An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis.

Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.

Recovery from anesthesia after craniotomy for supratentorial tumors: comparison of propofol-remifentanil and sevoflurane-sufentanil (the PROMIFLUNIL trial).

INTRODUCTION: Rapid recovery after supratentorial tumors (STT) removal is important. Short-acting anesthetics, such as propofol and remifentanil might favor this objective. The aim of this study was to compare the recovery of 2 Bispectral index (BIS)-guided anesthesia protocols combining sevoflurane-sufentanil (SS) or propofol-remifentanil (PR) administered during craniotomy for STT. MATERIALS AND METHODS: After IRB approval and written consent, patients scheduled for surgical removal of STT were randomized to receive PR or SS. Anesthesia was adjusted to maintain BIS values between 45 and 55. The primary outcome was the time from discontinuation of anesthetics to extubation. Secondary endpoints were: time to respond to a simple order, and to achieve spontaneous ventilation, agitation score at emergence, postoperative Mini Mental State, postoperative Aldrete score, pain Visual Analogical Score, simplified sedation score, Glasgow Coma Scale, and surgical complications. Statistical analyses were performed using analysis of variance. RESULTS: Thirty-five and 31 were included in the SS and PR groups, respectively. Times to extubation was not different between the 2 groups (11.8±6.9 vs. 13.0±8.1 min in PR and SS groups, respectively, P=0.577). Although times to achieve an Aldrete score to 10, a Glasgow Coma Scale to 15, and a MMS to 30 significantly were lower in SS group, no significant difference was found when analyzing time course of these 3 factors over the first postoperative day. All other secondary endpoints were not different between the 2 groups. CONCLUSION: During craniotomy for STT, we could not demonstrate a reduction in the time to extubation when comparing a BIS-guided anesthesia associating PR to a BIS-guided anesthesia associating SS (Clinicatrials.gov identifier: NCT00389883).