As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹

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The general pediatrician's role in managing an adolescent with an autism spectrum disorder depends largely on his or her comfort with doing counseling, testing, and medication management.

Most adolescents with an autism spectrum disorder already have a pretty thick chart from a history of pediatrician and pediatric subspecialist consultations, but the etiology question may remain. If a child's intelligence is within the normal range, a lot of elaborate medical testing generally is not necessary. If the child has cognitive dysfunction, such as an IQ below 70, there is a greater probability of finding an underlying cause for the disorder.

Consider separate counseling and procedural visits. Like many pediatric patients, one with an autism spectrum disorder can be anxious about vaccinations, needles, or any other unpleasant procedure. So if they know a particular visit is limited to a discussion of concerns, they are more likely to relax and be more communicative.

Counseling will depend on the cognitive and language abilities of the patient. Discussions will have to be tailored to the level of understanding of the teen with autism spectrum disorder.

Counseling can include addressing sexuality issues. Discuss physical and emotional changes associated with adolescence and the effects they can have on the patient and the family. Teenagers in general are often confused about these changes, and those with autism spectrum disorder are no exception.

Discussions of the sort of sexual interest the patient has or does not have will depend on the patient's expressive capacity. Ask open-ended questions about any situations that may have arisen or about any concerns the patient may have about the future.

Also, educate the teen about the prevention of unwanted pregnancy and sexually transmitted infections.

Medication management is important in this population. Many adolescents on the autism spectrum already take psychopharmacologic agents. There is a wide range of comfort levels among pediatricians regarding prescription of psychopharmacologic agents and management of behavioral challenges. Refer the patient to a specialist if you are not at ease in these situations.

Similarly, some pediatricians will be more comfortable than others in ordering and evaluating genetic testing.

Technology has advanced from general karyotype testing a decade ago to more accurate molecular fragile X assays and chromosome microarray analyses that are available today.

If you feel up to date based on your training and experience, go ahead and order initial testing or updated testing as indicated.

General pediatricians are well equipped to manage any underlying medical issues. For example, if a patient has spells that might suggest seizures, an EEG might be in order, especially in this higher-risk population.

Start a transition plan once the adolescent is in high school. Pediatricians are integral in creating this plan, along with family physicians, internists, and/or other adult care providers.

Also work with school personnel to ensure an optimal outcome. Specific goals can include preparing the patient for postsecondary education or having the patient get necessary vocational skills as he or she becomes more independent and joins the workforce.

Work with parents to clarify goals for future living arrangements. Also suggest that parents establish a special needs trust to protect assets designated for the adolescent while still maintaining eligibility for government benefit programs.

[email protected]

The general pediatrician's role in managing an adolescent with an autism spectrum disorder depends largely on his or her comfort with doing counseling, testing, and medication management.

Most adolescents with an autism spectrum disorder already have a pretty thick chart from a history of pediatrician and pediatric subspecialist consultations, but the etiology question may remain. If a child's intelligence is within the normal range, a lot of elaborate medical testing generally is not necessary. If the child has cognitive dysfunction, such as an IQ below 70, there is a greater probability of finding an underlying cause for the disorder.

Consider separate counseling and procedural visits. Like many pediatric patients, one with an autism spectrum disorder can be anxious about vaccinations, needles, or any other unpleasant procedure. So if they know a particular visit is limited to a discussion of concerns, they are more likely to relax and be more communicative.

Counseling will depend on the cognitive and language abilities of the patient. Discussions will have to be tailored to the level of understanding of the teen with autism spectrum disorder.

Counseling can include addressing sexuality issues. Discuss physical and emotional changes associated with adolescence and the effects they can have on the patient and the family. Teenagers in general are often confused about these changes, and those with autism spectrum disorder are no exception.

Discussions of the sort of sexual interest the patient has or does not have will depend on the patient's expressive capacity. Ask open-ended questions about any situations that may have arisen or about any concerns the patient may have about the future.

Also, educate the teen about the prevention of unwanted pregnancy and sexually transmitted infections.

