Acetaminophen Poisoning

Acetaminophen Poisoning

Basics

Description

• A disorder characterized by hepatic necrosis following large ingestions of acetaminophen. Symptoms may vary from initial nausea, vomiting, diaphoresis, and malaise to jaundice, confusion, somnolence, coma, and death. The clinical hallmark is the onset of symptoms within 24 hours of ingestion of acetaminophen-only or combination products.
• Acetaminophen poisoning is most often encountered following large single ingestions of acetaminophen-containing medications. Usual toxic doses are above 10 g in adults and 150 mg/kg in children. However, poisoning also occurs after acute and chronic ingestions of lesser amounts in susceptible individuals, including those who regularly abuse alcohol, are chronically malnourished, or take medications that affect hepatic metabolism of acetaminophen.
• Therapeutic adult doses are 0.5–1 g q4–6h, up to a maximum of 4 g/d. Therapeutic pediatric doses are 10–20 mg/kg q4–6h.
• System(s) affected: Gastrointestinal; Cardiovascular; Renal/Urologic:
  • Multisystem organ failure can occur.
• Synonym(s): Paracetamol poisoning

Geriatric Considerations

Hepatic damage may be increased if taking hepatotoxic medications chronically.

Pediatric Considerations

Hepatic damage at toxic acetaminophen levels is decreased in children <6 years.

Pregnancy Considerations

• Increased incidence of spontaneous abortion, especially with overdose at early gestational age
• Incidence of spontaneous abortion or fetal death appears to be increased when N-acetylcysteine (NAC) treatment is delayed.
• The optimal route for administration of NAC in pregnant patients remains debatable, although IV NAC may offer greater bioavailability.

Epidemiology

• Predominant age: Children and adults
• Predominant sex: No reported association

Incidence

• More than 50,000 calls placed to poison control centers in 2007 related to possible acetaminophen overdoses.
• 74 deaths in 2006, none in children <6 years of age

Prevalence

Approximately 29% of single exposures are in children <6 years.

Risk Factors

• Age >6 years
• Concurrent poisoning with other substances
• Psychiatric illness
• Previous toxic ingestions or suicide attempts
• Regular ingestion of large amounts of alcohol

General Prevention

Parent/caregiver education essential:

• Education during well-child exams regarding poisoning prevention
• Emergency telephone numbers

Etiology

• Accidental or intentional ingestion of acetaminophen or combination medications containing acetaminophen
• Approximately 96% of ingested acetaminophen is metabolized in the liver with only 2% to 4% excreted unchanged in the urine. When taken in therapeutic doses, 90–95% of hepatic metabolism occurs via glucuronidation and sulfation and results in the formation of benign metabolites. 5–10% of hepatic metabolism is by oxidation through the cytochrome P₄₅₀ enzyme system (CYP 3A4 and CYP 2E1) and results in the formation of the toxic metabolite N-acetyl-p-benzoquinoneimne (NAPQI). NAPQI is rapidly conjugated with glutathione to form a nontoxic metabolite. The metabolites are excreted in the urine along with the small amount of unchanged drug. Hepatocellular damage typically occurs when toxic doses of acetaminophen result in saturation of the glucuronidation and sulfation pathways with subsequent production of excessive amounts of NAPQI. Available glutathione stores become depleted, NAPQI accumulates, and hepatocellular damage occurs.

Diagnosis

• Signs and symptoms develop over the 1st 24 hours following large ingestions, and may last as long as 8 days.
• May develop gradually following long-term ingestion of near maximal-therapeutic amounts of acetaminophen. Such patients may present in stages 1–3, without a history of ingestion of the usual toxic doses.
• Severe symptoms indicate large ingestions or coingestants:
  • Stage 1: 1st 24 hours after time of ingestion:
    • Nausea
    • Vomiting
    • Diaphoresis
  • Stage 2: 24–48 hours:
    • Right upper quadrant pain
    • Typically less nausea, vomiting, diaphoresis, and malaise than in stage 1
  • Stage 3: 72–96 hours:
    • Nausea, vomiting, malaise reappear
    • Severe poisonings may result in jaundice, confusion, somnolence, and coma.
  • Stage 4: 7–8 days:
    • Resolution of clinical signs in survivors
• Fulminant hepatic failure occurs in <1% of adults and is very rare in children <6 years of age.
• Patients with an unexplained rise in liver function tests (LFTs) with negative acetaminophen levels may be overdose patients presenting in stage 3.

History

Ingestion or suspected ingestion of acetaminophen-containing product

Diagnostic Tests & Interpretation

Lab

• Plasma acetaminophen levels should be drawn on all patients 4 hours or more after ingestion (levels prior to 4 hours not helpful).
• At least 1 additional acetaminophen level drawn 4–6 hours after the 1st level is recommended if the ingested acetaminophen is an extended-release product (e.g., Tylenol Extended Relief) or is not known to be an immediate-release product.
• If the 2nd level is higher than the 1st level or is close to the “possible risk” level on the Rumack-Matthew nomogram, it may be prudent to obtain additional acetaminophen levels every 2 hours until the levels stabilize or decline.
• If coingestants include drugs that slow gastrointestinal (GI) motility, an acetaminophen level drawn 4–6 hours after the 2nd level may detect a late increase in serum acetaminophen concentration.
• Screens for suspected coingestants (aspirin, iron, and others) may be positive (especially when suicide attempt is a possibility).
• With toxic ingestions, aspartate transaminase (AST; serum glutamic-oxaloacetic transaminase), alanine transaminase (ALT; serum glutamic-pyruvic transaminase), and bilirubin levels begin to rise in stage 2 and peak in stage 3. In severe poisonings, the PT/INR will parallel these changes and should be monitored.
• AST levels >1,000 IU/L are consistent with the diagnosis, and levels of 20,000 IU/L are not uncommon.
• Laboratory abnormalities usually resolve by stage 4.
• Renal function abnormalities are common in patients with hepatotoxicity.
• Evidence of damage to the pancreas and heart may present following severe poisonings.
• Drugs that may alter lab results: None with clinically significant cross-reactivity with plasma acetaminophen assay
• Disorders that may alter lab results: Diseases or toxic substances that damage the liver, particularly alcohol.

Initial lab tests

• Acetaminophen serum concentration: 4 hours after ingestion and again per comments above (see General)
• AST, ALT (rise in first 72 hours, then slowly decline), prothrombin time (PT)/international normalized ration (INR), bilirubin, LDH
• Electrolytes, glucose, blood urea nitrogen (BUN), creatinine
• Pregnancy screen in females (urine or serum)
• Urinalysis
• Consider arterial blood gas if pH disturbance suspected on clinical or lab grounds.

