Applied Evidence

As you conclude a routine annual physical exam of a 14-year-old girl, you ask her if she has any questions. With some hesitation, she tells you about a “friend” of hers who recently had sex with her boyfriend. She has heard many rumors from her friends, television, and chat lines. She doesn’t think her friend got pregnant, but is worried that she might have caught something. She tells you that her friend is also uncertain about whether—and how—to tell her parents.

How would you respond? Would you be comfortable helping your patient, and her parents, discuss this delicate matter in a meaningful way?

Though most clinicians are adept at diagnosing and treating sexually transmitted infections, far fewer feel skilled enough to counsel teens and parents about them. STIs (the new and politically appropriate terminology for STDs) are commonly encountered in family medicine; knowing how to discuss the many associated issues with teens and parents is paramount—especially when you consider the statistics.

According to the Centers for Disease Control and Prevention’s Youth Risk Behavior Surveillance System (YRBSS):¹

• 47.8% of 9th to 12th graders have had sexual intercourse.
• 7.1% of children have had intercourse before age 13.
• 14.9% of high school students have had sexual intercourse with 4 or more people.
• 38.5% of sexually active 9th to 12th graders did not use condoms during their last sexual encounter.

Opening Pandora’s box—carefully

As family physicians, we must be willing not only to discuss sexual issues if asked, but to raise them with patients and parents, when appropriate. The CDC offers training for health professionals in obtaining a sexual history and counseling and educating patients (http://depts.washington.edu/nnptc). Unfortunately, little information exists on how to tailor education to the values and beliefs of an individual family or to the broader cultural mores of the society in which the young person lives.² Nonetheless, there are many things you can do to improve the conversations you have.

For starters, ask open-ended questions and use understandable and normalizing language.³ Educate patients regarding the various STIs and methods of prevention—ie, proper condom use, abstinence, limiting the number of sexual partners, changes in sexual practices, and vaccination.^4-6 Ask patients about their use of and motivation to use condoms and contraceptive methods, as well as their sexual orientation, number of sexual partners, if they have ever exchanged sex for money or drugs, and prior history of STIs.⁷ To facilitate communication, familiarize yourself with sexual slang terms.

Focus on dispelling myths such as the misconception that contraceptive pills protect against STIs ( TABLE W1 , available online at www.jfponline.com). Educate parents, too, about STIs, how to counsel their children, and prevention strategies, including available vaccinations.

TABLE W1
Dispelling common myths about STIs

TABLE W2
Additional recommended reading

When should I raise these issues?

As depicted in the opening vignette, an adolescent may raise a myriad of issues concerning sexual activity, which makes your preparedness all the more important.

Most of the time, however, you will need to broach the subject. Sports physicals and annual well-child/adolescent exams are ideal opportunities to bring up issues regarding sex. In fact, it is usually easier to address this topic—and information is better received—when children are in their late preteen years and seen during nonacute visits.

Other opportunities to address these issues are during an STI screening visit, upon discovery of an STI, or during evaluations for amenorrhea or dysmenorrhea (when concerns about pregnancy and sex would naturally arise).

How should I start the discussion?

It is difficult to address sensitive issues in a 15-minute visit. Consider scheduling an extended appointment so that critical messages are not rushed. Another option is to introduce the topic to the parent or patient, and then schedule a separate counseling visit to discuss things in detail. To create a relaxed atmosphere, conduct the initial interview (with patient alone or with parent attending) in your office rather than in an examination room.

Put patients at ease. Many young people feel shame and embarrassment when talking about their sexual activity or lack of sexual activity. They may also be self conscious about asking “stupid” questions. They may have difficulty making eye contact with you during the discussion, or may display such nervous behaviors as nail biting or foot shaking. However, they may also have a false sense of confidence about their activities. It could take time to get adolescents to open up. Victims of sexual assault may need much longer periods of time to get comfortable discussing sexual behavior.

To encourage rapport, put your pen away, sit down, make eye contact, and speak in a neutral, nonjudgmental tone ( TABLE 1 ). Talk with, and not at, the patient (with parents, too, if present) as you assess baseline knowledge and readiness to change behavior.⁸ After posing a question, listen without interrupting. Lean forward while listening, to let the patient know he or she has your complete attention. Once the patient or parent finishes stating their concerns, ask additional open-ended questions—eg, “Is there anything else you’d like to discuss?”

Promote risk reduction. Applaud any positive risk reduction the patient has already adopted, and offer other specific and achievable risk-reduction tactics. Suggest options rather than giving directives.⁸ Also explore any possible barriers to further risk reduction, such as mental health concerns, addiction, abuse, lack of education, or lack of social support.

Risk-reduction efforts include condom use, reducing or limiting the number of partners, enhancing partner communication, self-testing and partner-testing for STIs, and avoiding recreational drug use.⁸ Recommend that the patient ask his or her partner(s) about present and past sexual practices and prior partners.

Role playing, training in the use of condoms, or sessions with peer counselors can often help patients learn how to communicate with partners and take responsibility for their own behavior.

TABLE 1
Talking to teens about sex and their health: A conversation starter

Provide information on STI consequences. Several surveys and studies^4,6,9 have shown that most patients would like additional information about symptoms, treatment, and consequences of various STIs. The research suggests that you should tell patients which STIs are curable, merely treatable, or life threatening.⁹ Include information on asymptomatic conditions, carrier states, and false-negative results that can occur when testing for human immunodeficiency virus (HIV) and herpes virus.⁶

Set aside your biases and assumptions. Avoid using labels and making gender-role assumptions. Pay attention to the patient’s (and parent’s) emotions, mannerisms, omissions, and comprehension.¹⁰ Note nonverbal cues, and keep in mind that your own attitude and subtle nonverbal communication will be detected, and may determine how patients respond. (Cultural competence training is often invaluable in establishing rapport and avoiding an unintended connotation.)

Speak with patients alone, or with parents? It is not unusual for parents or teens who have not had much experience discussing physical anatomy to become embarrassed or anxious when the topic of sexuality comes up. Counseling teens alone or with their parents depends on the nature of the conversation.

Consider introducing the general topic of sexual health—physical anatomy, physiology, risks of STIs, myths—with the teen and parent together.

Meet with patients alone when questions relate directly to their sexual habits, activity, or preferences. You may want to start with an open invitation designed to engage the adolescent in a dialogue: “At your age, I was very confused and misinformed. I am here to answer any of your questions. I also want to remind you that everything we discuss stays here. I know you have some information about this, but I am here to help you understand what is true and what is not.”

Legality. With a few exceptions, adolescents in the United States can legally consent to the confidential diagnosis and treatment of STIs, and medical care for STIs can be provided without parental consent or knowledge. In addition, in the majority of states, adolescents can consent to HIV counseling and testing.³

Plan for follow-up visits. Rather than overwhelm a teen at the initial visit, answer pressing questions and provide an overview. Have the teen make a follow-up appointment for 1 to 2 weeks after the initial visit. Provide print or online resources and phone numbers to call for additional information, and say you’ll be happy to address any questions or concerns at the next visit. (For reimbursement, these sessions can be coded as time-based counseling visits. When done in conjunction with other problem visits, your counseling can be coded with modifiers for prolonged services.¹¹ )

How important is it to raise this topic?

Adolescents and teens are prone to receiving and accepting misinformation from a variety of sources, such as peers, the general media, and the Internet. Not providing them with sound, accurate information about risks puts their health in jeopardy.

Most parents want to discuss this issue with their children, but they are often afraid or ill prepared to do so. Based on the literature^2-4,6 and our conversations with therapists, it seems most parents don’t object to physicians giving their children sound information as much as they object to being left out of the process. One technique to encourage parental cooperation is to offer choices about the way information will be delivered.

How should I advise parents?

Parents who really want to talk with their teens about sexual behaviors will likely find it easier to ask questions of their child in the doctor’s office, and to accept in that setting the answers they receive. Parents and physicians can collaborate ( TABLE 2 ) to create a 3-way conversation with the child in which any topic can be discussed safely and objectively. Such discourse in your office will hopefully translate to the home, as well.

In addition to answering parents’ questions and giving them medical information and counseling suggestions, offer them handouts and a list of online resources. Many groups have used MySpace to deliver counseling and support group information to children and teens.^12-15 These include Congress (health promotion, safety); Rape, Abuse, & Incest National Network; National Suicide Prevention Hotline (20,000 hits/month on MySpace); and gay/lesbian counseling forums. We suggest parents get texting capabilities on their phones and set up MySpace accounts to augment communication with their teens.

TABLE 2
Gaining parental buy-in before the teen talk: A conversation starter

Remain vigilant

Actively screen patients (from preteen years onward) for STIs.^4-7,10 Screening may range from questions that assess risk to formal STI testing. According to The National Health and Social Life Survey, 71% of individuals with STIs were diagnosed and treated in a private clinic or emergency room.¹⁶ Only 29% of sexually active individuals sought care at an STI clinic. Thus, most patients present to the primary care office.^4-6 It is crucial that we become as familiar with the guidelines for reporting and partner testing and treatment as with knowing how to treat index patients for STIs.

Reporting specifics. Syphilis, gonorrhea, Chlamydia, chancroid, HIV infection, and AIDS are reportable in every state.¹⁷ Hospital and commercial laboratories report all abnormal findings of reportable diseases; however, it is ultimately the physician’s responsibility to report the STI to the local health department. Each state has a complete list of reportable conditions and the time frame for reporting, accessible through its Department of Health Services. Once reported, information becomes confidential, and public health officials may contact you to verify the diagnosis before initiating a follow-up protocol.

Consider notifying patients directly regarding negative and positive results so you can answer any questions they may have and discuss treatment for themselves—and their partners. (See “Getting treatment to partners: The expedited partner therapy option”.) Directly notifying patients offers another opportunity to further educate teens regarding prevention strategies and to dispel any misconceptions they may have.

Correspondence
Anush S. Pillai, DO, FAAFP, 424 Hahlo, Houston, TX 77020; [email protected]

As you conclude a routine annual physical exam of a 14-year-old girl, you ask her if she has any questions. With some hesitation, she tells you about a “friend” of hers who recently had sex with her boyfriend. She has heard many rumors from her friends, television, and chat lines. She doesn’t think her friend got pregnant, but is worried that she might have caught something. She tells you that her friend is also uncertain about whether—and how—to tell her parents.

How would you respond? Would you be comfortable helping your patient, and her parents, discuss this delicate matter in a meaningful way?

Though most clinicians are adept at diagnosing and treating sexually transmitted infections, far fewer feel skilled enough to counsel teens and parents about them. STIs (the new and politically appropriate terminology for STDs) are commonly encountered in family medicine; knowing how to discuss the many associated issues with teens and parents is paramount—especially when you consider the statistics.

According to the Centers for Disease Control and Prevention’s Youth Risk Behavior Surveillance System (YRBSS):¹

• 47.8% of 9th to 12th graders have had sexual intercourse.
• 7.1% of children have had intercourse before age 13.
• 14.9% of high school students have had sexual intercourse with 4 or more people.
• 38.5% of sexually active 9th to 12th graders did not use condoms during their last sexual encounter.

Opening Pandora’s box—carefully

As family physicians, we must be willing not only to discuss sexual issues if asked, but to raise them with patients and parents, when appropriate. The CDC offers training for health professionals in obtaining a sexual history and counseling and educating patients (http://depts.washington.edu/nnptc). Unfortunately, little information exists on how to tailor education to the values and beliefs of an individual family or to the broader cultural mores of the society in which the young person lives.² Nonetheless, there are many things you can do to improve the conversations you have.

For starters, ask open-ended questions and use understandable and normalizing language.³ Educate patients regarding the various STIs and methods of prevention—ie, proper condom use, abstinence, limiting the number of sexual partners, changes in sexual practices, and vaccination.^4-6 Ask patients about their use of and motivation to use condoms and contraceptive methods, as well as their sexual orientation, number of sexual partners, if they have ever exchanged sex for money or drugs, and prior history of STIs.⁷ To facilitate communication, familiarize yourself with sexual slang terms.

Focus on dispelling myths such as the misconception that contraceptive pills protect against STIs ( TABLE W1 , available online at www.jfponline.com). Educate parents, too, about STIs, how to counsel their children, and prevention strategies, including available vaccinations.

TABLE W1
Dispelling common myths about STIs

TABLE W2
Additional recommended reading

When should I raise these issues?

As depicted in the opening vignette, an adolescent may raise a myriad of issues concerning sexual activity, which makes your preparedness all the more important.

Most of the time, however, you will need to broach the subject. Sports physicals and annual well-child/adolescent exams are ideal opportunities to bring up issues regarding sex. In fact, it is usually easier to address this topic—and information is better received—when children are in their late preteen years and seen during nonacute visits.

Other opportunities to address these issues are during an STI screening visit, upon discovery of an STI, or during evaluations for amenorrhea or dysmenorrhea (when concerns about pregnancy and sex would naturally arise).

How should I start the discussion?

It is difficult to address sensitive issues in a 15-minute visit. Consider scheduling an extended appointment so that critical messages are not rushed. Another option is to introduce the topic to the parent or patient, and then schedule a separate counseling visit to discuss things in detail. To create a relaxed atmosphere, conduct the initial interview (with patient alone or with parent attending) in your office rather than in an examination room.

Put patients at ease. Many young people feel shame and embarrassment when talking about their sexual activity or lack of sexual activity. They may also be self conscious about asking “stupid” questions. They may have difficulty making eye contact with you during the discussion, or may display such nervous behaviors as nail biting or foot shaking. However, they may also have a false sense of confidence about their activities. It could take time to get adolescents to open up. Victims of sexual assault may need much longer periods of time to get comfortable discussing sexual behavior.

To encourage rapport, put your pen away, sit down, make eye contact, and speak in a neutral, nonjudgmental tone ( TABLE 1 ). Talk with, and not at, the patient (with parents, too, if present) as you assess baseline knowledge and readiness to change behavior.⁸ After posing a question, listen without interrupting. Lean forward while listening, to let the patient know he or she has your complete attention. Once the patient or parent finishes stating their concerns, ask additional open-ended questions—eg, “Is there anything else you’d like to discuss?”

Promote risk reduction. Applaud any positive risk reduction the patient has already adopted, and offer other specific and achievable risk-reduction tactics. Suggest options rather than giving directives.⁸ Also explore any possible barriers to further risk reduction, such as mental health concerns, addiction, abuse, lack of education, or lack of social support.

Risk-reduction efforts include condom use, reducing or limiting the number of partners, enhancing partner communication, self-testing and partner-testing for STIs, and avoiding recreational drug use.⁸ Recommend that the patient ask his or her partner(s) about present and past sexual practices and prior partners.

Role playing, training in the use of condoms, or sessions with peer counselors can often help patients learn how to communicate with partners and take responsibility for their own behavior.

TABLE 1
Talking to teens about sex and their health: A conversation starter

Provide information on STI consequences. Several surveys and studies^4,6,9 have shown that most patients would like additional information about symptoms, treatment, and consequences of various STIs. The research suggests that you should tell patients which STIs are curable, merely treatable, or life threatening.⁹ Include information on asymptomatic conditions, carrier states, and false-negative results that can occur when testing for human immunodeficiency virus (HIV) and herpes virus.⁶

Set aside your biases and assumptions. Avoid using labels and making gender-role assumptions. Pay attention to the patient’s (and parent’s) emotions, mannerisms, omissions, and comprehension.¹⁰ Note nonverbal cues, and keep in mind that your own attitude and subtle nonverbal communication will be detected, and may determine how patients respond. (Cultural competence training is often invaluable in establishing rapport and avoiding an unintended connotation.)

Speak with patients alone, or with parents? It is not unusual for parents or teens who have not had much experience discussing physical anatomy to become embarrassed or anxious when the topic of sexuality comes up. Counseling teens alone or with their parents depends on the nature of the conversation.

Consider introducing the general topic of sexual health—physical anatomy, physiology, risks of STIs, myths—with the teen and parent together.

Meet with patients alone when questions relate directly to their sexual habits, activity, or preferences. You may want to start with an open invitation designed to engage the adolescent in a dialogue: “At your age, I was very confused and misinformed. I am here to answer any of your questions. I also want to remind you that everything we discuss stays here. I know you have some information about this, but I am here to help you understand what is true and what is not.”

Legality. With a few exceptions, adolescents in the United States can legally consent to the confidential diagnosis and treatment of STIs, and medical care for STIs can be provided without parental consent or knowledge. In addition, in the majority of states, adolescents can consent to HIV counseling and testing.³

Plan for follow-up visits. Rather than overwhelm a teen at the initial visit, answer pressing questions and provide an overview. Have the teen make a follow-up appointment for 1 to 2 weeks after the initial visit. Provide print or online resources and phone numbers to call for additional information, and say you’ll be happy to address any questions or concerns at the next visit. (For reimbursement, these sessions can be coded as time-based counseling visits. When done in conjunction with other problem visits, your counseling can be coded with modifiers for prolonged services.¹¹ )

How important is it to raise this topic?

Adolescents and teens are prone to receiving and accepting misinformation from a variety of sources, such as peers, the general media, and the Internet. Not providing them with sound, accurate information about risks puts their health in jeopardy.

Most parents want to discuss this issue with their children, but they are often afraid or ill prepared to do so. Based on the literature^2-4,6 and our conversations with therapists, it seems most parents don’t object to physicians giving their children sound information as much as they object to being left out of the process. One technique to encourage parental cooperation is to offer choices about the way information will be delivered.

How should I advise parents?

Parents who really want to talk with their teens about sexual behaviors will likely find it easier to ask questions of their child in the doctor’s office, and to accept in that setting the answers they receive. Parents and physicians can collaborate ( TABLE 2 ) to create a 3-way conversation with the child in which any topic can be discussed safely and objectively. Such discourse in your office will hopefully translate to the home, as well.

In addition to answering parents’ questions and giving them medical information and counseling suggestions, offer them handouts and a list of online resources. Many groups have used MySpace to deliver counseling and support group information to children and teens.^12-15 These include Congress (health promotion, safety); Rape, Abuse, & Incest National Network; National Suicide Prevention Hotline (20,000 hits/month on MySpace); and gay/lesbian counseling forums. We suggest parents get texting capabilities on their phones and set up MySpace accounts to augment communication with their teens.

TABLE 2
Gaining parental buy-in before the teen talk: A conversation starter

Remain vigilant

Actively screen patients (from preteen years onward) for STIs.^4-7,10 Screening may range from questions that assess risk to formal STI testing. According to The National Health and Social Life Survey, 71% of individuals with STIs were diagnosed and treated in a private clinic or emergency room.¹⁶ Only 29% of sexually active individuals sought care at an STI clinic. Thus, most patients present to the primary care office.^4-6 It is crucial that we become as familiar with the guidelines for reporting and partner testing and treatment as with knowing how to treat index patients for STIs.

Reporting specifics. Syphilis, gonorrhea, Chlamydia, chancroid, HIV infection, and AIDS are reportable in every state.¹⁷ Hospital and commercial laboratories report all abnormal findings of reportable diseases; however, it is ultimately the physician’s responsibility to report the STI to the local health department. Each state has a complete list of reportable conditions and the time frame for reporting, accessible through its Department of Health Services. Once reported, information becomes confidential, and public health officials may contact you to verify the diagnosis before initiating a follow-up protocol.

Consider notifying patients directly regarding negative and positive results so you can answer any questions they may have and discuss treatment for themselves—and their partners. (See “Getting treatment to partners: The expedited partner therapy option”.) Directly notifying patients offers another opportunity to further educate teens regarding prevention strategies and to dispel any misconceptions they may have.

Correspondence
Anush S. Pillai, DO, FAAFP, 424 Hahlo, Houston, TX 77020; [email protected]

As you conclude a routine annual physical exam of a 14-year-old girl, you ask her if she has any questions. With some hesitation, she tells you about a “friend” of hers who recently had sex with her boyfriend. She has heard many rumors from her friends, television, and chat lines. She doesn’t think her friend got pregnant, but is worried that she might have caught something. She tells you that her friend is also uncertain about whether—and how—to tell her parents.

How would you respond? Would you be comfortable helping your patient, and her parents, discuss this delicate matter in a meaningful way?

Though most clinicians are adept at diagnosing and treating sexually transmitted infections, far fewer feel skilled enough to counsel teens and parents about them. STIs (the new and politically appropriate terminology for STDs) are commonly encountered in family medicine; knowing how to discuss the many associated issues with teens and parents is paramount—especially when you consider the statistics.

According to the Centers for Disease Control and Prevention’s Youth Risk Behavior Surveillance System (YRBSS):¹

• 47.8% of 9th to 12th graders have had sexual intercourse.
• 7.1% of children have had intercourse before age 13.
• 14.9% of high school students have had sexual intercourse with 4 or more people.
• 38.5% of sexually active 9th to 12th graders did not use condoms during their last sexual encounter.

Opening Pandora’s box—carefully

As family physicians, we must be willing not only to discuss sexual issues if asked, but to raise them with patients and parents, when appropriate. The CDC offers training for health professionals in obtaining a sexual history and counseling and educating patients (http://depts.washington.edu/nnptc). Unfortunately, little information exists on how to tailor education to the values and beliefs of an individual family or to the broader cultural mores of the society in which the young person lives.² Nonetheless, there are many things you can do to improve the conversations you have.

