Anesthetic Considerations in the Patient With

ANESTHETIC CONSIDERATIONS IN THE PATIENT WITH

DOWN SYNDROME

Melissa A. Ehlers, M.D.

Assistant Professor of Anesthesiology

Director of Pediatric Anesthesia

Albany Medical Center

Albany, NY

Address correspondence to:

Melissa A. Ehlers, M.D.

47 New Scotland Ave.

Albany Medical Center

PO Box 131

Albany, NY 12208

(518) 262-4305

(518) 262-4736 (fax)

Learning Objectives

Appreciate commonly found disease states in the population with Down syndrome (DS)
Understand how to quickly evaluate these common diseases
Learn how to evaluate a potentially unstable cervical spine
Be aware of the significantly increased mortality from pulmonary infection in the patient with DS
Recognize common forms of congenital heart disease (CHD) in this population
Understand some of the potential complications in the patient with CHD presenting for non-cardiac surgery
Be aware of differences in determination of tracheal tube size
Decide whether endocarditis prophylaxis is necessary
Evaluate the best method of post-operative pain control

Anesthetic care of the patient with Down syndrome (also known as Trisomy 21) can present a challenge to even the most seasoned practitioner. These patients may have a wide range of serious medical problems in combination with varied ability to realize that they are sick. Unfortunately, they rarely understand why the anesthesia caregivers must poke and prod them in an effort to “make them better.” In order to provide the best possible care for them the caregiver must understand the various physical and emotional characteristics of the patient with DS and be prepared for the special challenges that they may present.

Pre-operative considerations

Frequently the preoperative screen may be the most challenging part of the entire anesthetic. The intelligence quotient (IQ) in individuals with DS ranges from 20 to 70,[1] therefore commonly little or no detailed information may be obtained from the patient. Instead, a parent, sibling, other relative or caretaker must frequently be relied upon to furnish the medical history. Because this may be incomplete or abbreviated, the anesthesia provider must keep the common disease states associated with DS in mind and attempt to rule out or further explore as many as possible (see Table 1).

Mental Retardation

The IQ usually ranges from 20 to 70 in these patients and cooperation can be difficult to obtain. This is further compounded by a 30% incidence of mental illness in the DS population2 that can make communication even more difficult. For those patients able to understand, a calm, quiet explanation of the anesthetic plan can be reassuring; appropriate use of oral or intravenous sedative premedication may make the experience much more pleasant for everyone involved. With the extremely agitated, uncooperative patient, one must occasionally resort to intramuscular or rectal sedatives in order to sedate him/her to the point where the rest of the anesthetic plan can occur smoothly and safely.

Hypo-/hyper- thyroidism

Hypothyroidism may be seen in as many as 10 to 40% of patients with DS, and this population also has a higher-than-average prevalence of hyperthyroidism.[2] Many patients will have routine screening tests for this condition, but a well-directed history may elucidate symptoms (i.e., constipation, recent weight gain, sluggishness vs. diarrhea, heat intolerance, palpitations) that warrant further workup.

Diabetes Mellitus

The prevalence of type 1 diabetes mellitus is as high as 10.6% in patients with DS.[3] These patients are often treated with once daily insulin regimens that are surprisingly efficacious when compared to diabetics without DS who are matched for other variables (i.e., duration of diabetes, sex, age). If screening for diabetes has not been done recently in the patient, a history of prolonged flu-like illness, polyuria, polyphagia, and/or weight loss should raise the suspicion of diabetes.

Obesity

Although infants with DS typically follow height and weight curves lower than those of the rest of the population, by the age of 2 to 3 years they commonly start to exhibit excessive weight gain.[4] Upon reaching adulthood, as many as 50% of individuals with DS may be overweight in spite of evidence that their caloric intake may even be reduced.[5] Obesity in these patients may contribute to worsening of pre-existing conditions (i.e., diabetes, sleep apnea, pulmonary hypertension) or may cause new health conditions unrelated to the presence of DS, such as hypertension, arthritis, and gallbladder disease. Additionally, practitioners should be cognizant of the airway, ventilatory, and positioning challenges posed by the overweight patient.