Follow-Up & Special Considerations

• Repeat 4 hours after ingestion and possibly every 2 hours thereafter if long-acting product is ingested or acetaminophen ingested with other agents that slow GI passage.
• Arterial blood gas after hydration if pH is acidotic

Imaging

No specific imaging required

Pathological Findings

Centrilobular hepatic necrosis

Differential Diagnosis

• Consider presence of coingestants, especially alcohol and aspirin.
• Other ingested toxins that produce severe acute hepatic injury, including the mushroom Amanita phalloides and products containing yellow phosphorus or carbon tetrachloride

Treatment

• Contact a regional poison control center for management recommendations. In the US, a local poison control center can be reached by calling (800) 222-1222.
• NAC should be given when plasma acetaminophen concentrations measured 4 hours or more after ingestion are in the “possible risk” or higher levels on the Rumack-Matthew nomogram. This corresponds to acetaminophen levels >150 µg/mL (993 µmol/L), >75 µg/mL (497 µmol/L), and >37 µg/mL (244 µmol/L) at 4, 8, and 12 hours after ingestion, respectively. See http://www.ars-informatica.ca/toxicity_nomogram.php?calc = acetamin or http://www.merck.com/mmpe/sec21/ch326/ch326c.html
• NAC should be started within 8 hours of ingestion for best chance of hepatic protection. Patients presenting near 8 hours should empirically receive NAC while waiting for labs.
• All patients with acetaminophen liver injury (even after 8 hours) should receive NAC.
• NAC therapy may be effective up to 36 hours or more after ingestion.
• Single dose activated charcoal can be used (especially in cases of coingestants) (1,2)[C],(3)[A] but not within 1 hour of administration of the antidote NAC. Never delay NAC for activated charcoal.
• NAC should be initiated within 8 hours of ingestion whenever possible.
• Ipecac and gastric lavage are no longer recommended for routine use at home or in health care facilities (4)[C].

Medication

First Line

• Acetylcysteine (NAC, Mucomyst) should be initiated within 8 hours of ingestion whenever possible; single dose activated charcoal may be given 1 hour after oral NAC. NEVER delay oral NAC for activated charcoal.
• Acetylcysteine may be given p.o. or IV, depending on situation and availability: IV is often preferred, particularly if activated charcoal is given:
  • Currently, IV is the recommended form of administration:
    • Oral loading dose of 140 mg/kg, followed by 70 mg/kg q4h for 17 additional doses. IV loading dose of Acetadote 150 mg/kg over 15 to 60 minutes followed by an infusion of 50 mg/kg over 4 hours (12.5 mg/kg/hour); this is followed by an infusion of 100 mg/kg over the next 16 hours (6.25 mg/kg/hour).
• Contraindications: Medication allergies
• Precautions:
  • Oral NAC may cause significant nausea and vomiting due to its sulfur content; consider IV administration or by nasogastric tube.
  • Nausea can be treated with metoclopramide (Reglan), 0.5–1 mg/kg IV, or ondansetron (Zofran), 0.15 mg/kg IV (for age >4 years, usually 4 mg/dose).
  • IV NAC (Acetadote) may cause anaphylactoid reactions, including rash, bronchospasm, pruritus, angioedema, tachycardia, or hypotension (higher rates seen in asthmatics and those with atopic history) (5,6)[C].
• Reactions usually occur with loading dose. Slow or temporarily stop the infusion; may concurrently treat with antihistamines.
• Significant possible interactions: Activated charcoal given within 1 hour of oral NAC may adsorb the NAC, limiting its effectiveness.
• Activated charcoal: 1 g/kg p.o. for initial dose; preferably not within 1 hour of NAC administration. Additional concurrent use during NAC therapy is controversial.

Second Line

Oral racemethionine (methionine)

Additional Treatment

Issues for Referral

• Psychiatric and psychological evaluation in emergency room and close follow-up for all after intentional ingestions
• Consider child abuse reporting if neglect led to overdose.

In-Patient Considerations

Initial Stabilization

Aggressive age- and weight-appropriate IV hydration

Admission Criteria

• Toxic and intentional ingestions
• Any reported ingestion with increased LFTs, acidosis on arterial blood gas (ABG), elevated creatinine, etc.

Ongoing Care

Follow-Up Recommendations

• All patients should be evaluated at a health care facility.
• Patients with evidence of organ failure, increased LFTs, or coagulopathy should be evaluated for transfer to a site capable of liver transplant.
• Outpatient for nontoxic accidental ingestions
• Activity may be restricted if significant hepatic damage.

Patient Monitoring

Inquire as to possible ingestion by others (i.e., suicide pacts).

Diet

No special diet, except with severe hepatic damage

Patient Education

• Patients should be counseled to avoid Tylenol if already using combination product containing acetaminophen.
• Education of parents/caregivers during well-child visits
• Anticipatory guidance for caregivers, family, and cohabitants of potentially suicidal patients
• Patient brochure (item no. 1515), Child safety: keeping your home safe for your baby. American Academy of Family Physicians: www.familydoctor.org or http://familydoctor.org/online/famdocen/home/healthy/safety/kids-family/027.html
• Education of patients taking long-term acetaminophen therapy

Prognosis

• Complete recovery with early therapy
• <1% of adult patients develop hepatic failure. King criteria (pH <7.3, PT >100 s [INR >65], creatinine >3.4 mg/dL [>300 µmol/L]) are associated with a poor prognosis and possible need for liver transplant (7)[C].
• Hepatic failure is very rare in children <6 years of age.

Abscess, Psoas

Abscess, Psoas

Basics

Psoas abscess is a rare and potentially life-threatening suppurative myositis of the iliopsoas compartment (1).

Description

The iliopsoas compartment is an anatomic space comprised of the psoas major, psoas minor, and iliacus muscles, which mediate hip flexion (2). Commonly referred to as iliopsoas, this muscle group originates from the lateral borders of the 12th thoracic to 5th lumbar vertebrae, passes posterior to the inguinal ligament and anterior to the hip joint, and inserts on the lesser trochanter of the femur. Abscesses of the iliopsoas compartment are considered primary or secondary depending on infectious etiology.

