Downs syndrome (DS) was described in 1866by John Langdon Down, an English physician.He gave the condition the name mongolism,as he noted the similarities in physical charac-teristics he saw in institutionalised patients tothose of the Mongolian race. Since the early1960s, the syndrome has taken his name inrecognition of this first description. In 1959, thelink to a trisomy of chromosome 21 was identi-fied by Lejeune. Subsequently, it has beenestablished that 95% of people with DS havetrisomy 21, the remainder are associated with achromosomal translocation (4%) or mosaic tri-somy 21 (1%). The syndrome is the most com-mon chromosomal disorder, occurring inapproximately 1 in 700 live births. There is awell-recognised exponential increase in incid-ence with maternal age (1 in 1400 at 25 yearsold, 1 in 46 at 45 years old).

Fifty years ago, the life expectancy of men andwomen with DS was 9 years of age, 53% dying

in the first year of life. Today, 1-year survival is90% or more and 45% survive to 60 years old.This increase is predominantly due to improve-ment in surgical techniques and more aggressivetreatment of life-threatening anomalies. Withincreasing surgical interventions and lifeexpectancy, it is likely that anaesthetists willencounter patients with DS more frequently.

DS is a condition that affects many of theorgan systems. In this review, we shall considerthe congenital defects and pathological condi-tions which are associated with DS with specialreference to anaesthetic implications.

General appearancePatients with DS have a characteristic appear-ance which may lead to diagnosis at birth. Themost common features include brachycephaly, aflat nasal bridge, epicanthic folds, upwardlyslanting palpebral fissures, small mouth and ears,and a single transverse (Simian) palmar crease.

Neonates tend to be of low birth weight (20%less than 2500 g). Towards the end of infancy,they frequently start to develop obesity, a trendthat continues through their adult life. They tendto be of short stature and this may be compound-ed by chronic disease and social conditions.Institutionalised patients have been shown to besmaller than non-institutionalised patients.Anaesthetists need to consider weight and sizewhen calculating drug dosages and size of equip-ment used.

Respiratory involvementThe respiratory tract abnormalities may leadto a higher risk of peri-operative respiratorycomplications. Craniofacial anomalies lead toan incidence of obstructive sleep apnoea of5075%. Macroglossia, a narrow midface,oropharyngeal hypotonia, micrognathia, small

Downs syndromeJules E Allt MBChB FRCA

Charlotte J Howell MBBChir MA FRCA

83British Journal of Anaesthesia | CEPD Reviews | Volume 3 Number 3 2003

The Board of Management and Trustees of the British Journal of Anaesthesia 2003

Key points

Downs syndrome can beassociated with anom-alies in most organ sys-tems.

There is a high incidenceof upper airway compli-cations after surgery.

Congenital heart diseaseis very common.

There is a relatively highincidence of cervicalspine instability. Patientswho were previouslyasymptomatic, may devel-op symptoms of spinalcord compression post-operatively.

Peri-operative agitation iscommon, particularly inthe immediate postoper-ative period.

Jules E Allt MBChB FRCA

Specialist Registrar Anaesthetist,Stoke School of Anaesthesia,

Newcastle Road,Stoke on Trent ST4 6QG

Charlotte J Howell MBBChir MAFRCA

Consultant Anaesthetist,Department of Anaesthesia, NorthStaffordshire Hospital (NHS) Trust,

Newcastle Road,Stoke on Trent ST4 6QG

Tel: 01782 552484Fax: 01782 710936

E-mail: charlotte@kogs.freeserve.co.uk(for correspondence)

Table 1 Clinical features of Downs syndrome of par-ticular importance to the anaesthetist

General Low birth weightObesity in childhood through adult lifeShort stature

Respiratory Obstructive sleep apnoeaSubglottic and tracheal stenosisLower respiratory tract infection

Cardiovascular Congenital heart diseasePulmonary hypertensionValvular heart disease

Neurological Neonatal hypotoniaIntellectual impairmentPostoperative agitationAlzheimers diseaseEpilepsy

Spinal disease Atlanto-axial instabilityAtlanto-occipital instabilityCervical spondylitis

Gastrointestinal Gastro-oesophageal refluxGastrointestinal atresias

Endocrine Hypothyroidism

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mouth, short neck and adenotonisillar hypertrophy all con-tribute to difficulties and there is also dysfunction of the cen-tral ventilatory drive. Upper airway obstruction worsens inthe presence of central nervous system depressant drugs andthis may be a problem in the postoperative period. Childrenwith DS frequently undergo adenotonsillectomy to improvesymptoms.

