Cleveland Clinic Journal of Medicine

Urinary incontinence—the loss of bladder control—affects 15 million American women. Many endure it in silence, thinking that it is a normal part of aging or that no medical urinary incontinence treatments exist. But in many cases it can be managed through exercise, lifestyle changes, pelvic stimulation, and sometimes medicines or other treatments.

Types of urinary incontinence

Urgency incontinence causes an urgent desire to urinate (void), which is followed by involuntary loss of urine. This condition can be caused by an “overactive” bladder, or OAB. Normally, strong muscles (sphincters) control the flow of urine from the bladder. In OAB, the muscles contract or spasm with enough force to override the sphincter muscles of the urethra and allow urine to pass out of the bladder.

Stress incontinence occurs when an activity such as a coughing or sneezing increases pressure on the bladder. Typically, a small amount of urine leaks from the urethra. This problem can be caused by weak muscles of the pelvic floor, a weak sphincter muscle, or a problem with the way the sphincter muscle opens and closes. Women who have given birth are more likely to have stress incontinence.

Women with mixed incontinence have symptoms of both urgency and stress incontinence.

Treatment options

For urge incontinence, doctors generally recommend:

• Bladder training. You would complete a bladder diary to determine how often you urinate and then try to lengthen the time between voids.
• Kegel exercises. These help strengthen the pelvic muscles, improving pelvic support and the bladder’s ability to hold urine. When you try to stop the flow of urine or try not to pass gas, you are contracting the muscles of the pelvic floor. This is what happens when you do Kegel exercises. When doing the exercises, try not to move your legs, buttocks, or abdominal muscles. In fact, no one should be able to see that you are doing them. Do 5 sets of Kegel exercises a day. Each time you contract the muscles of the pelvic floor, hold for a slow count of 5 and then relax. Repeat this 10 times for 1 set of Kegels.
• Medications such as antidepressant drugs may be prescribed to relax the bladder. Other drugs, called anticholinergic drugs, help control muscle spasms in the bladder.

For stress incontinence, doctors generally recommend:

• Bladder training and Kegel exercises, as described above.
• Bulking agents, which are injected into the lining of the urethra. They increase the thickness of the lining of the urethra, which creates resistance against the flow of urine. Collagen is one bulking agent commonly used.

Treatments for either type of urinary incontinence include:

• Vaginal estrogen—this is used by women who are going through menopause or who are postmenopausal. Vaginal estrogen is provided in the form of creams, tablets, or a ring inserted into the vagina. It works in part by thickening the vaginal tissue, which increases pelvic support, and by relieving tissue irritation.
• Pelvic stimulation. Mild electrical impulses stimulate contractions of the pelvic floor muscles, and this eventually strengthens them. Some devices require a prescription and monthly office visits and are connected to biofeedback. Others, such as the Automatic Pelvic Exerciser (APEX M), are available over the counter.
• Biofeedback therapy with a physical therapist can help you learn how to perform Kegel exercises by letting you know if you are contracting your pelvic muscles correctly. Sensors are placed on the body or within the anus or vagina and provide feedback on a computer screen or through audio tones.
• Weight loss. Being overweight or obese can lead to urinary incontinence by increasing pressure in the abdomen. Losing even 5 pounds can make a big difference in bladder control.

This information is provided by your physician and the Cleveland Clinic Journal of Medicine. It does not replace your physician’s medical assessment and judgment.

This page may be reproduced noncommercially. For information on hundreds of health topics, see my.clevelandclinic.org/health.

Urinary incontinence—the loss of bladder control—affects 15 million American women. Many endure it in silence, thinking that it is a normal part of aging or that no medical urinary incontinence treatments exist. But in many cases it can be managed through exercise, lifestyle changes, pelvic stimulation, and sometimes medicines or other treatments.

Types of urinary incontinence

Urgency incontinence causes an urgent desire to urinate (void), which is followed by involuntary loss of urine. This condition can be caused by an “overactive” bladder, or OAB. Normally, strong muscles (sphincters) control the flow of urine from the bladder. In OAB, the muscles contract or spasm with enough force to override the sphincter muscles of the urethra and allow urine to pass out of the bladder.

Stress incontinence occurs when an activity such as a coughing or sneezing increases pressure on the bladder. Typically, a small amount of urine leaks from the urethra. This problem can be caused by weak muscles of the pelvic floor, a weak sphincter muscle, or a problem with the way the sphincter muscle opens and closes. Women who have given birth are more likely to have stress incontinence.

Women with mixed incontinence have symptoms of both urgency and stress incontinence.

Treatment options

For urge incontinence, doctors generally recommend:

• Bladder training. You would complete a bladder diary to determine how often you urinate and then try to lengthen the time between voids.
• Kegel exercises. These help strengthen the pelvic muscles, improving pelvic support and the bladder’s ability to hold urine. When you try to stop the flow of urine or try not to pass gas, you are contracting the muscles of the pelvic floor. This is what happens when you do Kegel exercises. When doing the exercises, try not to move your legs, buttocks, or abdominal muscles. In fact, no one should be able to see that you are doing them. Do 5 sets of Kegel exercises a day. Each time you contract the muscles of the pelvic floor, hold for a slow count of 5 and then relax. Repeat this 10 times for 1 set of Kegels.
• Medications such as antidepressant drugs may be prescribed to relax the bladder. Other drugs, called anticholinergic drugs, help control muscle spasms in the bladder.

For stress incontinence, doctors generally recommend:

• Bladder training and Kegel exercises, as described above.
• Bulking agents, which are injected into the lining of the urethra. They increase the thickness of the lining of the urethra, which creates resistance against the flow of urine. Collagen is one bulking agent commonly used.

Treatments for either type of urinary incontinence include:

• Vaginal estrogen—this is used by women who are going through menopause or who are postmenopausal. Vaginal estrogen is provided in the form of creams, tablets, or a ring inserted into the vagina. It works in part by thickening the vaginal tissue, which increases pelvic support, and by relieving tissue irritation.
• Pelvic stimulation. Mild electrical impulses stimulate contractions of the pelvic floor muscles, and this eventually strengthens them. Some devices require a prescription and monthly office visits and are connected to biofeedback. Others, such as the Automatic Pelvic Exerciser (APEX M), are available over the counter.
• Biofeedback therapy with a physical therapist can help you learn how to perform Kegel exercises by letting you know if you are contracting your pelvic muscles correctly. Sensors are placed on the body or within the anus or vagina and provide feedback on a computer screen or through audio tones.
• Weight loss. Being overweight or obese can lead to urinary incontinence by increasing pressure in the abdomen. Losing even 5 pounds can make a big difference in bladder control.

This information is provided by your physician and the Cleveland Clinic Journal of Medicine. It does not replace your physician’s medical assessment and judgment.

This page may be reproduced noncommercially. For information on hundreds of health topics, see my.clevelandclinic.org/health.

Urinary incontinence—the loss of bladder control—affects 15 million American women. Many endure it in silence, thinking that it is a normal part of aging or that no medical urinary incontinence treatments exist. But in many cases it can be managed through exercise, lifestyle changes, pelvic stimulation, and sometimes medicines or other treatments.

Types of urinary incontinence

Urgency incontinence causes an urgent desire to urinate (void), which is followed by involuntary loss of urine. This condition can be caused by an “overactive” bladder, or OAB. Normally, strong muscles (sphincters) control the flow of urine from the bladder. In OAB, the muscles contract or spasm with enough force to override the sphincter muscles of the urethra and allow urine to pass out of the bladder.

Stress incontinence occurs when an activity such as a coughing or sneezing increases pressure on the bladder. Typically, a small amount of urine leaks from the urethra. This problem can be caused by weak muscles of the pelvic floor, a weak sphincter muscle, or a problem with the way the sphincter muscle opens and closes. Women who have given birth are more likely to have stress incontinence.

Women with mixed incontinence have symptoms of both urgency and stress incontinence.

Treatment options

For urge incontinence, doctors generally recommend:

• Bladder training. You would complete a bladder diary to determine how often you urinate and then try to lengthen the time between voids.
• Kegel exercises. These help strengthen the pelvic muscles, improving pelvic support and the bladder’s ability to hold urine. When you try to stop the flow of urine or try not to pass gas, you are contracting the muscles of the pelvic floor. This is what happens when you do Kegel exercises. When doing the exercises, try not to move your legs, buttocks, or abdominal muscles. In fact, no one should be able to see that you are doing them. Do 5 sets of Kegel exercises a day. Each time you contract the muscles of the pelvic floor, hold for a slow count of 5 and then relax. Repeat this 10 times for 1 set of Kegels.
• Medications such as antidepressant drugs may be prescribed to relax the bladder. Other drugs, called anticholinergic drugs, help control muscle spasms in the bladder.

For stress incontinence, doctors generally recommend:

• Bladder training and Kegel exercises, as described above.
• Bulking agents, which are injected into the lining of the urethra. They increase the thickness of the lining of the urethra, which creates resistance against the flow of urine. Collagen is one bulking agent commonly used.

Treatments for either type of urinary incontinence include:

• Vaginal estrogen—this is used by women who are going through menopause or who are postmenopausal. Vaginal estrogen is provided in the form of creams, tablets, or a ring inserted into the vagina. It works in part by thickening the vaginal tissue, which increases pelvic support, and by relieving tissue irritation.
• Pelvic stimulation. Mild electrical impulses stimulate contractions of the pelvic floor muscles, and this eventually strengthens them. Some devices require a prescription and monthly office visits and are connected to biofeedback. Others, such as the Automatic Pelvic Exerciser (APEX M), are available over the counter.
• Biofeedback therapy with a physical therapist can help you learn how to perform Kegel exercises by letting you know if you are contracting your pelvic muscles correctly. Sensors are placed on the body or within the anus or vagina and provide feedback on a computer screen or through audio tones.
• Weight loss. Being overweight or obese can lead to urinary incontinence by increasing pressure in the abdomen. Losing even 5 pounds can make a big difference in bladder control.

This information is provided by your physician and the Cleveland Clinic Journal of Medicine. It does not replace your physician’s medical assessment and judgment.

This page may be reproduced noncommercially. For information on hundreds of health topics, see my.clevelandclinic.org/health.

Urinary incontinence can lead to a cascade of symptomatic burden on the patient, causing distress, embarrassment, and suffering.

See related patient information

Traditionally, incontinence has been treated by surgeons, and surgery remains an option. However, more patients are now being managed by medical clinicians, who can offer a number of newer therapies. Ideally, a medical physician can initiate the evaluation and treatment and even effectively cure some forms of urinary incontinence.

In 2014, the American College of Physicians (ACP) published recommendations on the medical treatment of urinary incontinence in women (Table 1).¹

This review describes the medical management of urinary incontinence in women, emphasizing the ACP recommendations¹ and newer over-the-counter options.

COMMON AND UNDERREPORTED

Many women erroneously believe that urinary incontinence is an inevitable consequence of aging and allow it to lessen their quality of life without seeking medical attention.

Indeed, it is common. The 2005–2006 National Health and Nutritional Examination Survey² found the prevalence of urinary incontinence in US women to be 15.7%. The prevalence increases with age from 6.9% in women ages 20 through 29 to 31.7% in those age 80 and older. A separate analysis of the same data found that 25.0% of women age 20 and older had 1 or more pelvic floor disorders.³ Some estimates are even higher. Wu et al⁴ reported a prevalence of urinary incontinence of 51.1% in women ages 31 through 54.

Too few of these women are identified and treated, for many reasons, including embarrassment and inadequate screening. Half of women with urinary incontinence do not report their symptoms because of humiliation or anxiety.⁵

The burden of urinary incontinence extends beyond the individual and into society. The total cost of overactive bladder and urgency urinary incontinence in the United States was estimated to be $65.9 billion in 2007 and is projected to reach $82.6 billion in 2020.⁶

THREE TYPES

There are 3 types of urinary incontinence: stress, urgency, and mixed.

Stress urinary incontinence is involuntary loss of urine associated with physical exertion or increased abdominal pressure, eg, with coughing or sneezing.

Urgency urinary incontinence is involuntary loss of urine associated with the sudden need to void. Many patients experience these symptoms simultaneously, making the distinction difficult.

Mixed urinary incontinence is loss of urine with both urgency and increased abdominal pressure or physical exertion.

Overactive bladder, a related problem, is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection or other obvious disease.⁷

Nongenitourinary causes such as neurologic disorders or even malignancy can present with urinary incontinence, and thus it is critical to perform a thorough initial evaluation.

A 2014 study revealed that by age 80, 20% of women may need to undergo surgery for stress urinary incontinence or pelvic organ prolapse. This statistic should motivate healthcare providers to focus on prevention and offer conservative medical management for these conditions first.⁸

QUESTIONS TO ASK

When doing a pelvic examination, once could inquire about urinary incontinence with questions such as:

Do you leak urine when you cough, sneeze, laugh, or jump or during sexual climax?

Do you have to get up more than once at night to urinate?

Do you feel the urge to urinate frequently?

BEHAVIORAL MODIFICATION AND BLADDER TRAINING

Bladder training is a conservative behavioral treatment for urinary incontinence that primary care physicians can teach. It is primarily used for urgency urinary incontinence but can also be useful in stress urinary incontinence.

After completing a bladder diary and gaining awareness of their daily voiding patterns, patients can learn scheduled voiding to train the bladder, gradually extending the urges to longer intervals.

Clinicians should instruct patients on how to train the bladder, using methods first described by Wyman and Fantl.⁹ (See Training the bladder.)

There is evidence that bladder training improves urinary incontinence compared with usual care.^10,11

The ACP recommends bladder training for women who have urgency urinary incontinence, but grades this recommendation as weak with low-quality evidence.