Epidemiology

• Mycobacterium tuberculosis (TB) with secondary vertebral osteomyelitis is a common cause of psoas abscess in countries where TB is prevalent (3). About 5% of patients with vertebral tuberculosis develop psoas abscess (4). In developed countries such as the United States, nearly 3/4 of psoas abscesses are due to hematogenous spread of infection (5). About 57% of psoas abscesses occur on the right side, 40% on the left side, and 3% bilaterally (6).
• Primary psoas abscess is most common in developing and tropical countries (4). About 83% of primary abscesses occur in patients younger than 30 years old (1). In contrast, secondary psoas abscess is more common in Europe and the United States. Older patients are more predisposed to secondary psoas abscess due to increased incidence of age-related diseases such as diverticulitis (7). A male preponderance of 3:1 for psoas abscess has been reported (6).

Incidence

• 3.9 cases per year before 1985 to about 12 cases per year in the 1990s (2)
• Rising incidence from increased prevalence of risk factors (immunosuppressant therapy, diabetes, etc.)
• Increased detection from improvement in quality and interpretation of cross-sectional imaging (8,9)

Risk Factors

• Primary psoas abscess: diabetes, HIV/AIDS, and other immunodeficiency states (1)
  • Other factors include trauma to the lumbar spinous processes, incurring psoas muscle damage, and hematoma formation such as in the setting of hematologic disorders (4).
• Secondary psoas abscess: Crohn's disease, ulcerative colitis, appendicitis, and vertebral osteomyelitis (1,10)
  • Complications of hip arthroplasty, spinal surgery, aortic surgery, and kidney transplantation (10,11,12,13)
  • Paraspinal abscess, anastomotic leak, and hematoma set the stage for postoperative infection and abscess formation.

Pathophysiology

• Primary psoas abscess results from hematogenous or lymphatic spread of infection from a distant source (1). Primary abscesses are often monomicrobial, with 80 percent of infections due to Staphylococcus aureus bacteremia or sepsis. Pseudomonas aeruginosa, Haemophilus aphrophilus, and Proteus mirabilis infections have also been reported (7).
• Secondary psoas abscess results from contiguous spread of infection from nearby structures of the musculoskeletal system, gastrointestinal tract, genitourinary tract, and vasculature. Secondary psoas abscesses are often polymicrobial, most commonly involving Escherichia coli and other enteric organisms such as Salmonella enteritidis, enterobacter species, and Methicillin resistant Staphylococcus aureus (MRSA) (14).

Commonly Associated Conditions

• Primary psoas abscess: Most common associated conditions include intravenous drug use, HIV/AIDS and other immunocompromised states, renal failure (9).
• Secondary psoas abscess: Most common associated conditions include inflammatory bowel disease, appendicitis, diverticulitis, osteomyelitis. Infrequently, secondary psoas abscess has been associated with septic arthritis, pancreatitis, and Henoch-Schönlein Purpura.

Diagnosis

Diagnosis of psoas abscess can be difficult and involves a thorough history, physical examination, and appropriate imaging studies (2). Computed tomography scan (CT) is the preferred imaging modality for identification of psoas abscess, and definitive diagnosis is made by image-guided drainage and microbial culture (6).

History

• Reported symptoms are often nonspecific indicators of generalized infection:
  • Fever, flank or abdominal pain with or without radiation to the anterior hip and thigh (1)
• Additional symptoms:
  • Limp, nausea, anorexia, malaise, and weight loss
  • The classic symptom triad described by Myntner in 1881 of fever, abdominal or flank pain, and limp is present in less than 8 percent of cases.
• Most patients will present with pain, while persistent low-grade fever is found in more than 75% of cases (14).

Physical Exam

• Maneuvers that stretch or contract the inflamed psoas compartment result in considerable pain on the affected side (1,6).
• Pain with extension and internal rotation of the hip (the “psoas sign”) is the most common physical exam finding.
  • A positive psoas sign may be elicited by the examiner by placing one hand proximal to the patient's knee on the affected side and asking the patient to raise the ipsilateral thigh against resistance.
  • A second psoas test is performed by asking the patient to lay on the unaffected side and hyperextend the contralateral hip, eliciting pain with stretching of the affected psoas muscle.
  • These maneuvers may also be positive in the setting of other conditions causing iliopsoas inflammation, including retrocecal appendicitis. Sensitivity and specificity of the psoas sign have been reported to be 16% and 95% respectively (15).
• Rectal examination may aid in differentiating psoas abscess from retrocecal appendicitis, with pain on palpation of the retrovesical pouch more consistent with appendicitis. While patients with psoas abscess may find relief from pain with full hip flexion, patients with hip pathology experience persistent or heightened pain. Distal extension of a psoas abscess may yield a painful or painless mass palpable below the inguinal ligament (8). About 50% of patients report abdominal tenderness, but guarding and rebound are uncommon (6).

Diagnostic Tests & Interpretation

Lab

• WBC >10,000/mL
• Anemia (hemoglobin <11g/L)
• Thrombocytosis (1,14)
• Elevations in blood urea nitrogen (BUN), sedimentation rate, and C-reactive protein (CRP) have been reported (10). CRP level has been shown to correspond with the severity of infection (3).

Imaging

• Computed tomography (CT) is the gold standard imaging modality:
  • Sensitivity rate between 88% and 100% (2)
  • Typically reveals a focal hypodense lesion consistent with an abscess
  • May demonstrate:
    • enlargement of the iliopsoas muscle
    • gas or air fluid levels within the muscle and fat stranding.
  • Constrast CT may show rim enhancement of the abscess wall (6).
• While not integral to the diagnosis of psoas abscess, magnetic resonance imaging (MRI) and technetium 99 m scintigraphy may elucidate local infectious sources, such as vertebral osteomyelitis (2).
• Plain abdominal radiographs occasionally reveal the outline of an inflammatory mass.
• Chest plain films may identify scant pleural effusions or raised hemidiaphragm (6).
• Ultrasound may disclose evidence of an inflammatory mass and is often diagnostic in cases of pediatric psoas abscess (16).
• An intravenous pyelogram may show deviation of the kidney and ureter, and barium studies may reveal bowel loop displacement and associated GI disease.

Diagnostic Procedures/Surgery

• Gram stain and culture of blood and aspirated abscess fluid confirm the diagnosis and guide antimicrobial treatment (1).
• AFB stain and mycobacterial culture if tuberculosis infection suspected

Differential Diagnosis

Differential diagnosis may include retrocecal appendicitis, bacterial infection or avascular necrosis of the hip, renal colic and pyelonephritis, arthritis, hip joint infection, S1 disc herniation, inflammatory bowel disease, epidural abscess, vertebral osteomyelitis, pelvic inflammatory disease (1,6).

Treatment

Most cases of psoas abscess will require percutaneous or surgical drainage as well as parental antibiotic treatment (1,14).

CT-guided percutaneous drainage is the initial procedure of choice, leading to successful decompression in the majority of cases (17).