For starters, ask open-ended questions and use understandable and normalizing language.³ Educate patients regarding the various STIs and methods of prevention—ie, proper condom use, abstinence, limiting the number of sexual partners, changes in sexual practices, and vaccination.^4-6 Ask patients about their use of and motivation to use condoms and contraceptive methods, as well as their sexual orientation, number of sexual partners, if they have ever exchanged sex for money or drugs, and prior history of STIs.⁷ To facilitate communication, familiarize yourself with sexual slang terms.

Focus on dispelling myths such as the misconception that contraceptive pills protect against STIs ( TABLE W1 , available online at www.jfponline.com). Educate parents, too, about STIs, how to counsel their children, and prevention strategies, including available vaccinations.

TABLE W1
Dispelling common myths about STIs

TABLE W2
Additional recommended reading

When should I raise these issues?

As depicted in the opening vignette, an adolescent may raise a myriad of issues concerning sexual activity, which makes your preparedness all the more important.

Most of the time, however, you will need to broach the subject. Sports physicals and annual well-child/adolescent exams are ideal opportunities to bring up issues regarding sex. In fact, it is usually easier to address this topic—and information is better received—when children are in their late preteen years and seen during nonacute visits.

Other opportunities to address these issues are during an STI screening visit, upon discovery of an STI, or during evaluations for amenorrhea or dysmenorrhea (when concerns about pregnancy and sex would naturally arise).

How should I start the discussion?

It is difficult to address sensitive issues in a 15-minute visit. Consider scheduling an extended appointment so that critical messages are not rushed. Another option is to introduce the topic to the parent or patient, and then schedule a separate counseling visit to discuss things in detail. To create a relaxed atmosphere, conduct the initial interview (with patient alone or with parent attending) in your office rather than in an examination room.

Put patients at ease. Many young people feel shame and embarrassment when talking about their sexual activity or lack of sexual activity. They may also be self conscious about asking “stupid” questions. They may have difficulty making eye contact with you during the discussion, or may display such nervous behaviors as nail biting or foot shaking. However, they may also have a false sense of confidence about their activities. It could take time to get adolescents to open up. Victims of sexual assault may need much longer periods of time to get comfortable discussing sexual behavior.

To encourage rapport, put your pen away, sit down, make eye contact, and speak in a neutral, nonjudgmental tone ( TABLE 1 ). Talk with, and not at, the patient (with parents, too, if present) as you assess baseline knowledge and readiness to change behavior.⁸ After posing a question, listen without interrupting. Lean forward while listening, to let the patient know he or she has your complete attention. Once the patient or parent finishes stating their concerns, ask additional open-ended questions—eg, “Is there anything else you’d like to discuss?”

Promote risk reduction. Applaud any positive risk reduction the patient has already adopted, and offer other specific and achievable risk-reduction tactics. Suggest options rather than giving directives.⁸ Also explore any possible barriers to further risk reduction, such as mental health concerns, addiction, abuse, lack of education, or lack of social support.

Risk-reduction efforts include condom use, reducing or limiting the number of partners, enhancing partner communication, self-testing and partner-testing for STIs, and avoiding recreational drug use.⁸ Recommend that the patient ask his or her partner(s) about present and past sexual practices and prior partners.

Role playing, training in the use of condoms, or sessions with peer counselors can often help patients learn how to communicate with partners and take responsibility for their own behavior.

TABLE 1
Talking to teens about sex and their health: A conversation starter

Provide information on STI consequences. Several surveys and studies^4,6,9 have shown that most patients would like additional information about symptoms, treatment, and consequences of various STIs. The research suggests that you should tell patients which STIs are curable, merely treatable, or life threatening.⁹ Include information on asymptomatic conditions, carrier states, and false-negative results that can occur when testing for human immunodeficiency virus (HIV) and herpes virus.⁶

Set aside your biases and assumptions. Avoid using labels and making gender-role assumptions. Pay attention to the patient’s (and parent’s) emotions, mannerisms, omissions, and comprehension.¹⁰ Note nonverbal cues, and keep in mind that your own attitude and subtle nonverbal communication will be detected, and may determine how patients respond. (Cultural competence training is often invaluable in establishing rapport and avoiding an unintended connotation.)

Speak with patients alone, or with parents? It is not unusual for parents or teens who have not had much experience discussing physical anatomy to become embarrassed or anxious when the topic of sexuality comes up. Counseling teens alone or with their parents depends on the nature of the conversation.

Consider introducing the general topic of sexual health—physical anatomy, physiology, risks of STIs, myths—with the teen and parent together.

Meet with patients alone when questions relate directly to their sexual habits, activity, or preferences. You may want to start with an open invitation designed to engage the adolescent in a dialogue: “At your age, I was very confused and misinformed. I am here to answer any of your questions. I also want to remind you that everything we discuss stays here. I know you have some information about this, but I am here to help you understand what is true and what is not.”

Legality. With a few exceptions, adolescents in the United States can legally consent to the confidential diagnosis and treatment of STIs, and medical care for STIs can be provided without parental consent or knowledge. In addition, in the majority of states, adolescents can consent to HIV counseling and testing.³

Plan for follow-up visits. Rather than overwhelm a teen at the initial visit, answer pressing questions and provide an overview. Have the teen make a follow-up appointment for 1 to 2 weeks after the initial visit. Provide print or online resources and phone numbers to call for additional information, and say you’ll be happy to address any questions or concerns at the next visit. (For reimbursement, these sessions can be coded as time-based counseling visits. When done in conjunction with other problem visits, your counseling can be coded with modifiers for prolonged services.¹¹ )

How important is it to raise this topic?

Adolescents and teens are prone to receiving and accepting misinformation from a variety of sources, such as peers, the general media, and the Internet. Not providing them with sound, accurate information about risks puts their health in jeopardy.

Most parents want to discuss this issue with their children, but they are often afraid or ill prepared to do so. Based on the literature^2-4,6 and our conversations with therapists, it seems most parents don’t object to physicians giving their children sound information as much as they object to being left out of the process. One technique to encourage parental cooperation is to offer choices about the way information will be delivered.

How should I advise parents?

Parents who really want to talk with their teens about sexual behaviors will likely find it easier to ask questions of their child in the doctor’s office, and to accept in that setting the answers they receive. Parents and physicians can collaborate ( TABLE 2 ) to create a 3-way conversation with the child in which any topic can be discussed safely and objectively. Such discourse in your office will hopefully translate to the home, as well.

In addition to answering parents’ questions and giving them medical information and counseling suggestions, offer them handouts and a list of online resources. Many groups have used MySpace to deliver counseling and support group information to children and teens.^12-15 These include Congress (health promotion, safety); Rape, Abuse, & Incest National Network; National Suicide Prevention Hotline (20,000 hits/month on MySpace); and gay/lesbian counseling forums. We suggest parents get texting capabilities on their phones and set up MySpace accounts to augment communication with their teens.

TABLE 2
Gaining parental buy-in before the teen talk: A conversation starter

Remain vigilant

Actively screen patients (from preteen years onward) for STIs.^4-7,10 Screening may range from questions that assess risk to formal STI testing. According to The National Health and Social Life Survey, 71% of individuals with STIs were diagnosed and treated in a private clinic or emergency room.¹⁶ Only 29% of sexually active individuals sought care at an STI clinic. Thus, most patients present to the primary care office.^4-6 It is crucial that we become as familiar with the guidelines for reporting and partner testing and treatment as with knowing how to treat index patients for STIs.

Reporting specifics. Syphilis, gonorrhea, Chlamydia, chancroid, HIV infection, and AIDS are reportable in every state.¹⁷ Hospital and commercial laboratories report all abnormal findings of reportable diseases; however, it is ultimately the physician’s responsibility to report the STI to the local health department. Each state has a complete list of reportable conditions and the time frame for reporting, accessible through its Department of Health Services. Once reported, information becomes confidential, and public health officials may contact you to verify the diagnosis before initiating a follow-up protocol.

Consider notifying patients directly regarding negative and positive results so you can answer any questions they may have and discuss treatment for themselves—and their partners. (See “Getting treatment to partners: The expedited partner therapy option”.) Directly notifying patients offers another opportunity to further educate teens regarding prevention strategies and to dispel any misconceptions they may have.

Correspondence
Anush S. Pillai, DO, FAAFP, 424 Hahlo, Houston, TX 77020; [email protected]

What is the best way to treat the bite of a brown recluse spider? Having treated more than 185 bite wounds on 150 patients over the past 30 years, I have found that an oral antihistamine works best and makes surgery unnecessary.

I did not arrive at this treatment protocol immediately but, rather, developed it in 4 phases, which I describe in this article. Not only does this conservative approach consistently heal confirmed brown recluse bite wounds, but should a bite be mistakenly attributed to the brown recluse (or one of its relatives in the Loxosceles genus of spider), there is no harm to the patient, nor any big expense.

Is a brown recluse to blame?

Due to limited experience among the wider medical community in identifying spider envenomation,^1-4 bite recognition and selection of appropriate therapy can be difficult.

Early findings can be confusing. Brown recluse bites typically feel like a pin prick. A vasoconstrictive halo may surround the bite, but this sign is inconsistent. Usually there is nothing to see immediately and pain from the bite goes away, so most patients dismiss the incident.⁵ Soon, however, pain from the envenomation begins and, importantly, becomes disproportionate to physical findings—the patient shows you where it hurts, but there is nothing visible to support a diagnosis or suggest a course of action.

Progression of the wound usually tells more than a captured specimen. If you are fortunate enough to examine an intact spider caught by the patient, a “fiddle” mark on the spider’s back confirms it is a brown recluse (FIGURE 1). However, most specimens brought in for examination are so misshapen from the patient’s retribution as to make identification futile. I focus instead on the resultant wound.

Spider’s venom causes the wound. Spiders lack a mechanical digestive system; their so-called venom actually is a set of enzymes that liquefy a prey’s tissues.⁶ In the 48 hours after a bite, these digestive enzymes cause a progressive necrosis of fat under the skin. Eventually the overlying skin also turns necrotic. The venom does not penetrate underlying fascia planes, as many infectious processes do.

Necrosis can, rarely, cause disseminated intravascular coagulation and death. A more likely scenario, though still relatively uncommon, is that the necrotic sequence leads to an indolent wound that heals only with difficulty. Most patients recover without medical care and do not even seek it.^7-9

Wounds can be categorized, as outlined by Auer et al,¹⁰ into groups 1 through 4, from least severe to most severe. However, this classification scheme has made no difference in my management decisions.

FIGURE 1
The distinctive “fiddle” mark

How my treatment protocol evolved

My protocol for treating necrotic bite wounds of the brown recluse, and similar wounds from other insects, progressed over 30 years through 4 phases of treatment concepts.

Phase 1: Surgical excision

From 1979 to 1980, I treated necrotic wounds with surgical excision and secondary closure or skin grafting.¹ Many patients complained of severe itching around these wounds, which I treated empirically with the antihistamine Benadryl. All patients experienced symptom relief and had a reasonable cosmetic result (FIGURE 2).

In writing up the case results for a presentation to the Society of Air Force Clinical Surgeons, I conducted background research and found a postulate suggesting that antigen recognition was an important factor in wound progression and that it took approximately 7 days to achieve. That postulate drove the second phase of discovery.¹

FIGURE 2
Bite wound treatment: Debridement and closure or skin grafting

From 1980 to 1981, I focused on the postulate, which also suggested that the antigen–antibody reaction following envenomation could make reactions to subsequent (“second set”) bites less severe.¹ This made sense, though good clinical data were lacking.

I decided to simply observe patients’ wounds for 7 to 10 days before performing debridement, advising patients to use an antihistamine to control symptoms during the waiting period. I took photographs to document clinical progression of wounds. In reviewing these photographs, I noted that the necrotic wounds stabilized immediately on starting an antihistamine—specifically, Benadryl, 5 mg/kg or 50 mg qid. After 7 to 10 days, I debrided the wounds, using fluorescein and a Woods lamp to guide the procedure. I found that tissue of doubtful viability survived if debridement was conservative and the patient had used an antihistamine (FIGURE 3).

FIGURE 3
Bite wound treatment: Observation for 7 to 10 days

In reviewing phase 2 results in preparation for a presentation to the Southwestern Surgical Congress, I realized that debridement was rarely indicated. So, from 1981 to 1982, I relied less on surgery and more on conservative therapy. Patients got better simply with antihistamine therapy. Redness diminished very quickly once patients took the antihistamine, and pockets of purulent material drained on their own.

This approach also allowed antigen recognition to occur and seemed to prove the postulate of a less severe second bite. I saw 4 patients with proven “second set” spider bites (intact specimens were available) and all had an immediate inflammatory response and no subsequent necrosis. An 18-month-old patient with a bite below her right eye healed with Benadryl therapy alone (FIGURE 4).

FIGURE 4
Bite wound treatment: Antihistamine alone

Phase 4: Exclusive antihistamine therapy

Since 1982, I have treated more than 100 patients (myself included) with necrotic bite wounds from spiders and other insects. None have required operative debridement, and all have achieved much more acceptable cosmetic results using Benadryl therapy than with surgical therapy.

My encounter with a brown recluse. The bite I received was rather typical. I felt a sharp sting when outside working on the lawn. I looked down, saw nothing, and assumed I had run into a pin or small stick that was now not visible. For 3 days I noticed nothing unusual. On day 4, after showering I noticed a large amount of purulent material on the towel after drying my anterior left leg. On inspecting the area, I saw an area of necrosis approximately 6 × 6 cm with a central area oozing a purulent material. This appeared just like the necrotic insect bites I had treated with antihistamines, so I started myself on that regimen. The redness cleared up in 2 days and the wound healed completely in 10 days without antibiotics. A 3 × 3 mm circular scar remained; I lost none of the surrounding marginal skin.

Further evidence of less severe second bites. Another physician—my coauthor on the presentation to the Southwestern Surgical Congress—was bitten at age 12 by an unidentified insect, resulting in a large necrotic wound on his thigh. The lesion, reportedly 10 to 12 cm in diameter, healed with topical treatment only. After our joint report in 1982, a brown recluse spider bit him on the abdomen while he was working in the yard. He captured the spider and verified its genus and species. Guessing that the bite he received as a 12 year old was also from a brown recluse, he decided to wait and see if he had a “second set” reaction to the bite. He had an immediate inflammatory reaction, no skin necrosis, and the entire area returned to normal in 3 days. His experience became the fifth “second set” spider bite reaction in our series.

Another dramatic experience. One 22-year-old woman’s experience is worth a longer discussion. She visited her physician because 4 small areas of necrosis on her lower abdomen and chest had lasted several days and were getting worse. He assumed these were small abscesses and treated her with antibiotics. The lesions slowly enlarged to become 6 to 8 cm in diameter, and the physician hospitalized her for intravenous (IV) antibiotic therapy.

When the patient worsened after 2 days of IV antibiotics and incision and drainage, I was called to examine her for possible surgical debridement. I thought the lesions were necrotic insect bites and recommended starting Benadryl, 50 mg qid. She improved remarkably over the next 24 hours, her wounds decreasing in size by 50%. She was discharged from the hospital and, against my advice, the Benadryl was stopped. Within 48 hours the area of inflammation around the wounds had doubled in size. She was readmitted and given Benadryl. Again she improved remarkably in 24 hours. The purulent discharge was sent for culture, which grew an organism resistant to all of her previous antibiotics. She healed uneventfully in 10 days on antihistamines, and without antibiotics. This is typical in my experience. Antibiotics have seldom proved useful, and culture results are generally confusing.

Broader support for my observations

On January 27, 2006, on eMedicine (link is no longer active), dermatologist Adam S. Stibich, MD, published a physiology review of the brown recluse bite. He acknowledged that neutrophils accumulate in the wound at 24 to 72 hours, consistent with the antigen–antibody response postulated in my clinical review. Neutrophils are products of the histamine cascade that most likely brings about tissue necrosis.

Stibich’s plea for conservative management was well founded. He noted that only 10% of envenomation episodes result in large open wounds. The physical findings he described were in keeping with my observation that a subcutaneous necrotic process precedes surface changes.

His treatment of choice was dapsone. He pointed out that other clinicians, too, had reported success with dapsone, and with steroids, antibiotics, hyperbaric oxygen, electric shock therapy, and surgical therapy.^3,4,11,12 Stibich commented extensively on these treatment modalities, except electrical shock. However, while the laboratory results achieved were good, clinical outcomes were mixed. Of these treatments, I have experience only with surgery, and I have found that it does not improve the healing process.

Antihistamine and observation: The ideal Tx

The ideal treatment for necrotic wounds from envenomation would account for an underlying antigen–antibody process, shorten the natural history of the illness, result in the least deformity, minimize cost, and allow for errors in diagnosis without harming patients.

Based on my observations since 1982, I am convinced these necrotic wounds involve an antigen–antibody reaction, are histamine driven, and are adequately treated with oral antihistamines. I now treat presumed necrotic spider bite with antihistamines only. Laboratory or serum testing to confirm a diagnosis has not been useful. It takes too long, costs too much, and does not contribute to management decisions.

If the wound improves dramatically in 24 hours, which is the norm, I continue the antihistamines for 7 to 10 days. If the wound does not improve, I suspect a bacterial component and add an antibiotic. Not once in the last 26 years have I had to resort to surgery.

Correspondence
Paul K. Carlton, Jr, MD, FACS, The Texas A&M University Health Science Center, Office of Homeland Security, 301 Tarrow, 7th Floor, John Connally Building, College Station, TX 77840; [email protected]

What is the best way to treat the bite of a brown recluse spider? Having treated more than 185 bite wounds on 150 patients over the past 30 years, I have found that an oral antihistamine works best and makes surgery unnecessary.

I did not arrive at this treatment protocol immediately but, rather, developed it in 4 phases, which I describe in this article. Not only does this conservative approach consistently heal confirmed brown recluse bite wounds, but should a bite be mistakenly attributed to the brown recluse (or one of its relatives in the Loxosceles genus of spider), there is no harm to the patient, nor any big expense.

Is a brown recluse to blame?

Due to limited experience among the wider medical community in identifying spider envenomation,^1-4 bite recognition and selection of appropriate therapy can be difficult.

Early findings can be confusing. Brown recluse bites typically feel like a pin prick. A vasoconstrictive halo may surround the bite, but this sign is inconsistent. Usually there is nothing to see immediately and pain from the bite goes away, so most patients dismiss the incident.⁵ Soon, however, pain from the envenomation begins and, importantly, becomes disproportionate to physical findings—the patient shows you where it hurts, but there is nothing visible to support a diagnosis or suggest a course of action.

Progression of the wound usually tells more than a captured specimen. If you are fortunate enough to examine an intact spider caught by the patient, a “fiddle” mark on the spider’s back confirms it is a brown recluse (FIGURE 1). However, most specimens brought in for examination are so misshapen from the patient’s retribution as to make identification futile. I focus instead on the resultant wound.

Spider’s venom causes the wound. Spiders lack a mechanical digestive system; their so-called venom actually is a set of enzymes that liquefy a prey’s tissues.⁶ In the 48 hours after a bite, these digestive enzymes cause a progressive necrosis of fat under the skin. Eventually the overlying skin also turns necrotic. The venom does not penetrate underlying fascia planes, as many infectious processes do.

Necrosis can, rarely, cause disseminated intravascular coagulation and death. A more likely scenario, though still relatively uncommon, is that the necrotic sequence leads to an indolent wound that heals only with difficulty. Most patients recover without medical care and do not even seek it.^7-9

Wounds can be categorized, as outlined by Auer et al,¹⁰ into groups 1 through 4, from least severe to most severe. However, this classification scheme has made no difference in my management decisions.

FIGURE 1
The distinctive “fiddle” mark

How my treatment protocol evolved

My protocol for treating necrotic bite wounds of the brown recluse, and similar wounds from other insects, progressed over 30 years through 4 phases of treatment concepts.

Phase 1: Surgical excision

From 1979 to 1980, I treated necrotic wounds with surgical excision and secondary closure or skin grafting.¹ Many patients complained of severe itching around these wounds, which I treated empirically with the antihistamine Benadryl. All patients experienced symptom relief and had a reasonable cosmetic result (FIGURE 2).

In writing up the case results for a presentation to the Society of Air Force Clinical Surgeons, I conducted background research and found a postulate suggesting that antigen recognition was an important factor in wound progression and that it took approximately 7 days to achieve. That postulate drove the second phase of discovery.¹

FIGURE 2
Bite wound treatment: Debridement and closure or skin grafting

From 1980 to 1981, I focused on the postulate, which also suggested that the antigen–antibody reaction following envenomation could make reactions to subsequent (“second set”) bites less severe.¹ This made sense, though good clinical data were lacking.

I decided to simply observe patients’ wounds for 7 to 10 days before performing debridement, advising patients to use an antihistamine to control symptoms during the waiting period. I took photographs to document clinical progression of wounds. In reviewing these photographs, I noted that the necrotic wounds stabilized immediately on starting an antihistamine—specifically, Benadryl, 5 mg/kg or 50 mg qid. After 7 to 10 days, I debrided the wounds, using fluorescein and a Woods lamp to guide the procedure. I found that tissue of doubtful viability survived if debridement was conservative and the patient had used an antihistamine (FIGURE 3).

