Stable and reproducible porcine model of acute lung injury induced by oleic acid

BACKGROUND AND METHODS: Previous studies on acute lung injury induced with oleic acid did not attempt to limit the influence of secondary changes on pulmonary circulation, and cardiopulmonary variable data were only collected and processed intermittently. Our study was designed to continuously monitor the following variables in five swine: systemic and pulmonary pressure; mixed venous oxygen saturation (SVO2) and arterial oxygen saturation (SaO2); minute oxygen consumption and CO2 production before, during, and for 4 hr after the infusion of oleic acid. A personal computer was programmed to produce 20-sec updates of deadspace ratio (VD/VT), venous admixture (Qsp/Qt), pulmonary (PVR) and systemic vascular resistance (SVR), and cardiac output (Qt) from these data. RESULTS: During the oleic acid infusion, there were increases in PVR, SVR, heart rate (HR), mean pulmonary arterial pressure (MPAP), Qsp/Qt, and VD/VT, and a decrease in Qt, SaO2, and SVO2. Thirty minutes after the oleic acid infusion, there was a further increase in HR, Qsp/Qt, and VD/VT, while MPAP, PVR, and SVR gradually decreased to pre-oleic acid infusion levels. No further decrease in SaO2, SVO2, and Qt was observed during that time. After the 30-min period, there was no further change in the cardiopulmonary variables. CONCLUSION: Our method of continuous monitoring was able to demonstrate in swine both the dynamic changes during, and stability after, the oleic acid infusion.     

Continuous, in vivo pulmonary venous admixture from fiberoptically measured hemoglobin saturations

In six anesthetized swine, pulmonary venous admixture (Qsp/Qt) was calculated by four methods: a) Qsp/Qt 1, fiberoptically measured arterial and mixed venous Hgb saturation (SaO2 and SvO2), PaO2 and PvO2 derived from saturations; b) Qsp/Qt 2, fiberoptically measured SaO2 and SvO2, PaO2 and PvO2 measured by blood gas analysis; c) Qsp/Qt 3, PaO2 and PvO2 measured by blood gas analysis, SaO2 and SvO2 derived from tensions; d) Qsp/Qt 4, SaO2 and SvO2 measured by bench oximetry, PaO2 and PvO2 derived from saturations. Input from the fiberoptic catheters was fed into a computer programmed to calculate Qsp/Qt 1 every 20 sec. Fifty-eight of these values were compared with simultaneously calculated Qsp/Qt 2, 3, and 4. There was no difference between fiberoptic and derived SaO2 or fiberoptic and cooximetric SvO2. Correlations and slopes for Qsp/Qt 1 with Qsp/Qt 2, 3, and 4 were significant (p less than .05). Comparing mean differences, Qsp/Qt 1 was significantly different only from Qsp/Qt 3 (p less than .01). We conclude that dual oximetry reliably tracks Qsp/Qt.     

Effect of hydralazine on intrapulmonary shunt

We compared the acute effects of bilateral arteriovenous may be related to levels of PvO2. The hydralazine-associated (p less than .05) decrease in resistance. Mixed venous oxygen fistulas to those of hydralazine infusion on hemodynamics and pulmonary gas exchange in dogs with pulmonary edema induced by administration of oleic acid. Oleic acid significantly (p less than .01) increased intrapulmonary shunt (Qsp/Qt) and pulmonary and systemic vascular resistance, and reduced cardiac output. Once the lesion stabilized, both opening the fistula and infusing hydralazine produced a similar and significant (p less than .01) increase in cardiac output, and a significant (p less than .05) decrease in resistance. Mixed venous oxygen tension (PvO2) closely followed the changes in cardiac output; however, PaO2 did not change. Qsp/Qt significantly (p less than .01) increased with the fistulas open and with hydralazine infusion. Closure of the fistulas or bleeding the animal at the end of the experiment reversed the changes in cardiac output and Qsp/Qt. The comparable increases in cardiac output and Qsp/Qt produced by opening the fistulas or infusing hydralazine may be related to levels of PvO2. The hydralazine-associated PvO2 increase indicates that this drug increased oxygen transport to the tissues even as Qsp/Qt became larger.     

