Musculoskeletal and Neurologic Considerations in Cardiac Rehabilitation

CARDIAC REHABILITATION: PART I

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MUSCULOSKELETAL AND NEUROLOGIC CONSIDERATIONS IN CARDIAC REHABILITATION Matthew P. Kaul, MD

The physiatrist is ideally qualified to provide comprehensive assessment of the cardiac rehabilitation patient. This assessment requires an understanding of the potential musculoskeletal and neurologic conditions associated with cardiopulmonary bypass (CPB) and cardiovascular disease. Recognition of the potential complications occasionally encountered in the cardiac rehabilitation patient is important for optimized rehabilitation and medical care. A careful physical examination can often provide critical information for diagnosis and treatment. Appropriate supplemental intervention to assist in the cardiac rehabilitation process can then be incorporated immediately where indicated. Numerous articles have reported on the changing profile of the coronary artery bypass graft patient.16. 34, 50, 66 This change appears to be associated with increased morbidity probably in large part due to the increasing age of the cardiac surgical patient. This increased age of patients presenting for CPB worldwide is thought to be due to improved pharmacologic treatment and nonsurgical interventional techniques. These older patients are presenting with more concurrent diseases and require more extensive revascularization.34, 66 These factors have led to increasing frequencies of postoperative cerebral complications. The spectrum of musculoskeletal and neurologic complications that can impede cardiac rehabilitation varies from subtle to profound impairments; however, even subtle impairments may be significant because of the weight placed on education and compliance in cardiac rehabilitation. From the Physical Medicine and Rehabilitation Service, Veterans Administration Hospital, Portland, Oregon

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The goal of this article is to convey the scope of potential neurologic and musculoskeletal conditions that may be encountered by the physiatrist. The importance of a detailed neurologic and musculoskeletal examination at the earliest stages of the cardiac rehabilitation process will become apparent. MUSCULOSKELETAL CONSIDERATIONS

Chest wall pain can mimic angina. Obviously, in the cardiac rehabilitation patient, certainty of diagnosis is important when distinguishing between chest wall pain and angina. Some chest wall syndromes will be elicited by clear mechanical causes (such as lifting the arm) and be reproduced with palpation. Others will not, and angina, infarction, infection, and graft occlusion need to be considered in the differential diagnosis. After CPB, musculoskeletal complications may significantly impact the ability of a patient to participate in the cardiac rehabilitation process. Fortunately, most of these complications can be treated successfully. Shoulder pain can result from pain referral from the heart, sympathetic mediated pain after myocardial infarction, and various neurologic and musculoskeletal complications resulting from CPB. Postcardiotomy pain syndromes include those related to nerve injury (brachial plexopathy), fractures,27,83infection,83 postpericardiotomy syndromeF5 poststernotomy neuralgia,l4 and tissue irritation from sternal wires.17 Other musculoskeletal considerations in cardiac rehabilitation include bone loss and osteonecrosis after transplant and musculoskeletal manifestations related to hyperlipidemia. Rib Fractures

Rib fractures complicating median sternotomy occur at a frequency of 6% to 16% when diagnosed radiographically27 and approach 10O0i'o when diagnosed with bone scan.26 Of those with positive bone scans, up to 37.5% of these fractures could have been symptomatic with moderate to severe pain of the chest wall or shoulder. Vander Salm et a181 found that rib fractures documented radiographically were symptomatic in 15% of cases. Woodring et a186 found that 45% of a small series of patients with upper rib fractures seen on radiographs were symptomatic. The mechanism of injury is most likely from force applied to the ribs during sternal retraction. Vander Salm et a181 demonstrated that low placement of sternal retractor reduces the incidence of rib fracture. By far the most common fracture is to the left first rib posteriorly. They are commonly asymptomatic but may cause neck, chest, or shoulder pain and mimic anginal symptoms, myocardial infarction, pulmonary embolism, or postcardiotomy syndrome. Evaluation of this potential postoperative complication should include an attempt to reproduce the symptoms by palpating the affected ribs. A potential complication associated with rib fracture is pneumothorax.

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Sternal Separation or Transverse Fractures of the Sternum

Sternal separation or transverse fracture of the sternum can occur from vigorous spreading, pressure with retractors, or during sternal closure with steel suture wires breaking or cutting through an asymmetric or softened sternal split.83 Loosened or broken wires can lead to sternal instability and cause chronic pain, swelling, and tenderness. Radiographs may show the fracture sites. When dehiscence occurs, however, the wire sutures typically pull through the bone instead of causing fractures, and this may be seen on radiographs. Again, palpation may provide important clues to the cause of the symptoms. Infections After Median Sternotomy

Infections usually occur within the first 2 weeks. They can occur in the mediastinum, costal cartilages, sternum, or incision. In most cases, infection is mild but must be recognized early to prevent spread to adjacent structures. Excessive incisional pain, localizing symptoms (redness, swelling), or dehiscence suggest the possibility of an infection.83 Systemic symptoms and signs are commonly present. Appropriate therapy depends on the depth of the infection, the severity of the symptoms, and the specific microorganism. In one large prospective series, the frequency of major infection in those younger than 65 years was 2.1%. It was 10.2% in those aged 75 or older. Less commonly, a later smoldering infection may develop after some months. Generally systemic signs or symptomsare lacking. Findings include localizing symptoms, wound drainage, or sinuses. The smoldering course often results in greater spread before detection. These patients typically need more extensive debridement and longer treatment. Also, they demonstrated a higher recurrent infection rate and a greater mortality rate.83 Postpericardiotomy Syndrome

