CVS Mitral valve Dysrhythmias
prolapse/regurgitation Bacterial endocarditis prophylaxis
Proximal aortic dilatation Rupture
Associated conditions include atrial septal defect, Tetralogy of Fallot, ureteropelvic anomalies and other cardiac anomalies.
IV Â¼ intravenous; GIT Â¼ gastrointestinal tract; CVS Â¼ cardiovascular system
connective tissue in skin, ligaments, tendons, and bone. The exact ruptured viscera (especially gastrointestinal tract), cervical incom-
biochemical abnormality differs in the various subgroups. petence, uterine prolapse, APH, PROM, lacerations of birth canal,
and postpartum hemorrhage (PPH).130,133,134 Other studies have
Mutations occur in the structural genes for type 1 (arthrochalasis
EDS), type 3 (vascular EDS), and type 5 collagen (classical EDS) or identified increased fetal risks including prematurity, IUGR, and
abnormal presentation.130,135 The increased risk of prematurity
in genes involved in protein modification of type 1 collagen
(kyphoscoliotic and dermatosparaxis EDS).124 Depending on the may be related to cervical incompetence or PROM. If the fetus is
type of EDS, these molecular lesions are associated with weakness affected by EDS, one would expect an increased frequency of
of the supporting structure of skin, joints, arteries, and visceral PROM as the membranes are of fetal origin. Possible reasons for
organs (see Table 8.18). increased malpresentation include increased joint laxity and
reduced muscle tone in the fetus affected with EDS.
The treatment of preterm labor in parturients with EDS is con-
Pregnancy and EDS
troversial but beta-mimetic tocolytics should probably be
Numerous reports of complications during pregnancy in women avoided in patients with type IV EDS following a case report of
fatal myocardial infarction and coronary artery dissection.136
with EDS have appeared in the literature. Unfortunately, many of
these reports are anecdotal and the subgroup of EDS not reported. Both vaginal delivery and C/S carry additional risks in these
The complications of pregnancy and delivery are clearly related to patients. Most clinicians prefer a vaginal birth in the majority of
the subgroup of EDS involved, although publication bias occurs in cases, and C/S for those with type IV EDS. It is difficult to provide
those patients where complications arise. For women with vascular dogmatic recommendations on the management of delivery due
EDS, (and occasionally in classical EDS), pregnancy may precipitate to the protean manifestations of this disease and differences in
serious internal complications, including spontaneous rupture of subgroups of EDS and individual presentations. However, forcep
arteries and veins, cardiac valve prolapse, perforation of the colon, deliveries are considered risky, because bladder and vaginal avul-
aortic dissection, pneumothorax, and uterine rupture.127,128,129 Early sion have occurred following their use. Vacuum extraction is
delivery (32 weeksâ€™ gestation), or termination prior to 16 weeksâ€™ thought to carry less risk of perineal injury, although there are
gestation, in type IV EDS has been recommended since this sub- concerns over an increased risk of cephalohematomas if the fetus
group of women has a high maternal mortality (20%).129,130 Death is affected by the disease.
