Pediatric cardiovascular intensive care: Current insights and future directions

ELSEVIER Progress in Pediatric Cardiology 4 (199.5) 111-115

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Pediatric Cardiology

Pediatric cardiovascular intensive care: Current insights and future directions

Thomas J. Kulik”, Macdonald Dick, II

Ditision of Pediatric Cardiology, The Department of Pediatrics, C.S. Mott Children’s Hospital, Uniwrsiy of Michigan Hospitals. MCHC F 1310, Box 0204, Ann Arbor, MI 48109-0204, USA

Abstract

The last 20 years have witnessed tremendous advances in the science and practice of pediatric cardiology and pediatric cardiac surgery. The development of pediatric cardiac intensive care has paralleled and contributed to these advances, providing the intensive cognitive and technologic milieu where the child with a cardiac defect moves from the operating room to recovery and home. Current practice and analysis point to the need for further investigation and new strategies to continue to manage successfully the pediatric cardiac patient in this technology and labor intensive, and thus very expensive, environment. This issue of Progress in Pediahic Cardiology focuses on these advances and underscores the challenges of the future.

Keywords: Intensive care; Cardiology; Cardiac surgery; Pediatrics

It seems likely that the last two decades will come to be regarded as the golden age of pediatric cardiology. The field has flourished remarkably, having grown in size, clinical efficacy, and intellectual vigor. Multiple factors have propelled this expansion: (1) New technologies, such as two-dimensional echocardiography, interventional catheterization and electro- physiology, have improved patient care, contributed to the fiscal foundation of the subspecialty, and added much more: these new diagnostic and therapeutic tools have enhanced our understanding of human physiology and pathophysiology, and have attracted the intellectually curious and able to the field, (2) the almost uncanny evolution of the ability to repair complex heart lesions in the neonate has also helped to invigorate the field, adding considerably to the sense of clinical potency and thus inspiring both once

and future pediatric cardiologists, (3) the as yet nascent but very promising application of molecular biology has begun to contribute to the forward mo- mentum m this field. Although the amount of human and other resources in this arena linked to molecular investigations is as yet relatively small, the critical mass is growing, suggesting that this discipline is poised to use the most advanced probes to revolution- ize the understanding, prevention, and treatment of cardiac malformations.

The pediatric cardiac intensive care unit has been a fortunate beneficiary of this vitalization of pediatric cardiology and cardiac surgery. For example, two dimensional echocardiography with Doppler has had a major impact on pre and postoperative management of both simple and complex heart lesions. Non-invasive imaging provides all necessary anatomic (and even physiologic) information prior to operation in many patients with congenital heart defects, thereby eliminating the need for potentially noxious invasive studies. Critically ill neonates in need of urgent operation, such as infants with total anomalous pulmonary

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112 T J. Kulik, ht. Dick, II / Progress in Pediatric Cardiology 4 (1995) 111-l 15

venous connection with obstruction, perhaps benefit the most, but the morbidity, mortality, and cost of treating many others (e.g., infants with interrupted aortic arch) is reduced appreciably thanks to echocardiography. Perhaps even more importantly for the cardiac intensivist, echo studies can be used to assess the adequacy of surgery and characterize the patient’s post-operative physiology, and thus can often elimi- nate the need for catheterization in the sick postoperative patient, when the risk of invasive studies the highest. Finally, this tool has enhanced our understanding of human physiology and biology, and thus impacted our approach to patient management in the intensive care unit. Consider, for example, the echocardiographic studies showing rapid changes in left ventricular mass and function following pulmonary artery banding in babies with transposition of the great arteries [l]. This sort of information - which could hardly have been obtained by any other means - has helped inform our approach to these and other patients following cardiac operations. It is also difficult to overestimate the effect that modern cardiac surgery, and more specifically the ability to successfully perform complex reparative surgery in virtually the smallest infants, has had on those who work in the intensive care unit. To some extent this impact has been psychological, or even aesthetic: The opportu- nity to participate in such a marvellous process of cardiac redesign is to some extent its own reward, and has understandably enticed at least a few workers to the intensive care unit. Modern cardiac surgery has served as the ‘mother of invention’, engendering advances in postoperative care. Patients with anatomi- cally and physiologically complex disease survive the operating room, but require fastidious care to successfully traverse the postoperative period. The challenges faced by intensivists and the solutions devised to address them would not have appeared during this period if surgery were still limited to simple palliative procedures, and those patients with the most complex lesions were still denied operation.