The anatomical features of the face and upper airway wouldlead one to expect difficulties with intubation. However, in prac-tice, there is rarely a problem, probably because of hypotonia andligamentous laxity around the temporomandibular joint and neck.

Subglottic or tracheal stenosis is seen in 26% of patients.One percent of DS patients have congenital subglottic steno-sis, which may present at birth if severe. However, most areasymptomatic for the first few months of life. The condition maybe under-diagnosed, as symptoms may be incorrectly attributedto cardiac disease. It may present at the time of assessment forsurgery, during intubation or during sedation for investigations. Ahistory of stridor, wheezing, recurrent pneumonia, a previouslydifficult intubation, cyanotic episodes or high ventilatory pres-sures should arouse suspicion.

A smaller endotracheal tube should be chosen initially inDS patients than would otherwise be chosen for age, not onlybecause of potential subglottic stenosis but also because thesepatients tend to be of shorter stature and have smaller airways.In a retrospective review of 100 DS patients, 23% required anendotracheal tube whose internal diameter was 12 mmsmaller than expected for age. A tube that is too large willcause airway oedema and obstruction. In two studies after car-diac surgery, 33% and 38% of children developed stridor,compared with 1.9% in a series of normal children. Therefore,when selecting an endotracheal tube, it is appropriate tochoose a tube with an internal diameter 1 mm less thanexpected for age and listen for an audible leak with positivepressure ventilation. A leak-test is more important than gener-al guidelines because of inter-individual variability.

Chronic lower respiratory tract infection is common in the DSpopulation; their respiratory system should be examined care-fully prior to surgery. Decreased immunity, gastro-oesophagealreflux and hypotonia are all contributory factors. For the samereasons, postoperative chest infections are common.

Cardiovascular involvement

There is a well-recognised association between DS and congen-ital heart disease (1660%). The commonest are atrioventricular

canal defects, atrial septal defects, ventricular septal defects,patent ductus arteriosus and tetralogy of Fallot. All, except thelatter, involve a left-to-right shunt, causing increased pul-monary blood flow and pulmonary vascular disease. Patientswith DS develop pulmonary hypertension to a greater severi-ty and at an earlier age than non-DS patients with similar car-diac lesions. Various mechanisms for this have been suggest-ed, including chronic hypoxia (secondary to chronic infection,hypoventilation, obstructive sleep apnoea syndrome and pul-monary hypoplasia) and a defect of pulmonary capillaries.Pulmonary hypertension has been reported in patients withDS in the absence of cardiac disease.

The degree of cardiac disease strongly influences long-termmorbidity and mortality. In the past, there has been a reluc-tance to operate on children with DS. More recent results sug-gest that patients with cardiac lesions that undergo surgeryhave broadly similar mortality rates to those patients withsimilar cardiac lesions without DS and those that do notundergo surgical repair have significantly worse cardiac mor-bidity and mortality than those that do. Furthermore, patientswith anomalies involving connections between pulmonaryand systemic circulations have been shown to develop pro-gressive pulmonary vascular disease and Eisenmengershaemodynamics at an early stage of life if corrective surgeryis not performed. It is therefore common now for children(preferably under 6 months of age) with DS to undergo car-diac evaluation. Echocardiography is the most sensitive andspecific investigation.

Cardiac conduction defects may be present following repairof atrioventricular canal and ventricular septal defects andrepair of tetralogy of Fallot. These patients may be receivingpharmacological therapy for dysrrhythmias, or have a perma-nent pacemaker fitted. There is some evidence that adult DSpatients may develop aortic regurgitation and mitral valveprolapse. Patients presenting for surgery in this age groupshould be considered for echocardiography if no recent car-diac evaluation has been performed. Patients with prostheticvalves or valvular pathology should receive appropriateantibiotic prophylaxis for endocarditis prior to surgery.

Anaesthetists in tertiary cardiac centres will frequentlyencounter DS patients for corrective surgery. However,patients with corrected cardiac disease, older patients whohave not undergone corrective surgery, and some youngerpatients with undiagnosed cardiac disease, will be encoun-tered in non-cardiac practice. Therefore an understanding of,and vigilance for, these conditions is important.

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Neurological involvementDS is an important cause of neonatal hypotonia. Generalised hypo-tonia and laxity of joint ligaments mean extra care must be takenwhen positioning patients under general anaesthesia to avoidperipheral nerve damage.

