William Rush

Effect of ventilation on resuscitation in an animal model of cardiac arrest.

BACKGROUNDThe need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest.METHODS AND RESULTSTwenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 ...

Effect of ventilation on acid-base balance and oxygenation in low blood-flow states.

Objectives: To investigate how minute ventilation affects the partial pressure of end‐tidal CO2 and arterial and mixed venous pH, Pco2, Po2, and the concentration of bicarbonate during low blood‐flow states. We tested the null hypothesis that acid‐base conditions during low rates of blood flow are not significantly different when minute ventilation is doubled or halved. Design: Prospective, experimental, animal study. Setting: University hospital laboratory. Subjects: Domestic swine. Interventions: We studied ten anesthetized and mechanically ventilated swine (weight, 43 to 102 kg) in a new model of controlled systemic and pulmonary blood flow in which each animal was maintained on ventricular assist devices. After electrical induction of ventricular fibrillation, ventricular assist device blood flow was decreased in steps. At each decrease, control minute ventilation, two times the control minute ventilation (hyperventilation), and onehalf the control minute ventilation (hypoventilation) were administered; each ventilatory change was maintained for 6 mins. Measurements and Main Results: Aortic, pulmonary arterial and central venous pressures, ventricular assist device blood flow, and endtidal CO2 were recorded continuously. Acid‐base conditions were studied at three different mean blood flow rates: 49%, 30%, and 12% of baseline prearrest cardiac index. Arterial pH and Pao2 and mixed venous pH varied directly ( p < .003) with minute ventilation, while Paco2 and mixed venous Pco2, and end‐tidal CO2 varied inversely ( p < .0001) with minute ventilation. Mixed venous Po2 was not significantly related to minute ventilation ( p = .6). Paco2 and arterial bicarbonate; mixed venous pH, mixed venous Po2, and mixed venous bicarbonate, and end‐tidal CO2 varied directly (p < .001) with blood flow, while mixed venous Pco2 varied inversely with blood flow (p < .05). Arterial pH was not significantly related to blood flow ( p = .3). When minute ventilation changed from hyperventilation to hypoventilation at a mean blood flow rate of 49%, mean arterial pH decreased 0.22 ± 0.06 (p < .05), mean Paco2 increased 28 ± 6 torr (3.7 ± 0.8 kPa) (p < .05), and mean Pao2 decreased 99 ± 77 torr (13.2 ± 10 kPa); mean mixed venous pH decreased 0.11 ± 0.02, mean mixed venous Pco2 increased 16 ± 2.2 torr (2.1 ± 0.3 kPa) (p < .05), and mean mixed venous Po2 did not change; mean endtidal CO2 increased 18 ± 2 torr (2.4 ± 0.3 kPa) ( p < .05). The effect of changes in minute ventilation on blood gases and end‐tidal CO2 was similar for mean blood flow rates of 30% and 12% of baseline cardiac index. Conclusions: During low rates of blood flow similar to those rates found in shock and cardiopulmonary resuscitation, alterations in minute ventilation significantly influenced end‐tidal CO2 and both arterial and mixed venous pH and Pco2. These findings may have clinical importance in improving the treatment of shock and cardiac arrest. (Crit Care Med 1994; 22:1827–1834)

End-tidal carbon dioxide during extremely low cardiac output

STUDY OBJECTIVE A number of studies have shown that expired CO2 concentration is closely related to cardiac output, but that cardiac output was not controlled as an independent variable. In addition, the partial pressure of end-tidal CO2 (PETCO2) during extremely low cardiac output has not been reported. The objective of the present study was to measure PETCO2 during well-controlled, very low blood flow rates under conditions of constant minute ventilation. DESIGN Ten anesthetized, intubated, and mechanically ventilated swine (weight, 43 to 102 kg) were placed on two ventricular assist devices in order to control cardiac output. Minute ventilation was measured and kept constant. Ventricular assist device output (measured with an ultrasonic flow probe); PETCO2; and aortic, pulmonary artery, and central venous pressures were recorded continuously. INTERVENTIONS After electrical induction of ventricular fibrillation, pump output was decreased in steps. MEASUREMENTS AND MAIN RESULTS Cardiac index ranged from 0 to 5,371 mL/min/m2; 59% of PETCO2 measurements were made at cardiac indexes of less than 1,313 mL/min/m2 (30 mL/min/kg). The relationship of PETCO2 levels to cardiac index was determined with linear regression analysis; P < .05 was statistically significant. PETCO2 correlated significantly with cardiac index (P < .0001). The best-fit line by least-squares analysis produced the equation: PETCO2 = 4.98 + 0.012 [cardiac index] (r2 = .82). CONCLUSION Under conditions of constant minute ventilation, PETCO2 correlated closely with cardiac index over a large range of blood flow rates, including extremely low rates.

