CHALLENGES IN CLINICAL PRACTICE
| ECTOPIC PREGNANCY: A MEDICAL DISEASE —John E. Buster, MD, Professor of Obstetrics and
Gynecology, Baylor College of Medicine, Houston
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| General considerations: ectopic pregnancy no longer always surgical disease; difficult to predict; presents
with pain, discomfort, and missed menses; outcome usually benign; unruptured ectopic pregnancy
should not be surgical disease
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| Factors contributing to rupture: biologic aggressiveness—data show significant number of ectopic pregnancies
that rupture euploid; euploid ectopic pregnancy distinguished by rapid increase in beta human
chorionic gonadotropin ( β-hCG) and lack of response to methotrexate; location—abortion or resorption
occurs more often if ectopic implants in distal portion of fallopian tube; more serious if in isthmic or cornual
portion of tube
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| Management: goals—diagnosis, treatment, and resolution before symptoms occur; methotrexate first-line
therapy; treatment before rupture prevents hemorrhage, optimizes fertility, and minimizes health care
costs; early diagnosis using serial hCG, transvaginal ultrasonography (US), and uterine curettage key to
successful medical therapy; surgery reserved for complicated cases
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| Risk factors: previous ectopic pregnancy (increases risk 6- to 8-fold), intrauterine device (IUD; does not
cause ectopic pregnancy), tubal surgery, emergency contraceptive pills, assisted reproductive technology
(ART), history of spontaneous abortion, and cigarette smoking; ≈50% of ectopic pregnancies occur in
women with no known risk factors; early prenatal care to rule out ectopic pregnancy important especially
for patient with risk factors
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| Serial β-hCG: indicates pregnancy viability; provides guidance as to when to do first transvaginal US and
helps assess effect of curettage; no rise in hCG in 48 hr suggestive of nonviable pregnancy; minimal rise
in serial hCG values for women with viable intrauterine pregnancy slower than previously reported;
number currently 50%, not 66%; discriminatory zone—refers to value at which normal intrauterine pregnancy
detected consistently and reliably; hCG >2000 mIU/mL used at speaker’s institution (speaker recommends
waiting for hCG to rise slightly >2000 mIU/mL to avoid risk for embryopathy)
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| Dilation and curettage (D&C): often only way to make diagnosis; drop in hCG after curettage suggests
completion of spontaneous abortion; hCG should drop by 15% in 12 hr after D&C
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| Transvaginal US: functions to detect intrauterine pregnancy (IUP) and to measure ectopic size; ectopics
with embryonic heartbeat likely euploid; not cost-effective to treat ectopic >4 cm or one with heartbeat
with methotrexate (surgery recommended); ability of transvaginal US to make diagnosis above discriminatory
zone good (positive predictive value for IUP 96% and for ectopic 86%); less effective below discriminatory
zone; data show 40% of ectopic pregnancies misdiagnosed when D&C not performed and
hCG levels below discriminatory zone
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| Laparoscopic salpingostomy: data show 94% cure rate; 86% of time, tube patent at location where surgery
done; rate of recurrence about 1 in 5; good chance of success for functionality of tube
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| Medical management with methotrexate: selection criteria—confirm ectopic pregnancy (may include
curettage); patient must be hemodynamically stable, ie, complete blood count (CBC), liver and renal
function tests; ensure no adverse interaction with other medications; ensure mass <4 cm and no embryonic
heartbeat; initial hCG should be <10,000 mIU/mL (surgery recommended with hCG >10,000
mIU/mL); methotrexate less expensive and associated with success and fertility rates similar to surgery
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 | Multi-dose regimen: 1 mg/kg; continue to administer until hCG drops; more effective than single-dose
regimen; side effects— stomatitis; hematocytopenia, anemia (short-term), sun sensitivity, hair loss,
chest pain, bloating, and colicky pain; no further intervention necessary, eg, transvaginal US; instruct
patient to avoid intercourse, nonsteroidal anti-inflammatory drugs (NSAIDs), prenatal vitamins, sun
exposure and gas-forming foods, eg, leeks, corn, cabbage
