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Mayo Clin Proc. 2009 June; 84(6): 546–550.
PMCID: PMC2688628

Clinical Pearls in Perioperative Medicine

At the 2001 annual conference of the American College of Physicians, a new teaching format to aid physician learning, Clinical Pearls, was introduced. Clinical Pearls is designed with the 3 qualities of physician-learners in mind. First, we physicians enjoy learning from cases. Second, we like concise, practical points that we can use in our practice. Finally, we take pleasure in problem solving.

In the Clinical Pearls format, speakers present a number of short cases in their specialty to a general internal medicine audience. Each case is followed by a multiple-choice question answered live by attendees using an audience response system. The answer distribution is shown to attendees. The correct answer is then displayed and the speaker discusses teaching points, clarifying why one answer is most appropriate. Each case presentation ends with a Clinical Pearl, defined as a practical teaching point that is supported by the literature but generally not well known to most internists.

Clinical Pearls is currently one of the most popular sessions at the American College of Physicians meeting. As a service to its readers, Mayo Clinic Proceedings has invited a selected number of these Clinical Pearl presentations to be published in our Concise Review for Clinicians section. “Clinical Pearls in Perioperative Medicine” is one of them.


A 75-year-old woman presents with a hip fracture. Her medical history is remarkable for coronary artery disease. Two months previously she had a non-ST-segment elevation myocardial infarction and had a drug-eluting stent (DES) placed. She has a history of type 2 diabetes, hypertension, and hyperlipidemia.

Current Medications

Aspirin, 81 mg/d

Clopidogrel, 75 mg/d

Atorvastatin, 20 mg/d

Metformin, 1000 mg twice daily

Enalapril, 40 mg/d

Hydrochlorothiazide, 25 mg/d


Which one of the following would be the most appropriate recommendation to the surgeon about this patient's antiplatelet therapy before hip fracture repair?

  1. Do not interrupt aspirin or clopidogrel therapy before surgery
  2. Stop both clopidogrel and aspirin therapy for 5 days before surgery
  3. Stop both clopidogrel and aspirin therapy for 5 days before surgery and bridge with low-molecular-weight heparin (LMWH)
  4. Stop clopidogrel therapy for 5 days before surgery but do not interrupt aspirin therapy
  5. Delay surgery until the 1-year anniversary of stent placement


Approximately 5% of patients who undergo coronary stenting will require surgery within the year after stent placement. Because of the need for uninterrupted dual antiplatelet therapy after these stents are deployed, elective procedures with a bleeding risk should be deferred. It is recommended that dual antiplatelet therapy be continued without interruption for 4 to 6 weeks after the placement of a bare metal stent (BMS) and for 12 months after a DES to minimize the risk of stent thrombosis.1 However, unplanned urgent surgeries may still be necessary during this critical re-endothelialization period. The generally accepted policy is to withdraw antiplatelet agents 7 to 10 days before a surgical or endoscopic procedure because of the fear of excessive bleeding. Premature discontinuation of antiplatelet therapy markedly increases the risk of stent thrombosis, a catastrophic event that frequently leads to myocardial infarction and/or death. Premature withdrawal of antiplatelet therapy is associated with a 5- to 10-fold increase in the perioperative cardiac death rate, with an average incidence of death of about 30%.1,2 The case fatality rate for patients who develop stent thrombosis is 45%.2 This obviously puts the physicians, surgeons, and patients in a difficult situation. In this case, it is best to consider the risks and benefits of continuation vs discontinuation of the antiplatelet therapy.

What is the risk of surgical bleeding with antiplatelet agents? Aspirin increases the rate of bleeding complications by 1.5 fold; however, for most surgical procedures, it does not increase the severity of or mortality due to bleeding complications.2 The exception would be for intracranial neurosurgical and transurethral prostate procedures. Aspirin in addition to clopidogrel is associated with a 30% to 50% increase in relative risk (absolute risk, 0.4%-1%) of major bleeding perioperatively compared with aspirin alone. Dual antiplatelet therapy does not result in increased operative mortality (except for intracranial neurosurgery) but is associated with a slight increase in the need for reoperation and a 30% increase in the need for transfusion.2 Therefore, most operations—with the exception of intracranial neurosurgery—can be performed while the patient is receiving dual antiplatelet therapy without significantly increasing morbidity and mortality. Other operations in which bleeding into a closed space could result in serious complications (ie, spinal cord surgery or posterior chamber eye surgery) should also be considered exceptions.

