Page 1781 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1250 PART 11: Special Problems in Critical Care

anti-B2-glycoprotein-I antibodies. These antibodies often, although not potent anti-inflammatory effects and are highly effective in patients
always, occur together. The clinical syndromes associated with these with rheumatoid arthritis. For purposes of controlling inflammation
antibodies belong to a growing list that can be explained largely by the and immunomodulation, “short-acting” glucocorticoids with little or no
capacity of these antibodies to induce thrombosis in the venous and mineralocorticoid activity are preferred. The oral drug of choice is pred-
arterial circulation. Thrombocytopenia and recurrent fetal loss are other nisone, which is converted to prednisolone in the liver. Whereas active
major consequences of APLA. The combination of APLA and one or liver disease impairs that conversion, it appears to be offset sufficiently
more of these clinical features has been termed the “antiphospholipid by decreased rate of elimination of prednisolone to obviate the need to
antibody syndrome.” Chronic false-positive serologic tests for syphilis preferentially use prednisolone in patients with cirrhosis or active liver
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are associated with autoimmune disease, notably SLE, and are found disease. The intravenous drug of choice is methylprednisolone. The dose
with increased frequency in patients with ACL and LA activity. Lupus equivalency is 4 mg methylprednisolone to 5 mg prednisone. The dose
anticoagulants are antibodies that prolong phospholipid-dependent of prednisone or methylprednisolone is largely empiric. For serious,
tests in vitro by interference with the calcium-dependent binding of life-threatening problems, 1 mg/kg per day of prednisone is a reason-
prothrombin (factor II) and factor Xa to phospholipids, thus inhibiting able starting point. Dividing the dose into a twice-a-day or other dose-
the generation of prothrombinase. This usually results in prolongation of divided schedule may increase the immunosuppressive effect (as well
the activated partial thromboplastin time (APTT) with or without slight as toxicity) and is recommended by some for initial therapy. Extremely
prolongation of the prothrombin time (PT) and INR. LA is a common large doses of intravenous methylprednisolone (500-1000 mg) daily have
cause of prolongation of the PTT, but not the only cause. Many patients been used for brief periods (3-5 days) with variable success in a variety
with LA do not have SLE. Usually ACL antibodies are detected in an of clinical settings, mostly in the context of SLE. Unique side effects to
enzyme-linked immunosorbent assay (ELISA) using bovine cardiolipin this form of therapy, including sudden overwhelming sepsis and sudden
as substrate. These are the most commonly detected antiphospho- death, are rare. This form of therapy is generally reserved for patients
lipid antibodies. They are generated transiently in the course of acute who have failed conventional high-dose therapy with corticosteroids
infections including mycoplasma and gram-negative infections. IgM with or without another immunosuppressive agent. Patient response to
ACL as well as the LA may be induced by a variety of drugs includ- corticosteroids varies. Failure to respond is likely a result of the nature
ing phenothiazines, procainamide, phenytoin, hydralazine, quinidine, and severity of the disease. The effectiveness of glucocorticoids may be
and streptomycin. These antibodies are most often not associated with reduced by simultaneous use of other drugs that induce hepatic micro-
thrombotic events, but exceptions to this rule occur. Antibodies to somal enzyme activity, such as phenytoin, barbiturates, and rifampin.