PELVIC FLOOR MUSCLE TRAINING

Introduced in 1948 by Dr. Arnold Kegel, pelvic floor muscle training has become widely adopted.¹²

The pelvic floor consists of a group of muscles, resembling a hammock, that support the pelvic viscera. These muscles include the coccygeus and the layers of the levator ani (Figure 1). A weak pelvic floor is one of many risk factors for developing stress urinary incontinence. Like other muscle groups, a weak pelvic floor can be rehabilitated through various techniques, often guided by a physical therapist.

Compared with those who received no treatment, women with stress urinary incontinence who performed pelvic floor muscle training were 8 times more likely to report being cured and 17 times more likely to report cure or improvement.¹³

To perform a Kegel exercise, a woman consciously contracts her pelvic floor muscles as if stopping the flow of urine.

The Knack maneuver can be used to prevent leakage during anticipated events that increase intra-abdominal pressure. For example, when a cough or sneeze is imminent, patients can preemptively contract their pelvic floor and hold the contraction through the cough or sneeze.

Although many protocols have been compared, no specific pelvic floor exercise strategy has proven superior. A systematic review assessed variations in pelvic floor interventions, exercises, and delivery and found that there was insufficient evidence to make any recommendations about the best approach. However, the benefit was greater with regular supervision during pelvic floor muscle training than with little or no supervision.¹⁴

Pelvic floor muscle training strengthens the pelvic floor, which better supports the bladder neck and anatomically compensates for defects in stress urinary incontinence. In urgency urinary incontinence, a strong pelvic floor created by muscle training prevents leaking induced by the involuntary contractions of the detrusor muscle.

Recommendation

The ACP recommends pelvic floor muscle training as first-line treatment for stress urinary incontinence and mixed urinary incontinence, and grades this recommendation as strong with high-quality evidence.

BIOFEEDBACK AND PELVIC STIMULATION

Although pelvic floor exercises are effective in urinary incontinence, 30% of patients perform them incorrectly.¹⁵

Biofeedback therapy uses visual, verbal, and acoustic signals to give the patient immediate feedback and a greater awareness of her muscular activity. A commonly used technique employs a vaginal probe to measure and display pressure changes as the patient contracts her levator ani muscles.

Women who received biofeedback in addition to traditional pelvic floor physical therapy had greater improvement in urinary incontinence than those who received pelvic physical therapy alone (risk ratio 0.75, 95% confidence interval 0.66–0.86).¹⁶

Pelvic stimulation can be used separately or in conjunction with biofeedback in both urgency and stress urinary incontinence. When pelvic stimulation is used alone, 9 women need to be treated to achieve continence in 1, and 6 women need to be treated to improve continence in 1.¹⁶ 

Traditionally delivered by a pelvic floor physical therapist, pelvic stimulation and biofeedback have also been validated for home use.^17,18 Several pelvic stimulation devices have been approved by the US Food and Drug Administration (FDA) for treating stress, urgency, and mixed urinary incontinence. These devices deliver stimulation to the pelvic floor at single or multiple frequencies. Although the mechanisms are not clearly understood, lower frequencies are used to treat urgency incontinence, while higher frequencies are used for stress incontinence. A theory is that higher-frequency stimulation strengthens the pelvic floor in stress urinary incontinence while lower frequency stimulation calms the detrusor muscle in urgency urinary incontinence.

The Apex and Apex M devices are both available over the counter, the former to treat stress urinary incontinence and the latter to treat mixed urinary incontinence, using pelvic stimulation alone. Other available devices, including the InTone and a smaller version, the InTone MV, are available by prescription and combine pelvic stimulation with biofeedback.¹⁸

Women who wish to avoid surgery, botulinum toxin injections, and daily oral medications, particularly those who are highly motivated, are ideal candidates for these over-the-counter automatic neuromuscular pelvic exercising devices.

PESSARIES AND OTHER DEVICES

Pessaries are commonly used to treat pelvic organ prolapse but can also be designed to help correct the anatomic defect responsible for stress urinary incontinence. Continence pessaries support the bladder neck so that the urethrovesicular junction is stabilized rather than hypermobile during the increased intra-abdominal pressure that occurs with coughing, sneezing, or physical exertion (Figure 2). In theory, this should decrease leakage.

A systematic review concluded that the value of pessaries in the management of incontinence remains uncertain. However, there are inherent challenges in conducting trials of such devices.¹⁹ A pessary needs to be fitted by an appropriately trained healthcare provider. The Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial²⁰ reported that behavioral therapy was more effective than a pessary at 3 months, but the treatments were equivalent at 12 months.

The FDA has approved a disposable, over-the-counter silicone intravaginal device for treating stress urinary incontinence. Patients initially purchase a sizing kit and subsequently insert the nonabsorbent temporary intravaginal bladder supportive device, which is worn for up to 8 hours.

Women may elect to use regular tampons to do the job of a pessary, as they are easy to use and low in cost. No large randomized trials have compared tampons and pessaries, and currently no one device is known to be superior to another.

Overall, these devices are temporizing measures that have few serious adverse effects.

WEIGHT LOSS AND DIETARY CHANGES

Obesity has become a national epidemic, with more than 68% of Americans found to be overweight or obese according to the National Institutes of Health.²¹

Several studies found obesity to be an independent risk factor for urinary incontinence. As early as 1946, the British Birth Cohort study found that women ages 48 through 54 who were obese earlier in life had a higher risk of urinary incontinence in middle age, and those who were obese by age 20 were more likely to report severe incontinence.²² Likewise, the Nurses’ Health Study showed that women with a body mass index (BMI) more than 30 kg/m² had 3.1 times the risk of severe incontinence compared with women with a normal BMI. Also, the Study of Women’s Health Across the Nation and the Leicestershire Medical Research Council (MRC) incontinence study both showed that a higher BMI and weight gain are strongly correlated with urinary incontinence.^23,24

Increased intra-abdominal pressure may be the causative mechanism of stress urinary incontinence in obesity. The Korean National Health and Nutrition Examination Survey showed that central adiposity correlated with urgency incontinence.^25,26

The MRC study was one of the largest to evaluate the effect of diet on urinary symptoms. Consuming a diet dense in vegetables, bread, and chicken was found to reduce the risk of urinary incontinence, while carbonated drinks were associated with a higher risk.²⁵ These studies and others may point to reducing calories, and thus BMI, as a conservative treatment for urinary incontinence.

Newer data show bariatric surgery is associated with a strong reduction in urinary incontinence, demonstrated in a study that followed patients for 3 years after surgery.²⁷ This encouraging result is but one of several positive health outcomes from bariatric surgery.

Recommendation

The ACP recommends both weight loss and exercise for overweight women with urinary incontinence, and grades this as strong with moderate-quality evidence.

DRUG THERAPY

The bladder neck is rich with sympathetic alpha-adrenergic receptors, and the bladder dome is dense with parasympathetic muscarinic receptors and sympathetic beta-adrenergic receptors. When the parasympathetic system is stimulated, the muscarinic receptors are activated, causing detrusor contraction and ultimately bladder emptying.

Agonism of beta-alpha adrenergic receptors and inhibition of parasympathetic receptors are both strategies of drug treatment of urinary incontinence.

Anticholinergic drugs

Anticholinergic medications function by blocking the muscarinic receptor, thereby inhibiting detrusor contraction.

Six oral anticholinergic medications are available: oxybutynin, tolterodine, fesoterodine, solifenacin, trospium, and darifenacin. These drugs have about the same effectiveness in treating urgency urinary incontinence, as measured by achieving continence and improving quality of life.²⁸ Given their similarity in effectiveness, the choice of agent typically relies on the side-effect profile. Extended-release formulations have a more favorable side-effect profile, with fewer cases of dry mouth compared with immediate-release formulations.²⁹

Overall, however, the benefit of these medications is small, with fewer than 200 patients achieving continence per 1,000 treated.²⁸

Other limitations of these medications include their adverse effects and contraindications, and patients’ poor adherence to therapy. The most commonly reported adverse effect is dry mouth, but other common side effects include constipation, abdominal pain, dyspepsia, fatigue, dry eye, and dry skin. Transdermal oxybutynin therapy has been associated with fewer anticholinergic side effects than oral therapy.³⁰

Contraindications to these medications include gastric retention, urinary retention, and angle-closure glaucoma.

Long-term adherence to anticholinergics is low, reported between 14% to 35% after 12 months, with the highest rates of adherence with solifenacin.³¹ The most commonly cited reason for discontinuation is lack of effect.³²

Caution is urged when considering starting anticholinergic medications in older adults because of the central nervous system side effects, including drowsiness, hallucinations, cognitive impairment, and dementia. After 3 weeks, oxybutynin caused a memory decline as measured by delayed recall that was comparable to the decline seen over 10 years in normal aging.³³ There is evidence suggesting trospium may cause less cognitive impairment, and therefore may be a better option for older patients.³⁴

Beta-3 adrenoreceptor agonists

Activation of beta-3 adrenergic receptors through the sympathetic nervous system relaxes the detrusor muscle, allowing the bladder to store urine.

Mirabegron is a selective beta-3 adrenoreceptor agonist that effectively relaxes the bladder and increases bladder capacity. It improves continence, treatment satisfaction, and quality of life.^35,36 There are fewer reports of dry mouth and constipation with this drug than with the anticholinergics; however, beta-3 adrenoreceptor agonists may be associated with greater risk of hypertension, nasopharyngitis, headache, and urinary tract infection.³⁷

Duloxetine

Duloxetine, an antidepressant, blocks the reuptake of both serotonin and norepinephrine. Consequently, it decreases parasympathetic activity and increases sympathetic and somatic activity in the urinary system.³⁸ While urine is stored, this cascade of neural activity is thought to collectively increase pudendal nerve activity and improve closure of the urethra.

Although duloxetine is approved to treat stress urinary incontinence in Europe, this is an off-label use in the United States.

A meta-analysis³⁹ found that duloxetine improved quality of life in patients with stress urinary incontinence and that subjective cure rates were 10.8% with duloxetine vs 7.7% with placebo (P = .04). However the rate of adverse events is high, with nausea most common. Given its modest benefit and high rate of side effects, physicians may consider starting duloxetine only if there are psychiatric comorbidities such as depression, anxiety, or fibromyalgia.

Recommendations

The ACP recommends against systemic pharmacologic therapy for stress urinary incontinence. For urgency urinary incontinence, pharmacologic therapy is recommended if bladder training fails, and should be individualized based on the patient’s preference and medical comorbidities and the drug’s tolerability, cost, and ease of use.

Hormone therapy

In 2014, the North American Menopause Society recommended replacing the term “vulvovaginal atrophy” with the term genitourinary syndrome of menopause, which better encompasses the postmenopausal changes to the female genital system.⁴⁰

Estrogen therapy is commercially available in both systemic and local preparations. The effect of exogenous estrogen on urinary incontinence may depend on whether it is given locally or systemically.

A systematic review⁴¹ definitively concluded that all commercially prepared local vaginal estrogen preparations can effectively relieve the genitourinary syndrome of menopause, including not only the common complaints of dryness, burning, and irritation but also urinary complaints of frequency, urgency, and urgency urinary incontinence.⁴¹ Additionally, the estradiol vaginal ring for vaginal atrophy (Estring) may have dual effects, functioning like an incontinence pessary by supporting the bladder neck while simultaneously providing local estrogen to the atrophied vaginal tissue.

However, in the Women’s Health Initiative,⁴² continent women who received either systemic estrogen therapy alone or systemic estrogen combined with progestin actually had a higher risk of developing urinary incontinence, and those already experiencing incontinence developed a worsening of their symptoms on systemic hormone therapy. The mechanism by which systemic hormone therapy causes urinary incontinence is unclear; however, previous studies showed that hormone therapy leads to a reduction in periurethral collagen and increased bladder contractility.^43,44

TAKE-HOME POINTS

• Half of women with symptomatic urinary incontinence never report their symptoms.
• Bladder training is recommended for urgency incontinence and pelvic floor muscle training for stress incontinence.
• Thirty percent of women perform pelvic floor exercises incorrectly.
• Devices can be considered, including automatic pelvic exercise devices for stress and urgency incontinence and incontinence pessaries and disposable intravaginal bladder support devices for stress incontinence.
• Higher BMIs are strongly correlated with urinary incontinence.
• Anticholinergic medications are recommended for urgency but not stress incontinence.
• Vaginal estrogen cream may help with symptoms of urinary urgency, recurrent bladder infections, and nocturia in addition to incontinence.

Urinary incontinence can lead to a cascade of symptomatic burden on the patient, causing distress, embarrassment, and suffering.

See related patient information

Traditionally, incontinence has been treated by surgeons, and surgery remains an option. However, more patients are now being managed by medical clinicians, who can offer a number of newer therapies. Ideally, a medical physician can initiate the evaluation and treatment and even effectively cure some forms of urinary incontinence.

In 2014, the American College of Physicians (ACP) published recommendations on the medical treatment of urinary incontinence in women (Table 1).¹

This review describes the medical management of urinary incontinence in women, emphasizing the ACP recommendations¹ and newer over-the-counter options.

COMMON AND UNDERREPORTED

Many women erroneously believe that urinary incontinence is an inevitable consequence of aging and allow it to lessen their quality of life without seeking medical attention.

Indeed, it is common. The 2005–2006 National Health and Nutritional Examination Survey² found the prevalence of urinary incontinence in US women to be 15.7%. The prevalence increases with age from 6.9% in women ages 20 through 29 to 31.7% in those age 80 and older. A separate analysis of the same data found that 25.0% of women age 20 and older had 1 or more pelvic floor disorders.³ Some estimates are even higher. Wu et al⁴ reported a prevalence of urinary incontinence of 51.1% in women ages 31 through 54.

Too few of these women are identified and treated, for many reasons, including embarrassment and inadequate screening. Half of women with urinary incontinence do not report their symptoms because of humiliation or anxiety.⁵

The burden of urinary incontinence extends beyond the individual and into society. The total cost of overactive bladder and urgency urinary incontinence in the United States was estimated to be $65.9 billion in 2007 and is projected to reach $82.6 billion in 2020.⁶

THREE TYPES

There are 3 types of urinary incontinence: stress, urgency, and mixed.

