Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 20 – The Geriatric Patient

Frederick E. Sieber, MD,
Jian Hang, MD, PhD






Huntington's Chorea (Huntington's Disease)



Zenker's Diverticulum






Acute Mesenteric Ischemia



Idiopathic Pulmonary Fibrosis



Polycythemia Vera



Essential Thrombocythemia



Myeloid Metaplasia with Myelofibrosis

Elderly surgical patients are subject to many of the same rare diseases seen in younger populations. The focus in this chapter is on several uncommon diseases that are more unique to aged individuals.


Poliomyelitis was common in the western world until the early 1960s. The disease has three distinct stages: acute poliomyelitis, recovery period, and stable disability. The acute disease is no longer a threat to most countries of the world thanks to the effort for worldwide eradication initiated by the World Health Organization (WHO) in 1988. The number of cases of poliomyelitis worldwide has dropped drastically from more than 350,000 per year in over 125 countries in 1988 to affecting fewer than 1,000 children in three countries in 2003. Currently, the epidemic areas are limited to five regions in India, Nigeria, and Pakistan. The Americas have been polio free since 1991. It is estimated, however, that there are 250,000[1] to 300,0002 survivors of poliomyelitis in the United States. The long-term effects and late sequelae of poliomyelitis have attracted attention recently as new-onset muscle weakness has been reported in survivors of polio many years after their initial illness.


Acute poliomyelitis (infantile paralysis) is a viral infection caused by poliovirus, a positive single-stranded RNA enterovirus (picornavirus) that is transmitted via the orofecal route. The virus has a predilection for the motor neurons of the anterior horn gray matter in the cervical and lumbar spinal cord, which can result in neuron injury or death. The damage or death of the motor neurons in the spinal cord results in wallerian degeneration of the axons and myelin. The associated muscle fibers become denervated and paralyzed, resulting in acute paralytic poliomyelitis. Worldwide vaccination efforts with oral polio vaccine (OPV) have drastically decreased the number of acute paralytic poliomyelitis cases.

History and Physical Findings Consistent with Diagnosis.

The vast majority of infected individuals remain asymptomatic or experience a self-limited illness. The clinical features of acute polio are listed in Table 20-1 . The muscles may be tender to palpation; tremors and muscle weakness may appear. Paralysis can occur at any time during the febrile period if the virus crosses the blood-brain barrier, attacking neurons in the brain, brainstem, and spinal cord.

TABLE 20-1   -- Acute Poliomyelitis



Clinical Features


















Neck, back, abdominal and extremity pain



Muscle spasm



Residual Complications



Muscle paresis and paralysis



Skeletal deformities



Joint contractures



Movement disability



Growth retardation of affected limb



Osteoporosis and pain from wear and tear



Compression neuropathy



Venous stasis



Chronic colonic distention



Respiratory insufficiency



Cold intolerance



Paralytic polio is classified into two forms: spinal polio and bulbar polio ( Table 20-2 ). Spinal polio is the most common type and involves damage to the motor neurons of the spinal cord. It is characterized by asymmetrical, flaccid paralysis of muscles, primarily in the lower limbs. Bulbar polio involves damage to neurons in the reticular formation and the nuclei of cranial nerves in the brain stem. Life-threatening respiratory failure, autonomic dysfunction, and cardiac arrhythmias may occur when bulbar polio involves the autonomic nuclei of the respiratory center.

TABLE 20-2   -- Classification of Paralytic Poliomyelitis



Spinal Poliomyelitis



Most common



Spinal motor neurons



Asymmetrical flaccid paralysis of extremity muscles, more commonly of the lower limbs than upper limbs and trunk



Bulbar Poliomyelitis



Less common



Reticular formation



The nuclei of cranial nerves



Facial weakness



Weakness of the sternocleidomastoid and trapezius muscles



Pharyngolaryngeal airway muscles



Dysphagia, dysphonia, nasal voice, regurgitation



Difficulty in chewing and inability to swallow or expel saliva and secretion



Involvement of autonomic nuclei



Respiratory failure



Autonomic dysfunction



Cardiac arrhythmia



Recovery Period from Acute Poliomyelitis.

In those patients who survive the acute illness, slow partial recovery of muscle strength occurs as a result of several physiologic processes, including terminal sprouting, myofiber hypertrophy, fiber type transformation, and ongoing denervation and reinnervation. The process can last over several months to years. The muscle may regain up to 80% of its strength in the first 6 months, and further improvement may continue over the next 2 years. There are many possible residual complications of acute poliomyelitis (see Table 20-1 ).

The Late Effects of Poliomyelitis.

Paralytic poliomyelitis has been eradicated from the western world for decades. Only polio survivors with late effects might be encountered in our practice. Numerous risk factors are associated with the development of late effects ( Table 20-3 ). There is no consensus on specific diagnostic criteria for this disease entity. Late effects of poliomyelitis refer to a diffuse group of symptoms (see Table 20-3 ).[3]The diagnosis is generally considered in paralytic polio survivors of many years who develop new-onset cluster of symptoms consistent with the disease after excluding relevant medical, orthopedic, and neurologic conditions.[4]

TABLE 20-3   -- Late Effects of Poliomyelitis



Risk Factors



Age at onset



Severity of paralysis



Use of ventilator






Years of acute polio infection






Polio to post-polio interval



Current age



Functional recovery



Residual impairment



Weight gain



Presence of muscle pain associated with exercise



Signs and Symptoms



Muscle pain, weakness, and atrophy



Joint pain



Musculoskeletal imbalance



Skeletal deformities



Growth retardation



Compression neuropathy



Degenerative arthritis



Repetitive motion problems



Respiratory insufficiency






Speech difficulty






Sleep impairment



Cold intolerance



Difficulties with activities of daily living



Preoperative Preparation.

Polio survivors should be specifically questioned concerning any new onset or increased muscle weakness, muscle pain, or fatigue. New weakness has been reported to occur in 20% to 60% of polio survivors. The time period between acute polio and the onset of late effectshas ranged from 8 to 71 years, with an average interval of 35 years. Patients with a history of polio who appear normal with good muscle strength clinically may have significant underlying denervation when tested with electromyography, which should be considered in all patients with prior history of polio to determine the severity of denervation.

Scoliosis, thoracic kyphosis, and deformed thoracic cage, along with muscle weakness, are very common in polio patients. New respiratory difficulties have been reported in 27% to 58% of subjects in surveys of late effects of poliomyelitis. Thus, comprehensive pulmonary evaluation, optimization of pulmonary function, and treatment of any pulmonary infections should be accomplished before surgery. Post-polio patients have a high incidence of sleep disturbances such as obstructive sleep apnea and/or central sleep apnea. Pulmonary hypertension may also exist secondary to chronic hypoxemia, hypercapnia, or obstructive sleep apnea.

Polio survivors may have increasing difficulty performing their daily activities as the result of respiratory insufficiency, muscle weakness and pain, deformity, and/ or coexisting cardiac diseases. In addition, information concerning chronic use of pain medicines should be sought.

Preoperative assessment of cognitive function in people with a history of polio is important. Cognitive problems reported by polio survivors suggest that the fatigue experienced cannot be explained merely by damage to the anterior horn motor neurons but may be related to changes and loss of brain activating system neurons that survive the acute polio infection.

Perioperative Considerations.