Postpericardiotomy syndrome (postcardiotomy syndrome) is a pleuropericarditis that occurs in up to 30% of patients after CPB. Tsai et a176 reported this complication in 7% of octogenarians after CPB. A central ache from pericarditis and a severe pleuritic pain from pleuritis are the most prominent features. Pleural and pericardial friction rubs are usually associated with this syndrome. Fever may or may not be associated with it. The syndrome appears a few weeks to a few months after CPB, and the duration of symptoms varies from a few days to a few months. Associated pericardial tamponade is uncommon. Recurrences may occur in up to 21% of patients.46 Symptoms often may be relieved by bed rest and aspirin. More severe cases can usually be effectively treated with a short course of corticosteroid therapy. It appears that the syndrome is due to an immunologic reaction to

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damaged tissue in the pericardial cavity. Heart-reactive antibodies appear in most patients after CPB but are seen in particularly high titers in those who develop this syndrome.20 Poststernotomy Neuralgia

Defalque and Bromleyl* reported on a series of 54 patients referred for evaluation of poststernotomy pain. Pain onset was 4 weeks to 4 months after surgery, with an average of 6 weeks. It was constant, sharp chest wall pain, radiating posteriorly in some, and exacerbated by chest wall and arm movements. Discrete tender points were elicited at the sternal margin of the upper interchondral spaces. In some patients, a number of tender points were found. Treatment was started with bupivacaine injections. If pain persisted after four injections, phenol was injected up to four times. If pain still persisted, absolute alcohol was injected. Of the 54 patients, 48 (87%) were relieved of pain for at least 6 months after bupivacaine or neurolytic block. Complications included two patients' developing pneumothorax. Tricyclic antidepressants (TCAs) are commonly employed to treat many types of neurogenic and musculoskeletal pain. A recent editorial advises extreme caution when considering treatment of depression with TCAs in all patients with ventricular arrhythmias, ischemic heart disease, or both.24 This warning is based on TCAs' cardiac effects being similar to class I antiarrhythmic drugs and the latter showing a trend toward increased mortality in randomized controlled trials. This TCA recommendation is acknowledged to be based on circumstantial evidence. The effective TCA dose for treating depression is much higher than for treating pain; nevertheless, this treatment should be considered in consultation with the cardiologist. Sternal Wire Sutures

Sternal wire sutures are an uncommon but potentially debilitating and remediable cause of delayed chest wall pain. Eastridge et all7 described a series of 18 patients with sternal wire pain. They found pain onset 2 to 84 months after CPB. The quality of pain was either sharp and stabbing or deep, ill-defined, and aching, located over the chest wall, neck, or anterior shoulder. Tenderness was present with pressure over the wire, and pain was also elicited by tissue tension as with arm abduction. Removal of the wires and scar tissue provided complete pain relief. The painful wires were found to be corroded with adjacent reactive tissue fibrosis and sensory nerve entrapment. Transplantation Osteoporosis, Pathologic Fractures, and Osteonecrosis

Osteoporosis, osteonecrosis, and related complications are potential results of organ transplantation. Osteoporosis may develop within 2 to 5

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years after transplantation. Its development has been thought to be due to inactivity, poor nutrition, loop diuretic therapy, and cigarette smoking.55 In one study, bone mineral density (BMD) in potential cardiac transplant 5 compared with agepatients was reduced by approximately 2 0 Y ~ ~when matched controls; however, others have found pretransplant osteopenia in only a minority of patients.38160 Shane et a160 studied 40 cardiac transplant recipients receiving immunosuppressive therapy approximately 2 years after receiving transplant. BMD was assessed, radiographs of the spine were obtained, and multiple biochemical indices of mineral metabolism were obtained. Eleven patients (28%) had evidence of vertebral osteopenia. They were younger, had their transplants longer, and had received larger cumulative dosages of prednisone. Of all of the patients, 35% had vertebral fractures, although lumbar BMD did not differ significantly between those with and without fractures, which may have been a result of small sample size. Vertebral fractures were diagnosed in patients with reasonably normal bone mass. Vertebral fractures were five times more common in patients with low femoral BMD. In posttransplant regimens that use prednisone in long-term maintenance, fractures can develop in up to 50% of patients.39 Posttransplant bone loss is thought to be multifactorial rather than just due to coricosteroid therapy. Other contributors include cyclosporine administration,55 altered vitamin D metabolism, reduced intestinal absorption of calcium, renal excretion of calcium and phosphate, decreased sex hormone, and direct effects on bone resorption and formation.60 In a series of 31 cardiac transplant recipients studied by Lee et a1,38 2 out of 31 (6.5%) patients developed avascular necrosis of the femoral head. Cumulative corticosteroid dosage did not correlate with the occurrence of osteonecrosis. Hyperlipidemia and Hypercholesterolemia

