variables. Use of PEEP had no significant effect on arterial oxygen saturation (SaO(2)), DO(2), and hemodynamic variables in normal dogs. PEEP had no effect on DO(2) in normal dogs undergoing open-chest 1-lung ventilation because it had no adverse effect on hemodynamic variables. PEEP in normal dogs during open-chest 1-lung ventilation for thoracoscopy is not detrimental to cardiac output and can be recommended in clinical patients.

High-frequency oscillatory ventilation in pediatric patients with acute respiratory failure

To evaluate the effectiveness of high-frequency oscillatory ventilation (HFOV) in pediatric patients with acute respiratory failure, failing conventional ventilation. A prospective, clinical study. Tertiary care pediatric intensive care unit. Twenty pediatric patients (ages 12 days to 5 yrs) with acute respiratory failure (pneumonia, 14; sepsis with acute respiratory distress syndrome, 3; pulmonary edema as a complication of upper airway obstruction, 2; salicylate intoxication with acute respiratory distress syndrome, 1), failing conventional ventilation (median alveolar-arterial oxygen difference [P(A-a)O2] 578 [489-624] torr, median oxygenation index 26 [21-32]. HFOV was instituted after a median length of conventional ventilation of 15.5 (3.3-43.5) hrs. Ventilator settings, arterial blood gases, oxygenation index, and P(A-a)O2 were recorded before HFOV (0 hrs) and at predetermined intervals during HFOV and compared using the one-way Friedman rank-sum procedure and a two-tailed Wilcoxon matched-pairs test. Initiation of HFOV caused a significant decrease in FiO2 at 1 hr that continued to 24 hrs (p <or= .04). In all patients, target ventilation was achieved, and 19 had improved oxygenation. After 1 hr, PaCO2 significantly decreased (p = .002) and remained within the target range thereafter. There were significant decreases in P(A-a)O2 and oxygenation index at 1 and 4 hrs, respectively, that were sustained up to 12 hrs (p <or= .04). No significant complications associated with HFOV were detected. Fifteen patients (75%) survived to hospital discharge. Only one patient died from respiratory failure. In pediatric patients with acute respiratory failure, failing conventional ventilation, HFOV improves gas exchange in a rapid and sustained fashion. However, randomized controlled trials are needed to identify its benefits over conventional modes of mechanical ventilation.

INVITED CRITIQUE

In this issue, Cancio et al1 report that, in a review of acute burn resuscitation, two measures obtained from blood gases—alveolar-arterial oxygen difference (AaDO2) and base deficit (BD)—did not improve mortality prediction when added to the universally accepted variables age, burn size, and inhalation injury. In that sense, the title of their reoirt is misleading; they could have claimed the opposite result with equal validity. This report complements a number of other of recent studies evaluating metabolic abnormalities as predictors of outcome. In trauma patients, increased levels of lactic acid (LA) predict ongoing hemorrhage and the need to escalate resuscitation2; in burns, increases in the levels of BD and LA have been variously found to correlate with increasing burn size, inhalation injury, systemic inflammation, fluid requirements, and rate of mortality.3,–6 Nonetheless, the clinical utility of these measurements remains unclear. Systemic acidosis is a valid marker for the unmet metabolic demands that define the shock state. However, as demonstrated, these values may not improve mortality prediction in burn patients, who already have uniquely quantifiable injuries. The authors deserve praise for their careful statistical analysis, which illuminated this point, and for thoughtfully discussing other limitations of their review. However, their study also is compromised by other considerations. First, they failed to measure LA, whichmay be a more accurate indicator of ongoing shock.7,8 Second, they used mean values of AaDO2 and BD collected during the first 2 days of treatment, so that patients with different amounts of data were compared and the most abnormal values were “diluted” as treatment proceeded. Finally, of the 55 deaths reviewed, 9 had support withdrawn, and 3 were the result of “hypoxia at the scene.” Correlation of death with physiologic parameters in these patients might be predictably poor. It was surprising that AaDO2 correlated more with early death because inhalation injury typically causes late deaths from pneumonia and multiple organ failure. BD, reflecting acute hypoperfusion, might have been predicted to be a better marker for early mortality.