A potentially difficult airway should be anticipated, especially in patients with chest deformity, scoliosis, thoracic kyphosis, or obstructive sleep apnea. Respiratory insufficiency and secondary muscle weakness, along with difficulty in clearing secretions, will make respiratory management challenging. Cautious extubation should be practiced in patients with obstructive or central sleep apnea. If a prior polio patient suffered cardiac disease, whether it is primary or secondary to polio, appropriate anesthetic techniques should be employed based on the cardiac status.

Affected muscles have varying degrees of denervation. Therefore, succinylcholine should be used with caution because of the risk of massive potassium release after depolarization. The pharmacology of nondepolarizing muscle relaxants may be unpredictable owing to neuromuscular junction transmission defects and muscle atrophy. Nondepolarizing muscle relaxants appear to have increased potency in poliomyelitis survivors.[5]

Prior polio patients often suffer cold intolerance. Vigilant efforts should be made to preserve heat and maintain patient's body temperature, especially during general anesthesia.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Huntington's chorea is a rare, autosomal dominant, inherited degenerative disorder of the nervous system. It was first described by George Huntington in 1872. Its incidence is 5 to 10/100,000. It is characterized by the clinical hallmarks of progressive chorea and dementia. The onset is usually in the fourth or fifth decade of life, but there is a wide range in age at onset, from childhood to late life (>75 years). Symptoms appear to progressively worsen with age.


Huntington's disease is an autosomal dominant disorder with complete penetrance. The Huntington's disease gene, IT15, is located on chromosome 4p, contains CAG-trinucleotide repeats, and codes for a protein called huntingtin. The protein is found in neurons throughout the brain; its normal function is unknown. Transgenic mice with an expanded CAG repeat in the Huntington's disease gene develop a progressive movement disorder.

Huntington's disease is a basal ganglia disease, with caudate and putamen being the regions most severely affected. The most significant neuropathologic change is a preferential loss of medium spiny neurons in the neostriatum. Neurochemically, there is a marked decrease of γ-aminobutyric acid (GABA) and its synthetic enzyme glutamic acid decarboxylase throughout the basal ganglia, as well as reductions of other neurotransmitters such as substance P and enkephalin. The movement disorder is slowly progressive and may eventually become disabling.


The DNA repeat expansion forms the basis of a diagnostic blood test for the disease gene. Persons having 38 or more CAG repeats in the Huntington's disease gene have inherited the disease mutation and will eventually develop symptoms if they live to an advanced age. Each of their children has a 50% risk of also inheriting the abnormal gene. There is a rough correlation between a larger number of repeats and an earlier age at onset.

Huntington's can also be diagnosed by caudate atrophy on magnetic resonance imaging in the context of an appropriate clinical history.

Differential Diagnosis.

Differential diagnosis of Huntington's disease includes other choreas, hepatocerebral degeneration, schizophrenia with tardive dyskinesia, Parkinson's disease, Alzheimer's disease, and other primary dementias and drug reactions.

Preoperative Preparation.

Even though memory in patients suffering from Huntington's disease is frequently not impaired until late in the disease, attention, judgment, awareness, and executive functions may be seriously deficient at an early stage. Depression, apathy, social withdrawal, irritability, fidgeting, and intermittent disinhibition are common. Delusions and obsessive-compulsive behavior may occur. These signs, along with poor articulation of speech, make preoperative evaluation and obtaining consent arduous tasks. Characteristic choreoathetoid movements, plus frequent, irregular, sudden jerks and movements of any of the limbs or trunk make physical examination, as well as regional anesthesia, difficult to perform.

Cachexia and frailty may be observed in the elderly Huntington's patient. Pharyngeal muscle involvement leads to dysphagia and makes these patients susceptible to pulmonary aspiration.[6] Before elective surgery, it is important to rule out ongoing aspiration pneumonitis or pneumonia by careful physical examination and chest radiography.

Chronic Medications for Condition.

There is no specific treatment to stop progression of the disease, but the movements and behavioral changes may partially respond to phenothiazines, haloperidol, benzodiazepines, or olanzapine. Selective serotonin reuptake inhibitors may help with associated depression.

Perioperative Considerations.

Major concerns in anesthetic management of Huntington's disease are potential difficult airway, sleep apnea, risk of aspiration, and altered reactions to various drugs. A difficult airway may result from a rigid, stiff, unstable posture with hyperextension of the neck. Sleep apnea may also be present.

It is controversial whether the pharmacology of anesthetic agents is altered in Huntington's disease. Authors have reported a decrease in plasma cholinesterase activity and a prolonged effect of succinylcholine.[7] In addition, there may be an exaggerated response to sodium thiopental[8] or midazolam.[9] On the other hand, both thiopental[10] and succinylcholine [10] [11] have been used safely in Huntington's patients. Other agents that have been used safely include propofol[12] and sevoflurane.[10] The safety profile and pharmacokinetics of the nondepolarizing muscle relaxants mivacurium and rocuronium are similar to those in patients without Huntington's disease. [10] [13] [14]

It is generally recommended that rapid-sequence or modified rapid-sequence induction with cricoid pressure be used for induction of general anesthesia in these patients. Other authors suggested using a total intravenous anesthesia technique to reduce the risk of postoperative shivering related to inhalational agents so as to avoid the precipitation of generalized tonic spasms.


Huntington's chorea is an inherited disease characterized by choreoathetosis, rigidity, and dementia that is most commonly seen in late life. Patients suffering from Huntington's disease are at higher risk of intraoperative complications, including pulmonary aspiration, altered anesthetic pharmacology, and worsening generalized tonic spasms. Rapid-sequence induction with cricoid pressure is recommended for induction of general anesthesia in these patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Zenker's diverticulum is an outpouching of the pharyngoesophageal mucosa in the natural zone of weakness of the posterior hypopharyngeal wall (Killian's triangle), between the inferior pharyngeal constrictor muscle and the cricopharyngeus muscle (upper esophageal sphincter). It always occurs above and never below the cricopharyngeus muscle. Its incidence is estimated to range from 0.01% to 0.11% of the population. Zenker's diverticulum is rare in patients younger than 30 years of age, with a peak incidence in the seventh to ninth decades. The prevalence is similar in Europe and the United States. It is rarely reported in the Middle and Far East.


The etiology of Zenker's diverticulum is not completely understood. The formation of pharyngoesophageal mucosa is thought to result from asynchronous coordination of the cricopharyngeus muscle during swallowing. Over time, the increased pressure causes herniation of the mucosa posteriorly through the single sheet of the thyropharyngeus (the dehiscence of Killian) between thyropharyngeus muscle and cricopharyngeus muscle.

Diagnosis/Differential Diagnosis.

The signs and symptoms of Zenker's diverticulum are shown in Table 20-4 . Most patients (98%) present with some degree of dysphagia, combined with regurgitation of undigested food particles. In this clinical context the differential diagnosis is mainly limited to Zenker's diverticulum and achalasia. Although the diverticulum can reach a size of 15 cm or more, it is rarely palpable. The diagnostic procedure of choice is barium swallow. Endoscopy is indicated to exclude neoplasia if the contrast study shows esophageal mucosal irregularities. Coexistent hiatal hernia, esophageal spasm, achalasia, and esophagogastroduodenal ulceration are common.