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| Single- vs multi-dose regimen—single-dose regimen not recommended; rupture rate 5 times higher than
multi-dose regimen
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| When to perform surgery: treat cases with poor prognosis surgically; normal hCG rise before diagnosing
implies pregnancy aggressive (likely euploid); patient hemodynamically unstable, fails medical therapy,
or has contraindications to medical therapy; perform surgery with rupture at diagnosis, ectopic size >4
cm, and detectable embryonic heartbeat; initial hCG >10,000 mIU/mL, rapidly rising hCG (doubling
over 2 days), and unremitting pain; identify methotrexate failures early—operate with falling hematocrit,
orthostatic hypotension, persistent and severe pain, and rapid rise in hCG during treatment
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| OPTIMIZING WOUND HEALING —Harriet W. Hopf, MD, Associate Professor, Departments of Anesthesia
and Surgery, University of California, San Francisco, School of Medicine
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| Processes involved in wound healing: aseptic technique and prophylactic antibiotics critical to optimal
wound healing
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| O2 : central to all wound healing processes; required for superoxide production and killing of intracellular
bacteria (primary defense against wound infection and collagen deposition)
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| Collagen: made initially as procollagen; proline and lysine hydroxylases required to allow collagen peptides
to aggregate into triple helices; activity of hydroxylases O2 -requiring process
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| Angiogenesis: requires high levels of O2 ; new blood vessels cannot mature without strong collagen matrix;
if patient hypoxic and unable to make collagen, blood vessels have no place to go
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| Epithelialization: requires O2 ; epithelial cells move and replicate in response to well-oxygenated tissue
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| Wound perfusion and oxygenation: wound hypoxia (defined as partial pressure of O2 <40 mm Hg in
wound) impairs resistance to infection, fibroplasia, and collagen deposition, angiogenesis, and epithelialization;
blood perfusion and arterial PO2 key factors in getting O2 to wound; right shift of O2 -hemoglobin
dissociation curve achieved with temperature; the warmer it is, the more O2 offloaded; data show
wound infection rate inversely proportional to wound O2 tension; 43% wound infection rate among patients
with lowest subcutaneous O2 levels; intercapillary distances large, and O2 consumption relatively
low; enzymatic reactions in wound healing require high concentration of O2 (20-50 mm Hg); pain, cold
exposure, hypovolemia, dehydration, and fear or anxiety can cause vasoconstriction; correction of hypothermia
shown to decrease wound infection and to increase collagen deposition in patients undergoing
colon surgery; increased anxiety also shown to impair wound healing
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| Intraoperative management: data show administration of 80% vs 30% O2 intraoperatively and for first 2
hr postoperatively significantly decreased wound infection rate (50% lower in 80% O2 group than in
30% O2 group); drug-induced hypoxemia common; supplemental O2 for entire postoperative time recommended;
enhance O2 delivery by replacing fluid loss, keeping patient warm or locally warming
wound, and administering adequate pain control
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| Key points for wound healing: wound healing requires inflammation, protein, O2 perfusion, and proper environment
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| Patients on steroid medications: inflammatory process halted; application of vitamin A & D ointment helps to
pull macrophages into wound and to restore healing
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| Optimize perfusion: encourage fluid and protein intake; wound should be kept warm; address patient’s
anxiety (anxiety shown to impair wound healing)
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| Ensure good pain control: speaker recommends acetaminophen and oxycodone (Percocet) over hydro-
codone (Vicodin); good pain control improves wound healing by reducing vasoconstriction; good pain
control makes it easier for patient to change dressing
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| Proper environment: wound should be open to allow for drainage and plenty of room for healing; deep
narrow wound heals poorly; wide shallow wound better for healing process; surrounding skin should