If the cardiac intensive care unit has been a beneficiary of a generation of technological and intellectual growth in pediatric cardiology, it has also been an important contributor. To some extent this has been by way of the aforementioned improvements in the pre and postoperative management of cardiac patients. Consider the ratio of resistance to blood flow in the pulmonary and systemic circulations. This ratio is of great importance in determining the hemodynamic stability - and ultimately, the outcome - of patients with aortopulmonary communications. While this has long been appreciated (a baby with a large ductus can be pretty sick), a heightened sensitivity to the importance of these variables, and methods of manipulating them, are a relatively recent development and have

flowed from experience developed in the intensive care unit (and the research lab). Successful palliation of at least one cardiac lesion - hypoplastic left heart syndrome - is probably as much dependent upon application of these principles as to advances in surgical technique.

A better appreciation of the salutary effects of analgesia and sedation in the postoperative period has also resulted from clinical experience and investigations in the intensive care unit. Of course, the need to provide analgesia sufficient to relieve pain, as an essential component of humane therapy, far ante- dates the invention of the intensive care unit. What has been applied in the intensive care unit is newer. As is so nicely outlined in the chapter by Drs. Zucker and Stafford, the concept has evolved that very large doses of analgesia - anesthetic doses - can blunt a variety of potentially pernicious responses to surgery and thus improve the physiology of the patient in multiple ways 121. The intensive care unit is also serving as a locus of investigation of the clinical utility of the latest wonder drug, inhaled nitric oxide. To what extent this agent will prove useful in reducing morbidity and mortality in patients with heart disease is unclear at present, but investigations conducted in the intensive care unit will clearly be required to answer this important question. A variety of other advances, some conceptual, some technical, have been made in the intensive care unit over the last several years (e.g., better therapy for postoperative arrhythmias, or keeping the chest open in the unstable postoperative patient).

The cardiac intensive care unit has served as an engine for advancing the clinical care of our patients, and it has also provided the matrix for studies which have augmented our understanding human biology and pathobiology. To some extent the advances in clinical care noted above are associated with an improved understanding of human physiology, but prospective investigations have also been conducted that more specifically address sharply defined physio- logical or biological questions. The effect of high- frequency jet ventilation on airway pressure and multiple hemodynamic parameters in the postoperative ‘Fontan’ patient has been carefully studied [3], and serves as an apt example of such an investigation. Though many unanswered questions remain, this study clearly shows that pulmonary vascular resistance is sensitive to changes in the mode of ventilation (given a fixed alveolar ventilation) and thereby usefully adds to our understanding of pulmonary physiology. The effect of cardiopulmonary bypass on pulmonary vascular endothelial function has also been investigated in the cardiac intensive care unit [4]. Although loose ends remain in this study as well, in demonstrating that postoperative patients have abnormal pulmonary

T.J. K&k, M. Dick, II /Progress ~11 Pediatric Curdiolop -I (1995) 111-115 113

endothelial function this work does yield useful in- sight into the biology of human endothelium.

The examples given are but two of many, although it must be admitted that many investigations in the pediatric cardiac intensive care unit have been of a pharmacologic nature (measuring the effect of an inotropic agent, for example), and usually directly analogous to comparable studies previously per- formed in adults. Nonetheless, what these investigations lack in novelty is made up for in utility, as developmental differences in the response to various drugs suggest that their effect in the immature organism need to be determined to guide their rational use. Still, there is a sense that the potential for the cardiac intensive care unit to serve as a platform for clinical research is as yet only incompletely realized. As is so cogently outlined in Drs. Wessel and Newberger’s chapter on research in the intensive care unit, where else can one observe, intensively monitor, and even alter (e.g., administer a drug or other treatment) the growing, developing human? Of course, multiple factors tend to complicate and limit such studies: the heterogenity of the ages, sizes, and anatomic and physiologic makeup of the patients; the fact that most patients are abnormal (either temporarily or perma- nently) in one or several ways makes studies of nor- mal biology problematic; many patients receive multiple medications or other treatments that many con- found the interpretation of observations. Adherence to strict ethical standards is obviously a major con- sideration, as is the natural and understandable reluc- tance of some parents to consent to investigation involving their children. All these constraints notwith- standing, it would seem that the surface has barely been scratched regarding clinical investigations in the pediatric cardiac intensive care unit.

If the preceding constitutes a very rough survey of how pediatric cardiac intensive care has related to the larger parent tield of pediatric cardiology, what does the future hold for this subdiscipline within a subdiscipline? One may be able to envisage some of the trails this endeavor must break in the coming years - if patient outcomes are to continue to improve - by considering the chapters in this issue of Progress in Pediatric Cardiology. They succinctly summarize the current state of knowledge in areas particularly ger- mane to this field, and in doing so, suggest problems needing to be solved, as well as potentially fruitful lines of investigation for pediatric cardiologists/intensivists.