TABLE 20-4   -- Signs and Symptoms of Zenker's Diverticulum









Halitosis and regurgitation of undigested food



Noisy deglutition



Weight loss



Poor nutrition



Pulmonary complications, such as aspiration and pneumonia



Perioperative Considerations.

The surgical procedure of choice in patients with symptomatic Zenker's diverticulum is cricopharyngeus myotomy. The surgery for Zenker's diverticulum can be done under general anesthesia as well as local or regional anesthesia. Local or regional anesthesia may facilitate the identification of the diverticulum intraoperatively and may reduce the mean postoperative stay, although no statistical difference has been demonstrated between different anesthetic techniques.[15]

The most important anesthetic complication that occurs in these patients is pulmonary aspiration. [16] [17] Preoperative fasting is important, although it does not guarantee an empty pouch. Surgery should be delayed if foreign bodies, food, or barium is known to be present in the diverticulum, and a reasonable time should be allowed for the material to be expelled. Oral premedication should be avoided. Because the contents of the pouch have an alkaline pH, the use of antacids or H2 blockers, such as sodium citrate or ranitidine, have no value. Manually emptying the contents of the diverticulum by exerting external pressure over the pouch before induction is the most important and effective maneuver to ensure decreased pressure within the pouch. Inserting a gastric tube should probably be avoided, because it may lead to the perforation of the diverticulum.

Patients with Zenker's diverticulum should be placed in a head-up position of 10 to 30 degrees to decrease the likelihood of regurgitation. Rapid-sequence induction without cricoid pressure should be used. Cricoid pressure during induction may not prevent regurgitation of diverticular contents and may even promote regurgitation because the diverticulum is above the cricopharyngeus muscle whereas the cricoid ring is below the neck of the diverticulum.[18] Intraoperatively, a moist gauze pack may be placed around the endotracheal tube to prevent aspiration.

Aspiration may still happen postoperatively,[18] and caution should be taken to maintain minimal sedation and a semi-sitting position when nursing the patient.


Zenker's diverticulum carries a high risk of aspiration during surgical correction. Manual emptying of the sac is an important preoperative maneuver in these patients. General anesthesia should be induced using a rapid-sequence intubation without cricoid pressure, with the patient positioned in a head-up tilt of 10 to 30 degrees. Aspiration precautions should also be taken postoperatively.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Amyloidosis results from the deposition of insoluble, fibrillar proteins (amyloid), mainly in the extracellular spaces of organs and tissues in amounts sufficient to impair normal function. Amyloid fibrils can be deposited locally or may involve virtually every organ system of the body. Symptoms and signs depend on the organs and tissues involved.


The cause of amyloid production and its deposition in tissues is unknown. All amyloid fibrils share an identical secondary structure, the β-pleated sheet conformation. The polypeptide backbone of these protein precursors assume similar fibrillar morphologies that render them resistant to proteolysis. The amyloidoses have been classified into 18 subtypes[19] based on the amyloid protein involved. The name of the amyloidosis subtype uses the capital letter A as the first letter of designation and is followed by the protein designation. Three major types of amyloid and several less common forms have been defined biochemically.

Whether an amyloidosis is systemic or localized (organ limited) depends on the biochemical structure of the amyloid protein. Systemic amyloidoses include biochemically distinct forms that are neoplastic, inflammatory, genetic, or iatrogenic, whereas localized or organ-limited amyloidoses are associated with aging and diabetes and occur in isolated organs, often endocrine, without evidence of systemic involvement. Despite their biochemical differences, the various amyloidoses share common pathophysiologic features ( Table 20-5 ).

TABLE 20-5   -- Amyloidosis: Multisystem Involvement and Clinical Manifestations


Clinical Features

Nervous System


Sensory loss; carpal tunnel syndrome; myopathy; myelopathy; vitreous opacities

 Autonomic neuropathy

Postural hypotension; inability to sweat; sphincter incompetence

Respiratory System

 Upper respiratory tract

Localized tumor can be found in respiratory tracts and lungs

 Nasal sinuses, larynx, and trachea

Tracheobronchial lesions, or diffuse alveolar deposits



 Lower respiratory tract and lung parenchyma

Accumulation of amyloid which block the ducts; may resemble a neoplasm


 Conduction system

Arrhythmia, heart block

 Endocardium and valves

Valvular diseases


Cardiomyopathy: dilated, restrictive and obstructive forms, congestive heart failure



Gastrointestinal System


Hepatomegaly; abnormal liver functions; portal hypertension

 Gastrointestinal tract

Unexplained gastrointestinal diseases, malabsorption; unexplained diarrhea or constipation; obstruction, ulceration and protein loss; esophageal motility disorders


Nephrotic syndrome, proteinuria, renal failure; renal tubular acidosis or renal vein thrombosis


Spleen enlargement; not associated with leukopenia and anemia

Musculoskeletal System

Pseudomyopathy; cystic bone lesions

Endocrine System

 Thyroid gland

Hypothyroidism; full-blown myxedema (almost invariably accompanies medullary carcinoma of thyroid)

 Adrenal gland

Type II diabetes

 Pituitary gland, pancreas

Other endocrine abnormalities


Lichen amyloidosis; papules; plaques; ecchymoses

Hematologic System

Fibrinogenopenia including fibrinolysis

Endothelial damage

Selective deficiency of clotting factors (factor X)


Clotting abnormalities, abnormal bleeding time


Rheumatoid arthritis, chronic inflammation and infection



Three major systemic clinical forms are currently recognized: primary or idiopathic (AL), secondary amyloidosis (AA), and hereditary amyloidosis ( Table 20-6 ). The most common form of systemic amyloidosis seen in current clinical practice is AL (light-chain amyloidosis, primary idiopathic amyloidosis, or that associated with multiple myeloma).

TABLE 20-6   -- Major Systemic Amyloidosis: Clinical Features and Diagnosis


Primary (AL) (or Idiopathic)

Secondary (AA) (or Secondary, Acquired, Reactive)


Commonly Involved Organs

Localized amyloid tumors may be found in the respiratory tract. Vascular system, especially the heart, is involved frequently. Other organs may also involved: tongue, thyroid gland, heart, lung, liver, intestinal tract, spleen, kidney and skin.

Spleen, liver, kidney, adrenal glands, lymph nodes and vascular involvement occurs. No organ is spared, but significant involvement of the heart is rare.

Peripheral sensory and motor neuropathy, often autonomic neuropathy Carpal tunnel syndrome Vitreous abnormalities Cardiovascular and renal amyloid

Associated Diseases

Multiple myeloma

Infection (tuberculosis, bronchiectasis, osteomyelitis, leprosy) Inflammation (rheumatoid arthritis, granulomatous ileitis) Familial Mediterranean fever Tumors such as Hodgkin's disease



Monoclonal immunoglobulin in urine or serum plus any of the following: macroglossia; cardiomyopathy; hepatomegaly; malabsorption or unexplained diarrhea or constipation; unexplained nephrotic syndrome; carpal tunnel syndrome; or peripheral neuropathy

Chronic infection (osteomyelitis, tuberculosis), chronic inflammation (rheumatoid arthritis, granulomatous ileitis) plus any of the following: hepatomegaly, unexplained gastrointestinal disease, or proteinuria

Family history of neuropathy plus any of the following: early sensorimotor disassociation, vitreous opacities, cardiovascular disease, gastrointestinal disease, autonomic neuropathy, or renal disease



Diagnosis/Differential Diagnosis.