occurs from uterine rupture or rupture of a major blood vessel (aorta
or vena cava). However, other reports have not described lethal
EDS and anesthesia
complications from EDS during pregnancy.127,131,132
Other potential complications of pregnancy related to EDS The choice of anesthetic technique will depend on the organs
include spontaneous abortion, symphysis pubis dysfunction, involved, as some types of the disease are innocuous, whereas
others are potentially lethal. A past or family history of visceral/
Table 8.19 Obstetric anesthetic checklist for Ehlers-Danlos
vessel rupture or excessive perioperative bleeding may alert the
anesthesiologist to potential ominous complications. It is useful
to characterize the type of EDS so that a more accurate prediction 1. Genetic assessment for severity and type of disease
of possible problems can be made. Adequate assessment of 2. Careful preoperative assessment (particularly cardiac and bleeding
coagulation status and cardiovascular function is important. tendency)
Cardiac problems associated with EDS include valvular disease, 3. Exclude concomitant coagulopathy
congenital heart disease, and conduction defects. In addition, 4. Ensure blood available for transfusion if needed
coronary artery disease and myocardial infarction have been 5. Ensure adequate intravenous access
described in association with type IV EDS.137 Price and collea- 6. Careful cannulations/intubation
gues138 reported a case of myocardial ischemia, without prior 7. Careful insertion of spinal/epidural (if not contraindicated)
symptoms, in a 38-year-old woman with type IV EDS, during 8. Maintenance of low airway pressure to reduce risk of
combined general and regional anesthesia for abdominal aortic pneumothorax
aneurysm repair. Evaluation of the EKG may be difficult in these 9. Avoid hypertension, which may result in the rupture of occult
patients due to the associated congenital cardiac abnormalities. aneurysm
However, appropriate investigations should be performed. Cardiac 10. Ready availability of methods of uterine contraction (oxytocin,
catheterization may be hazardous due to friable arteries, which ergotamine, prostaglandin) especially for cesarean section
makes hemorrhage at the entry site a real concern. Stress echocar-
diogram and thallium scans may be the investigations of choice.
Before induction of anesthesia, patients should have adequate Although SAB with a small-gauge needle minimizes the risk of
i.v. access, remembering that cannulation of all vessels (arterial bleeding within the epidural space, surgery for C/S in these
and venous) may be complicated by the absence of any sensation patients may be protracted due to difficulty in securing hemo-
stasis. Brighouse and Guard140 reported a case of pregnancy in a
of the needle and the cannula traversing the vessel wall. All
cannulations and intubations should be performed with care to woman with EDS type IV, who produced virtually no type III
avoid trauma and hematoma formation, and cannulation sites collagen. There were no bleeding problems prior to pregnancy,
should be reviewed regularly to avoid extravasation. A history of although abdominal pain in the third trimester was thought to be
excessive bleeding is an indication for coagulation evaluation. due to bleeding into the hepatic and splenic capsules. After
â€˜â€˜Easy bruisingâ€™â€™ to a variable degree is seen in all subgroups of obtaining a normal coagulation screen and full discussion of
EDS, and can be explained by capillary fragility. Fragility of risks and benefits of GA versus regional anesthesia, the patient
medium- and large-sized arteries and veins is also typically seen consented to be awake during C/S. A CSE was used and the
in the vascular subgroup of EDS and occasionally in the kypho- perioperative period was uncomplicated. The authors argued
scoliotic subgroup. Increased bleeding is largely due to a con- that a CSE offers a rapid, reliable block with the benefit of pro-
nective tissue defect in the capillary wall, in addition to longed anesthesia should protracted surgery occur.
contributory effects from lack of a tamponade effect from the When GA is undertaken, particular emphasis should be placed
surrounding tissues. Hematologic studies, including evaluation on careful, atraumatic intubation (to avoid oral/tracheal trauma
of clotting factors, platelet aggregation, and bleeding time, are and cervical injury), padding of areas vulnerable to pressure
usually normal in EDS patients. One exception is the Hess test, effects (to avoid injury to tissues), avoidance of sudden hyper-
which may be abnormal, indicating increased capillary fragility. tensive episodes (to prevent rupture in major vessels), and
Increased bleeding may be compounded by a clotting factor maintenance of low airway pressure (spontaneous pneumothorax
deficiency and platelet abnormalities in some patients.139 The due to ruptured cysts has been reported).141
use of ascorbic acid (a cofactor for crosslinking of collagen fibrils)
and deamino-8-D arginine vasopressin (DDAVP) may ameliorate
the bleeding tendency in some patients.