Continuous positive airway pressure is beneficial in treatment of smoke inhalation

This study demonstrates that continuous positive airway pressure (CPAP) improves pulmonary function after smoke inhalation by dogs. Sixteen dogs were anesthetized with iv sodium pentobarbital. Arterial and mixed venous blood gas tensions; carboxyhemoglobin concentration (COHgb); mean systemic arterial (MAP), mean pulmonary arterial (MPAP), and pulmonary arterial wedge (WP) pressures; heart (HR) and respiratory (f) rates; cardiac output (CO); and airway pressure (Paw) were measured. Intrapulmonary physiologic shunt (Qsp/Qt) and pulmonary (PVR) and systemic (SVR) vascular resistances were calculated. The animals then breathed an aerosol of smoke and were divided randomly into 2 groups. The treatment group breathed spontaneously on 8-torr CPAP whereas the control group continued to breathe spontaneously at ambient pressure. After inhalation of smoke, Qsp/Qt, MPAP, PVR, COHgb, HR, and f rose, whereas PaO2 and MAP fell in untreated animals. When CPAP was applied, PaO2 and Qsp/Qt returned nearly to baseline values. Mean f also was significantly lower in the treated animals. We found that the early institution of CPAP improves oxygen exchange in the lungs after the inhalation of smoke.     

Swine model of early adult respiratory distress syndrome induced by intravenous ethchlorvynol

Although ethchlorvynol (ECV) has been used to induce pulmonary damage in animals, changes after injection of this drug have not been studied, nor has the stability of the animal been assessed after injection. Continuously monitored hemodynamic and respiratory changes were followed during and after iv injection of 55 mg/kg ECV in ethanol into anesthetized, paralyzed, and ventilated swine (n = 5) and compared to changes in a control group given ethanol alone (n = 5). Arterial and mixed venous saturations were measured by fiberoptic vascular catheters and oxygen exchange by a gas monitor. Twelve direct and derived variables were monitored every 20 sec using a computer data acquisition system. Arterial oxygen saturation was kept at 90 +/- 2% by adjustment of FIO2. Ethanol produced only transitory changes during infusion. Significant elevations in pulmonary vascular resistance (PVR), shunt (Qsp/Qt) and deadspace (VD/VT) were observed during and after ECV. These were unaccompanied by changes in cardiac output or arterial pressure. PVR increased by 137%, Qsp/Qt by 67%, and VD/VT by 28% over 30 min. These changes were then sustained in the postinfusion period, producing a stable model of early adult respiratory distress syndrome for 3.5 h.     

Ketanserin in the treatment of pulmonary hypertension after valvular surgery: a comparison with sodium nitroprusside

In a prospective randomized trial in patients with a history of preoperative pulmonary hypertension who were undergoing surgery for valvular replacement or annuloplasty, the effects of ketanserin (KET) (12 patients) and sodium nitroprusside (SNP) (14 patients) on the systemic and pulmonary circulation and pulmonary shunt fraction (Qsp/Qt) were studied in the immediate postoperative period. The agents were administered at the moment that pulmonary arterial pressure (PAP) tended to rise and cardiac output started to decrease. After administration, systemic arterial BP, PAP, systemic and pulmonary (PVR) vascular resistance, and right ventricular stroke work (RVSW) decreased significantly in both groups. The decrease in mean pulmonary arterial pressure (p less than .01), PVR (p less than .01), and RVSW (p less than .05) was significantly more pronounced in the KET than in the SNP group. Qsp/Qt significantly (p less than .001) increased in the SNP group, but significantly (p less than .05) decreased in the KET group; the response was significantly different between the two groups (p less than .001). In six patients, SNP converted pacemaker-dependent heart rate into a spontaneous rhythm, whereas this occurred in only one patient in the KET group. We concluded that KET, as opposed to SNP, reduces PVR without increasing Qsp/Qt in the lung, which is particularly advantageous in patients after valvular surgery.     