Symptoms and signs vary depending on the involved systems and organs. The nephritic syndrome is the most striking early manifestation. The renal lesion is usually not reversible and progressively leads to azotemia and death.

Regardless of etiology, the clinical diagnosis of amyloidosis is usually not made until the disease is far advanced because of nonspecific symptoms and signs of the disease. The diagnosis is made by identification of amyloid fibrils in biopsy or necropsy tissue sections using Congo red stain. A unique protein (member of the pentraxin family of proteins) called AP (or serum AP) is universally associated with all forms of amyloid and forms the basis of a diagnostic test. Once amyloidosis is diagnosed, it can be further classified by genomic DNA, protein, and immunohistochemical studies; the relationship of immunoglobulin-related amyloid to multiple myeloma should be confirmed by electrophoretic and immunoelectrophoretic studies.

Preoperative Preparation.

A comprehensive survey of all systems should be performed, focusing on the most frequently involved organs. Careful evaluation for systemic involvement of amyloidosis or associated disease is important even in apparently isolated tumorous amyloidosis ( Table 20-7 ).

TABLE 20-7   -- Amyloidosis: Preoperative Assessment and Workup

Nervous System

Peripheral neuropathy: document preexisting peripheral neurologic symptoms


Autonomic neuropathy: orthostatic blood pressure, etc.




Diffuse dysfunction: pulmonary function tests


Arrhythmia, cardiomyopathy, and valvular involvement: cardiac function echocardiogram and electrocardiogram


Esophageal motility abnormality, intestinal obstruction


Liver function tests


Abnormal renal function: electrolytes, renal function tests


Enlarged spleen, check complete blood cell count: red blood cells, platelet, coagulation coagulopathy, and factor deficiency


Pancreatic or adrenal gland involvement; thyroid function test to rule out hypothyroidism



Chronic Medications/Treatment for Condition.

Treatment of localized amyloid tumors is surgical excision. However, there is no effective treatment of systemic amyloidosis. Current care is generally supportive, and therapy is directed at reducing production and promoting lysis of amyloid fibrils. Hemodialysis and immunosuppressive therapy may be useful. Current treatment of primary amyloidosis includes a program of prednisone/melphalan or prednisone/melphalan/colchicine. Liver transplantation, kidney transplantation, and stem cell transplants have yielded some promising results. In certain heredofamilial amyloidoses, genetic counseling is an important aspect of treatment. Ultimately some people with amyloidosis continue to deteriorate. The major causes of death are heart disease and renal failure. Sudden death, presumably due to arrhythmias, is common.

Perioperative Considerations.

Localized amyloid deposition has been reported at various sites. Amyloid in the tongue can cause macroglossia to a degree requiring glossectomy.[20] In addition, amyloid macroglossia may be associated with coexisting hypothyroidism.[21] Laryngeal amyloidosis is fragile and carries the risk of spontaneous massive hemorrhage even without manipulation.[22] The airway tumor should be assessed by noninvasive imaging, such as computed tomography (CT) or magnetic resonance imaging. Prior to intubation, preparations should be made for both difficult airway and massive hemorrhage.

A smaller endotracheal tube may be considered. In addition, direct laryngoscopy monitored by a fiberscope-video system, rather than blind insertion of the endotracheal tube through vocal cords over a fiberoptic bronchoscope,[23] has been advocated.

It is controversial whether depolarizing muscle relaxants should be administered to patients with amyloidosis, especially those with cardiac involvement. Patients with familial amyloid polyneuropathy have a high incidence of cardiac arrhythmias during anesthesia. It has been hypothesized that exaggerated elevations in potassium concentrations occur after succinylcholine administration and may be a contributing factor.[24] However, Viana and associates[25] reported that the average increase in plasma potassium concentrations after succinylcholine administration in patients with familial amyloid polyneuropathy was similar to the increase observed in a normal population by others. However, the authors could not exclude that a dangerous rise in serum potassium concentration might not occur in a certain percentage of patients with familial amyloid after administration of succinylcholine. This may also be true in patients with amyloidosis who also suffer from long-standing polyneuropathy.[26] Thus, it may be prudent to avoid administration of depolarizing muscle relaxants in patients with amyloidosis, especially in the presence of coexisting polyneuropathy and/or cardiac disease.

Autonomic dysfunction secondary to amyloidosis has dramatic perioperative ramifications.[25] In particular, the administration of anesthetic drugs to patients with amyloidotic polyneuropathy presents a risk of significant hypotension (even use of ketamine does not prevent hypotension). Patients with decreased preload are especially sensitive. In addition, hypotension is frequent even in patients with adequate preload as a result of low systemic vascular resistance. Given these observations, one should consider using invasive blood pressure monitoring and preparation of a vasoconstrictor infusion for effective anesthetic management of these patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Acute mesenteric ischemia primarily results from reduction of arterial blood supply and carries with it a high morbidity and mortality. Table 20-8 shows the subclassifications of this disease. Occlusion accounts for about 75% of acute mesenteric ischemia, which is a disease of the elderly; the median age of patients presenting with mesenteric arterial embolism is 70 years. The exact etiology of nonocclusive mesenteric ischemia is unclear. However, splanchnic vasoconstriction and reduced blood flow to the splanchnic bed have been proposed as possible mechanisms after initial insults such as shock, sepsis, hemorrhage, cardiac decompensation, or other conditions with profound physiologic stress ( Table 20-9 ). Mesenteric venous thrombosis is seen primarily in younger patients.

TABLE 20-8   -- Acute Mesenteric Ischemia: Clinical Profile


Incidence (%)


Risk Factors


Occlusive mesenteric ischemia




Systemic atherosclerosis

Very high









Coagulation disorders





Recent myocardial infarction





Congestive heart failure










Rheumatic fever





Valvular diseases


Nonocclusive mesenteric ischemia








Cardiogenic shock










Congestive heart failure










Cardiopulmonary bypass




















Vasopressors and digitalis


Mesenteric venous thrombosis








Portal hypertension










Prior surgery









TABLE 20-9   -- Acute Mesenteric Ischemia

Contributing Factors

Occlusive mesenteric ischemia: advancing age, hypertension, peripheral vascular disease, recent myocardial infarction, congestive heart failure, low flow states, atrial fibrillation


Nonocclusive mesenteric ischemia: congestive heart failure, systemic hypotension, hemorrhagic blood loss, sepsis and endotoxemia, digitalis and pressor use, dehydration can be contributing factors.

Differential Diagnosis

Primary gastrointestinal disease (peptic ulcer disease, bowel obstruction, diverticulitis, colon cancer, appendicitis, hernia)


Hepatic diseases


Biliary (cholecystitis)


Pancreas (pancreatitis)


Renal (pyelonephritis)


Urinary (cystitis, bladder obstruction)


Vascular emergency (leaking aneurysm)


Other (psoas abscess, abdominal wall hematoma)

Preoperative Preparation

Perform aggressive fluid resuscitation.


Establish hemodynamic monitoring and intravenous access.


Wean off aggravating pressors (e.g., norepinephrine and phenylephrine).


Switch to less offensive pressor such as dopamine.


Discontinue digitalis.


Decompress intestinal tract by placement of nasogastric tube.


