Definition and incidence

Ankylosing spondylitis (AS), also known as rheumatoid spondylitis and Marie-Strumpell disease, is a chronic inflammatory disorder that primarily affects the spine and sacroiliac joints and produces fusion of the spinal vertebrae and the costovertebral joints. It is a disease of adults younger than 40 years, and it demonstrates a predilection for males (male-to-female ratio is 9:1). The disease is rare in Caucasians.

Pathophysiology

The cause of AS remains unclear. However, it is strongly associated with the histocompatibility antigen HLA-B27, the presence of which is detected in more than 90% of Caucasians with the disease.

Clinical manifestations and diagnosis

Ankylosing spondylitis is diagnosed on the basis of clinical criteria that include: (1) chronic low back pain with limitation of spinal motion (<4 cm as measured by the Schober test), (2) radiographic evidence of bilateral sacroiliitis, and (3) limitation of chest wall expansion (<2.5-cm increase in chest circumference measured at the fourth intercostal space). Extraskeletal manifestations of this disease include iritis, cardiovascular involvement (cardiac conduction defects, aortitis, and aortic insufficiency in 20% of individuals), peripheral arthritis, fever, anemia, fatigue, weight loss, and fibrocavitary (fibrobullous) disease of the apexes of the lungs. The most limiting factors associated with the disease are pain, stiffness, and fatigue.

Complications

Pulmonary complications are reported to occur in 2% to 70% of patients with AS. Apical fibrosis is the most commonly occurring abnormality followed by aspergilloma and pleural effusion with nonspecific pleuritis. In apical fibrosis, the pulmonary lesion begins with apical pleural thickening and patchy consolidation of one or both apexes and often progresses to dense bilateral fibrosis and air space enlargement. Patients with apical fibrosis usually have advanced AS. Impaired thoracic cage excursion caused by AS results in a greater impairment of apical ventilation, and this may be one factor in the pathogenesis of apical fibrosis.

The most common thoracic complication is fixation of the thoracic cage as a result of costovertebral ankylosis, which can lead to pulmonary dysfunction. In patients with this complication, motion of the thoracic cage is restricted because of fusion of the costovertebral joints; this restriction leads to a decrease in thoracic excursion. Respiratory function typically demonstrates a restrictive pattern with mild diminution of total lung capacity (TLC), vital capacity (VC), and carbon monoxide diffusing capacity (Dlco) and normal or slightly increased residual volume (RV) and functional residual capacity (FRC). Pulmonary compliance, diffusion capacity, and arterial blood gas (ABG) values usually are normal. Despite having abnormal pulmonary function, the majority of patients with AS are able to perform normal physical activities without pulmonary symptoms. It has been suggested that patients who exercise regularly and thus improve cardiovascular fitness could maintain a satisfactory work capacity.

Bone ankylosis may occur in the numerous joints around the thorax (the thoracic vertebrae and the costovertebral, costotransverse, sternoclavicular, and sternomanubrial joints), resulting in limitation of chest wall movement. Patients with AS rarely complain of respiratory symptoms or functional impairment unless they have coexisting cardiovascular or respiratory disease. Progressive kyphosis is equivalent to progressive rigidity of the thorax. Increased diaphragmatic function compensates for decreased thoracic motion, allowing lung function to be well preserved. Patients with advanced disease may have an entirely diaphragmatic respiration. Regional lung ventilation in patients with AS is normal unless they have preexisting apical fibrosis.

Cervical spondylosis affects levels C5 to C6 and C6 to C7 most often and less frequently C4 to C5, C7 to T1, and C3 to C4. The degenerative changes may result in nerve root entrapment by foraminal encroachment. The phrenic nerve, which innervates the diaphragm, is supplied primarily by the C4 nerve root and to a lesser extent by the C3 and C5 nerve roots.