Effects of lidocaine and steroids on breast milk-induced lung injury in rabbits1

Local anesthetics inhibit mediator and free radical release from polymorphonuclear granulocytes and migration to their site of action. In a recent study, lidocaine significantly improved the alveolar-arterial oxygen difference gradients (A-aDO2) after tracheal instillation of acid in rabbits. The purpose of the current study was to evaluate the effects of lidocaine and pulse-dose steroids on human breast milk (HBM)-induced lung injury in rabbits. After Animal Care Committee approval, six adult rabbits were assigned to each of three treatments: control, lidocaine, and steroids. After induction of anesthesia and controlled ventilation, acidified HBM at pH 1.8 and volume 1.2 ml.kg(-1) was instilled into the trachea. Rabbits in the lidocaine group received lidocaine 2 mg.kg(-1) i.v. before tracheal instillation and then 2 mg.kg(-1).h(-1) i.v. continuously. Rabbits in the steroid group received 30 mg.kg(-1) methylprednisolone before tracheal instillation. A-aDO2, static compliance and blood for white cell count, and cytokine interleukin-8 (IL-8) concentration were obtained at baseline and at 1 and 4 h postinstillation. After 4 h, the rabbits were killed. The left upper lobe was isolated and excised to determine the wet/dry ratio. The right lung was lavaged with 30 ml normal saline to determine the white cell count and the concentrations of albumin and IL-8. Data were analyzed using one- or two-way anova with repeated measures and an Student-Newman-Keuls (SNK) posthoc test (P < 0.05). All rabbits completed the protocol. A-aDO2 and CO2 tensions increased significantly at 1 and 4 h compared with baseline, although there were no differences among the treatments (P < 0.05). Compliance in the control group decreased compared with lidocaine and steroids. We conclude that preemptive lidocaine and steroids attenuate in part HBM-induced lung injury in rabbits.

Massive pulmonary embolus without hypoxemia

To describe a patient who had been taking ibuprofen for 3 days before the diagnosis of a massive pulmonary embolus without hypoxemia. Institutional review board-approved case report. Pediatric intensive care unit. A 16-yr-old male with a history of supraventricular tachycardia. The patient underwent an electrophysiology study and developed mild shortness of breath and then chest pain 2 and 4 days later, respectively. He took ibuprofen for 3 days. Evaluation 1 wk following the procedure revealed dyspnea and tachycardia. Arterial blood gas in room air was significant for hypocarbia without hypoxemia (Pao2, 108 mm Hg; Paco2, 28 mm Hg). Ventilation perfusion scan and computed axial tomography with intravenous contrast were consistent with a massive pulmonary embolus and left external iliac vein thrombus. He received anticoagulation, thrombolysis, a stent in the left iliac vein, and a filter in the inferior vena cava. Perfusion gradually improved and he was discharged home on oral anticoagulation. The absence of hypoxemia (including a normal alveolar-arterial oxygen difference) in our patient with a massive pulmonary embolus may have been related to cyclooxygenase inhibition due to ibuprofen, with improvement in ventilation-perfusion mismatch.