DS is associated with intellectual impairment (IQ 2080).Learning difficulty may be compounded by poor social circum-stances, institutionalisation and sensory deficits. It is well knownthat patients with DS are generally calm and good-natured.However, a significant proportion become markedly agitated in theimmediate postoperative period, frequently requiring sedation.This agitation may jeopardise intravenous lines and dressings oreven spinal fixation devices. Sedation and opiates carry their ownrisks in the context of upper airway obstruction as already dis-cussed. These problems are familiar to paediatric anaesthetists butmay be overlooked by those more accustomed to adult patients.Close postoperative observation and sedation may require pre-operative planning of high-dependency care for types of surgerywhere patients would normally return to a general ward.

Much interest has surrounded the frequent development ofAlzheimers dementia in patients with DS at a young age. Studieshave suggested a gene-dosage effect of amyloid-coding genes locat-ed on chromosome 21. Epilepsy occurs in about 10% of the DSpopulation; it is usually related to other complications of the syn-drome. Therefore, patients may present for surgery taking anticon-vulsant medication. Patients with DS appear to require a lower min-imum alveolar concentration of volatile anaesthetic agents, possiblysecondary to decreased central catecholamine concentrations.

Sensory involvement

Ocular and acoustic impairment is common and may make com-munication with the patient more difficult. Ocular manifestations,such as squints or congenital and acquired cataracts, are commonreasons for surgery in patients with DS. Severe refractive errorsoccur in 50% of patients and glaucoma is more frequent than in thenon-DS population. Craniofacial anomalies may lead to hearingdeficits. Patients have smaller Eustachian tubes which tend to col-lapse and cause middle ear effusions. Sixty-five percent of DSchildren require tympanotomy and ventilation tubes. Accum-ulation of ear wax (due to narrow ear canals) is frequent and cancontribute to the degree of conductive deafness.

Gastrointestinal involvementPatients with DS may suffer from gastro-oesophageal reflux,which may in itself be a contributory factor to acute andchronic respiratory disease. Reflux may also increase the risks

of peri-operative aspiration of gastric contents. Therefore, appro-priate precautions should be considered.

Gastrointestinal anomalies occur in 7% of patients. Surgery maybe needed in the neonatal period for intestinal obstruction.Gastrointestinal atresias, particularly of the duodenum and oesoph-agus, are strongly associated with DS. Hirschprungs disease maypresent with intestinal obstruction, colonic perforation or entero-colitis in the neonatal period or with constipation in older children.The incidence of gallstones in children is increased (4.7% com-pared with 0.2%). Ceoliac disease is also more common.

Immunological involvementPatients with DS are prone to infection, especially of the res-piratory tract. Associated congenital defects of the respiratory,gastrointestinal and cardiovascular systems may contribute tothe incidence as may institutional care or poor social condi-tions. However, immune system dysfunction is also commonwith abnormalities of T cells, B cells, gamma globulins andneutrophil function. Patients may have received pneumococ-cal vaccine. Historically, the incidence of hepatitis B is greaterin the DS population. Thus, the anaesthetist should take allprecautions to reduce the risk of transmission of infection.

Haematological involvementNeonates with DS are prone to polycythaemia with haematocritvalues above 70%. There is a 1020-fold increased risk ofleukaemia with greater risk in patients under 5 years of age. By theage of 30 years, the cumulative risk is 2.7%. The risk is particular-ly high for acute myeloid leukaemias, particularly the normallyrare megakaryoblastic form. The markedly increased risk ofleukaemias has suggested that leukaemogenic genes may be locat-ed on chromosome 21. Neonates may develop transient abnormalmyelopoesis, a condition whereby leukaemic features developwhich spontaneously resolve. However, it may be associated withdevelopment of leukaemia later in life. It has also been reportedthat lymphomas occur more frequently. Historically, patients withleukaemia and DS were not subjected to intensive chemotherapy,possibly because of concerns regarding cardiac toxicity ofchemotherapeutic agents, or the effects of therapy on an alreadyimmunosuppressed population. However, in recent years studieshave suggested a good response to intensive therapy, possibly bet-ter than in the non-DS population.

Studies have shown that the risk of solid non-haematologicaltumours to be lower than in non-DS patients, possibly because ofa gene-dosage effect of tumour-suppressor genes located on chro-mosome 21.

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Endocrine involvementThere is a well-recognised association between DS and endocrinedisease, particularly thyroid. Congenital hypothyroidism occurs 30times more frequently. Hypothyroidism without thyroid antibodiesoccurs commonly in childhood, possibly due to an inadequategland size. In adolescent and older people with DS, thyroid anti-bodies become common, causing both hypothyroidism and hyper-thyroidism. Hypothyroidism has been reported in adult DS patientswith a widely varying incidence (354%). Insulin-dependent dia-betes mellitus occurs more frequently also.