Cricoarytenoid involvement may exist and can lead to respiratory dysfunction and upper airway obstruction. Cricoarytenoid dysfunction can manifest as a hoarse, weak voice. Respiratory failure from cricoarytenoid ankylosis has necessitated therapeutic tracheostomy. In all reported cases, laryngeal symptoms were present before cricoarytenoid arthritis caused airway compromise. A case of acute respiratory failure and cor pulmonale resulting from cricoarytenoid arthritis has also been reported in a patient with AS.

Treatment

Medical therapy for adult patients with AS is supportive and preventive. Most patients with AS are asymptomatic. Depending on the severity of disease involvement, management may consist of the use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients should refrain from smoking tobacco.

Anesthetic considerations

Patients with AS have specific anesthetic requirements. Management of the upper airway is the priority because of the potential for obstruction. Cervical spine involvement may result in limitation of movement. The ankylosed neck is more susceptible to hyperextension injury, and cervical fracture may occur. Intubation awake with or without the use of a fiberoptic bronchoscope is indicated. In rare situations, tracheostomy must be performed with the patient under local anesthesia before anesthesia can be induced. A regional anesthetic technique may not be feasible because of skeletal involvement that precludes access or because of neurologic complications such as spinal cord compression, cauda equina syndrome, focal epilepsy, vertebral basilar insufficiency, and peripheral nerve lesions. Patients with cardiovascular system involvement may require antibiotics, treatment of heart failure, or insertion of a temporary pacemaker before surgery. Restriction of chest expansion and, rarely, pulmonary fibrosis necessitate performance of a thorough preoperative assessment and immediate postoperative mechanical ventilation. Careful attention to positioning is essential.

Definition and incidence

Kyphosis is a deformity marked by an accentuated posterior curvature. Scoliosis is a lateral curvature of the spine. Kyphoscoliosis results when both kyphosis and scoliosis occur concomitantly, causing a lateral bending and rotation of the vertebral column. Scoliosis alone, despite its severity, does not cause sensory or motor impairment. In contrast, kyphosis and kyphoscoliosis may induce spinal cord damage because of the sharp angulation of the spine. Respiratory dysfunction is associated with scoliosis, significant kyphosis, and severe kyphoscoliosis. Scoliosis is the most common spinal deformity, with an incidence of four persons per 1000.

Scoliosis is classified in five categories: idiopathic, congenital, neuropathic (e.g., poliomyelitis, cerebral palsy, syringomyelia, and Friedreich ataxia), myopathic (e.g., muscular dystrophy and amyotonia), and traumatic. Idiopathic scoliosis is the most common deformity, accounting for 80% of all cases. On the basis of the time of onset, idiopathic scoliosis is divided into the following two categories: (1) the rare infantile form (male-to-female ratio is 6:4) and (2) the common adolescent form (male-to-female ratio is 1:9). The children in the adolescent group are born with straight spines; however, at some point during the growth period, their spines begin to bend and deform, with deformation progressively worsening until growth ends. In general, whereas curves associated with adolescent idiopathic scoliosis are convex and deviated to the right, those related to other disease may be deviated to the left. The presence of cervical scoliosis should alert anesthesia personnel to potential difficulties in airway management. Any significant curvature involving the thoracic spine may alter lung function. Unless the deformity is severe, patients with kyphosis are able to maintain normal pulmonary function; in contrast, even mild forms of scoliosis can result in impaired ventilatory function. Severe thoracic deformity may result in respiratory alterations during sleep. Several types of breathing abnormalities have been documented, including obstructive sleep apnea and hypopnea. The lowest HbO₂ saturations occurred during rapid eye movement sleep.

Pathophysiology

Diminution of pulmonary function occurs with curvatures of greater than 60 degrees, and pulmonary symptoms develop with curvatures greater than 70 degrees (as measured by the Cobb technique). Curvatures greater than 100 degrees may be associated with significant gas exchange impairment.