Musculoskeletal manifestations of hyperlipidemia and hypercholesterolernia frequently antedate their diagnosis. These musculoskeletal symptoms may interfere with cardiac rehabilitation. In a controlled study, Klemp et aP5 recently assessed 88 patients with either hypercholesterolemia or mixed hyperlipidemia in a controlled study. They found significantly increased frequencies of tendon xanthomas (especially in the Achilles tendon) and Achilles tenonitis. Oligoarthritis was seen more frequently in mixed hyperlipidemias but not in familial hypercholesterolemia. Many of the symptomatic patients thought they improved with lipid-lowering agents. PERIPHERAL NERVOUS SYSTEM DEFICITS

Brachial plexopathy has historically been considered to be the most frequent CPB-related neuropathy followed by ulnar plexopathy. Uncom-

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mon neuropathies after CPB include median, radia1,52 saphenous, and peroneal.37 Phrenic nerve injury was historically thought to be rare; however, more recent studies have found higher frequencies.18 The mechanism of peripheral nerve injury varies depending on the nerve in question. Shaw et a163 found, in a large prospective study of 312 CPB patients, that 6.7% developed brachial plexopathy, and 5.4% developed dysfunction of other peripheral nerves. In a prospective series of 162 patients assessed with physical examination at 1 month after CPB, Roy et a157 found that brachial plexopathy occurred in 7.4% (predominantly lower trunk), ulnar neuropathy occurred in 1.9%, and median neuropathy occurred in fewer than 1%.Vahl et a178 found, in a prospective study of 1000 CPB patients, that 2.7% developed brachial plexopathy (22%upper trunk, 78% lower trunk) and none developed ulnar neuropathy. Lederman et aP7 found brachial plexopathy in 5.5%, ulnar neuropathy in 1.2%, saphenous neuropathy ipsilateral to saphenous vein donor site in 3%, and peroneal neuropathy in 1.9% that was presumed compression neuropathy. Seyfer et a159found that those with a history of neuropathy who had become asymptomatic frequently reexperienced symptoms after CPB. Prognosis for peripheral nerve injury after CPB is generally reported to be quite favorable. Roy et a157 found from interview and questionnaire data that none of those with postoperative neuropathies thought they had significant functional disability. Morin et a144 followed 38 patients with neuropathy after CPB and found 92% with resolution 3 months after surgery. Hanson et a129 found that in those with postoperative brachial plexopathy, 73% had recovered by 4 months, and 27% had symptoms beyond 4 months. Only 4% of these patients had plexopathies classified as severe. In the series by Hickey et al,32 20% had immediate postoperative brachial plexopathy; however, this persisted beyond 1 week in only 6%. Vahl et a178 found that 30% of those with brachial plexopathy were symptomatic longer than 3 months after CPB. In contrast, Seyfer et a159 found in their prospective series that in those with neuropathy after CPB, 40% of patients had pain longer than 3 months, with most cases described as "severe." Despite the generally favorable prognosis, the physiatrist needs to prescribe appropriate treatment depending on the severity of injury, symptoms, concurrent pathology, and functional impairment. Although the patient can be reassured of favorable prognosis, this should obviously be tempered, depending on the findings in each case. In some cases, the profundity of a deficit may weigh against optimism. Interventions such as physical therapy for strengthening and range of motion may be indicated, as may be splinting and adaptive equipment to optimize function. Brachial Plexus Injuries

Brachial plexus injuries have been assessed in numerous studies with a frequency of 2% to 20% in CPB procedures. Proposed mechanisms of

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plexus injury include traction from positioning the arm in hyperabduction, compression of the plexus between the clavicle and the rib cage during retraction, ischemia, rib fracture, and needle trauma during internal jugular cannulation. Watershed infarction can mimic brachial plexopathy and should be remembered when evaluating brachial weakness after CPB. Hickey et a132 recently reassessed the mechanism of plexus injury in open heart surgery. They studied 30 patients undergoing open heart surgery with perioperative and intraoperative somatosensory evoked potentials (SEP). Three events of interest were assessed, including central venous cannulation, Favoloro retractor placement, and Canadian retractor placement. Internal jugular venous cannulation was associated with significant SEP changes in 13% of patients; however, all changes were transient. Favoloro retractor placement produced significant SEP changes in 58% of patients, and Canadian retractor placement produced significant changes in 56% of patients. Retractor placement produced persistent SEP changes in 17% of patients. SEP changes in five of the six patients with persistent neurologic deficits included a change of more than three standard deviations in both latency and amplitude. In that series, the frequency of immediate postoperative peripheral neurologic deficit was 20%; however, most resolved. At 1 week, persistent deficit was seen in 6% of patients. The one patient with peripheral nerve findings but normal SEP had only a motor deficit of the ulnar nerve. Magnitude of sternal retraction was not associated with the development of plexus lesion. Rather, the retraction event itself appeared to be the cause in affected patients. The SEP changes demonstrated 100%sensitivity for sensory nerve dysfunction and 100% specificity in predicting peripheral sensory nerve injury. Electrophysiologic monitoring may have particular relevance in the already neurologically compromised patient in whom additional weakness could be potentially devastating. Risk factors for brachial plexus injuries have been assessed in multiple studies. The study by Hickey et a132 demonstrates that brachial plexopathy is associated with sternal retraction. One study demonstrated an association between brachial plexopathy and ipsilateral internal jugular vein ~ a n n u l a t i o nhowever, ~~; others have not found this as~ociation.3~, 57, 74, 78 Some early studies suggested that brachial plexopathy was due to hyperabduction of the arm; however, multiple recent prospective studies have not found arm position to be important in causing brachial plexopathy.29,57,78,84 Width of chest retraction has not been convincingly demonstrated as a cause of brachial plexopathy.29.32 Rib fracture is thought to be only an infrequent cause of brachial plexopathy.78, 81 Type of operation influenced frequency of brachial plexopathy in one study78 but not in others.57, 74 The study by Vahl et a178 was well done, with a large prospective series (1000 patients) and electromyographicand nerve conduction velocity confirmation of diagnosis. They found brachial plexopathy occurred in 0.2% of coronary artery bypass graft (CABG) patients and 10.6% of CABG patients whose internal mammary artery was dissected (such dissection requires wide retraction).