Sleep Apnea

Obstructive sleep apnea (OSA) has a reported prevalence of 54% to 100% in the population with DS compared with only 2% in the rest of the population.[6] Typical characteristics of the DS patient, which include midface hypoplasia, micrognathia, small larynx, obesity and muscular hypotonia, all predispose them to potentially significant OSA. Besides these potential causes of mechanical obstruction, there is evidence that some individuals with DS may have centrally mediated sleep apnea, perhaps secondary to an abnormal respiratory drive with hypoxic stimulation (Ondine’s curse).[7] If adenotonsillar hypertrophy is present, their removal may improve symptoms, but quite often these patients have relative hypoplasia of these structures and other surgical alternatives would include uvulopalatopharyngoplasty and/or possible partial tongue-base resection or genioglossal advancement. Nonsurgical therapy may include continuous positive airway pressure (CPAP), weight loss programs, and occasionally, medications to stimulate respiratory drive.[6] The consequences of undiagnosed/untreated OSA may include “minor” symptoms such as daytime sleepiness or behavioral difficulties, but major problems such as cor pulmonale (especially in this population which is more susceptible to pulmonary hypertension) or arrhythmias may develop. Obviously, because of the high prevalence in this population, one should assume the DS patient has OSA and try to rule it out by a history of surgical or non-surgical treatment or a negative polysomnography test. Otherwise, anesthetic preparation should include the assumption that some degree of obstruction may be encountered during most anesthetics, and pulmonary hypertension may also be present.

Otitis Media/ Hearing Loss

Patients with DS are predisposed to frequent middle ear infections and/or effusions because of abnormal eustachian tube architecture (including hypotonicity of the musculature, a decreased diameter, and abnormal cartilage). Stasis within the eustachian tube permits bacteria to migrate from the nasopharynx.[7] Recurrent infections along with an increased incidence of inner ear abnormalities (progressive ossification of the basal spiral tract, shortened organ of Corti, decreased spiral ganglion cells) all contribute to the increased incidence of hearing loss in individuals with DS which may be as high as 78%.[8] Whether presenting for middle/inner ear surgery or some other procedure, these patients may find communication even more difficult because of their hearing loss. Also, they may be more prone to post-operative nausea and vomiting if their vestibular pathways have been affected.

Gastrointestinal Disorders

Newborns with DS have up to a 12% prevalence of various gastrointestinal (GI) atresias,[1] which usually necessitate surgery within the first few days of life. Other frequent GI abnormalities include pyloric stenosis, imperforate anus, tracheo-esophageal fistula, and Hirschsprung’s Disease. In addition, patients with DS are prone to develop celiac disease (occurs in 7 to 16%[9]) that requires lifelong adherence to a special diet in order to prevent small bowel mucosal damage.

Hematologic Abnormalities

Children with DS are known to have a 10-to 20-fold increase in their risk of developing acute leukemia,[10] although it is still only found in less than 1% of individuals with DS.[1] With chemotherapy, the long-term prognosis for acute lymphocytic leukemia (ALL) is similar to that for non-DS patients, but interestingly, patients with DS have higher survival rates for the various myeloid leukemias. This has led some authors to speculate that there may be increased expression of a gene on chromosome 21 that allows improved chemosensitivity of the dysplastic cells.[11] In contrast to the increased risk of ALL, the risk of developing most solid tumors is lower in the DS population, and breast cancer is rarely seen.

Approximately 10% of newborns with DS will exhibit transient abnormal myelopoiesis (TAM) that almost always spontaneously resolves within 3 months.[12] Characteristics of this condition include megakaryocytes in peripheral blood, variable thrombocytopenia, and rare progression to hydrops fetalis or hepatic fibrosis.[13] This disorder is considered to be indistinguishable from acute megakaryocytic leukemia (AML-M7), and only its spontaneous regression points to the diagnosis of TAM. Of these patients, approximately 25% will go on to develop AML in the first four years of life, which is fatal if left untreated.[12]

Other common hematologic anomalies of the newborn with DS are thrombocytopenia and thrombocytosis.[14] Both appear to spontaneously regress, but severe or symptomatic thrombocytopenia may need to be treated with transfusion.

