Keywords
Neuromuscular, critical care, heart failure, respiratory failure, ethics, pharmacology
Historical Background
Patients with neuromuscular diseases may present with cardiac dysfunction, arrhythmia, or respiratory failure. Information in the literature regarding intensive care for these patients continues to evolve and single institution results have been published. Standards of care have been established for neuromuscular diseases. Close interaction among the specialties of cardiology, critical care, neurology, and pulmonary medicine are necessary for optimal outcomes. This chapter will provide a brief overview of the management of life-threatening cardiopulmonary complications of pediatric neuromuscular disease.
Intensive Care
In general, intensive care is not precisely defined. It is often characterized by the location of the patient and the services provided. Guidelines for pediatric transport and intensive care serve as a basis for the specialized care required by patients with neuromuscular disease. ICU care includes more frequent and detailed cardiorespiratory assessment, establishment of central venous and arterial access, assisted ventilation, administration of vasoactive medications, and acute therapy for arrhythmia, all in an environment with continuous monitoring and low nurse-to-patient ratios. Specific indications for critical care ( Box 44.1 ) include respiratory failure, heart failure, life threatening arrhythmia, and resuscitated sudden death. The ICU may also be used for recovery following sedation or anesthesia. For the neuromuscular patient, expectant admission is appropriate in the presence of rapidly progressive weakness, markedly reduced vital capacity, bulbar palsy, and autonomic instability.
Cardiac
Unstable congestive heart failure
Life-threatening arrhythmias
Bradycardia requiring cardiac pacing
Respiratory
Perioperative recovery in presence of chronic respiratory insufficiency
FiO 2 requirement greater than 50%
Rising pCO 2 (>70 or with symptoms)
Markedly reduced vital capacity
Compromised airway
Endotracheal intubation
Neurologic
Rapidly progressive weakness
Bulbar palsy
Severe autonomic instability
The care of the critically ill patient begins prior to admission to the ICU and continues after discharge to the inpatient unit. Individuals skilled in pediatric intensive care should transport the critically ill child to the ICU. Ideally, the patient should be stabilized before transport. During appropriate transport, the supportive measures routinely available in the ICU should be available, including oxygen, assisted ventilation, and antiarrhythmic and cardiovascular support medications. The key to successful transport is excellent communication between the referring and accepting facilities as well as the transport team. A pediatric intensivist, pulmonologist, and cardiologist, all of whom are familiar with the complications of neuromuscular disease, should be involved early, before transfer as well as during the hospitalization. Comprehensive discharge planning is necessary to successfully transition from the ICU to an inpatient unit and subsequently home.
Ethics
The indication for pursuing intensive care support for any patient is a balance between the perceived risks and benefits. In the child with progressive disease, it is often difficult to be certain when aggressive interventions become futile. The patient, depending upon developmental age, and the family must be involved in all decisions regarding extraordinary support measures or withdrawal thereof. Ethics consultation is often appropriate. In a disease known to have progressive deterioration and limited therapies to impact the natural history, the physician should encourage frank discussions about end of life decisions before an acute event occurs.
Normal Physiology
Cardiac
A complex control mechanism modulates the pumping action of the heart. Interdependent determinants of systolic function are: preload, the degree to which the ventricle is filled in diastole; afterload, the resistance to forward blood flow; heart rate and contractility, the latter of which describes the ability of the cardiac fibers to shorten. Active relaxation and the resting stiffness of the heart modulate diastolic function.
Normal conduction proceeds from the sinus node to the atria, through the atrioventricular node to the bundle of His, which subsequently divides into the major bundle branches. The electrical impulse utilizes these bundle branches for rapid distribution to the working myocardium of the ventricles. Short- and long-term variation is modulated by the autonomic nervous system and by the local tissue environment including pH, oxygen level, potassium, and calcium .
Respiratory
Ventilation is regulated by the autonomic nervous system, with limited voluntary override. Inspiration is achieved with the contraction of the diaphragm and intercostal muscles, and is dependent upon chest wall compliance and lung volumes. Optimum gas exchange occurs when all alveoli have adequate opening and circulation (ventilation perfusion matching).
Equally important is effective clearance of secretions through an adequate cough, which requires good inspiration, glottic closure, and sufficient contraction of the expiratory muscles to generate high pressure.