FIGURE 3
Bite wound treatment: Observation for 7 to 10 days

In reviewing phase 2 results in preparation for a presentation to the Southwestern Surgical Congress, I realized that debridement was rarely indicated. So, from 1981 to 1982, I relied less on surgery and more on conservative therapy. Patients got better simply with antihistamine therapy. Redness diminished very quickly once patients took the antihistamine, and pockets of purulent material drained on their own.

This approach also allowed antigen recognition to occur and seemed to prove the postulate of a less severe second bite. I saw 4 patients with proven “second set” spider bites (intact specimens were available) and all had an immediate inflammatory response and no subsequent necrosis. An 18-month-old patient with a bite below her right eye healed with Benadryl therapy alone (FIGURE 4).

FIGURE 4
Bite wound treatment: Antihistamine alone

Phase 4: Exclusive antihistamine therapy

Since 1982, I have treated more than 100 patients (myself included) with necrotic bite wounds from spiders and other insects. None have required operative debridement, and all have achieved much more acceptable cosmetic results using Benadryl therapy than with surgical therapy.

My encounter with a brown recluse. The bite I received was rather typical. I felt a sharp sting when outside working on the lawn. I looked down, saw nothing, and assumed I had run into a pin or small stick that was now not visible. For 3 days I noticed nothing unusual. On day 4, after showering I noticed a large amount of purulent material on the towel after drying my anterior left leg. On inspecting the area, I saw an area of necrosis approximately 6 × 6 cm with a central area oozing a purulent material. This appeared just like the necrotic insect bites I had treated with antihistamines, so I started myself on that regimen. The redness cleared up in 2 days and the wound healed completely in 10 days without antibiotics. A 3 × 3 mm circular scar remained; I lost none of the surrounding marginal skin.

Further evidence of less severe second bites. Another physician—my coauthor on the presentation to the Southwestern Surgical Congress—was bitten at age 12 by an unidentified insect, resulting in a large necrotic wound on his thigh. The lesion, reportedly 10 to 12 cm in diameter, healed with topical treatment only. After our joint report in 1982, a brown recluse spider bit him on the abdomen while he was working in the yard. He captured the spider and verified its genus and species. Guessing that the bite he received as a 12 year old was also from a brown recluse, he decided to wait and see if he had a “second set” reaction to the bite. He had an immediate inflammatory reaction, no skin necrosis, and the entire area returned to normal in 3 days. His experience became the fifth “second set” spider bite reaction in our series.

Another dramatic experience. One 22-year-old woman’s experience is worth a longer discussion. She visited her physician because 4 small areas of necrosis on her lower abdomen and chest had lasted several days and were getting worse. He assumed these were small abscesses and treated her with antibiotics. The lesions slowly enlarged to become 6 to 8 cm in diameter, and the physician hospitalized her for intravenous (IV) antibiotic therapy.

When the patient worsened after 2 days of IV antibiotics and incision and drainage, I was called to examine her for possible surgical debridement. I thought the lesions were necrotic insect bites and recommended starting Benadryl, 50 mg qid. She improved remarkably over the next 24 hours, her wounds decreasing in size by 50%. She was discharged from the hospital and, against my advice, the Benadryl was stopped. Within 48 hours the area of inflammation around the wounds had doubled in size. She was readmitted and given Benadryl. Again she improved remarkably in 24 hours. The purulent discharge was sent for culture, which grew an organism resistant to all of her previous antibiotics. She healed uneventfully in 10 days on antihistamines, and without antibiotics. This is typical in my experience. Antibiotics have seldom proved useful, and culture results are generally confusing.

Broader support for my observations

On January 27, 2006, on eMedicine (link is no longer active), dermatologist Adam S. Stibich, MD, published a physiology review of the brown recluse bite. He acknowledged that neutrophils accumulate in the wound at 24 to 72 hours, consistent with the antigen–antibody response postulated in my clinical review. Neutrophils are products of the histamine cascade that most likely brings about tissue necrosis.

Stibich’s plea for conservative management was well founded. He noted that only 10% of envenomation episodes result in large open wounds. The physical findings he described were in keeping with my observation that a subcutaneous necrotic process precedes surface changes.

His treatment of choice was dapsone. He pointed out that other clinicians, too, had reported success with dapsone, and with steroids, antibiotics, hyperbaric oxygen, electric shock therapy, and surgical therapy.^3,4,11,12 Stibich commented extensively on these treatment modalities, except electrical shock. However, while the laboratory results achieved were good, clinical outcomes were mixed. Of these treatments, I have experience only with surgery, and I have found that it does not improve the healing process.

Antihistamine and observation: The ideal Tx

The ideal treatment for necrotic wounds from envenomation would account for an underlying antigen–antibody process, shorten the natural history of the illness, result in the least deformity, minimize cost, and allow for errors in diagnosis without harming patients.

Based on my observations since 1982, I am convinced these necrotic wounds involve an antigen–antibody reaction, are histamine driven, and are adequately treated with oral antihistamines. I now treat presumed necrotic spider bite with antihistamines only. Laboratory or serum testing to confirm a diagnosis has not been useful. It takes too long, costs too much, and does not contribute to management decisions.

If the wound improves dramatically in 24 hours, which is the norm, I continue the antihistamines for 7 to 10 days. If the wound does not improve, I suspect a bacterial component and add an antibiotic. Not once in the last 26 years have I had to resort to surgery.

Correspondence
Paul K. Carlton, Jr, MD, FACS, The Texas A&M University Health Science Center, Office of Homeland Security, 301 Tarrow, 7th Floor, John Connally Building, College Station, TX 77840; [email protected]

What is the best way to treat the bite of a brown recluse spider? Having treated more than 185 bite wounds on 150 patients over the past 30 years, I have found that an oral antihistamine works best and makes surgery unnecessary.

I did not arrive at this treatment protocol immediately but, rather, developed it in 4 phases, which I describe in this article. Not only does this conservative approach consistently heal confirmed brown recluse bite wounds, but should a bite be mistakenly attributed to the brown recluse (or one of its relatives in the Loxosceles genus of spider), there is no harm to the patient, nor any big expense.

Is a brown recluse to blame?

Due to limited experience among the wider medical community in identifying spider envenomation,^1-4 bite recognition and selection of appropriate therapy can be difficult.

Early findings can be confusing. Brown recluse bites typically feel like a pin prick. A vasoconstrictive halo may surround the bite, but this sign is inconsistent. Usually there is nothing to see immediately and pain from the bite goes away, so most patients dismiss the incident.⁵ Soon, however, pain from the envenomation begins and, importantly, becomes disproportionate to physical findings—the patient shows you where it hurts, but there is nothing visible to support a diagnosis or suggest a course of action.

Progression of the wound usually tells more than a captured specimen. If you are fortunate enough to examine an intact spider caught by the patient, a “fiddle” mark on the spider’s back confirms it is a brown recluse (FIGURE 1). However, most specimens brought in for examination are so misshapen from the patient’s retribution as to make identification futile. I focus instead on the resultant wound.

Spider’s venom causes the wound. Spiders lack a mechanical digestive system; their so-called venom actually is a set of enzymes that liquefy a prey’s tissues.⁶ In the 48 hours after a bite, these digestive enzymes cause a progressive necrosis of fat under the skin. Eventually the overlying skin also turns necrotic. The venom does not penetrate underlying fascia planes, as many infectious processes do.

Necrosis can, rarely, cause disseminated intravascular coagulation and death. A more likely scenario, though still relatively uncommon, is that the necrotic sequence leads to an indolent wound that heals only with difficulty. Most patients recover without medical care and do not even seek it.^7-9

Wounds can be categorized, as outlined by Auer et al,¹⁰ into groups 1 through 4, from least severe to most severe. However, this classification scheme has made no difference in my management decisions.

FIGURE 1
The distinctive “fiddle” mark

How my treatment protocol evolved

My protocol for treating necrotic bite wounds of the brown recluse, and similar wounds from other insects, progressed over 30 years through 4 phases of treatment concepts.

Phase 1: Surgical excision

From 1979 to 1980, I treated necrotic wounds with surgical excision and secondary closure or skin grafting.¹ Many patients complained of severe itching around these wounds, which I treated empirically with the antihistamine Benadryl. All patients experienced symptom relief and had a reasonable cosmetic result (FIGURE 2).

In writing up the case results for a presentation to the Society of Air Force Clinical Surgeons, I conducted background research and found a postulate suggesting that antigen recognition was an important factor in wound progression and that it took approximately 7 days to achieve. That postulate drove the second phase of discovery.¹

FIGURE 2
Bite wound treatment: Debridement and closure or skin grafting

From 1980 to 1981, I focused on the postulate, which also suggested that the antigen–antibody reaction following envenomation could make reactions to subsequent (“second set”) bites less severe.¹ This made sense, though good clinical data were lacking.

I decided to simply observe patients’ wounds for 7 to 10 days before performing debridement, advising patients to use an antihistamine to control symptoms during the waiting period. I took photographs to document clinical progression of wounds. In reviewing these photographs, I noted that the necrotic wounds stabilized immediately on starting an antihistamine—specifically, Benadryl, 5 mg/kg or 50 mg qid. After 7 to 10 days, I debrided the wounds, using fluorescein and a Woods lamp to guide the procedure. I found that tissue of doubtful viability survived if debridement was conservative and the patient had used an antihistamine (FIGURE 3).

FIGURE 3
Bite wound treatment: Observation for 7 to 10 days

In reviewing phase 2 results in preparation for a presentation to the Southwestern Surgical Congress, I realized that debridement was rarely indicated. So, from 1981 to 1982, I relied less on surgery and more on conservative therapy. Patients got better simply with antihistamine therapy. Redness diminished very quickly once patients took the antihistamine, and pockets of purulent material drained on their own.

This approach also allowed antigen recognition to occur and seemed to prove the postulate of a less severe second bite. I saw 4 patients with proven “second set” spider bites (intact specimens were available) and all had an immediate inflammatory response and no subsequent necrosis. An 18-month-old patient with a bite below her right eye healed with Benadryl therapy alone (FIGURE 4).

FIGURE 4
Bite wound treatment: Antihistamine alone

Phase 4: Exclusive antihistamine therapy

Since 1982, I have treated more than 100 patients (myself included) with necrotic bite wounds from spiders and other insects. None have required operative debridement, and all have achieved much more acceptable cosmetic results using Benadryl therapy than with surgical therapy.

My encounter with a brown recluse. The bite I received was rather typical. I felt a sharp sting when outside working on the lawn. I looked down, saw nothing, and assumed I had run into a pin or small stick that was now not visible. For 3 days I noticed nothing unusual. On day 4, after showering I noticed a large amount of purulent material on the towel after drying my anterior left leg. On inspecting the area, I saw an area of necrosis approximately 6 × 6 cm with a central area oozing a purulent material. This appeared just like the necrotic insect bites I had treated with antihistamines, so I started myself on that regimen. The redness cleared up in 2 days and the wound healed completely in 10 days without antibiotics. A 3 × 3 mm circular scar remained; I lost none of the surrounding marginal skin.

Further evidence of less severe second bites. Another physician—my coauthor on the presentation to the Southwestern Surgical Congress—was bitten at age 12 by an unidentified insect, resulting in a large necrotic wound on his thigh. The lesion, reportedly 10 to 12 cm in diameter, healed with topical treatment only. After our joint report in 1982, a brown recluse spider bit him on the abdomen while he was working in the yard. He captured the spider and verified its genus and species. Guessing that the bite he received as a 12 year old was also from a brown recluse, he decided to wait and see if he had a “second set” reaction to the bite. He had an immediate inflammatory reaction, no skin necrosis, and the entire area returned to normal in 3 days. His experience became the fifth “second set” spider bite reaction in our series.

Another dramatic experience. One 22-year-old woman’s experience is worth a longer discussion. She visited her physician because 4 small areas of necrosis on her lower abdomen and chest had lasted several days and were getting worse. He assumed these were small abscesses and treated her with antibiotics. The lesions slowly enlarged to become 6 to 8 cm in diameter, and the physician hospitalized her for intravenous (IV) antibiotic therapy.

When the patient worsened after 2 days of IV antibiotics and incision and drainage, I was called to examine her for possible surgical debridement. I thought the lesions were necrotic insect bites and recommended starting Benadryl, 50 mg qid. She improved remarkably over the next 24 hours, her wounds decreasing in size by 50%. She was discharged from the hospital and, against my advice, the Benadryl was stopped. Within 48 hours the area of inflammation around the wounds had doubled in size. She was readmitted and given Benadryl. Again she improved remarkably in 24 hours. The purulent discharge was sent for culture, which grew an organism resistant to all of her previous antibiotics. She healed uneventfully in 10 days on antihistamines, and without antibiotics. This is typical in my experience. Antibiotics have seldom proved useful, and culture results are generally confusing.

Broader support for my observations

On January 27, 2006, on eMedicine (link is no longer active), dermatologist Adam S. Stibich, MD, published a physiology review of the brown recluse bite. He acknowledged that neutrophils accumulate in the wound at 24 to 72 hours, consistent with the antigen–antibody response postulated in my clinical review. Neutrophils are products of the histamine cascade that most likely brings about tissue necrosis.

Stibich’s plea for conservative management was well founded. He noted that only 10% of envenomation episodes result in large open wounds. The physical findings he described were in keeping with my observation that a subcutaneous necrotic process precedes surface changes.

His treatment of choice was dapsone. He pointed out that other clinicians, too, had reported success with dapsone, and with steroids, antibiotics, hyperbaric oxygen, electric shock therapy, and surgical therapy.^3,4,11,12 Stibich commented extensively on these treatment modalities, except electrical shock. However, while the laboratory results achieved were good, clinical outcomes were mixed. Of these treatments, I have experience only with surgery, and I have found that it does not improve the healing process.

Antihistamine and observation: The ideal Tx

The ideal treatment for necrotic wounds from envenomation would account for an underlying antigen–antibody process, shorten the natural history of the illness, result in the least deformity, minimize cost, and allow for errors in diagnosis without harming patients.

Based on my observations since 1982, I am convinced these necrotic wounds involve an antigen–antibody reaction, are histamine driven, and are adequately treated with oral antihistamines. I now treat presumed necrotic spider bite with antihistamines only. Laboratory or serum testing to confirm a diagnosis has not been useful. It takes too long, costs too much, and does not contribute to management decisions.

If the wound improves dramatically in 24 hours, which is the norm, I continue the antihistamines for 7 to 10 days. If the wound does not improve, I suspect a bacterial component and add an antibiotic. Not once in the last 26 years have I had to resort to surgery.

Correspondence
Paul K. Carlton, Jr, MD, FACS, The Texas A&M University Health Science Center, Office of Homeland Security, 301 Tarrow, 7th Floor, John Connally Building, College Station, TX 77840; [email protected]

Basal cell carcinoma (BCC) is the most common skin malignancy, but it can still be a tricky and difficult diagnosis even in the most experienced hands. Many BCCs exhibit only some of the defining clinical characteristics, and even when these findings are present, they can be hard to detect without excellent background and oblique lighting and handheld magnification that is 5-power or greater.

Most clinicians are familiar with classic BCC characteristics of pearliness, rolled edges, telangiectasia, bleeding, and crusting. However, the telangiectasias may be so fine that they are difficult or impossible to see, even with excellent lighting and magnification. FIGURE 1A illustrates a histologically verified nodular BCC with telangiectasias that are not readily visible, even with camera macro magnification.

Some BCC papules or plaques lack the classic rolled edges, even when viewed with oblique lighting and magnification. Some lesions may be more scaly than pearly, and others do not bleed and crust until later in their clinical course. With such variation in clinical presentation, all possible clues to BCC are welcome.

Dark dots: Connecting them to BCC

One underappreciated sign that may help with the diagnosis of BCC is the “dark dot sign.”^1,2 Dermoscopists are familiar with patterns of pigmentation associated with BCCs, and introductory dermoscopy texts contain pictures of these patterns (blue/blue-gray blotches, maple leaf structures, and spoke-wheel structures).^3,4 What is less well known is that this pigmentation may be visible on routine skin examination as “dark dots”—blue, gray, black, or a combination thereof, such as blue-gray. When visible clinically, these dark dots may bolster one’s confidence in the diagnosis—or, in my experience, occasionally even be the best visible hint for a tentative diagnosis of BCC.

Case in point. During a routine skin examination of a patient’s back, I identified an asymptomatic lesion the patient was unaware of, exhibiting no bleeding or crusting. It drew attention because it was different from surrounding lesions (FIGURE 2A), which has been called the “ugly duckling sign.”⁵ On closer examination, I noted the lesion had a pearly sheen, telangiectasias, and a plethora of dark dots (FIGURE 2B)—the poster child for the “dark dot sign.” Unlike this profound example, most lesions that have dark dots have just one or a few visible dots.

Now review FIGURE 1A again carefully. Above the lesion’s central crater there is an arcuate hemorrhagic crust, and, between the 12 and 1 o’clock positions, a small dark dot, which helps corroborate the clinical impression of BCC. FIGURE 1B is a dermoscopic image of the same lesion. It shows the dark dot well and illustrates the ease with which telangiectasias are seen on dermoscopy, lending a high degree of certainty to the diagnosis of BCC.

Dermoscopy (FIGURE 2C) for the lesion on the patient’s back in FIGURE 2B, however, adds nothing (beyond magnification) because telangiectasias and dark dots were visible clinically.

Two cases demonstrate usefulness of dark dot sign

CASE #1

FIGURE 1A

Basal cell carcinoma. Even with photography, which is often clearer than magnified clinical inspection, telangiectasias are not well seen in this basal cell carcinoma. A dark dot, however, is visible between the 12 and 1 o’clock positions.

FIGURE 1B

A dermoscopic view of the BCC in FIGURE 1A clearly shows telangiectasias and a dark dot.

CASE #2

FIGURE 2A

Ugly duckling sign. The circled lesion on this patient’s back wasn’t crusty or bleeding, but it drew attention because it was different from surrounding lesions. This has been called the “ugly duckling sign.”

FIGURE 2B

Dark dots. A closer look at the lesion on the patient’s back revealed multiple dark dots and telangiectasias, virtually diagnostic of basal cell carcinoma.

FIGURE 2C

A dermoscopic view of the lesion in FIGURE 2B adds little to what was well visualized clinically.

Caution: Context is critical

Because dots or blotches of pigment may occur in squamous cell carcinoma, pigmented actinic keratoses, seborrheic keratoses, and hypomelanotic or “amelanotic” melanoma, it is not possible clinically to confirm a diagnosis of BCC solely on the basis of dark dots. (In fact, even in the absence of pigment, any “red and white” lesion could be an amelanotic melanoma.) However, when added to other findings, such as a firm, pearly papule, the finding increases the likelihood of BCC.

How to proceed to biopsy

Lesions such as the ones I’ve shown should never be treated without preserving a specimen for pathology examination (eg, directly frozen). That said, there is no one right biopsy technique. The choice will depend on your clinical suspicion and perhaps other factors in your patient’s circumstance.

If you believe the lesion could be a cutaneous melanoma, the ideal option is full excision (to reduce sampling error pathologically), with a narrow margin (to preserve lymphatics, should sentinel node biopsy be considered later) and full thickness (to subcutaneous fat for prognostic staging; remember the dermis on the back is very thick). If you are confident the lesion is BCC, an initial shave biopsy preserves the option for treatment via curettage should the histology reveal superficial or nodular BCC. Pathology findings that indicate infiltrative, morpheaform, or micronodular BCC require excision; curettage is not adequate treatment for these lesions.

Treating the 2 patients

The patient in FIGURE 1A had no symptoms and no history of skin cancer. Because he was skeptical of the diagnosis, I performed a shave biopsy for histologic verification. The pathology report confirmed nodular BCC. We discussed options, and the patient elected excision.

In the case of the second lesion (FIGURE 2B), the diagnosis of BCC was fairly certain. Because of the patient’s advanced age, declining health, and difficulty arranging transportation, we decided to perform a primary excision at the outset. Had histology shown BCC with micronodular architecture or infitrative features, a shave biopsy for diagnosis, plus curettage, would not have been ideal treatment. Histology showed a nodular BCC.

Acknowledgements

The author thanks the St. Vincent Mercy Medical Center (Toledo) staff for its expert assistance.

Correspondence
Gary N. Fox, MD, Defiance Clinic, 1400 E 2nd Street, Defiance, OH 43512; [email protected]

Basal cell carcinoma (BCC) is the most common skin malignancy, but it can still be a tricky and difficult diagnosis even in the most experienced hands. Many BCCs exhibit only some of the defining clinical characteristics, and even when these findings are present, they can be hard to detect without excellent background and oblique lighting and handheld magnification that is 5-power or greater.

Most clinicians are familiar with classic BCC characteristics of pearliness, rolled edges, telangiectasia, bleeding, and crusting. However, the telangiectasias may be so fine that they are difficult or impossible to see, even with excellent lighting and magnification. FIGURE 1A illustrates a histologically verified nodular BCC with telangiectasias that are not readily visible, even with camera macro magnification.