Open drainage may be indicated:

• For large, complex, and multiloculated abscesses.
• If imaging shows gross involvment of adjacent structures or when percutaneous drainage fails (4,14).

Psoas abscess associated with conditions such as inflammatory bowel disease may be effectively managed with open drainage and surgical treatment of the underlying disease process.

Medication

• Broad-spectrum empiric antibiotics targeting staphylococcal and enteric organisms are indicated in most cases (14).
• Intravenous monotherapy with Unasyn, Zosyn, or a carbapenem is effective as initial treatment.
• Dual therapy with a third-generation cephalosporin such as Ceftriaxone with Metronidazole is also adequate.
• Suspected MRSA infection is best treated with Vancomycin, and alternatively, Linezolid or Daptomycin.
• Coverage should be determined by culture sensitivity results from aspirated fluid.
• While most psoas abscesses require a drainage procedure, abscesses 3 cm or less in size have been successfully managed by antibiotics alone.

Ongoing Care

Following drainage, pigtail catheter placement permits continued decompression of the abscess cavity and monitoring of purulent output for improvement (2).

Follow-Up Recommendations

Duration of antibiotic treatment should be tailored to the patient and may be continued for two to six weeks (3,14).

Patient Monitoring

Patients should be assessed for symptomatic relief, defervescence, and resolving white blood cell count (3). Follow-up imaging may be warranted to verify adequate drainage of the fluid collection.

Diet

Patients should be kept NPO for percutaneous and surgical drainage procedures.

Prognosis

A high index of suspicion for abscess in the iliopsoas compartment is crucial as early intervention is associated with favorable outcomes. Delays in diagnosis can lead to serious complications including septic shock, reported in up to 20% of cases (14). Mortality is reported to range from 2.4% to 19% for treated patients with primary and secondary abscesses respectively (7,14). Untreated cases face a near 100% mortality rate (10).

Complications

Risk factors for unfavorable outcomes include delays in treatment, bacteremia, and inadequate treatment (percutaneous drainage or antibiotics only) in patients with advanced age (4,14). About 40% of patients require more than one drainage procedure for full recovery. Incomplete drainage or suboptimal antibiotic treatment may lead to relapses of psoas abscess up to a year after initial presentation in 15–36% of cases (3,14).

Abruptio Placentae

Abruptio Placentae

Basics

Description

• Premature separation of an otherwise normally implanted placenta
• Grades:
  • Grade 1: Minimal or no bleeding; detected as retroplacental clot after delivery of viable fetus. Mild uterine irritability (40% of cases).
  • Grade 2: Viable fetus with bleeding and tender, irritable uterus. Mild-to-moderate bleeding; fibrinogen level decreased (45% of cases).
  • Grade 3: Type A with dead fetus and no coagulopathy; type B with dead fetus and coagulopathy (Types A and B = 15% of all cases)

Epidemiology

Incidence

• 0.5–1.2% of all deliveries:
  • Placental abruption is the most common cause of serious vaginal bleeding in late pregnancy (1).
• 15% if 1 prior abruption
• 25% if 2 or more prior abruptions
• 80% of cases occur prior to onset of delivery.
• Peaks at 24–26 weeks, then decreases with increasing gestation
• Rising in the US from 0.8% 1979–1981 to 1.2% 1999–2001

Risk Factors

• Prior abruption: Increases 15–20-fold (2)
• Increasing maternal age and parity
• Advanced maternal age
• Maternal smoking: dose–response relationship (2)
• Cocaine use and abuse
• Factor V Leiden and other thrombophilic disorders
• Hypertensive disorders
• Uterine anomalies
• Multiple-gestation pregnancies (3)[B]
• 1st- or 2nd-trimester bleeding
• Preeclampsia: Mild and severe
• Increased risk if hypertension and parity >3
• Preterm rupture of membranes (4)[B]
• Hydramnios
• Severe small-for-gestational-age birth
• Blunt trauma/motor vehicle accident

Genetics

• Genetic predisposition may be the cause of abruption in women with no other inciting factor discovered.
• Placental growth is primarily under control of paternally inherited fetal genes.

General Prevention

Eliminate risk factors when possible: Quit smoking and cocaine use, control hypertension, use seat belts, etc.

Pathophysiology

Exact cause is unknown: Appears to be the final common clinical event secondary to a variety of causes

Etiology

• Acute:
  • Trauma of variable amounts, especially blunt abdominal trauma in which external signs of trauma may be incongruent with fetal injury
  • Sudden decompression of overdistended uterus, as in hydramnios or twin gestation
  • Vasospasm secondary to cocaine use
• Chronic (majority of cases):
  • Hypertensive disorders and growth restriction associated with chronic process
  • Early bleeding in pregnancy releases thrombin, which is a potent uterotonic agent

Commonly Associated Conditions

• Preeclampsia and other forms of hypertension in pregnancy
• Uteroplacental insufficiency
• Postpartum hemorrhage
• Disseminated intravascular coagulation (DIC)
• Rupture of membranes

Diagnosis

History

• Classic triad of vaginal bleeding, abdominal pain, and contractions
• Abruption in prior pregnancy
• Early trimester bleeding
• Recent trauma
• Cocaine or tobacco use
• Back pain
• Frequent or tetanic contractions
• May present in active labor

Physical Exam

• Vital signs: Tachycardia, hypotension:
  • Because blood volumes increase in pregnancy, volume lost may exceed 30% before signs of shock or hypovolemia occur.
• Uterine tenderness, hypertonia, or high-frequency contractions
• Vaginal bleeding (not always present):
  • Clinical signs of shock may occur with little vaginal bleeding.
• Fetal distress or demise
• Idiopathic preterm labor with or without fetal distress

Diagnostic Tests & Interpretation

Lab

Initial lab tests

• Blood type, Rh, cross-match for possible transfusion:
  • RHoD immune globulin administered <12 weeks prior may affect antibody test.
• Complete blood count with platelet count
• Prothrombin time (PT)/partial thromboplastin time (PTT)
• Kleihauer-Betke test checks for evidence of fetal blood in maternal circulation; >30 mL fetal blood indicative of large fetal blood loss:
  • 300 µg dose of RhoGAM will cover up to 30 mL whole fetal blood in maternal circulation
• Bedside clot test: Red-top tube of maternal blood with poor or nonclotting blood after 7–10 minutes indicates coagulopathy.

