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Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation.

BACKGROUND: Sufficient cardiac pre-load for maintaining adequate cardiac output is a major goal in the treatment of critically ill patients. We studied the effects of increasing cardiac output by fluid loading on the indocyanine green plasma disappearance rate (ICG-PDR) and gastric mucosal regional CO2 tension (PRco2) as an indicator of splanchnic microcirculation. METHODS: With approval by our ethics committee and written consent, we studied post-operatively 12 patients (1 female, 11 males; 66 +/- 13 years) with elective coronary artery bypass grafting (n = 10) or aortic valve replacement (n = 2). All patients had received pulmonary artery and left atrial catheterization previously for clinical indications. Cardiac output and filling pressures were measured immediately after intensive care unit (ICU) admission and 1 h after the beginning of fluid loading. RESULTS: Overall, 630 +/- 130 ml of 6% hydroxyethylstarch (130 kDa) was infused with the splanchnic perfusion pressure remaining constant. Norepinephrine and epinephrine dosages were unchanged. The cardiac index increased significantly from 2.8 +/- 0.7 to 3.5 +/- 0.6 l/min/m2 and the stroke volume index from 30 +/- 7 to 38 +/- 8 ml/m2. ICG-PDR showed no significant change, i.e. from 21.2 +/- 6.5 to 21.6 +/- 6.5%/min. Gastric mucosal PRco2 and the Pco2 gap (difference between regional and end-tidal CO2 tension) were constant, i.e. changed from 5.1 +/- 0.8 to 5.5 +/- 1.1 kPa and from 0.9 +/- 0.5 to 1.0 +/- 0.7 kPa, respectively. CONCLUSION: Increasing cardiac output to supranormal values by fluid loading is not associated with a significant change in ICG-PDR or gastric mucosal PRco2.

APACHE↗

Thoracic electrical bioimpedance: a non-invasive measure of cardiac output for porcine research.

A comparison of two techniques for measuring cardiac output, thermodilution (TD) and thoracic electrical bioimpedance (TEB), was undertaken in a porcine model. Eight anaesthetized large white pigs were studied. A total of 436 paired measurements were performed over a range of cardiac outputs from 1.7 to 15.1 l/min as measured by thermodilution. The Pearson product moment correlation coefficient was r = 0.963 with P < 0.001. Analysis by Bland and Altman statistics revealed a mean difference (bias) of -0.02 l/min and the limits of agreement were +/- 1.6 l/min, similar to figures found in human comparative studies. These results confirm that thoracic electrical bioimpedance is a valid method of measuring cardiac output in pigs. It has significant advantages compared to thermodilution, in particular it is cheap, simple to use, non-invasive and provides continuous data.

Animals↗

In vitro evaluation of a new lithium dilution method of measuring cardiac output and shunt fraction in patients undergoing venovenous extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate, in vitro, a method of measuring cardiac output and shunt fraction during venovenous extracorporeal membrane oxygenation (ECMO). DESIGN: Experimental study using an in vitro model. SETTING: A teaching hospital. MODEL: An ECMO circuit was set up in parallel with a patient circuit consisting of tubing through which saline was circulated from a 50-L reservoir by a pump which was set at 3 L/min to represent cardiac output. A second pump in the ECMO circuit drew saline from the patient circuit and passed it through a membrane oxygenator. The flow from the membrane oxygenator either returned directly to the patient circuit or was diverted, via a third pump, back into the ECMO circuit, thereby producing a shunt. INTERVENTIONS: By adjusting the flow rates of the second (ECMO) and third (shunt) pumps, three shunt fractions of 12%, 25%, and 50% were produced at three different ECMO flow rates. Lithium chloride (0.15 mmol) was injected just downstream of the membrane oxygenator; the lithium ion concentration-time curves were recorded simultaneously in the flow returning to the saline reservoir and in the flow just upstream of the membrane oxygenator using lithium selective electrodes. MEASUREMENTS AND MAIN RESULTS: Nine pairs of curves were recorded, one pair for each combination of ECMO and shunt flow rates. Analysis of these curves allowed shunt flow and "cardiac output" to be calculated and compared with the flow rates delivered by the pumps. Mean "cardiac output" derived from the lithium dilution curves was 2.98 +/- 0.18 (SD) L/min, compared with a delivered pump flow of 3 L/min. Measured shunt flow = 0.008 + 1.09 x actual shunt flow (R = 0.997). CONCLUSIONS: This method would allow cardiac output and shunt flow to be measured in patients undergoing venovenous ECMO. It could result in better patient management and improved cannula design.

