Effect of venous hypercarbia and hyperventilation on myocardial contractility in canine haemorrhagic shock.
DR Karnad, SJ Apte, AN Supe
Dept of Medicine, Seth GS Medical College, Bombay, Maharashtra.
D R Karnad
Dept of Medicine, Seth GS Medical College, Bombay, Maharashtra.
To study the effect of venous hypercarbia on myocardial contractility, haemorrhagic shock was produced in six healthy mongrel dogs by ex-sanguination of 15 ml of blood/kg body weight every 20 minutes till a loss of 45 ml/kg was achieved. After recording haemodynamic and respiratory parameters, the dogs were hyperventilated by positive pressure ventilation for 30 minutes and haemodynamic and blood gas parameters reassessed. During haemorrhagic shock, mean cardiac output decreased from 4.23 l min to 0.98 l min (p < 0.01), stroke index from 2.25 to 0.35 ml/kg (p < 0.05) and left ventricular stroke work index from 3.72 to 0.19 g. m/kg. The mean mixed venous pCO2 increased from 35 mmHg to 56.7 mmHg (p < 0.05). During hypoventilation, mixed venous pCO2 decreased to 40 mmHg (p < 0.05) and without any volume replacement, mean cardiac output increased 2.5 l min (P < 0.05), stroke index to 1.13 ml/kg (p < 0.05) and left ventricular stroke work index, and index of myocardial contractility, increased to 0.78 g.m/kg (p < 0.05). Thus, although hypovolaemia is the major cause of low cardiac output in haemorrhagic shock, this study shows that venous hypercarbia (which probably indicates tissue respiratory acidosis) further worsens circulatory failure by decreasing myocardial contractility. Hyperventilation improves cardiac functions and increases output by relieving tissue hypercarbia in spite of persistent hypovolaemia.
|How to cite this article:|
Karnad D R, Apte S J, Supe A N. Effect of venous hypercarbia and hyperventilation on myocardial contractility in canine haemorrhagic shock. J Postgrad Med 1993;39:68-71
|How to cite this URL:|
Karnad D R, Apte S J, Supe A N. Effect of venous hypercarbia and hyperventilation on myocardial contractility in canine haemorrhagic shock. J Postgrad Med [serial online] 1993 [cited 2020 Jul 3 ];39:68-71
Available from: http://www.jpgmonline.com/text.asp?1993/39/2/68/633
Studies in both animals and humans have shown that acute circulatory failure (shock) causes venous hypercarbia,. With a decline in cardiac output and tissue perfusion, more carbon dioxide is added to a smaller volume of blood in unit time. Thus, by the Fick principle, the difference between the partial pressures of carbon dioxide (PCO2) in arterial and venous blood increases, causing venous hypercarbia. However, the clinical significance of this is not clear, because it is not possible to separately identify the effects of venous hypercarbia on tissue function from those resultingfrom cellular hypoxia, ischaemia, lactic acidosis, or other metabolic abnormalities that characterize the shock state. We therefore approached the problem in reverse-if venous hypercarbia could be corrected without altering otherfactors, then any change in tissue function could be assumed to reflect the effects of hypercarbia.
Carbon dioxide diffuses from tissues into the capillary down a concentration gradient. Therefore, when mixed venous PCO2 is elevated, we expected that the tissue CO2 content too is increased. Hyperventilation results in a parallel decrease in both arterial and venous PCO2, leaving the arteriovenous PCO2 difference unchanged but total body carbon dioxide content is decreased as a result of washing out carbon dioxide in the lung,. Previous studies in dogs suggest that respiratory acidosis impairs cardiac contractility,,. We therefore studied myocardial contractility in canine haemorrhagic shock before and after hyperventilation.
Six healthy mongrel dogs were studied after anaesthetising with intramuscular ketamine (10 mg/kg). Suceinylcholine was administered to facilitate endotracheal intubation and the dogs were ventilated mechanically till the effects of succinylcholine wore off, after which spontaneous breathing was permitted. Ketamine was preferred because it does not interfere with cardiovascular and respiratory reflexes that are activated in shock,.