Stress urinary incontinence is involuntary loss of urine associated with physical exertion or increased abdominal pressure, eg, with coughing or sneezing.

Urgency urinary incontinence is involuntary loss of urine associated with the sudden need to void. Many patients experience these symptoms simultaneously, making the distinction difficult.

Mixed urinary incontinence is loss of urine with both urgency and increased abdominal pressure or physical exertion.

Overactive bladder, a related problem, is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection or other obvious disease.⁷

Nongenitourinary causes such as neurologic disorders or even malignancy can present with urinary incontinence, and thus it is critical to perform a thorough initial evaluation.

A 2014 study revealed that by age 80, 20% of women may need to undergo surgery for stress urinary incontinence or pelvic organ prolapse. This statistic should motivate healthcare providers to focus on prevention and offer conservative medical management for these conditions first.⁸

QUESTIONS TO ASK

When doing a pelvic examination, once could inquire about urinary incontinence with questions such as:

Do you leak urine when you cough, sneeze, laugh, or jump or during sexual climax?

Do you have to get up more than once at night to urinate?

Do you feel the urge to urinate frequently?

BEHAVIORAL MODIFICATION AND BLADDER TRAINING

Bladder training is a conservative behavioral treatment for urinary incontinence that primary care physicians can teach. It is primarily used for urgency urinary incontinence but can also be useful in stress urinary incontinence.

After completing a bladder diary and gaining awareness of their daily voiding patterns, patients can learn scheduled voiding to train the bladder, gradually extending the urges to longer intervals.

Clinicians should instruct patients on how to train the bladder, using methods first described by Wyman and Fantl.⁹ (See Training the bladder.)

There is evidence that bladder training improves urinary incontinence compared with usual care.^10,11

The ACP recommends bladder training for women who have urgency urinary incontinence, but grades this recommendation as weak with low-quality evidence.

PELVIC FLOOR MUSCLE TRAINING

Introduced in 1948 by Dr. Arnold Kegel, pelvic floor muscle training has become widely adopted.¹²

The pelvic floor consists of a group of muscles, resembling a hammock, that support the pelvic viscera. These muscles include the coccygeus and the layers of the levator ani (Figure 1). A weak pelvic floor is one of many risk factors for developing stress urinary incontinence. Like other muscle groups, a weak pelvic floor can be rehabilitated through various techniques, often guided by a physical therapist.

Compared with those who received no treatment, women with stress urinary incontinence who performed pelvic floor muscle training were 8 times more likely to report being cured and 17 times more likely to report cure or improvement.¹³

To perform a Kegel exercise, a woman consciously contracts her pelvic floor muscles as if stopping the flow of urine.

The Knack maneuver can be used to prevent leakage during anticipated events that increase intra-abdominal pressure. For example, when a cough or sneeze is imminent, patients can preemptively contract their pelvic floor and hold the contraction through the cough or sneeze.

Although many protocols have been compared, no specific pelvic floor exercise strategy has proven superior. A systematic review assessed variations in pelvic floor interventions, exercises, and delivery and found that there was insufficient evidence to make any recommendations about the best approach. However, the benefit was greater with regular supervision during pelvic floor muscle training than with little or no supervision.¹⁴

Pelvic floor muscle training strengthens the pelvic floor, which better supports the bladder neck and anatomically compensates for defects in stress urinary incontinence. In urgency urinary incontinence, a strong pelvic floor created by muscle training prevents leaking induced by the involuntary contractions of the detrusor muscle.

Recommendation

The ACP recommends pelvic floor muscle training as first-line treatment for stress urinary incontinence and mixed urinary incontinence, and grades this recommendation as strong with high-quality evidence.

BIOFEEDBACK AND PELVIC STIMULATION

Although pelvic floor exercises are effective in urinary incontinence, 30% of patients perform them incorrectly.¹⁵

Biofeedback therapy uses visual, verbal, and acoustic signals to give the patient immediate feedback and a greater awareness of her muscular activity. A commonly used technique employs a vaginal probe to measure and display pressure changes as the patient contracts her levator ani muscles.

Women who received biofeedback in addition to traditional pelvic floor physical therapy had greater improvement in urinary incontinence than those who received pelvic physical therapy alone (risk ratio 0.75, 95% confidence interval 0.66–0.86).¹⁶

Pelvic stimulation can be used separately or in conjunction with biofeedback in both urgency and stress urinary incontinence. When pelvic stimulation is used alone, 9 women need to be treated to achieve continence in 1, and 6 women need to be treated to improve continence in 1.¹⁶ 

Traditionally delivered by a pelvic floor physical therapist, pelvic stimulation and biofeedback have also been validated for home use.^17,18 Several pelvic stimulation devices have been approved by the US Food and Drug Administration (FDA) for treating stress, urgency, and mixed urinary incontinence. These devices deliver stimulation to the pelvic floor at single or multiple frequencies. Although the mechanisms are not clearly understood, lower frequencies are used to treat urgency incontinence, while higher frequencies are used for stress incontinence. A theory is that higher-frequency stimulation strengthens the pelvic floor in stress urinary incontinence while lower frequency stimulation calms the detrusor muscle in urgency urinary incontinence.

The Apex and Apex M devices are both available over the counter, the former to treat stress urinary incontinence and the latter to treat mixed urinary incontinence, using pelvic stimulation alone. Other available devices, including the InTone and a smaller version, the InTone MV, are available by prescription and combine pelvic stimulation with biofeedback.¹⁸

Women who wish to avoid surgery, botulinum toxin injections, and daily oral medications, particularly those who are highly motivated, are ideal candidates for these over-the-counter automatic neuromuscular pelvic exercising devices.

PESSARIES AND OTHER DEVICES

Pessaries are commonly used to treat pelvic organ prolapse but can also be designed to help correct the anatomic defect responsible for stress urinary incontinence. Continence pessaries support the bladder neck so that the urethrovesicular junction is stabilized rather than hypermobile during the increased intra-abdominal pressure that occurs with coughing, sneezing, or physical exertion (Figure 2). In theory, this should decrease leakage.

A systematic review concluded that the value of pessaries in the management of incontinence remains uncertain. However, there are inherent challenges in conducting trials of such devices.¹⁹ A pessary needs to be fitted by an appropriately trained healthcare provider. The Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial²⁰ reported that behavioral therapy was more effective than a pessary at 3 months, but the treatments were equivalent at 12 months.

The FDA has approved a disposable, over-the-counter silicone intravaginal device for treating stress urinary incontinence. Patients initially purchase a sizing kit and subsequently insert the nonabsorbent temporary intravaginal bladder supportive device, which is worn for up to 8 hours.

Women may elect to use regular tampons to do the job of a pessary, as they are easy to use and low in cost. No large randomized trials have compared tampons and pessaries, and currently no one device is known to be superior to another.

Overall, these devices are temporizing measures that have few serious adverse effects.

WEIGHT LOSS AND DIETARY CHANGES

Obesity has become a national epidemic, with more than 68% of Americans found to be overweight or obese according to the National Institutes of Health.²¹

Several studies found obesity to be an independent risk factor for urinary incontinence. As early as 1946, the British Birth Cohort study found that women ages 48 through 54 who were obese earlier in life had a higher risk of urinary incontinence in middle age, and those who were obese by age 20 were more likely to report severe incontinence.²² Likewise, the Nurses’ Health Study showed that women with a body mass index (BMI) more than 30 kg/m² had 3.1 times the risk of severe incontinence compared with women with a normal BMI. Also, the Study of Women’s Health Across the Nation and the Leicestershire Medical Research Council (MRC) incontinence study both showed that a higher BMI and weight gain are strongly correlated with urinary incontinence.^23,24

Increased intra-abdominal pressure may be the causative mechanism of stress urinary incontinence in obesity. The Korean National Health and Nutrition Examination Survey showed that central adiposity correlated with urgency incontinence.^25,26

The MRC study was one of the largest to evaluate the effect of diet on urinary symptoms. Consuming a diet dense in vegetables, bread, and chicken was found to reduce the risk of urinary incontinence, while carbonated drinks were associated with a higher risk.²⁵ These studies and others may point to reducing calories, and thus BMI, as a conservative treatment for urinary incontinence.

Newer data show bariatric surgery is associated with a strong reduction in urinary incontinence, demonstrated in a study that followed patients for 3 years after surgery.²⁷ This encouraging result is but one of several positive health outcomes from bariatric surgery.

Recommendation

The ACP recommends both weight loss and exercise for overweight women with urinary incontinence, and grades this as strong with moderate-quality evidence.

DRUG THERAPY

The bladder neck is rich with sympathetic alpha-adrenergic receptors, and the bladder dome is dense with parasympathetic muscarinic receptors and sympathetic beta-adrenergic receptors. When the parasympathetic system is stimulated, the muscarinic receptors are activated, causing detrusor contraction and ultimately bladder emptying.

Agonism of beta-alpha adrenergic receptors and inhibition of parasympathetic receptors are both strategies of drug treatment of urinary incontinence.

Anticholinergic drugs

Anticholinergic medications function by blocking the muscarinic receptor, thereby inhibiting detrusor contraction.

Six oral anticholinergic medications are available: oxybutynin, tolterodine, fesoterodine, solifenacin, trospium, and darifenacin. These drugs have about the same effectiveness in treating urgency urinary incontinence, as measured by achieving continence and improving quality of life.²⁸ Given their similarity in effectiveness, the choice of agent typically relies on the side-effect profile. Extended-release formulations have a more favorable side-effect profile, with fewer cases of dry mouth compared with immediate-release formulations.²⁹

Overall, however, the benefit of these medications is small, with fewer than 200 patients achieving continence per 1,000 treated.²⁸

Other limitations of these medications include their adverse effects and contraindications, and patients’ poor adherence to therapy. The most commonly reported adverse effect is dry mouth, but other common side effects include constipation, abdominal pain, dyspepsia, fatigue, dry eye, and dry skin. Transdermal oxybutynin therapy has been associated with fewer anticholinergic side effects than oral therapy.³⁰

Contraindications to these medications include gastric retention, urinary retention, and angle-closure glaucoma.

Long-term adherence to anticholinergics is low, reported between 14% to 35% after 12 months, with the highest rates of adherence with solifenacin.³¹ The most commonly cited reason for discontinuation is lack of effect.³²

Caution is urged when considering starting anticholinergic medications in older adults because of the central nervous system side effects, including drowsiness, hallucinations, cognitive impairment, and dementia. After 3 weeks, oxybutynin caused a memory decline as measured by delayed recall that was comparable to the decline seen over 10 years in normal aging.³³ There is evidence suggesting trospium may cause less cognitive impairment, and therefore may be a better option for older patients.³⁴

Beta-3 adrenoreceptor agonists

Activation of beta-3 adrenergic receptors through the sympathetic nervous system relaxes the detrusor muscle, allowing the bladder to store urine.

Mirabegron is a selective beta-3 adrenoreceptor agonist that effectively relaxes the bladder and increases bladder capacity. It improves continence, treatment satisfaction, and quality of life.^35,36 There are fewer reports of dry mouth and constipation with this drug than with the anticholinergics; however, beta-3 adrenoreceptor agonists may be associated with greater risk of hypertension, nasopharyngitis, headache, and urinary tract infection.³⁷

Duloxetine

Duloxetine, an antidepressant, blocks the reuptake of both serotonin and norepinephrine. Consequently, it decreases parasympathetic activity and increases sympathetic and somatic activity in the urinary system.³⁸ While urine is stored, this cascade of neural activity is thought to collectively increase pudendal nerve activity and improve closure of the urethra.

Although duloxetine is approved to treat stress urinary incontinence in Europe, this is an off-label use in the United States.

A meta-analysis³⁹ found that duloxetine improved quality of life in patients with stress urinary incontinence and that subjective cure rates were 10.8% with duloxetine vs 7.7% with placebo (P = .04). However the rate of adverse events is high, with nausea most common. Given its modest benefit and high rate of side effects, physicians may consider starting duloxetine only if there are psychiatric comorbidities such as depression, anxiety, or fibromyalgia.

Recommendations

The ACP recommends against systemic pharmacologic therapy for stress urinary incontinence. For urgency urinary incontinence, pharmacologic therapy is recommended if bladder training fails, and should be individualized based on the patient’s preference and medical comorbidities and the drug’s tolerability, cost, and ease of use.

Hormone therapy

In 2014, the North American Menopause Society recommended replacing the term “vulvovaginal atrophy” with the term genitourinary syndrome of menopause, which better encompasses the postmenopausal changes to the female genital system.⁴⁰

Estrogen therapy is commercially available in both systemic and local preparations. The effect of exogenous estrogen on urinary incontinence may depend on whether it is given locally or systemically.

A systematic review⁴¹ definitively concluded that all commercially prepared local vaginal estrogen preparations can effectively relieve the genitourinary syndrome of menopause, including not only the common complaints of dryness, burning, and irritation but also urinary complaints of frequency, urgency, and urgency urinary incontinence.⁴¹ Additionally, the estradiol vaginal ring for vaginal atrophy (Estring) may have dual effects, functioning like an incontinence pessary by supporting the bladder neck while simultaneously providing local estrogen to the atrophied vaginal tissue.