Follow-Up & Special Considerations

• DIC can result from a large abruption. Best to stabilize patient without waiting for DIC labs. This is typically a clinical diagnosis.
• Can send PT/PTT, fibrinogen levels at clinician discretion when stable or following resolution of DIC:
  • Fibrinogen levels climb to 350–550 mg/dL in 3rd trimester and must fall to 100–150 mg/dL before PTT will rise.
  • Fibrin split or degradation products are elevated in pregnancy and are not specific in assessing DIC.

Imaging

Initial approach

• Placental abruption is a clinical diagnosis.
• Ultrasound can help to make the diagnosis, but has low sensitivity and is only helpful in cases of a large abruption.

Follow-Up & Special Considerations

Ultrasound: Appearance depends on size and location of the bleed:

• With acute bleed, nothing may be seen.
• Will fail to detect at least 50% of abruptions
• Retroplacental clot is diagnostic of abruption (2):
  • If incidental abruption is found in a patient at term, delivery is reasonable.
  • A preterm patient with an incidental abruption may be managed conservatively if stable.

Diagnostic Procedures/Surgery

• Tocometer often shows elevated baseline pressure and frequent low-amplitude contractions.
• External fetal monitoring may show recurrent late decelerations, variable decelerations, sinusoidal fetal heart tracing, bradycardia, or decreased variability—all indicative of fetal stress.

Pathological Findings

• Placental examination after delivery may show a retroplacental clot, pathologic signs of early separation/inflammation
• Normocytic normochromic anemia with acute bleeding
• Elevated PT/PTT, fibrinogen levels <100–150 mg/dL (1.0–1.5 g/L), platelets 20,000–50,000/µL if DIC is active
• Positive Kleihauer-Betke reaction if fetal–maternal transfusion has occurred
• Positive antibody if RhoD isosensitization has occurred

Differential Diagnosis

• Placenta previa or vasa previa (1)
• Uterine rupture
• Bloody show associated with labor
• Cervical and vaginal infections (e.g., chlamydia or gonorrhea with bloody, friable cervix)
• Other painful abdominal conditions (e.g., appendicitis, pyelonephritis)
• Fibroid degeneration
• Ovarian pathology: Torsed ovary, ruptured cyst

Treatment

Medication

First Line

• Tocolytics are generally contraindicated in presence of abruption:
  • Tocolytics, such as nifedipine or terbutaline, may be used in mild noncompromising preterm abruption (specific cases only, such as for fetal lung maturity)
• RhoD immune globulin for RhoD-negative mother if undelivered or indicated after delivery if Kleihauer-Betke is positive
• Fluid resuscitation as required for signs of shock

Second Line

• Transfuse packed red blood cells (PRBC) or other factors to stabilize patient as needed.
• Steroids for fetal lung maturation, if fetus is viable

Additional Treatment

Issues for Referral

• If preterm and hemodynamically stable, refer to tertiary care center.
• Alert anesthesia if delivery via cesarean section is likely.

Surgery/Other Procedures

• May need cesarean delivery after maternal stabilization if fetus is viable, remote from delivery, and nonreassuring fetal heart tracing is present.
• Postpartum hemorrhage/DIC may be treated medically or with uterine packing, embolization, or hysterectomy.

In-Patient Considerations

Initial Stabilization

• History and physical exam with medical history, allergies, prior ultrasounds (present gestation), and time of last meal
• Management depends on presentation, gestational age, and degree of maternal and fetal compromise:
  • In general, severe abruption is best managed by delivery of fetus.
  • Grade 1: Usual labor protocol
  • Grade 2: Rapid delivery, most often by cesarean delivery (if mother stable)
  • Grade 3: Vaginal delivery preferable if mother stable
• In trauma (2)[B], monitor in the inpatient setting for at least 4 hours for evidence of fetal insult, abruption, fetal–maternal transfusion. If contractions or preterm labor occur, patient should be monitored for at least 24 hours. Risk factors for contractions with trauma include:
  • Gestational age >35 weeks
  • Assaults and pedestrian/vehicular collisions, even without direct abdominal trauma
  • Ejections from vehicle or lack of restraints
• Early aggressive restoration of maternal physiology to protect fetus and maternal organs from hypoperfusion/DIC
• Stabilize vitals
• Bedrest with external fetal and labor monitoring, if fetus is viable
• Large-bore, 16- to 18-gauge IV crystalloid infusion to maintain volume
• Transfusions of whole blood and PRBCs as necessary
• Fresh frozen plasma and platelet transfusions for coagulopathy, with cryoprecipitate and fibrinogen given if indicated
• Follow hemoglobin/hematocrit and coagulation status.
• Consider internal monitoring of fetus if patient is in active labor.
• Role of amniotomy to prevent amniotic fluid embolism is debatable, but may speed delivery
• Positioning on left side may enhance venous return and cardiac output
• Oxygen as needed

Admission Criteria

Patients with suspected placental abruption should be admitted for workup until deemed clinically stable and ready for discharge/outpatient follow-up or delivered for medical indication.

IV Fluids

Saline or Ringer's lactate to restore maternal vascular volume

Nursing

• Bed rest until status defined
• Frequent vital sign monitoring
• Record fluid ins and outs

Discharge Criteria

• 2nd trimester suspected abruption may be managed on outpatient basis if hemodynamically stable
• Viable patients may be discharged if maternal/fetal status is stable.

Ongoing Care

Follow-Up Recommendations

• Monthly growth ultrasonograms for those patients where conservative management is possible.
• Serial ultrasounds may also be used to follow regression or progression of abruption (2).

Patient Monitoring

Severe cases or unstable patients may require critical care unit admission.

Diet

n.p.o. until status is defined and possibility of immediate cesarean delivery ruled out

Patient Education

• Call physician or proceed to hospital whenever patient experiences vaginal bleeding or if severe uterine or back pain or decreased fetal movement occurs.
• Wear seat belts while in automobile.
• Discontinue use of cocaine, tobacco
• Visit Mayo Health: http://mayohealth.org

Prognosis

• 0.5–1% fetal mortality and 30–50% perinatal mortality:
  • 1/2 of perinatal deaths due to preterm delivery
• With trauma and abruption, 1% maternal and 30–70% fetal mortality

Complications

• Maternal complications include anemia, stroke, myocardial infarction, DIC, and Sheehan's syndrome, and may include maternal death with severe hemorrhage.
• Surgical interventions and transfusion carry their own morbidity/mortality.
• Amniotic fluid embolism is rare, but may present with severe respiratory distress.