Arterial blood gas derived variables as estimates of intrapulmonary shunt in critically ill children

Oxygen transport data, prospectively collected from 52 critically ill children, were analyzed to determine whether any derived variable accurately estimated intrapulmonary shunt (Qsp/Qt). Arterial hemoglobin saturation was more closely correlated with Qsp/Qt than was PaO2, alveolar-arterial oxygen gradient, arterial mixed venous oxygen difference (C[a-v]O2), arterial/alveolar oxygen ratio, and the ratio of PaO2 to inspired oxygen (FIO2) (r = 0.8, p less than .0001). When C(a-v)O2 was normal, hemoglobin saturation became a very accurate (r = 0.96) assessment of Qsp/Qt. We conclude that various arterial blood gas derived variables do not accurately reflect Qsp/Qt in critically ill children. In these patients, a pulmonary artery catheter is needed to accurately assess intrapulmonary shunt.     

Sodium nitroprusside and positive end-expiratory pressure are not detrimental in canine asymmetric pulmonary edema

The effects of PEEP and subsequent augmentation of cardiac output by sodium nitroprusside (SNP) were examined in a canine model of asymmetric oleic acid injury to the right lung. PEEP (9.2 +/- 0.5 cm H2O) was added to six animals to decrease venous admixture (Qsp/Qt) from 50.6 +/- 4.4% to 16.0 +/- 1.3% (p less than .05). With PEEP, intrapulmonary blood flow distribution (assessed by radioactive microspheres) decreased significantly to nondependent lung regions while increasing to dependent regions. In six other animals, zero end-expiratory pressure (ZEEP) did not alter intrapulmonary blood flow distribution. SNP was then administered to increase cardiac output by 40% (to 2.60 +/- 0.21 L/min in the ZEEP group and to 1.75 +/- 0.27 L/min in the PEEP group). SNP produced no adverse effects on Qsp/Qt or intrapulmonary blood flow distribution. Specifically, SNP did not preferentially dilate pulmonary vessels injured by oleic acid with or without end-expiratory pressure. Thus, administration of a vasodilator drug in asymmetric pulmonary edema appears well tolerated.     

Respiratory index/pulmonary shunt relationship: quantification of severity and prognosis in the post-traumatic adult respiratory distress syndrome

The relationship between the respiratory index (RI = alveolar-arterial oxygen gradient [P(A-a)O2] normalized by PaO2) and the pulmonary shunt (Qsp/Qt) has been examined in 929 studies from 240 critically ill post-traumatic patients. Of these, 88 patients (443 studies) were individuals who developed post-traumatic adult respiratory distress syndrome (ARDS) and 152 were patients (486 studies) who did not develop ARDS. This study demonstrates that the RI to Qsp/Qt [RI/(Qsp/Qt)] relationship was significantly (p less than .0001) increased in patients who developed fatal ARDS compared with those who did not develop ARDS, or with those whose ARDS resolved. Because of the increased oxygen consumption (VO2) in ARDS patients in association with their severe limitations in gas exchange (RI) and increased Qsp/Qt, surviving ARDS patients had a significant increase in the cardiac index which resulted in a higher oxygen delivery to VO2 ratio. ARDS patients showed significant (p less than .0001) evidence of increased pulmonary vascular tone, correlated with the increase in the RI/(Qsp/Qt) relationship. In addition, those patients with high RI/(Qsp/Qt) also had increased right ventricular (RVSW) to left ventricular work (LVSW) ratios which were shown to be a direct function of the rise in RI. This increase in both RVSW/LVSW and RI/(Qsp/Qt) ratios was significantly (p less than .0001) correlated with an increased mortality. Thus, the RI/(Qsp/Qt) relationship, which can be obtained from arterial and mixed venous blood gases and saturations only, can be used to predict the severity of the ARDS process as well as important pulmonary vascular and right ventricular overload consequences.     

