INFO - Perioperative Management of the Rheumatic Disease Patient

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Bulletin of the Rheumatic Diseases

Volume 51, Number 6

2002

Perioperative Management of the Rheumatic Disease Patient

Joe T. Kelley III, MD

Doyt L. Conn, MD

Emory University School of Medicine

Atlanta, GA

Medications

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with rheumatic

diseases commonly use aspirin and nonaspirin NSAIDs. Nonselective NSAIDs

inhibit platelet cyclooxygenase-1 (COX-1) thus blocking the formation of

thromboxane A2. The result is impairment of thromboxane-dependent platelet

aggregation and prolongation of the bleeding time. Aspirin irreversibly

blocks COX; therefore, its actions persist for the circulating lifetime of

the platelet, which is about 10 days. Nonaspirin NSAIDs inhibit COX

reversibly so the duration of their action depends on the specific drug

dose, serum level, and half-life (1). The selective COX-2 inhibitors -

celecoxib, rofecoxib, and valdecoxib - do not inhibit COX-1; therefore,

platelet aggregation is not inhibited.

Because nonselective NSAIDs can prolong the bleeding time, physicians are

often asked about the potential for clinically significant bleeding in the

perioperative period. Perioperative bleeding time however has not been shown

to correlate strongly with surgical bleeding (2,3). Although preoperative

bleeding time does not seem to predict surgical bleeding, several studies

have suggested that the use of NSAIDs in the preoperative period does lead

to significantly increased perioperative blood loss (4,5).

Given the available data, we suggest discontinuing aspirin at least 10 days

prior to surgery since the life span of platelets is 10 days. Nonaspirin,

nonselective NSAIDs should be discontinued in time for complete elimination

of the drug to occur which is about 5 half-lives. Ibuprofen has a half-life

of about 2.5 hours so it should be stopped one day prior to surgery. The

half-life of naproxen is about 15 hours so discontinuation should occur 4

days prior to surgery.

For pain relief in the preoperative period, acetaminophen or a narcotic such

as codeine could be used.

Glucocorticoids. Glucocorticoids are produced in the adrenal cortex under

the feedback control of both the hypothalamus and pituitary gland

(hypothalamic-pituitary-adrenal [HPA] axis). The rate of cortisol secretion

is equivalent to 20 to 30 mg/day of hydrocortisone or 5 to 7 mg/day of

prednisone (6). This basal rate increases under conditions of severe stress,

and the increase is essential for the maintenance of homeostasis.

Patients on chronic glucocorticoids are frequently given " stress dose "

steroids despite little evidence to support this practice. Three recent

reviews have addressed the topic of glucocorticoid supplementation, and

these expert recommendations call for lower doses and shorter duration of

therapy than textbooks traditionally suggest (6,7,8). One supplemental

glucocorticoid dose does not accommodate all patients or procedures.

Excessive doses may lead to hyperglycemia, immunosuppression, accelerated

protein catabolism leading to altered wound healing, hypertension, volume

overload, and acute psychosis (6,7,8).

All patients on chronic glucocorticoids who undergo any type of procedure or

have a medical illness require their normal daily glucocorticoid therapy

(Table 2). It is especially important to continue glucocorticoid therapy in

patients with rheumatic diseases, as discontinuing even low doses of

glucocorticoids may cause a significant flare of disease activity. Patients

who receive 5 mg/day or less of prednisone do not require additional

supplementation, regardless of the procedure or illness (6,7,8,9). Patients

who undergo a superficial procedure of less than one hour under local

anesthesia, such as routine dental work, skin biopsy, or minor orthopedic

surgery, require their normal daily dose without additional supplementation

(6,7,8).

Minor medical illnesses and surgical procedures, such as inguinal hernia

repair and colonoscopy, require hydrocortisone (25 mg) or methylprednisolone

(5 mg intravenous) on the day of procedure only (6).

Moderately stressful illnesses or procedures, such as a significant febrile

illness, pneumonia, severe gastroenteritis, open cholecystectomy, and

hemicolectomy, require hydrocortisone (50 to 75 mg) or methylprednisolone

(10 to15 mg intravenous) on the day of procedure with a rapid taper over 1

to 2 days to the patient's usual dose (6).