Medication management is important in this population. Many adolescents on the autism spectrum already take psychopharmacologic agents. There is a wide range of comfort levels among pediatricians regarding prescription of psychopharmacologic agents and management of behavioral challenges. Refer the patient to a specialist if you are not at ease in these situations.

Similarly, some pediatricians will be more comfortable than others in ordering and evaluating genetic testing.

Technology has advanced from general karyotype testing a decade ago to more accurate molecular fragile X assays and chromosome microarray analyses that are available today.

If you feel up to date based on your training and experience, go ahead and order initial testing or updated testing as indicated.

General pediatricians are well equipped to manage any underlying medical issues. For example, if a patient has spells that might suggest seizures, an EEG might be in order, especially in this higher-risk population.

Start a transition plan once the adolescent is in high school. Pediatricians are integral in creating this plan, along with family physicians, internists, and/or other adult care providers.

Also work with school personnel to ensure an optimal outcome. Specific goals can include preparing the patient for postsecondary education or having the patient get necessary vocational skills as he or she becomes more independent and joins the workforce.

Work with parents to clarify goals for future living arrangements. Also suggest that parents establish a special needs trust to protect assets designated for the adolescent while still maintaining eligibility for government benefit programs.

[email protected]

The general pediatrician's role in managing an adolescent with an autism spectrum disorder depends largely on his or her comfort with doing counseling, testing, and medication management.

Most adolescents with an autism spectrum disorder already have a pretty thick chart from a history of pediatrician and pediatric subspecialist consultations, but the etiology question may remain. If a child's intelligence is within the normal range, a lot of elaborate medical testing generally is not necessary. If the child has cognitive dysfunction, such as an IQ below 70, there is a greater probability of finding an underlying cause for the disorder.

Consider separate counseling and procedural visits. Like many pediatric patients, one with an autism spectrum disorder can be anxious about vaccinations, needles, or any other unpleasant procedure. So if they know a particular visit is limited to a discussion of concerns, they are more likely to relax and be more communicative.

Counseling will depend on the cognitive and language abilities of the patient. Discussions will have to be tailored to the level of understanding of the teen with autism spectrum disorder.

Counseling can include addressing sexuality issues. Discuss physical and emotional changes associated with adolescence and the effects they can have on the patient and the family. Teenagers in general are often confused about these changes, and those with autism spectrum disorder are no exception.

Discussions of the sort of sexual interest the patient has or does not have will depend on the patient's expressive capacity. Ask open-ended questions about any situations that may have arisen or about any concerns the patient may have about the future.

Also, educate the teen about the prevention of unwanted pregnancy and sexually transmitted infections.

Medication management is important in this population. Many adolescents on the autism spectrum already take psychopharmacologic agents. There is a wide range of comfort levels among pediatricians regarding prescription of psychopharmacologic agents and management of behavioral challenges. Refer the patient to a specialist if you are not at ease in these situations.

Similarly, some pediatricians will be more comfortable than others in ordering and evaluating genetic testing.

Technology has advanced from general karyotype testing a decade ago to more accurate molecular fragile X assays and chromosome microarray analyses that are available today.

If you feel up to date based on your training and experience, go ahead and order initial testing or updated testing as indicated.

General pediatricians are well equipped to manage any underlying medical issues. For example, if a patient has spells that might suggest seizures, an EEG might be in order, especially in this higher-risk population.

Start a transition plan once the adolescent is in high school. Pediatricians are integral in creating this plan, along with family physicians, internists, and/or other adult care providers.

Also work with school personnel to ensure an optimal outcome. Specific goals can include preparing the patient for postsecondary education or having the patient get necessary vocational skills as he or she becomes more independent and joins the workforce.

Work with parents to clarify goals for future living arrangements. Also suggest that parents establish a special needs trust to protect assets designated for the adolescent while still maintaining eligibility for government benefit programs.