Initiate broad-spectrum antibiotics.

Multisystem Failure in Severe Acute Mesenteric Ischemia

Cardiac (myocardial infarction, congestive heart failure, arrhythmia)


Pulmonary (respiratory failure, pneumonia, acute respiratory distress syndrome)


Liver (hepatic dysfunction)


Renal (renal failure)


Gastrointestinal (recurrent ischemia, bleeding)


Coagulation (coagulopathy)




Early diagnosis is often difficult because symptoms and signs are few, nonspecific, and unreliable and the severity of the objective findings is disproportionate to patient symptoms.

In addition, the differential diagnosis encompasses many acute abdominal processes. Definitive diagnosis is made by angiography in suspected patients presenting with sudden onset of severe, poorly localized periumbilical pain associated with fever, nausea, vomiting, and diarrhea.


Early operative treatment to reestablish blood flow by removing the embolus, bypassing the thrombosis, and resecting nonviable intestine is the key to a successful outcome. Many patients are poor surgical candidates owing to advanced age, hemodynamic instability, metabolic derangement, and sepsis. Angiography has been used as a therapeutic maneuver. Papaverine, a potent local vasodilator, can be selectively infused as a temporizing measure while surgical decisions are being deliberated.

The primary treatment of nonocclusive mesenteric ischemia is pharmacologic. Most experience has been reported with papaverine delivered by selective catheter placed by an interventional radiologist.

Preoperative Preparation.

Acute mesenteric ischemia is a true medical and surgical emergency and requires vigorous resuscitation. Patients with acute mesenteric ischemia lose substantial amounts of protein-rich fluid into the gut. Aggressive fluid resuscitation should be ongoing and guided by urine output, central venous pressure, and pulmonary artery catheter in the setting of a history of cardiac disease. Invasive blood pressure monitoring is indicated for hemodynamic instability.

The goal of fluid resuscitation is to maintain blood pressure without pharmacologic support, because many vasopressors further aggravate mesenteric ischemia. Norepinephrine and phenylephrine are particularly deleterious. Dopamine may act as a mesenteric vasodilator at low doses and produce less severe mesenteric vasoconstriction. Digitalis is also a well-recognized mesenteric vasoconstrictor. The stomach should be decompressed via nasogastric tube to promote intestinal perfusion and minimize risk of aspiration. Anticoagulation should be stopped preoperatively.

Perioperative Management.

Vigorous fluid resuscitation should be continued intraoperatively, including use of blood products and electrolyte-rich fluid. Metabolic abnormalities should be corrected and arrhythmias treated accordingly.

Sepsis is common in patients with acute mesenteric ischemia, and broad-spectrum antibiotics should be continued intraoperatively. One must be on the alert for the development of multiple organ system failure (see Table 20-9 ).

If appropriate, total parenteral nutrition should be initiated as soon as possible postoperatively. Despite aggressive surgical and medical treatment, acute mesenteric ischemia has an overall mortality rate in excess of 60%.[27]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Idiopathic pulmonary fibrosis is also known as fibrosing alveolitis, alveolocapillary block, cryptogenic fibrosing alveolitis, diffuse fibrosing alveolitis, Hamman-Rich syndrome, or interstitial diffuse pulmonary fibrosis.


The pathophysiology of idiopathic pulmonary fibrosis is not currently understood. It may represent a model of chronic dysregulated repair and lung remodeling, resulting from an epithelial/endothelial insult and persistent inflammatory cell activation.[28] The initial injury event remains undefined. However, evidence has suggested that viral infections or environmental factors may provide mediating events. Interestingly, a majority of patients with idiopathic pulmonary fibrosis have a smoking history. Current theories suggest that ongoing epithelial cell damage and/or inflammation produces abnormal mesenchymal cell activation. With activation, the phenotype of mesenchymal cells may be altered, for example from fibroblast to myofibroblast. In addition, activation of mesenchymal cells leads to enhanced matrix production and deposition. The end stage of pulmonary fibrosis is the culmination of this abnormal wound healing process involving an ongoing interaction between epithelium and mesenchymal cells.

History and Physical Findings Consistent with Diagnosis.

Symptoms associated with idiopathic pulmonary fibrosis ( Table 20-10 ) include breathlessness, fatigue, weight loss, and a chronic dry cough. On physical examination dry “Velcro” crackles may be heard throughout the lung fields. Cyanosis and clubbing may also be observed. As the disease progresses, signs of pulmonary hypertension and right-sided heart failure (loud S2 heart sound, right ventricular heave, or pedal edema) may be present.

TABLE 20-10   -- Idiopathic Pulmonary Fibrosis


Breathlessness; dry cough; weight loss; fatigue

Physical Findings

Change in shape of fingers and toenails (clubbing); cyanosis (late stages of disease); dry “Velcro” crackles throughout lung fields on auscultation

Differential Diagnosis

Pathologic distinction from other types of fibrosing interstitial pneumonia—desquamative interstitial pneumonia (respiratory bronchitis, interstitial lung disease); acute interstitial pneumonia; nonspecific interstitial pneumonia; cryptogenic organizing pneumonia (bronchiolitis obliterans, organizing pneumonia)


Pulmonary fibrosis resulting from occupational or environmental exposure—asbestosis; silicosis; farmer's lung; bird breeder's lung; exposure to metal, dust, bacteria, fumes, animals, dust, gases


Fibrosis resulting from infection—tuberculosis; pneumococcus; Pneumocystis carinii; bacterial, fungal, viral pneumonia


Drug exposure—bleomycin


Connective tissue disease—rheumatoid arthritis; systemic sclerosis




Respiratory failure; chronic hypoxemia; cor pulmonale; polycythemia; increased incidence of lung cancer

Critical Questions Influencing Patient Care

Is the patient approaching end-stage disease?


Is there a history of respiratory failure?


Is there a need for home oxygen?


Are there any signs and symptoms of chronic hypoxemia?


Is there any evidence of cor pulmonale?

Chronic Medications

Corticosteroids; cyclophosphamide (Cytoxan); oxygen; colchicine



Laboratory tests are important in making a diagnosis. A chest radiograph may show interstitial infiltrates in the lung bases. CT is more sensitive than a chest radiograph for detecting disease early. Typically, CT shows a pattern of patchy white lines in the lower lungs. In areas of more severe involvement, the thick scarring often creates a honeycombing appearance. Pulmonary function tests show a restrictive pattern. Arterial blood gas analysis may show hypoxemia with minimal exercise and, as the disease progresses, even at rest. However, the definitive test to confirm diagnosis is lung biopsy.

Differential Diagnosis.

The diagnosis of idiopathic pulmonary fibrosis should be reserved for patients with a specific type of fibrosing interstitial pneumonia known as usual interstitial pneumonia. Foremost in the differential diagnosis is to distinguish usual interstitial pneumonia from other idiopathic interstitial pneumonias. This distinction is made on a pathologic basis.[29]

Numerous other disease processes may lead to pulmonary fibrosis and should be ruled out as diagnoses. Fibroses may occur as a result of occupational or environmental exposure to toxic substances, lung infection, drug exposure, connective tissue disease, and sarcoidosis.

Comorbidities Commonly Seen with Condition.

Idiopathic pulmonary fibrosis may be associated with respiratory failure and chronic hypoxemia in the later stages of the disease. Polycythemia also occurs in this context. Cor pulmonale should be specifically sought for in evaluation of these patients. There is an increased incidence of bronchogenic carcinoma with this disease.