Blood Flow Velocity↗

Impedance cardiography derived cardiac output in hemodialysis patients: a study of reproducibility and comparison with echocardiography.

BACKGROUND: Hemodialysis patients experience a variety of hemodynamic abnormalities that contribute to cardiovascular disease mortality which is the leading cause of death in these patients. Impedance cardiography has been utilized in order to monitor cardiac hemodynamics with lower cost and inconvenience, but it has not been appropriately validated in the hemodialysis population. AIM: We repeatedly used impedance cardiography to assess short- (48 hours) and long-term (15 days) reproducibility of cardiac output measurements and we compared baseline impedance cardiography measurements with echocardiographic measurements. PATIENTS AND METHODS: We studied 109 stable hemodialysis patients, aged 59.70 +/- 11.97 years being on hemodialysis for 67.59 +/- 40.15 months, on a non-dialysis day. Cardiac output was obtained with the BioZ impedance cardiography system (Cardiodynamics, San Diego, Ca, USA). Baseline echocardiography was performed using a Hewlett-Packard Sonos 2500 (Andover, Mass., USA). RESULTS: The values of impedance cardiography derived cardiac output were 5.28 +/- 0.79, 5.27 +/- 0.75 and 5.25 +/- 0.74 l/min at baseline (107 patients), 48 hours (107 patients) and 15 days (98 patients) respectively, showing high reproducibility. Bland and Altman analysis estimated that bias at 48 hours and at 15 days were: -0.013 (95% confidence intervals = -0.045 to 0.019) and 0.028, (95% confidence intervals = -0.044 to 0.101), respectively. In addition baseline impedance cardiography derived cardiac output was significantly correlated with the echocardiographic derived cardiac output (r = 0.9, p < 0.0001). CONCLUSION: Impedance cardiography is a simple non invasive technique for cardiac output estimation in hemodialysis patients which has high reproducibility when performed under controlled conditions, and is closely correlated with echocardiographic measurements of cardiac output.

Aged↗

Cardiac output measurement with a simplified thermodilution technique. Comparison with the Fick method.

A simplified thermodilution technique for cardiac output measurement is compared with the Fick method in dogs, over a wide range of cardiac output values. The reproducibility of the method is satisfactory (differences less than 10 per cent for 95 per cent of the measurements). The overall correlation factor (r = 0.97) is highly significant for cardiac outputs ranging from 750 to 7,500 ml.mn(-1). The influence of hematocrit (when lower than 30%) and of the injection site of indicator are discussed. Present experiments confirm that the use of pre-set factors allow for the thermal loss inside the catheter does not obviate the accuracy of thermodilution method for cardiac output measurements. The slope of the regression line is very close to 1. Lack of fit to linearity is tested and is found not significant throughout the explored range. This technique should therefore have extensive clinical applications.

Animals↗

Unreliability of M-mode left ventricular dimensions for calculating stroke volume and cardiac output in patients without heart disease.

Single-dimension left ventricular echocardiographic measurements are currently being used in investigational studies as the basis for evaluating cardiac output parameters in normal subjects, even though validity of the method for normal subjects has not been established. We prospectively compared stroke volume derived from M mode left ventricular dimensions (LVID) to Fick stroke volume in 20 patients with no objective evidence of cardiac disease. Based on simultaneous studies, stroke volume by Fick ranged from 39 to 121 ml and cardiac output ranged from 3.9 to 10.4 L/min. Comparing the LVID cubed method with Fick, the correlation coefficient was r = .47 for stroke volume and r = .36 for cardiac output. LVID absolute error in cardiac output ranged -2.11 to +3.21 L/min. Use of other published formulas for calculating stroke volume from LVID did not improve accuracy. These data indicate that stroke volume and cardiac output cannot be accurately measured or reliably estimated from M mode left ventricular internal dimensions.

Adult↗

Measurement of cardiac output with the Quantascope, a novel Doppler device: comparison with thermodilution.