Methylene Blue and Indocyanine Green Artfactually Lower Pulse Oximetry Readings of Oxygen Saturation. Studies in Dogs

The effects of fluorescein, methylene blue, and indocyanine green on hemodynamic variables and on pulse oximetry and co-oximetry measurements of arterial hemoglobin oxygen saturation (SaO2) and oxyhemoglobin percentage (% HbO2) were evaluated in 16 anesthetized dogs in vitro by cooximetry (% HbO2) and in vivo by pulse oximetry (SaO2). The light absorbance (optical density) in plasma (range 500 to 800 nm) was measured by a spectrophotometer. Fluorescein did not affect oximetry measurements, plasma light absorbance in the range measured, or hemodynamic variables. Methylene blue caused dose-dependent decreases in measurements made with both forms of oximetry for up to 30 minutes, the decrease being greater and longer lasting with pulse oximetry (P < 0.05). Hemodynamic measurements in 5 dogs showed that methylene blue (1 to 5 mg/kg) increased arterial pressure transiently, after which cardiac output, stroke index, and left ventricular stroke work index decreased and left ventricular end-diastolic pressure and systemic and pulmonary vascular resistances increased (P < 0.05 with 5 mg/kg). Methemoglobin concentration measured by co-oximetry increased significantly (to 19.9 ± 1.4%, P < 0.05) 1 minute after 5 mg/kg of methylene blue was injected. Methylene blue had a dose- and time-dependent effect on plasma light absorbance, and this effect peaked in the 660- to 670-nm range. The data do not distinguish the relative contributions of physiology (hemodynamic change), chemistry (methemoglobin production), and physics (optical properties) to the decrease in pulse oximetry and co-oximetry measurements that follows injection of methylene blue. Indocyanine green affected neither hemodynamic variables nor co-oximetry readings but decreased pulse oximetry readings for up to 10 minutes dose dependently. With doses of 0.1 to 3.0 mg/kg of indocyanine green plasma light absorbance peaked at 805 nm but increased dose dependently for up to 30 minutes at 660 nm. Methylene blue and indocyanine green (and, by implication, other dyes with plasma light absorbance peaks in the 600- to 1,000-nm range) artifactually alter oximetric detection of arterial hemoglobin oxygen saturation and oxyhemoglobin percentage.

Adenosine Decreases the Minimum Alveolar Concentration of Halothane in Dogs

Adenosine has sedative properties, and adenosine-receptor agonists have been found to reduce anesthetic requirements in rodents. This study determined whether adenosine, in hypotensive doses, reduces anesthetic requirements in halothane-anesthetized dogs. In seven animals, minimum alveolar concentration (MAC) for halothane was determined by a tail-clamp technique at three time points: after 2 h of halothane anesthesia, during adenosine-induced hypotension (mean arterial pressure: 55 mmHg), and 1 h after adenosine was discontinued. In other dogs, the effects of aminophylline, dipyridamole, or the specific adenosine-receptor antagonist 8-phenyl-theophylline (8-PT) on the halothane-adenosine interaction were studied. Adenosine significantly reduced halothane MAC, by 49%, from 0.76 +/- 0.05 to 0.39 +/- 0.05 vol% (mean +/- SEM). This effect was blocked by the concurrent administration of aminophylline (n = 5, P less than 0.05) or 8-PT (n = 4 of 4). When dipyridamole, which increases the plasma concentrations of endogenous adenosine, was administered alone, halothane MAC was reduced from 0.79 +/- 0.03 to 0.67 +/- 0.05 vol% (n = 5, P = 0.09). We conclude that exogenous adenosine substantially reduces halothane MAC in dogs and that this effect is blocked by the concurrent administration of the adenosine-receptor antagonists aminophylline or 8-PT. Relatively small alterations of endogenous adenosine concentrations, however, do not substantially reduce halothane MAC.