Cardiovascular adjustments and gas exchange during extreme hemodilution in humans

OBJECTIVE: To examine the cardiovascular adjustments and pattern of gas exchange that occur during hemodilution. DESIGN: Nonrandomized prospective study. SETTING: Operating room in a university hospital. PATIENTS: Seven patients undergoing elective aortocoronary artery bypass surgery. INTERVENTIONS: Before initiating cardiopulmonary bypass, the patients' hematocrit levels were decreased to approximately 15%. This hemodilution was done by removing a sufficient amount of autologous blood from the aortic cannula and replacing it with a sufficient amount of crystalloid solution. After the discontinuation of cardiopulmonary bypass, measurements were made at a hematocrit of approximately 15%. Then, after autologous blood infusion, measurements were made at a hematocrit of 20%, followed by more blood infusion to approximately 25% with repeat measurements. MEASUREMENTS AND MAIN RESULTS: The following measurements were made before hemodilution and then at all three levels of hemodilution: heart rate, mean arterial pressure (MAP), right atrial pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output. From these measurements, the following derived variables were calculated: cardiac index, systemic vascular resistance, and pulmonary vascular resistance. From measurements of arterial oxygen content, mixed venous oxygen content, and cardiac output, intrapulmonary shunt (Qsp/Qt), oxygen uptake (VO2), oxygen extraction ratio, and oxygen delivery (DO2) were derived. The MAP was lowest (57 +/- 3 [SD] vs. 92 +/- 3 mm Hg) at the lowest hematocrit. The cardiac index was highest (4.0 +/- 0.3 vs. 2.3 +/- 0.6 L/min.m2) at the lowest hematocrit. DO2 was lowest at the lowest hematocrit but VO2 remained constant at all levels of hematocrit. The oxygen extraction ratio increased as hematocrit decreased. With progressive increases in hematocrit, DO2 increased and Qsp/Qt decreased. CONCLUSIONS: The data suggest that, during hemodilution, tissue autoregulation of VO2 and utilization are not impaired, but gas exchange function (Qsp/Qt) is impaired.     

Effect of high-frequency ventilation on histamine-induced lung injury in dogs

We compared the effects of high-frequency oscillation (HFO) and conventional mechanical ventilation (CMV) on dynamic lung compliance (Cdyn), venous admixture (Qsp/Qt), cardiac output, and total lung resistance (RL) in seven mongrel dogs with histamine-induced lung injury. Baseline measurements during CMV were followed by iv infusion of histamine at 100 micrograms/min. Cdyn, Qsp/Qt, cardiac output, and RL were measured in triplicate during CMV and then during HFO. Subsequently, at least one complete set of measurements was recorded again on CMV. During HFO, animals were ventilated at 15 Hz with a tidal volume of 70 to 80 ml. CMV was delivered at 15 to 18 breath/min with a tidal volume of 15 ml/kg. Histamine infusion produced a marked fall in Cdyn, a variable rise in RL, an inconsistent but usually progressive rise in Qsp/Qt, and hypotension. A period of ventilation with HFO made no difference in the Cdyn, Qsp/Qt, or cardiac output changes produced by histamine infusion.     

Mechanical ventilation with permissive hypercapnia increases intrapulmonary shunt in septic and nonseptic patients with acute respiratory distress syndrome