Critical Questions to Ask Patient and/or Primary Care Physician.

The critical questions to ask the patient and/or family doctor should be focused on determining how advanced the disease has become and how much pulmonary reserve is present (see Table 20-10 ). In appropriate patients, one should assess for the long-term complications of corticosteroid administration.

List of Chronic Medications for Condition.

At present, the therapeutic options available to treat idiopathic pulmonary fibrosis are limited (see Table 20-10 ). Many patients receive corticosteroids or immunosuppressants despite the fact that no studies have clearly documented their efficacy. The same is true of colchicine. Many patients require home oxygen.

Perioperative Considerations.

Typical surgical procedures where one may encounter idiopathic pulmonary fibrosis include open or thoracoscopic lung biopsy and lung transplantation. In these procedures, one-lung ventilation is often required. Therefore, the major anesthetic consideration is the inability to tolerate one-lung ventilation secondary to hypoxemia or the generation of high airway pressures.[30] In addition, hypercapnia may occur in these patients during one-lung ventilation.[31] An arterial catheter is indicated when anesthetizing these patients, because frequent blood gas studies may be required. In addition, central venous access should be strongly considered.

These patients may generate large negative intrathoracic pressures during spontaneous ventilation. Therefore, special care must be taken to prevent air emboli during placement of the central line. Access to inhaled nitric oxide should be available for patients with cor pulmonale.[32]

In patients with limited pulmonary reserve, regional or local anesthesia should be considered if the surgical procedure permits.


Idiopathic pulmonary fibrosis is characterized by an exaggerated fibroproliferative response, ultimately leading to the end point of pulmonary fibrosis. Symptoms associated with idiopathic pulmonary fibrosis include breathlessness, fatigue, weight loss, and a chronic dry cough. A chest radiograph may show interstitial infiltrates in the lung bases. Pulmonary function tests show a restrictive pattern. Arterial blood gas analysis may show hypoxemia with minimal exercise and, as the disease progresses, even when the person is resting. Anesthetic evaluation and plan should be focused on determining how advanced the disease has become and how much pulmonary reserve is present.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier



Polycythemia vera is a clonal stem cell disorder in which all three myeloid components are involved. Erythrocytosis is the foremost expression of the disease. Studies suggest that impaired signaling of hematopoietic growth factors may be an underlying pathophysiologic mechanism of polycythemia vera. This hypothesis is based on several findings. For instance, erythropoietin levels are lower in polycythemia vera than in any other disease, and in vitro erythroid colony formation can occur independently of erythropoietin.[33] In addition, erythroid precursors have shown both hypersensitivity to growth factors as well as increased expression of anti-apoptotic proteins.[34]

Patients with polycythemia vera are prone to both thrombotic and hemorrhagic events. The mechanisms underlying thrombotic complications may be related to the increased red cell mass.[35] An elevated hematocrit increases both blood viscosity and red cell aggregation, inducing a hypercoagulable state.[34] Hemorrhagic events are associated with elevations in the absolute platelet count. Defects in platelet function have been reported in polycythemia vera. In addition, an acquired von Willebrand's disease occurs with elevated platelet counts in myeloproliferative syndromes. This acquired von Willebrand's disease is characterized by decreased large von Willebrand multimers and increased cleavage products.[35]

History and Physical Findings Consistent with Diagnosis.

Polycythemia can evoke both general symptoms or those secondary to underlying thrombotic or hemorrhagic pathologic processes. General symptoms include bone pain and tingling or burning of the hands and feet ( Table 20-11 ). In addition, exposure to warm water may provoke an intense pruritus. Patients may initially present with ischemic or thrombotic vascular symptoms, including stroke, intermittent claudication, or angina. Signs of a bleeding diathesis can also be present, such as epistaxis or gastrointestinal bleeding.

TABLE 20-11   -- Polycythemia Vera


General: headaches, tinnitus, fatigue, shortness of breath, pruritus (aquagenic), tingling or burning of hands and feet, visual changes, bone pain, weight loss, night sweats, vertigo


Thrombotic: stroke, myocardial infarction, angina, intermittent claudication


Hemorrhagic: bleeding diathesis, gastrointestinal bleeding, unusual bleeding from minor cuts, epistaxis

Physical Findings

Splenomegaly (later stages), hepatomegaly, retinal vein engorgement, ruddy complexion, hypertension

Differential Diagnosis

Is there an underlying decrease in tissue oxygenation secondary to lung disease, high altitude, intracardiac shunt, hypoventilation syndromes, abnormal hemoglobin, smoking, or carbon monoxide poisoning?


Is there aberrant erythroprotein production secondary to tumors (brain, liver, uterus) or cysts (especially renal)?


Has hemoconcentration occurred secondary to diuretics, burns, diarrhea, or stress?

Comorbid Conditions

Hemorrhagic: gastric ulcer; epistaxis


Thrombotic: Budd-Chiari syndrome; cerebral, coronary, mesenteric, or pulmonary thrombosis


Other: gout

Critical Questions Influencing Perioperative Care

Does the patient undergo phlebotomy?


Is the patient on myelosuppressive therapy?


What is the most recent hematocrit and platelet count?


What are the results of the most recent coagulation studies?

Chronic Medications

Cytoreductive drugs including 32P


Alkylating agents (chlorambucil, busulfan)









Intraoperative Management

Ensure adequate access and availability of blood products, including platelets.


Use of regional techniques is controversial.



On physical examination a ruddy complexion or plethora may be noted. Polycythemia vera is also associated with hypertension. Patients may complain of visual changes, and retinal vein engorgement may be noted. Hepatomegaly and splenomegaly occur late in the course of the disease.

Differential Diagnosis.

Alternative conditions that should be considered when presented with a polycythemic patient include any underlying mechanism that decreases blood oxygenation. Second, aberrant erythropoietin production may cause polycythemia. Third, polycythemia may result from hemoconcentration (see Table 20-11 ).

Comorbidities Commonly Seen with the Condition.

The comorbidities observed with polycythemia vera may be of a hemorrhagic or thrombotic nature (see Table 20-11 ). In addition, gout commonly occurs in these patients.

Preoperative Preparation.

Before surgery it is important to ascertain how the elevated red cell mass has been treated, if at all. There is strong evidence that phlebotomy is the most effective remedy for the hypercoagulability observed with polycythemia vera. A recommended therapeutic end point is a hematocrit less than 42% in women and 45% in men.[36] Optimally, the hematocrit should be normalized 2 to 4 months before elective surgery. Patients who are older than 60 years or who have had a previous thrombotic episode are defined as high risk. These individuals may also receive cytoreductive treatment in an attempt to aggressively treat the disease. Perioperative risk of thrombotic or hemorrhagic events is influenced by how aggressively the polycythemia has been treated. Thus, it is important to obtain a history of the platelet counts and hematocrit values to determine past treatment of the disease.

Coagulation studies, including bleeding time, should be obtained before surgery.

Chronic Medications for Condition.

Cytoreductive agents are administered in high-risk patients. Aspirin is often used as adjunctive therapy, even in low-risk individuals. Patients with severe pruritus may be treated with interferon alfa or paroxetine (see Table 20-11 ).

Perioperative Considerations.