Some BCC papules or plaques lack the classic rolled edges, even when viewed with oblique lighting and magnification. Some lesions may be more scaly than pearly, and others do not bleed and crust until later in their clinical course. With such variation in clinical presentation, all possible clues to BCC are welcome.

Dark dots: Connecting them to BCC

One underappreciated sign that may help with the diagnosis of BCC is the “dark dot sign.”^1,2 Dermoscopists are familiar with patterns of pigmentation associated with BCCs, and introductory dermoscopy texts contain pictures of these patterns (blue/blue-gray blotches, maple leaf structures, and spoke-wheel structures).^3,4 What is less well known is that this pigmentation may be visible on routine skin examination as “dark dots”—blue, gray, black, or a combination thereof, such as blue-gray. When visible clinically, these dark dots may bolster one’s confidence in the diagnosis—or, in my experience, occasionally even be the best visible hint for a tentative diagnosis of BCC.

Case in point. During a routine skin examination of a patient’s back, I identified an asymptomatic lesion the patient was unaware of, exhibiting no bleeding or crusting. It drew attention because it was different from surrounding lesions (FIGURE 2A), which has been called the “ugly duckling sign.”⁵ On closer examination, I noted the lesion had a pearly sheen, telangiectasias, and a plethora of dark dots (FIGURE 2B)—the poster child for the “dark dot sign.” Unlike this profound example, most lesions that have dark dots have just one or a few visible dots.

Now review FIGURE 1A again carefully. Above the lesion’s central crater there is an arcuate hemorrhagic crust, and, between the 12 and 1 o’clock positions, a small dark dot, which helps corroborate the clinical impression of BCC. FIGURE 1B is a dermoscopic image of the same lesion. It shows the dark dot well and illustrates the ease with which telangiectasias are seen on dermoscopy, lending a high degree of certainty to the diagnosis of BCC.

Dermoscopy (FIGURE 2C) for the lesion on the patient’s back in FIGURE 2B, however, adds nothing (beyond magnification) because telangiectasias and dark dots were visible clinically.

Two cases demonstrate usefulness of dark dot sign

CASE #1

FIGURE 1A

Basal cell carcinoma. Even with photography, which is often clearer than magnified clinical inspection, telangiectasias are not well seen in this basal cell carcinoma. A dark dot, however, is visible between the 12 and 1 o’clock positions.

FIGURE 1B

A dermoscopic view of the BCC in FIGURE 1A clearly shows telangiectasias and a dark dot.

CASE #2

FIGURE 2A

Ugly duckling sign. The circled lesion on this patient’s back wasn’t crusty or bleeding, but it drew attention because it was different from surrounding lesions. This has been called the “ugly duckling sign.”

FIGURE 2B

Dark dots. A closer look at the lesion on the patient’s back revealed multiple dark dots and telangiectasias, virtually diagnostic of basal cell carcinoma.

FIGURE 2C

A dermoscopic view of the lesion in FIGURE 2B adds little to what was well visualized clinically.

Caution: Context is critical

Because dots or blotches of pigment may occur in squamous cell carcinoma, pigmented actinic keratoses, seborrheic keratoses, and hypomelanotic or “amelanotic” melanoma, it is not possible clinically to confirm a diagnosis of BCC solely on the basis of dark dots. (In fact, even in the absence of pigment, any “red and white” lesion could be an amelanotic melanoma.) However, when added to other findings, such as a firm, pearly papule, the finding increases the likelihood of BCC.

How to proceed to biopsy

Lesions such as the ones I’ve shown should never be treated without preserving a specimen for pathology examination (eg, directly frozen). That said, there is no one right biopsy technique. The choice will depend on your clinical suspicion and perhaps other factors in your patient’s circumstance.

If you believe the lesion could be a cutaneous melanoma, the ideal option is full excision (to reduce sampling error pathologically), with a narrow margin (to preserve lymphatics, should sentinel node biopsy be considered later) and full thickness (to subcutaneous fat for prognostic staging; remember the dermis on the back is very thick). If you are confident the lesion is BCC, an initial shave biopsy preserves the option for treatment via curettage should the histology reveal superficial or nodular BCC. Pathology findings that indicate infiltrative, morpheaform, or micronodular BCC require excision; curettage is not adequate treatment for these lesions.

Treating the 2 patients

The patient in FIGURE 1A had no symptoms and no history of skin cancer. Because he was skeptical of the diagnosis, I performed a shave biopsy for histologic verification. The pathology report confirmed nodular BCC. We discussed options, and the patient elected excision.

In the case of the second lesion (FIGURE 2B), the diagnosis of BCC was fairly certain. Because of the patient’s advanced age, declining health, and difficulty arranging transportation, we decided to perform a primary excision at the outset. Had histology shown BCC with micronodular architecture or infitrative features, a shave biopsy for diagnosis, plus curettage, would not have been ideal treatment. Histology showed a nodular BCC.

Acknowledgements

The author thanks the St. Vincent Mercy Medical Center (Toledo) staff for its expert assistance.

Correspondence
Gary N. Fox, MD, Defiance Clinic, 1400 E 2nd Street, Defiance, OH 43512; [email protected]

Basal cell carcinoma (BCC) is the most common skin malignancy, but it can still be a tricky and difficult diagnosis even in the most experienced hands. Many BCCs exhibit only some of the defining clinical characteristics, and even when these findings are present, they can be hard to detect without excellent background and oblique lighting and handheld magnification that is 5-power or greater.

Most clinicians are familiar with classic BCC characteristics of pearliness, rolled edges, telangiectasia, bleeding, and crusting. However, the telangiectasias may be so fine that they are difficult or impossible to see, even with excellent lighting and magnification. FIGURE 1A illustrates a histologically verified nodular BCC with telangiectasias that are not readily visible, even with camera macro magnification.

Some BCC papules or plaques lack the classic rolled edges, even when viewed with oblique lighting and magnification. Some lesions may be more scaly than pearly, and others do not bleed and crust until later in their clinical course. With such variation in clinical presentation, all possible clues to BCC are welcome.

Dark dots: Connecting them to BCC

One underappreciated sign that may help with the diagnosis of BCC is the “dark dot sign.”^1,2 Dermoscopists are familiar with patterns of pigmentation associated with BCCs, and introductory dermoscopy texts contain pictures of these patterns (blue/blue-gray blotches, maple leaf structures, and spoke-wheel structures).^3,4 What is less well known is that this pigmentation may be visible on routine skin examination as “dark dots”—blue, gray, black, or a combination thereof, such as blue-gray. When visible clinically, these dark dots may bolster one’s confidence in the diagnosis—or, in my experience, occasionally even be the best visible hint for a tentative diagnosis of BCC.

Case in point. During a routine skin examination of a patient’s back, I identified an asymptomatic lesion the patient was unaware of, exhibiting no bleeding or crusting. It drew attention because it was different from surrounding lesions (FIGURE 2A), which has been called the “ugly duckling sign.”⁵ On closer examination, I noted the lesion had a pearly sheen, telangiectasias, and a plethora of dark dots (FIGURE 2B)—the poster child for the “dark dot sign.” Unlike this profound example, most lesions that have dark dots have just one or a few visible dots.

Now review FIGURE 1A again carefully. Above the lesion’s central crater there is an arcuate hemorrhagic crust, and, between the 12 and 1 o’clock positions, a small dark dot, which helps corroborate the clinical impression of BCC. FIGURE 1B is a dermoscopic image of the same lesion. It shows the dark dot well and illustrates the ease with which telangiectasias are seen on dermoscopy, lending a high degree of certainty to the diagnosis of BCC.

Dermoscopy (FIGURE 2C) for the lesion on the patient’s back in FIGURE 2B, however, adds nothing (beyond magnification) because telangiectasias and dark dots were visible clinically.

Two cases demonstrate usefulness of dark dot sign

CASE #1

FIGURE 1A

Basal cell carcinoma. Even with photography, which is often clearer than magnified clinical inspection, telangiectasias are not well seen in this basal cell carcinoma. A dark dot, however, is visible between the 12 and 1 o’clock positions.

FIGURE 1B

A dermoscopic view of the BCC in FIGURE 1A clearly shows telangiectasias and a dark dot.

CASE #2

FIGURE 2A

Ugly duckling sign. The circled lesion on this patient’s back wasn’t crusty or bleeding, but it drew attention because it was different from surrounding lesions. This has been called the “ugly duckling sign.”

FIGURE 2B

Dark dots. A closer look at the lesion on the patient’s back revealed multiple dark dots and telangiectasias, virtually diagnostic of basal cell carcinoma.

FIGURE 2C

A dermoscopic view of the lesion in FIGURE 2B adds little to what was well visualized clinically.

Caution: Context is critical

Because dots or blotches of pigment may occur in squamous cell carcinoma, pigmented actinic keratoses, seborrheic keratoses, and hypomelanotic or “amelanotic” melanoma, it is not possible clinically to confirm a diagnosis of BCC solely on the basis of dark dots. (In fact, even in the absence of pigment, any “red and white” lesion could be an amelanotic melanoma.) However, when added to other findings, such as a firm, pearly papule, the finding increases the likelihood of BCC.

How to proceed to biopsy

Lesions such as the ones I’ve shown should never be treated without preserving a specimen for pathology examination (eg, directly frozen). That said, there is no one right biopsy technique. The choice will depend on your clinical suspicion and perhaps other factors in your patient’s circumstance.

If you believe the lesion could be a cutaneous melanoma, the ideal option is full excision (to reduce sampling error pathologically), with a narrow margin (to preserve lymphatics, should sentinel node biopsy be considered later) and full thickness (to subcutaneous fat for prognostic staging; remember the dermis on the back is very thick). If you are confident the lesion is BCC, an initial shave biopsy preserves the option for treatment via curettage should the histology reveal superficial or nodular BCC. Pathology findings that indicate infiltrative, morpheaform, or micronodular BCC require excision; curettage is not adequate treatment for these lesions.

Treating the 2 patients

The patient in FIGURE 1A had no symptoms and no history of skin cancer. Because he was skeptical of the diagnosis, I performed a shave biopsy for histologic verification. The pathology report confirmed nodular BCC. We discussed options, and the patient elected excision.

In the case of the second lesion (FIGURE 2B), the diagnosis of BCC was fairly certain. Because of the patient’s advanced age, declining health, and difficulty arranging transportation, we decided to perform a primary excision at the outset. Had histology shown BCC with micronodular architecture or infitrative features, a shave biopsy for diagnosis, plus curettage, would not have been ideal treatment. Histology showed a nodular BCC.

Acknowledgements

The author thanks the St. Vincent Mercy Medical Center (Toledo) staff for its expert assistance.

Correspondence
Gary N. Fox, MD, Defiance Clinic, 1400 E 2nd Street, Defiance, OH 43512; [email protected]

Atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, affects an estimated 2.2 million American adults.¹ The condition is associated with a 1.5- to 1.9-fold mortality risk independent of other risk factors² and about a 4- to 5-fold increase in the risk of strokes.³ Achieving rate control; restoring or maintaining sinus rhythm, when it’s feasible; and preventing stroke are the primary goals in treating patients with AF. Yet many physicians are not always sure about the best ways to achieve them.

Failure to provide adequate anticoagulation therapy—despite clear evidence that anticoagulation significantly reduces the risk of thromboembolic complications—may be the most common misstep physicians make in treating AF.⁴ But anticoagulation is not the only trouble spot. Choosing between a rate-control and rhythm-control strategy also has its share of challenges, as does deciding which drugs are best for which patients.

AF is an age-related condition, with the prevalence increasing from 0.5% among individuals <60 years old to 9% of those >80.⁵ An aging population will make your ability to manage AF even more critical in the years ahead. The text and tables that follow will help you refine your care. But first, a quick review.

Classification, causes, and clinical features

AF is classified primarily on the basis of duration:

Paroxysmal AF is the term for brief episodes (lasting <24 hours) and episodes that last up to 7 days but terminate spontaneously. Cardioversion is not needed for this self-limiting condition.

Persistent AF lasts longer than 7 days, and often requires electrical or pharmacological cardioversion.

Permanent AF is used to describe instances in which cardioversion has failed (or has not been attempted) and the arrhythmia is continuous.

These categories are not mutually exclusive—a patient may primarily have paroxysmal AF, with an occasional episode of persistent AF. The term recurrent AF is used when 2 or more episodes of paroxysmal or persistent AF occur.

Warfarin or aspirin? An anticoagulation risk tool

CHADS₂ is a validated risk stratification scheme that offers help in making decisions about anticoagulation therapy. Each of the letters in this acronym represents a risk factor, and carries a certain number of points:

Congestive heart failure (1 point)
Hypertension (1 point)
Age >75 years (1 point)
Diabetes (1 point)
Stroke (2 points)

Patients with a score of ≥3 are at high risk and need to be treated with warfarin; those with a score of 0 are at low risk and can be managed with aspirin. For patients with a score of 1 or 2, the choice of warfarin or aspirin should be based on clinician assessment and patient preference.

Source: Gage BF, et al. JAMA. 2001.²⁴

AF typically linked to heart conditions—but not always

Chronic cardiac conditions commonly associated with AF include ischemic heart disease, congestive heart failure (CHF), hypertension, and rheumatic mitral valve disease. Recurrent AF may also be associated with atrial flutter, Wolff-Parkinson-White (WPW) syndrome, or atrioventricular (AV) nodal reentrant tachycardia. It is essential to recognize the presence of such conditions, because treatment of the primary arrhythmia may reduce or eliminate the incidence of recurrent AF. ⁶

There are also noncardiac causes of AF—eg, excessive alcohol intake (“holiday heart syndrome”), pulmonary embolism and other pulmonary diseases, and hyperthyroidism and other metabolic disorders. Lone AF, a term used when the patient is younger than 60 years of age and has neither clinical nor echocardiographic evidence of cardiopulmonary disease, is a diagnosis of exclusion. About 30% to 45% of cases of paroxysmal AF and 20% to 25% of persistent AF are considered to be lone AF.¹

EKG, x-ray, and echo: The role of each

Although some patients are asymptomatic, AF patients typically present with palpitations, dyspnea, fatigue, chest pain, or dizziness. A stroke may also be the first indication that a patient has AF.

A normal pulse rules out AF,⁷ and an irregular pulse should be an indication for an electrocardiogram (EKG). In most cases, a diagnosis can be made from the results of a 12-lead EKG. However, when diagnosis is uncertain or symptoms are paroxysmal, a Holter monitor or event recorder may be required.

Thyroid, renal, and hepatic function tests, serum electrolytes, and hemograms may help to rule out reversible causes of AF. Chest x-ray is valuable in diagnosing CHF, as well as lung pathology. Recent guidelines recommend that all patients who present with AF undergo echocardiography to evaluate for valvular heart disease, left and right atrial size, left ventricular size and function, left ventricular hypertrophy, and pericardial disease.¹ Transesophageal echocardiogram (TEE) should be used to detect intracardiac clots in patients who have had an embolic event or when AF has lasted for more than 48 hours and cardioversion is being considered.

Rate vs rhythm control: What the research reveals

For hemodynamically unstable patients who present with AF and a rapid rate associated with cardiogenic shock, pulmonary edema, acute myocardial infarction, or unstable angina, urgent direct-current cardioversion is indicated. In less urgent cases, treatment is not so clear cut. Spontaneous conversion to sinus rhythm occurs in up to 60% of patients within 24 hours, and in about 80% of patients within 48 hours.⁸

Intuitively, restoring normal sinus rhythm seems superior to rate control, but several randomized trials^9-12 and one meta-analysis¹³ found no support for that belief when researchers looked at mortality, thromboembolic events, and major hemorrhage.

One of the largest studies was the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), which involved more than 4000 patients with paroxysmal and persistent AF who were randomized to either rate control or rhythm control.⁹ The research revealed a nonsignificant trend toward an increased death rate with the rhythm-control strategy—a 5-year mortality rate of 24% vs 21% for patients in the rate-control group. A trend toward higher risk of ischemic stroke, particularly associated with the lack of anticoagulation therapy, was also found in the rhythm-control group. That finding emphasizes the need for indefinite anticoagulation, independent of the use of a rate-control or rhythm-control approach.

A retrospective subanalysis of the AFFIRM trial that evaluated patients on the basis of a number of independent treatment variables found that sinus rhythm, in and of itself, was actually associated with a lower risk of death. But the antiarrhythmic agents that are often needed to achieve sinus rhythm are not associated with higher rates of survival. According to the researchers, this finding suggests that the drugs’ beneficial antiarrhythmic effects are offset by their adverse effects.¹⁴

Age is another confounding factor. Most of the AFFIRM subjects were relatively older, with a mean age of 69.7 years. In another study, rhythm control was found to be beneficial in young patients (mean age of 38.6 years) with AF and rheumatic valvular heart disease, in terms of morbidity and mortality.¹⁵

With no single treatment strategy emerging as the best approach, guidelines offer help in determining whether to pursue a rate-control or rhythm-control strategy for a particular patient. The recommendations of the British National Institute for Health and Clinical Excellence (NICE) guideline for AF,¹⁶ developed on the basis of a systematic literature review as well as expert consensus, are summarized here.

When should you opt for rate control?

The NICE guideline recommends rate control as the initial choice for patients who have persistent AF and:

• are >65 years of age
• have coronary artery disease
• do not have CHF
• are not candidates for cardioversion
• have contraindications to antiarrhythmic drugs.¹⁶

The American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) guidelines recommend maintaining a ventricular rate during AF of 60 to 80 beats per minute at rest and 90 to 115 beats per minute during exercise.¹

Which drug for which patient?

Beta-blockers and nondihydropyridine calcium channel blockers (verapamil and diltiazem) and digoxin slow conduction through the AV node. Compared with placebo, beta-blockers and calcium channel blockers are effective for controlling the ventricular rate in patients with AF, both at rest and during exercise.¹⁷ In the AFFIRM trial, rate control was achieved in 70% of patients treated with beta-blockers vs 54% of patients taking calcium channel blockers.⁹

That said, the type of drug you use to achieve rate control should be an individual decision based on characteristics of your particular patient. In general, beta-blockers are preferable for patients with myocardial infarction or ischemia, and for any patient in a high adrenergic state, whereas calcium channel blockers should be used for patients with severe asthma or chronic obstructive pulmonary disease. Consider using digoxin for patients with CHF or hypotension, because both beta-blockers and calcium channel blockers can precipitate hemodynamic deterioration in these patients.

Digoxin has a relatively slow onset of action, however, and is less effective than beta-blockers or calcium channel blockers for rate control. What’s more, digoxin is ineffective for slowing the heart rate during exercise or in hyperadrenergic states. Thus, combination therapy will be needed to achieve adequate rate control in many cases.

Agents that predominantly block AV conduction, such as beta-blockers, calcium channel blockers, and digoxin, are contraindicated in patients with WPW syndrome and wide-complex ventricular response related to the preexcitation syndrome. That’s because these drugs can trigger an antegrade conduction along the accessory pathway.¹⁸ In this subset of patients, use a Class 1 antiarrhythmic such as flecainide or procainamide, or amiodarone for rate control¹ (TABLE 1).

TABLE 1
Rate-control agents: A review of the options

When should you consider cardioversion?

The NICE guidelines recommend rhythm control as the initial choice for patients who:

• are symptomatic
• are <65 years old
• are presenting for the first time with lone AF or AF secondary to a condition that has been treated or corrected
• have CHF.¹⁶

While the guidelines recommend restoring sinus rhythm in patients with heart failure, a recent study suggests that rhythm control is no more effective for reducing the rate of death from cardiovascular causes compared to a rate-control strategy in this patient population.¹⁹ As with other aspects of AF management for which there is no definitive approach, individualized factors—including patient preference—should be your guide.

Electrical vs pharmacological cardioversion. Sinus rhythm can be established with electrical or pharmacological cardioversion. Electrical cardioversion, in which an external defibrillator delivers an electric shock that’s synchronized with the QRS complex, is usually well tolerated; embolization, pulmonary edema, and other arrhythmias are infrequent complications. Cardioversion with biphasic waveform defibrillation typically uses less energy and may have greater efficacy than monophasic waveforms.

The success rate of electrical cardioversion is higher than that of pharmacological cardioversion.⁸ But the use of electrical cardioversion is limited by the need for general anesthesia or conscious sedation for pain control. Pharmacological cardioversion is more effective for patients who have had AF for <48 hours; after that, the conversion rate drops considerably, and electrical cardioversion is often needed to restore sinus rhythm in a patient whose AF has lasted more than 7 days. A variety of antiarrhythmic drugs (TABLE 2), including propafenone, flecainide, ibutilide, and amiodarone, can be used to restore sinus rhythm. But because of the proarrhythmic potential of most of these agents, patients should be monitored in the hospital while drug therapy is initiated. After sinus rhythm is restored, maintenance therapy may be required.