OBJECTIVE: To compare the effects of conventional mechanical ventilation with low-volume, pressure-limited ventilation (LVPLV) and permissive hypercapnia on ventilation-perfusion (V/Q) distributions in patients with acute respiratory distress syndrome. We hypothesized that the advantageous cardiopulmonary effects of LVPLV would be greater in patients with sepsis than in those without sepsis. PATIENTS AND INTERVENTIONS: Twenty-two patients with acute respiratory distress syndrome were studied (group 1: 12 patients with hyperdynamic sepsis; group 2: 10 nonseptic patients). Intrapulmonary shunt (Qsp/Qt) (percentage of cardiac output), perfusion of "low" V/Q areas (percentage of cardiac output), ventilation of "high" V/Q areas (percentage of total ventilation [VE]), and deadspace ventilation (percentage of VE) were calculated from the retention/excretion data of six inert gases. Data were obtained during conventional mechanical ventilation and during LVPLV. MEASUREMENTS AND MAIN RESULTS: In group 1, LVPLV increased PaCO(0)rom 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 61 +/- 12 torr (8.1 +/- 1.6 kPa). Qsp/Qt increased from 28 +/- 16% to 36 +/- 17%, whereas Pao2 (84 +/- 15 torr [11.1 +/- 2.0 kPa] vs. 86 +/- 21 torr [11.5 +/- 2.8 kPa]) and Qt (10.6 +/- 2.3 vs. 11.5 +/- 2.5 L x -1) remained unchanged and PVO(2) (40 +/- 4 [5.3 +/- 0.5 kPa] vs. 49 +/- 6 torr [6.5 +/- 0.3]) increased. In group 2, LVPLV increased PaCO(2) from 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 63 +/- 11 torr (8.4 +/- 1.5 kPa). For Qsp/Qt (24 +/- 9% to 34 +/- 16%), the increase was not significant, whereas Qt (7.4 +/- 1.8 vs. 10.2 +/- 2.2 L x -1), PVO(2)(38 +/- 4 torr [5.1 +/- 0.5 kPa] vs. 50 +/- 6 mm Hg [6.7 +/- 0.8 kPa]), and PaO(2) (89 +/- 16 torr [11.9 +/- 2.1 kPa] vs. 98 +/- 19 torr [13.1 +/- 2.5 kPa]) increased. In both groups, the scatter of perfusion distribution (log SDQ) was greater than expected for normal subjects but was not different between the groups or altered by the treatments. CONCLUSIONS: In patients with acute respiratory distress syndrome, LVPLV with permissive hypercapnia, tended to increase Qsp/Qt, without a concomitant decrease of PaO(2). This occurs because, although atelectasis and increased shunt result from the low ventilatory volume, the effects on PaO(2) are offset by increased PVO(2) resulting from the hypercapnic stimulation of cardiac output. This result was independent of the presence or absence of sepsis.     

Unreliability of oxygen tension-based indices in reflecting intrapulmonary shunting in critically ill patients

Measurement of intrapulmonary shunting (Qsp/Qt), a widely used method for monitoring disturbances of pulmonary oxygen transfer in critically ill patients, involves calculation of arterial and mixed venous oxygen contents. In circumstances where mixed venous blood samples are not readily available, oxygen tension-based indices such as the alveolar to arterial oxygen tension differences (P[A-a]O2), arterial oxygen tension to alveolar oxygen tension ratio (PaO2/PAO2), PaO2 to FIO2 ratio (PaO2/FIO2) and respiratory index (RI) are widely utilized to reflect Qsp/Qt. Oxygen content-based indices such as the estimated shunt are not as widely utilized as the oxygen tension indices. In 75 critically ill patients in whom a pulmonary artery catheter was being utilized to augment clinical care, comparisons were made between Qsp/Qt and P(A-a)O2, PaO2/PAO2, PaO2/FIO2, RI, and estimated shunt to determine which index best reflected Qsp/Qt. Correlations between Qsp/Qt and estimated shunt were good (r = .94) and poor for the P(A-a)O2 (r = .62), PaO2/PAO2 (r = .72), PaO2/FIO2 (r = .71), and RI (r = .74). We conclude that there are no real substitutes for venous oxygen contents in critically ill patients. When pulmonary artery blood is not available for analysis, oxygen tension-based indices are unreliable reflectors of Qsp/Qt while the estimated shunt, an oxygen content-based index, provides a more reliable reflection of Qsp/Qt.     

Comparison between selective and nonselective nitric oxide synthase inhibition and phenylephrine in normal and endotoxic swine