Another option that is often considered is to stop only the clopidogrel but continue the aspirin therapy. This option may be the most appropriate for patients who have stents and are beyond the critical period of stent endothelialization (6 weeks for BMS, 12 months for DES). However, stopping clopidogrel during the critical period places the patient at increased risk of stent thrombosis, even if aspirin is continued. Aspirin alone is not sufficient to prevent stent thrombosis in patients who are not beyond the critical period of stent endothelialization.

Although some physicians may advocate the use of bridging therapy with glycoprotein 2b/3a inhibiting agents or heparin for the period when the patient is not receiving antiplatelet agents, no data support this practice, nor is there evidence that it actually decreases the risk of stent thrombosis or death.

Given the risks and benefits for this patient, the best option would be to proceed with the surgical procedure without interruption of the antiplatelet agents. The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines also address this issue in the section on the perioperative management of antithrombotic therapy.3 These guidelines recommend that patients with a DES who require surgery within 12 months of stent placement continue aspirin and clopidogrel therapy in the perioperative period. Additionally, patients with a BMS who require surgery within 6 weeks of stent placement should also continue aspirin and clopidogrel therapy in the perioperative period.

Clinical Pearl

Most operations (except neurosurgery) can be performed in patients who have recent coronary artery stents and who are receiving dual antiplatelet therapy without increasing mortality.


A 62-year-old man presents for an evaluation before an open cholecystectomy for acute cholecystitis under general anesthesia. He has a history of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea and is actively smoking. He has no history of coronary artery disease. His functional capacity is about 4 to 5 metabolic equivalents. His inhalers include ipratropium, salmeterol, and albuterol, as needed. He uses continuous positive airway pressure at night. Pulmonary function testing 1 year previously revealed a forced expiratory volume in 1 second of 60% of predicted.

Findings on Examination

Oxygen saturation, 91% while breathing room air

Lungs: prolonged expiration phase, otherwise clear

Unremarkable findings on remainder of examination


Which one of the following strategies will most effectively reduce this patient's risk of postoperative pulmonary complications?

  1. Smoking cessation
  2. Postoperative incentive spirometry
  3. Switching to a laparoscopic surgical technique
  4. Postoperative nasogastric decompression
  5. Preoperative oral corticosteroid therapy


This patient has multiple risk factors that increase his risk of postoperative pulmonary complications, including COPD, current smoking, age, upper abdominal surgical procedure, general anesthesia, and obstructive sleep apnea. To help decrease his risk of pulmonary complications in the postoperative period, several strategies can be considered, including lung-specific strategies, operative technique, anesthesia technique, and postoperative strategies.

In 2006, Lawrence et al4 published a systematic review of strategies to reduce pulmonary complications after noncardiothoracic surgery for the American College of Physicians. In this review, the authors reported the strength of the evidence for specific interventions to reduce the risk of postoperative pulmonary complications. The best evidence exists for lung-expansion therapy (eg, incentive spirometry, deep breathing exercises, and continuous positive airway pressure) for reducing pulmonary risk after abdominal surgery. However, the comparative effectiveness of different lung-expansion modalities has not been well studied. Strategies of probable benefit are selective nasogastric tube decompression after abdominal surgery and the use of short-acting neuromuscular blocking agents during anesthesia. Strategies of possible benefit include a laparoscopic rather than an open surgical approach for abdominal surgeries; however, the evidence is insufficient to determine whether laparoscopic procedures prevent clinically important pulmonary complications. Strategies of unclear benefit include preoperative smoking cessation. The authors reported no benefit with the routine use of parenteral or enteral hyperalimentation or with the use of invasive perioperative monitoring with pulmonary artery catheterization.

Preoperative use of oral corticosteroids is probably effective in decreasing postoperative pulmonary complications in patients with COPD who have uncontrolled symptoms on examination; however, in our case, the patient was asymptomatic and the lung examination did not suggest an exacerbation.