In general, the greater the curvature, the greater the loss of pulmonary function. Because of this, mechanical ventilation becomes inefficient; this inefficiency is the major factor causing respiratory compromise. At the time of diagnosis, it often is possible to document a reduction in lung capacity. The characteristic deformity seen in scoliosis causes one hemithorax to become relatively smaller than the other.

Skeletal chest wall deformity in kyphoscoliosis leads to a reduction in lung volumes and the pulmonary vascular bed. Ventilatory failure associated with severe kyphoscoliosis produces a lung size that is 30% to 65% of normal. As the patient ages, the chest wall becomes less compliant; this increases the work of breathing and leads to hypoventilation and respiratory muscle weakness.

The main features of lung mechanics in the patient with early-stage scoliosis are reduced lung volumes (VC, TLC, FRC, and RV) and reduced chest wall compliance; in the late stages of disease, ventilation/perfusion mismatching with hypoxemia (attributed to alveolar hypoventilation because of a decrease in tidal volume [Vt]), increased pulmonary artery pressure (PAP), hypercapnia, abnormal response to CO₂ stimulation, increased work of breathing, and cor pulmonale occur and eventually lead to cardiorespiratory failure. Reduction in VC to 60% to 80% of the predicted value is a typical finding. The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) is normal unless other pulmonary diseases are present. Although normocarbia prevails for most of the clinical course, an elevated Paco₂ signifies the onset of respiratory failure. The severity of hypercapnia most closely correlates with the patient’s age and inspiratory muscle strength.

Associated conditions

Scoliosis may be associated with several cardiovascular abnormalities, of which mitral valve prolapse is the most common. If mitral regurgitation is present, antibiotic prophylaxis is indicated before surgical manipulation. Other common changes include an increase in pulmonary vascular resistance (PVR) and ensuing pulmonary hypertension (PH), which leads to the development of right ventricular hypertrophy. Several contributing factors are thought to be responsible for the development of increased PVR. First, arterial hypoxemia results in pulmonary vasoconstriction. Second, changes in the pulmonary arterioles consequent to the increased pulmonic pressure may cause narrowing and result in irreversible PH. Third, a compressed chest wall may increase vascular resistance in affected areas. Fourth, development of scoliosis at an early age inhibits growth of the pulmonary vascular bed. Alveolar multiplication is nearly complete by 2 years of age but continues until the age of 8 years. During the first few years, lung growth occurs primarily by enlargement of existing alveoli.

Treatment

The management of scoliosis may include the following: (1) observation of the problem without active medical treatment; (2) treatment by nonoperative methods that include the use of braces or electronic stimulators; and (3) operative methods such as anterior or posterior spinal fusion and instrumentation, such as Harrington rod insertion. The mortality rate among persons with untreated scoliosis is twice that of the normal population, and the rate for those with thoracic curvatures alone was fourfold that of the normal population. Patients with congenital thoracic scoliosis are particularly at risk for cor pulmonale.

Anesthetic considerations

Postoperative implications

The decision whether to use mechanical ventilation postoperatively is based on the severity of scoliosis and intraoperative events. Most patients with mild to moderate pulmonary dysfunction are able to undergo safe extubation in the operating room. Those with severe deformity or patients who have received massive fluid and blood replacement therapy should be weaned slowly.

Incidence

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease that classically occurs in patients with malignant disease, particularly small cell carcinoma of the bronchi. One-third to half of patients, however, have no evidence of carcinoma. Most patients with myasthenic syndrome are men between the ages of 50 and 70 years.

Pathophysiology

The basic defect associated with LEMS appears to be an autoantibody-mediated derangement in presynaptic Ca²⁺ channels leading to a reduction in Ca²⁺-mediated exocytosis of acetylcholine (ACh) at neuromuscular and autonomic nerve terminals. The decreased release of ACh quanta from the cholinergic nerve endings produces a reduced postjunctional response. Unlike in myasthenia gravis, the number and the quality of postjunctional AChRs remain unaltered, and the end plate sensitivity is normal. The neuromuscular junction abnormality of LEMS is similar in location to that of Mg²⁺ intoxication or botulism poisoning, in which the release of presynaptic ACh is attenuated.