OBJECTIVE: To compare the cardiopulmonary and peripheral circulatory effects of the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea (SMT) and to phenylephrine (PE) in endotoxic and normal swine. DESIGN: Prospective, randomized, unblinded study. SETTING: Research laboratory of academic medical center. SUBJECTS: Nonanesthetized, sedated, mechanically ventilated, minimally invasive swine model. INTERVENTIONS: Animals received either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline (normal groups). LPS animals were further randomized into four groups when mean arterial pressure (MAP) had dropped to <60 mm Hg: the LPS/saline group received saline only; the other groups received either L-NAME, SMT, or PE. These were titrated to elevate MAP by 20-25 mm Hg, and animals were followed for another 3 hrs. Pulmonary artery occlusion pressure was maintained at one to two times baseline with the infusion of saline. Normal groups received the same agents 1 hr after baseline measurements, and drugs were titrated to achieve similar increases in MAP. We measured gastric-arterial PCO2 gradient by tonometry as an index of gastric mucosal perfusion. Left ventricular volumes were determined echocardiographically; right ventricular volumes were determined by a pulmonary arterial catheter equipped with a rapid thermistor. Plasma nitrite/nitrate (NOx) concentrations were measured hourly. MEASUREMENTS AND MAIN RESULTS: In the LPS groups, all agents elevated MAP and systemic vascular resistance similarly. By hr 4, cardiac output had decreased in all groups, but the decrease with L-NAME (35% +/- 16%) occurred earlier (at hr 3) and was larger than the decrease with SMT at hrs 3 and 5 and larger than the decrease with saline at hrs 3 to 5. L-NAME resulted in a larger increase in mean pulmonary arterial pressure (MPAP) when compared with saline (130% +/- 44% vs. 61% +/- 25%; p < .001) and SMT groups (130% vs. 97% +/- 80%; p < .007). Only L-NAME had detrimental effects on right ventricular function as indicated by an increase in right ventricular end-systolic volume (54 +/- 10 to 87 +/-6 mL; p < .05) and right ventricular end-diastolic volume (90 +/-11 to 128 +/- 18 mL; p < .05). SMT decreased both left ventricular end-systolic volume (10.4 +/- 2 to 7.7 +/- 4 mL; p < .05) and left ventricular end-diastolic volume (18.5 +/- 3 to 14.2 +/- 5 mL; p < .05), indicating improved left ventricular function, whereas L-NAME did not affect left ventricular volumes. Both SMT and PE corrected LPS-induced gastric mucosal acidosis, but L-NAME did not. We did not detect changes in plasma NOx concentrations in any of LPS groups. In the normal groups, all agents increased MAP without changes in plasma NOx concentrations. L-NAME caused a larger decrease in cardiac output, but the increase in MPAP was higher with SMT. Both NOS inhibitors led to left ventricular dilation, but PE did not. Only L-NAME caused right ventricular dilation. There were no changes in gastric-arterial PCO2 gradient. CONCLUSIONS: In LPS animals, we failed to detect changes in plasma NOx concentrations. Furthermore, for similar increases in MAP, SMT improved gastric mucosal acidosis, had less adverse effects on right ventricular function and MPAP, and may have improved left ventricular function. However, apart from its bene-ficial effects on left ventricular function, SMT was not superior to PE. The results from normal animals indicate that both NOS inhibitors have adverse effects on cardiac function beyond those attributed to increased MAP.     

Frequency and percent inspiratory time for high-frequency jet ventilation

A variety of frequencies and percent inspiratory times (%TI) may be used for high-frequency jet ventilation (HFJV). Five physiologic criteria were used to evaluate various combinations of frequency and %TI: mean airway pressure (Paw), cardiac output, PaCO2, PaO2, and intrapulmonary shunt (Qsp/Qt). At a constant drive pressure, the effects of frequencies of 100, 200, 300, 450, 600, 750, and 900 cycle/min at %TI values of 20%, 30%, and 40% of the respiratory cycle were evaluated and compared with the effects of controlled mechanical ventilation (CMV) at 8 to 12 breath/min. Only at 200 cycle/min and 20% TI, were Paw, cardiac output, PaCO2, PaO2, and Qsp/Qt all the same as the CMV values. At 100 cycle/min and 20% TI, CO2 elimination increased without significantly affecting Paw, cardiac output, PaO2, or Qsp/Qt. These data suggest that HFJV might compromise one or more physiologic variables at certain combinations of frequency and %TI. Therefore, at a fixed drive pressure, there appears to be a narrow range of HFJV ventilator settings that should be considered.     