In his chapter on myocardial perfusion, Dr. Julien Hoffman beautifully summarizes the fundamental determinants of myocardial oxygen demand and what is known of how the coronary circulation meets this requirement. For many patients in the cardiac intensive care unit myocardial oxygen demand and supply

are well-matched, and this issue therefore pretty much takes care of itself. Yet, unfortunately, in the occasio- nal patient with elevated demand or limited supply (or both), myocardial ischemia, dysfunction, and fail- ure (in the starkest sense> can rapidly follow. Particu- larly vulnerable are patients with a large aortopulmonary shunt, inflicted with the pernicious combination of ventricular volume overload, low diastolic pressure, and low PO:, although mismatch between myocardial demand and supply can occur in other circumstances. While drugs are available which can influence coronary perfusion pressure and cardiac output. what we currently lack is the information necessary to use them optimally to increase the oxygen supply to demand ratio. While adrenergic agonists increase aortic diastolic pressure and therefore coronary perfusion, they also increase myocardial oxygen demand: because there is no clinically available means of measuring the balance between myocardial oxygen demand and supply, pressor use is guided more by intuition than biochemistry. The ability to sensitively detect and quantify myocardial ischemia would also help to determine which patients might benefit from other forms of therapy (e.g., extracorporeal life support). Many other related questions persist: What is the optimal pharmacologic therapy for depressed myocardial function secondary to cardiopulmonary bypass‘? What is the most effective way to promote recovery of function in the ‘stunned’ myocardium? How can the noncompliant ventricle be made more compliant? Clearly, advances from both the laboratory and the intensive care unit will be needed to provide answers.

Drs. Fineman and Soifer very nicely summarize the enormous amount that has been learned regarding the multiple factors which can influence resistance to blood flow through the lungs. While it is true, as they relate, that a variety of strategies are available to influence pulmonary vascular resistance, the grail of a selective, reliable pulmonary vasodilator has yet to be found (the jury still being out on inhaled nitric oxide). Conversely, a pharmacologic agent with the seemingly perverse quality of selectively conswicfing pulmonary vessels would also be of considerable use, reducing pulmonary blood flow in patients with excessive shunting through aortopulmonary communications. These and other puzzles continue to pose questions: By what mechanism(s) does airway pressure influence pulmonary vascular resistance? What is the optimal hematocrit, given the twin considerations of pulmonary vascular resistance and oxygen delivery, for patients particularly sensitive to pulmonary resistance [e.g., ‘Fontan’ patients]? How do pathological condi- tions, such as cardiopulmonary bypass, cardiac malformations, and lung disease, affect the physiology and pharmacology of the lung’s circulation? These queries and others like them will keep devotees of the

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pulmonary circulation usefully occupied for the inde- finite future. Although laboratory investigations will obviously play the major role in solving some of these problems, studies in the intensive care unit will ultimately be required for their resolution. In fact, in some cases - for example, answering the question of optimal hematocrit - explorations in the intensive care unit may be the only practical means of obtain- ing the needed data.

How mechanical ventilation figures into the tight linkage between the heart and lungs is the subject of Dr. Melione’s chapter. As is nicely reviewed there, the interactions between natural and mechanical ventilation and the heart have been mostly well worked out, and practical application of these principles a part of routine practice in most intensive care units. Further advances in care will undoubtedly be made on several fronts, including new modes of mechanical ventilation, ‘liquid’ ventilation, practical application of left ventricular augmentation by mechanical ventilation, and others.

If ventilator management of cardiac patients has improved greatly over the last 20 years, so to has the management of arrhythmias in the intensive care unit, as is reviewed by Drs. Dorostakar and Dick. Major advances during the past 20 years in the understanding of the fundamental and clinical mechanisms of arrhythmias has led to more precise diagnosis and more effective treatment. A number of new anti- arrhythmic drugs - verapamil and other calcium channel blockers, esmolol and other selective beta blockers, adenosine, and amiodarone - have appeared and find use in the intensive care unit. The use of epicardial electrodes, as well as esophageal electode catheters, to aid the diagnosis and treatment of arrhythmias is both relatively recent and tremen- dously helpful. More effective regimens for con- trolling junctional ectopic tachycardia have also evolved, although therapy for this tachycardia still leaves much to be desired. Further advances in prevention and therapy of pre and postoperative arrhythmia’s will largely hinge on pharmaceutical dis- coveries, although electrical and surgical ablation of accessory conduction pathways will also help reduce the incidence of arrhythmia in the intensive care unit.