Pathophysiology
Heart Failure
Heart failure results when the pump function of the heart is inadequate to meet the metabolic needs of the body. The clinical signs and symptoms of heart failure are age dependent. In the infant, feeding intolerance, irritability, tachypnea, and tachycardia are most prevalent. The older child and adolescent are more likely to complain of activity intolerance or fatigue. In the patient with skeletal muscle weakness, activity related symptoms may be masked.
Once a specific neuromuscular diagnosis has been established, screening is directed to the associated type of cardiomyopathy. Conversely, if a patient has an unknown neuromuscular disorder, then the presence and the characteristics of a cardiomyopathy may aid in obtaining the correct diagnosis. The two cardiomyopathies associated with neuromuscular diseases that ultimately lead to heart failure are dilated and hypertrophic.
Cardiomyopathy
Dilated cardiomyopathy is the result of decreased contractility and loss of myocardium. Initially dilation is a compensatory mechanism that augments systolic function by increasing the preload. However, left ventricular dilation without increasing wall thickness increases wall stress, and oxygen supply and demand become mismatched. Mechanical stress may accelerate this process. It has been postulated that skeletal muscle weakness may be associated with slower progression of cardiac disease because the heart is never required to respond to exertion or physical stress. For example, motor dysfunction progresses more slowly in Becker muscular dystrophy (BMD) than in Duchenne muscular dystrophy (DMD), but symptoms of cardiomyopathy are common in carriers of the DMD gene. Thus, asymptomatic carriers of neuromuscular disease who have little or no limb weakness may present with cardiomyopathy or conduction disturbances.
In DMD, clinically apparent cardiomyopathy is first evident after 10 years of age and increases in incidence with age; it is present in all patients over 18 years of age. Cardiac dysfunction typically manifests as left ventricular wall motion abnormalities and dilated cardiomyopathy. Histologic studies indicate that heart muscle from DMD and BMD patients is deficient in dystrophin affecting membrane integrity, calcium movement, and stretch receptor activation. Additional factors contributing to cardiomyopathy may include an abnormal coronary reserve, such that patients are unable to augment myocardial oxygen at times of increased demand.
Barth’s syndrome presents in infancy and is an example of rapidly fatal dilated cardiomyopathy with skeletal muscle weakness, neutropenia, 3-methylglutaconic aciduria, and abnormal mitochondria.
In hypertrophic cardiomyopathy , there is abnormal wall thickness that commonly impairs relaxation and ventricular filling; less commonly there is sufficient hypertrophy to obstruct ventricular emptying. Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophies, myofibrillar and metabolic myopathies, and Friedreich’s ataxia (FA) have been associated with hypertrophic cardiomyopathy. The hypertrophy of the left ventricle in FA appears to correlate with a large number of trinucleotide repeats.
Arrhythmia
The two broad mechanisms of arrhythmia are abnormal impulse formation (automaticity), and abnormal impulse conduction (reentry or block). All clinical arrhythmias involve one or both of these mechanisms. Arrhythmia classification is further subdivided into tachycardia and bradycardia as well as the involved chambers of the heart.
Examples of reentrant tachycardia that are seen in neuromuscular disease include atrioventricular nodal reentrant tachycardia, and atrial flutter. Atrial fibrillation may be due to abnormal automaticity or reentry.
Ventricular tachycardia arises below the level of the AV node and is characterized by a QRS complex that is wider than normal. This also may be due to automatic or reentrant mechanisms.
Bradycardia is due to sinus node dysfunction (abnormal automaticity) or failure of the electrical impulse to conduct to the ventricle (block). Sinus bradycardia has been reported in muscular dystrophy and mitochondrial disease.
Heart block may occur anywhere within the cardiac specialized conductions system. Block can be intermittent, known as second degree ( Figure 44.1 ), or permanent, known as complete or third degree atrioventricular block.
Arrhythmias associated with neuromuscular disease are extensive. Significant arrhythmia frequently coexists with asymptomatic left ventricular dysfunction and wall motion abnormalities. In EDMD, cardiac abnormalities become apparent in the teenage years and are characterized by cardiac conduction defects and infiltration of the myocardium by fibrous and adipose tissue. Usually atrial paralysis is the first manifestation. Subsequent atrioventricular nodal dysfunction may result in progressive heart block and the potential for sudden death. Treatment with ventricular pacing is usually needed and is instituted with the onset of conduction system impairment. Female carriers of EDMD are also at risk of sudden death. Relatives of affected patients should be offered screening with electrocardiography (ECG) and echocardiography. Patients with myotonic dystrophy often develop progressive ECG changes without obvious clinical symptoms until the development of complete heart block when, again, there is the risk of sudden death. The severity of the rhythm disturbance seems to correlate with the expansion of unstable repeats. Some clinicians recommend prophylactic placement of a pacemaker in the adult myotonic dystrophy patient.