Basal state: An 18G canula was placed in the femoral artery to monitor arterial pressure and to obtain blood samples. Mixed venous blood was obtained from a balloon tipped catheter with the tip positioned in the pulmonary artery. Expired air was collected in a modified Douglas bag and mean expired oxygen and carbon dioxide concentrations were determined using an automated blood gas analyzer (IL 1306, instrumentation Laboratories, Milan, Italy), which was also used for arterial and mixed venous blood gas estimation. Heart rate, respiratory rate, mean arterial pressure, central venous pressure, minute ventilation, oxygen and carbon dioxide contents of expired air, and arterial and mixed venous blood gas contents were measured in the basal state.
Haemorrhagic shock: A step-wise blood loss was produced: aliquots of 15 ml of blood per kg body weight were removed every 20 minutes, to produce a total blood loss of 45 ml/kg. After allowing 20 minutes for homeostatic reflexes adjustments, all parameters were measured again.
Hyperventilation: The dogs were then hyperventilated mechanically by intermittent positive pressure respiration (IPPR) such that both tidal volume and respiratory rate were 25% more than values observed during spontaneous breathing during haemorrhagic shock. All parameters were measured after 30 minutes of hyperventilation.
Cardiac output was calculated by the Fick equation from measured oxygen consumption and arterial and mixed venous oxygen content. From the cardiac output and other measured parameters, stroke index, systemic vascular resistance, and left ventricular stroke index, systemic vascular resistance, and left ventricular stroke work index were calculated.
Statistical methods: Mann Whitney ‘U’ test was used to compare cardiac output, stroke index and left ventricular stroke work index in the basal state, shock and during hyperventilation. The student's ‘t’ test was used for other comparisons.
Hemodynamics: The cardiac output fell from a mean basal value of 4.23 1/min (cardiac index 0.273 ml/kg) to 0.98 1/min (cardiac index 0.031 1/kg) after haemorrhage (p < 0.05), while heart rate showed a significant increase from 125 to 173 beats / min (p < 0.05) and stroke index and left ventricular stoke work index decreased significantly (p < 0.05 for both). On hyperventilation by IPPR, the cardiac output increased to 2.5 1/min (cardiac index 0.13 1/kg; p < 0.05), heart rate decreased (p=0.06), stroke index increased from 0.35 ml/kg to 1.13 ml/kg (p < 0.05) and left ventricular stroke work index increased from 0.19 g. m/kg to 0.78 g. m/kg (p< 0.05) [Figure:1]. Meanwhile, the mean arterial pressure, which had decreased from 119 to 37 mmHg (15.5 to 4.9 kPa) in haemorrhagic shock (p< 0.025), increased to 48 mmHg (6.3 kPa; p= 0.07) on hyperventilation, while central venous pressure remained low [Table:1]. Systemic vascular resistance, which had increased from 2585 to 7825 dyne.sec/cm (p< 0.05) with hemorrhagic shock, decreased to 5518 dynes. sec/cm on hyperventilation (p value not significant).
Blood gases: Mean arterial pH decreased from 7.34 in the basal state to 7.2 with the development of haemorrhagic shock, and arterial bicarbonate concentration decreased from 16 mmol/L to 9.8 mmol/L (p < 0.025), arterial pCO2 decreased from 32 to 25.4 mmHg (4.16 to 3.3 kPa) while arterial oxygen saturation remained unchanged [Table:2]. Venous PC02, on the other hand, increased from 35.2 mmHg (4.58 kPa) to 56.7 mmHg (7.37 kPa) with shock (p < 0.025) and venous pH decreased from 7.31 to 7.05 (p < 0.025).
On hyperventilating the dogs with hemorrhagic shock by mechanical ventilation, arterial pH, bicarbonate concentration and oxygen saturation remained unchanged while arterial PCO2 decreased further to 20.7 mmHg (2.69 kPa; p=0.05). Venous PCO2 too decreased from 56.7 mmHg (7.37 kPa) to 40 mmHg (5.2 kPa; p < 0.05) as pulmonary carbon dioxide excretion increased.
