|
|
PAEDIATRIC PERFUSION: WEANING FROM CARDIOPULMONARY BYPASS IN NEONATES AND INFANTS WITH PULMONARY HYPERTENSION |
The pulmonary circulation and the right heart are often referred to as the lesser circulation. From the perspective of heart disease in the adult, ischemia frequently results in the disordered function of the left ventricle. In congenital heart disease abnormalities of the right ventricle and pulmonary circulation assume much more prominence. From the time of birth, great changes take place in the pulmonary circulation in order to adapt it for a role that it was never required to perform during fetal life, the pumping of the total cardiac output through the lungs. Nor is the right ventricle morphologically designed to perform as a high-pressure pumping chamber, and consequently, abnormalities of the pulmonary valve or pulmonary vascular bed, which place increased resistive loads on the right ventricle, cause problems early in neonatal life. To understand the changes in the pulmonary circulation that occur with congenital heart disease, it is necessary to trace the development of the pulmonary vascular bed during fetal life and the adaptation that occurs in the neonatal period and childhood.
Obstructive lesions of the right ventricle and pulmonary circulation, including pulmonary valve stenosis and lesions involving the pulmonary arterial tree, account for 25 to 30% of all congenital heart lesions [1]. Where these lesions are associated with an intact intraventricular septum, there is no route for decompression of the right ventricle, and the characteristic features common to all these anomalies are increased impedance and hypertrophy of the right ventricle. During fetal life, obstructive lesions of this type results in hyperplasia and hypertrophy of the myocardium, which is different from that seen in adult life. In adult hypertrophy of the cardiac muscle result without hyperplasia [1]. In the fetus and neonate obstructive lesions result in the formation of capillary supply that keeps pace with the hyperplasia of cardiac muscle, so that there is an adequate blood supply to the hypertrophied muscle. Without this, the newborn infant would be unable to generate the increased intraventricular pressures necessary to maintain blood flow across a fixed obstruction.
Physiology and Pathophysiology of the Pulmonary Circulation in Congenital Heart Disease:
The pulmonary circulation has the ability to constrict rapidly and dilate in response to stimuli owing to the fact that its arterial walls are well endowed with smooth muscle, which is sensitive to hypoxia and hydrogen ion, especially in newborn [2]. Two other factors also contribute to resistance within the pulmonary vascular bed: 1) the lumen size as determined by the amount of medial hypertrophy of vessel wall, and 2) the ratio of alveoli to vessels, decreasing from 20 alveoli to 1 artery in the newborn, to 12:1 at 2 years, and 6:1 in the adult [3]. The presence of congenital heart defect profoundly influences the orderly adaptation of pulmonary circulation from fetal to adult life.
The importance of pulmonary vascular endothelium in the modulation of PVR has only recently been recognized. Abnormal reactivity have been obtained from investigations of endothelial function, which is known to be abnormal in situations of congenital heart disease with increased PBF [4,5,6], pulmonary hypertension [7,8], and congestive heart failure [9]. Normal vascular endothelium produces the endothelium-dependent relaxing factor (EDRF), and the failure of secretion of EDRF by damaged endothelium may lead to vasoconstriction. Studies have demonstrated the failure of this mechanism of relaxation in small- to medium sized pulmonary arteries in the lungs in children with congenital heart disease with increased PBF [5].
There are investigations for the account of endothelial production of nitric oxide (NO), because of the role it may play in normal homeostasis and the hypertensive lung, because of its possible therapeutic potential. Some data suggest that NO may partially account for the pulmonary vasodilatation that occurs at birth [10], and it modulates the pulmonary vasoconstrictor response to hypoxia and other vasoconstrictors [11]. NO can reduce vascular smooth muscle profileration [12] and total protein and connective tissue synthesis [13], and its possible that it can influence normal growth or pathologic vascular remodelling in the lung [14].
Cardiopulmonary Bypass and the Pulmonary Circulation:
Cardiopulmonary bypass is known to alter pulmonary vascular resistance. There are investigations that documented significant increase in PVR for up to 3 hours postbypass in a group of adult patient undergoing coronary artery bypass grafting [15]. Several factors may contribute to increased PVR, including lung injury caused by compliment activation with intrapulmonary sequestration of neutrophils, free radical formation, vasoactive mediator generation [16,17] and damage to blood constituents by the extracorporal ciculation. The extravascular lung water accumulation following cardiopulmonary bypass [18] may also contribute to increase in PVR . There are studies that point toward abnormal endothelial function secondary to cardiopulmonary bypass as being responsible for the enhanced vascular reactivity seen in the postoperative period. There is speculation that pulmonary vasoreactivity is due to a combination of abnormal preoperative function and ischemic injury produced by the cessation of pulmonary blood [6,19,20].