Sometimes conventional therapy is not sufficient to support life in a patient with a potentially recoverable condition. Drs. Mosca and Bove succinctly discuss the various mechanical means available to temporarily assist the failing circulation, and review the devices’ many limitations. While these mechanical devices have proven life saving, in some patients, they have too often been unsuccessful in delivering long term sur- vivors. The experience at many centers with the extracorporeal membrane oxygenator (ECMO) in critical post-operative cardiac patients perhaps best illus-

trates the discrepancy between the promise and the reality of this recent technology. To some extent this relatively poor survival rate is due to the complications which can attend the use of these devices (e.g., bleeding, emboli, infection). A poorly quantified frac- tion of the mortality resides in patients who are treated with mechanical support but ultimately prove to have an unremediable lesion. In addition, these techniques are relatively cumbersome and costly. De- vices which are less expensive to operate and cause fewer complications obviously need to be developed. In addition, cardiac intensivists need to become better at identifying those who both need and are likely to benefit from extracorporeal mechanical assistance.

If the last 20 years have seen extensive publication on medical and surgical techniques aimed at securing survival for patients with cardiac malformations, much less has been established concerning the ultimate quality of life for those who survive. While this topic is a difficult one for many reasons, its importance is rapidly growing, and will doubtlessly consume a considerable amount of effort in the years ahead. Be- cause neurological outcome is one of the most important determinants of quality, Dr. du Plessis’ exposition is particularly apt and important. Specific curative therapy for the neurological lesions seen in the ICU is pretty much lacking, although attention to certain details in the postoperative period, such as appropriate anticoagulation, may help prevent certain complications, as Dr. Du Plessis implies. Further reductions in neurological complications will doubtlessly require efforts made in many settings, including preopera- tively and in the operating room itself, but the intensive care unit may be the site of greatest activity. For one thing, neurological complications related to thrombi, emboli, hemorrhage, or insufficient brain perfusion often originate in the intensive care unit, and hence need to be prevented there. For another, if neurological damage is often related to events that occur after the initial insult (e.g., reperfusion injury), the intensive care unit will be the locus of therapy for injury which originates elsewhere.

One final general observation might be made. Given the high rate of survival for the vast majority of cardiac lesions treated in the intensive care unit, reduction of mortality per se is no longer the major concern for the pediatric cardiac intensivist: Improwd outcomes, especially neurologic and hemodynamic, and reduced cost of care will be among the chief preoccupations for the coming years. Both of these are in large part served by reducing complications associated with the cardiac lesion or the therapy. As implied above, the development of new technologies and techniques may ultimately prove to be the most powerful strategy for reducing such complications. In fact, it is this promise of ultimately less expensive care

T.J. Ku& M. Dick, II /Progress in Pediattic Cardiology 4 (1995) 111 -I15 115

that most powerfully argues - in a system increasingly preoccupied with cost - for continued expendi- ture of resources on intensive care related research. Unfortunately, such advancement tends to proceed at an unpredictable and sometimes chelonian pace. On the other hand, fastidious application of known technology is also effective in reducing complications of care. Strategies to maximize application of current knowledge and skills, such as optimal training of health care personnel, and application of ‘critical pathways’ or similar protocols designed to assure uni- form optimal therapy, can be applied immediately in any intensive care unit. To what extent ‘critical pathways’ and ‘continuous quality improvement’ will help reduce complications in the cardiac intensive care unit - given its kaleidoscopic mix of complex patients - has yet to be determined, but they will likely be significant preoccupations for at least the near term.

Reducing the time a patient spends in the intensive care unit - surely the chief factor in determining the true cost of intensive care - will also be achieved by a better appreciation of how our patients get sick and get well. For example, a better understanding of the biology of edema formation following cardiopulmonary bypass, how it might be best prevented, and how its natural resolution can be accelerated would reduce the intensive care unit stay for a significant number of infants. Our understanding of the postoperative heal- ing process in general, and especially how patients with residual cardiopulmonary lesions adjust and adapt to their (abnormal) physiology is only rudimen- tary, limiting our ability to influence its pace. We are only able to poorly quantify the factors which limit the rate of recovery (e.g., respiratory muscle weak- ness, residual cardiac and pulmonary disease) and hence cannot optimally manipulate them. Research aimed specifically at these and related topics will not only yield fascinating insights into the biology of the

human organism, but will ultimately serve to conserve limited resources.

If the Golden Age of pediatric cardiology is to continue into the next century, new technologies and ideas will need to supplement and replace mature ones. Unfortunately, unlike the advances made over the last 20 years, these innovations will perforce be made in the context of increasingly severe financial constraints. Partly because of these economic pres- sures, it seems likely that the cardiac intensive care unit will need to be a major contributor to the ad- vance of the subspeciality in this new environment: Given its position as a significant consumer of increasingly limited resources, the fields of pediatric cardiology and cardiac surgery as a whole will be either enhanced or constrained by advances made, or not made, in the intensive care unit. It therefore seems likely that this subdiscipline within a subdiscipline will play an increasingly important role in shap- ing the future for our field, making this issue of Progms in Pediatric Cardiology particularly timely and appropriate.

References

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Pediatric cardiovascular intensive care: Current insights and future directions