The Quantascope is a novel non-imaging echo-Doppler device designed to measure cardiac output. We have compared this device with thermodilution. Twenty-five patients with suspected coronary artery disease undergoing diagnostic coronary arteriography simultaneously had cardiac output measured with the Quantascope and with thermodilution. Doppler systematically underestimated cardiac output, when compared with thermodilution, by a mean (SD) of 0.9 (1.5) l.min-1 (P < 0.01). The cardiac output derived by the Doppler technique did not correlate with that derived by thermodilution (r = 0.36, P = NS). Compared with the currently accepted reference technique of thermodilution, we found measurement of cardiac output by the Quantascope to be inaccurate: this contradicts previous reports.

Aged↗

Measurement of cardiac output using Physio Flow with different positions of electrode placement.

INTRODUCTION: Physio Flow is a non-invasive impedance cardiograph device that measures cardiac output. Recommended electrode placements involve six electrodes, including two near the xiphisternum (Z3 and Z4/ ECG3/neutral). This study aims to evaluate if changing the positions of these two leads to the left fourth and fifth intercostal spaces along the mid-axillary line results in a change in the cardiac output measurement. METHODS: This was a prospective, controlled, crossover, paired study of 30 patients where electrodes were placed in the recommended positions and cardiac output (CO1) obtained after two minutes. The second cardiac output (CO2) was then obtained with the electrodes Z3 and Z4/ECG3/neutral repositioned at the left mid-axillary line at the fourth and fifth intercostal spaces. The final step involved switching the Z3 and Z4/ECG3/neutral leads back to the recommended position and the cardiac output (CO3) was measured. RESULTS: The average of the initial and third readings (COave) was compared with the measured CO2 and analysed. The regression equation was: CO at the proposed site (CO2) = COave at the recommended site + 0.058. The paired samples correlation was 0.995. Within the 95 percent limits of agreement, the bias with CO measured at the proposed site of electrode placement was 0.046 L/min with the limits at -0.24 L/min and 0.34 L/min. The mean difference was 0.86% of the average CO. CONCLUSION: A small positive bias was demonstrated when Physio Flow measurements were taken with the leads Z3 and Z4/ECG3/neutral placed in the mid-axillary line fourth and fifth intercostal spaces.

Cardiac Output↗

Effects of reduced rebreathing time, in spontaneously breathing patients, on respiratory effort and accuracy in cardiac output measurement when using a partial carbon dioxide rebreathing technique: a prospective observational study.

INTRODUCTION: New technology using partial carbon dioxide rebreathing has been developed to measure cardiac output. Because rebreathing increases respiratory effort, we investigated whether a newly developed system with 35 s rebreathing causes a lesser increase in respiratory effort under partial ventilatory support than does the conventional system with 50 s rebreathing. We also investigated whether the shorter rebreathing period affects the accuracy of cardiac output measurement. METHOD: Once a total of 13 consecutive post-cardiac-surgery patients had recovered spontaneous breathing under pressure support ventilation, we applied a partial carbon dioxide rebreathing technique with rebreathing of 35 s and 50 s in a random order. We measured minute ventilation, and arterial and mixed venous carbon dioxide tension at the end of the normal breathing period and at the end of the rebreathing periods. We then measured cardiac output using the partial carbon dioxide rebreathing technique with the two rebreathing periods and using thermodilution. RESULTS: With both rebreathing systems, minute ventilation increased during rebreathing, as did arterial and mixed venous carbon dioxide tensions. The increases in minute ventilation and arterial carbon dioxide tension were less with 35 s rebreathing than with 50 s rebreathing. The cardiac output measures with both systems correlated acceptably with values obtained with thermodilution. CONCLUSION: When patients breathe spontaneously the partial carbon dioxide rebreathing technique increases minute ventilation and arterial carbon dioxide tension, but the effect is less with a shorter rebreathing period. The 35 s rebreathing period yielded cardiac output measurements similar in accuracy to those with 50 s rebreathing.

Adult↗

Thoracic electrical bioimpedance measurement of cardiac output in postaortocoronary bypass patients.

