Page 1784 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 126: Rheumatology in the ICU 1253

4 (CTLA4) linked to the Fc portion of immunoglobulin G1. It is appro- • What do I suspect the patient may have? It should be possible to
ved for use in combination with methotrexate (not in combination with formulate a plausible if unprovable diagnostic hypothesis. Such a
other biologics) to treat rheumatoid arthritis and given via intravenous hypothesis is critical to the rest of the experiment. If it is impossible to
infusion monthly. There is a newer regimen that uses subcutaneous generate a “working diagnosis,” it is doubtful that the therapeutic trial
administration. The half-life is approximately 14 to 17 days and admin- will work. Autopsy study of these patients is likely to reveal cancer
istration can be associated with infusion reactions. A meta-analysis of or no diagnosis.
published RCTs showed no significant increase in the risk of serious • What is adequate therapy for this suspected diagnosis? Treatment
infections comparing the use of abatacept with those of placebo. The for a suspected diagnosis ranges from adequate to aggressive. In the
risk of malignancy in patients treated with abatacept does not appear to absence of a definite diagnosis, it is reasonable to choose a level of
be higher than that seen in placebo-treated patients. There is no recom- therapeutic intensity that is usually adequate for the suspected dis-
mended adjustment for renal or hepatic disease at this time. Common order. Aggressive treatment approaches to an unconfirmed illness
https://kat.cr/user/tahir99/
side effects include headache, hypertension nausea/vomiting/diarrhea, create another set of confounding variables and may place the patient
and upper respiratory infections. To date, no black box warnings are at a further disadvantage.
published for abatacept. As with most biologics, baseline hepatitis serol-
ogies and a PPD need to be documented as negative prior to starting. 76,78 • What will I use as my parameters to judge therapeutic success?
Empiric therapy should proceed with a clear understanding of
■ PLASMAPHERESIS/THERAPEUTIC PLASMA EXCHANGE the yardsticks that will measure therapeutic responsiveness. These
parameters can then be rigorously monitored. Furthermore, blind
Therapeutic plasmapheresis is a procedure where the plasma compo- spots in the baseline data can be addressed before therapy is begun.
nent of blood is separated and removed. When the removed plasma is • What is the duration of a reasonable trial for this disorder? Agreement
replaced with albumin or fresh frozen plasma, the process is referred on the duration of a therapeutic trial should precede its initiation.
to as therapeutic plasma exchange (TPE). TPE is thought to effect Failure to develop such an end point can result in excessively long
rapid removal of circulating antigens, immune complexes, pathologic and risky therapy on the one hand, or a course that falls short of an
antibodies, and circulating cytokines. TPE appears to be a fast-acting adequate trial on the other. Furthermore, spontaneous improvement
therapeutic adjunct to immunosuppressive therapy for some acute inflam- or improvement in response to other therapies may result in pro-
matory/autoimmune disorders and may have a role in treating refractory longed and unnecessary treatment.
disease. TPE is indicated in the treatment of patients with thrombotic
thrombocytopenic purpura (TTP); also in patients with antiglomerular • Involve the patient and the family in the decision to treat empirically.
basement membrane disease (Goodpasture syndrome) or GPA with The clinician needs to be vigilant about the risks associated with any
diffuse alveolar hemorrhage and/or with dialysis independent renal trial of empiric therapy. However, after addressing the above questions,
involvement. TPE is second-line therapy for patients suffering from such a trial may represent both rational and compassionate care.
CAPS and severe SLE (with manifestations such as cerebritis or diffuse
alveolar hemorrhage). The procedure has a wide margin of safety and is
commonly associated with mild side effects such as electrolyte distur- KEY REFERENCES
bances. Adverse effects were seen in 5.7% of one registry with no related
deaths. Another analysis reported 0.4% serious adverse effects (requiring • Asherson RA. The catastrophic antiphospholipid (Asherson’s)
syndrome. Autoimmun Rev. December 2006;6(2):64-67.
discontinuation of the procedure) and three related deaths (complicated
vascular access and transfusion-related lung injury). Anaphylaxis and • Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis.
hemorrhage have also been reported and are more common with the use Lancet. September 20, 2003;362(9388):971-982.
of plasma than with albumin. A 1.0 to 1.5 plasma volume exchange will • George JN. Clinical practice. Thrombotic thrombocytopenic pur-
remove approximately 70% to 80% of the target substance (eg, immuno- pura. N Engl J Med. May 4, 2006;354(18):1927-1935.
globulin). A common rationale used to determine the frequency of plas- • Godeau B, Mortier E, Roy PM, et al. Short and longterm outcomes
mapheresis is based on “resting” the patient on alternate days to allow for patients with systemic rheumatic diseases admitted to intensive
re-equilibration between extravascular and intravascular IgG; typically care units: a prognostic study of 181 patients. J Rheumatol. July
5 to 7 exchanges are required to 75% of a pathologic antibody. 82,83 1997;24(7):1317-1323.

• Hant FN, Herpel LB, Silver RM. Pulmonary manifestations of
EMPIRICAL THERAPY FOR SUSPECTED scleroderma and mixed connective tissue disease. Clin Chest Med.
RHEUMATIC DISEASE September 2010;31(3):433-449.
In puzzling cases the rheumatologist may discern from the nuances of • Kamen DL, Strange C. Pulmonary manifestations of systemic lupus
the clinical examination, serologic testing, and invasive procedures that erythematosus. Clin Chest Med. September 2010;31(3):479-488.
the patient has rheumatic disease. Sometimes the rheumatologist, like • Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune
the intensivist, cannot make a definite diagnosis, yet confronts a criti- and inflammatory diseases with intravenous immune globulin. N
cally ill patient who may have a rheumatic disease. The clinical status of Engl J Med. September 6, 2001;345(10):747-755.
such patients is usually at an unacceptable plateau or even more likely • Kronzon I, Saric M. Cholesterol embolization syndrome.
deteriorating. Should that patient be given empiric therapy? Recognition Circulation. August 10, 2010;122(6):631-641.
of our shortcomings in diagnosis and the inability of some patients to
tolerate a critical invasive test may lead to the recommendation of such • Lateef A, Petri M. Biologics in the treatment of systemic lupus ery-
thematosus. Curr Opin Rheumatol. September 2010;22(5):504-509.
a course in selected patients. Prior to initiation of empirical therapy, it is
helpful to ask a series of related questions: • Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and
giant-cell arteritis. Lancet. July 19, 2008;372(9634):234-245.
• Has infection been reasonably excluded? Infection and cancer most
commonly mimic rheumatic disease. Since empiric therapy usually
implies immunosuppressive drugs, most commonly corticosteroids,
infection must be ruled out. Here the emphasis should be on rea- REFERENCES
sonably making such an assessment. Endless sets of blood cultures
should not delay a difficult decision. Complete references available online at www.mhprofessional.com/hall

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