Sudden death may be arrhythmic, circulatory, or noncardiac. Noncardiac causes are numerous, but include neurologic events, respiratory failure, and trauma. Arrhythmia and congestive heart failure account for the vast majority of sudden deaths in neuromuscular patients. Tachyarrhythmia (ventricular tachycardia or fibrillation) or bradyarrhythmia (atrioventricular block or asystole) may cause sudden death. Complex ventricular ectopy, left ventricular dysfunction, and dilated cardiomyopathy are risk factors for sudden death. Specific risk factors for sudden death in myotonic dystrophy include increased PR interval or QRS duration, abnormal QT intervals, atrial arrhythmia, and a positive family history.
Respiratory Failure
Acute respiratory illness leading to respiratory compromise was the leading cause of unplanned admission to the ICU in children with neuromuscular disease ( Figure 44.2 ). The number of patients placed on home mechanical ventilation has increased dramatically, as has the need for ICU care. For the majority, initiation of mechanical ventilation was unplanned.
There are three primary causes responsible for respiratory failure in neuromuscular diseases. Respiratory muscle weakness (pump failure) impairs ventilation. Inefficacy of cough is due to expiratory muscle weakness, upper airway (glottic) muscle weakness, and inspiratory muscle weakness. Glottic muscle weakness may lead to aspiration and pneumonia. Abnormal chest wall and lung compliance contribute to respiratory insufficiency.
Cardiopulmonary Interactions/Pulmonary Hypertension
Pulmonary hypertension may occur as a result of two independent processes. Chronic hypoventilation secondary to weakness in the muscles that control respiration leads to chronic CO 2 retention and elevation of pulmonary arterial pressure. Secondly, cardiac insufficiency leads to an increase in filling pressure in the left ventricle as a compensatory mechanism to augment contractility. This results in an increase in pulmonary venous and, ultimately, pulmonary arterial pressure. These two processes may be additive in their effects on pulmonary pressure.
Evaluation
Patient History
Historical information is vital to appropriate management. A history of palpitations or syncope is important and mandates further evaluation. Sleep disordered breathing or abnormal pulmonary function testing are also important to note. Prior and current therapy for cardiac and respiratory function should be reviewed in detail.
Physical Examination
Patients with congestive heart failure are typically tachypneic and tachycardic. Blood pressure is usually maintained until heart failure becomes severe or terminal. The precordial activity is usually diminished, but the point of maximal precordial impulse may be displaced secondary to cardiac enlargement. This finding may be obscured by chest wall abnormalities such as occur with scoliosis. There may be a murmur from mitral regurgitation and a gallop is frequently present. Hepatomegaly results from impairment of venous return. Capillary refill time is prolonged. Edema is a very late finding. It should be noted that children who are nonambulatory often develop dependent edema from sitting in a wheelchair for several hours at a time. The diagnosis of dependent edema is confirmed when it is relieved by elevating the child’s legs.
Diagnostic Testing
Patients admitted to an ICU routinely have comprehensive laboratory evaluation. Among these, hemoglobin to assess capacity for oxygen delivery, arterial blood gas primarily to evaluate ventilation, and lactate as a measure of overall perfusion are all important first assessments. Brain natriuretic peptide is often evaluated in the presence of congestive heart failure and pulmonary hypertension.
Noninvasive studies on admission include chest X-ray, electrocardiogram, and echocardiogram.
Monitoring
Critically ill patients must be monitored continuously with at least two simultaneous ECG leads. Staff should be skilled in the recognition of rhythm abnormalities as well as the recognition of artifact from patient movement and equipment. All of these data should be archived in a system allowing for simultaneous review for a minimum of 72 hours.
The respiratory rate and the work of breathing supply important information regarding the patient’s overall status. Tachypnea is commonly seen in association with respiratory distress. It is also a very early sign of congestive heart failure. Patients with diaphragmatic or chest wall muscle weakness may not manifest the usual signs of respiratory distress and are at high risk for respiratory failure, defined as apnea, or CO 2 retention with intact respiration. Hypoventilation develops insidiously in pediatric neuromuscular patients and can result in “sudden” death because CO 2 retention may cause cardiac arrhythmia. Oxygen supplementation in neuromuscular patients must be followed by frequent monitoring of blood gases. If there is retention of CO 2 , the patient requires ventilation rather than O 2 supplementation. Without adequate ventilation, O 2 supplementation depresses inspiration, increases the pCO 2 , and worsens respiratory failure.