Clinical Pearl

Lung-expansion modalities (eg, postoperative incentive spirometry) are most effective for reducing the risk of postoperative pulmonary complications in high-risk patients.


A 62-year-old woman with chronic renal insufficiency is evaluated the day after total hip replacement surgery for recommendations regarding prophylaxis for deep venous thrombosis (DVT). She has recently begun walking again. While she was in surgery, graduated compression stockings were used for DVT prophylaxis. The patient is overweight (body mass index [calculated as the weight in kilograms divided by the height in meters squared], 35 kg/m2) and has a creatinine level of 3.5 mg/dL (to convert to μmol/L, multiply by 88.4).


Given that the patient has recently become ambulatory, which one of the following is the best approach to DVT prophylaxis?

  1. Unfractionated heparin, 5000 U subcutaneously every 8 hours until hospital discharge
  2. Fondaparinux, 2.5 mg/d subcutaneously for 10 days
  3. Enoxaparin, 30 mg/d subcutaneously for 10 days
  4. Warfarin with a target international normalized ratio (INR) of 2.0 to 3.0 for 4 weeks
  5. Dalteparin, 5000 U/d subcutaneously for 4 weeks


Patients who have hip or knee replacement or hip fracture surgery are at very high risk of developing venous thromboembolism in the perioperative period. Without prophylaxis, 40% to 60% of these patients will develop DVT.

The American College of Chest Physicians guidelines on prevention of venous thromboembolism,5 updated in 2008, recommend the use of LMWH (in a high-risk dose), fondaparinux, or adjusted-dose warfarin (INR, 2.0-3.0) for DVT prophylaxis in patients undergoing hip replacement surgery. The guidelines specifically advise against the use of aspirin, low-dose unfractionated heparin, compression stockings, or venous foot pumps as the sole method of DVT prophylaxis in this high-risk group of patients. The duration of thromboprophylaxis should be extended beyond 10 days and up to 35 days after surgery.

The use of LMWHs and fondaparinux can be difficult in patients with renal insufficiency because renal clearance is the primary mode of elimination. Increased drug accumulation can lead to a substantial bleeding risk. Considerable variation is seen in the relationship between renal impairment and drug accumulation for the different LMWHs, perhaps because of the chain-length distribution of the different LMWH preparations. Many experts recommend avoiding LMWHs altogether in patients with substantial renal insufficiency. However, if LMWHs are used in this patient population, monitoring anti-Xa levels at 4 to 6 hours after administration of the LMWH is recommended if the creatinine clearance rate is less than 30 mL/min. Dose reductions are recommended when using fondaparinux in patients with mild renal insufficiency, but this drug is contraindicated when the creatinine clearance rate is less than 30 mL/min. For our patient, who has a substantial degree of renal insufficiency, warfarin would be the best choice.

Clinical Pearls

  1. Thromboprophylaxis should be extended beyond 10 days and up to 35 days after total hip or knee replacement surgery or hip fracture repair.
  2. Avoid LMWHs and fondaparinux in patients with a creatinine clearance rate of less than 30 mL/ min.


A 65-year-old man with known coronary artery disease is referred for preoperative cardiac risk assessment. After review of the patient's history, you have decided that he needs to have a cardiac stress test preoperatively to help with risk stratification.


Lisinopril, 20 mg/d

Aspirin, 81 mg/d

Pravastatin, 40 mg/d

Metoprolol, 50 mg twice daily

The patient's medical history is remarkable for a non-ST-segment elevation myocardial infarction 3 years earlier. He was found to have an 80% left anterior descending (LAD) lesion and was treated with angioplasty and BMS. His history revealed his functional capacity to be about 3 metabolic equivalents. He has a blood pressure of 140/80 mm Hg and a regular pulse of 60 beats/min.

Findings on electrocardiography (ECG) are unremarkable except for a left bundle branch block (LBBB) that has not changed since being detected by ECG 2 years earlier.


Which one of the following stress tests would be most useful in ruling out ischemia in this patient?