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Ulnar Nerve Injury Ulnar neuropathy has been described as occurring after CPB in 0.2% to 1.0% of patients in retrospective studies and 0.8% to 38% of patients in prospective studies. The latter high frequency of ulnar neuropathy was found by Seyfer et a1.59 They studied 53 patients prospectively with preoperative and postoperative physical examination (the time of examination was not stated), which included two-point discrimination testing. They stated that all neuropathies were of the ulnar nerve, with 37.7% of patients affected; however, they also state that the medial antebrachial cutaneous nerve was involved in an unspecified number of patients. Therefore, they probably combined ulnar neuropathies with brachial plexopathies. It is not possible from their study to distinguish those patients with ulnar neuropathy from those with brachial plexopathy. Wey and Guinng* assessed 68 CPB patients with preoperative and postoperative electrodiagnosis. Postoperatively, in those patients positioned with their arms at their sides, 41 (60%) demonstrated slowing of nerve conduction velocity across the elbow, but only 17% with ulnar slowing were symptomatic. In those positioned with their forearms behind their heads, 17% demonstrated ulnar slowing across the elbow. None were symptomatic. Therefore, arm position appears to be able to influence frequency of CPB-related ulnar neuropathy. Watson et a182 found 15% of their prospective series of 30 CPB patients to develop ulnar slowing across the elbow on electrodiagnostic studies after CPB. Only one patient, however, was symptomatic. In both of these studies, electrodiagnostic screening before CPB demonstrated a significant number of patients who met electrodiagnosticcriteria for ulnar neuropathy at the elbow but were asymptomatic. Ulnar neuropathies associated with CPB usually occur at the elbow. They are commonly asymptomatic. One study appeared to demonstrate that arm position can influence frequency of occurrence. From the available studies, it is difficult to determine prognosis and functional consequences of ulnar nerve injury in CPB patients, but prognosis will depend on the severity of injury and should be assessed on a case by case basis.

Phrenic Nerve Injury Phrenic nerve injury may be unilateral or bilateral. When unilateral, it is most commonly left sided. It occurs radiologically after CPB in 30% to 75% of patients,l8 although others have suggested a frequency of only 2%.41 The proposed causes for diaphragmatic paralysis include phrenic nerve hypothermic injury, injury from dissection (especially if the nerve is obscured by adhesions from prior open heart surgery), and complications of central venous cannulation. Unilateral diaphragmatic paralysis was evaluated recently by Efthimiou et a1.18 They assessed 100 consecutive CPB patients in an attempt to determine the frequency, natural history, and causes of dia-

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phragm paralysis. Fifty patients received ice or slush topical hypothermia and 50 did not. Other surgical variables were the same. Patients were assessed with chest radiography and phrenic nerve conduction studies. Those performing the tests were blinded to the group assignment. In patients receiving ice or slush topical hypothermia, partial left lower lobe collapse was seen in 82% on radiographs. Fluoroscopic screening demonstrated unilateral diaphragm paralysis in 329'0, with all of these demonstrating absent phrenic nerve conductions. In the group who did not receive ice or slush topical hypothermia, partial left lower lobe collapse was seen in 329'0, but only 2% had diaphragmatic paralysis on fluoroscopy. The natural history of unilateral diaphragmatic paralysis was assessed by following these patients for 2 years. Of those with diaphragmatic paralysis initially, in 75% it was still evident at 1 month, in 44% at 7 months, in 31% at 12 months, and in 6% at 24 months. In 94% of the cases, diaphragmatic paralysis was left sided and thought to be the result of the closer juxtaposition of the left phrenic nerve to the ice or slush saline placed in the pericardial sac. The study demonstrates that diaphragmatic paralysis is due to phrenic nerve hypothermic injury and that it is usually reversible, although it may take more than 1 year for recovery. In the patients who received ice or slush and developed diaphragmatic paralysis, hospital stay was approximately 2 days longer. Bilateral diaphragmatic paralysis has been discussed typically in isolated case reports; however, Chandler et all2 reported on 5 cases, Chan et all1 reported on 5 cases, and Diehl et a115 reported on 13 patients. Out of 1478 CPB patients, Diehl et all5 followed those requiring prolonged mechanical ventilation after CPB or who had unexplained difficulty in weaning from the ventilator. With this criteria, 13 patients were identified who were all found to have bilateral diaphragmatic dysfunction. Out of 1478 patients, they found clinically relevant diaphragmatic dysfunction in 2.1% when ice or slush was used and 0.5% when it was not used. Chandler et a112 estimated bilateral diaphragmatic paralysis occurred with a frequency of 1 in 500 patients after CPB. Bilateral diaphragmatic dysfunction presents with signs and syrnptoms including orthopnea, exertional dyspnea, daytime somnolence, failure to wean from the ventilator, and paradoxic respiration (inward motion of the anterior abdominal wall with inspiration). In the study by Chandler et a1,12 recognition was delayed with initial diagnoses varying from anxiety neurosis to congestive heart failure to mitral regurgitation. The phrenic nerve is vulnerable as it travels within the fibrous pericardium, with the mechanism of injury thought to be due to hypothermic damage. Bilateral diaphragmatic paralysis is associated with high rates of severe life-threatening complications, such as pneumonia, mediastinitis, cardiorespiratory arrest after extubation, prolonged mechanical ventilation, and death in 3 of 13 in the series by Diehl et a1.15 Diagnosis is provided by spirometry (sitting and supine vital capacity [VC]),12transdiaphragmatic pressure (Gilbert index, sniff test),l5 and electromyography and phrenic nerve conduction studies.72 Fluoroscopy