Hemodialysis hemodynamics in an animal model: effect of using an acetate-buffered dialysate

Acetate-buffered dialysis (procedure A) was performed in conscious, nonuremic, splenectomized dogs. In some animals, dialysis was repeated after sympathectomy with 6-hydroxydopamine. During procedure A, hemodynamic changes were most pronounced 1 minute after starting dialysate flow (acute phase), and included a marked rise in cardiac output, pulse rate, and mean pulmonary artery pressure, but no change in mean arterial pressure (MAP) in intact animals. However, a precipitous fall in MAP was noted in sympathectomized dogs. Plasma acetate levels at this time averaged 2.0 +/- 0.5 mmol/L. Six to 30 minutes into procedure A, hypotension could be demonstrated in the intact, but not in the sympathectomized animals, at which time plasma acetate levels averaged 2.2 to 2.7 mmol/L. At 60 to 90 minutes into dialysis, when plasma acetate levels averaged 3.0 +/- 0.8 mmol/L, hypotension with procedure A was no longer significantly greater than with bicarbonate-buffered dialysis (procedure B). Plasma acetate levels at 30 to 90 minutes correlated with the change in cardiac output (r = 0.86, P less than 0.05) and total peripheral resistance (r = -0.76, P less than 0.05), but not with the decrease in MAP (r = -0.43, P not significant). Substantial hemodynamic changes were not seen when bicarbonate-buffered dialysis was used. Our results suggest that acute hypotension during procedure A in the dog model is prevented by an intact sympathetic nervous system. Hypotension occurring later during procedure A is difficult to demonstrate and does not appear to be accentuated after chemical sympathectomy. During procedure A the increase in cardiac output correlates with plasma acetate level.     

Sequential cardiopulmonary variables of infants and children in septic shock

Sequential cardiopulmonary variables were analyzed in 32 infants and children with septic shock. Variables were staged by a system based on therapeutic efforts to control blood pressure. There were 14 survivors and 18 nonsurvivors. Systemic circulation variables (MAP, cardiac index [CI], systemic vascular resistance index [SVRI], wedge pressure [WP], left cardiac work index [LCWI]) and pulmonary circulation variables (mean pulmonary artery pressure [MPAP], pulmonary vascular resistance index [PVRI], CVP, right cardiac work index [RCWI]) were similar in survivors and nonsurvivors. Pulmonary variables (intrapulmonary shunt [Qsp/Qt], fraction of inspired oxygen [FIO2], Pao2, PaCO2) revealed significantly more dysfunction in nonsurvivors than survivors during the postresuscitation (PR) and middle (M) shock stages. Even though oxygen delivery was equivalent in survivors and nonsurvivors, nonsurvivors demonstrated decreased oxygen utilization variables (oxygen consumption [Vo2], arteriovenous oxygen content difference [C(a-v)O2], O2 extraction index, core temperature) during the resuscitation (RS) and PR stages.     

Haemodynamic effects of pressure-controlled ventilation versus volume-controlled ventilation in patients submitted to cardiac surgery.

