A 2-year-old girl with periprocedural anaphylaxis.

Periprocedural or perioperative anaphylaxis is rare, with an estimated incidence of 1 in 10,000 to 40,000 sedation cases. During such procedures, patients are often exposed to numerous medications, such as antimicrobials, neuromuscular blocking agents, sedative and/or hypnotics, and opioids. The most commonly implicated agents include antibiotics (in the United States) and neuromuscular blocking agents (in Europe). In this article, we explore the differential diagnosis and laboratory investigation of a case of periprocedural anaphylaxis.

The immunomodulatory effect of ketamine in depression.

Major depression is one of the most frequent psychiatric conditions. Despite many available treatment methods, more than 30% of patients do not achieve remission, even after trying several antidepressants and augmentation strategies. S-enantiomer of ketamine, well-known anesthetic and analgesic, has been recently approved by Food and Drug Administration in the intranasal form as a new generation antidepressant. However, the mechanism in which ketamine reduces depressive symptoms in treatment-resistant depression patients is still not completely understood. There are several theories explaining how ketamine might reduce depressive symptoms, which have been described in detail; one of them is immunomodulatory effect of ketamine, according to the inflammatory theory of depression. In the review authors present and summarize studies showing ketamine effect on human immune system ex vivo and in vitro, including changes in cytokine levels, number, ratio and activity of various immune cell population and the correlation with clinical improvement in depressive symptoms. Most of the results confirm the anti-inflammatory effect of ketamine. There are only a few studies in the population of patients suffering from depression receiving ketamine, focused on correlation between immunological changes and clinical outcome of the therapy; further studies of that area are neccesary for understanding the immunomodulatory effect of ketamine in depression.

Development of a sensitive biotin-avidin amplified enzyme-linked immunosorbent assay for the determination of ketamine in biological samples.

An effective biotin-avidin amplified enzyme-linked immunosorbent assay (BA-ELISA) was developed to determine ketamine in biological samples. A conjugate of ketamine and ovalbumin (OVA) was used for immunization to produce polyclonal antibody. The conjugate of ketamine and bovine serum albumin (BSA) with polyclonal antibody was calculated to have an affinity constant (K(aff)) of 3.30 x 10(8)(mol/L)(-1). The linear range of ketamine was 0.1-1000 microg/L with recoveries from 89.6% to 99.9% in spiked sample analysis. The detection limit of ketamine was 0.03 microg/L, which is more sensitive than that of the traditional ELISA. The results obtained by BA-ELISA agreed well with that of the traditional ELISA, with a correlation coefficient of 0.98.

Immunomodulation by cocaine and ketamine in postnatal rats.

The abuse of cocaine (COC) in combination with ketamine (KET) among pregnant women was shown to be high. Transplacental exposure is not the only route by which a newborn may be exposed to these agents, but they can also distribute into breast milk. Chronic COC exposure is associated with immunological modulation in human and animal models. The effect of sub-chronic exposure to COC and KET alone and in combination on the developing immune system was assessed in neonatal male Sprague-Dawley (SD) rats. To simulate the route of exposure during lactation, newborn male rats were treated orally with saline, COC alone (20 mg/kg), KET alone (50 mg/kg), or KET (50 mg/kg) followed 15 min later by COC (20 mg/kg) from days 1 to 21 of life. Pups were sacrificed 30 min following the last treatment. Total circulating leukocyte and lymphocyte counts were decreased with relative neutrophilia, while spleen/body weight ratio and IgM antibody response to sheep red blood cells (SRBCs) were increased in animals treated with COC. Moreover, treatment with COC alone increased serum interleukin 10 (IL-10) concentration; however, it did not affect serum interferon gamma (IFN-gamma) concentration. On the other hand, KET treatment did not produce any significant change of any of these parameters. However, when co-administered with COC, the immunomodulatory effects of COC were prevented. COC caused a significant increase in serum corticosterone concentration that KET effectively prevented. Lack of significant change of plasma and tissue concentrations of norcocaine (NC) suggested no role for COC metabolism in COC-induced immunomodulation. However, the results of this study indicate that COC-induced immunomodulatory reactions and their prevention by KET most likely occurred through neuroendocrinal mechanisms.

Incidence of histamine release after the administration of midazolam-ketamine in allergic patients.

OBJECTIVE: We examined the effects of midazolam-ketamine which was used during the induction of anesthesia against histamine release, skin reactions and hemodynamic changes in patients with a history of allergy. SUBJECTS: Forty allergic patients and 40 non-allergic patients undergoing oral surgery were examined. METHODS: Midazolam ketamine was used for the induction of anesthesia in 40 patients with a history of allergy (M-K group) and thiamylal was used for the induction of anesthesia in 40 patients without any history of allergy (BARB group). Venous blood samples were obtained before induction as a control and 0.5, 1, 3, 5 minutes after the administration of each drug in order to measure the plasma histamine level. In addition, any observed hemodynamic changes were simultaneously recorded. The plasma histamine level was measured using the HPLC (high performance liquid chromatography) post-label system. RESULTS: The incidence of histamine release, skin reactions and hemodynamic changes were 37.5%, 10.0% and 7.5%, in the M-K group, and 40.0%, 12.5% and 12.5%, in the BARB group, respectively. Although the mean basal plasma histamine level in the M-K group (0.46 +/- 0.23 ng/ml) who had a history of allergy was much higher than that in the BARB group (0.28 +/- 0.17 ng/ml) (p < 0.001), the incidence of histamine release and clinical symptoms were similar between the two groups. CONCLUSIONS: The induction of anesthesia with midazolam-ketamine was thus found to be a valuable method for allergic patients, because the incidence of histamine release, skin reactions and hemodynamic changes in allergic patients were similar to those in non-allergic patients induced by thiamylal and no significant changes were observed in the plasma histamine level after the administration of midazolam-ketamine in spite of the high level of basal plasma histamine.

Anesthesia-induced modulation of in vivo antibody levels: a study of pentobarbital, chloral hydrate, methoxyflurane, halothane, and ketamine/xylazine.

The influence of anesthesia on long-term changes in in vivo antibody levels after antigen challenge was examined. Rats experienced a surgical plane of various anesthetics alone (anesthesia/intact) or in combination with laparatomy (anesthesia/laparatomy) and were given 1 or 3 wk to recover. Antigen, keyhole limpet hemocyanin, was then administered, and antibody levels specific to the antigen were measured during the next 14 days. Comparisons were made between anesthesia-treated animals and home cage controls. Pentobarbital and chloral hydrate produced decreases in in vivo antibody levels even 3 wk after exposure, whereas halothane, methoxyflurane, and ketamine/xylazine did not. Ketamine/xylazine produced moderate but not significant decreases in antibody levels when 1 wk intervened between exposure and antigen administration, but not when 3 wk intervened. Surgery did not produce larger changes in antibody levels than did anesthesia itself. These data suggest the possibility that some anesthetics, per se, may contribute to infection that may occur postoperatively.

Reaction to ketamine: anaphylactoid or anaphylactic?

A 3-year-old child developed extensive macular rash after ketamine. The mechanism of this reaction was investigated by the Prausnitz-Kutzner (P-K) test. It demonstrated that the histamine release was not the result of an anaphylactic reaction, but rather a direct pharmacological effect of the drug. The result suggests that this child can receive ketamine in the future without any severe manifestations. The mechanisms of histamine release are discussed and the treatment of its clinical manifestations is reviewed.