Spinal diseaseThe high incidence of atlanto-axial instability (AAI) in DS has gen-erated much discussion in the literature. Asymptomatic AAI isfound in 1020% of children when screened. Symptomatic AAI isfound in 1.5%.

The are several causes of AAI. The transverse ligaments, whichhold the odontoid peg to the anterior arch of the atlas, are lax, prob-ably as part of the generalised ligamentous laxity seen in DS. Bonyanomalies, in particular malformation of the odontoid peg, are alsothought to contribute to AAI. Excessive movement of spinal verte-brae in these patients can lead to compression of the spinal cord inthe spinal foramen. The possibility of neurological trauma inpatients with AAI has led to the introduction of the SpecialOlympics Radiological Screening Program, supported by theAmerican Academy of Pediatrics. The program consists of lateralneutral, flexion and extension views of the cervical spine obtainedbetween the ages of 2 and 5 years. DS children with abnormal radi-ographs are excluded from sports considered as high risk. The pro-gram uses an upper limit of 4.0 mm between the odontoid peg andthe anterior arch of the atlas, although other sources suggest anupper limit of 4.5 mm. The radiographic appearances can changeover time. In a follow-up study 36 years after the first set of radi-ographic investigations, 20% of those with abnormal radiographshad normal radiographs, whilst only 7% progressed from a normalto an abnormal appearance. Other studies have supported thisimprovement in radiographic appearance over time, probablybecause of tightening of lax ligaments with age.

The use of radiographic investigation for AAI in DS has been atopic of much debate. Some studies have suggested that radi-ographic appearances are unreliable, possibly due to inadequateflexion during the investigation, whilst others have shown consis-tent results. There is little firm evidence that DS patients withasymptomatic AAI go on to develop symptoms of spinal cord com-pression. There is a distinction between acute and chronic sympto-matic disease. Patients with normal radiographs have developed

acute neurological symptoms after trauma and anaesthesia. Otherpatients may develop progressive disease. Case reports exist ofpatients who have developed acute disease after surgery who retro-spectively had unrecognised chronic disease. The consensus is thatsymptoms of spinal cord compression prior to surgery are the bestpredictive factor of poor postoperative neurological outcome. Spinabifida of the atlas and atlanto-occipital instability also occur withincreased frequency in DS.

An unstable spine should be considered for surgical fixationprior to other surgery. Care should be taken with neck movementand positioning in any DS patient, even those with normal radi-ographic investigations. Hypotension should be avoided in order topreserve spinal cord perfusion. Postoperatively, any new neurolog-ical abnormalities should be promptly investigated.

Other cervical spine abnormalities seen in DS include cervicalspondylosis; one study found an incidence of 70% by 40 years ofage. Cervical spine ankylosis (Klippel-Feil syndrome) is one of therarer cervical spine abnormalities seen in DS, the presence of whichshould lead to anticipated difficulties with performing laryngoscopy.

Response to atropineA possible sensitivity to atropine has generated much discussionsince it was first reported in the 1950s. Increased magnitude andduration of pupillary dilatation to ocular atropine and excessiveheart rate response to parenteral atropine have been reported,although the latter has not been supported by subsequent studies. Ithas been suggested that the former is caused by a structural anom-aly of the iris of patients with DS. There is a case report of paralyt-ic ileus in a DS child undergoing treatment with ocular atropinewhich resolved on cessation of the drug.

Atropine may be advantageous for two reasons. First, the chrono-tropic effects of atropine might be useful in the presence of low plas-ma catecholamine concentrations. Second, its antisialogogue effectsmay attenuate the frequent peri-operative respiratory complications.

The general consensus is that the perceived sensitivity toatropine may be erroneous, or at least of little clinical significanceand atropine may be a useful drug for this group of patients.

Key referencesAmerican Academy of Pediatrics,Committee on Sports Medicine.Atlantoaxial

instability in Down syndrome: subject review. Pediatrics 1995; 96: 1514

Aquino A, Domini M, Rossi C, Sardella L, Palka G, Chiesa PL. Correlationbetween Downs syndrome and malformations of pediatric surgical inter-est. J Pediatr Surg 1998; 33: 13802

Shott SR. Down syndrome: analysis of airway size and a guide for appropriateintubation. Laryngoscope 2000; 110: 58592

The Downs Syndrome Medical Interest Group.

See multiple choice questions 6163.

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