Atlanto-axial Instability

Up to 20 % of children with DS have radiographic evidence of atlantoaxial instability (AAI), but only approximately 1% of all patients with DS will exhibit any symptoms[15] (see Table 2).

Pre-operative evaluation of the individual with DS for AAI remains controversial. All patients should have annual neurologic exams and certainly a patient who exhibits any of the above symptoms should have neck radiographs taken. Lateral views in extension, neutral position, and flexion are termed a “Down series”[16]. A distance 4.5 mm or greater between the anterior arch of the atlas and odontoid process of the axis is regarded as potentially unstable.[17] The asymptomatic child with DS without previous screening presenting for tonsillectomy is a common workup dilemma for many practitioners. If the patient has competed in Special Olympics, screening for AAI is required before participation and any evidence of AAI should have been communicated to the caregivers. Otherwise, a brief inquiry as to any evidence of ligamentous laxity or instability elsewhere (i.e. frequent patellar dislocation, ability to fold thumb back to touch wrist) should alert one to a greater likelihood that some degree of AAI is present. Regardless, without overt neurological symptoms, it does not seem reasonable to recommend radiographs in these asymptomatic patients as long as some standard precautions are taken, such as minimal manipulation of the head for intubation (ideally one has an assistant stabilize the head/neck in the neutral position) as well as avoidance of further surgical manipulation of the head and neck whenever possible. Although many people assume that extension of the head is most compromising to the spinal cord, lateral or axial rotation can also cause damage[18] and this should be kept in mind when placing internal jugular venous lines. For those patients who already have diagnosed AAI, consideration should be given to placing a hard or soft collar perioperatively to protect the cervical spine.

Recurrent Pulmonary Infections

Numerous studies have found the lungs of patients with DS to be abnormal; grossly they exhibit a sponge-like appearance due to enlargement of alveoli and terminal bronchioles that is accompanied by a reduction in the overall number of alveoli.[19] Although some investigators feel that these abnormalities are present antenatally,[20] others have found that these differences only start to occur after birth.[21] This has led to the hypothesis that intrauterine pulmonary development may be mediated by maternal-placental factors, while post-natal development is mainly genetic in nature.[22] Another unusual feature in these patients is the presence of a double capillary network around the alveoli, a normal feature of all human fetuses, but abnormal in its persistence into adult life.[21]

Another abnormality in patients with DS is their state of relative immunodeficiency due to decreases in both cell and antibody-mediated immunity.[23] All of the above factors, combined with reduced mucociliary clearance and the presence of heart disease in many patients (which can increase interstitial fluid in the lungs, cause compression of the left-mainstem bronchus, etc.) all contribute to a mortality from respiratory infection that is 124 times greater than that of the non-DS population.[22] For this reason, the presence of any pulmonary infection in a patient with DS presenting for surgery should be treated with careful consideration, and the threshold for postponement of an elective case may be much lower than usual.