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is unreliable in detecting bilateral diaphragmatic paralysis. Other pathology that may need to be considered in the differential diagnosis of diaphragmatic paralysis includes critical illness neuropathy (CIN),previously unrecognized neuromuscular or genetic disorders that are unmasked by drug therapy or infection, metabolic abnormalities, and Guillain-Barre syndrome.lo, 72 Quantitative electromyography and sensory and motor nerve conduction velocity tests can guide the clinician in decisions about the need for biopsy and be helpful in determining the mechanism of weakness in patients with respiratory muscle weakness. Neuromuscular junction assessment in the absence of clinical indications was thought to be unnecessary by Spitzer et al.72 CENTRAL NERVOUS SYSTEM COMPLICATIONS

Profound CNS deficits are uncommon, but subtle CNS deficits are common yet rarely cause significant disability. Obvious deficits will draw attention immediately, but more subtle deficits may be more perplexing, although they may still impact the cardiac rehabilitation process. CNS complications after CPB include stroke, transient and persistent neuropsychologic deterioration, cerebral hypoxic and ischemic injury from profound intraoperative hypotension, depression of the consciousness level for more than 24 hours after surgery, ophthalmologic abnormalities, new onset of primitive reflexes, and postoperative psychosis. Causes of postoperative CNS complications are thought to be due to macroembolism from air embolization or particulate matter (dislodgement of atheromatous debris from the aorta or release of left ventricular thrombus)47,65,69;micr~embolizationof fat, air, platelet aggregates, fibrin or silicone43; or cerebral hypoperfusion.31 The literature is so variable with regard to methodology that, in categorization of cerebral complications, it is often not possible to compare categories of complications from different studies. The following is an attempt to classify similar pathology from disparate methodology. Stroke

Historically intracardiac procedures such as valve replacements have had a higher risk (4.1%to 14%)for perioperative stroke than extracardiac procedures such as coronary artery bypass grafting (CABG, 0.3% to 5.4%). The differences in study results are due to differences in study design, method of evaluation, and whether studies were prospective or retrospective. One recent study suggests this historical difference may be shifting. Kuroda et a136 assessed 638 patients having isolated CABG and 345 patients having isolated valve repairs. They found a combined neurologic morbidity of 11% in the CABG group with a significantly lower incidence of 7% in the valvular surgery group. With both intracardiac and extracardiac surgery, the preponderance

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of evidence suggests that macroembolism from the surgical field is the most common cause of neurologic complications. Air embolism is more common with intracardiac procedures than extracardiac procedures. Echocardiography may be used to detect air retained in the cardiac chamber after intracardiac repair and thus facilitate removal.47 It has not been determined whether solid emboli are more common after intracardiac or extracardiac procedures. van der Linden and Casimir-Ah1179 used transcranial Doppler continuously in 10 patients undergoing valve replacement. Scattered emboli were observed during aortic cannulation, with the onset of bypass, immediately after release of the aortic cross-clamp, during procedures to remove air, and during reperfusion with the heart beating empty. The period of greatest risk for embolization is during redistribution of blood from the heart-lung machine to the empty, beating heart. The cerebral consequences of these emboli are unknown. Albin et a13 found that embolic events occurred more frequently with valve replacement than CABG when measured by transcranial Doppler. Breuer et a18 found that 55% of the cerebral infarctions related to CABG were right or left cerebral hemispheric, 23% were brainstem infarctions, and 32% were retinal or optic nerve infarctions. Mortality in patients with stroke complicating CPB occurs in 23% to 36% of patients. Other infarction syndromes that may be encountered related to CPB include watershed or border-zone infarction, the cause of which is generally accepted to be cerebral hypoperfusion from profound hypotension.25 Watershed infarction may affect either cerebral border-zone regions or occur in internal border-zone regions. Watershed areas occur at the junction between major cerebral33 or medullary arteries.6 Common features of cerebral watershed infarctions include cerebral blindness and visual disorientation. Some patients will have bibrachial sensorimotor impairment. Features of internal watershed infarction may also include brachiofacial sensorimotor impairment with cortical signs often only demonstrated on neuropsychologic testing. Risk Factors for Stroke After Cardiopulmonary Bypass