OBJECTIVE: To compare the haemodynamic effects of pressure-controlled ventilation (PCV) with volume-controlled ventilation (VCV) in patients after cardiac surgery. DESIGN: Prospective clinical study. SETTING: Post-operative cardiac surgical ICU. SUBJECTS: Twenty sequential elective adult patients with no previous chronic lung disease and aged less than 70 years old. INTERVENTIONS: One hour after ICU admission and receiving mechanical ventilation utilising sinusoidal flow, patients were divided into two groups according to cardiac index (CI): group I: CI > 2.5 l/min/M2 and group II: CI < 2.5 l/min/M2. They were submitted randomly to 15 minutes' PC or VC mode, a 30-minute wash-out period of mechanical ventilation with a sinusoidal flow pattern, and then alternate PC or VC mode for 15 more minutes. Data were statistically compared using analysis of variance (ANOVA) with a significance level of 5%. Sedatives and muscle relaxants were given as necessary. ENDPOINTS: Data were obtained at the end of 15 minutes under each ventilatory mode, observing a 30-minute interval between each. MEASUREMENTS: Standard cardiorespiratory parameters were measured or calculated using conventional monitoring (including cardiac output), Qs/Qt, A-aDO2 alveolar-arterial oxygen difference, peak inspiratory pressure, mean airway pressure and dynamic compliance (C). RESULTS: No significant differences between PCV and VCV modes, or between groups, were seen in MPAP, MAP, PCWP, RAP, heart rate, O2ER, VO2I, Paw, C, A-aDO2 and Qs/Qt. However, DO2I (p = 0.0063), LVSWI, (p = 0.0001) and RVSWI (p = 0.0053) showed a statistically significant difference between groups I and II. No influence of VCV or PCV on these parameters was seen. There was a slight significant difference between groups for PVR (p = 0.0205). In contrast, CI (p = 0.0001) and SVR (p = 0.0062) showed significant differences among groups, but also a significantly favourable effect of PCV over VCV (p = 0.0239 and p = 0.0318 respectively). Finally, a significant reduction (p = 0.0001) in peak inspiratory pressure with PCV was observed. CONCLUSION: PC and VC ventilatory modes had comparable effects on patients with preserved or depressed cardiac output. Patients ventilated with PCV showed significantly higher values for cardiac index, a decreased SVR, as well as significantly lower values for inspiratory pressure when compared with VCV patients.     

Sequential cardiorespiratory patterns in septic shock

Sequential hemodynamic and oxygen transport monitoring was performed in 33 patients with septic shock to define the temporal pattern of physiologic events. Measurements taken over a 24-h period before the hypotensive crisis, defined as the lowest initial mean arterial pressure (MAP), were compared to those taken during the 48 h thereafter. In the 24-h period before the hypotensive crisis, there were increases in cardiac index (CI), central venous pressure (CVP), pulmonary capillary wedge pressure (WP), pulmonary vascular resistance index (PVRI), and pulmonary shunt (Qsp/Qt), but decreases in MAP, systemic vascular resistance index (SVRI) and oxygen delivery (Do2). When sequential cardiorespiratory patterns were examined, oxygen consumption (VO2) fell transiently to significantly low values 12 h before as well as at the time of the hypotensive crisis. SVRI fell and CI rose to values significantly different from normal in the 4 h before the low MAP. During the subsequent 48 h after the hypotensive crisis, CI, CVP, WP, PVRI and Qsp/Qt remained elevated. Values for MAP, SVRI, DO2, and VO2 were significantly reduced. These results demonstrate the existence of antecedent cardiorespiratory alterations that precede the hypotensive episode in septic shock and suggest that flow maldistribution in the systemic circulation is an early event with possible pathogenic significance.     

Cardiopulmonary effects of Intralipid infusion in critically ill patients

Cardiopulmonary effects of 500 ml of 20% iv fat emulsion (Intralipid) infusion in two groups of patients who required mechanical ventilation were evaluated in our Critical Care Center. Group 1 included ten patients void of signs or symptoms of sepsis. Group 2 consisted of ten patients exhibiting clinical and laboratory signs and symptoms of sepsis. Data were measured before and immediately after Intralipid infusion and when serum lipemia cleared. Intralipid infusion precipitated a significant increase in venous admixture (Qsp/Qt) from 13.7 +/- 3.6 (SEM) to 18.0 +/- 6.5% and from 22.0 +/- 4.8 to 25.8 +/- 7.0% in groups 1 and 2, respectively. Mean pulmonary artery pressure (MPAP) increased from 22.7 +/- 4.2 to 29.2 +/- 8.1 mm Hg and 26.4 +/- 6.8 to 28.0 +/- 4.0 mm Hg in groups 1 and 2, respectively. When serum lipemia cleared, Qsp/Qt and MPAP returned to preinfusion levels. We conclude that Intralipid infusion increases pulmonary artery pressure and venous admixture in critically ill patients. These changes are temporary and coincidental with serum lipemia rather than presence or absence of sepsis. Adequate levels of oxygenation should be confirmed during Intralipid infusion in patients with borderline oxygenation.