OBJECTIVE: To assess the degree of correlation and agreement between cardiac output by thermodilution and bioimpedance using the BoMed NCCOM3-R7 monitor in postaortocoronary bypass patients. DESIGN: Prospective, randomized sampling. SETTING: Military teaching hospital intensive care unit. PATIENTS: Fifty patients undergoing coronary artery bypass surgery with thermodilution pulmonary artery catheters in place. Simultaneous determination of cardiac output by thermodilution and thoracic bioimpedance was performed. Readings were taken between 8 and 24 hrs after surgery. Forty patients were intubated; 19 patients had left-sided tube thoracotomy in addition to two mediastinal tubes, and 19 patients were obese. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall degree of correlation between the two measures was fair (r2 = .24). The bias and precision measurements were inaccurate as well (-0.33 +/- 3.14). Patients with normal body habitus or who were not receiving mechanical ventilation showed the best correlation (r2 = .40 and r2 = .45, respectively). Only 62% (31/50) of all patients had simultaneous measurements fall within 20% of each other, and there were no clinical features that made identification of those patients possible. CONCLUSIONS: Use of the BoMed NCCOM3-R7 bioimpedance monitor as a replacement for thermodilution-derived cardiac output cannot be recommended in postaortocoronary bypass patients. The distortions of patients' normal anatomy and physiology, coupled with the presence of endotracheal tubes and mechanical ventilation, mediastinal tubes and chest tubes, result in only fair correlation, significant bias, and poor precision between the two measures of cardiac output.

Adult↗

Comparison between cardiac output measured by thermodilution technique and calculated by O2 and modified CO2 Fick methods using a new metabolic monitor.

OBJECTIVE: To calculate cardiac ouptut from dual oximetry with carbon dioxide production (VCO2) and oxygen consumption (VO2) measured by a new metabolic monitor, and to compare these values with measurements made simultaneously using the thermodilution method during the steady state condition. DESIGN: Prospective, comparative clinical study. SETTING: The adult postsurgical intensive care unit (ICU) of a University Hospital. PATIENTS: Twenty mechanically ventilated postsurgical patients (70.7 +/- 7.8 years of age; range 50-84). MEASUREMENTS AND RESULTS: A new metabolic monitor (Puritan-Bennett 7250, Carlsbard, USA) connected to a ventilator (Puritan-Bennett 7200) was used to measure VCO2 and VO2. Measurements of arterial (SaO2) and mixed venous (SvO2) oxygen saturations were made using pulse and venous fiberoptic oximeters. Cardiac output starting from VCO2 (COVCO2) was obtained according to Mahutte's formula: COVCO2 = VCO2/[k (SaO2-SvO2)], where k represents a constant. The value for each patient was determined from the initial measurements of thermodilution cardiac output (COtd), VCO2, SaO2 and SvO2. COVCO2 calculated from the previous equation was compared to the COtd. Cardiac output calculated from the traditional O2 Fick equation (COVO2) was compared to the COtd. All patients were studied over a period of 120 min at 15-min intervals in reasonably stable conditions. COVCO2 was closely related to COtd (r = 0.94; SEE = 0.79; p = 0.0001; n = 180) with a bias of -0.10 and a precision of 0.45 l/min. The mean percent difference between the two methods was -2.2 +/- 8.3%. COVO2 was related to COtd (r = 0.77; SEE = 0.79; p = 0.0001; n = 180) with a bias of -0.57 and precision of 0.86 l/min. The mean percent difference between the two methods was -10.8 +/- 16.0%. CONCLUSIONS: In stable patients, cardiac output measurements obtained from dual oximetry with VO2 and VCO2 measured by this new metabolic monitor, show good correlation with measurements made using the thermodilution method. The values of cardiac output calculated from VCO2 are more accurate and precise than values from VO2. The validity of these measurements in hemodynamically unstable patients and during various modes of mechanical ventilation seems warranted.

Aged↗

The decreased oxygen uptake during progressive exercise in ischemia-induced heart failure is due to reduced cardiac output rate.