Intraosseous and central venous blood acid-base relationship during cardiopulmonary resuscitation

Objective The objectives of this study were: 1) to determine whether obtaining intraosseous (IO) blood samples was practical during cardiopulmonary resuscitation (CPR), and 2) to compare the acid-base status (pH and partial pressure of CO2 (Pco2) of venous and IO blood during CPR. Design A prospective repeated measure study. Setting An animal laboratory at a university medical center. Interventions Nine mixed breed piglets (mean weight 43 kg) were anesthetized, tracheotomized, and placed on a ventilator (Siemens 900C Elema, Sweden). Placement of a pulmonary artery catheter was done via a surgical incision in the neck. An IO cannula was then placed in the tibial marrow cavity. The animals were positioned under a mechanical thumper (Thumper,™ Michigan Instruments, Grand Rapids, MI) for chest compressions. Blood gases were analyzed during steady state (baseline) after five minutes of ventricular fibrillation and during CPR at seven, nine, 11, 13, 15, and 18 minutes. Main results Blood samples for acid-base analysis were easily obtained from the IO sites during all sampling times. Mixed venous blood was slightly more acidic than IO blood, especially at 13, 15, and 18 minutes. However, there were no significant differences in pH and Pco2 values between IO and central venous (CV) gases at all time intervals except the Pco2. At nine minutes, a significant difference (P < 0.006) was found in Pco2 (59 ± 4 vs 47 ± 5 torr) for the CV versus IO sample, respectively. As the duration of CPR progressed, the differences in PCO2 between IO and CV sites were clinically relevant (though not statistically significant). Conclusion Obtaining blood from the IO site is practical during CPR. The divergence in values as CPR progresses suggests that, during longer periods of CPR, IO blood may reflect local acidosis and yield lower Pco2 and higher pH values that CV blood. This finding may limit the usefulness of IO blood to judge acid base status as CPR progresses.

Pulse oximetry fails to accurately detect low levels of arterial hemoglobin oxygen saturation in dogs.

The accuracy of two commercially available pulse oximeters (the Ohmeda Biox 3700, software version “J,” and the Nellcor N-100) in detecting low levels of arterial hemoglobin oxygen saturation (SaO2) was evaluated in 10 dogs in which hypoxia was induced by stopping the fresh gas flow into the anesthesia machine circle system. Measurements made in vivo with the pulse oximeters, with detectors placed on the tongue, were compared with measurements made in vitro using an IL 282 CO-Oximeter as SaO2 decreased toward zero. Measurements from the two oximeters correlated poorly over the range from 0 to 100% SaO2 (r = 0.69). In this range, the correlation between Nellcor N-100 measurements and those of the CO-Oximeter had an r of 0.82, a regression line slope of 0.82, and a y intercept of 14.8; the correlation between the Ohmeda Biox 3700 and the CO-Oximeter had an r of 0.83, a regression line slope of 0.66, and a y intercept of 32.7. The correlation with the CO-Oximeter was similar for both the Ohmeda and the Nellcor pulse oximeters at an SaO2 of 80% or more. However, when SaO2 was less than 80%, measurements by pulse oximetry correlated less well with CO-Oximeter measurements (r = 0.62, slope = 0.64, and y intercept = 21.0 for Nellcor; r = 0.71, slope = 0.67, and y intercept = 32.4 for Ohmeda). When SaO2 was less than 60%, both oximeters inaccurately indicated the co-oximetry values (r = 0.36 and y intercept = 26.1 for the Nellcor; r = 0.48 and y intercept = 33.2 for the Ohmeda). In this animal model, with pulse oximeter measurements obtained from the tongue and with rapidly decreasing SaO2, measurements of SaO2 by pulse oximetry become inaccurate in comparison with co-oximetry measurements at low levels of SaO2.