However, in the Women’s Health Initiative,⁴² continent women who received either systemic estrogen therapy alone or systemic estrogen combined with progestin actually had a higher risk of developing urinary incontinence, and those already experiencing incontinence developed a worsening of their symptoms on systemic hormone therapy. The mechanism by which systemic hormone therapy causes urinary incontinence is unclear; however, previous studies showed that hormone therapy leads to a reduction in periurethral collagen and increased bladder contractility.^43,44

TAKE-HOME POINTS

• Half of women with symptomatic urinary incontinence never report their symptoms.
• Bladder training is recommended for urgency incontinence and pelvic floor muscle training for stress incontinence.
• Thirty percent of women perform pelvic floor exercises incorrectly.
• Devices can be considered, including automatic pelvic exercise devices for stress and urgency incontinence and incontinence pessaries and disposable intravaginal bladder support devices for stress incontinence.
• Higher BMIs are strongly correlated with urinary incontinence.
• Anticholinergic medications are recommended for urgency but not stress incontinence.
• Vaginal estrogen cream may help with symptoms of urinary urgency, recurrent bladder infections, and nocturia in addition to incontinence.

Urinary incontinence can lead to a cascade of symptomatic burden on the patient, causing distress, embarrassment, and suffering.

See related patient information

Traditionally, incontinence has been treated by surgeons, and surgery remains an option. However, more patients are now being managed by medical clinicians, who can offer a number of newer therapies. Ideally, a medical physician can initiate the evaluation and treatment and even effectively cure some forms of urinary incontinence.

In 2014, the American College of Physicians (ACP) published recommendations on the medical treatment of urinary incontinence in women (Table 1).¹

This review describes the medical management of urinary incontinence in women, emphasizing the ACP recommendations¹ and newer over-the-counter options.

COMMON AND UNDERREPORTED

Many women erroneously believe that urinary incontinence is an inevitable consequence of aging and allow it to lessen their quality of life without seeking medical attention.

Indeed, it is common. The 2005–2006 National Health and Nutritional Examination Survey² found the prevalence of urinary incontinence in US women to be 15.7%. The prevalence increases with age from 6.9% in women ages 20 through 29 to 31.7% in those age 80 and older. A separate analysis of the same data found that 25.0% of women age 20 and older had 1 or more pelvic floor disorders.³ Some estimates are even higher. Wu et al⁴ reported a prevalence of urinary incontinence of 51.1% in women ages 31 through 54.

Too few of these women are identified and treated, for many reasons, including embarrassment and inadequate screening. Half of women with urinary incontinence do not report their symptoms because of humiliation or anxiety.⁵

The burden of urinary incontinence extends beyond the individual and into society. The total cost of overactive bladder and urgency urinary incontinence in the United States was estimated to be $65.9 billion in 2007 and is projected to reach $82.6 billion in 2020.⁶

THREE TYPES

There are 3 types of urinary incontinence: stress, urgency, and mixed.

Stress urinary incontinence is involuntary loss of urine associated with physical exertion or increased abdominal pressure, eg, with coughing or sneezing.

Urgency urinary incontinence is involuntary loss of urine associated with the sudden need to void. Many patients experience these symptoms simultaneously, making the distinction difficult.

Mixed urinary incontinence is loss of urine with both urgency and increased abdominal pressure or physical exertion.

Overactive bladder, a related problem, is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection or other obvious disease.⁷

Nongenitourinary causes such as neurologic disorders or even malignancy can present with urinary incontinence, and thus it is critical to perform a thorough initial evaluation.

A 2014 study revealed that by age 80, 20% of women may need to undergo surgery for stress urinary incontinence or pelvic organ prolapse. This statistic should motivate healthcare providers to focus on prevention and offer conservative medical management for these conditions first.⁸

QUESTIONS TO ASK

When doing a pelvic examination, once could inquire about urinary incontinence with questions such as:

Do you leak urine when you cough, sneeze, laugh, or jump or during sexual climax?

Do you have to get up more than once at night to urinate?

Do you feel the urge to urinate frequently?

BEHAVIORAL MODIFICATION AND BLADDER TRAINING

Bladder training is a conservative behavioral treatment for urinary incontinence that primary care physicians can teach. It is primarily used for urgency urinary incontinence but can also be useful in stress urinary incontinence.

After completing a bladder diary and gaining awareness of their daily voiding patterns, patients can learn scheduled voiding to train the bladder, gradually extending the urges to longer intervals.

Clinicians should instruct patients on how to train the bladder, using methods first described by Wyman and Fantl.⁹ (See Training the bladder.)

There is evidence that bladder training improves urinary incontinence compared with usual care.^10,11

The ACP recommends bladder training for women who have urgency urinary incontinence, but grades this recommendation as weak with low-quality evidence.

PELVIC FLOOR MUSCLE TRAINING

Introduced in 1948 by Dr. Arnold Kegel, pelvic floor muscle training has become widely adopted.¹²

The pelvic floor consists of a group of muscles, resembling a hammock, that support the pelvic viscera. These muscles include the coccygeus and the layers of the levator ani (Figure 1). A weak pelvic floor is one of many risk factors for developing stress urinary incontinence. Like other muscle groups, a weak pelvic floor can be rehabilitated through various techniques, often guided by a physical therapist.

Compared with those who received no treatment, women with stress urinary incontinence who performed pelvic floor muscle training were 8 times more likely to report being cured and 17 times more likely to report cure or improvement.¹³

To perform a Kegel exercise, a woman consciously contracts her pelvic floor muscles as if stopping the flow of urine.

The Knack maneuver can be used to prevent leakage during anticipated events that increase intra-abdominal pressure. For example, when a cough or sneeze is imminent, patients can preemptively contract their pelvic floor and hold the contraction through the cough or sneeze.

Although many protocols have been compared, no specific pelvic floor exercise strategy has proven superior. A systematic review assessed variations in pelvic floor interventions, exercises, and delivery and found that there was insufficient evidence to make any recommendations about the best approach. However, the benefit was greater with regular supervision during pelvic floor muscle training than with little or no supervision.¹⁴

Pelvic floor muscle training strengthens the pelvic floor, which better supports the bladder neck and anatomically compensates for defects in stress urinary incontinence. In urgency urinary incontinence, a strong pelvic floor created by muscle training prevents leaking induced by the involuntary contractions of the detrusor muscle.

Recommendation

The ACP recommends pelvic floor muscle training as first-line treatment for stress urinary incontinence and mixed urinary incontinence, and grades this recommendation as strong with high-quality evidence.

BIOFEEDBACK AND PELVIC STIMULATION

Although pelvic floor exercises are effective in urinary incontinence, 30% of patients perform them incorrectly.¹⁵

Biofeedback therapy uses visual, verbal, and acoustic signals to give the patient immediate feedback and a greater awareness of her muscular activity. A commonly used technique employs a vaginal probe to measure and display pressure changes as the patient contracts her levator ani muscles.

Women who received biofeedback in addition to traditional pelvic floor physical therapy had greater improvement in urinary incontinence than those who received pelvic physical therapy alone (risk ratio 0.75, 95% confidence interval 0.66–0.86).¹⁶

Pelvic stimulation can be used separately or in conjunction with biofeedback in both urgency and stress urinary incontinence. When pelvic stimulation is used alone, 9 women need to be treated to achieve continence in 1, and 6 women need to be treated to improve continence in 1.¹⁶ 

Traditionally delivered by a pelvic floor physical therapist, pelvic stimulation and biofeedback have also been validated for home use.^17,18 Several pelvic stimulation devices have been approved by the US Food and Drug Administration (FDA) for treating stress, urgency, and mixed urinary incontinence. These devices deliver stimulation to the pelvic floor at single or multiple frequencies. Although the mechanisms are not clearly understood, lower frequencies are used to treat urgency incontinence, while higher frequencies are used for stress incontinence. A theory is that higher-frequency stimulation strengthens the pelvic floor in stress urinary incontinence while lower frequency stimulation calms the detrusor muscle in urgency urinary incontinence.

The Apex and Apex M devices are both available over the counter, the former to treat stress urinary incontinence and the latter to treat mixed urinary incontinence, using pelvic stimulation alone. Other available devices, including the InTone and a smaller version, the InTone MV, are available by prescription and combine pelvic stimulation with biofeedback.¹⁸

Women who wish to avoid surgery, botulinum toxin injections, and daily oral medications, particularly those who are highly motivated, are ideal candidates for these over-the-counter automatic neuromuscular pelvic exercising devices.

PESSARIES AND OTHER DEVICES

Pessaries are commonly used to treat pelvic organ prolapse but can also be designed to help correct the anatomic defect responsible for stress urinary incontinence. Continence pessaries support the bladder neck so that the urethrovesicular junction is stabilized rather than hypermobile during the increased intra-abdominal pressure that occurs with coughing, sneezing, or physical exertion (Figure 2). In theory, this should decrease leakage.

A systematic review concluded that the value of pessaries in the management of incontinence remains uncertain. However, there are inherent challenges in conducting trials of such devices.¹⁹ A pessary needs to be fitted by an appropriately trained healthcare provider. The Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial²⁰ reported that behavioral therapy was more effective than a pessary at 3 months, but the treatments were equivalent at 12 months.

The FDA has approved a disposable, over-the-counter silicone intravaginal device for treating stress urinary incontinence. Patients initially purchase a sizing kit and subsequently insert the nonabsorbent temporary intravaginal bladder supportive device, which is worn for up to 8 hours.

Women may elect to use regular tampons to do the job of a pessary, as they are easy to use and low in cost. No large randomized trials have compared tampons and pessaries, and currently no one device is known to be superior to another.

Overall, these devices are temporizing measures that have few serious adverse effects.

WEIGHT LOSS AND DIETARY CHANGES

Obesity has become a national epidemic, with more than 68% of Americans found to be overweight or obese according to the National Institutes of Health.²¹

Several studies found obesity to be an independent risk factor for urinary incontinence. As early as 1946, the British Birth Cohort study found that women ages 48 through 54 who were obese earlier in life had a higher risk of urinary incontinence in middle age, and those who were obese by age 20 were more likely to report severe incontinence.²² Likewise, the Nurses’ Health Study showed that women with a body mass index (BMI) more than 30 kg/m² had 3.1 times the risk of severe incontinence compared with women with a normal BMI. Also, the Study of Women’s Health Across the Nation and the Leicestershire Medical Research Council (MRC) incontinence study both showed that a higher BMI and weight gain are strongly correlated with urinary incontinence.^23,24

Increased intra-abdominal pressure may be the causative mechanism of stress urinary incontinence in obesity. The Korean National Health and Nutrition Examination Survey showed that central adiposity correlated with urgency incontinence.^25,26

The MRC study was one of the largest to evaluate the effect of diet on urinary symptoms. Consuming a diet dense in vegetables, bread, and chicken was found to reduce the risk of urinary incontinence, while carbonated drinks were associated with a higher risk.²⁵ These studies and others may point to reducing calories, and thus BMI, as a conservative treatment for urinary incontinence.

Newer data show bariatric surgery is associated with a strong reduction in urinary incontinence, demonstrated in a study that followed patients for 3 years after surgery.²⁷ This encouraging result is but one of several positive health outcomes from bariatric surgery.

Recommendation

The ACP recommends both weight loss and exercise for overweight women with urinary incontinence, and grades this as strong with moderate-quality evidence.

DRUG THERAPY

The bladder neck is rich with sympathetic alpha-adrenergic receptors, and the bladder dome is dense with parasympathetic muscarinic receptors and sympathetic beta-adrenergic receptors. When the parasympathetic system is stimulated, the muscarinic receptors are activated, causing detrusor contraction and ultimately bladder emptying.

Agonism of beta-alpha adrenergic receptors and inhibition of parasympathetic receptors are both strategies of drug treatment of urinary incontinence.

Anticholinergic drugs

Anticholinergic medications function by blocking the muscarinic receptor, thereby inhibiting detrusor contraction.

Six oral anticholinergic medications are available: oxybutynin, tolterodine, fesoterodine, solifenacin, trospium, and darifenacin. These drugs have about the same effectiveness in treating urgency urinary incontinence, as measured by achieving continence and improving quality of life.²⁸ Given their similarity in effectiveness, the choice of agent typically relies on the side-effect profile. Extended-release formulations have a more favorable side-effect profile, with fewer cases of dry mouth compared with immediate-release formulations.²⁹

Overall, however, the benefit of these medications is small, with fewer than 200 patients achieving continence per 1,000 treated.²⁸

Other limitations of these medications include their adverse effects and contraindications, and patients’ poor adherence to therapy. The most commonly reported adverse effect is dry mouth, but other common side effects include constipation, abdominal pain, dyspepsia, fatigue, dry eye, and dry skin. Transdermal oxybutynin therapy has been associated with fewer anticholinergic side effects than oral therapy.³⁰

Contraindications to these medications include gastric retention, urinary retention, and angle-closure glaucoma.

Long-term adherence to anticholinergics is low, reported between 14% to 35% after 12 months, with the highest rates of adherence with solifenacin.³¹ The most commonly cited reason for discontinuation is lack of effect.³²

Caution is urged when considering starting anticholinergic medications in older adults because of the central nervous system side effects, including drowsiness, hallucinations, cognitive impairment, and dementia. After 3 weeks, oxybutynin caused a memory decline as measured by delayed recall that was comparable to the decline seen over 10 years in normal aging.³³ There is evidence suggesting trospium may cause less cognitive impairment, and therefore may be a better option for older patients.³⁴

Beta-3 adrenoreceptor agonists

Activation of beta-3 adrenergic receptors through the sympathetic nervous system relaxes the detrusor muscle, allowing the bladder to store urine.

Mirabegron is a selective beta-3 adrenoreceptor agonist that effectively relaxes the bladder and increases bladder capacity. It improves continence, treatment satisfaction, and quality of life.^35,36 There are fewer reports of dry mouth and constipation with this drug than with the anticholinergics; however, beta-3 adrenoreceptor agonists may be associated with greater risk of hypertension, nasopharyngitis, headache, and urinary tract infection.³⁷

Duloxetine

Duloxetine, an antidepressant, blocks the reuptake of both serotonin and norepinephrine. Consequently, it decreases parasympathetic activity and increases sympathetic and somatic activity in the urinary system.³⁸ While urine is stored, this cascade of neural activity is thought to collectively increase pudendal nerve activity and improve closure of the urethra.