Whether cardioversion is achieved by electrical or pharmacological means, it is associated with an increased risk of thromboembolism, especially in patients whose AF has persisted for >48 hours. Adequate anticoagulation with warfarin (international normalized rate of 2-3) should be achieved 3 weeks prior to cardioversion and continued for 4 weeks thereafter. Alternatively, excluding atrial thrombus by TEE paves the way for early cardioversion, using IV heparin or low-molecular-weight heparin for anticoagulation.

TABLE 2
Pharmacological cardioversion: Typical drugs and doses

Maintaining sinus rhythm: Choosing the right drug

Without chronic antiarrhythmic therapy, only about 30% of patients with AF will remain in normal sinus rhythm after a year.²⁰ Of the drugs that can be used to maintain sinus rhythm—amiodarone, disopyramide, flecainide, propafenone, and sotalol—amiodarone is the most effective. In the Canadian Trial of Atrial Fibrillation,²¹ 403 patients treated with amiodarone, sotalol, or propafenone were followed for 16 months. The recurrence rate for the amiodarone group was 35%, compared with 63% for those being treated with sotalol or propafenone.

Adverse effects to consider

Amiodarone is less proarrhythmic than the other antiarrhythmic agents, but it is associated with serious noncardiac toxicities, including pulmonary, thyroid, neurologic, hepatic, optic, and dermatologic adverse effects. In addition, amiodarone can increase plasma levels of several drugs, including digoxin and warfarin, and periodic monitoring of the doses of these medications is essential. Adding enalapril, an angiotensin-converting enzyme inhibitor, or irbesartan, an angiotensin receptor blocker, can enhance the efficacy of amiodarone in maintaining normal sinus rhythm after cardioversion.

Thus, the choice of medication to maintain sinus rhythm should be individualized, based on the patient’s underlying cardiac condition and the safety profile of the antiarrhythmics being considered. (TABLE 3). The ACC/AHA/ESC guidelines recommend class 1C agents flecainide and propafenone as first-line therapy for maintaining sinus rhythm in patients with structurally normal hearts.¹ But because of their proarrhythmic and negative ionotropic effects, class 1C agents should not be given to patients who have heart failure or ischemia. Amiodarone and dofetilide are the preferred agents for maintaining sinus rhythm in patients with heart failure and severe left ventricular hypertrophy, and dofetilide, amiodarone, and sotalol are best suited for patients with ischemic heart disease.

Pill-in-the-pocket. For selected patients with paroxysmal AF and a structurally normal heart, a “pill-in-the-pocket” strategy is an option—provided it has been tried in the hospital and proven to be safe. A patient using this strategy would self-administer a single dose of a class 1C antiarrhythmic agent—eg, 600 mg propafenone or 300 mg flecainide—at the onset of an acute episode of AF. Concomitant administration of a beta-blocker or calcium channel blocker is recommended to prevent development of atrial flutter with rapid AV conduction.

TABLE 3
Maintaining sinus rhythm in patients with AF

Using anticoagulation as prophylaxis

Judicious use of antithrombotic prophylaxis can significantly reduce the incidence of strokes associated with AF, regardless of whether you pursue a rate-control or rhythm-control strategy. Despite clear evidence of the efficacy of warfarin and aspirin in this patient population, anticoagulation remains underused in clinical practice.

If AF recurs or the patient develops chronic AF, the AFFIRM trial suggests the need for long-term anticoagulation for patients with thromboembolic risk factors.⁹

Adjusted-dose warfarin gets best results. A meta-analysis of 29 randomized trials from 1996 to 2007 involving 28,044 patients (mean age, 71 years; mean follow-up, 1.5 years) assessed the benefits of antithrombotic therapy for patients with AF.²² Compared with the controls, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% confidence interval [CI], 49%-74%) and 22% (95% CI, 6%-35%), respectively.

Adjusted-dose warfarin was substantially more effective than antiplatelet therapy (12 trials, 12,963 participants; relative risk reduction, 39% [95% CI, 22%-52%]). The absolute risk reduction (ARR) with adjusted-dose warfarin in all strokes was 2.7% per year (number needed to treat [NNT] for 1 year to prevent 1 stroke was 37) for primary prevention and 8.4% per year (NNT, 12) for secondary prevention. Aspirin showed an ARR of 0.8% per year (NNT, 125) for primary prevention trials and 2.5% per year (NNT, 40) for secondary prevention trials. The absolute increase in major extracranial hemorrhage was small (≤0.3% per year).²²

A recent Cochrane review of 8 randomized trials with a total of 9598 patients concluded that adjusted-dose warfarin reduces stroke and other major vascular events in patients with nonvalvular AF by about one third, compared with antiplatelet therapy alone.²³

Warfarin or aspirin? Tools to help you decide

The risk of stroke varies considerably among patients with AF, depending on age and history of thromboembolic events, among other risk factors. What’s more, anticoagulation therapy carries an inherent risk of increased bleeding, making its use a complicated decision. A validated stroke risk stratification scheme like the CHADS₂ can help.²⁴ (See “Warfarin or aspirin? An anticoagulation risk tool”.)

The ACC/AHA/ESC guidelines recommend an alternate means of determining when anticoagulation is needed. The recommended risk stratification scheme divides risk factors for stroke into 3 categories:

• weak/less validated (female gender, age 65-74 years, coronary artery disease, thyrotoxicosis)
• moderate (≥75 years of age, hypertension, heart failure, LV ejection fraction ≤35%, diabetes mellitus)
• high (previous stroke, TIA, or embolism; mitral stenosis, prosthetic heart valve).

The guidelines recommend warfarin therapy for any patient with any high-risk factor or 2 or more moderate-risk factors; aspirin therapy for patients with no moderate- or high-risk factors; and aspirin or warfarin for patients with 1 moderate-risk factor.¹

When conventional therapy fails

For patients who do not respond to conventional therapy, other options, including radiofrequency catheter ablation and pacemakers, may be effective in controlling symptoms and improving quality of life. In a recent RCT of 70 patients 18 to 75 years of age who experienced monthly symptomatic episodes of AF, the recurrence rate at the end of the 12-month follow-up was 13% after pulmonary vein isolation with radiofrequency ablation compared with 63% after treatment with antiarrhythmic drugs (P<.001). The rate of hospitalization was also significantly lower in the radiofrequency ablation group: 9% compared with 54% in the antiarrhythmia group (P<.001).²⁵ Another option to consider for patients who require cardiac surgery for other reasons is left atrial appendage (LAA) occlusion or ligation at the time of surgery. This may prevent cardiac embolization, because the vast majority of thrombi in nonvalvular AF involve the LAA.

Correspondence
Shobha Rao, MD, University of Texas Southwestern Family Medicine Residency Program, 6263 Harry Hines Blvd., Clinical 1 Building, Dallas, TX 75390; [email protected].

Atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, affects an estimated 2.2 million American adults.¹ The condition is associated with a 1.5- to 1.9-fold mortality risk independent of other risk factors² and about a 4- to 5-fold increase in the risk of strokes.³ Achieving rate control; restoring or maintaining sinus rhythm, when it’s feasible; and preventing stroke are the primary goals in treating patients with AF. Yet many physicians are not always sure about the best ways to achieve them.

Failure to provide adequate anticoagulation therapy—despite clear evidence that anticoagulation significantly reduces the risk of thromboembolic complications—may be the most common misstep physicians make in treating AF.⁴ But anticoagulation is not the only trouble spot. Choosing between a rate-control and rhythm-control strategy also has its share of challenges, as does deciding which drugs are best for which patients.

AF is an age-related condition, with the prevalence increasing from 0.5% among individuals <60 years old to 9% of those >80.⁵ An aging population will make your ability to manage AF even more critical in the years ahead. The text and tables that follow will help you refine your care. But first, a quick review.

Classification, causes, and clinical features

AF is classified primarily on the basis of duration:

Paroxysmal AF is the term for brief episodes (lasting <24 hours) and episodes that last up to 7 days but terminate spontaneously. Cardioversion is not needed for this self-limiting condition.

Persistent AF lasts longer than 7 days, and often requires electrical or pharmacological cardioversion.

Permanent AF is used to describe instances in which cardioversion has failed (or has not been attempted) and the arrhythmia is continuous.

These categories are not mutually exclusive—a patient may primarily have paroxysmal AF, with an occasional episode of persistent AF. The term recurrent AF is used when 2 or more episodes of paroxysmal or persistent AF occur.

Warfarin or aspirin? An anticoagulation risk tool

CHADS₂ is a validated risk stratification scheme that offers help in making decisions about anticoagulation therapy. Each of the letters in this acronym represents a risk factor, and carries a certain number of points:

Congestive heart failure (1 point)
Hypertension (1 point)
Age >75 years (1 point)
Diabetes (1 point)
Stroke (2 points)

Patients with a score of ≥3 are at high risk and need to be treated with warfarin; those with a score of 0 are at low risk and can be managed with aspirin. For patients with a score of 1 or 2, the choice of warfarin or aspirin should be based on clinician assessment and patient preference.

Source: Gage BF, et al. JAMA. 2001.²⁴

AF typically linked to heart conditions—but not always

Chronic cardiac conditions commonly associated with AF include ischemic heart disease, congestive heart failure (CHF), hypertension, and rheumatic mitral valve disease. Recurrent AF may also be associated with atrial flutter, Wolff-Parkinson-White (WPW) syndrome, or atrioventricular (AV) nodal reentrant tachycardia. It is essential to recognize the presence of such conditions, because treatment of the primary arrhythmia may reduce or eliminate the incidence of recurrent AF. ⁶

There are also noncardiac causes of AF—eg, excessive alcohol intake (“holiday heart syndrome”), pulmonary embolism and other pulmonary diseases, and hyperthyroidism and other metabolic disorders. Lone AF, a term used when the patient is younger than 60 years of age and has neither clinical nor echocardiographic evidence of cardiopulmonary disease, is a diagnosis of exclusion. About 30% to 45% of cases of paroxysmal AF and 20% to 25% of persistent AF are considered to be lone AF.¹

EKG, x-ray, and echo: The role of each

Although some patients are asymptomatic, AF patients typically present with palpitations, dyspnea, fatigue, chest pain, or dizziness. A stroke may also be the first indication that a patient has AF.

A normal pulse rules out AF,⁷ and an irregular pulse should be an indication for an electrocardiogram (EKG). In most cases, a diagnosis can be made from the results of a 12-lead EKG. However, when diagnosis is uncertain or symptoms are paroxysmal, a Holter monitor or event recorder may be required.

Thyroid, renal, and hepatic function tests, serum electrolytes, and hemograms may help to rule out reversible causes of AF. Chest x-ray is valuable in diagnosing CHF, as well as lung pathology. Recent guidelines recommend that all patients who present with AF undergo echocardiography to evaluate for valvular heart disease, left and right atrial size, left ventricular size and function, left ventricular hypertrophy, and pericardial disease.¹ Transesophageal echocardiogram (TEE) should be used to detect intracardiac clots in patients who have had an embolic event or when AF has lasted for more than 48 hours and cardioversion is being considered.

Rate vs rhythm control: What the research reveals

For hemodynamically unstable patients who present with AF and a rapid rate associated with cardiogenic shock, pulmonary edema, acute myocardial infarction, or unstable angina, urgent direct-current cardioversion is indicated. In less urgent cases, treatment is not so clear cut. Spontaneous conversion to sinus rhythm occurs in up to 60% of patients within 24 hours, and in about 80% of patients within 48 hours.⁸

Intuitively, restoring normal sinus rhythm seems superior to rate control, but several randomized trials^9-12 and one meta-analysis¹³ found no support for that belief when researchers looked at mortality, thromboembolic events, and major hemorrhage.

One of the largest studies was the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), which involved more than 4000 patients with paroxysmal and persistent AF who were randomized to either rate control or rhythm control.⁹ The research revealed a nonsignificant trend toward an increased death rate with the rhythm-control strategy—a 5-year mortality rate of 24% vs 21% for patients in the rate-control group. A trend toward higher risk of ischemic stroke, particularly associated with the lack of anticoagulation therapy, was also found in the rhythm-control group. That finding emphasizes the need for indefinite anticoagulation, independent of the use of a rate-control or rhythm-control approach.

A retrospective subanalysis of the AFFIRM trial that evaluated patients on the basis of a number of independent treatment variables found that sinus rhythm, in and of itself, was actually associated with a lower risk of death. But the antiarrhythmic agents that are often needed to achieve sinus rhythm are not associated with higher rates of survival. According to the researchers, this finding suggests that the drugs’ beneficial antiarrhythmic effects are offset by their adverse effects.¹⁴

Age is another confounding factor. Most of the AFFIRM subjects were relatively older, with a mean age of 69.7 years. In another study, rhythm control was found to be beneficial in young patients (mean age of 38.6 years) with AF and rheumatic valvular heart disease, in terms of morbidity and mortality.¹⁵

With no single treatment strategy emerging as the best approach, guidelines offer help in determining whether to pursue a rate-control or rhythm-control strategy for a particular patient. The recommendations of the British National Institute for Health and Clinical Excellence (NICE) guideline for AF,¹⁶ developed on the basis of a systematic literature review as well as expert consensus, are summarized here.

When should you opt for rate control?

The NICE guideline recommends rate control as the initial choice for patients who have persistent AF and:

• are >65 years of age
• have coronary artery disease
• do not have CHF
• are not candidates for cardioversion
• have contraindications to antiarrhythmic drugs.¹⁶

The American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) guidelines recommend maintaining a ventricular rate during AF of 60 to 80 beats per minute at rest and 90 to 115 beats per minute during exercise.¹

Which drug for which patient?

Beta-blockers and nondihydropyridine calcium channel blockers (verapamil and diltiazem) and digoxin slow conduction through the AV node. Compared with placebo, beta-blockers and calcium channel blockers are effective for controlling the ventricular rate in patients with AF, both at rest and during exercise.¹⁷ In the AFFIRM trial, rate control was achieved in 70% of patients treated with beta-blockers vs 54% of patients taking calcium channel blockers.⁹

That said, the type of drug you use to achieve rate control should be an individual decision based on characteristics of your particular patient. In general, beta-blockers are preferable for patients with myocardial infarction or ischemia, and for any patient in a high adrenergic state, whereas calcium channel blockers should be used for patients with severe asthma or chronic obstructive pulmonary disease. Consider using digoxin for patients with CHF or hypotension, because both beta-blockers and calcium channel blockers can precipitate hemodynamic deterioration in these patients.

Digoxin has a relatively slow onset of action, however, and is less effective than beta-blockers or calcium channel blockers for rate control. What’s more, digoxin is ineffective for slowing the heart rate during exercise or in hyperadrenergic states. Thus, combination therapy will be needed to achieve adequate rate control in many cases.

Agents that predominantly block AV conduction, such as beta-blockers, calcium channel blockers, and digoxin, are contraindicated in patients with WPW syndrome and wide-complex ventricular response related to the preexcitation syndrome. That’s because these drugs can trigger an antegrade conduction along the accessory pathway.¹⁸ In this subset of patients, use a Class 1 antiarrhythmic such as flecainide or procainamide, or amiodarone for rate control¹ (TABLE 1).

TABLE 1
Rate-control agents: A review of the options

When should you consider cardioversion?

The NICE guidelines recommend rhythm control as the initial choice for patients who:

• are symptomatic
• are <65 years old
• are presenting for the first time with lone AF or AF secondary to a condition that has been treated or corrected
• have CHF.¹⁶

While the guidelines recommend restoring sinus rhythm in patients with heart failure, a recent study suggests that rhythm control is no more effective for reducing the rate of death from cardiovascular causes compared to a rate-control strategy in this patient population.¹⁹ As with other aspects of AF management for which there is no definitive approach, individualized factors—including patient preference—should be your guide.

Electrical vs pharmacological cardioversion. Sinus rhythm can be established with electrical or pharmacological cardioversion. Electrical cardioversion, in which an external defibrillator delivers an electric shock that’s synchronized with the QRS complex, is usually well tolerated; embolization, pulmonary edema, and other arrhythmias are infrequent complications. Cardioversion with biphasic waveform defibrillation typically uses less energy and may have greater efficacy than monophasic waveforms.

The success rate of electrical cardioversion is higher than that of pharmacological cardioversion.⁸ But the use of electrical cardioversion is limited by the need for general anesthesia or conscious sedation for pain control. Pharmacological cardioversion is more effective for patients who have had AF for <48 hours; after that, the conversion rate drops considerably, and electrical cardioversion is often needed to restore sinus rhythm in a patient whose AF has lasted more than 7 days. A variety of antiarrhythmic drugs (TABLE 2), including propafenone, flecainide, ibutilide, and amiodarone, can be used to restore sinus rhythm. But because of the proarrhythmic potential of most of these agents, patients should be monitored in the hospital while drug therapy is initiated. After sinus rhythm is restored, maintenance therapy may be required.

Whether cardioversion is achieved by electrical or pharmacological means, it is associated with an increased risk of thromboembolism, especially in patients whose AF has persisted for >48 hours. Adequate anticoagulation with warfarin (international normalized rate of 2-3) should be achieved 3 weeks prior to cardioversion and continued for 4 weeks thereafter. Alternatively, excluding atrial thrombus by TEE paves the way for early cardioversion, using IV heparin or low-molecular-weight heparin for anticoagulation.

TABLE 2
Pharmacological cardioversion: Typical drugs and doses

Maintaining sinus rhythm: Choosing the right drug

Without chronic antiarrhythmic therapy, only about 30% of patients with AF will remain in normal sinus rhythm after a year.²⁰ Of the drugs that can be used to maintain sinus rhythm—amiodarone, disopyramide, flecainide, propafenone, and sotalol—amiodarone is the most effective. In the Canadian Trial of Atrial Fibrillation,²¹ 403 patients treated with amiodarone, sotalol, or propafenone were followed for 16 months. The recurrence rate for the amiodarone group was 35%, compared with 63% for those being treated with sotalol or propafenone.

Adverse effects to consider

Amiodarone is less proarrhythmic than the other antiarrhythmic agents, but it is associated with serious noncardiac toxicities, including pulmonary, thyroid, neurologic, hepatic, optic, and dermatologic adverse effects. In addition, amiodarone can increase plasma levels of several drugs, including digoxin and warfarin, and periodic monitoring of the doses of these medications is essential. Adding enalapril, an angiotensin-converting enzyme inhibitor, or irbesartan, an angiotensin receptor blocker, can enhance the efficacy of amiodarone in maintaining normal sinus rhythm after cardioversion.

Thus, the choice of medication to maintain sinus rhythm should be individualized, based on the patient’s underlying cardiac condition and the safety profile of the antiarrhythmics being considered. (TABLE 3). The ACC/AHA/ESC guidelines recommend class 1C agents flecainide and propafenone as first-line therapy for maintaining sinus rhythm in patients with structurally normal hearts.¹ But because of their proarrhythmic and negative ionotropic effects, class 1C agents should not be given to patients who have heart failure or ischemia. Amiodarone and dofetilide are the preferred agents for maintaining sinus rhythm in patients with heart failure and severe left ventricular hypertrophy, and dofetilide, amiodarone, and sotalol are best suited for patients with ischemic heart disease.

Pill-in-the-pocket. For selected patients with paroxysmal AF and a structurally normal heart, a “pill-in-the-pocket” strategy is an option—provided it has been tried in the hospital and proven to be safe. A patient using this strategy would self-administer a single dose of a class 1C antiarrhythmic agent—eg, 600 mg propafenone or 300 mg flecainide—at the onset of an acute episode of AF. Concomitant administration of a beta-blocker or calcium channel blocker is recommended to prevent development of atrial flutter with rapid AV conduction.

TABLE 3
Maintaining sinus rhythm in patients with AF

Using anticoagulation as prophylaxis

Judicious use of antithrombotic prophylaxis can significantly reduce the incidence of strokes associated with AF, regardless of whether you pursue a rate-control or rhythm-control strategy. Despite clear evidence of the efficacy of warfarin and aspirin in this patient population, anticoagulation remains underused in clinical practice.

If AF recurs or the patient develops chronic AF, the AFFIRM trial suggests the need for long-term anticoagulation for patients with thromboembolic risk factors.⁹

Adjusted-dose warfarin gets best results. A meta-analysis of 29 randomized trials from 1996 to 2007 involving 28,044 patients (mean age, 71 years; mean follow-up, 1.5 years) assessed the benefits of antithrombotic therapy for patients with AF.²² Compared with the controls, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% confidence interval [CI], 49%-74%) and 22% (95% CI, 6%-35%), respectively.

Adjusted-dose warfarin was substantially more effective than antiplatelet therapy (12 trials, 12,963 participants; relative risk reduction, 39% [95% CI, 22%-52%]). The absolute risk reduction (ARR) with adjusted-dose warfarin in all strokes was 2.7% per year (number needed to treat [NNT] for 1 year to prevent 1 stroke was 37) for primary prevention and 8.4% per year (NNT, 12) for secondary prevention. Aspirin showed an ARR of 0.8% per year (NNT, 125) for primary prevention trials and 2.5% per year (NNT, 40) for secondary prevention trials. The absolute increase in major extracranial hemorrhage was small (≤0.3% per year).²²

A recent Cochrane review of 8 randomized trials with a total of 9598 patients concluded that adjusted-dose warfarin reduces stroke and other major vascular events in patients with nonvalvular AF by about one third, compared with antiplatelet therapy alone.²³

Warfarin or aspirin? Tools to help you decide

The risk of stroke varies considerably among patients with AF, depending on age and history of thromboembolic events, among other risk factors. What’s more, anticoagulation therapy carries an inherent risk of increased bleeding, making its use a complicated decision. A validated stroke risk stratification scheme like the CHADS₂ can help.²⁴ (See “Warfarin or aspirin? An anticoagulation risk tool”.)