Early administration of amrinone does not impair regional metabolism of O2 or lactate and, by improving myocardial performance, preserves myocardial blood flow in the ischemic canine heart

The inotropic and vasodilating effects of amrinone can upset the balance of O2 supply and demand by changing those components in opposite directions simultaneously. We used a canine model of acute coronary artery occlusion to test our hypothesis that early administration of amrinone (before failure of the heart) would have beneficial effects on hemodynamic status and regional metabolism during ischemia, even before heart failure. Twenty dogs anesthetized with thiamylal were subjected to 50%, 75%, and 100% occlusion of the left anterior descending coronary artery. Half of the dogs were given a bolus injection of amrinone (0.75 mg/kg) 1-2 min before each occlusion, immediately followed by continuous infusion (10 micrograms.kg-1 x min-1) during occlusion; the other half did not receive amrinone (control). Hemodynamic and metabolic variables were measured in the ischemic area (the left anterior descending coronary artery) and in a nonischemic area (the circumflex vein). Amrinone not only decreased heart rate, left ventricular systolic and end-diastolic pressures, and mean pulmonary arterial pressure during constrictions but also maintained contractility, stroke volume index, and stroke volume index/left ventricular end-diastolic pressure before and during constrictions. Regional myocardial blood flow in ischemic areas decreased with amrinone during constrictions but was still higher than in untreated animals. Regional ischemic and nonischemic metabolic variables (metabolism of intracoronary potassium, CO2, O2, glucose, and lactate) were similar for both groups and changed to the same extent. Amrinone appears to improve left ventricular performance and increase blood flow to ischemic myocardium while not worsening regional metabolic effects during various grades of ischemia in the dog.

Decreased regional lactate production and output due to intracoronary continuous infusion of esmolol during acute coronary occlusion in dogs.

This study was designed to test the hypothesis that intracoronary administration of esmolol can confer metabolic protection during coronary constriction or occlusion, without affecting hemodynamic parameters, in a canine model. Seventeen anesthetized open-chest dogs underwent direct cannulation of the left anterior descending coronary artery (LADa), its companion vein (LADv), and the distal circumflex vein (CFXv). LADa flow was measured with an electromagnetic flowmeter. Using a micrometer-driven snare around the LADa, flow was reduced by 50%, 75%, and 100% for 15 minutes, with 1 hour of normal flow before each constriction. In 7 dogs (group 1) chosen randomly, esmolol, 15 to 20 micrograms/kg/min, was infused continuously into the LADa; the rate was adjusted to maintain baseline hemodynamic values. The second group (10 dogs) was not treated with esmolol. Heart rate (HR), electrocardiogram (ECG), LADa flow, LV dP/dt, and aorta (Ao), pulmonary artery (PA), LADa, and left ventricular (LV) pressures were recorded continuously. Cardiac output (CO) (thermodilution) was measured and blood was sampled from all catheters before and after constrictions for analysis of glucose, lactate, sodium, potassium, and blood gases. Flow and pressure in the LADa in both groups decreased similarly during each corresponding constriction. Systolic LV pressure, LV dP/dt, and LV stroke work index were affected in both groups only during 100% constriction. HR, Ao, and PA pressures, and total and peripheral pulmonary resistances were affected similarly in both groups during each constriction. Myocardial lactate extraction and consumption were less negative (negative = net production and output) in the LAD perfusion bed during corresponding constrictions with esmolol than without it.(ABSTRACT TRUNCATED AT 250 WORDS)

Automatic Mechanical Device to Standardize Active Compression–Decompression CPR

STUDY OBJECTIVE To develop an automatic mechanical device capable of performing active compression-decompression (ACD) CPR in laboratory animals. DESIGN A swine model was used to study standard and ACD CPR. One-minute periods of standard mechanical chest compressions were alternated with mechanical ACD CPR. SETTING University hospital laboratory. INTERVENTIONS A commercially available device that provided standard chest compressions only was modified to deliver ACD CPR. RESULTS The absolute difference in intrapleural pressure and tidal volume almost doubled during ACD CPR compared with that with standard CPR. CONCLUSION The presence of a greater negative change in intrapleural pressure confirmed that active decompression of the chest had occurred and that the device was capable of performing ACD CPR. The device provides consistent rate, depth, force, and duty cycle.