Although duloxetine is approved to treat stress urinary incontinence in Europe, this is an off-label use in the United States.

A meta-analysis³⁹ found that duloxetine improved quality of life in patients with stress urinary incontinence and that subjective cure rates were 10.8% with duloxetine vs 7.7% with placebo (P = .04). However the rate of adverse events is high, with nausea most common. Given its modest benefit and high rate of side effects, physicians may consider starting duloxetine only if there are psychiatric comorbidities such as depression, anxiety, or fibromyalgia.

Recommendations

The ACP recommends against systemic pharmacologic therapy for stress urinary incontinence. For urgency urinary incontinence, pharmacologic therapy is recommended if bladder training fails, and should be individualized based on the patient’s preference and medical comorbidities and the drug’s tolerability, cost, and ease of use.

Hormone therapy

In 2014, the North American Menopause Society recommended replacing the term “vulvovaginal atrophy” with the term genitourinary syndrome of menopause, which better encompasses the postmenopausal changes to the female genital system.⁴⁰

Estrogen therapy is commercially available in both systemic and local preparations. The effect of exogenous estrogen on urinary incontinence may depend on whether it is given locally or systemically.

A systematic review⁴¹ definitively concluded that all commercially prepared local vaginal estrogen preparations can effectively relieve the genitourinary syndrome of menopause, including not only the common complaints of dryness, burning, and irritation but also urinary complaints of frequency, urgency, and urgency urinary incontinence.⁴¹ Additionally, the estradiol vaginal ring for vaginal atrophy (Estring) may have dual effects, functioning like an incontinence pessary by supporting the bladder neck while simultaneously providing local estrogen to the atrophied vaginal tissue.

However, in the Women’s Health Initiative,⁴² continent women who received either systemic estrogen therapy alone or systemic estrogen combined with progestin actually had a higher risk of developing urinary incontinence, and those already experiencing incontinence developed a worsening of their symptoms on systemic hormone therapy. The mechanism by which systemic hormone therapy causes urinary incontinence is unclear; however, previous studies showed that hormone therapy leads to a reduction in periurethral collagen and increased bladder contractility.^43,44

TAKE-HOME POINTS

• Half of women with symptomatic urinary incontinence never report their symptoms.
• Bladder training is recommended for urgency incontinence and pelvic floor muscle training for stress incontinence.
• Thirty percent of women perform pelvic floor exercises incorrectly.
• Devices can be considered, including automatic pelvic exercise devices for stress and urgency incontinence and incontinence pessaries and disposable intravaginal bladder support devices for stress incontinence.
• Higher BMIs are strongly correlated with urinary incontinence.
• Anticholinergic medications are recommended for urgency but not stress incontinence.
• Vaginal estrogen cream may help with symptoms of urinary urgency, recurrent bladder infections, and nocturia in addition to incontinence.

To the Editor: I enjoyed Dr. Galicia-Castillo’s article about long-term opioid therapy in older adults,¹ which reaffirmed the imperative to “start low and go slow” to minimize the risk of addiction. However, the article missed an opportunity to raise awareness regarding another extremely important side effect of chronic prescription opioid consumption, that of ingestion prior to sleep, with consequent cessation of breathing leading to death.

According to the Drug Enforcement Administration,² most narcotic deaths are a result of respiratory depression. And the American Pain Society has stated, “No patient has succumbed to [opioid] respiratory depression while awake.”³

Dr. Galicia-Castillo noted that the prevalence of central sleep apnea in chronic opioid users is 24%, based on a review by Correa et al.⁴ As alarming as this number is, other investigators have estimated it to be even higher—as high as 50% to 90%.⁵

Walker et al,⁶ in a study of 60 patients, found that the higher the opioid dose the patients were on, the more episodes of obstructive sleep apnea and central sleep apnea per hour they had. Yet prescribing a low dose does not adequately protect the chronic opioid user. Farney et al⁷ reported that oxygen saturation dropped precipitously—from 98% to 70%—15 minutes after a patient took just 7.5 mg of hydrocodone in the middle of the night. Mogri et al⁸ reported that a patient had 91 apnea events within 1 hour of taking 15 mg of oxycodone at 2 am.

Opioids, benzodiazepines, barbiturates, and ethanol individually and additively suppress medullary reflex ventilatory drive during sleep, especially during non–rapid-eye-movement (non-REM) sleep.⁶ During waking hours, in contrast, there is redundant backup of cerebral cortical drive, ensuring that we keep breathing. Therefore, people are most vulnerable to dying of opioid ingestion during sleep.

Moreover, oxygen desaturation during episodes of sleep apnea may precipitate seizures (which may be lethal) or coronary vasospasm with consequent malignant arrhythmias and myocardial ischemia.

Continuous positive airway pressure protects against obstructive sleep apnea, but not against central sleep apnea.⁹

Patients need to be aware of the danger, and physicians need to consider the pharmacokinetic profiles of the opioid preparations they prescribe. If patients are taking an opioid that has a short half-life, such as immediate-release oxycodone, they should not take it within 5 hours of sleep. Longer-lasting preparations need a longer interval, and some, such as extended-release tramadol, may need to be taken only on awakening.

Safe sleep can be facilitated by medications that are sedating but do not compromise ventilation. Optimal agents also enhance restorative REM and stage III and IV deep-sleep duration, and some may have the additional benefit of reducing the risk of cancer.^10,11 Such agents may include baclofen, cyproheptadine, gabapentin, mirtazepine, and melatonin. Nonpharmacologic measures include sleep hygiene, aerobic exercise, and cognitive behavioral therapy.

A retrospective study¹² found that 301 (60.4%) of 498 patients who died while on opioid therapy and whose death was judged to be related to the opioid were also taking benzodiazepines. Patients who take opioids should avoid taking benzodiazepines, barbiturates, or alcohol before going to sleep, and physicians should be extremely cautious about prescribing benzodiazepines and barbiturates to patients who are on opioids. 

To the Editor: I enjoyed Dr. Galicia-Castillo’s article about long-term opioid therapy in older adults,¹ which reaffirmed the imperative to “start low and go slow” to minimize the risk of addiction. However, the article missed an opportunity to raise awareness regarding another extremely important side effect of chronic prescription opioid consumption, that of ingestion prior to sleep, with consequent cessation of breathing leading to death.

According to the Drug Enforcement Administration,² most narcotic deaths are a result of respiratory depression. And the American Pain Society has stated, “No patient has succumbed to [opioid] respiratory depression while awake.”³

Dr. Galicia-Castillo noted that the prevalence of central sleep apnea in chronic opioid users is 24%, based on a review by Correa et al.⁴ As alarming as this number is, other investigators have estimated it to be even higher—as high as 50% to 90%.⁵

Walker et al,⁶ in a study of 60 patients, found that the higher the opioid dose the patients were on, the more episodes of obstructive sleep apnea and central sleep apnea per hour they had. Yet prescribing a low dose does not adequately protect the chronic opioid user. Farney et al⁷ reported that oxygen saturation dropped precipitously—from 98% to 70%—15 minutes after a patient took just 7.5 mg of hydrocodone in the middle of the night. Mogri et al⁸ reported that a patient had 91 apnea events within 1 hour of taking 15 mg of oxycodone at 2 am.

Opioids, benzodiazepines, barbiturates, and ethanol individually and additively suppress medullary reflex ventilatory drive during sleep, especially during non–rapid-eye-movement (non-REM) sleep.⁶ During waking hours, in contrast, there is redundant backup of cerebral cortical drive, ensuring that we keep breathing. Therefore, people are most vulnerable to dying of opioid ingestion during sleep.

Moreover, oxygen desaturation during episodes of sleep apnea may precipitate seizures (which may be lethal) or coronary vasospasm with consequent malignant arrhythmias and myocardial ischemia.

Continuous positive airway pressure protects against obstructive sleep apnea, but not against central sleep apnea.⁹

Patients need to be aware of the danger, and physicians need to consider the pharmacokinetic profiles of the opioid preparations they prescribe. If patients are taking an opioid that has a short half-life, such as immediate-release oxycodone, they should not take it within 5 hours of sleep. Longer-lasting preparations need a longer interval, and some, such as extended-release tramadol, may need to be taken only on awakening.

Safe sleep can be facilitated by medications that are sedating but do not compromise ventilation. Optimal agents also enhance restorative REM and stage III and IV deep-sleep duration, and some may have the additional benefit of reducing the risk of cancer.^10,11 Such agents may include baclofen, cyproheptadine, gabapentin, mirtazepine, and melatonin. Nonpharmacologic measures include sleep hygiene, aerobic exercise, and cognitive behavioral therapy.

A retrospective study¹² found that 301 (60.4%) of 498 patients who died while on opioid therapy and whose death was judged to be related to the opioid were also taking benzodiazepines. Patients who take opioids should avoid taking benzodiazepines, barbiturates, or alcohol before going to sleep, and physicians should be extremely cautious about prescribing benzodiazepines and barbiturates to patients who are on opioids. 

To the Editor: I enjoyed Dr. Galicia-Castillo’s article about long-term opioid therapy in older adults,¹ which reaffirmed the imperative to “start low and go slow” to minimize the risk of addiction. However, the article missed an opportunity to raise awareness regarding another extremely important side effect of chronic prescription opioid consumption, that of ingestion prior to sleep, with consequent cessation of breathing leading to death.

According to the Drug Enforcement Administration,² most narcotic deaths are a result of respiratory depression. And the American Pain Society has stated, “No patient has succumbed to [opioid] respiratory depression while awake.”³

Dr. Galicia-Castillo noted that the prevalence of central sleep apnea in chronic opioid users is 24%, based on a review by Correa et al.⁴ As alarming as this number is, other investigators have estimated it to be even higher—as high as 50% to 90%.⁵

Walker et al,⁶ in a study of 60 patients, found that the higher the opioid dose the patients were on, the more episodes of obstructive sleep apnea and central sleep apnea per hour they had. Yet prescribing a low dose does not adequately protect the chronic opioid user. Farney et al⁷ reported that oxygen saturation dropped precipitously—from 98% to 70%—15 minutes after a patient took just 7.5 mg of hydrocodone in the middle of the night. Mogri et al⁸ reported that a patient had 91 apnea events within 1 hour of taking 15 mg of oxycodone at 2 am.

Opioids, benzodiazepines, barbiturates, and ethanol individually and additively suppress medullary reflex ventilatory drive during sleep, especially during non–rapid-eye-movement (non-REM) sleep.⁶ During waking hours, in contrast, there is redundant backup of cerebral cortical drive, ensuring that we keep breathing. Therefore, people are most vulnerable to dying of opioid ingestion during sleep.

Moreover, oxygen desaturation during episodes of sleep apnea may precipitate seizures (which may be lethal) or coronary vasospasm with consequent malignant arrhythmias and myocardial ischemia.

Continuous positive airway pressure protects against obstructive sleep apnea, but not against central sleep apnea.⁹

Patients need to be aware of the danger, and physicians need to consider the pharmacokinetic profiles of the opioid preparations they prescribe. If patients are taking an opioid that has a short half-life, such as immediate-release oxycodone, they should not take it within 5 hours of sleep. Longer-lasting preparations need a longer interval, and some, such as extended-release tramadol, may need to be taken only on awakening.

Safe sleep can be facilitated by medications that are sedating but do not compromise ventilation. Optimal agents also enhance restorative REM and stage III and IV deep-sleep duration, and some may have the additional benefit of reducing the risk of cancer.^10,11 Such agents may include baclofen, cyproheptadine, gabapentin, mirtazepine, and melatonin. Nonpharmacologic measures include sleep hygiene, aerobic exercise, and cognitive behavioral therapy.

A retrospective study¹² found that 301 (60.4%) of 498 patients who died while on opioid therapy and whose death was judged to be related to the opioid were also taking benzodiazepines. Patients who take opioids should avoid taking benzodiazepines, barbiturates, or alcohol before going to sleep, and physicians should be extremely cautious about prescribing benzodiazepines and barbiturates to patients who are on opioids. 

In Reply: Dr. Geller makes some excellent points about sleep and opioid use.

Opioids pose risks,¹ just like any other type of medication. In particular, opioids have been linked to sleep-disordered breathing, which affects 70% to 85% of patients taking opioids.^2–4

Other options can be used in some older adults, but they are not always successful. Ideally, nonpharmacologic strategies and nonopioid medications such as acetaminophen, nonsteroidal anti-inflammatory agents, antidepressants, and anticonvulsants should be used, although these medications have their own side effects. Optimum pain control may offer the potential for significant improvement in function, and opioids are but one tool in the clinician’s kit.

Ongoing discussions of the risks and benefits are necessary, along with continuous re-evaluation of the need for and effect of opioids.

In Reply: Dr. Geller makes some excellent points about sleep and opioid use.

Opioids pose risks,¹ just like any other type of medication. In particular, opioids have been linked to sleep-disordered breathing, which affects 70% to 85% of patients taking opioids.^2–4

Other options can be used in some older adults, but they are not always successful. Ideally, nonpharmacologic strategies and nonopioid medications such as acetaminophen, nonsteroidal anti-inflammatory agents, antidepressants, and anticonvulsants should be used, although these medications have their own side effects. Optimum pain control may offer the potential for significant improvement in function, and opioids are but one tool in the clinician’s kit.

Ongoing discussions of the risks and benefits are necessary, along with continuous re-evaluation of the need for and effect of opioids.

In Reply: Dr. Geller makes some excellent points about sleep and opioid use.

Opioids pose risks,¹ just like any other type of medication. In particular, opioids have been linked to sleep-disordered breathing, which affects 70% to 85% of patients taking opioids.^2–4

Other options can be used in some older adults, but they are not always successful. Ideally, nonpharmacologic strategies and nonopioid medications such as acetaminophen, nonsteroidal anti-inflammatory agents, antidepressants, and anticonvulsants should be used, although these medications have their own side effects. Optimum pain control may offer the potential for significant improvement in function, and opioids are but one tool in the clinician’s kit.