Weaning from Cardiopulmonary Bypass:
Successful management of patients with abnormalities of the right heart and pulmonary circulation is based on the understanding that are changes not only in the RV and pulmonary vascular bed, but also within the systemic circulation, that may profoundly influence cardiac output and PBF. The weaning should be ,, slowly and careful,, in patients with a reactive pulmonary vascularture, for this reason a pulmonary artery, a right and left atrial pressure catheter should be placed before weaning from cardiopulmonary bypass. A venous and an arterial online blood gas measurement like the CDI from Terumo has proved to be a reliable and accurate method of continuously monitoring for oxygen saturation and blood gas in the weaning period and identifying factors leading to a decreased arterial PO2 and increased PAP.
Blood gas management: Changes in oxygen tension, carbon dioxide, and hydrogen ion concentration have profound effects on PVR, especially in the presence of pulmonary disease. PAP and PVR increase sharply when arterial oxygen tension decreases below 50 mmHg, with an exaggerated response at a pH below 7,4. Both hypoxia and hypoxemia are potent vasoconstrictors, and acidosis, either respiratory or metabolic, induces pulmonary vasoconstriction both independently [21,22]. Although hyperventilation is a accepted method of treating increased PAP in infants. Drummond noted that hyperventilation to a PaCO2 of less than 25 mmHg and a pH greater than 7,6 resulted in a marked in PaO2 secundary to a reduction in the PAP:SAP ratio [23]. The ph affects the pulmonary circulation in a way opposite that of the systemic vasculature. Acidose is a pulmonary vasoconstructor, and it acts synergistically with alveolar hypoxia to increase PVR [2]. Controversly, alkalosis is a pulmonary vasodilatator. Experimental studies have shown that blood ph alone is also a operative factor, because alkalosis produced by infusion of base is as effective in decreasing PVR as is respiratory alkalosis. The effect of ph on pulmonary vascular smooth muscle is unclear [24,25].
Volume management: In the slowly weaning phase of the CPB, changes in cardiac output and left ventricular performance have major effects on the pulmonary vascular bed, because the perfusionist induced the filling volume of the heart. As cardiac output and pulmonary blood flow decrease, PVR increase even though PAP may be unchanged or even increased. Changes in PAP should always be referenced to changes in systemic pressure and cardiac output to assess events in the pulmonary vascular bed accurately. In this respect, the ratio between mean PAP and mean systemic artery pressure (SAP), as well as measurment of PVR and systemic vascular resistance (SVR), are particularly important. One of the cardinal objectives in treating abnormalities of the right heart and pulmonary circulation is the maintenance of adequate output from the RV and, therefore, left ventricular preload. Acute increases in PVR in patients with a reactive pulmonary vasculature initiate a devastating cycle of events resulting in acute right heart failure with increased right ventricular end-diastolic volume and pressure. The thin-walled RV normally compensates poorly for increased impedance to outflow in the acute situation, particularly in the immediate weaning period when the ventricle is vulnerable following the ischemic injury of aortic cross-clamping.
Optimal Hematocrit:
As the hematocrit increases so does oxygen carrying capacity and therefore oxygen delivery, on the other hand, resistance to blood flow through the lungs increase with hematocrit and therefore blood viscosity. When we wean the patient from CPB, we look about a hematocrit from 30 % - 34 %. Lister et al. calculated, based on both empirically derived data and considerations that PVR is 36% greater at a hematocrit of 55% than at a hematocrit of 33% [26].
Hemofiltration/Ultrafiltration:
Multiple studies have documented the deleterious effect of CPB on pulmonary structure and function [27,28]. A large number of inflammatory mediators are released in response to CPB [30,31] which may lead to leukocyte activation and sequestration in the lung [29]. This may largely account for the alterations in surfactant [30] and lung compliance [27,31,32]. Ratliff [33] demonstrated these changes correlated directly to the duration of CPB. Hemo- or ultrafiltration during the rewarming phase of CPB has been shown by Journois and colleagues to reduce many of these inflammatory mediators substantially and to lead postoperativly to improved hemodynamics, reduced blood loos, and shortened duration of ventilation [34].
| Weaning Guidelines from CPB in Pulmonary Hypertension | |
|---|---|
| pH | 7,6 |
| PaCO2 | 25 mmHg |
| PaO2 | 300 mmHg |
| Hct | 32 - 34% |
Anesthetic Management:
The other aspect of patient management with increased pulmonary vascular reactivity is the manipulation of cardiac output. An adequate preload and augmentation of ventricular performance with the use of inotropes and systemic vasodilatators maintain optimum cardiac output with low PVR. Also high dose of fentanyl and sufentanil in infants have benefical effect on the pulmonary circulation [35,36].