Abortion, Spontaneous (Miscarriage)

Abortion, Spontaneous (Miscarriage)

Basics

Description

• Separation of products of conception from the uterus prior to the potential for fetal survival outside the uterus
• Spontaneous abortion (SAb):
  • Expulsion or extraction from the uterus of an embryo or fetus weighing ≤500 g
• Threatened abortion:
  • Vaginal bleeding early in pregnancy without dilatation of the cervix, rupture of the membranes, or expulsion of products of conception
• Inevitable abortion:
  • Cervical dilatation, rupture of membranes, or expulsion of products in the presence of vaginal bleeding
• Complete abortion:
  • Entire contents of uterus expelled; common before 12 weeks' gestation
• Incomplete abortion:
  • Abortion with retained products of conception, generally placental tissue; more common after 12 weeks' gestation
• Missed abortion:
  • In utero death of embryo/fetus prior to 20 weeks' gestation; products of conception retained
• Induced abortion:
  • Evacuation of uterine contents or products of conception medically or surgically
• Septic abortion:
  • Common complication of illegally performed induced abortions; a spontaneous or therapeutic abortion complicated by pelvic infection
• Habitual spontaneous abortion:
  • 2 or more consecutive pregnancy losses at <15 weeks' gestation
• Synonym(s): Miscarriage; Habitual abortion; Recurrent abortion; Involuntary pregnancy loss

Epidemiology

Predominant age: Increases with advancing age, especially >35 years; at age 40, the loss rate is twice that of age 20

Prevalence

• ∼8–20% of all clinically recognized pregnancies end in spontaneous abortion, 80% of these in the first 12 weeks.
• When both clinical and biochemical (B-HCG detected) pregnancies are considered, up to 50% of pregnancies end in spontaneous abortion.

Risk Factors

Most cases of spontaneous abortion occur in patients without identifiable risk factors; however, risk factors listed in order of importance include:

• Chromosomal abnormalities
• Advancing maternal age
• Uterine abnormalities
• Maternal chronic disease (diabetes mellitus, polycystic ovarian syndrome, systemic lupus erythematosus, hypertension, antiphospholipid antibodies, thyroid disease, renal disease)
• Other possible contributing factors include smoking, alcohol, infection, and luteal phase defect, although conclusive data are currently lacking.

Genetics

∼50–65% of 1st-trimester spontaneous abortions have significant chromosomal anomalies, with 1/2 of these being autosomal trisomies and the remainder being triploidy, tetraploidy, or 45X monosomies.

General Prevention

• Progestogens: Currently, there is no evidence that routine use of oral or IM progestogens prevents miscarriage in early to mid-pregnancy. However, there is some evidence that women with a history of recurrent miscarriage may benefit from this type of treatment (1)[A].
• Immunotherapy: No current evidence to support use of immunotherapy in patients with a history of recurrent miscarriage (2)[A]

Etiology

• Chromosomal anomalies
• Congenital anomalies
• Trauma
• Maternal factors: Uterine abnormalities, infection (toxoplasma, other viruses, rubella, cytomegalovirus, herpesvirus), maternal endocrine disorders, hypercoagulable state

Diagnosis

History

• Consider any reproductive-age woman with vaginal bleeding to be pregnant until proven otherwise.
• Vaginal bleeding:
  • Characteristics (amount, color, consistency, associated symptoms), onset (abrupt or gradual), duration, intensity/quantity, and exacerbating/precipitating factors
• Abdominal pain/uterine cramping
• Rupture of membranes
• Passage of products of conception
• Prenatal course: Toxic or infectious exposures, family or personal history of genetic abnormalities, past history of ectopic pregnancy or spontaneous abortion, endocrine disease, autoimmune disorder, bleeding/clotting disorder

Physical Exam

• Any pregnant woman with vaginal bleeding needs immediate evaluation.
• Estimate hemodynamic stability:
  • Obtain orthostatic vital signs.
• Abdominal exam for tenderness (SAb), guarding, rebound, bowel sounds (peritoneal signs more likely seen with ectopic pregnancy)
• Pelvic exam for cervical dilation, blood, products of conception, uterine size/tenderness

Diagnostic Tests & Interpretation

Lab

Initial lab tests

• Urine human chorionic gonadotropin (HCG)
• Complete blood count
• Rh type
• Cultures: Gonorrhea/chlamydia
• Serial serum HCG measurements can assess viability of the pregnancy. Serum HCG should rise at least 67% every 48 hours in early pregnancy.

Pregnancy Considerations

HCG levels are particularly useful in cases where an intrauterine pregnancy (IUP) has not been documented by ultrasound.

Follow-Up & Special Considerations

• In the case of vaginal bleeding with no documented IUP, follow serum HCG levels weekly to zero to ensure complete expulsion of all products of conception.
• If levels plateau, suspect ectopic pregnancy or retained products of conception.

Imaging

Initial approach

• Ultrasound (US) exam to evaluate fetal viability and to rule out ectopic pregnancy:
  • HCG >2,000 U/L necessary to detect IUP via transvaginal US (TVUS), >6,500 U/L for abdominal ultrasound
• TVUS criteria for nonviable intrauterine gestation include 5-mm fetal pole without cardiac activity or 16-mm gestational sac without a fetal pole.

Follow-Up & Special Considerations

• If initial HCG level does not permit documentation of IUP by TVUS, follow serum HCG in 48 hrs to ensure appropriate rise.
• Follow HGC and repeat US once HCG at a level commensurate with visualization on US (see above).
• Provide patient with ectopic precautions in interim.

Diagnostic Procedures/Surgery

• Fetal heart tones can be auscultated with Doppler starting between 10–12 weeks' gestation from last menstrual period for a viable pregnancy.
• 90–96% of pregnancies with fetal cardiac activity and vaginal bleeding at 7–11 weeks' gestation result in continued pregnancy.

Pathological Findings

Products of conception, placental villi

Differential Diagnosis

• Ectopic pregnancy: Potentially life-threatening; must be ruled out with US in any woman of childbearing age with abdominal pain and vaginal bleeding
• Cervical polyps, neoplasias, and/or inflammatory conditions can cause vaginal bleeding.
• Hydatidiform mole pregnancy
• HCG-secreting ovarian tumor
• Physiologic bleeding in normal pregnancy (implantation bleeding)

Treatment

Medication

• Long-term conception rate and pregnancy outcomes are similar for women who undergo medical or surgical evacuation.
• Postinfection rates lower with medical vs surgical management

First Line

• Misoprostol: Most common agent for inducing passage of tissue in missed or incomplete abortion:
  • Not approved by Food and Drug Administration for treatment of early pregnancy failure
  • Efficacy: Complete expulsion of products of conception in 71% by day 3, 84% by day 8
  • Efficacy depends on route of administration, gestational age of pregnancy, and dose
  • Recommended dose 800 µg vaginally (3)[A]; alternate regimens exist including World Health Organization regimen of 800 µg vaginally or 600 µg sublingually q.3 hours for up to 3 doses; multidose regimens and oral dosing may result in increased side effects
• Common adverse effects include abdominal pain/cramping, nausea, and diarrhea. Pain increases at higher doses, but manageable with analgesia. No increase in nausea/diarrhea with higher dose.
• Recommended for stable patients who decline surgery but do not want to wait for spontaneous passage of products of conception

Second Line

Rh-negative patients should be given Rh immune globulin following spontaneous abortion (4)[C].