Age. A number of studies have found age to be an independent risk factor for stroke.23, 77 Tuman et a177 prospectively evaluated 2000 CABG patients to determine the effect of age on morbidity. Neurologic deficits after CPB occurred nine times as frequently in patients aged 75 years or older (8.9%) compared with patients younger than 65 years (0.9%) and more than twice as frequently compared with patients between 65 and 74 years of age (3.6%).A number of preoperative variables were examined in this study, and age was found to be the single most important variable associated with neurologic deficits after CPB. In patients older than 65 years, severity of illness was increased based on greater incidence of unstable angina, congestive heart failure, and a greater incidence of classification in New York Heart Association class IV than those younger than 65 years. In a classic study, Gardner et a123 found the incidence of

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stroke for patients aged 41 to 50 years to be 0.42% and 7.14% for patients older than 75 years. Aortic Atherosclerosis. In a series of 630 consecutive patients, Bar-El and Goor4 reported the lowest prevalence of CPB-related strokes in the literature. They palpated the ascending aorta for atheroma, and whenever possible, these areas were not cannulated, grafted, or clamped. Their overall stroke rate was 0.32%, and in their 107 patients aged 70 years or older, no perioperative strokes occurred. The factor most significantly associated with atheromata was age. Finger palpation of the aorta appears to be as effective as ultrasound identification of atheroma in guiding preventive measure^.^ Concomitant Cerebrovascular Disease. Although concomitant cerebrovascular disease is a risk factor for stroke with CPB,13, 23, 54 it is generally accepted that asymptomatic carotid bruits should not be operated on prophylactically, either before or at the time of cardiac surg e r ~ .47 ~ ,They do not present a great enough risk to warrant the added risk of stroke from the carotid endarterectomy. Symptomatic carotid stenosis may warrant surgical intervention in the cardiac surgical patient.47 Others. Prolonged perfusion time is associated with a higher risk for poor neurologic outcome in most studies.23.77 The presence of preoperative neurologic abnormalities, perioperative hypotension, and diabetes have also been implicated as factors that can increase risk for CPB-related 77 neurologic ~omplications.47~ Cerebral protection is conferred by hypothermia during circulatory arrest, but routine CPB does not use circulatory arrest. In a recent study by Martin et al,40 1001 patients having elective CABG were randomized to receive either normothermic CPB or hypothermic CPB. Risk of neurologic complication was substantially increased in the warm cardioplegic group (4.5%) compared with the cold cardioplegic group (1.4%).Barbiturate administration appears to reduce neurologic morbidity during intracardiac surgery but not extracardiac surgery.47 Stroke is a potential complication of acute myocardial infarction (MI). With the use of thrombolytic treatment, increase in the frequency of this complication has not been significant. (Patients at high risk are typically excluded from this type of therapy.73) The incidence of stroke during acute MI varies from 0.9 to 2.4%. The most reliable predictors of stroke during MI were older age, high enzyme levels, anterior site of MI, impaired left ventricular function, atrial arrhythmias, and prior cerebrovascular disease.73 Nonhemorrhagic stroke is the most common form seen in patients with MI who are receiving thrombolytic therapy. The mortality of patients developing stroke or transient ischemic attack (TIA)during hospitalization for MI was threefold compared with those without stroke or TIA.73 Tame et a173 assessed the frequency of stroke or TIA in the year after acute MI in 4808 survivors. One percent experienced a stroke or TIA within a year, and 31% of these events occurred in the first month after hospital discharge. Although the incidence of stroke is relatively low in the year after MI, it is higher in comparison with rates in the general population. Six factors contributed independently to increased risk, in-

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cluding chronic atrial fibrillation, older age, a history of MI, anterior site of MI, serum aspartate transaminase (AST) levels more than four times higher than normal levels, and previous stroke. Low-intensity anticoagulation with warfarin can prevent most of the additional stroke risks caused by atrial fibrillation.21The age-adjusted, 1-year mortality rate was 31% in those who developed stroke or TIA after discharge for MI compared with 9% in those without stroke or TIA. Most of these deaths occurred within 2 weeks of the cerebral event (74%~).~3 Neuropsychologic Deficits After Cardiopulmonary Bypass

Of all patients after CPB, 50% to 70% experience a measurable transient decrement in neuropsychologic function.42 The most frequently reported deficits after CPB are those of concentration, memory, learning, and speed of visual-motor responses. These changes are distinct from the transient delirium that can occur at a frequency of approximately 3%with CPB. Persistent neuropsychologic changes beyond a few weeks occur at a rate of 5% to 117b.28, 61, 71 Many studies have assessed neuropsychologic status after CPB compared with control groups undergoing other types of surgery.l, 28, 48, 53, 63 Compared with surgical control groups, studies demonstrate that postoperative deficits in neuropsychologic status are almost exclusively found in patients undergoing CPB. Shaw et a163 assessed 312 CPB patients and 50 controls undergoing major vascular surgery with preoperative neurologic and neuropsychologic tests and reassessment at approximately 1week after surgery. Of the CPB patients, 79% deteriorated on at least one neuropsychologic test postoperatively, whereas deterioration occurred in only 31% of controls. Of those CPB patients who deteriorated on postoperative neuropsychologic testing, 38% had symptoms of intellectual impairment, and 10% were overtly disabled in their everyday activities in the hospital. They found potential risk factors for cerebral injury failed to provide an explanation for the difference in outcome between the two groups. The operations were similar in terms of duration, anesthetic methods, and time spent in an intensive therapy unit after surgery. The major difference between the two groups was the type of surgical procedure. Smith et a167 found that postoperative neurologic abnormalities, including stroke, impaired coordination, depressed reflexes, and transient drowsiness, were significantly more common in the CABG group compared with their surgical control group. They found impaired neuropsychologic status as commonly in the control group as the CABG group, although in the CABG group, these deficits were usually more severe. All other studies with surgical control groups demonstrated significantlymore frequent and severe neuropsychologic deficits in CPB patients.', 28,53,63 It therefore seems likely that the differences in outcome between CPB and surgical controls reflects neurologic injury related to CPB.