  1. Exercise ECG with no imaging
  2. Exercise ECG with thallium imaging
  3. Exercise ECG with sestamibi imaging
  4. Dobutamine stress echocardiography
  5. Pharmacologic vasodilator stress test (dipyridamole or adenosine) with sestamibi imaging


In patients with LBBB, exercise-induced tachycardia may result in reversible septal defects, even in the absence of LAD disease (false-positive test).6 The reversible defects are seen in 40% to 50% of patients with LBBB during exercise and are more frequent with faster peak heart rates. Tachycardia induced by dobutamine stress has also been associated with this false-positive reversible anteroseptal defect, although less so. The false-positive septal defect associated with LBBB is thought to occur because of delayed and asynchronous activation of the left side of the septum. Because septal contraction occurs at the end of systole with LBBB, the compressive effects of the septum, as a result in part of delayed ventricular relaxation, could restrict blood flow in early diastole, at which time most myocardial perfusion occurs. Septal hypoperfusion would become more apparent with the exercise-induced tachycardia because diastole is shortened.

Although vasodilator stress can be associated with a slight increase in heart rate, it is not increased to the extent that it is with exercise and is not associated with false-positive findings in patients with LBBB.

In general, dobutamine stress echocardiography is still fairly accurate in patients with LBBB, but this accuracy decreases considerably in patients with LAD disease. The vasodilator stress test with myocardial perfusion imaging is the best choice for this patient because the area of interest is in the LAD distribution.

Clinical Pearl

The vasodilator stress test with myocardial perfusion studies is recommended as a cardiac stress test for patients with LBBB (especially in the presence of LAD disease).


A 65-year-old man who underwent a total knee arthroplasty 2 days earlier reports feeling well except for mild postoperative knee pain. You are called to evaluate him for postoperative fever.

Findings on Examination

Temperature, 39°C

Pulse, 95 beats/min

Blood pressure, 138/90 mm Hg

Respiratory rate, 16 breaths/min

Oxygen saturation, 92% while breathing room air

Lungs: normal except for a few crackles with first inspiration

Foley catheter in place; urine looks clear

Findings on remainder of examination are unremarkable

Medications and Findings

Dalteparin, 5000 U/d

Lopressor, 50 mg twice daily

Cefazolin, given for 24 hours at time of surgery, now stopped

White blood cell count, 10.5 × 109/L


Which one of the following is the next best step in the management of this patient?

  1. Observation only
  2. Blood and urine cultures
  3. Blood and urine cultures, chest radiography
  4. Blood and urine cultures, chest radiography, and stool sample for Clostridium difficile toxin
  5. Blood and urine cultures, chest radiography, and empiric vancomycin therapy


Less than 10% of patients who develop fever within 48 hours of surgery do so as a result of infection. Our patient has benign postoperative fever that started within the first 48 hours after surgery and is likely associated with pyrogenic cytokine release due to tissue trauma from surgery. Benign postoperative fever is very common and is the cause of approximately 90% of postoperative fever within the first 48 hours.7 The magnitude of the febrile response does not predict if the patient is more likely to have an infection.

In this patient, who is completely asymptomatic, who does not have symptoms of toxicity, and who has no clear focus of infection, observation is the best approach to management because benign postoperative fever will usually resolve spontaneously within 72 hours.8 Reserve fever work-up for patients with clinical signs and symptoms of infection. This patient had physical examination findings consistent with atelectasis. Atelectasis does not cause postoperative fever.

Clinical Pearl

Benign postoperative fever is the most common cause of elevated temperature in the first 48 hours after surgery and resolves spontaneously without therapy.


You are asked to evaluate a 76-year-old woman who is agitated and confused. She had a right L5 foraminotomy and L5-S1 fusion 3 days earlier. Her medical history is remarkable for mixed connective-tissue disease but is otherwise unremarkable. Her usual home medications are prednisone, celecoxib, nortriptyline, warfarin, and tramadol.

On the day of surgery, she had evening confusion and slept little. On postoperative day 1, she did not sleep and had increasing confusion. On postoperative day 2, she did not sleep; was not oriented to time, place, or person; and was agitated and calling out. She has no focal neurologic findings. No underlying cause for delirium was identified by initial work-up.