The ACC/AHA/ESC guidelines recommend an alternate means of determining when anticoagulation is needed. The recommended risk stratification scheme divides risk factors for stroke into 3 categories:

• weak/less validated (female gender, age 65-74 years, coronary artery disease, thyrotoxicosis)
• moderate (≥75 years of age, hypertension, heart failure, LV ejection fraction ≤35%, diabetes mellitus)
• high (previous stroke, TIA, or embolism; mitral stenosis, prosthetic heart valve).

The guidelines recommend warfarin therapy for any patient with any high-risk factor or 2 or more moderate-risk factors; aspirin therapy for patients with no moderate- or high-risk factors; and aspirin or warfarin for patients with 1 moderate-risk factor.¹

When conventional therapy fails

For patients who do not respond to conventional therapy, other options, including radiofrequency catheter ablation and pacemakers, may be effective in controlling symptoms and improving quality of life. In a recent RCT of 70 patients 18 to 75 years of age who experienced monthly symptomatic episodes of AF, the recurrence rate at the end of the 12-month follow-up was 13% after pulmonary vein isolation with radiofrequency ablation compared with 63% after treatment with antiarrhythmic drugs (P<.001). The rate of hospitalization was also significantly lower in the radiofrequency ablation group: 9% compared with 54% in the antiarrhythmia group (P<.001).²⁵ Another option to consider for patients who require cardiac surgery for other reasons is left atrial appendage (LAA) occlusion or ligation at the time of surgery. This may prevent cardiac embolization, because the vast majority of thrombi in nonvalvular AF involve the LAA.

Correspondence
Shobha Rao, MD, University of Texas Southwestern Family Medicine Residency Program, 6263 Harry Hines Blvd., Clinical 1 Building, Dallas, TX 75390; [email protected].

Atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, affects an estimated 2.2 million American adults.¹ The condition is associated with a 1.5- to 1.9-fold mortality risk independent of other risk factors² and about a 4- to 5-fold increase in the risk of strokes.³ Achieving rate control; restoring or maintaining sinus rhythm, when it’s feasible; and preventing stroke are the primary goals in treating patients with AF. Yet many physicians are not always sure about the best ways to achieve them.

Failure to provide adequate anticoagulation therapy—despite clear evidence that anticoagulation significantly reduces the risk of thromboembolic complications—may be the most common misstep physicians make in treating AF.⁴ But anticoagulation is not the only trouble spot. Choosing between a rate-control and rhythm-control strategy also has its share of challenges, as does deciding which drugs are best for which patients.

AF is an age-related condition, with the prevalence increasing from 0.5% among individuals <60 years old to 9% of those >80.⁵ An aging population will make your ability to manage AF even more critical in the years ahead. The text and tables that follow will help you refine your care. But first, a quick review.

Classification, causes, and clinical features

AF is classified primarily on the basis of duration:

Paroxysmal AF is the term for brief episodes (lasting <24 hours) and episodes that last up to 7 days but terminate spontaneously. Cardioversion is not needed for this self-limiting condition.

Persistent AF lasts longer than 7 days, and often requires electrical or pharmacological cardioversion.

Permanent AF is used to describe instances in which cardioversion has failed (or has not been attempted) and the arrhythmia is continuous.

These categories are not mutually exclusive—a patient may primarily have paroxysmal AF, with an occasional episode of persistent AF. The term recurrent AF is used when 2 or more episodes of paroxysmal or persistent AF occur.

Warfarin or aspirin? An anticoagulation risk tool

CHADS₂ is a validated risk stratification scheme that offers help in making decisions about anticoagulation therapy. Each of the letters in this acronym represents a risk factor, and carries a certain number of points:

Congestive heart failure (1 point)
Hypertension (1 point)
Age >75 years (1 point)
Diabetes (1 point)
Stroke (2 points)

Patients with a score of ≥3 are at high risk and need to be treated with warfarin; those with a score of 0 are at low risk and can be managed with aspirin. For patients with a score of 1 or 2, the choice of warfarin or aspirin should be based on clinician assessment and patient preference.

Source: Gage BF, et al. JAMA. 2001.²⁴

AF typically linked to heart conditions—but not always

Chronic cardiac conditions commonly associated with AF include ischemic heart disease, congestive heart failure (CHF), hypertension, and rheumatic mitral valve disease. Recurrent AF may also be associated with atrial flutter, Wolff-Parkinson-White (WPW) syndrome, or atrioventricular (AV) nodal reentrant tachycardia. It is essential to recognize the presence of such conditions, because treatment of the primary arrhythmia may reduce or eliminate the incidence of recurrent AF. ⁶

There are also noncardiac causes of AF—eg, excessive alcohol intake (“holiday heart syndrome”), pulmonary embolism and other pulmonary diseases, and hyperthyroidism and other metabolic disorders. Lone AF, a term used when the patient is younger than 60 years of age and has neither clinical nor echocardiographic evidence of cardiopulmonary disease, is a diagnosis of exclusion. About 30% to 45% of cases of paroxysmal AF and 20% to 25% of persistent AF are considered to be lone AF.¹

EKG, x-ray, and echo: The role of each

Although some patients are asymptomatic, AF patients typically present with palpitations, dyspnea, fatigue, chest pain, or dizziness. A stroke may also be the first indication that a patient has AF.

A normal pulse rules out AF,⁷ and an irregular pulse should be an indication for an electrocardiogram (EKG). In most cases, a diagnosis can be made from the results of a 12-lead EKG. However, when diagnosis is uncertain or symptoms are paroxysmal, a Holter monitor or event recorder may be required.

Thyroid, renal, and hepatic function tests, serum electrolytes, and hemograms may help to rule out reversible causes of AF. Chest x-ray is valuable in diagnosing CHF, as well as lung pathology. Recent guidelines recommend that all patients who present with AF undergo echocardiography to evaluate for valvular heart disease, left and right atrial size, left ventricular size and function, left ventricular hypertrophy, and pericardial disease.¹ Transesophageal echocardiogram (TEE) should be used to detect intracardiac clots in patients who have had an embolic event or when AF has lasted for more than 48 hours and cardioversion is being considered.

Rate vs rhythm control: What the research reveals

For hemodynamically unstable patients who present with AF and a rapid rate associated with cardiogenic shock, pulmonary edema, acute myocardial infarction, or unstable angina, urgent direct-current cardioversion is indicated. In less urgent cases, treatment is not so clear cut. Spontaneous conversion to sinus rhythm occurs in up to 60% of patients within 24 hours, and in about 80% of patients within 48 hours.⁸

Intuitively, restoring normal sinus rhythm seems superior to rate control, but several randomized trials^9-12 and one meta-analysis¹³ found no support for that belief when researchers looked at mortality, thromboembolic events, and major hemorrhage.

One of the largest studies was the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), which involved more than 4000 patients with paroxysmal and persistent AF who were randomized to either rate control or rhythm control.⁹ The research revealed a nonsignificant trend toward an increased death rate with the rhythm-control strategy—a 5-year mortality rate of 24% vs 21% for patients in the rate-control group. A trend toward higher risk of ischemic stroke, particularly associated with the lack of anticoagulation therapy, was also found in the rhythm-control group. That finding emphasizes the need for indefinite anticoagulation, independent of the use of a rate-control or rhythm-control approach.

A retrospective subanalysis of the AFFIRM trial that evaluated patients on the basis of a number of independent treatment variables found that sinus rhythm, in and of itself, was actually associated with a lower risk of death. But the antiarrhythmic agents that are often needed to achieve sinus rhythm are not associated with higher rates of survival. According to the researchers, this finding suggests that the drugs’ beneficial antiarrhythmic effects are offset by their adverse effects.¹⁴

Age is another confounding factor. Most of the AFFIRM subjects were relatively older, with a mean age of 69.7 years. In another study, rhythm control was found to be beneficial in young patients (mean age of 38.6 years) with AF and rheumatic valvular heart disease, in terms of morbidity and mortality.¹⁵

With no single treatment strategy emerging as the best approach, guidelines offer help in determining whether to pursue a rate-control or rhythm-control strategy for a particular patient. The recommendations of the British National Institute for Health and Clinical Excellence (NICE) guideline for AF,¹⁶ developed on the basis of a systematic literature review as well as expert consensus, are summarized here.

When should you opt for rate control?

The NICE guideline recommends rate control as the initial choice for patients who have persistent AF and:

• are >65 years of age
• have coronary artery disease
• do not have CHF
• are not candidates for cardioversion
• have contraindications to antiarrhythmic drugs.¹⁶

The American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) guidelines recommend maintaining a ventricular rate during AF of 60 to 80 beats per minute at rest and 90 to 115 beats per minute during exercise.¹

Which drug for which patient?

Beta-blockers and nondihydropyridine calcium channel blockers (verapamil and diltiazem) and digoxin slow conduction through the AV node. Compared with placebo, beta-blockers and calcium channel blockers are effective for controlling the ventricular rate in patients with AF, both at rest and during exercise.¹⁷ In the AFFIRM trial, rate control was achieved in 70% of patients treated with beta-blockers vs 54% of patients taking calcium channel blockers.⁹

That said, the type of drug you use to achieve rate control should be an individual decision based on characteristics of your particular patient. In general, beta-blockers are preferable for patients with myocardial infarction or ischemia, and for any patient in a high adrenergic state, whereas calcium channel blockers should be used for patients with severe asthma or chronic obstructive pulmonary disease. Consider using digoxin for patients with CHF or hypotension, because both beta-blockers and calcium channel blockers can precipitate hemodynamic deterioration in these patients.

Digoxin has a relatively slow onset of action, however, and is less effective than beta-blockers or calcium channel blockers for rate control. What’s more, digoxin is ineffective for slowing the heart rate during exercise or in hyperadrenergic states. Thus, combination therapy will be needed to achieve adequate rate control in many cases.

Agents that predominantly block AV conduction, such as beta-blockers, calcium channel blockers, and digoxin, are contraindicated in patients with WPW syndrome and wide-complex ventricular response related to the preexcitation syndrome. That’s because these drugs can trigger an antegrade conduction along the accessory pathway.¹⁸ In this subset of patients, use a Class 1 antiarrhythmic such as flecainide or procainamide, or amiodarone for rate control¹ (TABLE 1).

TABLE 1
Rate-control agents: A review of the options

When should you consider cardioversion?

The NICE guidelines recommend rhythm control as the initial choice for patients who:

• are symptomatic
• are <65 years old
• are presenting for the first time with lone AF or AF secondary to a condition that has been treated or corrected
• have CHF.¹⁶

While the guidelines recommend restoring sinus rhythm in patients with heart failure, a recent study suggests that rhythm control is no more effective for reducing the rate of death from cardiovascular causes compared to a rate-control strategy in this patient population.¹⁹ As with other aspects of AF management for which there is no definitive approach, individualized factors—including patient preference—should be your guide.

Electrical vs pharmacological cardioversion. Sinus rhythm can be established with electrical or pharmacological cardioversion. Electrical cardioversion, in which an external defibrillator delivers an electric shock that’s synchronized with the QRS complex, is usually well tolerated; embolization, pulmonary edema, and other arrhythmias are infrequent complications. Cardioversion with biphasic waveform defibrillation typically uses less energy and may have greater efficacy than monophasic waveforms.

The success rate of electrical cardioversion is higher than that of pharmacological cardioversion.⁸ But the use of electrical cardioversion is limited by the need for general anesthesia or conscious sedation for pain control. Pharmacological cardioversion is more effective for patients who have had AF for <48 hours; after that, the conversion rate drops considerably, and electrical cardioversion is often needed to restore sinus rhythm in a patient whose AF has lasted more than 7 days. A variety of antiarrhythmic drugs (TABLE 2), including propafenone, flecainide, ibutilide, and amiodarone, can be used to restore sinus rhythm. But because of the proarrhythmic potential of most of these agents, patients should be monitored in the hospital while drug therapy is initiated. After sinus rhythm is restored, maintenance therapy may be required.

Whether cardioversion is achieved by electrical or pharmacological means, it is associated with an increased risk of thromboembolism, especially in patients whose AF has persisted for >48 hours. Adequate anticoagulation with warfarin (international normalized rate of 2-3) should be achieved 3 weeks prior to cardioversion and continued for 4 weeks thereafter. Alternatively, excluding atrial thrombus by TEE paves the way for early cardioversion, using IV heparin or low-molecular-weight heparin for anticoagulation.

TABLE 2
Pharmacological cardioversion: Typical drugs and doses

Maintaining sinus rhythm: Choosing the right drug

Without chronic antiarrhythmic therapy, only about 30% of patients with AF will remain in normal sinus rhythm after a year.²⁰ Of the drugs that can be used to maintain sinus rhythm—amiodarone, disopyramide, flecainide, propafenone, and sotalol—amiodarone is the most effective. In the Canadian Trial of Atrial Fibrillation,²¹ 403 patients treated with amiodarone, sotalol, or propafenone were followed for 16 months. The recurrence rate for the amiodarone group was 35%, compared with 63% for those being treated with sotalol or propafenone.

Adverse effects to consider

Amiodarone is less proarrhythmic than the other antiarrhythmic agents, but it is associated with serious noncardiac toxicities, including pulmonary, thyroid, neurologic, hepatic, optic, and dermatologic adverse effects. In addition, amiodarone can increase plasma levels of several drugs, including digoxin and warfarin, and periodic monitoring of the doses of these medications is essential. Adding enalapril, an angiotensin-converting enzyme inhibitor, or irbesartan, an angiotensin receptor blocker, can enhance the efficacy of amiodarone in maintaining normal sinus rhythm after cardioversion.

Thus, the choice of medication to maintain sinus rhythm should be individualized, based on the patient’s underlying cardiac condition and the safety profile of the antiarrhythmics being considered. (TABLE 3). The ACC/AHA/ESC guidelines recommend class 1C agents flecainide and propafenone as first-line therapy for maintaining sinus rhythm in patients with structurally normal hearts.¹ But because of their proarrhythmic and negative ionotropic effects, class 1C agents should not be given to patients who have heart failure or ischemia. Amiodarone and dofetilide are the preferred agents for maintaining sinus rhythm in patients with heart failure and severe left ventricular hypertrophy, and dofetilide, amiodarone, and sotalol are best suited for patients with ischemic heart disease.

Pill-in-the-pocket. For selected patients with paroxysmal AF and a structurally normal heart, a “pill-in-the-pocket” strategy is an option—provided it has been tried in the hospital and proven to be safe. A patient using this strategy would self-administer a single dose of a class 1C antiarrhythmic agent—eg, 600 mg propafenone or 300 mg flecainide—at the onset of an acute episode of AF. Concomitant administration of a beta-blocker or calcium channel blocker is recommended to prevent development of atrial flutter with rapid AV conduction.

TABLE 3
Maintaining sinus rhythm in patients with AF

Using anticoagulation as prophylaxis

Judicious use of antithrombotic prophylaxis can significantly reduce the incidence of strokes associated with AF, regardless of whether you pursue a rate-control or rhythm-control strategy. Despite clear evidence of the efficacy of warfarin and aspirin in this patient population, anticoagulation remains underused in clinical practice.

If AF recurs or the patient develops chronic AF, the AFFIRM trial suggests the need for long-term anticoagulation for patients with thromboembolic risk factors.⁹

Adjusted-dose warfarin gets best results. A meta-analysis of 29 randomized trials from 1996 to 2007 involving 28,044 patients (mean age, 71 years; mean follow-up, 1.5 years) assessed the benefits of antithrombotic therapy for patients with AF.²² Compared with the controls, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% confidence interval [CI], 49%-74%) and 22% (95% CI, 6%-35%), respectively.

Adjusted-dose warfarin was substantially more effective than antiplatelet therapy (12 trials, 12,963 participants; relative risk reduction, 39% [95% CI, 22%-52%]). The absolute risk reduction (ARR) with adjusted-dose warfarin in all strokes was 2.7% per year (number needed to treat [NNT] for 1 year to prevent 1 stroke was 37) for primary prevention and 8.4% per year (NNT, 12) for secondary prevention. Aspirin showed an ARR of 0.8% per year (NNT, 125) for primary prevention trials and 2.5% per year (NNT, 40) for secondary prevention trials. The absolute increase in major extracranial hemorrhage was small (≤0.3% per year).²²

A recent Cochrane review of 8 randomized trials with a total of 9598 patients concluded that adjusted-dose warfarin reduces stroke and other major vascular events in patients with nonvalvular AF by about one third, compared with antiplatelet therapy alone.²³

Warfarin or aspirin? Tools to help you decide

The risk of stroke varies considerably among patients with AF, depending on age and history of thromboembolic events, among other risk factors. What’s more, anticoagulation therapy carries an inherent risk of increased bleeding, making its use a complicated decision. A validated stroke risk stratification scheme like the CHADS₂ can help.²⁴ (See “Warfarin or aspirin? An anticoagulation risk tool”.)

The ACC/AHA/ESC guidelines recommend an alternate means of determining when anticoagulation is needed. The recommended risk stratification scheme divides risk factors for stroke into 3 categories:

• weak/less validated (female gender, age 65-74 years, coronary artery disease, thyrotoxicosis)
• moderate (≥75 years of age, hypertension, heart failure, LV ejection fraction ≤35%, diabetes mellitus)
• high (previous stroke, TIA, or embolism; mitral stenosis, prosthetic heart valve).

The guidelines recommend warfarin therapy for any patient with any high-risk factor or 2 or more moderate-risk factors; aspirin therapy for patients with no moderate- or high-risk factors; and aspirin or warfarin for patients with 1 moderate-risk factor.¹

When conventional therapy fails

For patients who do not respond to conventional therapy, other options, including radiofrequency catheter ablation and pacemakers, may be effective in controlling symptoms and improving quality of life. In a recent RCT of 70 patients 18 to 75 years of age who experienced monthly symptomatic episodes of AF, the recurrence rate at the end of the 12-month follow-up was 13% after pulmonary vein isolation with radiofrequency ablation compared with 63% after treatment with antiarrhythmic drugs (P<.001). The rate of hospitalization was also significantly lower in the radiofrequency ablation group: 9% compared with 54% in the antiarrhythmia group (P<.001).²⁵ Another option to consider for patients who require cardiac surgery for other reasons is left atrial appendage (LAA) occlusion or ligation at the time of surgery. This may prevent cardiac embolization, because the vast majority of thrombi in nonvalvular AF involve the LAA.

Correspondence
Shobha Rao, MD, University of Texas Southwestern Family Medicine Residency Program, 6263 Harry Hines Blvd., Clinical 1 Building, Dallas, TX 75390; [email protected].

JC, a 23-year-old man, is in your office for evaluation of high blood pressure, after failing a commercial driver’s license exam the previous week. He has been your patient for the past 10 years, and his previous annual physicals have been unremarkable. He is 5’10’’ tall, weighs 209 pounds, and has a muscular build. His blood pressure today is 160/90 and his heart rate is 62 and regular. The rest of his physical exam is normal.

He is a nonsmoker, rarely uses alcohol, and denies illicit drug use. He exercises regularly, has been taking some protein shakes and what he refers to as a “natural” supplement. His lab work shows some elevation in his aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with a negative hepatitis panel. The rest of his metabolic panel is within normal limits.

JC was on the track team in high school, and since graduation has continued to work out and stay fit. You ask him if he takes steroids, and he tells you he was warned about the risks of anabolic androgenic steroids (AAS) in high school. He sticks to a “natural” supplement, which he buys online or through friends at the gym. Still, you know that elevated liver enzymes and hypertension can be associated with AAS use and that dietary supplements don’t have to meet the same standards the Food and Drug Administration (FDA) imposes on drugs. (See “What’s in that supplement? Labels don’t always help” on page 18.) You warn him that supplements aren’t always safe, and ask him to bring in his supplement bottle so you can go over the label and, possibly, have the contents tested.

Pursuit of that “edge” extends beyond Olympians

Even before the start of the modern Olympic games, athletes have used ergogenic aids—substances used to enhance performance, energy, or work capacity—to give themselves a “competitive edge.”^1,2 Athletes still use these substances today, and they have been joined by nonathletes—some of whom simply want to look good.

A 2004 Internet study of AAS users reported that the majority are recreational bodybuilders or nonathletes. Twenty-five percent of participants in this survey reported starting using steroids during their teenage years.³

An ongoing study of high school students and young adults indicates an AAS use prevalence rate of 1.1% to 2.3% in boys and 0.4% to 0.6% in girls. Approximately 40% of survey participants noted that obtaining steroids was relatively easy.⁴

The Centers for Disease Control and Prevention (CDC) reports that 4.4% to 5.7% of boys (grades 9 through 12) have used illegal steroids and that 1.9% to 3.8% of girls have.⁵

Few AAS users tell their physicians of their steroid use. Part of the reason, of course, is that illegal substance use is stigmatized and can lead to prosecution. Another reason, though, is that these patients think physicians don’t know much about these substances.³ Still other patients, like JC, don’t tell because they may not even be aware that some substances billed as “natural” conceal potential dangers.