Ongoing discussions of the risks and benefits are necessary, along with continuous re-evaluation of the need for and effect of opioids.

To the Editor: I read with interest the review on submassive pulmonary embolism by Ataya et al¹ in the December 2016 issue. I had 3 questions or observations for the authors

First, systemic thrombolytic therapy for massive or hemodynamically unstable pulmonary embolism is given a grade 2C recommendation, similar to the level for select patients with submassive pulmonary embolism with low bleeding risk but at high risk of developing hypotension. The reference for this is the 2012 American College of Chest Physicians guidelines.² I would like to point out that these guidelines were updated and published in February 2016,³ and systemic thrombolytic therapy for massive pulmonary embolism now carries a grade 2B recommendation. Thrombolytic therapy still has a grade 2C recommendation for select patients with submassive pulmonary embolism.

Second, the Moderate Pulmonary Embolism Treated With Thrombolysis (MOPETT) trial is described as a randomized trial in patients with moderate pulmonary hypertension and right ventricular dysfunction. I would like to point out that right ventricular dysfunction was not a criterion for enrollment in the trial.⁴

Finally, catheter-directed thrombolytic therapy is mentioned as an option for select patients with submassive and massive pulmonary embolism. The advantage is believed to be due to local action of the drug with fewer systemic effects. Since the protocol involves alteplase for 12 or 24 hours with a maximum dose of 24 mg, and since in most cases pulmonary embolism originates in the lower extremity, are we not exposing these patients to further clot propagation for 12 or 24 hours without the benefit of concomitant systemic anticoagulation or an inferior vena cava filter?

To the Editor: I read with interest the review on submassive pulmonary embolism by Ataya et al¹ in the December 2016 issue. I had 3 questions or observations for the authors

First, systemic thrombolytic therapy for massive or hemodynamically unstable pulmonary embolism is given a grade 2C recommendation, similar to the level for select patients with submassive pulmonary embolism with low bleeding risk but at high risk of developing hypotension. The reference for this is the 2012 American College of Chest Physicians guidelines.² I would like to point out that these guidelines were updated and published in February 2016,³ and systemic thrombolytic therapy for massive pulmonary embolism now carries a grade 2B recommendation. Thrombolytic therapy still has a grade 2C recommendation for select patients with submassive pulmonary embolism.

Second, the Moderate Pulmonary Embolism Treated With Thrombolysis (MOPETT) trial is described as a randomized trial in patients with moderate pulmonary hypertension and right ventricular dysfunction. I would like to point out that right ventricular dysfunction was not a criterion for enrollment in the trial.⁴

Finally, catheter-directed thrombolytic therapy is mentioned as an option for select patients with submassive and massive pulmonary embolism. The advantage is believed to be due to local action of the drug with fewer systemic effects. Since the protocol involves alteplase for 12 or 24 hours with a maximum dose of 24 mg, and since in most cases pulmonary embolism originates in the lower extremity, are we not exposing these patients to further clot propagation for 12 or 24 hours without the benefit of concomitant systemic anticoagulation or an inferior vena cava filter?

To the Editor: I read with interest the review on submassive pulmonary embolism by Ataya et al¹ in the December 2016 issue. I had 3 questions or observations for the authors

First, systemic thrombolytic therapy for massive or hemodynamically unstable pulmonary embolism is given a grade 2C recommendation, similar to the level for select patients with submassive pulmonary embolism with low bleeding risk but at high risk of developing hypotension. The reference for this is the 2012 American College of Chest Physicians guidelines.² I would like to point out that these guidelines were updated and published in February 2016,³ and systemic thrombolytic therapy for massive pulmonary embolism now carries a grade 2B recommendation. Thrombolytic therapy still has a grade 2C recommendation for select patients with submassive pulmonary embolism.

Second, the Moderate Pulmonary Embolism Treated With Thrombolysis (MOPETT) trial is described as a randomized trial in patients with moderate pulmonary hypertension and right ventricular dysfunction. I would like to point out that right ventricular dysfunction was not a criterion for enrollment in the trial.⁴

Finally, catheter-directed thrombolytic therapy is mentioned as an option for select patients with submassive and massive pulmonary embolism. The advantage is believed to be due to local action of the drug with fewer systemic effects. Since the protocol involves alteplase for 12 or 24 hours with a maximum dose of 24 mg, and since in most cases pulmonary embolism originates in the lower extremity, are we not exposing these patients to further clot propagation for 12 or 24 hours without the benefit of concomitant systemic anticoagulation or an inferior vena cava filter?

In Reply: We thank Dr. Katyal for his thoughtful comments.

Dr. Katyal points out that the grade of recommendation for thrombolysis in patients with massive pulmonary embolism was upgraded from 2C to 2B in the 2016 American College of Chest Physicians (ACCP) guidelines¹ compared with the 2012 guidelines² that we cited. The upgrade in this recommendation was owing to 2 small trials and 1 large randomized controlled trial that included patients with submassive pulmonary embolism.^3–5 Interestingly, these 3 studies led to an upgrade in the level of recommendation for thrombolysis in the treatment of massive pulmonary embolism, perhaps more from a safety aspect (in view of the incidence of major bleeding vs mortality). Regardless, Dr. Katyal is correct in highlighting that the new 2016 ACCP guidelines now give a grade of 2B for thrombolytic therapy in the treatment of massive pulmonary embolism. These guidelines had not been published at the time of submission of our manuscript.

Dr. Katyal is also correct that patients were not required to have right ventricular dysfunction to be enrolled in the MOPETT trial.³ As we pointed out, “Only 20% of the participants were enrolled on the basis of right ventricular dysfunction on echocardiography, whereas almost 60% had elevated cardiac biomarkers.”⁶

Regarding catheter-directed therapy, patients who received low-dose catheter-directed alteplase were also concurrently anticoagulated with systemic unfractionated heparin in the Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism (ULTIMA) trial.⁷ The ULTIMA trial authors commented that unfractionated heparin was started with an 80-U/kg bolus followed by an 18-U/kg/hour infusion to target an anti-factor Xa level of 0.3 to 0.7 μg/mL, which is considered therapeutic anticoagulation. The investigators in the SEATTLE II trial⁸ continued systemic unfractionated heparin but targeted a lower “intermediate” anticoagulation target (an augmented partial thromboplastin time of 40–60 seconds), so these patients weren’t completely without systemic anticoagulation either. At our institution, the current practice is to target an anti-Xa level of 0.3 to 0.7 μg/mL in patients receiving catheter-directed therapy for large-volume pulmonary embolism.

In Reply: We thank Dr. Katyal for his thoughtful comments.

Dr. Katyal points out that the grade of recommendation for thrombolysis in patients with massive pulmonary embolism was upgraded from 2C to 2B in the 2016 American College of Chest Physicians (ACCP) guidelines¹ compared with the 2012 guidelines² that we cited. The upgrade in this recommendation was owing to 2 small trials and 1 large randomized controlled trial that included patients with submassive pulmonary embolism.^3–5 Interestingly, these 3 studies led to an upgrade in the level of recommendation for thrombolysis in the treatment of massive pulmonary embolism, perhaps more from a safety aspect (in view of the incidence of major bleeding vs mortality). Regardless, Dr. Katyal is correct in highlighting that the new 2016 ACCP guidelines now give a grade of 2B for thrombolytic therapy in the treatment of massive pulmonary embolism. These guidelines had not been published at the time of submission of our manuscript.

Dr. Katyal is also correct that patients were not required to have right ventricular dysfunction to be enrolled in the MOPETT trial.³ As we pointed out, “Only 20% of the participants were enrolled on the basis of right ventricular dysfunction on echocardiography, whereas almost 60% had elevated cardiac biomarkers.”⁶

Regarding catheter-directed therapy, patients who received low-dose catheter-directed alteplase were also concurrently anticoagulated with systemic unfractionated heparin in the Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism (ULTIMA) trial.⁷ The ULTIMA trial authors commented that unfractionated heparin was started with an 80-U/kg bolus followed by an 18-U/kg/hour infusion to target an anti-factor Xa level of 0.3 to 0.7 μg/mL, which is considered therapeutic anticoagulation. The investigators in the SEATTLE II trial⁸ continued systemic unfractionated heparin but targeted a lower “intermediate” anticoagulation target (an augmented partial thromboplastin time of 40–60 seconds), so these patients weren’t completely without systemic anticoagulation either. At our institution, the current practice is to target an anti-Xa level of 0.3 to 0.7 μg/mL in patients receiving catheter-directed therapy for large-volume pulmonary embolism.

In Reply: We thank Dr. Katyal for his thoughtful comments.

Dr. Katyal points out that the grade of recommendation for thrombolysis in patients with massive pulmonary embolism was upgraded from 2C to 2B in the 2016 American College of Chest Physicians (ACCP) guidelines¹ compared with the 2012 guidelines² that we cited. The upgrade in this recommendation was owing to 2 small trials and 1 large randomized controlled trial that included patients with submassive pulmonary embolism.^3–5 Interestingly, these 3 studies led to an upgrade in the level of recommendation for thrombolysis in the treatment of massive pulmonary embolism, perhaps more from a safety aspect (in view of the incidence of major bleeding vs mortality). Regardless, Dr. Katyal is correct in highlighting that the new 2016 ACCP guidelines now give a grade of 2B for thrombolytic therapy in the treatment of massive pulmonary embolism. These guidelines had not been published at the time of submission of our manuscript.

Dr. Katyal is also correct that patients were not required to have right ventricular dysfunction to be enrolled in the MOPETT trial.³ As we pointed out, “Only 20% of the participants were enrolled on the basis of right ventricular dysfunction on echocardiography, whereas almost 60% had elevated cardiac biomarkers.”⁶

Regarding catheter-directed therapy, patients who received low-dose catheter-directed alteplase were also concurrently anticoagulated with systemic unfractionated heparin in the Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism (ULTIMA) trial.⁷ The ULTIMA trial authors commented that unfractionated heparin was started with an 80-U/kg bolus followed by an 18-U/kg/hour infusion to target an anti-factor Xa level of 0.3 to 0.7 μg/mL, which is considered therapeutic anticoagulation. The investigators in the SEATTLE II trial⁸ continued systemic unfractionated heparin but targeted a lower “intermediate” anticoagulation target (an augmented partial thromboplastin time of 40–60 seconds), so these patients weren’t completely without systemic anticoagulation either. At our institution, the current practice is to target an anti-Xa level of 0.3 to 0.7 μg/mL in patients receiving catheter-directed therapy for large-volume pulmonary embolism.

The article by Hagerty and Rich in this issue of the Cleveland Clinic Journal of Medicine¹ covers an important topic—whether elderly patients with atrial fibrillation should receive anticoagulant therapy for it, or whether the risk of bleeding with this therapy outweighs the benefit of preventing stroke.

See related article

BETTER RISK PREDICTORS ARE NEEDED

Prediction tools are available for estimating the risk of stroke in patients with atrial fibrillation without anticoagulation^2,3 and to estimate bleeding risk from anticoagulation^4–7 (Table 1). Both tools have limitations, but as Hagerty and Rich point out, the stroke risk scales are likely better than the bleeding risk scales.

For example, Fang et al⁸ note that the risk of intracranial hemorrhage increases significantly after age 85. The bleeding risk scales use lower age cutoffs than this, perhaps increasing their sensitivity but decreasing their specificity.

Although HAS-BLED^5,6 includes antiplatelet drugs such as nonsteroidal anti-inflammatory drugs and aspirin as risk factors for bleeding, ATRIA⁴ and HEMORR₂HAGES⁷ do not.

Other drugs such as macrolides, quinolones, and high-dose corticosteroids raise the international normalized ratio (INR). These are typically used short-term, but can cause major fluctuations in the INR that may not be detected by monthly INR checks. Incorporating the short-term use of such drugs into bleeding risk scales would be difficult if not impossible a priori. Yet clinicians should be aware that these drugs can affect bleeding risk.

As Hagerty and Rich note,¹ the bleeding risk scores were developed for warfarin, and their applicability to patients treated with novel oral anticoagulants is uncertain.

All three of the available bleeding risk scales consider prior bleeding as a risk factor, but the severity of the prior bleeding varies. Although it is understandable to include major bleeding as a risk factor since it carries an increased risk of death, minor bleeding can affect morbidity and quality of life. Only the ATRIA score⁴ considers both major and minor bleeding, while HEMORR₂HAGES⁷ does not specify bleeding severity, and HAS-BLED^5,6 considers only major bleeding. Clearly, there is a need to update these existing bleeding risk scores so that they can apply to novel oral anticoagulants and consider both major and minor bleeding.

As the authors note, for predicting the risk of stroke, the CHA₂DS₂-VASc score³ provides more precision than the CHADS₂ score² at the lower end of the benefit spectrum. Unfortunately, there is no similar screening tool to predict bleeding risk from anticoagulation with greater precision in the middle to lower part of the risk spectrum.

THE PATIENT’S PREFERENCES MATTER

The patient’s life expectancy and personal preferences are important independent factors that affect the decision of whether to anticoagulate or not. It is the responsibility of clinicians who care for older adults to make sure that these two important considerations are included in any anticoagulation decision-making for this group of patients.

The article by Hagerty and Rich in this issue of the Cleveland Clinic Journal of Medicine¹ covers an important topic—whether elderly patients with atrial fibrillation should receive anticoagulant therapy for it, or whether the risk of bleeding with this therapy outweighs the benefit of preventing stroke.

See related article

BETTER RISK PREDICTORS ARE NEEDED

Prediction tools are available for estimating the risk of stroke in patients with atrial fibrillation without anticoagulation^2,3 and to estimate bleeding risk from anticoagulation^4–7 (Table 1). Both tools have limitations, but as Hagerty and Rich point out, the stroke risk scales are likely better than the bleeding risk scales.