B2-glycoprotein-1 are more specific for the diagnosis of APLA syn- Bioavailability of prednisone may be reduced by antacids sometimes
drome than the anticardiolipin test. ACL antibodies have been found in prescribed for concurrent use. Cortisol and its synthetic derivatives
2.5% of the general population. For most of these patients, the antibodies are bound to corticosteroid-binding globulin and albumin. The bound
have no clinical significance. The risk of thrombosis and fetal loss has steroid is not active. Increased frequency of prednisone side effects
been generally associated with higher levels of antibody and the IgG iso- has been observed at low serum albumin levels, probably reflecting
type, though exceptions occur. Thus the presence of ACL antibody as an an increase in the unbound, active fraction of the drug. Patients who
isolated finding should not prompt therapeutic intervention. A myriad have a positive purified protein derivative (PPD) test about to undergo
of neurologic events including stroke, transient ischemic attacks, and corticosteroid therapy (particularly with doses of prednisone of 20 mg/d
amaurosis fugax have been associated with the presence of LA and ACL or greater) should be considered for isoniazid (INH) prophylaxis
antibody. Their presence should be suspected in patients who have no (300 mg/d orally). The reported risk of reactivation ranges from low in
risk factors for thrombosis or who have associated autoimmune disease asthmatics to higher in the elderly and in patients immunosuppressed
or suggestive screening laboratory abnormalities, including prolonged by virtue of other drugs or their primary disease. The patient with a
PTT or false-positive serologic tests for syphilis. Skin lesions secondary positive PPD and either a normal chest x-ray or a single calcified nodule
to LA and ACL include livedo reticularis, purpura, hemorrhage, and may not require prophylaxis. If the patient has significant impairment
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ischemia leading to gangrene. The vasculopathy of APLA syndrome of the immune system or the chest film shows fibronodular scarring, the
is not vasculitis, but primarily thrombosis of large or small arteries or risk is enhanced considerably, and prophylaxis with INH is advisable.
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veins. Treatment for major thrombotic complications of this syndrome Steroid therapy suppresses cutaneous delayed hypersensitivity responses
is anticoagulation. Steroids are indicated for associated clinical features by inhibiting recruitment of macrophages to the skin test site. This
related to systemic inflammation. Rarely patients may present with phenomenon is reversible on stopping the drug. In one study, treatment
evidence of widespread vascular occlusion and multiorgan failure occur- with 10 mg prednisone daily totally inhibited cutaneous tuberculin
ring concurrently or over a short period of time related to antiphospho- sensitivity in both active and inactive cases of tuberculosis, with a mean
lipid antibodies. Kidneys, bowels, lungs, brain, and heart are frequently reversion time of 13.6 days and reconversion time of 6 days following
involved. The catastrophic antiphospholipid syndrome (CAPS) is associ- discontinuation of the drug. Acute adrenocortical insufficiency may
ated with significant morbidity and mortality in spite of empiric therapy occur in critically ill patients who have been treated with chronic glu-
with corticosteroids, anticoagulation, and apheresis. CAPS needs to be cocorticoid therapy. On the basis of available data, any patient who has
distinguished from thrombotic thrombocytopenia purpura (TTP) and received a glucocorticoid at a dose greater than 20 to 30 mg prednisone
diffuse intravascular coagulation. Precipitating events, such as infection, daily for longer than a week should be suspected of having hypotha-
trauma, surgical procedures, or reduction in anticoagulation therapy, lamic-pituitary-adrenal (HPA) axis suppression. At doses closer to but
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may contribute to the development of CAPS. 66-68 above the physiologic range, a month is probably the minimum dura-
tion required for HPA suppression. Patients receiving the equivalent
USE OF CORTICOSTEROIDS, replacement doses of steroid (5 mg prednisone) as single morning dose
therapy are at low risk of iatrogenic adrenal insufficiency. In the absence
IMMUNOSUPPRESSIVES, AND ANTI-INFLAMMATORY of hemodynamic instability, these patients do not require full “stress
DRUGS IN THE CRITICALLY ILL PATIENT dose” replacement therapy. Low baseline cortisol levels or an adreno-
■ CORTICOSTEROIDS corticotropic hormone stimulation test may help resolve the question of
adrenal suppression, but the clinical reality usually dictates empirical
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Corticosteroids have potent immunosuppressive and anti-inflammatory coverage with “stress doses” of corticosteroids. This can be accom-
properties that, in combination with rapid onset of action, make them plished with 50 to 100 mg hydrocortisone intravenously every 8 hours.
the drugs of choice for the initial therapy of most acute, life-threatening This is approximately the equivalent of 30 to 60 mg prednisone. Higher
rheumatic disorders. Even low doses of prednisone (<10 mg/d) have doses are not necessary and are potentially more hazardous. Use of

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