For help in spotting patients who are using these agents, see “Red flags for performance-enhancing drug use” on page 20.

Performance-enhancing drugs go by many names

Refining your care of patients who are taking performance-enhancing drugs requires that you know the various names these drugs go by, the reason your patients may be taking them, and the adverse effects associated with them. This review, and the TABLE, will help.

Table
Performance-enhancing agents: What to watch for

Anabolic androgenic steroids: Often paired with energy drinks

Teenagers may refer to AAS as “pumpers,” “gym candy,” or “juice.” Trade names for AAS are Dianabol, Anadrol, Deca Durabolin, Parabolin, and Winstrol. AAS are often used with nutritional supplements like creatine, multivitamins, and energy drinks, in the belief that these regimens will make the user stronger, more muscular, and a better athlete.^6,7

AAS are synthetic analogues of testosterone and come in oral, injectable, and transdermal forms.^8,9 At supraphysiologic doses, testosterone has been found to increase lean body (fat-free) mass and muscle strength in humans.¹⁰ The anabolic effects are more pronounced when AAS are used at higher doses over longer periods of time, especially when combined with a strength training program.^9,10 AAS have also been found to stimulate the production of growth hormone and insulin-like growth factor and to counteract the catabolic effects of cortisol.¹¹

The use and possession of AAS without a doctor’s prescription is illegal in the United States. A majority of AAS users buy their medications through Internet suppliers, with some of the drugs being manufactured overseas or in illicit labs.³ Substandard quality control in manufacture poses an increased health risk to consumers.

Adverse effects include injection site pain, acne, baldness, gynecomastia, testicular atrophy, sexual dysfunction, and psychological disturbances (also known as “roid rage”).^8,9,11-13 Increases in liver enzymes with the oral forms of AAS have also been noted.⁸ In the prepubertal athlete, premature physeal closure may occur, resulting in permanent short stature.¹⁴ Women who take AAS may have virilization effects, menstrual irregularities, and early menopause.¹¹

The cardiovascular risks of AAS use are substantial. High-dose and long-term AAS use has been linked to cardiomyopathy and sudden death.^15-20 Some data suggest the development of accelerated atherosclerosis with AAS use, leading to hypertension, coronary artery disease (CAD), and acute myocardial infarction.^15,16,18-21 An unfavorable lipid panel has also been noted, with an increase in LDL and decreased HDL.^18-21

Tetrahydrogestrinone: A “designer” steroid

Tetrahydrogestrinone (THG) was initially developed to avoid detection by testing protocols current at the time.^22-24 This drug has garnered significant media attention in the past few years because of scandals involving professional and Olympic athletes. THG is chemically related to 2 other banned steroids, trenbolone and gestrinone.^22,24 It is used similarly to AAS to increase muscle bulk and enhance performance. It is more hepatotoxic than AAS, with highly potent androgenic and progestin properties in in vitro bioassay studies.^22,25

Marketing of this agent is banned in the United States. There are no long-term studies of its effectiveness or side effect profile.

Androstenedione: Initially an anti-aging drug

Androstenedione, aka Andromax and Androstat 100, is a precursor of testosterone. This substance is produced in the adrenal glands and gonads.² Initially marketed as a dietary supplement and anti-aging drug, it was banned by the FDA in 2004 because of its potent anabolic and androgenic effects.²⁶ Ergogenic use includes promoting muscle building and strength and fat reduction.² Studies on healthy young men found no improvement in skeletal muscle adaptation to resistance training with androstenedione supplementation for 8 to 12 weeks.^27,28 Studies of its effect on increasing blood testosterone levels are conflicting.^27,29 Several studies noted an increase in estradiol levels after oral androstenedione supplementation.^9,11,27-29

Endocrine pathways with this drug are similar to AAS, and the side effect profile is similar as well, although not as pronounced. Larger, long-term studies are needed to fill out this drug’s profile and document its effects on the athletes who use it.

Dehydroepiandrosterone: Marketed as a “wonder drug”

Dehydroepiandrosterone (DHEA), marketed under the names Prastera, Fidelin, and Fluasterone, is another precursor of testosterone. It is produced in the adrenal cortex and has weak androgenic properties.² DHEA is a dietary supplement marketed as a “wonder drug” and, like androstenedione, is advertised to promote muscle-building and fat-burning. It is also said to have anti-aging properties.^11,14 DHEA has been used by athletes in the belief that it will increase testosterone levels and muscle bulk.³⁰

In studies done in healthy men, however, even large doses of DHEA (1600 mg/d) did not result in an increase in testosterone levels. An increase in estradiol levels was noted in elderly men. Women who supplement with DHEA were found to have increased levels of testosterone and virilization effects, even at small doses (25-50 mg/d).³¹ Because of the risk of these side effects and the lack of long-term studies, DHEA supplementation is not recommended for use by adolescents or women.³⁰ There is no convincing evidence to support claims of the anabolic and anti-aging effects of DHEA.

Human growth hormone: Side effects include hypertension

Human growth hormone (HGH) is an endogenous pituitary hormone with anabolic functions that increases muscle mass without the androgenic side effects. It is used medically for patients with decreased endogenous levels of GH or dwarfism. As an ergogenic aid, it has been found to increase levels of insulin-like growth factors, and the combination leads to increased protein synthesis and muscle mass.³²

Side effects of HGH include insulin resistance, GH-induced myopathy, and acromegaly-like effects.¹¹ There have been reports of hypertension, cardiomegaly, ventricular hypertrophy, and abnormal lipids with excessive use.^19,33 Premature physeal closure may occur in the adolescent HGH user.⁸ It’s unclear whether HGH actually enhances sports performance, because the evidence is insufficient.³⁴

Ephedrine: Used by hockey players

Ephedrine is a stimulant derived from the herb ma huang. It goes by many names, among them Ma Huang, Bolt-ephedrine, Asia Black 25, Hot Body Ephedra, and Thin Quick. Its chemical structure is related to amphetamine. Among college athletes, ephedrine and amphetamine use is more common in power sports, those requiring increased concentration (eg, rifle shooting, fencing), ice hockey, and field sports.³⁵ Users feel less fatigue, experience bursts of energy, and lose weight.^8,36

Users may experience irritability, anxiety, insomnia, and tremors, especially if stimulants are used in conjunction with high doses of caffeine.^35,37 Ephedrine stimulates the release of norepinephrine, which produces increases in blood pressure, peripheral vascular resistance, and heart rate. These norepinephrine effects are the proposed mechanism for reported cases of myocardial infarction, cerebral artery vasoconstriction, and stroke associated with ephedrine use.¹³

Marketing of dietary supplements that contain ephedrine has been banned by the FDA because of the stimulant’s potential for increasing cardiovascular and stroke risks.³⁸

Caffeine: May give sprinters a leg up

Caffeine—which is found in everything from coffee to energy tablets and energy drinks—increases a person’s energy level. In endurance sports, it also increases time to exhaustion.³² Studies in endurance-trained cyclists have shown that caffeine intake reduced leg pain, increased maximal leg force, and lengthened time to fatigue.^39,40 A recent study in Australia also showed that caffeine may improve intermittent-sprint performance in competitive male athletes.⁴¹

Serious cardiovascular risks and even death have been documented when caffeine has been used with other stimulants, such as ephedrine or amphetamines. The combination of high doses of caffeine and ephedrine has a potential for life-threatening arrhythmia, hypertension, and stroke.⁴² Other psychomotor side effects include anxiety, irritability, tremor, and the potential for withdrawal symptoms.^42,43 Because of caffeine’s stimulant nature, the International Olympic Committee and the National Collegiate Athletic Association have set urinary thresholds for its use in competition.

Erythropoietin: Promotes endurance

Erythropoietin (EPO) is a hormone produced in the kidneys that stimulates production of red blood cells (erythropoiesis). Marketed under the brand names Epogen and Procrit, EPO has legitimate medical uses. As an ergogenic substance, EPO is used to promote endurance by increasing the oxygen-carrying capacity of the blood with the increased red blood cell mass. In endurance athletes, the benefits of recombinant erythropoietin (rEpo) may last several weeks.²³ There is also a practice called “blood doping,” which is a transfusion prior to competition, to produce the same effect.

Adverse effects of EPO use are attributed to increased blood viscosity and thrombotic potential. Pulmonary embolism, stroke, myocardial infarction, and sudden death can occur.¹⁹ Cases of death due to severe bradycardia, usually occurring during the night, have also been reported.²³ Development of anti-EPO antibodies may also occur, causing paradoxical anemia.²³ Athletes found to be using rEPO are banned from competition by sports-governing organizations.

Creatine: Popular among body builders

Creatine is a popular supplement used by athletes and recreational bodybuilders to provide energy to skeletal muscles in short-duration, maximal exercise.⁴⁴ It is an endogenous substance found mainly in skeletal muscle and is synthesized by the liver from the amino acids glycine, arginine, and methionine.^11,44 It is also found in meat.

Creatine monohydrate supplements have been found to increase creatine stores in muscles.⁴⁵ In the phosphorylated form, creatine serves as a substrate for adenosine triphosphate resynthesis during intense anaerobic exercise.^11,44-46 Numerous studies support its ergogenic effect on short-term, intermittent maximal activities such as bodybuilding, swimming, and jumping. Similar benefits have not been proven for endurance aerobic activities, such as long-distance cycling or running.^46,47

This supplement is sold in many forms under such names as Rejuvinix, Cell Tech Hardcore, Muscle Marketing, Femme Advantage, and NOZ. Although not recommended for those under age 18, creatine is actually used by approximately 5.6% of high school athletes, with the highest levels of use (44%) occurring in the 11th and 12th grades.⁴⁸ Reported side effects of creatine include muscle cramps, weight gain, and some minor gastrointestinal upset. Long-term studies on creatine supplementation are still needed.

Viagra (that’s right, Viagra)

Viagra (sildenafil) is the latest entry in the list of drugs competitive athletes may be using to try to improve sports performance. The World Anti-Doping Agency is financing a study investigating whether sildenafil can create an unfair competitive advantage by dilating blood vessels and increasing oxygen-carrying capacity.⁴⁹ Studies of the impact of sildenafil on exercise capacity of climbers at the Mt. Everest base camp and on exercise performance during acute hypoxia have been published.^50,51 Sildenafil was found to improve athletic capacity in both. To date, no action has been taken to ban the substance in athletic competition.

Are your patients using these agents? Ask them

Family physicians need to be alert to the red flags that may indicate steroid use and gently explore the full list of medications, over-the-counter products, and dietary supplements patients may be using. Take advantage of annual checkups and sports physicals to ask about use of performance-enhancing substances, educate patients on the risks involved, and emphasize good nutrition and sensible exercise routines as healthy ways to build a strong, attractive physique.

Education was certainly in order for your patient, JC, described at the beginning of this article. He thought the dietary supplement he used was natural and therefore harmless. Not so. It contained potentially dangerous substances, so you advised him to stop using it. Nutritional counseling and a vigorous exercise routine have allowed JC to maintain his fitness ideal. His blood pressure and liver enzymes returned to normal levels, and he passed his commercial driver’s license exam.

Correspondence
Marifel Mitzi F. Fernandez, MD, 600 Woodside Drive, Cornell, WI 54732; [email protected]

JC, a 23-year-old man, is in your office for evaluation of high blood pressure, after failing a commercial driver’s license exam the previous week. He has been your patient for the past 10 years, and his previous annual physicals have been unremarkable. He is 5’10’’ tall, weighs 209 pounds, and has a muscular build. His blood pressure today is 160/90 and his heart rate is 62 and regular. The rest of his physical exam is normal.

He is a nonsmoker, rarely uses alcohol, and denies illicit drug use. He exercises regularly, has been taking some protein shakes and what he refers to as a “natural” supplement. His lab work shows some elevation in his aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with a negative hepatitis panel. The rest of his metabolic panel is within normal limits.

JC was on the track team in high school, and since graduation has continued to work out and stay fit. You ask him if he takes steroids, and he tells you he was warned about the risks of anabolic androgenic steroids (AAS) in high school. He sticks to a “natural” supplement, which he buys online or through friends at the gym. Still, you know that elevated liver enzymes and hypertension can be associated with AAS use and that dietary supplements don’t have to meet the same standards the Food and Drug Administration (FDA) imposes on drugs. (See “What’s in that supplement? Labels don’t always help” on page 18.) You warn him that supplements aren’t always safe, and ask him to bring in his supplement bottle so you can go over the label and, possibly, have the contents tested.

Pursuit of that “edge” extends beyond Olympians

Even before the start of the modern Olympic games, athletes have used ergogenic aids—substances used to enhance performance, energy, or work capacity—to give themselves a “competitive edge.”^1,2 Athletes still use these substances today, and they have been joined by nonathletes—some of whom simply want to look good.

A 2004 Internet study of AAS users reported that the majority are recreational bodybuilders or nonathletes. Twenty-five percent of participants in this survey reported starting using steroids during their teenage years.³

An ongoing study of high school students and young adults indicates an AAS use prevalence rate of 1.1% to 2.3% in boys and 0.4% to 0.6% in girls. Approximately 40% of survey participants noted that obtaining steroids was relatively easy.⁴

The Centers for Disease Control and Prevention (CDC) reports that 4.4% to 5.7% of boys (grades 9 through 12) have used illegal steroids and that 1.9% to 3.8% of girls have.⁵

Few AAS users tell their physicians of their steroid use. Part of the reason, of course, is that illegal substance use is stigmatized and can lead to prosecution. Another reason, though, is that these patients think physicians don’t know much about these substances.³ Still other patients, like JC, don’t tell because they may not even be aware that some substances billed as “natural” conceal potential dangers.

For help in spotting patients who are using these agents, see “Red flags for performance-enhancing drug use” on page 20.

Performance-enhancing drugs go by many names

Refining your care of patients who are taking performance-enhancing drugs requires that you know the various names these drugs go by, the reason your patients may be taking them, and the adverse effects associated with them. This review, and the TABLE, will help.

Table
Performance-enhancing agents: What to watch for

Anabolic androgenic steroids: Often paired with energy drinks

Teenagers may refer to AAS as “pumpers,” “gym candy,” or “juice.” Trade names for AAS are Dianabol, Anadrol, Deca Durabolin, Parabolin, and Winstrol. AAS are often used with nutritional supplements like creatine, multivitamins, and energy drinks, in the belief that these regimens will make the user stronger, more muscular, and a better athlete.^6,7

AAS are synthetic analogues of testosterone and come in oral, injectable, and transdermal forms.^8,9 At supraphysiologic doses, testosterone has been found to increase lean body (fat-free) mass and muscle strength in humans.¹⁰ The anabolic effects are more pronounced when AAS are used at higher doses over longer periods of time, especially when combined with a strength training program.^9,10 AAS have also been found to stimulate the production of growth hormone and insulin-like growth factor and to counteract the catabolic effects of cortisol.¹¹

The use and possession of AAS without a doctor’s prescription is illegal in the United States. A majority of AAS users buy their medications through Internet suppliers, with some of the drugs being manufactured overseas or in illicit labs.³ Substandard quality control in manufacture poses an increased health risk to consumers.

Adverse effects include injection site pain, acne, baldness, gynecomastia, testicular atrophy, sexual dysfunction, and psychological disturbances (also known as “roid rage”).^8,9,11-13 Increases in liver enzymes with the oral forms of AAS have also been noted.⁸ In the prepubertal athlete, premature physeal closure may occur, resulting in permanent short stature.¹⁴ Women who take AAS may have virilization effects, menstrual irregularities, and early menopause.¹¹

The cardiovascular risks of AAS use are substantial. High-dose and long-term AAS use has been linked to cardiomyopathy and sudden death.^15-20 Some data suggest the development of accelerated atherosclerosis with AAS use, leading to hypertension, coronary artery disease (CAD), and acute myocardial infarction.^15,16,18-21 An unfavorable lipid panel has also been noted, with an increase in LDL and decreased HDL.^18-21

Tetrahydrogestrinone: A “designer” steroid

Tetrahydrogestrinone (THG) was initially developed to avoid detection by testing protocols current at the time.^22-24 This drug has garnered significant media attention in the past few years because of scandals involving professional and Olympic athletes. THG is chemically related to 2 other banned steroids, trenbolone and gestrinone.^22,24 It is used similarly to AAS to increase muscle bulk and enhance performance. It is more hepatotoxic than AAS, with highly potent androgenic and progestin properties in in vitro bioassay studies.^22,25

Marketing of this agent is banned in the United States. There are no long-term studies of its effectiveness or side effect profile.

Androstenedione: Initially an anti-aging drug

Androstenedione, aka Andromax and Androstat 100, is a precursor of testosterone. This substance is produced in the adrenal glands and gonads.² Initially marketed as a dietary supplement and anti-aging drug, it was banned by the FDA in 2004 because of its potent anabolic and androgenic effects.²⁶ Ergogenic use includes promoting muscle building and strength and fat reduction.² Studies on healthy young men found no improvement in skeletal muscle adaptation to resistance training with androstenedione supplementation for 8 to 12 weeks.^27,28 Studies of its effect on increasing blood testosterone levels are conflicting.^27,29 Several studies noted an increase in estradiol levels after oral androstenedione supplementation.^9,11,27-29

Endocrine pathways with this drug are similar to AAS, and the side effect profile is similar as well, although not as pronounced. Larger, long-term studies are needed to fill out this drug’s profile and document its effects on the athletes who use it.

Dehydroepiandrosterone: Marketed as a “wonder drug”

Dehydroepiandrosterone (DHEA), marketed under the names Prastera, Fidelin, and Fluasterone, is another precursor of testosterone. It is produced in the adrenal cortex and has weak androgenic properties.² DHEA is a dietary supplement marketed as a “wonder drug” and, like androstenedione, is advertised to promote muscle-building and fat-burning. It is also said to have anti-aging properties.^11,14 DHEA has been used by athletes in the belief that it will increase testosterone levels and muscle bulk.³⁰

In studies done in healthy men, however, even large doses of DHEA (1600 mg/d) did not result in an increase in testosterone levels. An increase in estradiol levels was noted in elderly men. Women who supplement with DHEA were found to have increased levels of testosterone and virilization effects, even at small doses (25-50 mg/d).³¹ Because of the risk of these side effects and the lack of long-term studies, DHEA supplementation is not recommended for use by adolescents or women.³⁰ There is no convincing evidence to support claims of the anabolic and anti-aging effects of DHEA.

Human growth hormone: Side effects include hypertension

Human growth hormone (HGH) is an endogenous pituitary hormone with anabolic functions that increases muscle mass without the androgenic side effects. It is used medically for patients with decreased endogenous levels of GH or dwarfism. As an ergogenic aid, it has been found to increase levels of insulin-like growth factors, and the combination leads to increased protein synthesis and muscle mass.³²

Side effects of HGH include insulin resistance, GH-induced myopathy, and acromegaly-like effects.¹¹ There have been reports of hypertension, cardiomegaly, ventricular hypertrophy, and abnormal lipids with excessive use.^19,33 Premature physeal closure may occur in the adolescent HGH user.⁸ It’s unclear whether HGH actually enhances sports performance, because the evidence is insufficient.³⁴

Ephedrine: Used by hockey players

Ephedrine is a stimulant derived from the herb ma huang. It goes by many names, among them Ma Huang, Bolt-ephedrine, Asia Black 25, Hot Body Ephedra, and Thin Quick. Its chemical structure is related to amphetamine. Among college athletes, ephedrine and amphetamine use is more common in power sports, those requiring increased concentration (eg, rifle shooting, fencing), ice hockey, and field sports.³⁵ Users feel less fatigue, experience bursts of energy, and lose weight.^8,36

Users may experience irritability, anxiety, insomnia, and tremors, especially if stimulants are used in conjunction with high doses of caffeine.^35,37 Ephedrine stimulates the release of norepinephrine, which produces increases in blood pressure, peripheral vascular resistance, and heart rate. These norepinephrine effects are the proposed mechanism for reported cases of myocardial infarction, cerebral artery vasoconstriction, and stroke associated with ephedrine use.¹³

Marketing of dietary supplements that contain ephedrine has been banned by the FDA because of the stimulant’s potential for increasing cardiovascular and stroke risks.³⁸

Caffeine: May give sprinters a leg up

Caffeine—which is found in everything from coffee to energy tablets and energy drinks—increases a person’s energy level. In endurance sports, it also increases time to exhaustion.³² Studies in endurance-trained cyclists have shown that caffeine intake reduced leg pain, increased maximal leg force, and lengthened time to fatigue.^39,40 A recent study in Australia also showed that caffeine may improve intermittent-sprint performance in competitive male athletes.⁴¹

Serious cardiovascular risks and even death have been documented when caffeine has been used with other stimulants, such as ephedrine or amphetamines. The combination of high doses of caffeine and ephedrine has a potential for life-threatening arrhythmia, hypertension, and stroke.⁴² Other psychomotor side effects include anxiety, irritability, tremor, and the potential for withdrawal symptoms.^42,43 Because of caffeine’s stimulant nature, the International Olympic Committee and the National Collegiate Athletic Association have set urinary thresholds for its use in competition.