For example, Fang et al⁸ note that the risk of intracranial hemorrhage increases significantly after age 85. The bleeding risk scales use lower age cutoffs than this, perhaps increasing their sensitivity but decreasing their specificity.

Although HAS-BLED^5,6 includes antiplatelet drugs such as nonsteroidal anti-inflammatory drugs and aspirin as risk factors for bleeding, ATRIA⁴ and HEMORR₂HAGES⁷ do not.

Other drugs such as macrolides, quinolones, and high-dose corticosteroids raise the international normalized ratio (INR). These are typically used short-term, but can cause major fluctuations in the INR that may not be detected by monthly INR checks. Incorporating the short-term use of such drugs into bleeding risk scales would be difficult if not impossible a priori. Yet clinicians should be aware that these drugs can affect bleeding risk.

As Hagerty and Rich note,¹ the bleeding risk scores were developed for warfarin, and their applicability to patients treated with novel oral anticoagulants is uncertain.

All three of the available bleeding risk scales consider prior bleeding as a risk factor, but the severity of the prior bleeding varies. Although it is understandable to include major bleeding as a risk factor since it carries an increased risk of death, minor bleeding can affect morbidity and quality of life. Only the ATRIA score⁴ considers both major and minor bleeding, while HEMORR₂HAGES⁷ does not specify bleeding severity, and HAS-BLED^5,6 considers only major bleeding. Clearly, there is a need to update these existing bleeding risk scores so that they can apply to novel oral anticoagulants and consider both major and minor bleeding.

As the authors note, for predicting the risk of stroke, the CHA₂DS₂-VASc score³ provides more precision than the CHADS₂ score² at the lower end of the benefit spectrum. Unfortunately, there is no similar screening tool to predict bleeding risk from anticoagulation with greater precision in the middle to lower part of the risk spectrum.

THE PATIENT’S PREFERENCES MATTER

The patient’s life expectancy and personal preferences are important independent factors that affect the decision of whether to anticoagulate or not. It is the responsibility of clinicians who care for older adults to make sure that these two important considerations are included in any anticoagulation decision-making for this group of patients.

The article by Hagerty and Rich in this issue of the Cleveland Clinic Journal of Medicine¹ covers an important topic—whether elderly patients with atrial fibrillation should receive anticoagulant therapy for it, or whether the risk of bleeding with this therapy outweighs the benefit of preventing stroke.

See related article

BETTER RISK PREDICTORS ARE NEEDED

Prediction tools are available for estimating the risk of stroke in patients with atrial fibrillation without anticoagulation^2,3 and to estimate bleeding risk from anticoagulation^4–7 (Table 1). Both tools have limitations, but as Hagerty and Rich point out, the stroke risk scales are likely better than the bleeding risk scales.

For example, Fang et al⁸ note that the risk of intracranial hemorrhage increases significantly after age 85. The bleeding risk scales use lower age cutoffs than this, perhaps increasing their sensitivity but decreasing their specificity.

Although HAS-BLED^5,6 includes antiplatelet drugs such as nonsteroidal anti-inflammatory drugs and aspirin as risk factors for bleeding, ATRIA⁴ and HEMORR₂HAGES⁷ do not.

Other drugs such as macrolides, quinolones, and high-dose corticosteroids raise the international normalized ratio (INR). These are typically used short-term, but can cause major fluctuations in the INR that may not be detected by monthly INR checks. Incorporating the short-term use of such drugs into bleeding risk scales would be difficult if not impossible a priori. Yet clinicians should be aware that these drugs can affect bleeding risk.

As Hagerty and Rich note,¹ the bleeding risk scores were developed for warfarin, and their applicability to patients treated with novel oral anticoagulants is uncertain.

All three of the available bleeding risk scales consider prior bleeding as a risk factor, but the severity of the prior bleeding varies. Although it is understandable to include major bleeding as a risk factor since it carries an increased risk of death, minor bleeding can affect morbidity and quality of life. Only the ATRIA score⁴ considers both major and minor bleeding, while HEMORR₂HAGES⁷ does not specify bleeding severity, and HAS-BLED^5,6 considers only major bleeding. Clearly, there is a need to update these existing bleeding risk scores so that they can apply to novel oral anticoagulants and consider both major and minor bleeding.

As the authors note, for predicting the risk of stroke, the CHA₂DS₂-VASc score³ provides more precision than the CHADS₂ score² at the lower end of the benefit spectrum. Unfortunately, there is no similar screening tool to predict bleeding risk from anticoagulation with greater precision in the middle to lower part of the risk spectrum.

THE PATIENT’S PREFERENCES MATTER

The patient’s life expectancy and personal preferences are important independent factors that affect the decision of whether to anticoagulate or not. It is the responsibility of clinicians who care for older adults to make sure that these two important considerations are included in any anticoagulation decision-making for this group of patients.

People who have been exposed to an infectious disease should be evaluated promptly and systematically, whether they are healthcare professionals at work,¹ patients, or contacts of patients. The primary goals are to prevent acquisition and transmission of the infection, allay the exposed person’s anxiety, and avoid unnecessary interventions and loss of work days.^1,2 Some may need postexposure prophylaxis.

ESSENTIAL ELEMENTS OF POSTEXPOSURE MANAGEMENT

Because postexposure management can be challenging, an experienced clinician or expert consultant (eg, infectious disease specialist, infection control provider, or public health officer) should be involved. Institution-specific policies and procedures for postexposure prophylaxis and testing should be followed.^1,2

Postexposure management should include the following elements:

• Immediate care of the wound or other site of exposure in cases of blood-borne exposures and tetanus- and rabies-prone injuries. This includes thoroughly washing with soap and water or cleansing with an antiseptic agent, flushing affected mucous membranes with water, and debridement of devitalized tissue.^1–6
• Deciding whether postexposure prophylaxis is indicated and, if so, the type, dose, route, and duration.
• Initiating prophylaxis as soon as possible.
• Determining an appropriate baseline assessment and follow-up plan for the exposed individual.
• Counseling exposed women who are pregnant or breast-feeding about the risks and benefits of postexposure prophylaxis to mother, fetus, and infant.
• Identifying required infection control precautions, including work and school restriction, for exposed and source individuals.
• Counseling and psychological support for exposed individuals, who need to know about the risks of acquiring the infection and transmitting it to others, infection control precautions, benefits, and adverse effects of postexposure prophylaxis, the importance of adhering to the regimen, and the follow-up plan. They must understand that this treatment may not completely prevent the infection, and they should seek medical attention if they develop fever or any symptoms or signs of the infection of concern.^1,2

IS POSTEXPOSURE PROPHYLAXIS INDICATED?

Postexposure management begins with an assessment to determine whether the exposure is likely to result in infection; whether the exposed individual is susceptible to the infection of concern or is at greater risk of complications from it than the general population; and whether postexposure prophylaxis is needed. This involves a complete focused history, physical examination, and laboratory testing of the potentially exposed individual and of the source, if possible.^1,2

Postexposure prophylaxis should begin as soon as possible to maximize its effects while awaiting the results of further diagnostic tests. However, if the exposed individual seeks care after the recommended period, prophylactic therapy can still be effective for certain infections that have a long incubation period, such as tetanus and rabies.^5,6 The choice of regimen should be guided by efficacy, safety, cost, toxicity, ease of adherence, drug interactions, and antimicrobial resistance.^1,2

HOW GREAT IS THE RISK OF INFECTION?

Exposed individuals are not all at the same risk of acquiring a given infection. The risk depends on:

• Type and extent of exposure (see below)
• Characteristics of the infectious agent (eg, virulence, infectious dose)
• Status of the infectious source (eg, whether the disease is in its infectious period or is being treated); effective treatment can shorten the duration of microbial shedding and subsequently reduce risk of transmission of certain infections such as tuberculosis, meningococcal infection, invasive group A streptococcal infection, and pertussis^7–10
• Immune status of the exposed individual (eg, prior infection or vaccination), since people who are immune to the infection of concern usually do not need postexposure prophylaxis²
• Adherence to infection prevention and control principles; postexposure prophylaxis may not be required if the potentially exposed individual was wearing appropriate personal protective equipment such as a surgical mask, gown, and gloves and was following standard precautions.¹

WHO SHOULD BE RESTRICTED FROM WORK OR SCHOOL?

Most people without symptoms who were exposed to most types of infections do not need to stay home from work or school. However, susceptible people, particularly healthcare providers exposed to measles, mumps, rubella, and varicella, should be excluded from work while they are capable of transmitting these diseases, even if they have no symptoms.^11,12 Moreover, people with symptoms with infections primarily transmitted via the airborne, droplet, or contact route should be restricted from work until no longer infectious.^1,2,7,9–15

Most healthcare institutions have clear protocols for managing occupational exposures to infectious diseases, in particular for blood-borne pathogens such as human immunodeficiency virus (HIV). The protocol should include appropriate evaluation and laboratory testing of the source patient and exposed healthcare provider, as well as procedures for counseling the exposed provider, identifying and procuring an initial prophylactic regimen for timely administration, a mechanism for formal expert consultation (eg, with an in-house infectious diseases consultant), and a plan for outpatient follow-up.

The next section reviews postexposure management of common infections categorized by mode of transmission, including the risk of transmission, initial and follow-up evaluation, and considerations for postexposure prophylaxis.

BLOOD-BORNE INFECTIONS

Blood-borne pathogens can be transmitted by accidental needlesticks or cuts or by exposure of the eyes, mucous membranes, or nonintact skin to blood, tissue, or other potentially infectious body fluids—cerebrospinal, pericardial, pleural, peritoneal, synovial, and amniotic fluid, semen, and vaginal secretions. (Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are considered noninfectious for blood-borne pathogens unless they contain blood.¹⁶)

Healthcare professionals are commonly exposed to blood-borne pathogens as a result of needlestick injuries, and these exposures tend to be underreported.¹⁷

When someone has been exposed to blood or other infectious body fluids, the source individual and the exposed individual should be assessed for risk factors for hepatitis B virus, hepatitis C virus, HIV, and other blood-borne pathogens.^3,4,16,18 If the disease status for these viruses is unknown, the source and exposed individual should be tested in accordance with institutional policies regarding consent to testing. Testing of needles or sharp instruments implicated in an exposure is not recommended.^3,4,16,18

Determining the need for prophylaxis after exposure to an unknown source such as a disposed needle can be challenging. Assessment should be made on a case-by-case basis, depending on the known prevalence of the infection of concern in the local community. The risk of transmission in most source-unknown exposures is negligible.^3,4,18 However, hepatitis B vaccine and hepatitis B immunoglobulin should be used liberally as postexposure prophylaxis for previously unvaccinated healthcare providers exposed to an unknown source.^3,4,16,18

Hepatitis B

Hepatitis B virus (Table 1) is the most infectious of the common blood-borne viruses. The risk of transmission after percutaneous exposure to hepatitis B-infected blood ranges from 1% to 30% based on hepatitis Be antigen status and viral load (based on hepatitis B viral DNA).^1,2,4,16

Hepatitis B vaccine or immunoglobulin, or both, are recommended for postexposure prophylaxis in pregnant women, based on evidence that perinatal transmission was reduced by 70% to 90% when these were given within 12 to 24 hours of exposure.^4,16,19

Hepatitis C

The risk of infection after percutaneous exposure to hepatitis C virus-infected blood is estimated to be 1.8% per exposure.¹⁶ The risk is lower with exposure of a mucous membrane or nonintact skin to blood, fluids, or tissues from hepatitis C-infected patients.^16,18

Since there is no effective postexposure prophylactic regimen, the goal of postexposure assessment of hepatitis C is early identification of infection (by monitoring the patient to see if he or she seroconverts) and, if infection is present, referral to an experienced clinician for further evaluation (Table 1). However, data supporting the utility of direct-acting anti-hepatitis C antiviral drugs as postexposure prophylaxis after occupational exposure to hepatitis C are lacking.

Human immunodeficiency virus

The estimated risk of HIV transmission from a known infected source after percutaneous exposure is 0.3%, and after mucosal exposures it is 0.09%.²⁰

If postexposure prophylaxis is indicated, it should be a three-drug regimen (Table 1).^3,18 The recommended antiretroviral therapies have been proven effective in clinical trials of HIV treatment, not for postexposure prophylaxis per se, but they are recommended because they are effective, safe, tolerable, and associated with high adherence rates.^3,16,18,21 If the source individual is known to have HIV infection, information about his or her stage of infection, CD4+ T-cell count, results of viral load testing, current and previous antiretroviral therapy, and results of any genotypic viral resistance testing will guide the choice of postexposure prophylactic regimen.^3,18

The clinician should give the exposed patient a starter pack of 5 to 7 days of medication, give the first dose then and there, and arrange follow-up with an experienced clinician within a few days of the exposure to determine whether a complete 30-day course is needed.^3,16,18

SEXUALLY TRANSMITTED INFECTIONS

In the case of sexually transmitted infections, “exposure” means unprotected sexual contact with someone who has a sexually transmitted infection.²² People with sexually transmitted infections often have no symptoms but can still transmit the infection. Thus, people at risk should be identified and screened for all suspected sexually transmitted infections.^23–25

Patients with sexually transmitted infections should be instructed to refer their sex partners for evaluation and treatment to prevent further transmission and reinfection. Assessment of exposed partners includes a medical history, physical examination, microbiologic testing for all potential sexually transmitted infections, and eligibility for hepatitis A virus, hepatitis B virus, and human papillomavirus vaccines.²² Ideally, exposed partners should be reassessed within 1 to 2 weeks to follow up testing results and to monitor for side effects of and adherence to postexposure prophylaxis, if applicable.