Inhaled Nitric Oxide:
Nitric Oxide (NO) is an endothelium-derived relaxing factor (EDRF) and a gas [37]. When inhaled at a low concentrations it can relax constricted pulmonary vascular smooth muscle. Hemoglobin rapidly inactivates any NO that crosses the alveolar epithelium and vascular wall to reach the capillary lumen, promoting clinical investigations in diseases where selective pulmonary vasodilation would be beneficial. Optimal dosing of NO to maximize pulmonary vascular relaxation without incurring toxic side effects, systemic hypotension, or an increased venous admixture is unclear. It is a selective pulmonary vasodilator with minimal adverse hemodynamic effects when administered and monitored in a judicious fashion. Its hemodynamic benefit has been demonstrated in patients with pulmonary hypertension associated with anomalous pulmonary venous connection [38], congenital mitral stenosis [39], Fontan physiology [40], and patients with pre-existing left-to-right shunts, and it can be used effectively in the treatment or prevention of pulmonary hypertensive crises after CPB [41].
| Factors influencing Pulmonary Vascular Resistance: | |
|---|---|
| Increase PVR | Decrease PVR |
| Lower pH | increased pH |
| Acidosis | Alcalosis |
| Hypocarbia | Hypercarbia |
| High hematocrit | Low hematocrit |
| Hypoxia | Hyperoxia (Increased FiO2) |
| Mechanical obstruction | Deep Fentanyl anaesthesia |
| Atelectasis/pleural effusion capacity | Hemofiltration ? |
Conclusion:
In children, significant increases in PVR after CPB increase right ventricular afterload and may be poorly tolerated if sustained. In the weaning period, right ventricular function may be transiently impaired by such factors as right ventriculotomy or prolonged aortic crossclamping. In addition to blood -borne and mechanical factors that may transiently elevate PVR. For this reason, a concept which has focused the previously descriebed factors must be applied for weaning from CPB in neonates and children, and the mechanical cardiopulmonary support should be the last exit and should be described in other literature [42].
References:
1) Emmanouilides GC, Baylen BG In Heart Disease in Infants, Children and Adolecents. Baltimore: Williams & Wilkins, (1983): 234-262
2) Rudolph AM, Yuan S Response of pulmonary vasculature to hypoxia and H+ ion concentrations changes. J. Clin Invest. (1966) 45: 399-411
3) Rabinovitch M, Lung biopsy in congenital heart defects: A morphometric approach to pulmonary vascular disease. Circulation (1978) 58:1107
4) Celermajer DS, Cullen S, Deanfield JE Endothelial dysfunction occur early in the pulmonary circulation of children with congenital heart defects. Circulation (1992) 86: suppl 1, 775
5) Celermajer DS, Cullen S, Deanfield JE Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics. Circulation (1993) 87: 440-446
6) Wessel DW, Adatia I, Giglia TM et al Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation (1993) 88:2128-2138
7) Dinh-Xuan AT, Higgenbottam TW et al Impairment of endothelium-dependent relaxation in patients with Eisenmenger syndrome. Br.J.Parmacol (1989) 99:9-10
8) Dinh-Xuan AT, Higgenbottam TW et al Impairment of endothelium-dependent relaxation in chronic obstructive lung disease. N.Engl.J.Med. (1991) 324:1539-1547
9) Drexler H,Hayoz D, Munzel T et al Endothelial function in chronic congestive heart failure. Am.J.Cardiol. (1992) 69:1596-1601
10) Moore P, Velvis H, Fineman JR et al EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs. J.Appl.Physiol. (1992)73:2151-2157
11) Fineman JR, Chang R, Soifer SJ. EDRF inhibition augments pulmonary hypertension in intact newborn lambs. Am.J.Physiol. (1992) 262: 1365-1371
12) Garg UC, Hassid A Nitric oxid-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cell. J.Clin.Invest (1989) 83:1774-1777
13) Kolpakov V,Gordon D, Kulik TJ Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circ.Res. (1995) 76:305-309
14) Roberts JD, Roberts CT, Jones RC et al Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy, and growth retardation in the hypoxic newborn rat. Circ.Res. (1995) 76:215-222
15) HeinonenJ, Salmenpera M, Takkunen O. Increased pulmonary artery diastolic-pulmonary wedge pressure gradient after cardiopulmonary bypass. Can.Anaesth.Soc.J. (1985) 32:165-170