Uncontrolled polycythemia vera is associated with a high risk of perioperativebleeding and postoperative thrombosis. Control of the disease before surgery will reduce the incidence of these complications.

It is important to ensure adequate vascular access in case bleeding occurs. In addition, the ready availability of platelet transfusion should be ensured in larger blood loss cases. At the present time there is insufficient evidence to determine whether antiplatelet drugs are contraindicated during the perioperative management of the polycythemic patient.

The use of regional versus general anesthesia is controversial. Both techniques have been used successfully in patients with polycythemia vera. Studies suggest a lower incidence of deep vein thrombosis with regional techniques. However, this moderate effect must be weighed against the risk of epidural or subarachnoid hemorrhage in a patient who may be predisposed toward bleeding events.


Uncontrolled polycythemia vera is associated with a high risk of perioperative bleeding and postoperative thrombosis. Aggressive control of the disease before surgery will reduce the incidence of these complications.

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Copyright © 2005 Saunders, An Imprint of Elsevier


The World Health Organization has defined essential thrombocythemia as a sustained platelet count of greater than 600,000 with a bone marrow biopsy showing mainly proliferation of the megakaryocytic lineage. In addition, patients must show no evidence of polycythemia vera, chronic myeloid leukemia, idiopathic myelofibrosis, myelodysplastic syndrome, or reactive thrombocytosis.[37]


The principal feature of essential thrombocythemia is an increase in megakaryocytes and platelets. Disease pathogenesis more than likely involves alterations in the signaling pathways that regulate thrombopoiesis ( Fig. 20-1 ). Alterations in several regulatory proteins, including thrombopoietin, the thrombopoietin receptor c-Mpl, and transforming growth factor-β have been suggested as possible candidates. Currently, none of these proteins has panned out as the precise molecular mechanism behind alterations in platelet number. Other possible contributing factors may include modifications in the sensitivity of megakaryocytes to certain cytokine regulators as well as accessory cell defects.


FIGURE 20-1  Pathophysiology of essential thrombocytosis. Increased platelet production from megakaryocytes occurs as a result of several hypothesized mechanisms, including autonomous production, increased sensitivity to cytokines, decreased sensitivity to platelet-inhibiting factors, and accessory cell defects. The resulting thrombosis and hemorrhage may occur secondary to hyperaggregation, decreased platelet aggregation, decreased von Willebrand's ristocetin cofactor activity (vWF:RcoF), and decreased high-molecular-weight von Willebrand's (vWF) multimers.



The principal pathophysiologic features of essential thrombocytosis are thrombosis and hemorrhage. Thrombosis may involve the microcirculation or large vessel occlusions, predominantly of the arteries. The incidence rate is approximately 8.0% per patient year in untreated patients.[38] Hemorrhagic complications only occur with very high platelet counts and may be associated withdecreases in von Willebrand's ristocetin cofactor activity, as well as decreased high-molecular-weight von Willebrand's multimers.[39]

History and Physical Findings Consistent with Diagnosis.

Symptoms of essential thrombocythemia are associated with vasomotor changes in the cerebral and peripheral circulation. These may include headache, transient ischemic attacks, or migraines ( Table 20-12 ).

TABLE 20-12   -- Essential Thrombocythemia


Splenomegaly; digital pain that increases with heat, improves with cold; sweating; pruritus; low-grade fever; hepatomegaly; bleeding from skin, gums, nose


Vasomotor symptoms of cerebral circulation: headache; dizziness; visual disturbance; transient ischemic attacks; migraines


Vasomotor symptoms of peripheral circulation: paresthesias; acrocyanosis; erythromelalgia


Thrombotic symptoms: venous thrombotic events; superficial thrombophlebitis; deep venous thrombosis; portal or splenic venous thrombosis; major arterial thrombosis, including stroke


Hemorrhagic symptoms: bleeding diathesis, especially gastrointestinal bleeding

Differential Diagnosis

Clonal thrombocytosis: associated with other chronic myeloproliferative disorders


Reactive thrombocytosis: acute bleeding; hemolysis; iron deficiency anemia; acute and chronic inflammatory conditions such as arthritis; stress or surgery; osteoporosis; metastatic cancer; severe trauma; splenectomy; medication

Critical Questions Influencing Perioperative Care

Does the patient have a history of previous thrombosis?


Platelet count?








Any evidence of ongoing bleeding?


How has the platelet count been managed?

Chronic Medications

Cytoreductive drugs, including hydroxyurea, anagrelide, interferon-⟨, or 32P Low-dose aspirin

Perioperative Management

Platelet counts should be normalized before surgery.


Consider plateletpheresis in emergency situations to achieve a rapid decrease in platelet count.


Administer cytoreductive therapy to decrease platelet count before surgery.



The principal clinical features of essential thrombocythemia are thrombosis affecting the arterial more frequently than venous circulation and hemorrhage. Major arterial thrombosis may include both stroke and peripheral arterial occlusion. The most common presentation of bleeding involves the gastrointestinal tract, although bleeding may occur from the skin, gums, and nose.

Patients may present with splenomegaly and/or hepatomegaly secondary to extramedullary hematopoiesis. In the peripheral circulation acrocyanosis and erythromelalgia are common complaints. Erythromelalgia is characterized by burning pain and erythema of the digits, especially of the lower extremity. Of note, the pain associated with this condition increases with heat and improves with cold. Likewise, pruritus may occur in the extremities when exposed to warmth but improves with colder temperatures.

Differential Diagnosis.

In particular, two differential diagnoses should be considered when encountering a patient with essential thrombocytosis (see Table 20-12 ). First, essential thrombocytosis may represent part of a continuum of the myeloproliferative disorders. Over the course of time patients with essential thrombocytosis may develop myelofibrosis, myelodysplastic syndrome, or acute myelocytic leukemia. In addition, both polycythemia vera and myelofibrosis may present as thrombocytosis. Second, reactive thrombocytosis must be ruled out. Numerous conditions, both acute and chronic, may produce thrombocytosis.

Comorbidities Commonly Seen with Condition.

The comorbidities of interest to the anesthesiologist that occur with essential thrombocytosis are associated with the complications of hemorrhage and thrombosis.

Critical Questions to Ask Patient and/or Primary Care Physician.

One must first assess a patient's risk of thrombosis (see Table 20-12 ). Several studies have shown that the primary risk factors for a thrombotic event are history of previous thrombosis and age. Other less significant risk factors include a history of smoking and obesity. Retrospective studies have shown that the incidence of thrombotic events per year is 1.7%, 6.3%, and 15.1%, at younger than 40 years, 40 to 60 years, and older than 60 years of age, respectively.[40] In addition, the incidence rate of thrombosis has been reported at 31.4% and 3.4% per year in patients with and without a history of previousthrombosis.[40] The absolute platelet count cannot provide a definitive assessment of thrombotic risk. Thrombotic events have been reported with platelet counts in the range of 400,000 to 600,000/mm3.[41] Although the platelet count does not necessarily predict the risk of thrombosis, evidence suggests that controlling the platelet count does decrease the incidence of thrombosis. Prospective studies comparing long-term risk of thrombosis in patients treated with myelosuppressive therapy versus those without found incidence rates of 8.0% versus 1.5% per patient year in untreated and treated patients, respectively.[38]Hence, the degree of controlling the platelet count assumes importance in assessing thrombotic risk. The main risk factor for hemorrhage is a platelet count greater than 1.5 million.[36]

List of Chronic Medications for Condition.