Although only a dilemma in type IV patients, one still has to Osteogenesis imperfecta (OI) or â€˜â€˜brittle bone diseaseâ€™â€™ is a rare
consider the appropriateness of regional anesthesia in each indivi- inherited connective tissue disorder with a variable clinical spec-
dual patient. However, if there were a history of prior bleeding trum of disease severity. The underlying condition involves osteo-
problems, such as prolonged epistaxis or excessive bleeding after penia with primary defects in the protein matrix of bone and other
dental extraction, I would personally prefer not to insert an epi- connective tissue. Bone fragility, resulting in an increased risk of
dural. The risk of epidural hematoma and neurologic complica- fractures, is the hallmark of the disease. The incidence of OI is
tions are likely to be higher due to rupture of vessels from approximately one per 20 000 births although this may be an
hypertensive responses to painful stimuli. Sudden increases in underestimation due to the occurrence of milder forms of the
disease.147 Clinical manifestations of OI include excessive bone
arterial pressure should be avoided and consideration given to
the use of antihypertensive therapy to avoid vessel wall rupture. fragility with predisposition to fracture, short stature, scoliosis,
Obstetric anesthetic implications are discussed in several case triangular facial configuration (large vault, small jaw), cervical
reports with the majority of reported cases occurring in the classi- and basilar skull deformities, hearing loss, blue sclerae (decreased
cal and vascular forms of EDS (see Table 8.19).140,141,142,143,144,145,146 collagen content results in pigmented choroid becoming visible),
2 Musculoskeletal disorders
dentinogenesis imperfecta, predisposition to bruising, and
Table 8.20 Classification of osteogenesis imperfecta increased laxity of other connective tissue (skin, ligaments, heart
valves). Osteogenesis imperfecta is classified into seven different
Type Effects Inheritence Manifestations
subgroups, although the major entities are groups Iâ€“IV (see
I Mild AD Variable bone fragility
Table 8.20).148 There is significant clinical variability within each
subgroup. Type I is the commonest form of the disease and occurs
in the majority of reported parturients. Diagnosis is made on
clinical grounds and family history. Although definitive laboratory
tests are currently unavailable, the analysis of type I collagen genes
may be useful. Treatment normally involves a multidisciplinary
Presenile hearing loss
approach in order to maximize functional capacity, in addition to
minimizing fracture rates, deformity, and chronic pain.
II Lethal AD/AR Death in utero or in
Fertility in patients with type 1 (mild) OI is unaffected by the
Multiple fractures at
disease. Musculoskeletal problems, particularly back pain, is com-
mon in parturients with OI and may be the result of pregnancy-
induced joint laxity.149 Genetic counseling and prenatal diagnosis
should be offered to all affected mothers. Antenatal diagnosis
involves a detailed anomaly scan together with biochemical ana-
III Progressively AD/AR Severe but variable
lysis obtained from chorionic villus sampling. Controversy exists
deforming bone fragility
regarding optimal delivery mode in these patients. Previous
Severe deformities of
recommendations have been based on limited numbers of case
reports. Labor and vaginal delivery is of concern due to a specu-
lated risk of maternal pelvic fractures and fractures in an affected
fetus.150,151 However, Cubert and coworkers152 reviewed 167 preg-
nancies in patients with OI and found that C/S did not result in a
reduced fracture rate at birth in infants with nonlethal forms of the
disease, nor did it prolong survival for those with lethal forms. A
White or blue sclerae
high rate of breech presentation was noted and hypothesized to be
IV Moderateâ€“ AD Variable skeletal
related to abnormal uterine accommodation of the affected fetus
severely deformity and
(with disproportionately large head, short extremities, and poss-
ible fracture deformities). Individual patients should be evaluated
to determine the safest mode of delivery. Cesarean section may be
less severe than III
necessary for those with crippling skeletal deformities or severe
White sclerae but may
fetal deformities and absolute cephalopelvic disproportion.