16) Chenoweth DE, Cooper SW, Hugli TE et al Complement activation during cardiopulmonary bypass : Evidence for generatio of C3a and C5a anaphylatoxins. N.Engl.J.Med. (1981) 304: 497-503
17) Moorita K, Ihnken K, Buckberg GD et al Pulmonary vasoconstriction due to impaired nitric oxide production after cardiopulmonary bypass. Ann.Thorac.Surg. (1996) 61:1775-1780
18) Lesage AM, Tsuchoika H, Young WG, Pathogenesis of pulmonary damage during extracorporeal perfusion. Arch.Surg. (1966) 93:1002-1008
19) Anyanwu E, Diettrich H, Gieseking R, Enders HJ. Ultrastructural changes in the human lung following cardiopulmonary bypass. Bas.Res.Cardiol. (1982) 77:309-322
20) Fishman A. Hypoxie on the pulmonary circulation: How and where it acts. Circulation Res. (1976) 38:221-231
21) Hauge A. Hypoxia and pulmonary vascular resistance: The relative effects of pulmonary arterial and alveolar PO2. Acta Physiol.Scand. (1969) 76 : 121-130
22) Sylvester JT, Harabin AL, Peake ME et al Vasodilator and constrictor responsees to hypoxia in isolated pig lungs. J.Appl.Physiol. (1980) 49:820-825
23) Drummond WH, Gregory GA, Heymann MA et al The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension. J.Pediatr. (1981) 98:63-611
24) Brimioulle S, Lejeune P, Vachiery J, et al Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. Am.J.Physiol. (1990) 258:347-353
25) Schreiber MD, Heymann, Soifer SJ. Increased arterial ph, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs. Pediatr:Res (1986) 20:113-117
26) Lister G, Hellenbrand WE, Kleinman CS et al Physiologic effects of increasing hemoglobin concentration in left-to-right shunting in infants with ventricular septal defect. N.Engl.J.Med. (1982) 306:502-506
27) Jonmarker C, Larsson A, Werner O. Changes in lung voume and lung-thorax compliance during cardiac surgery in children 11 days to 4 years of age. Anesthesiology (1986) 65: 259-265
28) Gale GD, Teasdale SKJ, Sanders DE. Pulmonary atelectasis and other respiratory complications after cardiopulmonary bypass, an investigation of eatiological factors. Can.Anaesth.Soc.J (1979) 26:15-26
29) Howard RJ, Crain CC,Franzini DA et al Effects of cardiopulmonary bypass on pulmonary leukostasis and complement activation. Arch.Surg. (1988) 123:1496-1501
30) McGowan FX, Ikegami M, delNido PJ et al Cardiopulmonary bypass significantly reduces surfactant activity in children. J.Thorac.Cardiovasc.Surg. (1993) 106:968-977
31) Turnbull KN, Miyagishima BA, Gerein AN. Pulmonary complications and cardiopulmonary bypass: A clinical study in adults. Can.Anes.Soc.J (1974) 21:181-194
32) Rea HH, Harris EA, Seelye ER et al The effects of cardiopulmonary bypass upon pulmonary gasexchange. J.Thorac.Cardiovasc.Surg. (1978) 75:1ß4-120
33) Ratliff NB, Young CNG, Hackel DB et al Pulmonary injury secondary to extracorporeal circulation: An ultrastructural study. J.Thorac.Cardiovasc.Surg. (1973) 65:425-432
34) Journois D, Pouard P, Greeley WJ et al Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology (1994) 81: 1181-1189
35) Hickey PR, Hansen DD. Fentanyl and sufentanil-oxygen-pancuronium anesthesia for cardiac surgery in infants. Anesth.Analg. (1984) 63:117-124
36) Hickey PR, Hansen DD, Wessel D et al Blunting of stress responses in the pulmonary circulation of infants by fentanyl. Anesth.Analg. (1985) 64:1137-1142
37) Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol.Rev. (1991) 43:109-142
38) Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of nitric oxide. Ann.Thorac.Surg. (1996) 62:1759-1764
39) Atz AM, Adatia I, Jonas RA et al Inhaled nitric oxide in children with pulmonary hypertension and congenital mitral stenosis. Am.J.Cardiol. (1996) 77: 316-319
40) Goldman AP, Delius RE, Deanfield JE et al Pharmacologic control of pulmonary blood flow with inhaled nitric oxide after the fenestrated Fontan operation. Circulation (1996) 94: suppII 44-48
41) Journois D, Pouard P, Mauriat P et al Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects. J.Thorac.Cardiovasc.Surg. (1994) 107:1129-1135
42) Barrtlet R, Zwischenberger J Extracorporeal membran oxygenation (ELSO-The red book) 2ed 2000
43) Castaneda A, jonas RA, Mayer J, Hanley F. Management of infant and neonate with congenital heart disease. 65 - 87 In Cardiac surgery of the neonate and infant, WB Saunders (1994) Philadelphia