Noninvasive measurement of blood pressure is adequate for the patient whose condition is stable as it correlates well with simultaneous radial arterial measurements. Complications of noninvasive blood pressure measurement include nerve palsies, particularly from inappropriately placed cuffs that are frequently inflated.
The unstable patient should have arterial pressure continuously monitored using an indwelling catheter. Complications include infection, vascular compromise, and embolization.
Significant deviations from normothermia place additional stress on critically ill patients, particularly neonates and small infants. Additionally, central fever, particularly in conjunction with cool extremities, may be a marker of a low cardiac output state or a significant infection.
Pulse oximetry is a valuable noninvasive tool to monitor the patient’s oxygenation. Normal values are 95% to 100%. If any doubts exist regarding accuracy, a blood gas should be obtained.
Blood gas measurements provide pO 2 or dissolved oxygen, pCO 2 , and pH as a determination of acid-base status. Venous blood gases are not useful in children with neuromuscular disease because an accurate pCO 2 measure is crucial to their management.
Supplemental Monitoring
Large catheters placed in the central venous circulation allow monitoring of the filling pressure of the right heart and can provide access for frequent laboratory analysis. Moreover, potent vasoactive infusions are more safely administered in the central circulation. A catheter with more than one lumen facilitates simultaneous sampling, pressure monitoring, and medication administration. Complications include infection, bleeding, arterial or nerve injury, thromboembolism, and air embolism.
Pulmonary arterial catheterization provides precise measures of cardiac output and left heart filling pressures. Potential pulmonary complications are significant, which limits its use.
Input and Output
Judicious fluid management is imperative to properly care for the patient with impaired cardiac function. Sufficient circulatory volume must be present to maintain cardiac output, but the primary problem in congestive heart failure is excess fluid retention. Intake and output should be totaled every shift and a running total of the net fluid balance should be maintained. Inputs include all enteral and parenteral fluids including blood products and medication infusions. Outputs include urine, stool, phlebotomy, and those from drainage tubes. Insensible losses include evaporative fluid loss, which are often elevated in patients with fever or receiving assisted ventilation.
Laboratory
The ECG is a standardized recording of the electrical activation and recovery of the heart. The ECG provides an assessment of overall rhythm, cardiac chamber enlargement, and the electrical recovery or repolarization process. Abnormalities associated with cardiomyopathies include left and right ventricular hypertrophy, left and right atrial enlargement, ST segment changes, and arrhythmia. Abnormal Q waves suggest myocardial injury, a very common finding in DMD. Hypertrophy is typical with FA.
Attempts have been made to prognosticate from the ECG. An index to correlate the severity of cardiomyopathy has been proposed. ECG findings correlated with increased risk of death resulting from cardiac failure include decreased R wave amplitude in precordial leads, conduction abnormalities, ventricular ectopy, and sinus tachycardia. Abnormal repolarization is also associated with increased risk of ventricular arrhythmia and sudden death.
Imaging
The chest X-ray often shows cardiomegaly in the presence of cardiomyopathy. The cardiothoracic ratio is the maximum dimension of the heart divided by the thoracic cavity width at the diaphragm on a standard posteroanterior chest film. A cardiothoracic ratio of 0.6 is normal in newborns, whereas 0.45 is normal in older children and adolescents. This measurement may be confounded by kyphoscoliosis as well as lung pathology, including atelectasis (particularly left lower lobe), infiltrate, effusion, or eventration of the diaphragm. There may be passive congestion of the lungs secondary to heart failure. Furthermore, for the intensive care patient, the X-ray can confirm the location of endotracheal tubes, catheters within the circulatory system, and enteral feeding and drainage tubes.
Echocardiography is a standard means to assess cardiac structure and function ( Figure 44.3 ). With chest wall abnormalities, imaging may not be adequate. Better image resolution can be obtained with transesophageal imaging, but requires very heavy sedation or general anesthesia. The echocardiogram provides comprehensive information about the patient’s overall anatomy and function and is vital to the assessment of the critically ill patient. It is not routinely used as a tool for daily examination.