Additional Treatment

General Measures

Explore any 1st-trimester vaginal bleeding.

Issues for Referral

Patients should be monitored for up to 1 year for the development of psychosomatic symptoms such as depression and anxiety (5)[A].

Complementary and Alternative Medicine

Vitamin supplementation does not appear to prevent miscarriage (6)[A].

Surgery/Other Procedures

• Uterine aspiration (dilation and curettage or via vacuum aspiration) is the conventional treatment.
• Indications: Septic abortion, heavy bleeding, hypotension, patient choice
• Risks: Anesthesia, uterine perforation, intrauterine adhesions, cervical trauma, infection that may lead to infertility or increased risk of ectopic pregnancy
• Surgical intervention leads to fewer days of vaginal bleeding, with a lower risk of incomplete abortion and heavy bleeding. It does carry a higher risk of infection (7)[A].
• Vacuum aspiration may be less painful than dilatation and curettage (D & C), and does not require general anesthesia (8)[B].
• Data from induced abortions suggests that antibiotic prophylaxis with doxycycline 100 mg b.i.d. substantially reduces postprocedure infection risk; however, data for incomplete abortions treated surgically is inconclusive (9)[A].
• For patients who desire contraception after completion of a spontaneous abortion, immediate insertion of an intrauterine device is acceptable and safe (10)[A].

In-Patient Considerations

Initial Stabilization

If patient with orthostatic vital signs, initiate resuscitation with IV fluids and/or blood products if needed

IV Fluids

Hemodynamically unstable patients may require IV fluids and/or blood products to maintain blood pressure.

Ongoing Care

Follow-Up Recommendations

All patients should be seen in 2–6 weeks to monitor for resolution of bleeding, reestablishment of menses, review of contraception plan, and psychosomatic symptoms.

Patient Monitoring

• Identification of products of conception within material expelled from the uterus or D & C specimen (important to distinguish villi and sac from decidua)
• If abortion is complete, observe the patient for further bleeding.
• Pelvic rest until 2 weeks after evacuation
• If spontaneous abortion occurs in setting of previously documented IUP and abortion is completed with resumption of normal menses, it is not necessary to check or follow serum HCG to 0.

Prognosis

• If bleeding ceases, prognosis is excellent.
• Habitual abortion:
  • Prognosis depends on etiology.
  • Prognosis is still excellent, with up to 70% rate of success with subsequent pregnancy.

Complications

• Potential complications of D & C include uterine perforation, bleeding, adhesions, cervical trauma, infection that may lead to infertility, or increased risk of ectopic pregnancy.
• Retained products of conception
• Psychological morbidity, including depression, anxiety, feelings of guilt

Abnormal Pap and Cervical Dysplasia

Abnormal Pap and Cervical Dysplasia

Basics

Description

Cervical dysplasia: Precancerous epithelial changes in the transformation zone of the uterine cervix almost always associated with human papillomavirus (HPV) infections:

• Mild dysplasia (cervical intraepithelial neoplasia [CIN] I): Cellular changes are limited to the lower 1/3 of the squamous epithelium.
• Moderate dysplasia (CIN II): Cellular changes are limited to the lower 2/3 of the squamous epithelium.
• Severe dysplasia (CIN III or carcinoma in situ): Cellular changes involve the full thickness of the squamous epithelium.
• Pap smear:
  • Screening test for cervical cellular pathology. In many laboratories, automated cervical screening complements the Pap smear or supersedes it.
  • Abnormal cervical smear results can range from benign cellular changes to suggestion of invasive cancer.
• System(s) affected: Reproductive

Alert

Cervical cancer arises from HPV, which is a sexually acquired disease. Good evidence that screening for cervical cancer with Pap smears reduces incidence of and mortality from cervical cancer (1)[A].

Geriatric Considerations

Natural progression of cervical dysplasia involves acquisition of HPV at or after first coitus with a small percentage of lesions progressing. See guidelines below.

Pregnancy Considerations

• Squamous intraepithelial lesions can progress during pregnancy, but often regress postpartum.
• Colposcopy only to rule out invasive cancer in high-risk women (2)

Epidemiology

• Predominant age: Can occur at any age
• Incidence of CIN III peaks between ages 25 and 29; invasive disease peaks 15 years later.

Incidence

• Low-grade squamous intraepithelial lesion ranges from 2–3% of all Pap smears.
• High-grade squamous intraepithelial lesion and invasive cancer present on 1% of Pap smears.
• Other reactive, reparative, and ASC-US (atypical squamous cells of undetermined significance) results are difficult to assess because of the lack of reporting mechanisms.

Prevalence

26.8% of women are HPV-positive.

Risk Factors

• Cigarette smoking
• Possible deficiency of antioxidants
• Early age at first coitus
• Multiple sexual partners
• Some correlation to low socioeconomic level
• Intercourse with a high-risk male partner
• HPV infection
• Immunosuppression

General Prevention

• HPV immunization of girls and women prior to first intercourse (e.g., Gardasil) 3 doses (0, 2, 6 months) (3)[C] reduces dysplasia due to covered and related HPV strains; long-term effect on cancer as yet uncertain. Role of immunization of boys and men not yet established.
• Delay first intercourse beyond early adolescence
• Monogamous relationship for both partners
• Smoking cessation
• Adequate antioxidant-rich food intake has been associated with decreased risk
• Obtain routine Pap smears (see guidelines below)
• Use barrier methods of birth control if in nonmonogamous relationship (likely decreases but does not eliminate HPV transmission)
• Screening guidelines:
  • Screening indicated for woman beginning at age 21
  • Frequency of screening recommendations vary:
    • United States Preventive Services Task Force: Every 3 years
    • American Cancer Society/American Congress of Obstetricians and Gynecologists: Every 2 years until age 30 then every 3 years if normal
    • May be beneficial to do combined cellular screening (Pap) and high-risk HPV test in women >age 30. If normal cytology and high-risk HPV negative, screening should be repeated in no less than 3 years. If cytology is normal but HPV is positive, repeat BOTH cytology and HPV in 1 year, and if HPV remains positive (or if abnormal cytology), proceed to colposcopy (2,4).
• Screen until age 65–70. May discontinue if 3 or more consecutive, satisfactory normal or negative smears, no abnormal smears in past 10 years, or until total hysterectomy for benign conditions (1,5)

Pathophysiology

• HPV DNA is found in virtually all cervical carcinomas and precursor lesions worldwide.
• HPV viral types 16, 18, 31, 35, 45, 51, 52, 56, and 58 are common high-risk or oncogenic virus types for cervical cancer.
• HPV viral types 6, 11, 42, 43, and 44 are considered common low-risk types, and may cause genital warts.