A new study on the efficacy of surgical masks compared with respirator masks in combating the spread of influenza shouldn’t lead directly to increased prophylactic mask usage, one hospitalist group leader says. In fact, with hospitals and patients fully aware of another potential H1N1 flu pandemic this winter, HM groups should focus more on traditional hygiene issues and staff management to stem the impact of flu season, says William Ford, MD, FHM, medical director at Cogent Healthcare and director of the hospitalist program at Temple University in Philadelphia.

The randomized controlled trial published online (JAMA. October 2009. doi:10.1001/jama.2009.1466) ) tracked 446 nurses in EDs, medical units, and pediatric units in eight tertiary-care hospitals in Ontario. Researchers found that influenza infection occurred in 23.6% of nurses in the surgical-mask group and in 22.9% of nurses in the N95 respirator group (absolute risk difference –0.73%; 95% CI, –8.8% to 7.3%; P=0.86).

Dr. Ford says masks "can't hurt" as helpful barriers against the spread of influenza among hospital workers, but HM directors would be better served planning for staffing issues and emphasizing prevention. That includes harping on "hand-washing, hand-washing, and hand-washing," as well as being prepared to implement emergency schedules to rotate physicians into floor shifts should rank-and-file hospitalists call out sick.

"As hospitalist directors, I'd be very cognizant of my backup contingency plan," Dr. Ford says. "We have to take certain steps this year in a worst-case scenario."

A new study on the efficacy of surgical masks compared with respirator masks in combating the spread of influenza shouldn’t lead directly to increased prophylactic mask usage, one hospitalist group leader says. In fact, with hospitals and patients fully aware of another potential H1N1 flu pandemic this winter, HM groups should focus more on traditional hygiene issues and staff management to stem the impact of flu season, says William Ford, MD, FHM, medical director at Cogent Healthcare and director of the hospitalist program at Temple University in Philadelphia.

The randomized controlled trial published online (JAMA. October 2009. doi:10.1001/jama.2009.1466) ) tracked 446 nurses in EDs, medical units, and pediatric units in eight tertiary-care hospitals in Ontario. Researchers found that influenza infection occurred in 23.6% of nurses in the surgical-mask group and in 22.9% of nurses in the N95 respirator group (absolute risk difference –0.73%; 95% CI, –8.8% to 7.3%; P=0.86).

Dr. Ford says masks "can't hurt" as helpful barriers against the spread of influenza among hospital workers, but HM directors would be better served planning for staffing issues and emphasizing prevention. That includes harping on "hand-washing, hand-washing, and hand-washing," as well as being prepared to implement emergency schedules to rotate physicians into floor shifts should rank-and-file hospitalists call out sick.

"As hospitalist directors, I'd be very cognizant of my backup contingency plan," Dr. Ford says. "We have to take certain steps this year in a worst-case scenario."

A new study on the efficacy of surgical masks compared with respirator masks in combating the spread of influenza shouldn’t lead directly to increased prophylactic mask usage, one hospitalist group leader says. In fact, with hospitals and patients fully aware of another potential H1N1 flu pandemic this winter, HM groups should focus more on traditional hygiene issues and staff management to stem the impact of flu season, says William Ford, MD, FHM, medical director at Cogent Healthcare and director of the hospitalist program at Temple University in Philadelphia.

The randomized controlled trial published online (JAMA. October 2009. doi:10.1001/jama.2009.1466) ) tracked 446 nurses in EDs, medical units, and pediatric units in eight tertiary-care hospitals in Ontario. Researchers found that influenza infection occurred in 23.6% of nurses in the surgical-mask group and in 22.9% of nurses in the N95 respirator group (absolute risk difference –0.73%; 95% CI, –8.8% to 7.3%; P=0.86).

Dr. Ford says masks "can't hurt" as helpful barriers against the spread of influenza among hospital workers, but HM directors would be better served planning for staffing issues and emphasizing prevention. That includes harping on "hand-washing, hand-washing, and hand-washing," as well as being prepared to implement emergency schedules to rotate physicians into floor shifts should rank-and-file hospitalists call out sick.

"As hospitalist directors, I'd be very cognizant of my backup contingency plan," Dr. Ford says. "We have to take certain steps this year in a worst-case scenario."