be blue in
However, if vaginal delivery is chosen, trauma from instrumenta-
tion should be minimized in order to avoid fetal injury. Case
V Moderately AD Moderate bone
reports have highlighted the risk of uterine rupture and PPH in
affected patients.151,153 Di Lieto and coworkers found a dimin-
Mild to moderate
ished collagen content in the uterine myometrium of a patient
with type I OI compared with normal controls.154 They postulated
that the underlying myometrial biochemical modifications were
VI Moderateâ€“ Unknown Moderate bone
responsible for the increased risk of uterine rupture. To minimize
the risk of PPH, an oxytocin infusion should be commenced after
deforming Mild to moderate
delivery to keep the uterus contracted. Osteoporosis accelerated
by pregnancy and later by breast feeding may potentially increase
the risk of fractures during pregnancy or in the early postpartum
VII Moderately AR Moderate bone
period. Calcium and vitamin D supplementation are important
There have been several reports describing the successful use of
AD Â¼ autosomal dominant; AR Â¼ autosomal recessive
general,155,156 epidural,155,157 and spinal157,158 anesthesia for C/S
Table 8.21 Osteogenesis imperfecta and anesthetic implications
Organ Dysfunction Anesthetic/surgical implication
Musculoskeletal Bone fragility Care with handling patient, protection of pressure areas during
Care with use of tourniquet
Avoid use of automated BP devices in severe OI
Use manual BP devices or invasive monitoring
Kyphoscoliosis (due to joint hyperdistensibility and Possible neurological deficit (from nerve compression)
vertebral collapse) Regionals â€“ technically difficult, unpredictable spread
Reduced respiratory reserve
Fragile cervical spine/airway/teeth Avoidance of trauma to cervical spine/jaw/teeth during
intubation, fiberoptic intubation may be necessary
Cervical instability (odontoid hypoplasia) Fiberoptic intubation may be necessary
Chest wall deformities (from previous fractures) Reduced respiratory reserve
Hematologic Predisposition to bleeding (possible quantitative/ Spinal hematoma risk
qualitative platelet abnormality, vessel fragility) Increased risk of perioperative hemorrhage
Thyroid Hyperthyroidism (40%) Awareness and correction of thyroid function
Cardiovascular Aortic incompetence, aortic root widening, mitral Dysrhythmias, bacterial endocarditis prophylaxis, rupture
Auditory Deafness Communication problems
Cellular metabolism Probable deranged cellular energy metabolism Intraoperative temperature monitoring, ETCO2 monitoring
(? hypermetabolic state â€“ hyperthermia during GA)
BP Â¼ blood pressure; OI Â¼ osteogenesis imperfecta; GA Â¼ general anesthesia
in patients with OI. Early antenatal assessment is important in Regional anesthesia may be challenging due to kyphoscoliosis,
order that appropriate analgesic and anesthetic methods are dis- short stature, and problems positioning patients with fracture
deformities. Hathaway and Solomons160 found platelet adhesion
cussed. Clinicians should be aware of possible anesthetic and
surgical implications of the disease (see Table 8.21). Particular abnormalities in some patients with OI. Before regional techni-
concerns to the anesthesiologist include patient fragility, airway ques, coagulation and platelet studies should be performed in
abnormalities, vertebral-column abnormalities, and bleeding patients with a history of bleeding tendency. A thromboelasto-
predisposition. Clearly, care should be taken when transferring gram may be useful to provide a rapid global assessment of
and positioning patients, although degree of patient fragility is coagulation. Parturients undergoing operative procedure should
variable and some patients have a much greater risk of injury. have blood â€˜â€˜typed and savedâ€™â€™ or crossmatched prior to surgery.
Vogel and colleagues155 argue that titrated spinal anesthesia may
Tourniquets should be used cautiously and automatic blood-
pressure cuffs avoided due to excessive inflation, especially dur- be easier in patients with severe scoliosis, and that incremental
ing the initial reading. Manual blood pressure measurement or spinal anesthesia (via a subarachnoid catheter) avoids unpredict-
the use of invasive monitoring may be less traumatic. able spread and diminishes the risk of an unintentionally high
Airway examination is important to establish any potential block in patients with limited respiratory reserve. A titrated epi-
difficulty with intubation. Shortened cervical vertebrae, mal- dural or CSE would be suitable alternatives.
formed teeth, micrognathia, and previous fracture deformities
have all been described in these patients.150,155,156 If GA is con-
templated, tracheal intubation should be secured with minimal
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