The death rate from the Guillain Barré syndrome in the U. S. is less than 2%. This is a substantial reduction over the situation 40 years ago, and reflects the effectiveness of modern intensive care. Patients who appear to be progressing toward insufficient strength to breathe, are having trouble swallowing, or have unstable bold pressure or pulse are candidates for move to the intensive care unit. When breathing difficulties develop, a tube placed though the mouth into the airway allows connection to a ventilator and assisted ventilation for a period of time. Looking back, many patients describe this period as frightening and recall the difficulty communicating needs without speech.
The major reduction of mortality in GBS has been due to advances in supportive care of critically ill patients. Most recently, an increased understanding of the immunologic basis of this disease over the past 15 years has allowed us to change the natural course of this disease. Plasmapheresis was the first therapy shown to be effective in speeding up recovery. In this procedure, a patient's blood is removed, and then centrifuged to separate the cellular and plasma components. The cellular components are then diluted with artificial plasminate and reinfused into the patient. The therapeutic effect is presumably due to the removal of inciting circulating factors such as antibodies.
Another effective therapy is intravenous human immunoglobulins (IVIG). There have been two controlled studies showing that IVIG is as effective as plasmapheresis is in the treatment of GBS. The mechanism of action of infused immunoglobulin is not clear, but one possibility is that pooled immunoglobulins contain anti-idiotypic antibodies that inactivate the disease-specific antibodies. Because infusion of intravenous immunoglobulin does not entail the difficulties in line placement sometimes encountered with plasmapheresis, and because it can be easily arranged on any time, it is now the first choice of therapy. For both infusions of HIG and plasmapheresis, it is important to check serum immunoglobulin levels. Patients with very low IgA levels (due to congenital abnormalities of IgA) are likely to develop anti-IgA antibodies and are at potential risk for anaphylaxis. Although the risk of anaphylaxis may be more true in patient receiving the HIG therapy, there is sufficient IgA in the salt-poor albumin used in plasmapheresis that patients with anti-IgA antibodies are at risk with plasmapheresis as well.
All commercial products appear to be equally effective, and all are expensive. The record of safety is excellent, although concern about possible transmission of hepatitis C with one product occurred in 1994. However, since the implementation of new viral inactivation procedure, no case of hepatitis C transmission has been reported in the United States. The two main complications of infusion of HIG are headache and acute renal failure. Headaches are self-limited and may occur more often in migraineurs. The headaches are often associated with a CSF pleocytosis suggesting possible aseptic meningitis. More dangerous is the development of acute tubular necrosis and renal failure. Pre-existing renal disease is unquestionably a predisposing factor. We have seen acute renal failure develop in patients with vasculitis and with diabetic nephrosclerosis. The renal involvement is always reversible, but a period of dialysis may be required. Finally, patients with high levels of immunoglobulin, as encountered occasionally in patients with HIV infections and in patients with monoclonal gammopathies, may develop hypervisosity syndrome. Infusion of 1g per kilogram of HIG can raise the immunoglobulin level to over 3g per deciliter.
The usual recommendation is for infusion of 0.4 g per kilogram per day for 5 days (total dose, 2.0 g per kilogram). A test dose of 0.2 g per kilogram is infused. If this is well tolerated, on that same night the remaining 0.8 g per kilogram is infused.
Use of Plasma Exchange
In patients with relative contraindications to the use of HIG, plasma exchange (PE) is an equally effective alternative, and is also an extremely safe procedure. The biggest risk is the necessity to obtain and maintain venous access in patients with inadequate veins. This often requires placement of a Shiley catheter. The continuos-flow plasmapheresis machines appear to be preferable. The replacement fluid is a 5% salt-poor albumin. Four or five exchanges over a period of 8 to 10 days, to a total of 250 cc per kilogram of body weight, are the standard approach. Daily plasmapheresis is disadvantageous, both because of the procedure in removing in large part the replacement fluid from previous pheresis, and because the shorter total pheresis time appears to predispose the patient to relapses.Are some instances of GBS too mild to required therapy? As the evidence mounts that early immunotherapy can forestall or prevent progression to more advanced forms, a higher proportion of patients are receiving therapy. A study by the French Cooperative group on Plasma Exchange in Guillain-Barré syndrome suggests that even for patients who have mild weakness (able to walk but not run), two PEs were more effective than none comparing the time to onset of motor recovery. Multi-center study has shown only a non-significant trend with combined treatment with PE followed by HIG. Thus, combined therapy should only be given on selected patient who have one form of immunotherapy early after onset but who continues to progress.
It is not known whether the responsiveness to either immunotherapy is different among the different GBSs. At present the evidence for an antibody- and complement-mediated injury is greatest for the AMAN and AMSAN patterns. For this reason, they will likely respond to immunotherapy like AIDP.