Israel Medical Association Journal

Objective: To report our experience with terlipressin treatment for facilitation of transport to distant facilities for diagnostic or therapeutic procedures in septic patients treated with norepinephrine.

Methods:  We conducted a retrospective analysis of the records of our ICU[1], identifying the patients with septic shock who required norepinephrine for hemodynamic support.

Results: Terlipressin was given to 30 septic shock patients (15 females and 15 males) who were on high dose norepinephrine (10 μg/min or more) in order to facilitate their transport outside the ICU. The dose of terlipressin ranged from 1 to 4 mg, with a mean of 2.13 ± 0.68 mg. The dose of norepinephrine needed to maintain systolic blood pressure above 100 mmHg decreased following terlipressin administration, from 21.9 ± 10.4 μg/min (range 5–52 μg/min) to 1.0 ± 1.95 (range 0–10) (P < 0.001). No patients required norepinephrine dose adjustment during transport. No serious complications or overshoot in blood pressure values were observed following terlipressin administration. Acrocyanosis occurred only in eight patients receiving more than 1 mg of the drug. The overall mortality rate was 50%.

Conclusions: Our data suggest that terlipressin is effective in septic shock. Because it is long-acting and necessitates less titration it might be indicated for patient transportation.

Background: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65[1] and human HSP60 have been established in a number of human autoimmune diseases.

Objective: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjogren's syndrome as compared to normal subjects.

Methods: Thirty-seven patients with SS[2] were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs[3] and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens.

Results: The levels of both anti-HSP60 and -HSP65 were lower among patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 ± 55.1 ng/ml in controls versus 112.3 ± 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among patients: 111.6 ± 33.4 U/ml versus 96.1 ± 8.9 U/ml (P = 0.01).

Conclusions: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies on larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

Vasopressin is a potent endogenous vasoconstrictor that increases blood pressure and systemic vascular resistance. The administration of exogenous vasopressin during closed and open cardiopulmonary resuscitation in humans was shown to be more effective than optimal doses of epinephrine in several clinical studies. We summarize here the recent experimental and clinical data on the use of vasopressin in cardiopulmonary resuscitation and septic shock. As the use of vasopressin in human resuscitation is now in its early stages, it is expected that accumulated future experience will shed more light regarding the risk-benefit aspects of its use.

Sepsis is an inflammatory syndrome caused by infection. Consequently, anti-inflammatory therapies in sepsis have been a subject of extensive research and corticosteroids have been used for years in the therapy of severe infections. However, studies conducted in the 1980s failed to demonstrate any beneficial effects of high dose, short-term steroid therapy in sepsis and this therapy was therefore abandoned during the last decade. Recently, a new concept has emerged with more promising results - low dose, long-term hydrocortisone therapy – and this approach is now being evaluated in the treatment of septic shock. It is supported by the observation that many sepsis patients have relative adrenal insufficiency. Moreover, the anti-inflammatory effects of steroids and their ability to improve reactivity to catecholamines further contribute to their effects in sepsis. Large randomized clinical trials will be required to determine the exact role of corticosteroids in septic shock.

Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.

Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.

Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.

Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.

Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.