Congenital Heart Disease

Cardiac defects are recognized in 40-50% of the population with DS while alive, and in up to 66% of these patients at autopsy. Additionally, subtle abnormalities of morphology or cardiovascular function can be seen in almost everyone with DS.[24] The most common type of congenital heart disease (CHD) in this population is complete atrioventricular septal defect (cAVSD) where the lower part of the atrial septum and the upper part of the ventricular septum are missing, and there is a common atrioventricular valve that must be divided into the tricuspid and mitral valves. CAVSD has a prevalence of approximately 50-60% of all CHD cases with DS.[25] Ventricular septal defects (VSD) account for about 12%, and Tetralogy of Fallot (TOF) is the third most common being found in approximately 8% of cases. Interestingly, Chinese and Mexican DS patients are more likely to have a VSD than cAVSD suggesting that trisomy of the 21st chromosome does not by itself account for the constellation of heart diseases seen, and instead, there are other genetic and environmental factors that must be important as well.[26] Because the prevalence of CHD is so high in this population, almost all infants with DS will be evaluated at birth, preferably by a pediatric cardiologist, for the presence of heart disease. Since most forms of CHD in the population with DS involve a large left-to-right shunt (especially with CAVSD and VSDs), signs of pulmonary overcirculation develop quite quickly. For this reason, these patients tend to have repair fairly early (i.e., within the first year of life) since morphologic differences in their lung parenchyma make them much more susceptible to the development of irreversible pulmonary vascular occlusive disease.[27] Even the adult patient with DS and no history of CHD is at greater risk of acquired heart disease; mitral valve prolapse is found in 50 – 60% of these patients while valvular incompetence is seen in 17%.[2] It is of interest that coronary artery disease is much less prevalent in individuals with DS than the rest of the population. Recently, a group from the University of Vermont demonstrated that adult patients with DS have reduced plasminogen activator type-1 in their blood compared with control subjects, and they theorize that this may explain the decreased incidence of coronary plaque formation and rupture in this population.[28]-

Intraoperative Considerations

In 1957, McKusick[29] was the first person to report a hypersensitivity to atropine in the population with DS and several other authors reported similar findings. Based on these papers, pediatric manuals for many years warned of the potentially fatal effect of atropine use in these patients. Starting in 1973, however, other authors[30] have shown that there is no difference in the cardio-acceleratory effects of atropine in the patient with DS compared to the rest of the population. Interestingly, ophthalmic instillation of atropine drops does cause a more rapid mydriasis in the patient with DS but the duration and degree of papillary dilation are the same as in the patient without DS.

If the anesthetic plan includes tracheal intubation, one special consideration in the patient with DS is the appropriate size of tracheal tube (TT). This population has a higher incidence of congenital narrowing of the subglottis, and they are also more likely to develop significant subglottic stenosis following tracheal intubation.[6] In a study performed at the Children’s Hospital Medical Center in Cincinnati, Ohio, Shott[31] determined the proper size of TT in 42 children with DS compared to 32 control subjects, using an audible air leak around the TT between 10 and 30 cm of H2O pressure as the guide. In addition, the author assessed the tracheal diameter found on MRI of another 18 patients with DS. Shott’s conclusions led her to recommend that for the patient with DS, the initial intubation should be performed with a TT that is two half-sizes smaller than that normally used as determined by the standard formula TT size = 4 + age/4. Since numerous other authors have found very high rates of post-extubation croup (Kobel et al[32]) or stridor (Sherry[33]) in the population with DS, it would seem prudent to follow these recommendations.

The patient with DS and uncorrected CHD presenting for non-cardiac surgery may be intimidating for many anesthesiologists. Keeping a few simple things in mind, however, can enable one to deliver a safe anesthetic. First, one must make sure that the cardiac anatomy and the direction of any intracardiac shunts are understood. Second, if intracardiac shunts are present, one must be hypervigilant about not allowing air in the intravenous line to enter the patient as this may find its way to the left side of the heart and out into the systemic circulation to possibly cause myocardial or cerebral ischemia. Third, one must be conscious of the increased propensity in these patients to have a pulmonary hypertensive crisis that may cause a left-to-right shunt to become right-to-left, which leads to cyanosis and possibly acidosis. Immediate measures that should be taken to reverse pulmonary hypertension include increasing the PaO2 and decreasing the PaCO2 (but avoid overdistension of the lungs which can also increase pulmonary vascular resistance or PVR). In addition, one should consider administration of volume to increase preload, sodium bicarbonate to reverse any acidosis that may have developed, phenylephrine to increase the systemic vascular resistance (SVR), or opioids to reduce sympathetic outflow to the pulmonary bed (care must be taken as this may decrease the SVR as well). Table 3 shows a more comprehensive list of common causes of an increase in the PVR, and methods of treatment. Finally, one must not forget to administer subacute bacterial endocarditis (SBE) prophylaxis when indicated (see Table 4).