257 Malondialdehyde in Plasma and Exhaled Breath Condensate Collected from Ventilated Infants

Aim: Malondialdehyde (MDA) is a product of lipid peroxidation that is a marker of oxygen free radical damage. The aim of our study was to measure MDA in exhaled breath condensate (EBC) collected from ventilated infants and to use it as a marker of oxidative stress in the lungs of these patients. Methods: MDA concentration was determined by high-performance liquid chromatography in plasma and EBC collected from 17 ventilated infants with humidification. In 11 infants, blood was taken at the same time as EBC collection. FiO2, alveolar-arterial oxygen difference (AaDO2), mean airway pressure (MAP), oxygenation index (OI) and peak inspiratory pressure (PIP) were recorded at the time of sample collection to estimate potential oxidative stress to the lungs, and correlated with MDA concentration. Results: The detection limit for breath condensate MDA was 0.0015 micromolar. MDA was measurable in breath condensate in 13 patients, but was below the detection limit in 4 patients. Median MDA concentration was 0.004 (range: 0 − 0.022) micromolar in EBC. Median MDA plasma concentration was 0.375 (range: 0.054 − 5.171) micromolar. Plasma MDA concentration was strongly correlated with both FiO2 (r squared=0.22; p=0.008) and AaDO2 (r squared=0.28; p=0.006), and weakly correlated with MAP (r squared=0.14; p=0.04). There was no relationship between plasma MDA and either OI or PIP. Although we found a significant correlation between the concentration of MDA in plasma and in EBC (r squared=0.32; p<0.03), EBC MDA concentration did not significantly correlate with FiO2, MAP, PIP or OI. Conclusion: Our results suggest that MDA concentration in plasma correlates with oxidative stress of the lungs of ventilated infants. Although MDA can be measured in EBC collected from ventilated infants, even during humidication, and correlates with MDA concentration in plasma, the amounts are very low and normalisation to EBC electrolytes may be necessary.

High-frequency oscillatory ventilation in paediatric patients with acute respiratory distress syndrome--early rescue use.

In order to determine the response to high-frequency oscillatory ventilation (HFOV), used as an “early rescue” therapy, in a cohort of paediatric patients with acute respiratory distress syndrome (ARDS), a prospective clinical study was performed in a tertiary care paediatric intensive care unit. Ten consecutive patients, aged 12 days to 5 years with ARDS and hypoxaemic respiratory failure on conventional ventilation (CV), using a lung protective strategy, were managed with HFOV early in the course of the disease process (median length of CV 4 h). Arterial blood gases, oxygenation index (OI), alveolar-arterial oxygen difference (P(A-a)O2) and PaO2/FIO2 ratio were prospectively recorded prior to HFOV (0 h) and at predetermined intervals throughout the course of the HFOV protocol. There was a significant improvement in PaCO2 4 h after institution of HFOV ( P =0.012). A significant and sustained increase ( P <0.001) in PaO2/FIO2 ratio and a significant and sustained decrease ( P <0.001) in OI and P(A-a)O2 were demonstrated during the HFOV trial. These improvements were achieved 4 h after initiating HFOV ( P <0.05). Eight patients survived. There were no deaths from respiratory failure. Conclusion: In paediatric patients with acute respiratory distress syndrome and hypoxaemic respiratory failure on conventional ventilation, using a lung protective strategy, high-frequency oscillatory ventilation used as an “early rescue” therapy, improves gas exchange in a rapid and sustained fashion and provides a good outcome. Use of this therapy should probably be considered early in the course of the disease process.

Pulmonary blood transit time and impaired arterial oxygenation in patients with chronic liver disease

Contrast-enhanced echocardiography (CEE) using agitated saline can detect intrapulmonary vasodilatation (IPVD) in patients with hepatopulmonary syndrome (HPS). We estimated the pulmonary transit time of erythrocytes (PTT) by CEE, using microbubbles, and studied its relationship to arterial oxygenation in chronic liver disease. Sixteen patients with chronic liver disease and seven healthy subjects were studied. PTT was defined as the time between opacification of the right atrium and left atrium on CEE, using human serum albumin-air microbubble complexes with a mean diameter of 4 microm (Albunex). IPVD was detected by CEE with agitated saline. Arterial blood gases were analyzed with patients in the supine position, and while they were seated. Cardiac output (CO) was determined by Doppler echocardiography. The mean PTT value for all of the patients was 4.0 +/- 1.4 s. One of the 3 patients who showed IPVD was normoxemic. Mild orthodeoxia was observed in the patients with abnormal alveolar-arterial oxygen difference (A-aDO2) values (>15 mmHg), but not in those with normal A-aDO2 values, or in the healthy subjects. PTT was correlated with PaO2 (r = 0.52; P < 0.05; n = 16) and A-aDO2 (r = -0.54; P < 0.05; n = 16) in the seated position. CO was significantly correlated with PTT (r = -0.62; P < 0.05; n = 15), but not with PaO2 and A-aDO2, in both positions. PTT may be a useful parameter for evaluating arterial oxygenation in patients with chronic liver disease with early HPS.