Clinical manifestations

Muscle weakness, fatigue, hyporeflexia, and proximal limb muscle aches are the dominant features of LEMS. The diaphragm and other respiratory muscles are also involved. Autonomic nervous system dysfunction is often present and is manifested as impaired gastric motility, orthostatic hypotension, and urinary retention.

Patients with LEMS experience a brief increase in muscle strength with voluntary contraction, distinguishing it from myasthenia gravis. Tetanic stimulation results in a progressive augmentation in muscle strength as the frequency of the stimulation is increased. Post-tetanic potentiation is also enhanced.

Treatment

There is no cure for LEMS. Treatment is aimed at removal of the small cell carcinoma if present improving muscle strength and reversing autonomic deficits. 3,4-Diaminopyridine improves muscle strength in some patients by promoting presynaptic Ca²⁺ influx and increasing the number of ACh quanta that are liberated by a single nerve action potential. Anticholinesterase agents, plasmapheresis, corticosteroids, intravenous immunoglobulin, and immunosuppressive drugs provide improvement for some patients with LEMS.

Anesthetic considerations

An index of suspicion for LEMS should be maintained in surgical patients with a history of muscle weakness and suspected or diagnosed carcinoma of the lung. Patients with LEMS are extremely sensitive to the relaxant effects of both depolarizing and nondepolarizing muscle relaxants. Inhalational anesthetics alone may provide adequate relaxation, but if muscle relaxants are required, their dosages should be reduced and the neuromuscular blockade closely monitored. Neuromuscular reversal with an anticholinesterase agent may be used. Prolonged ventilatory assistance may be required postoperatively.

Definition and incidence

Malignant hyperthermia is an uncommon, life-threatening hypermetabolic disorder of skeletal muscle triggered in susceptible individuals by potent inhalation agents, including sevoflurane, desflurane, isoflurane, and halothane and the depolarizing muscle relaxant succinylcholine. About 52% of cases occur in patients younger than age 15 years, with a mean age of 18.3 years. The exact incidence of MH is unknown, but the rate of occurrence has been estimated to be one in 50,000 in adults and one in 15,000 in children.

Pathophysiology

Although the cause of MH is not yet known with certainty, it is generally agreed that MH is an inherited disorder of skeletal muscle in which a defect in calcium regulation is expressed by exposure to triggering anesthetic agents; intracellular hypercalcemia results. The ryanodine receptor is the major calcium release channel of the sarcoplasmic reticulum, and much attention has been focused on this receptor as the site of the MH defect. The defect involves skeletal muscle, and there is no evidence for a primary defect in cardiac or smooth muscle cells.

Malignant hyperthermia is initiated when specific triggering agents induce increased concentrations of calcium in the muscle cells of MH-susceptible (MHS) patients. Actomyosin cross-bridging, sustained muscle contraction, and rigidity result. Energy-dependent reuptake mechanisms attempt to remove excess calcium from the myoplasm, increasing muscle metabolism two- to threefold. The accelerated cellular processes increase oxygen consumption, augment carbon dioxide and heat production, deplete adenosine triphosphate (ATP) stores, and generate lactic acid. Acidosis, hyperthermia, and ATP depletion cause sarcolemma destruction, producing a marked regress of potassium, myoglobin, and creatine kinase (CK) to the extracellular fluid. Skeletal muscle constitutes 40% to 50% of our body mass, so relatively small changes in muscle metabolism may produce the dramatic systemic biochemical changes observed with MH.