Pulmonary gas exchange: With shock, alveolar ventilation in the spontaneously breathing dogs increased from 2.44 1/min to 3.94 1/min (p < 0.05) but oxygen consumption declined from 105 to 33 mi/min (p < 0.025). Hyperventilation caused a washout of carbon dioxide and the pulmonary carbon dioxide excretion increased from 136 ml/min to 206 mi/min. Oxygen consumption too increased (p < 0.025) as the delivery of oxygen to tissue improved.
Typical features of severe haemorrhagic shock were observed eg. hypotension, low central venous pressure, decreased cardiac output, increased systemic vascular resistance in order to maintain blood pressure, reduced oxygen delivery to tissues, and metabolic acidosis resulting from cellular hypoxia were seen. Respiratory compensation for metabolic acidosis reduced the mean arterial PCO2 in the spontaneously breathing dogs to 25.4 mmHg (3.3 kPa), but the arteriovenous PCO2 difference increased to such an extent that mean mixed venous PCO2 increased from 35.2 mmHg (3.58 kPa) to 56.7 mmHg (7.37 kPa) during hemorrhagic shock. When the dogs were hyperventilated by IPPR, mean alveolar ventilation increased by 66%, arterial PCO2 increased from 25.4 mmHg (3.3 kPa) to 20.7 mmHg (2.69 kPa). Cardiac output, left ventricular stroke work index and mean arterial pressure improved without any correction of hypovolaemia.
Carbon dioxide, an end product of cellular energy metabolism, is transported from the cells where it is produced to the extracellular fluid and capillary blood by passive diffusion. Therefore, cellular PCO2 always exceeds capillary PCO2. Thus when mixed venous (capillary effluent) blood shows hypercarbia, the PCO2 of the tissues from which this blood is drained will rise proportionately,. Thus, mixed venous blood reflects the total body CO2 content,. The dogs in our study had significant venous hypercarbia. We therefore believe that their tissues were subjected to a dual acidosis; metabolic acidosis as indicated by decreased blood bicarbonate content, and respiratory acidosis as indicated by the venous hypercarbia, and both types of acidosis are potent inhibitors of myocardial contractility,,.
Hyperventilation causes a reduction in both arterial and venous pCO2, and reduces total body carbon dioxide content by increasing pulmonary carbon dioxide exertion,. On hyperventilation, we found that cardiac output and stroke index increased, while systemic vascular resistance decreased. Meanwhile, left ventricular stroke work index, an excellent indicator of overall myocardial systolic function,, increased significantly. Arterial oxygen content did not increase significantly with hyperventilation. Thus, increased myocardial contractility could not have been due to improved myocardial oxygenation. A decrease in myocardial PCO2 due to carbon dioxide washout is more likely to have improved myocardial contractility, and therefore, the cardiac output.
The phasic rise in intrathoracic pressure during positive pressure respiration has been shown to impair venous return to the heart by compression of the heart and reduced ventricular compliance,,,. This fall in cardiac output is more pronounced if cardiac preload is low, as was present in our study. Thus the mechanical effects of IPPR cannot explain the increase in cardiac output observed.
A decrease in systemic vascular resistance (after load) as seen in our study is known to improve cardiac output in cardiogenic shock by reducing myocardial wall tension,. However, this occurs only when the cardiac end-diastolic pressures are elevated. Moreover, when mean arterial pressure is below 60 mmHg, further vasodilatation decreases the cardiac output as coronary perfusion starts declining and this outstrips any benefit from afterload reduction. Our dogs had both reduced preload and also severe hypotension (mean arterial pressure was 37 mmHg). Thus afterload reduction was more likely to be the effect of increased cardiac output rather than the cause.
Thus, we have indirectly demonstrated a detrimental effect of venous hypercarbia on the myocardium by showing that partial correction of this abnormality results in improved cardiac output without correction of the hypovolaemia. This negative inotropic effect is probably a result of the tissue respiratory acidosis that probably accompanies venous hypercarbia. It is therefore evident that though hypovolaemia is the initiating event and the main factor responsible for the fall in cardiac output in haemorrhagic shock, tissue hypercarbia that results from the fall in cardiac output impairs myocardial contractility and further worsens circulatory failure. Similar hypercarbia has been shown to occur during shock in humans too. Further studies are needed to evaluate whether the improvement in cardiac function with hyperventilation is sustained, and occurs in shock due to other causes too. Hyperventilation may have some therapeutic value in such situations.