Detection of early central circulatory transits in patients with cirrhosis by gamma variate fit of indicator dilution profiles

Patients with cirrhosis have hyperdynamic circulation with abnormally distributed blood volume and widespread arteriovenous communications. We aimed to detect possible very early (i.e., before 4 s) and early (i.e., after 4 s) central circulatory transits and their potential influence on determination of central and arterial blood volume (CBV). Thirty-six cirrhotic patients and nineteen controls without liver disease undergoing hemodynamic catheterization were given central bolus injections of albumin with different labels. Exponential and gamma variate fits were applied to the indicator dilution curves, and the relations between flow, circulation times, and volumes were established according to kinetic principles. No significant very early central circulatory transits were identified. In contrast, early (i.e., 4 s to maximal) transits corresponding to a mean of 5.1% (vs. 0.8% in controls; P < 0.005) of cardiac output (equivalent to 0.36 vs. 0.05 l/min; P < 0.01) were found in cirrhotic patients. These early transits averaged 7.7 vs. 12.7 and 17.2 s of ordinary central transits of cirrhotic patients and controls, respectively (P < 0.001). Early transits were directly correlated to the alveolar-arterial oxygen difference in the cirrhotic patients (r = 0.46, P < 0.01) but not in controls (r = 0.04; not significant). There was good agreement between the CBV determined by the conventional indicator dilution method and that determined by separation of early and ordinary transits by the gamma variate fit method (1.51 vs. 1.53 liter; not significant). In conclusion, no very early central circulatory transits were identified in cirrhotic patients. A significant part of the cardiac output undergoes an early transit, probably through pulmonary shunts or areas with low ventilation-perfusion ratios in cirrhotic patients. Composite determination of CBV by the gamma variate fit method is in close agreement with established kinetic methods. The study provides further evidence of abnormal central circulation in cirrhosis.

Gas exchange during separate diaphragm and intercostal muscle breathing.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.

Comparison of Pulmonary Gas Exchange in OPCAB Versus Conventional CABG

Background. Cardiopulmonary bypass has been implicated as a cause of acute lung injury in cardiac surgical patients. This could be avoided with off-pump coronary artery bypass surgery. Aim. To ascertain the possible benefit of OPCAB surgery on pulmonary gas exchange. Methods. We randomized 75 consecutive patients (mean age 57 years) into two groups: Group 1 off-pump coronary artery bypass surgery (OPCAB), n=37, Group 2 conventional coronary artery bypass grafting (con CABG), n=38. Alveolar-arterial oxygen difference (A-aO 2 difference) was calculated pre-operatively, then 2 and 4 h post-operatively. PaO 2/FiO 2 ratio and respiratory index (RI) were calculated 2 and 4 h post-operatively. Results. Alveolar-arterial O 2 gradient sharply increased in the immediate post-operative period, from 27 mmHg pre-operatively, to 227 mmHg 2 h post-operatively, then declined to 152 mmHg 4 h post-operatively. PaO 2/FiO 2 ratio and RI also showed severe worsening 2 h post-operatively, with marked improvement at 4 h. The pattern of physiological deterioration of gas exchange was similar in both the groups. Conclusion. In terms of pulmonary gas exchange, similar degree of deterioration is noticed in CABG patients with or without cardiopulmonary bypass. OPCAB seems to provide no physiological benefit of gas exchange at the alveolar capillary membrane when compared to conventional CABG.

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass.

To investigate the effects of PARP inhibition on cardiac and pulmonary function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the potent PARP-inhibitor PJ34 (5 mg/kg; n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodium-nitroprusside and pulmonary function were also determined. The cardiac and pulmonary activation of PARP was detected by poly(ADP-ribose) immunohistochemistry. Administration of PJ34 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the PJ34 treated group (P < 0.05) PJ34 treatment preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05) Pulmonary function in terms of alveolar arterial oxygen difference was better maintained in the PJ34 treated animals (P < 0.05). Immunohistochemical staining revealed PARP activation after cardiopulmonary bypass in both the heart and lung, which was prevented by PJ34. PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and protects against the development of remote pulmonary injury during cardiopulmonary bypass.