We tested the hypothesis that the inability to increase cardiac output during exercise would explain the decreased rate of oxygen uptake (VO2) in recent onset, ischemia-induced heart failure rats. Nine normal control rats and 6 rats with ischemic heart failure were studied. Myocardial infarction was induced by coronary ligation. VO2 was measured during a ramp protocol test on a treadmill using a metabolic mask. Cardiac output was measured with a flow probe placed around the ascending aorta. Left ventricular end-diastolic pressure was higher in ischemic heart failure rats compared with normal control rats (17 +/- 0.4 vs 8 +/- 0.8 mmHg, P = 0.0001). Resting cardiac index (CI) tended to be lower in ischemic heart failure rats (P = 0.07). Resting heart rate (HR) and stroke volume index (SVI) did not differ significantly between ischemic heart failure rats and normal control rats. Peak VO2 was lower in ischemic heart failure rats (73.72 +/- 7.37 vs 109.02 +/- 27.87 mL min(-1) kg(-1), P = 0.005). The VO2 and CI responses during exercise were significantly lower in ischemic heart failure rats than in normal control rats. The temporal response of SVI, but not of HR, was significantly lower in ischemic heart failure rats than in normal control rats. Peak CI, HR, and SVI were lower in ischemic heart failure rats. The reduction in VO2 response during incremental exercise in an ischemic model of heart failure is due to the decreased cardiac output response, largely caused by depressed stroke volume kinetics.

Animals↗

Effect of region of interest selection on first-pass radionuclide cardiac output determination.

In principle, region of interest (ROI) selection should not affect the measurement of cardiac output by the first-pass technique with a radioactive intravascular indicator. Clinical application of the method requires that this theoretical hypothesis be tested. Sixty-eight left anterior oblique first-pass studies were acquired with a scintillation camera and computer using red blood cells labeled in vitro with 99mTc. Calculated mean cardiac output varied in the following order with respect to ROI: lung greater than right heart greater than left ventricle greater than whole heart (both ventricles) greater than aorta. Similar variations were observed in patients both with and without valvular regurgitation. Regions of interest over left ventricle or whole heart yielded the best correlations with cardiac output by thermodilution (r = 0.96, 0.95, respectively, n = 28) as well as the smallest interobserver variations (r = 0.994, 0.995, respectively, n = 33). First-pass studies with [99mTc]red blood cells labeled in vitro can yield accurate, reproducible determinations of cardiac output provided that the effect of ROI selection is recognized and that regions are properly selected.

Adolescent↗

Accuracy of cardiac output estimation with biplane transesophageal echocardiography.

To evaluate the accuracy of cardiac output measurements with biplane transesophageal Doppler echocardiography, we examined 26 sets of observations in 14 patients using thermodilution technique as the standard. A mitral inflow method by single-plane combined the time-velocity integral of mitral inflow at the mitral annulus with the area of mitral annulus, assuming it to be a circular shape, by use of either the four- or the two-chamber view. With both views, a mitral inflow method by biplane combined the average of time-velocity integral of mitral inflow from the four- and the two-chamber views with the area of mitral annulus, assuming it to be an ellipsoid shape. The correlation coefficients between thermodilution and single-plane method of cardiac output were 0.81 (SEE = 0.72 L/min) and 0.85 (SEE = 0.79 L/min) for the four- and the two-chamber views, respectively. The correlation coefficient with biplane method was 0.93 (SEE = 0.47 L/min). Thus, biplane transesophageal Doppler echocardiography can be used for more accurate estimation of cardiac output.

Aged↗

Influence of nitroglycerin on splanchnic capacity and splanchnic capacity-cardiac output relationship.

It has been postulated, but not tested directly, that nitroglycerin's venodilatory effects attenuate cardiac output. Thus, the present study examined the importance of changes in splanchnic capacity, as assessed by scintigraphy, in the regulation of cardiac output during nitroglycerin administration in 16 anesthetized pigs under conditions of carotid sinus denervation and cervical vagotomy. With nitroglycerin administration (0.5 mg/min i.v.) for 5 min, systemic arterial pressure decreased from 115 +/- 7 to 95 +/- 7 mmHg (P < 0.0001), portal vein pressure decreased from 9.0 +/- 0.5 to 8.5 +/- 0.5 mmHg (P < 0.0001), portal flow increased from 637 +/- 49 to 668 +/- 60 ml/min (P = 0.09), and transhepatic resistance decreased from 7.5 +/- 1.5 to 6.5 +/- 1.0 mmHg.min.l-1 (P < 0.01), but cardiac output was unchanged (1,929 +/- 126 to 1,890 +/- 138 ml/min). Total splanchnic intravascular volume (VI) increased 1.6 +/- 1.0% (P < 0.05, 14 +/- 10 ml). This increase was due to an increment in extrahepatosplenic (mesenteric) VI (12.9 +/- 1.9%, P < 0.0001), since splenic VI decreased (9.6 +/- 2.8%, P < 0.0001) and hepatic VI did not change. After splenectomy, nitroglycerin infusions at doses of 0.5 and 2 mg/min were associated with increases in total splanchnic VI of 3.7 +/- 1.2% (P < 0.0001, 30 +/- 10 ml) and 7.6 +/- 1.7% (P < 0.001, 59 +/- 10 ml) due entirely to increases in mesenteric volume of 9.9 +/- 2.7% (P < 0.0001) and 16.5 +/- 1.9% (P < 0.0001), respectively, but cardiac output was unchanged at the end of infusion at either dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Echographic method for the estimation of cardiac output from mitral-valve area, heart rate, and diastolic-filling period in conditions of mitral stenosis: correlation with cardiac catheterization.