Diagnosis

Frequently no symptoms

History

• Occasionally vaginal discharge related to sexually transmitted disease
• Rarely vaginal bleeding

Physical Exam

Pelvic exam occasionally reveals external HPV lesions.

Diagnostic Tests & Interpretation

• ThinPrep is a fluid-based collection and thin-layer preparation for cervical cancer screening.
• Sensitivity of a single Pap smear for HSIL ∼70%; specificity of ∼90%

Lab

• Bethesda system for reporting Pap/cervical smear results (cytologic grading) (6)
• Specimen adequacy
• Presence of endocervical cells:
  • Negative for intraepithelial lesion or malignancy
  • Epithelial cell abnormalities:
    • ASC: Atypical squamous cells
    • ASC-US: ASC of undetermined significance
    • ASC-H: Atypical cells cannot exclude high-grade squamous intraepithelial lesion (SIL)
    • LSIL: Low-grade SIL (combines mild dysplasia (CIN I) with HPV)
    • HSIL: High-grade SIL (combines CIN II and III)
    • Squamous cell carcinoma
    • Glandular cells
    • AGC: Atypical glandular cells
    • AGCs of undetermined significance
    • Atypical glandular cells, favor neoplasia
    • Endocervical adenocarcinoma in situ
    • Adenocarcinoma

Diagnostic Procedures/Surgery

• Colposcopy with or without biopsy recommended for the following (2) (and see algorithms):
  • Initial Pap smear with LSIL (exception for adolescent, although screening of adolescents no longer recommended), HSIL; ASCUS that is + for high-risk HPV types on (reflex) HPV hybrid capture 2 test.
  • ASC-US present on 2 Pap smears 6 months apart if HPV testing not available
  • ASC-H needs colposcopic evaluation.
  • Any abnormal or suspicious lesion of the cervix or vagina that is visualized by the eye
  • Atypical glandular cells (mandate colposcopy and uterine sampling)
• HPV viral typing:
  • Hybrid capture 2 test has 2 viral type probes: a low-risk probe and a high-risk probe.
  • High-risk (HR) probe can be used to identify patients with ASC-US who need colposcopy follow-up.
    P.3
    
    
  • HPV typing may be used in combination with Pap smear for women ≥30.
    • Low-risk women with negative cytology and who are negative for high-risk HPV may be followed every 3 years.
    • Women with negative cytology but positive (HR) probe may be approached with 1 of 2 strategies (optimal strategy uncertain): Repeat Pap and HPV in 1 year. If either Pap abnormal or HPV HR positive, then colposcopy. Order an HPV 16/18-specific probe on cytology fluid. If either probe for 16 or 18 is positive, evidence suggests the risk of a high-grade lesion is still similar to the risk for ASCUS/HPV+, and colposcopy is recommended. If HPV 16 and 18 are negative with a negative Pap and a high-risk HPV screen positive, the risk of a high-grade lesion is about 15-fold less, and repeat Pap plus HPV screen in 1 year is recommended. At 1 year, if either the Pap or the HPV test is NOT negative, then colposcopy is recommended.
  • Little utility for low-risk viral type screening
• Loop electrosurgical excision procedure (LEEP):
  • “See and treat” for HSIL in nonadolescent age groups acceptable, but not for adolescents (as they should no longer be screened).
• Cone biopsy
• Cervicography: Photographic evaluation of cervix

Pathological Findings

• Atypical squamous or columnar cells
• Coarse nuclear material
• Increased nuclear diameter
• Koilocytosis (HPV hallmark)

Differential Diagnosis

• Acute or chronic cervicitis
• Cervical squamous intraepithelial neoplasia
• Cervical glandular neoplasia
• Invasive cervical malignancy
• Uterine malignancy (rare)

Treatment

Evidence-based management algorithms guide Pap smear and post-colposcopic diagnostics and therapeutics (2,4).

Medication

• Infective/reactive Pap smear:
  • Metronidazole 250 mg t.i.d. p.o. for 7 days
• Condyloma acuminatum:
  • Cryotherapy
  • Podophyllin topically q1–2wk
  • Trichloroacetic acid, applied topically by a physician and covered for 5–6 days

Additional Treatment

General Measures

• Office evaluation and observation
• Promote smoking cessation.
• Promote protected intercourse.

Surgery/Other Procedures

• LSILs and HSILs and carcinoma in situ can be treated with outpatient surgery:
  • Cryotherapy, laser ablation, LEEP/large loop excision of transition zone, or cold-knife conization all effective, but requiring different training and with different side effects for patient
• If cervical malignancy, see Cervical Malignancy.

Ongoing Care

Follow-Up Recommendations

• LSIL/CIN1: Observation with Pap smear repeated every 6 months or high-risk HPV testing every year is appropriate for young women with LSIL, especially with confirmed CIN I.
• HPV-related CIN I typically resolves within 2–3 years.
• LSIL persisting beyond 2–3 years in a young woman is indication for colposcopy

Diet

Promote increased intake of antioxidant-rich foods.

Patient Education

• Promote HPV immunization.
• Promote smoking cessation.
• Promote protected intercourse.
• Promote regular Pap smears according to recognized guidelines.
• Reschedule follow-up consultation for any abnormality.

Prognosis

• Generally excellent
• <50% of persistent infective, reactive, reparative, or ASC-US Pap/cervical smears will have more advanced lesions.
• Only a small percentage of LSILs will progress to more advanced lesion (80% or more of adolescent and young adult CIN I resolves in 2–3 years).
• Lesions discovered early are amenable to treatment, with excellent results and few recurrences.

Complications

• Minor abnormalities on Pap/cervical smears can mask more advanced lesions.
• HSIL does progress to invasive cancer. Best estimate of risk of CIN III progression to invasive cervical cancer is >50% (7).
• Aggressive cervical surgery may be associated with cervical stenosis, cervical incompetence, and scarring affecting cervical dilatation in labor.