be dry; traditional saline and gauze (wet-to-damp) dressings weep on surrounding skin
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| Shower or wash wound every day: instruct patient to use mild soap, eg, Dove, Ivory, Johnson’s Baby
Shampoo; avoid soaps with dye or antibacterial agents; use warm water; no bleach, povidone iodine
(Betadine Solution), or Dakins Solution; wet-to-damp wound care not recommended
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| Exudating wounds: use calcium alginate in wound; silver-containing calcium alginate may reduce bacterial
load
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| Dry wound (nonexudating): hydrogel for small-volume wound; Vaseline gauze or Aquaphor in gauze for
bigger-volume wound
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| Protect skin: Vaseline gauze, Aquaphor, Adaptic, or zinc oxide recommended; wound covering—
polyurethane foam recommended (especially for exudating wound) or dry gauze; tape or Flexinet underwear;
change wound once daily; facilitates faster healing and more cost-effective than tid changes
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| Vacuum Assisted Closure (VAC) therapy: good for obese patient with large wound; removes edema and
infectious materials; draws wound closed by applying controlled localized negative pressure; increases
perfusion, possibly by reducing edema and sucking blood into wound; place foam in wound, cover with
OpSite dressing, and hook to suction; speaker changes foam in postpartum wound daily for 2 days; line
wound with Adaptic sterile dressing if foam sticking to wound; take stitches out before starting VAC
therapy (stitches impede healing process)
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Educational Objectives
| The goal of this program is to educate the listener about the treatment of ectopic pregnancy and how to optimize
postoperative wound healing. After hearing and assimilating this program, the clinician will be better
able to:
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| 1. Describe 2 factors that contribute to the rupture of an ectopic pregnancy.
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| 2. List the risk factors for ectopic pregnancy and the 3 modalities used in diagnosing ectopic pregnancy.
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| 3. Determine if a patient with ectopic pregnancy is a good candidate for treatment with methotrexate.
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| 4. Identify processes involved in wound healing.
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| 5. Care for patients with postoperative wounds.
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Discussed on This Program
Aquaphor Natural Healing (ointment containing petrolatum, mineral oil, lanolin, alcohol, panthenol, and
glycerin)
Hydrocodone bitarate and acetaminophen [Vicodin, others]
Methotrexate (amethopterin; MTX) [Methotrexate LPF, Rheumatrex Dose Pack, Trexall]
Oxycodone and acetaminophen [Percocet, others]
Suggested Reading
Barnhart KT et al: The medical management of ectopic pregnancy: a meta-analysis comparing “single
dose” and “multidose” regimens. Obstet Gynecol 101(4):778, 2003; Hopf HW et al: Wound tissue oxygen
tension predicts the risk of wound infection in surgical patients. Arch Surg 132(9):997, 1997; Hunt TK et al:
Wound healing and wound infection. What surgeons and anesthesiologist can do. Surg Clin North Am 77(3),
1997; Jonsson K et al: Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical
patients. Ann Surg 214(5), 1991; Kurz A et al: Perioperative normothermia to reduce the incidence of surgical-wound
infection and shorten hospital. Study of Wound Infection and Temperature Group. N Engl J Med
334(19):1209, 1996; Lipscomb GH et al: Comparison of multidose and single-dose methotrexate protocols
for the treatment of ectopic pregnancy. Am J Obstet Gynecol 192(6):1844, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any
significant financial relationship with the manufacturer or provider of any commercial product or service
discussed. The following has been disclosed: Dr. Buster is a grant recipient of Procter & Gamble.
Dr. Buster was recorded at the 27th Annual Postgraduate Course in Obstetrics & Gynecology, sponsored by the
University of Vermont, and held on September 26-28, 2005 in Burlington, Vermont. Dr. Hopf was recorded
at Antepartum & Intrapartum Management, sponsored by the University of California, San Francisco,
School of Medicine, and held on June 9-11, 2005, in San Francisco. The Audio-Digest Foundation thanks
the speakers and the sponsors for their cooperation in the production of this program.
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