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Prolonged neuropsychologic impairment beyond a few weeks has been noted by a number of investigators.2,58, 61,62,70,71 Others have not found evidence of long-term intellectual deficits after CPB.19.22 Nevertheless, the consensus appears to indicate that a small percentage of patients (5% to 11%)after CPB demonstrate prolonged intellectual deficits related to CPB. Shaw et a161found that 6.6% of 259 patients assessed at 6 months showed deterioration in three or more test scores in contrast to the period soon after surgery, when 24% of patients showed deterioration in three or more test scores. In the study by Shaw et a1,61 they found that 71% of those with performance deficits were without symptoms, and 27% mentioned minor symptoms but were not significantly incapacitated. Of the entire cohort, 1% had psychometric dysfunction that resulted in disability; out of those with neuropsychologic impairment, 2% were disabled. Harrison et a130 assessed 47 CPB patients with a battery of 10 neuropsychologic tests and found impairment was still present in 36% at 8 weeks. Aberg and Kihlgrenl found that 11% to 23% of CPB patients had intellectual impairment 12 months after CPB. Savageau et a158 found that 20% of those with early neuropsychologic deterioration after CPB were still impaired at 6 months. Late deterioration in neuropsychologic performance after being unimpaired soon after surgery occurred in 7.3% of the 259 CPB patient cohort in the study by Shaw et a1.61 Others have also noted this delayed deterioration in 3.7%58 and 4%68 of their cohorts. The cause of neuropsychologic impairments related to CPB surgery has been much debated, and evidence exists for both CPB-related cerebral hypoperfusion and microembolization. CPB-related cerebral hypoperfusion has been demonstrated by Henriksen3l who studied 37 patients after CPB and found significantly reduced regional cerebral blood flow in 65% as measured by single photon emission computed tomography. This reduction in cerebral perfusion was also present at day 4 and day 8 after CPB. Age, duration of bypass, and mean arterial pressure were significantly correlated with cerebral blood flow reduction after bypass surgery. Microemboli may play a role in this reduction, but this was not assessed. In a control group of 15 patients undergoing carotid endarterectomy or extracranial-intracranial bypass operations, no reduction in cerebral blood flow was seen. Microembolization has been demonstrated by Blauth et a17 with retinal fluorescein angiography and by van der Linden and Casimir-Ah79 with transcranial Doppler studies. Blauth et a17 found more retinal microemboli in patients with neuropsychologic deficits than in those without neuropsychologic deficits, although all 21 patients demonstrated microemboli. The study was small and not blinded and should be considered preliminary from the standpoint of increased retinal microemboli associated with greater likelihood of neuropsychologic impairment. van der Linden and Casimir-Ahn79 used transcranial Doppler continuously in 10 patients undergoing valve replacement and demonstrated scattered emboli during many of the CPB procedures. The cerebral consequences of these emboli are unknown. One study reported patients ran-

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domized to arterial filters had fewer embolic events (detected via Doppler) and improved verbal memory at 8 weeks compared with the control group without arterial filters.79 Other support for microembolic causes of neurologic dysfunction derives from pathologic microvascular anomalies called small capillary and arteriolar dilatations (SCAD) found exclusively in the cerebral circulation of patients exposed to CPB or proximal aortography.43

Risk Factors for Neuropsychologic Deficits After Cardiopulmonary Bypass The most consistent risk factor for neuropsychologic deficits after CPB is older age.49.63 Concomitant cerebrovascular disease is not thought to be a risk factor for neuropsychologic deficits after CPB as it is for stroke.30 Some studies have found intraoperative variables, such as length of CPB and intraoperative hypotension, to negatively influence neuropsychologic outcome,58, 68 whereas others have not found intraoperative factors to be ~ignificant.~9, 63, 65, 75 Cerebral Hypoxic Injury Shaw et a1,61 in a prospective study of 312 CPB patients, found 1 patient (0.3%) who died from an episode of profound intraoperative hypotension. No patients in their surgical control group had this complication. Cerebral anoxic syndromes include anoxic encephalopathy, persistent vegetative state, extrapyramidal tract dysfunction, myoclonic jerks, arnnestic syndrome, and delayed anoxic leukoencephalopathy.9 These complications are rare and are usually a manifestation of intraoperative hypotension, hypoxia, stroke, aortic dissection, air emboli, or severe postoperative metabolic dysfunction.13 Coffey et a113 found hypoxic-metabolic encephalopathy in 1.4% of the patients in their series. Mortality was 71% in this setting, and functional recovery in the survivors was stated to be prolonged. Postoperative arrhythmias occurred significantly more frequently in these patients than in their cohort controls. Tuman et a177 reported that 1%of their CPB patients remained unresponsive for at least 10 days after surgery. Most of these cases were thought to be due to hypotension or low flow states. A 74% mortality rate was seen in these Breuer et a18 found that 11.6% of their prospective series of 421 CABG patients were encephalopathic at postoperative day 4 without focal neurologic findings. They did not include patients who had confusion that resolved by day 4. Use of an intra-aortic balloon pump and a pressor drug did correlate significantly with confusion (both markers for hypotension). Of these patients, 80%had a normal mental status by the time of discharge. This study did not attempt to separate those with depression of consciousness versus those with anoxic encephalopathy, and this probably accounts for their higher frequency of deficits.