Public health departments should be notified of sexually transmitted infections such as gonorrhea, chlamydia, chancroid, and syphilis.²²

Expedited partner therapy, in which index patients deliver the medication or a prescription for it directly to their partners, is an alternative for partner management where legally allowed by state and local health departments (see www.cdc.gov/std/ept/legal/).²²

Recommended postexposure prophylactic regimens for sexually transmitted infections (Table 2) are based on their efficacy in the treatment of these infections.^22,26–28 The regimen for HIV prophylaxis is the same as in Table 1.^3,18,26

Chlamydia

Chlamydia is the most commonly reported communicable disease in the United States. The risk of transmission after sexual intercourse with a person who has an active infection is approximately 65% and increases with the number of exposures.^22,29

Gonorrhea

Infection with Neisseria gonorrhoeae is the second most commonly reported communicable disease in the United States. The transmission rate of gonorrhea after sex with someone who has it ranges from 50% to 93%.²² When prescribing postexposure prophylaxis for gonorrhea, it is essential to consider the risk of antimicrobial resistance and local susceptibility data.²²

Human immunodeficiency virus

Risk of HIV transmission through sexual contact varies depending on the nature of the exposure, ranging from 0.05% to 0.5%.³⁰

Syphilis

The risk of transmission of syphilis in its early stages (primary and secondary) after sexual exposure is approximately 30%. Transmission requires open lesions such as chancres in primary syphilis and mucocutaneous lesions (mucous patches, condyloma lata) in secondary syphilis.²²

After sexual assault

In cases of sexual assault, the risk of sexually transmitted infections may be increased due to trauma and bleeding. Testing for all sexually transmitted infections, including HIV, should be considered on a case-by-case basis.²²

Survivors of sexual assault have been shown to be poorly compliant with follow-up visits, and thus provision of postexposure prophylaxis at the time of initial assessment is preferable to deferred treatment.²² The recommended regimen should cover chlamydia, gonorrhea, and trichomoniasis (a single dose of intramuscular ceftriaxone 250 mg, oral azithromycin 1 g, and either oral metronidazole 2 g or tinidazole 2 g), in addition to HIV if the victim presents within 72 hours of exposure (Table 2).^22,26

Hepatitis B virus vaccine, not immunoglobulin, should be given if the hepatitis status of the assailant is unknown and the survivor has not been previously vaccinated. Both hepatitis B vaccine and immunoglobulin should be given to unvaccinated survivors if the assailant is known to be hepatitis B surface antigen-positive.²²

Human papillomavirus vaccination is recommended for female survivors ages 9 to 26 and male survivors ages 9 to 21.

Emergency contraception should be given if there is a risk of pregnancy.^22,26

In many jurisdictions, sexual assault centers provide trained examiners through Sexual Assault Nurse Examiners to perform evidence collection and to provide initial contact with the aftercare resources of the center. 

Advice on medical management of sexual assault can be obtained by calling National PEPline (888–448–4911).

INFECTIONS TRANSMITTED BY THE AIRBORNE ROUTE

Airborne transmission of infections occurs by inhalation of droplet nuclei (diameter ≤ 5 μm) generated by coughing and sneezing. Certain procedures (eg, administration of nebulized medication, sputum induction, bronchoscopy) also generate droplets and aerosols, which can transmit organisms.¹

Measles

Measles (Table 3) is highly contagious; up to 90% of susceptible individuals develop measles after exposure. The virus is transmitted by direct contact with infectious droplets and by the airborne route. It remains infectious in the air and on surfaces for up to 2 hours; therefore, any type of exposure, even transient, is an indication for postexposure prophylaxis in susceptible individuals.¹¹

Both the measles, mumps, rubella (MMR) vaccine and immune globulin may prevent or modify disease severity in susceptible exposed individuals if given within 3 days of exposure (for the vaccine) or within 6 days of exposure (for immune globulin).^31,32

Tuberculosis

Mycobacterium tuberculosis is transmitted from patients with pulmonary or laryngeal tuberculosis, particularly if patients cough and are sputum-positive for acid-fast bacilli. Patients with extrapulmonary tuberculosis or latent tuberculosis infection are not infectious.^1,7

Postexposure management of tuberculosis occurs through contact investigation of a newly diagnosed index case of tuberculosis disease. Contacts are categorized as household contacts, close nonhousehold contacts (those having regular, extensive contact with the index case), casual contacts, and transient community contacts. The highest priority for contact investigations should be household contacts, close nonhousehold or casual contacts at high risk of progressing to tuberculosis disease (eg, those with HIV, those on dialysis, or transplant recipients), and unprotected healthcare providers exposed during aerosol-generating procedures.^7,33

Postexposure management includes screening exposed individuals for tuberculosis symptoms and performing tuberculin skin testing or interferon-gamma release assay (blood testing) for those who had previously negative results (Table 3). Chest radiography is recommended for exposed immunocompromised individuals, due to high risk of tuberculosis disease and low sensitivity of skin or blood testing, and for those with a documented history of tuberculosis or previous positive skin or blood test.^7,33,34

A positive tuberculin skin test for persons with recent contact with tuberculosis is defined as a wheal 5 mm or larger on baseline or follow-up screening. Prior bacillus Calmette-Guérin vaccination status should not be used in the interpretation of tuberculin skin testing in the setting of contact investigation.^7,33

All exposed asymptomatic people with a positive result on testing should be treated for latent tuberculosis infection, since treatment reduces the risk of progression to tuberculosis disease by 60% to 90% .^7,33,35–37

Varicella and disseminated herpes zoster

Varicella zoster virus is transmitted by direct contact with vesicular fluid of skin lesions and inhalation of aerosols from vesicular fluid or respiratory tract secretions. Varicella (chickenpox) is highly contagious, with a secondary attack rate in susceptible household contacts of 85%.¹² Herpes zoster is less contagious than varicella.³⁸

Postexposure prophylaxis against varicella is recommended for susceptible individuals who had household exposure, had face-to-face contact with an infectious patient while indoors, or shared the same hospital room with the patient.¹²

Postexposure prophylactic options for varicella and herpes zoster include varicella vaccine (not zoster vaccine) and varicella zoster immune globulin (Table 3).^12,38–40

Varicella vaccine is approximately 90% effective if given within 3 days of exposure, and 70% effective if given within 5 days.^12,39

Antiviral agents should be given if the exposed individual develops manifestations of varicella or herpes zoster.^12,38

INFECTIONS TRANSMITTED BY THE DROPLET ROUTE

Droplet transmission occurs when respiratory droplets carrying infectious agents travel directly across short distances (3–6 feet) from the respiratory tract of the infected to mucosal surfaces of the susceptible exposed individual. Droplets are generated during coughing, sneezing, talking, and aerosol-generating procedures. Indirect contact with droplets can also transmit infection.¹

Group A streptococcal infection

Although group A streptococcal infection (Table 4) may spread to close contacts of the index case and in closed populations (eg, military recruit camps, schools, institutions), secondary cases of invasive group A streptococcal infection rarely occur in family and institutional contacts.^9,41,42

Postexposure prophylaxis for contacts of people with invasive group A streptococcal infection is debated, because it is unknown if antibiotic therapy will decrease the risk of acquiring the infection. It is generally agreed that it should not be routinely given to all contacts. The decision should be based on the clinician’s assessment of each individual’s risk and guidance from the local institution. If indicated, postexposure prophylaxis should be given to household and close contacts, particularly in high-risk groups (eg, Native Americans  and those with risk factors such as old age, HIV infection, diabetes mellitus, heart disease, chickenpox, cancer, systemic corticosteroid therapy, other immunosuppressive medications, intravenous drug use, recent surgery or childbirth).^9,41,42

Influenza

Influenza (Table 4) causes a significant burden in healthcare settings, given its prevalence and potential to cause outbreaks of severe respiratory illness in hospitalized patients and residents of long-term-care facilities.^13,43

Neuraminidase inhibitors are effective as prophylaxis after unprotected exposure to influenza, particularly in outbreak situations. However, their use is not widely recommended, since overuse could lead to antiviral resistance. In selected cases, postexposure prophylaxis may be indicated for close contacts who are at high risk of complications of influenza (eg, age 65 or older, in third trimester of pregnancy or 2 weeks postpartum, morbid obesity, chronic comorbid conditions such as a cardiopulmonary and renal disorder, immunocompromising condition) or who are in close contact with persons at high risk of influenza-related complications.^13,44,45

Meningococcal disease

N meningitidis is transmitted from individuals with meningococcal disease or from asymptomatic carriers.⁸

Postexposure prophylaxis is effective in eradicating N meningiditis and is recommended for all close contacts of patients with invasive meningococcal disease (Table 4).⁴⁶­ Close contacts include household contacts, childcare and preschool contacts, contacts exposed in dormitories or military training centers, those who had direct contact with the index case’s respiratory secretions (eg, intimate kissing, mouth-to-mouth resuscitation, unprotected contact during endotracheal intubation or endotracheal tube management), and passengers seated directly next to an index case on airplane flights of longer than 8 hours.

Postexposure prophylaxis is not indicated for those who had brief contact, those who had contact that did not involve exposure to oral or respiratory secretions, or for close contacts of patients with N meningitidis isolated in nonsterile sites only (eg, oropharynyx, trachea, conjunctiva).^8,46

Pertussis

Pertussis is highly contagious, with a secondary attack rate of approximately 80% in susceptible individuals. Approximately one-third of susceptible household contacts develop pertussis after exposure.¹⁰

Postexposure prophylaxis for pertussis should be given to all household and close contacts (Table 4).^10,47

Rubella

Transmission occurs through droplets or direct contact with nasopharyngeal secretions of an infectious case. Neither MMR vaccine nor immunoglobulin has been shown to prevent rubella in exposed contacts, and they are not recommended.¹¹

INFECTIONS TRANSMITTED BY DIRECT CONTACT

Direct contact transmission includes infectious agents transmitted from an infected or colonized individual to another, whereas indirect contact transmission involves a contaminated intermediate object or person (eg, hands of healthcare providers, electronic thermometers, surgical instruments).¹

There are no available postexposure prophylactic regimens for the organisms most commonly transmitted by this route (eg, methicillin-resistant Staphylococcus aureus, Clostridium difficile), but transmission can be prevented with adherence to standard precautions, including hand hygiene.¹

Hepatitis A

Person-to-person transmission of hepatitis A virus occurs via the fecal-oral route. Common-source outbreaks and sporadic cases can occur from exposure to food or water contaminated with feces.^1,15

Postexposure prophylaxis is indicated only for nonimmune close contacts (eg, household and sexual contacts) (Table 5). Without this treatment, secondary attack rates of 15% to 30% have been reported among households.^15,48 Both hepatitis A vaccine and immune globulin are effective in preventing and ameliorating symptomatic hepatitis A infection. Advantages of vaccination include induction of longer-lasting immunity (at least 2 years), greater ease of administration, and lower cost than immune globulin.^15,48

Scabies

Scabies is an infestation of the skin by the mite Sarcoptes scabiei var hominis. Person-to-person transmission typically occurs through direct, prolonged skin-to-skin contact with an infested person (eg, household and sexual contacts). However, crusted scabies can be transmitted after brief skin-to-skin contact or by exposure to bedding, clothing, or furniture used by the infested person.

All potentially infested persons should be treated concomitantly (Table 5).^14,49

INFECTIONS TRANSMITTED BY MAMMAL BITES AND INJURIES

Bites and injury wounds account for approximately 1% of all visits to emergency departments.⁵⁰ Human bites are associated with a risk of infection by blood-borne pathogens, herpes simplex infection, and bacterial infections (eg, skin and soft-tissue infections, bacteremia). Animal bites are associated with a risk of bacterial infections, rabies, tetanus, hepatitis B virus, and monkeypox.⁵⁰

Rabies

Human rabies (Table 5) is almost always fatal. Essential factors in determining the need for postexposure prophylaxis include knowledge of the epidemiology of animal rabies in the area where the contact occurred and the species of animal involved, availability of the animal for observation or rabies testing, health status of the biting animal, and vaccination history of both the animal and exposed individual.⁶ Clinicians should seek assistance from public health officials for evaluating exposures and determining the need for postexposure prophylaxis in situations that are not routine.⁵¹

High-risk wild animals associated with rabies in North America include bats, raccoons, skunks, foxes, coyotes, bobcats, and woodchucks. Bats are the most common source of human rabies infections in the United States, and transmission can occur from minor, sometimes unnoticed, bites. The types of exposures that require postexposure prophylaxis include bites, abrasions, scratches, and contamination of mucous membranes or open wound with saliva or neural tissue of a suspected rabid animal.

Human-to-human transmission of rabies can rarely occur through exposure of mucous membrane or nonintact skin to an infectious material (saliva, tears, neural tissue), in addition to organ transplantation.⁶

Animal capture and testing is a strategy for excluding rabies risk and reducing the need for postexposure prophylaxis. A dog, cat, or ferret that bites a person should be confined and observed for 10 days without administering postexposure prophylaxis for rabies, unless the bite or exposure is on the face or neck, in which case this treatment should be given immediately.⁶ If the observed biting animal lives and remains healthy, postexposure prophylaxis is not recommended. However, if signs suggestive of rabies develop, postexposure prophylaxis should be given and the animal should be euthanized, with testing of brain tissue for rabies virus. Postexposure prophylaxis should be discontinued if rabies testing is negative.

The combination of rabies vaccine and human rabies immunoglobulin is nearly 100% effective in preventing rabies if administered in a timely and accurate fashion after exposure (Table 5).⁶

Tetanus

Tetanus transmission can occur through injuries ranging from small cuts to severe trauma and through contact with contaminated objects (eg, bites, nails, needles, splinters, neonates whose umbilical cord is cut with contaminated surgical instruments, and during circumcision or piercing with contaminated instruments).⁵

Tetanus is almost completely preventable with vaccination, and timely administration of postexposure prophylaxis (tetanus toxoid-containing vaccine, tetanus immune globulin) decreases disease severity (Table 5).^2,5,52