Severe medical or surgical stress, such as experience with pancreatitis,

major cardiothoracic surgery, Whipple procedure, and liver resection,

require hydrocortisone (100 to 150 mg) or methylprednisolone (20 to 30 mg

intravenous) on the day of the procedure with a taper over 1 to 2 days to

the patient's usual dose (6).

Critically ill patients, such as those with shock or sepsis-induced

hypotension, require hydrocortisone 50 to 100 mg intravenous every 6 to 8

hours or 0.18 mg/kg/hour as continuous infusion plus 50 mg/day of

fludrocortisone until shock resolves. The taper may take several days to a

week and should be gradual with attention paid to vital signs and serum

sodium (6).

Methotrexate. Weekly methotrexate therapy became popular among

rheumatologists in the 1980s and continues to be one of the most commonly

used disease-modifying antirheumatic drugs (DMARDs). The relationship

between methotrexate and postoperative complications, such as local

infections and poor wound healing, has been a controversial topic over the

past decade due to the lack of definitive studies (10). Most of the studies

have involved rheumatoid arthritis patients undergoing elective orthopedic

surgery.

A small retrospective study published in 1991 suggested that methotrexate

increases the risk of postoperative complications (11). The authors were

unable to draw any definite conclusions, however, due to the small number of

patients and the nonrandomized selection of therapy. Other small studies

around the same time failed to show a significant increase in complications

in patients taking methotrexate perioperatively (12,13,14).

In 2001, a prospective randomized study of postoperative infection or

surgical complications in patients with rheumatoid arthritis who underwent

elective orthopedic surgery was published (15). Three hundred eighty-eight

patients with rheumatoid arthritis who were to undergo elective orthopedic

surgery were divided into two groups. One group continued methotrexate and

the other group discontinued methotrexate from 2 weeks before surgery until

2 weeks after surgery. Their complication rates were compared with

complications occurring in 228 rheumatoid arthritis patients not receiving

methotrexate who also underwent elective orthopedic surgery. Methotrexate

use was not associated with an increased incidence of complications and, in

fact, those patients that continued methotrexate had significantly less

complications or infections than either of the other two groups (p < 0.003).

Additionally, discontinuation of methotrexate led more commonly to disease

flares within 6 weeks following surgery (15).

With the information available, it would be reasonable to continue the

methotrexate weekly administration schedule pre- and postoperatively in most

situations. Situations in which methotrexate could be withheld the week

before and after surgery might be in the elderly, frail patient on many

other drugs and with some renal insufficiency. If methotrexate therapy is

interrupted, it is imperative to reinitiate therapy as soon as possible

given the risk of having a disease flare (15).

Other Medications. Other medications frequently used in patients with

rheumatic conditions include hydroxychloroquine, sulfasalazine,

azathioprine, leflunomide, and cyclophosphamide. Although little data exist

on the use of these agents in the perioperative period, it is reasonable to

withhold medications that are excreted renally, such as cyclophosphamide. To

avoid hematologic concerns, we suggest discontinuing sulfasalazine and

azathioprine several days before surgery and resuming a few days

postoperatively. Hydroxychloroquine can probably be continued without

interruption.

There is no information about the potential risk of leflunomide in the

perioperative period. Because of its long half-life, if side effects occur,

it would have to be washed out with cholestyramine. A reasonable approach

would be to stop it 2 weeks before elective surgery and resume it after

surgery.

The tumor necrosis factor (TNF) inhibitors - etanercept and infliximab - and

the interleukin-1 antagonist anakinra are being used, but no data exist

regarding their safety in the perioperative period. We suggest

discontinuation of these agents 1 week prior to surgery and resume therapy 1

week after surgery, but a study addressing these issues would be valuable.

http://www.arthritis.org/research/bulletin/vol51no6/51_6_Medications.asp

http://www.arthritis.org/research/Bulletin/vol51no6/51_6_Printable.htm

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