Which one of the following is the best treatment option for this patient?

  1. Restraints
  2. Restraints, 24-hour supervision
  3. Restraints, scheduled haloperidol
  4. Protocol to ensure adequate sleep, enlistment of family support, haloperidol for agitation
  5. Protocol to ensure adequate sleep, enlistment of family support, diazepam for sleep


Delirium is quite common postoperatively in the elderly population. Identification and treatment of the underlying cause(s) are essential.9 A variety of supportive measures have been shown to be effective in managing delirium. For example, the patient's environment can be controlled, ensuring that lighting is adequate but not excessive, that objects are familiar, that clocks and calendars are present, and that the patient has access to all normal sensory input (with the aid of glasses, dentures, hearing aids). The presence of family members and their help with frequent reorientation can be comforting to the patient. Of course, it is important to ensure adequate nutrition, hydration, oxygenation, and sleep.

When the patient is agitated or aggressive and a concern for patient or staff safety exists, other measures need to be considered. Restraints should generally be avoided if at all possible because they often lead to increased agitation. Pharmacologic measures can be considered for symptom control and safety. Antipsychotic agents have been used for this purpose; however, no drugs have been approved by the Food and Drug Administration (FDA) for the treatment of delirium. Benzodiazepines should be reserved for treatment of patients with delirium due to alcohol or benzodiazepine withdrawal. Both conventional and atypical antipsychotic agents have been used off label for treatment of delirium; however, no convincing evidence has shown that newer antipsychotic agents are any better than haloperidol. Haloperidol is the preferred agent because of its minimal anticholinergic adverse effects and lack of active metabolites. Oral doses can be started quite low (0.25-0.50 mg every 4 hours, as needed) with good response.

In June 2008, the FDA issued a black box warning for conventional (typical) antipsychotic agents indicating their association with increased risk of mortality in elderly patients undergoing short- or long-term treatment with these agents for dementia-related psychosis.10 A similar FDA warning for atypical antipsychotic agents preceded this in 2005. Major contributors to the increased mortality were cardiovascular causes and sudden death. If these agents are used for this purpose, physicians are advised that the risk of increased mortality should be clearly discussed with patients and families.

Clinical Pearl

No drugs have been approved by the FDA for the treatment of delirium. Antipsychotic agents can be used for symptoms of agitation in patients with delirium, but their use may be associated with increased short- and long-term mortality.11


See end of article for correct answers to questions.

Correct answers: Case 1: a, Case 2: b, Case 3: d, Case 4: e, Case 5: a, Case 6: d


1. Grines CL, Bonow RO, Casey DE, Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. J Am Coll Cardiol. 2007;49(6):734-739 [PubMed]
2. Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth. 2007. September;99(3):316-328 Epub 2007 Jul 23 [PubMed]
3. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133(6)(suppl):299S-339S [PubMed]
4. Lawrence VA, Cornell JE, Smetana GW. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med. 2006;144(8):596-608 [PubMed]
5. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133(6)(suppl):381S-453S [PubMed]
6. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery [published correction appears in J Am Coll Cardiol. 2007;50(17):e242] J Am Coll Cardiol. 2007;50(17):e159-e241 [PubMed]
7. Pile JC. Evaluating postoperative fever: a focused approach. Cleve Clin J Med. 2006;73(supp 1):S62-S66 [PubMed]
8. Shaw JA, Chung R. Febrile response after knee and hip arthroplasty. Clin Orthop Relat Res. 1999. October;(367):181-189 [PubMed]
9. Bagri AS, Rico A, Ruiz JG. Evaluation and management of the elderly patient at risk for postoperative delirium. Clin Geriatr Med. 2008;24(4):667-686, viii [PubMed]
10. Information for healthcare professionals: antipsychotics. US Food and Drug Administration Website. Accessed April 23, 2009.
11. Schneeweiss S, Setoguchi S, Brookhart A, Dormuth C, Wang PS. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients [published correction appears in CMAJ. 2007; 176(11):1613] CMAJ 2007;176(5):627-632 [PMC free article] [PubMed]

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