Clinical manifestations

Not all cases of MH are fulminant, but rather there is a spectrum or continuum of severity, ranging from an insidious onset with mild complications to an explosive response with pronounced rigidity, temperature rise, arrhythmias, and death. Although MH may present in several ways, a typical MH episode begins while the patient is under general anesthesia with a volatile anesthetic. Use of succinylcholine may or may not precede the MH episode. The onset of MH symptoms may occur immediately after induction of anesthesia or several hours into the surgery. Desflurane is a weaker MH trigger and has been associated with delayed onset of MH, as long as 6 hours after induction of anesthesia. Succinylcholine appears to accelerate the onset and increase the severity of the MH episode. The presentation of MH may follow a dose-dependent response, with lower concentrations of volatile anesthetics resulting in a more protracted onset of hypermetabolic symptoms. Rarely, MH occurs in the recovery room, usually within 1 hour after general anesthesia.

The clinical features of MH reflect increased intracellular muscle Ca²⁺ concentration and greatly increased body metabolism and are listed in the following section. Common signs of MH include tachycardia, tachypnea, skin mottling, cyanosis, and total body or jaw muscle rigidity. Muscle rigidity is clinically apparent in 75% of cases. The most sensitive indicator of MH is an unanticipated increase in end-tidal carbon dioxide (ETCO₂) levels out of proportion to minute ventilation. The increased ETCO₂ may be abrupt, or it may rise gradually over the course of the anesthetic. Hyperthermia, which may climb at a rate of 1° to 2° C every 5 minutes and exceed 43.3° C (110° F), is often a late but confirming sign of MH.

Clinical events

Laboratory results

The combination of acidosis, hyperkalemia, and hyperthermia leads to cardiac irritability, a labile blood pressure, and arrhythmias that can rapidly progress to cardiac arrest. Laboratory findings mirror the muscle breakdown and include myoglobinuria and increased serum potassium and CK. Serum CK levels peak 12 to 24 hours after the onset of MH. Myoglobin appears in the plasma within minutes of the hypermetabolic muscle response. Arterial and venous blood gas analysis reveals decreased oxygen tension and mixed metabolic and respiratory acidosis. Late complications may include cerebral edema, myoglobinuric renal failure, disseminated intravascular coagulopathy, hepatic dysfunction, and pulmonary edema.

The variable time course and the nonspecific clinical features and laboratory findings can make the diagnosis of MH difficult. Insufficient anesthetic depth, hypoxia, neuroleptic malignant syndrome, propofol infusion syndrome, thyrotoxicosis, pheochromocytoma, and sepsis can share several characteristics with MH, making the clinical picture ambiguous and the differential diagnosis challenging to even the most experienced practitioner. Surgical procedures performed of necessity in a darkened operating room can further compromise the practitioner’s diagnostic acumen.

In addition to being a trigger of MH, succinylcholine may also induce hyperkalemic-mediated cardiac arrest in children with occult myopathies. Because of this concern, most anesthetists use nondepolarizing muscle relaxants for elective intubation in children and reserve the use of succinylcholine for treatment of laryngospasm or emergency airway management.

Preoperative assessment and prevention

Malignant hyperthermia–susceptible patients may be otherwise healthy and completely unaware of their risk until exposed to a triggering anesthetic. Furthermore, not everyone who has the MH gene develops an MH episode upon each exposure to triggering anesthetics. It is estimated that about 21% of MHS patients have at least one uneventful anesthetic before having an MH episode. Although MH susceptibility cannot be ruled out by history alone, every surgical patient should be questioned about the following information:

Because MH is considered an inherited disorder, all members of a family in which MH has occurred must be considered MHS unless proven otherwise. Moreover, the absence of a positive family history does not preclude MH susceptibility.

Certain disorders should alert the anesthetist to an increased possibility of MH susceptibility. A clear genetic association between MH and the inherited myopathy central core disease has been demonstrated. Case reports have also linked MH or an MH-like disorder to DMD and BMD dystrophy and forms of periodic paralysis and myotonia. MH-triggering agents should not be administered to patients with these disorders. This caveat is especially consequential in patients undergoing outpatient procedures, who may have more limited postoperative observation.