| Perioperative
Management of the Rheumatic Disease Patient
Joe T. Kelley III, MD
Doyt L. Conn, MD
Emory University School of Medicine
Atlanta,
GA
Summary
Points
The
appropriate use of antirheumatic drugs for patients in the perioperative period is
critical to maintaining control of disease and minimizing side effects of surgery.
Aspirin
should be stopped 10 days before surgery, and nonselective NSAIDs should be stopped 1 to 4
days before surgery, depending on the half-life of the drug.
The
selective COX-2 inhibitors do not affect platelets and may not need to be discontinued,
depending on the surgical procedure.
The usual dose of glucocorticoids should be continued throughout the pre- and
postsurgical period. Depending on the type of surgery, a boost in the steroid dose on the
day of the surgery may be necessary to cover stress.
Introduction
The perioperative evaluation of
the patient with rheumatic disease should include the usual medical evaluation with
special attention to medications and assessing disease activity (Table 1). Three important
classes of medications are nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids,
and disease-modifying antirheumatic drugs (DMARDs). Patients should be carefully
questioned regarding their use of over-the-counter NSAIDs as many patients fail to mention
these to their physicians.
It
is vital to continue glucocorticoid therapy during the entire perioperative period.
Discontinuing even low doses of glucocorticoids may cause a significant flare of disease
activity with profound consequences. As will be discussed, recommendations for
glucocorticoid supplementation in the perioperative period have changed during the past
few years. We will also discuss another important issue, fractures in potentially
osteoporotic patients.
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 (6-8). 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 (6-8).
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 (6,9). 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 (6-8).
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 (12-14).
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.
Disease-Specific
Issues
Osteoporosis. Patients with osteoporosis are
usually asymptomatic and are likely to come to the attention of the medical profession
with fractures as a result of minimal trauma (16). These patients are at increased risk of
sustaining another fracture as compared with patients who have not sustained an
osteoporotic fracture (17). This is true for both men and women, as wrist fractures in men
have been shown to be powerful predictors of subsequent hip fracture risk (18,19).
Recent studies have shown that
physicians frequently overlook osteoporosis in these patients and do not offer
information, diagnostic testing, or treatment (16,20-22).
Physicians
should always consider osteoporosis in patients presenting with a fracture, especially
after minor trauma. In those patients with risk factors for osteoporosis, appropriate
diagnostic testing should be performed and patient education and treatment should be
initiated while patient is hospitalized or very shortly thereafter. Certain medications to
treat osteoporosis (eg, bisphosphonates), however, have significant risk of esophageal
toxicity and probably should be discontinued while the patient is supine in the
hospital.
In
patients with osteoporosis who are hospitalized for surgery, it must be remembered that
these patients may be at risk for fractures with minor trauma. This risk might be
increased with prolonged bed rest and resultant weakening of muscles. For example,
coughing may result in rib fractures. Physical therapists should be involved with these
patients with admission to the hospital.
Rheumatoid Arthritis (RA). The importance of continuing
glucocorticoid therapy cannot be stressed enough in patients with RA. As stated
previously, all patients on chronic glucocorticoids who undergo any type of procedure or
have a medical illness require at least their normal daily glucocorticoid therapy.
Discontinuing glucocorticoids preoperatively can lead to postoperative flares of disease
and these patients have difficulty with postoperative rehabilitation and therefore may be
at higher risk for complications.
Active
RA can manifest with both articular and systemic symptoms. Systemic symptoms include
low-grade fever, fatigue, weight loss, and significant morning stiffness. Joint
examination may reveal tender, swollen joints and the temperature over the involved joints
may be elevated. Laboratory evaluation may reveal evidence of systemic inflammation with
mild leukocytosis, thrombocytosis, normochromic anemia, elevated erythrocyte sedimentation
rate, and elevated C-reactive protein. In the perioperative period, active disease can be
treated by a short-term increase in the glucocorticoid dose with prednisone 10 mg/day or 5
mg bid being sufficient (23). If DMARDs, such as methotrexate, or TNF inhibitors, such as
etanercept or infliximab, are discontinued in the perioperative period, glucocorticoids
can be adjusted to control disease. Restarting DMARDs and TNF inhibitors and tapering
glucocorticoids to the previous dose is important because the side effects of
glucocorticoids are dependent on cumulative dose.
Although
RA rarely involves the thoracic, lumbar, or sacral spine, cervical spine involvement is
common. Radiographic cervical spine subluxation in one form or another is estimated to
affect 43% to 80% of RA patients and atlantoaxial (C1-2) subluxation is the most common
type (24,25). Anterior subluxation is the most prevalent form and is best demonstrated on
lateral cervical spine x-ray with the neck in the flexed position. The most common symptom
of cervical subluxation is neck pain radiating into the occiput, and patients may report a
clicking in the neck on flexion and sometimes perceive an anterior movement of the head on
the neck (26).
Less
commonly, patients develop slowly progressive spastic quadriparesis, frequently with
painless sensory loss in the hands or transient episodes of medullary dysfunction
sometimes with paresthesias in the shoulders or arms during movement of the head (26).
Rheumatoid arthritis patients at high risk for cervical spine involvement are those with
neck symptoms, longstanding disease, erosive disease, subcutaneous nodules, and the
elderly.
Importantly,
in routine clinical practice it is unnecessary to image the cervical spine unless
suggestive symptoms are present. Rheumatoid arthritis patients undergoing surgery with the
potential for endotracheal intubation should have preoperative routine anteroposterior,
lateral, and open-mouth cervical spine radiographs since the presence of even subtle
degrees of atlantoaxial instability may be an indication for fiberoptic intubation
(24).
In the
postoperative period it is important to get physicical therapy involved, to continue ROM
exercises, and encourage early ambulation to prevent joint contractures.
Systemic Lupus Erythematosus (SLE). Preoperative assessment of the patient
with SLE is directed at determining disease activity and making decisions regarding
medications. Medications were discussed earlier in the chapter but it should be stressed
that patients should receive at least their normal daily glucocorticoid therapy. If
necessary, glucocorticoids can be increased to control disease activity prior to surgery.
Many patients with lupus are on hydroxychoquine, which should be continued during the
perioperative period.
History,
physical examination, and selective laboratory evaluation can assess disease activity.
Suggestive historical features include fever, oral ulcers, rash, especially in a malar
distribution, joint pain with or without swelling, pleuritic chest pain, and seizure or
psychosis in the absence of offending drugs or metabolic derangements. Clotting problems,
such as clotting of venous lines, DVTs, and digital tip infarcts, might suggest a
circulating anticoagulant and should be investigated. A physical examination is essential
to careful detect abnormalities of skin, joints, and circulation.
Laboratory
evaluation should include complete blood count to evaluate for cytopenias (especially
hemolytic anemia, leukopenia, lymphopenia, and thrombocytopenia) and urinalysis and
chemistry profile to assess renal function. Elevated serum anti-DS DNA antibodies and
decreased complement levels (C3 and C4) also suggest active disease.
Appropriate
management of lupus disease activity should be accomplished, which might include some
increase in the prednisone dose. A rheumatologist should be consulted regarding assessment
of disease activity and treatment.
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