Erythropoietin: Promotes endurance

Erythropoietin (EPO) is a hormone produced in the kidneys that stimulates production of red blood cells (erythropoiesis). Marketed under the brand names Epogen and Procrit, EPO has legitimate medical uses. As an ergogenic substance, EPO is used to promote endurance by increasing the oxygen-carrying capacity of the blood with the increased red blood cell mass. In endurance athletes, the benefits of recombinant erythropoietin (rEpo) may last several weeks.²³ There is also a practice called “blood doping,” which is a transfusion prior to competition, to produce the same effect.

Adverse effects of EPO use are attributed to increased blood viscosity and thrombotic potential. Pulmonary embolism, stroke, myocardial infarction, and sudden death can occur.¹⁹ Cases of death due to severe bradycardia, usually occurring during the night, have also been reported.²³ Development of anti-EPO antibodies may also occur, causing paradoxical anemia.²³ Athletes found to be using rEPO are banned from competition by sports-governing organizations.

Creatine: Popular among body builders

Creatine is a popular supplement used by athletes and recreational bodybuilders to provide energy to skeletal muscles in short-duration, maximal exercise.⁴⁴ It is an endogenous substance found mainly in skeletal muscle and is synthesized by the liver from the amino acids glycine, arginine, and methionine.^11,44 It is also found in meat.

Creatine monohydrate supplements have been found to increase creatine stores in muscles.⁴⁵ In the phosphorylated form, creatine serves as a substrate for adenosine triphosphate resynthesis during intense anaerobic exercise.^11,44-46 Numerous studies support its ergogenic effect on short-term, intermittent maximal activities such as bodybuilding, swimming, and jumping. Similar benefits have not been proven for endurance aerobic activities, such as long-distance cycling or running.^46,47

This supplement is sold in many forms under such names as Rejuvinix, Cell Tech Hardcore, Muscle Marketing, Femme Advantage, and NOZ. Although not recommended for those under age 18, creatine is actually used by approximately 5.6% of high school athletes, with the highest levels of use (44%) occurring in the 11th and 12th grades.⁴⁸ Reported side effects of creatine include muscle cramps, weight gain, and some minor gastrointestinal upset. Long-term studies on creatine supplementation are still needed.

Viagra (that’s right, Viagra)

Viagra (sildenafil) is the latest entry in the list of drugs competitive athletes may be using to try to improve sports performance. The World Anti-Doping Agency is financing a study investigating whether sildenafil can create an unfair competitive advantage by dilating blood vessels and increasing oxygen-carrying capacity.⁴⁹ Studies of the impact of sildenafil on exercise capacity of climbers at the Mt. Everest base camp and on exercise performance during acute hypoxia have been published.^50,51 Sildenafil was found to improve athletic capacity in both. To date, no action has been taken to ban the substance in athletic competition.

Are your patients using these agents? Ask them

Family physicians need to be alert to the red flags that may indicate steroid use and gently explore the full list of medications, over-the-counter products, and dietary supplements patients may be using. Take advantage of annual checkups and sports physicals to ask about use of performance-enhancing substances, educate patients on the risks involved, and emphasize good nutrition and sensible exercise routines as healthy ways to build a strong, attractive physique.

Education was certainly in order for your patient, JC, described at the beginning of this article. He thought the dietary supplement he used was natural and therefore harmless. Not so. It contained potentially dangerous substances, so you advised him to stop using it. Nutritional counseling and a vigorous exercise routine have allowed JC to maintain his fitness ideal. His blood pressure and liver enzymes returned to normal levels, and he passed his commercial driver’s license exam.

Correspondence
Marifel Mitzi F. Fernandez, MD, 600 Woodside Drive, Cornell, WI 54732; [email protected]

JC, a 23-year-old man, is in your office for evaluation of high blood pressure, after failing a commercial driver’s license exam the previous week. He has been your patient for the past 10 years, and his previous annual physicals have been unremarkable. He is 5’10’’ tall, weighs 209 pounds, and has a muscular build. His blood pressure today is 160/90 and his heart rate is 62 and regular. The rest of his physical exam is normal.

He is a nonsmoker, rarely uses alcohol, and denies illicit drug use. He exercises regularly, has been taking some protein shakes and what he refers to as a “natural” supplement. His lab work shows some elevation in his aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with a negative hepatitis panel. The rest of his metabolic panel is within normal limits.

JC was on the track team in high school, and since graduation has continued to work out and stay fit. You ask him if he takes steroids, and he tells you he was warned about the risks of anabolic androgenic steroids (AAS) in high school. He sticks to a “natural” supplement, which he buys online or through friends at the gym. Still, you know that elevated liver enzymes and hypertension can be associated with AAS use and that dietary supplements don’t have to meet the same standards the Food and Drug Administration (FDA) imposes on drugs. (See “What’s in that supplement? Labels don’t always help” on page 18.) You warn him that supplements aren’t always safe, and ask him to bring in his supplement bottle so you can go over the label and, possibly, have the contents tested.

Pursuit of that “edge” extends beyond Olympians

Even before the start of the modern Olympic games, athletes have used ergogenic aids—substances used to enhance performance, energy, or work capacity—to give themselves a “competitive edge.”^1,2 Athletes still use these substances today, and they have been joined by nonathletes—some of whom simply want to look good.

A 2004 Internet study of AAS users reported that the majority are recreational bodybuilders or nonathletes. Twenty-five percent of participants in this survey reported starting using steroids during their teenage years.³

An ongoing study of high school students and young adults indicates an AAS use prevalence rate of 1.1% to 2.3% in boys and 0.4% to 0.6% in girls. Approximately 40% of survey participants noted that obtaining steroids was relatively easy.⁴

The Centers for Disease Control and Prevention (CDC) reports that 4.4% to 5.7% of boys (grades 9 through 12) have used illegal steroids and that 1.9% to 3.8% of girls have.⁵

Few AAS users tell their physicians of their steroid use. Part of the reason, of course, is that illegal substance use is stigmatized and can lead to prosecution. Another reason, though, is that these patients think physicians don’t know much about these substances.³ Still other patients, like JC, don’t tell because they may not even be aware that some substances billed as “natural” conceal potential dangers.

For help in spotting patients who are using these agents, see “Red flags for performance-enhancing drug use” on page 20.

Performance-enhancing drugs go by many names

Refining your care of patients who are taking performance-enhancing drugs requires that you know the various names these drugs go by, the reason your patients may be taking them, and the adverse effects associated with them. This review, and the TABLE, will help.

Table
Performance-enhancing agents: What to watch for

Anabolic androgenic steroids: Often paired with energy drinks

Teenagers may refer to AAS as “pumpers,” “gym candy,” or “juice.” Trade names for AAS are Dianabol, Anadrol, Deca Durabolin, Parabolin, and Winstrol. AAS are often used with nutritional supplements like creatine, multivitamins, and energy drinks, in the belief that these regimens will make the user stronger, more muscular, and a better athlete.^6,7

AAS are synthetic analogues of testosterone and come in oral, injectable, and transdermal forms.^8,9 At supraphysiologic doses, testosterone has been found to increase lean body (fat-free) mass and muscle strength in humans.¹⁰ The anabolic effects are more pronounced when AAS are used at higher doses over longer periods of time, especially when combined with a strength training program.^9,10 AAS have also been found to stimulate the production of growth hormone and insulin-like growth factor and to counteract the catabolic effects of cortisol.¹¹

The use and possession of AAS without a doctor’s prescription is illegal in the United States. A majority of AAS users buy their medications through Internet suppliers, with some of the drugs being manufactured overseas or in illicit labs.³ Substandard quality control in manufacture poses an increased health risk to consumers.

Adverse effects include injection site pain, acne, baldness, gynecomastia, testicular atrophy, sexual dysfunction, and psychological disturbances (also known as “roid rage”).^8,9,11-13 Increases in liver enzymes with the oral forms of AAS have also been noted.⁸ In the prepubertal athlete, premature physeal closure may occur, resulting in permanent short stature.¹⁴ Women who take AAS may have virilization effects, menstrual irregularities, and early menopause.¹¹

The cardiovascular risks of AAS use are substantial. High-dose and long-term AAS use has been linked to cardiomyopathy and sudden death.^15-20 Some data suggest the development of accelerated atherosclerosis with AAS use, leading to hypertension, coronary artery disease (CAD), and acute myocardial infarction.^15,16,18-21 An unfavorable lipid panel has also been noted, with an increase in LDL and decreased HDL.^18-21

Tetrahydrogestrinone: A “designer” steroid

Tetrahydrogestrinone (THG) was initially developed to avoid detection by testing protocols current at the time.^22-24 This drug has garnered significant media attention in the past few years because of scandals involving professional and Olympic athletes. THG is chemically related to 2 other banned steroids, trenbolone and gestrinone.^22,24 It is used similarly to AAS to increase muscle bulk and enhance performance. It is more hepatotoxic than AAS, with highly potent androgenic and progestin properties in in vitro bioassay studies.^22,25

Marketing of this agent is banned in the United States. There are no long-term studies of its effectiveness or side effect profile.

Androstenedione: Initially an anti-aging drug

Androstenedione, aka Andromax and Androstat 100, is a precursor of testosterone. This substance is produced in the adrenal glands and gonads.² Initially marketed as a dietary supplement and anti-aging drug, it was banned by the FDA in 2004 because of its potent anabolic and androgenic effects.²⁶ Ergogenic use includes promoting muscle building and strength and fat reduction.² Studies on healthy young men found no improvement in skeletal muscle adaptation to resistance training with androstenedione supplementation for 8 to 12 weeks.^27,28 Studies of its effect on increasing blood testosterone levels are conflicting.^27,29 Several studies noted an increase in estradiol levels after oral androstenedione supplementation.^9,11,27-29

Endocrine pathways with this drug are similar to AAS, and the side effect profile is similar as well, although not as pronounced. Larger, long-term studies are needed to fill out this drug’s profile and document its effects on the athletes who use it.

Dehydroepiandrosterone: Marketed as a “wonder drug”

Dehydroepiandrosterone (DHEA), marketed under the names Prastera, Fidelin, and Fluasterone, is another precursor of testosterone. It is produced in the adrenal cortex and has weak androgenic properties.² DHEA is a dietary supplement marketed as a “wonder drug” and, like androstenedione, is advertised to promote muscle-building and fat-burning. It is also said to have anti-aging properties.^11,14 DHEA has been used by athletes in the belief that it will increase testosterone levels and muscle bulk.³⁰

In studies done in healthy men, however, even large doses of DHEA (1600 mg/d) did not result in an increase in testosterone levels. An increase in estradiol levels was noted in elderly men. Women who supplement with DHEA were found to have increased levels of testosterone and virilization effects, even at small doses (25-50 mg/d).³¹ Because of the risk of these side effects and the lack of long-term studies, DHEA supplementation is not recommended for use by adolescents or women.³⁰ There is no convincing evidence to support claims of the anabolic and anti-aging effects of DHEA.

Human growth hormone: Side effects include hypertension

Human growth hormone (HGH) is an endogenous pituitary hormone with anabolic functions that increases muscle mass without the androgenic side effects. It is used medically for patients with decreased endogenous levels of GH or dwarfism. As an ergogenic aid, it has been found to increase levels of insulin-like growth factors, and the combination leads to increased protein synthesis and muscle mass.³²

Side effects of HGH include insulin resistance, GH-induced myopathy, and acromegaly-like effects.¹¹ There have been reports of hypertension, cardiomegaly, ventricular hypertrophy, and abnormal lipids with excessive use.^19,33 Premature physeal closure may occur in the adolescent HGH user.⁸ It’s unclear whether HGH actually enhances sports performance, because the evidence is insufficient.³⁴

Ephedrine: Used by hockey players

Ephedrine is a stimulant derived from the herb ma huang. It goes by many names, among them Ma Huang, Bolt-ephedrine, Asia Black 25, Hot Body Ephedra, and Thin Quick. Its chemical structure is related to amphetamine. Among college athletes, ephedrine and amphetamine use is more common in power sports, those requiring increased concentration (eg, rifle shooting, fencing), ice hockey, and field sports.³⁵ Users feel less fatigue, experience bursts of energy, and lose weight.^8,36

Users may experience irritability, anxiety, insomnia, and tremors, especially if stimulants are used in conjunction with high doses of caffeine.^35,37 Ephedrine stimulates the release of norepinephrine, which produces increases in blood pressure, peripheral vascular resistance, and heart rate. These norepinephrine effects are the proposed mechanism for reported cases of myocardial infarction, cerebral artery vasoconstriction, and stroke associated with ephedrine use.¹³

Marketing of dietary supplements that contain ephedrine has been banned by the FDA because of the stimulant’s potential for increasing cardiovascular and stroke risks.³⁸

Caffeine: May give sprinters a leg up

Caffeine—which is found in everything from coffee to energy tablets and energy drinks—increases a person’s energy level. In endurance sports, it also increases time to exhaustion.³² Studies in endurance-trained cyclists have shown that caffeine intake reduced leg pain, increased maximal leg force, and lengthened time to fatigue.^39,40 A recent study in Australia also showed that caffeine may improve intermittent-sprint performance in competitive male athletes.⁴¹

Serious cardiovascular risks and even death have been documented when caffeine has been used with other stimulants, such as ephedrine or amphetamines. The combination of high doses of caffeine and ephedrine has a potential for life-threatening arrhythmia, hypertension, and stroke.⁴² Other psychomotor side effects include anxiety, irritability, tremor, and the potential for withdrawal symptoms.^42,43 Because of caffeine’s stimulant nature, the International Olympic Committee and the National Collegiate Athletic Association have set urinary thresholds for its use in competition.

Erythropoietin: Promotes endurance

Erythropoietin (EPO) is a hormone produced in the kidneys that stimulates production of red blood cells (erythropoiesis). Marketed under the brand names Epogen and Procrit, EPO has legitimate medical uses. As an ergogenic substance, EPO is used to promote endurance by increasing the oxygen-carrying capacity of the blood with the increased red blood cell mass. In endurance athletes, the benefits of recombinant erythropoietin (rEpo) may last several weeks.²³ There is also a practice called “blood doping,” which is a transfusion prior to competition, to produce the same effect.

Adverse effects of EPO use are attributed to increased blood viscosity and thrombotic potential. Pulmonary embolism, stroke, myocardial infarction, and sudden death can occur.¹⁹ Cases of death due to severe bradycardia, usually occurring during the night, have also been reported.²³ Development of anti-EPO antibodies may also occur, causing paradoxical anemia.²³ Athletes found to be using rEPO are banned from competition by sports-governing organizations.

Creatine: Popular among body builders

Creatine is a popular supplement used by athletes and recreational bodybuilders to provide energy to skeletal muscles in short-duration, maximal exercise.⁴⁴ It is an endogenous substance found mainly in skeletal muscle and is synthesized by the liver from the amino acids glycine, arginine, and methionine.^11,44 It is also found in meat.

Creatine monohydrate supplements have been found to increase creatine stores in muscles.⁴⁵ In the phosphorylated form, creatine serves as a substrate for adenosine triphosphate resynthesis during intense anaerobic exercise.^11,44-46 Numerous studies support its ergogenic effect on short-term, intermittent maximal activities such as bodybuilding, swimming, and jumping. Similar benefits have not been proven for endurance aerobic activities, such as long-distance cycling or running.^46,47

This supplement is sold in many forms under such names as Rejuvinix, Cell Tech Hardcore, Muscle Marketing, Femme Advantage, and NOZ. Although not recommended for those under age 18, creatine is actually used by approximately 5.6% of high school athletes, with the highest levels of use (44%) occurring in the 11th and 12th grades.⁴⁸ Reported side effects of creatine include muscle cramps, weight gain, and some minor gastrointestinal upset. Long-term studies on creatine supplementation are still needed.

Viagra (that’s right, Viagra)

Viagra (sildenafil) is the latest entry in the list of drugs competitive athletes may be using to try to improve sports performance. The World Anti-Doping Agency is financing a study investigating whether sildenafil can create an unfair competitive advantage by dilating blood vessels and increasing oxygen-carrying capacity.⁴⁹ Studies of the impact of sildenafil on exercise capacity of climbers at the Mt. Everest base camp and on exercise performance during acute hypoxia have been published.^50,51 Sildenafil was found to improve athletic capacity in both. To date, no action has been taken to ban the substance in athletic competition.

Are your patients using these agents? Ask them

Family physicians need to be alert to the red flags that may indicate steroid use and gently explore the full list of medications, over-the-counter products, and dietary supplements patients may be using. Take advantage of annual checkups and sports physicals to ask about use of performance-enhancing substances, educate patients on the risks involved, and emphasize good nutrition and sensible exercise routines as healthy ways to build a strong, attractive physique.

Education was certainly in order for your patient, JC, described at the beginning of this article. He thought the dietary supplement he used was natural and therefore harmless. Not so. It contained potentially dangerous substances, so you advised him to stop using it. Nutritional counseling and a vigorous exercise routine have allowed JC to maintain his fitness ideal. His blood pressure and liver enzymes returned to normal levels, and he passed his commercial driver’s license exam.

Correspondence
Marifel Mitzi F. Fernandez, MD, 600 Woodside Drive, Cornell, WI 54732; [email protected]

Janet M, a 69-year-old woman with a history of hypertension, comes for a visit because she thinks she has Alzheimer’s disease (AD). She recently had an episode of acute confusion while shopping at the mall; when she returned to her car, she couldn’t remember how to get home. The episode cleared within minutes and hasn’t recurred.

Jack S, an 84-year-old man, seeks medical care for pain in his right shoulder. He injured the rotator cuff several years ago, but it’s been fine since he completed physical therapy—until he tripped and fell while walking outside about a week ago. His daughter is concerned about his “forgetfulness” and increasing inability to remember certain words, but the patient thinks this is a natural consequence of age.

Fran B, a 72-year-old, presents with complaints of memory problems that began about 6 months ago. She’s worried about her son and has had increasing difficulty concentrating, sleeping, and keeping track of her things.

If these were your patients, whom would you screen for dementia? Would you decide whether to screen based on your “gut,” or a defined set of criteria? Would you have several screening tools on hand, and know enough about them to determine which one might be best suited for a particular patient?

If you make decisions about screening based on your gut or aren’t sure which tools are best for which patients, you’re far from alone. Cognitive impairment, particularly in the early stages, can be difficult and time-consuming to detect, and community physicians fail to diagnose mild-to-moderate dementia more than 50% of the time.^1-5

Family members and caregivers often overlook declines in cognitive function, as well. In a study of 741 caregivers of patients with AD, an average of 4 months went by between the time symptoms were first noticed and the patient was seen by a physician—and 22% of the caregivers waited more than a year.⁶

Cognitive decline can be slowed with early Dx

Early diagnosis of AD or any dementia is important for a number of reasons. In some cases, cognitive impairment may be related to medical conditions—head trauma, Parkinson’s disease, human immunodeficiency virus, thyroid disorder, among others—that can be modified or reversed with treatment.⁷ There is evidence, too, that medical, behavioral, and social interventions can delay the cognitive and functional decline associated with AD, thereby helping to prolong the time the patient can remain at home. Early diagnosis also facilitates legal and financial family planning, and makes it possible to take appropriate safety measures.^8-13

AD affects approximately 5 million US residents.¹⁴ With an aging population, that number is expected to surge in the decades ahead. To help you provide optimal care for your geriatric patients, this review will detail when to screen, which tools to use, and how best to care for the 3 elderly patients in the opener.

When and whether to screen

Despite the benefits of early detection, population-based screening based on age alone is not recommended. Guidelines recommend focused screening of patients in high-risk groups and on a case-by-case basis.¹⁵

US Preventive Services Task Force (USPSTF) guidelines recommend that physicians evaluate older patients for dementia whenever there is a suggestion of cognitive impairment, based on clinical observation or concern expressed by the individuals themselves or by family members, caretakers, or friends.¹⁵

However, cognitive screening generally provides better results in populations at higher risk of dementia.^16,17 With that in mind, the Assessing Care of Vulnerable Elders (ACOVE), a collaborative project to develop a set of quality indicators for care of the elderly, recently recommended cognitive and functional screening of all “vulnerable elderly.”^18,19

Who are the vulnerable elderly?

ACOVE defines the vulnerable elderly as individuals who are 65 years of age and older who live in the community and are at high risk of death or functional decline over the next 2 years. You can use a screening tool to identify members of this high-risk group. Or you can simply ask a few questions and classify any noninstitutionalized older person who reports being in poor health and/or acknowledges difficulty with activities of daily living—eg, money or medication management, dressing, grooming, or preparing simple meals—as a vulnerable elderly patient.

ACOVE recommends screening all vulnerable elderly patients who are new to a primary care practice or inpatient service, and following up with an annual evaluation to detect any changes in memory and function.^18,19 Based on the recommendations of ACOVE and the USPSTF, all 3 patients described earlier would be candidates for screening.

Choosing the best screening tool