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Neuropsychologic sequelae of cardiac arrest have been recently assessed by Roine et a1.56 They followed patients resuscitated from out-ofhospital ventricular fibrillation by a trained response team excluding those who responded to verbal commands immediately after resuscitation. Of the 155 patients who met their inclusion criteria, the 143 survivors were assessed at 1 week, 3 months, and 1 year with neuropsychologic testing. Moderate to severe memory impairment, dyscalculia, or visuoconstructive dyspraxia occurred in 30% to 33% of patients at 12 months. Depression occurred in approximately 30% of patients at 3 and 12 months. Moderate to severe cognitive deficits were seen in 60% of patients at 3 months and 48% of patients at 12 months. Delayed memory was the neuropsychologic impairment most commonly seen. Postoperative Psychosis

Shaw et a163 observed a paranoid hallucinatory state in 1.3%of patients from their large prospective series. They considered this category separately from altered consciousness without paranoid hallucinations. No patients in their surgical control group had this complication. Coffey et a113 included patients with psychosis with their patients who had altered consciousness. Tsai et a176 reported that 14.6% of their octogenarians developed postoperative psychosis. Depression of Consciousness

Depression of conscious level for more than 24 hours after surgery not attributable to sedative drugs has historically been considered one of the most common neurologic sequelae of cardiac surgery.9 More recently, depression of consciousness after CPB has been described in 2.0% to 3.2% of patients.13.63 In the study by Shaw et al,63 90%regained a normal level of alertness by the 12th day after surgery. Coffey et a1 state that "in general, it was [a] benign, self-limited condition."l3 They found a significantly higher occurrence of postoperative arrhythmia in these patients compared with their control cohort. Primitive Reflexes

Shaw et a163 assessed 312 patients for primitive reflexes preoperatively and at approximately 1 week after CPB. They found that 39.4% of patients developed primitive reflexes after CPB, whereas only 4%in the surgical control group developed primitive reflexes. The development of primitive reflexes was thought to be a reflection of mild cerebral injury. Their development showed a significant association with stroke and depression of consciousness.

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Other Complications Isolated spinal cord infarction has been reported without any cotemporal cerebral injury by Silver and Buxton.64 They described a series of 11 patients who developed flaccid paralysis of the lower extremities and urinary retention. The "watershed" areas in the thoracic and lumbar regions of the spinal cord are at risk from profound drops in perfusion pressure. Seizures may occur rarely. When they do occur, they are usually associated with stroke or hypoxic-metabolic encephalopathy.13 Shaw et a163 assessed 312 patients preoperatively and at approximately 1week after CPB and found that 25% developed ophthalmologic abnormalities. These abnormalities included retinal infarction or emboli in 20%, visual field defect in 2.69'0, and reduced visual acuity in 4.5%. In their surgical control group, no ophthalmologic abnormalities were found. In a study of 21 patients with retinal fluorescein angiography, Blauth et a17 found microembolism in 100%; however, only one patient (4.8%) had impairment of vision (decreased visual acuity), and 9.5% had evidence of retinal ischemia. Breuer et a18 found that 0.l0/0of 421 consecutive CABG patients had retinal infarction. SUMMARY

Our understanding of the musculoskeletal and neurologic conditions encountered in the potential cardiac rehabilitation patient continues to evolve. It is important that the physiatrist be aware of the differential diagnosis, examination, natural history, treatment, and implications for rehabilitation of these conditions. References 1. Aberg T, Kihlgren M: Effect of open-heart surgery on intellectual function. Scand J Thorac Cardiovasc Surg 15(suppl):l-63, 1974 2. Aberg T, Ahlund P, Kihlgren M: Intellectual function late after open-heart operation. Ann Thorac Surg 36680-683, 1983 3. Albin MS, Hantler CB, Mitzel H, et al: Aeric microemboli and the transcranial Doppler (TCD):Episodic frequency and timing in 62 cases of open heart surgery. Anesthesiology 75:A53, 1991 4. Bar-El Y, Goor DA: Clamping of the atherosclerotic ascending aorta during coronary artery bypass operations. Its cost in strokes. J Thorac Cardiovasc Surg 104:469-474,1992 5. Bamett HJM, Mohr JP, Stein BM, et al: Stroke: Pathophysiology, Diagnosis, and Management, ed 2. New York, Churchill Livingstone, 1992, p 1026 6. Bladin CF, Chambers BR: Clinical features, pathogenesis, and computed tomographic characteristics of internal watershed infarction. Stroke 24:1925-1932, 1993 7. Blauth CI, Amold JV, Schulenberg WE, et al: Cerebral microembolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg 95:668-676,1988 8. Breuer AC, Furlan AJ, Hanson MR, et al: Central nervous system complications of coronary artery bypass graft surgery: Prospective analysis of 421 patients. Stroke 14682-687, 1983

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