Treatment of essential thrombocytosis consists of myelosuppressive drugs. These are administered on a chronic basis to manage the platelet count in high-risk individuals. Antiplatelet drugs may also be included in the regimen. Low-dose aspirin has been shown to be efficacious in managing both erythromelalgia and transient ischemic attacks associated with essential thrombocytosis.[42]

Perioperative Considerations.

The most important issue in perioperative management of the patient with essential thrombocythemia is whether to normalize the platelet count before surgery. There are no clear guidelines as to which patients should be aggressively normalized preoperatively, and consultation with a hematologist should be pursued. However, suffice it to say that elderly patients with consistently elevated platelet counts and a history of prior thrombosis represent a high-risk group requiring aggressive management. Elective surgical patients may have adequate time to undergo cytoreductive therapy preoperatively. In the case of urgent or emergency surgery the use of plateletpheresis may be considered.


Essential thrombocytosis is a myeloproliferative disorder characterized by chronic elevation of the platelet count. Thrombosis and hemorrhagic events are frequent with this disorder. Patients at high risk for these complications include the elderly and those with a prior history of a thrombotic event. The most important issue in perioperative management of the patient with essential thrombocythemia is whether to normalize the platelet count before surgery.

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The intrinsic characteristics of this disease include both myeloproliferation and myelofibrosis ( Fig. 20-2 ). There is tri-lineage myeloproliferation (granulocytic, erythroid, and megakaryocytic) that results from a clonal amplification of primitive progenitor cells.[43] However, the fibroblast proliferation of myelofibrosis appears to be polyclonal, suggesting that myelofibrosis is a reactive process. It is currently hypothesized that the stromal reaction of the bone marrow occurs as a result of elevations in cytokines produced by the cells involved in clonal myeloproliferation. Evidence suggests that cytokines produced by megakaryocytes and monocytes enhance fibroblast proliferation (platelet-derived growth factor, calmodulin), collagen synthesis (transforming growth factor-β), angiogenesis (vascular endothelial growth factor, basic fibroblast growth factor), and osteogenesis (transforming growth factor-β, basic fibroblast growth factor).


FIGURE 20-2  Proposed pathophysiology of myeloid metaplasia with myelofibrosis. Primitive progenitor cells undergo clonal amplification resulting in tri-lineage myeloproliferation with increases in platelets, megakaryocytes, and monocytes. Increased production of cytokines by megakaryocytes and monocytes is thought to mediate fibroblast proliferation and myelofibrosis.



Physical Findings Consistent with Diagnosis.

Myeloid metaplasia with myelofibrosis may present in a variety of ways. Constitutional symptoms may relate to the catabolic aspects of this disease and include cachexia, fatigue, weight loss, low-grade fever, and night sweats ( Table 20-13 ).

TABLE 20-13   -- Myeloid Metaplasia with Myelofibrosis


Constitutional symptoms, including weight loss, night sweats, low-grade fever

Physical Findings

Splenomegaly; anemia; pallor; petechiae and ecchymosis; gout

Findings Related to Extramedullary Hematopoiesis

Acute cardiac tamponade; hematuria; lymphadenopathy; papular skin nodes; pleural effusion; spinal cord compression

Laboratory Findings

Anemia; white blood cell count increased or decreased; platelet count increased or decreased; myelophthisis

Differential Diagnosis

Malignancies that may display bone marrow fibrosis


Essential thrombocythemia


Granulomatous involvement of bone marrow such as histoplasmosis, tuberculosis

Associated Conditions

Portal hypertension


Splenic infarction


Complications related to extramedullary hematopoiesis


Obtain complete blood cell count and platelet count


Consider cytoreductive therapy in patients without significant thrombocytopenia


Bleeding may require platelet transfusion or cryoprecipitate


Obtain disseminated intravascular coagulation panel



Extramedullary hematopoiesis may evoke a constellation of symptoms and signs. The most common presenting feature is hypersplenism. Extramedullary hematopoiesis may also occur in other organ systems such that lymphadenopathy, acute cardiac tamponade, hematuria, papular skin nodes, pleural effusion, pulmonary hypertension, and spinal cord compression may be observed. Of note, pulmonary hypertension has a poor prognosis.

Fifty to 75 percent of patients are anemic at diagnosis, whereas the white blood cell count and platelet count initially may be either increased or decreased. An early finding on peripheral blood smear is myelophthisis. Myelophthisis is characterized by teardrop-shaped red blood cells, immature granulocytes, and nucleated red cells.

Differential Diagnosis.

Several disorders are also associated with myelophthisis and possible myelofibrosis (see Table 20-13 ). Therefore, the differential diagnosis must include other malignancies such as chronic myeloid leukemia, myelodysplastic syndrome, metastatic cancer, lymphoma, Hodgkin's disease, and plasma cell dyscrasia. Granulomatous involvement of the bone marrow may cause myelofibrosis. Thus, tuberculosis and histoplasmosis must also be entertained as possible diagnoses. In patients presenting with elevated platelet counts and minimal myelofibrosis it may be difficult to exclude the diagnosis of essential thrombocythemia.

Comorbidities Commonly Seen with Condition.

The conditions commonly associated with myelofibrosis and myeloid metaplasia result from the underlying pathophysiology (see Table 20-13 ). Portal hypertension may result from either increased portal flow secondary to splenomegaly or thrombotic obstruction of small hepatic veins. The complications of extramedullary hematopoiesis have been discussed previously.

Perioperative Considerations.

The greatest experience in perioperative management of myelofibrosis and myeloid metaplasia has occurred with splenectomy. Indications for splenectomy include splenomegaly refractory to chemotherapy, portal hypertension, or progressive anemia. Morbidity and mortality after this procedure have been reported at 30.5% and 9%, respectively.[44] Significant perioperative complications after splenectomy include hemorrhage (14.8%), infection (8.5%), and thrombosis (7.5%).[44] The primary cause of death includes hemorrhage (4.5%), infection (2.7%), and thrombosis (1.3%).[44] The only preoperative variable that correlates with increased hemorrhage or thrombosis is a platelet count of less than 100,000.[44] With the above in mind, the critical information and/or interventions before surgery would include a complete blood cell count and platelet count. In patients without thrombocytopenia, prophylactic cytoreductive therapy should be considered to reduce the risk of perioperative thrombosis. Adequate blood products should be available before surgery, including access to platelets and cryoprecipitate. Occult disseminated intravascular coagulation (DIC) has been associated with perioperative bleeding.[43] Therefore, a preoperative DIC panel should be performed. Splenectomy should be postponed in patients with D-dimer levels greater than 0.5 μg/mL.[44]


The intrinsic characteristics of myeloid metaplasia with myelofibrosis include both myeloproliferation and myelofibrosis. Extramedullary hematopoiesis occurs in this disease and may evoke a constellation of symptoms, signs, and complications. The greatest experience of perioperative management of patients with myelofibrosis and myeloid metaplasia has occurred with splenectomy, where complications included hemorrhage (14.8%), infection (8.5%), and thrombosis (7.5%). Perioperative management of this disease should include careful management of the platelet count as well as attention to the ability to adequately treat hemorrhagic complications.

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