An orifice equation for the non-invasive measurement of mitral-valve area is demonstrated. It is shown that by combining this expression with the assumption of mitral-valve area invariance an orifice equation for the non-invasive assessment of cardiac output in conditions of mitral stenosis using simple echographically measureable variables can be developed. This equation is V = (21)-1 R X A X T2, where V = cardiac output in ml, R = heart frequency, A = mitral-valve area in cm2 and T = diastolic-filling period in sec X min-1. These results suggest that when mitral-valve area is accurately measured at one point in time, cardiac output may be measured at subsequent times at a clinically useful level from a knowledge of the echographically measurable variables of heart rate and diastolic-filling period.

Cardiac Catheterization↗

The thermal-dye method of lung water measurement is reliable at a low cardiac output.

The measurement of lung water by the thermal-dye double indicator dilution technique was evaluated in dogs with normal and edematous lungs during a state of reduced cardiac output. The technique used cold indocyanine green dye to measure extravascular thermal volume (EVTV) as an estimate of extravascular lung water (EVLW). Anesthesia was maintained with pentobarbital. In 15 of 21 animals, pulmonary edema was first induced with oleic acid (0.75 to 0.18 ml/kg). Cardiac output (CO) was then decreased by a combination of propranolol and slow exsanguination (mean CO reduction to 36% of baseline). Extravascular lung water produced in this model ranged from 1.4 to 30.2 ml/kg. Predetermination measurements of EVTV correlated closely with EVLW as determined by gravimetric analysis (EVTV = 1.1 EVLW + 4.7 ml/kg, n = 21, r = 0.93, P less than 0.001). Thermodilution cardiac output measured in the abdominal aorta (used in the calculation of the EVTV) correlated well with simultaneous measurements of cardiac output by both indocyanine green dye dilution and pulmonary artery thermodilution (r = 0.86 and r = 0.88, respectively, pretermination). The thermal-dye technique appears to provide an accurate reflection of lung water in normal and edematous lungs, even in the presence of a low cardiac output.

Animals↗

Effect of enkephalins on cardiac output and regional blood flow in conscious dogs.

To investigate the effects of enkephalins on cardiac output and regional blood flow, we administered D-Ala-D-Leu-enkephalin (DADLE) intracisternally (ic) to 14 chronically instrumented unanesthetized dogs. Measurements were made at base line, 20, 45, and 75 min after DADLE (25 or 125 micrograms/kg) and 15 min after naloxone (5 micrograms/kg ic). After 125 micrograms/kg DADLE, all animals developed hypoventilation, bradycardia, and decreased O2 consumption without hypotension. Cardiac output decreased (-34%), but brain blood flow increased (+110%). Blood flow decreased to the diaphragm (-38%), heart (-21%), skeletal muscle (-40%), skin (-67%), pancreas (-79%), and gastrointestinal tract (-26%). After 25 micrograms/kg DADLE, there were no consistent changes in cardiac output or regional blood flow. Four additional animals (without DADLE) were exposed to altered inspired gases to reproduce the blood gas changes after DADLE. These animals developed hyperventilation without bradycardia and increased brain (+114%) and diaphragm (+649%) blood flow. We conclude that centrally administered enkephalins produce 1) a parallel decrease in ventilation, heart rate, O2 consumption, and cardiac output and 2) a major blood flow redistribution, primarily dictated by the effects of opioids on ventilation, heart rate, and metabolism.

Animals↗