Mathias DW, Clifford PS, Kdopfenstein HS. Mixed venous blood gases are superior to arterial blood gases in assessing acid-base status and oxygenation during acute cardiac tamponade in dogs. J Clin Invest 1988; 82:833-838.|
|2||Adrogue HJ, Rashad MN, Gorin AB, Yacoub K, Madias NE. Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood. N Engl J Med 1989; 320:1312-1316.|
|3||Snyder JV, Elliot JL, Grenvik A. Capnography. In: Spence AA, editor. Respiratory Monitoring in Intensive Care. Edinburgh: Churchill Livingstone; 1982, pp 100-121.|
|4||Bleich HL. The clinical implications of venous blood gas tension. N Engl J Med 1989; 320:1345-1346.|
|5||Relman AS. "Blood gases": arterial or venous? N Engl J Med 1986; 315:188-189.|
|6||Kinney JM. Transport of carbon dioxide in blood. Anesthesiology 1960; 21:615-619.|
|7||Fahri LE, Rahn H. Dynamics of changes of carbon dioxide stores. Anesthesiology 1960; 21:604-614.|
|8||Cgerniak NS, Longobardo GS, Staw I, Heymann M. Dynamics of carbon dioxide stores changes following an alteration in ventilation. J Appl Physiol 1966; 21:785-793.|
|9||Khuri SF, Flaherty JT, O'Riordan JB, Pitt B, Brawley RK, Donahoo JS, Gott VL, et al. Changes in intramyocardial ST segment voltage and gas tensions with regional myocardial ischemia in dogs. Circ Res 1975; 37:455-463.|
|10||Ng NL, Levy MN, Zieske HA. Effects of change of pH and carbon dioxide tensions on left ventricular performance. Am J Physiol 1967; 213:115-120.|
|11||Dowing SE, Talner NS, Gardner TH. Influence of hypoxemia and acidemia on left ventricular function. Am J Physiol 1966; 210:1327-1334.|
|12||Bond AC, Davies CK. Ketamine and pancuronium for the shocked patient. Anaesthesia 1974; 29:59-62.|
|13||Hirshman CA, McCullough RE, Cohen PJ, Weil JV. Hypoxic ventilatory drive in dogs during thiopental, ketamine or pentobarbital anesthesia. Anesthesiology 1975; 43:628-634.|
|14||Yang SS, Bentivoglio LG, Maranhao V, Goldberg H. From Cardiac Catheterisation to Hemodynamic Parameters, 3rd ed. Philadelphia: FA Davis; 1988, pp 201-205.|
|15||Shoemaker WC. Pathophysiology, monitoring, outcome prediction and therapy of shock states. Crit Care Clin 1987; 3:307-357.|
|16||Grossman W. Cardiac Catheterization and Angiography. Philadelphia: Lea and Febiger; 1986, 301-319.|
|17||Culver BH, Marini JJ, Butler J. Lung volume and pleural pressure effects on ventricular function. J Appl Physiol 1981; 50:630-635.|
|18||Pinsky MR. Determinants of pulmonary arterial flow variation during respiration. J Appl Physiol 1984; 56:1237-1245.|
|19||Marini JJ, Culver BH, Butler J. Mechanical effects of lung distension with positive pressure on cardiac function. Am Rev Respir Dis 1981; 124:382-386.|
|20||Butler J. The heart is in good hands. Circulation 1983; 67:1163-1168.|
|21||Parmley WW, Chatterjee K. The role of vasodilator therapy in heart failure. Progr Cardiovasc Dis 1977; 19:301-325.|
|22||Chatterjee K, Parmley WW, Ganz W, Forrester J, Walinsky P, Crexells C, Swan HJC, et al. Hemodynamic and metabolic responses to vasodilator therapy in acute myocardial infarction. Circulation 1973; 48:1183-1193.|
|23||Wyatt HL, Forrester JS, Tyberg JV, Gold ner S, Logan SE, Parmley WW, Swan HJC, et al. Effects of graded reductions in coronary perfusion on regional and total cardiac function. Am J Cardiol 1975; 36:185-192.