Are women more sensitive to a pre-curarization dose of rocuronium than men?

BACKGROUND: There is increasing evidence that there are gender-related differences in the pharmacodynamics of neuromuscular blocking drugs. However, it is not known whether gender influences the pharmacodynamics of a pre-curarizing dose. METHODS: In the first part, we measured the neuromuscular blockade after administration of rocuronium 0.03 mg/kg (10% of ED(95)) after induction of anaesthesia in 20 patients (10 female and 10 male patients) by electromyography. In the second part, 40 female and 40 male patients were observed for signs and symptoms of muscle weakness 2.5 min after injection of rocuronium 0.03 mg/kg before loss of consciousness. Succinylcholine-associated post-operative myalgia (POM) was also assessed. RESULTS: Median twitch heights were comparable between the two groups: 95.5 (range: 85-97; female) vs. 96.0 (range: 85-99; male), (NS). Train-of-four ratios were 97.5 (range: 64-100; female) vs. 99.0 (range: 52-100; male) (NS). Signs and symptoms of muscle weakness were observed in 64 (80%) patients, but there were no gender-related differences. The incidence and severity of POM did not differ significantly between the study groups. CONCLUSIONS: Pre-curarization with rocuronium 0.03 mg/kg affected men and women equally. Nor was the incidence and the severity of muscle weakness affected by gender.

Morphine inhibits AP-1 activity and CD14 expression in leukocytes by a nitric oxide and opioid receptor-dependent mechanism.

BACKGROUND: Activator protein 1 is a transcription factor involved in the regulation of proinflammatory mediators. Activation of phagocytes by lipopolysaccharide depends on the expression of CD14 on the cell surface. In this study, we investigated the effects of morphine and nitric oxide on CD14 expression and activator protein 1 activation in human blood monocytes and neutrophils as well as the leukocyte cell line HL-60. METHODS: Whole blood was incubated with morphine, the nitric oxide donor S-nitroso-N-acetyl-penicillamine, naloxone or nitric oxide synthase inhibitors Nomega-nitro-l-arginine and Nomega-nitro-l-arginine-methylester and stimulated with lipopolysaccharide. Activator protein 1 nuclear content was determined by flow cytometry in human blood neutrophils and monocytes. CD14 expression on neutrophils was measured after incubation with fluorescein isothiocyanate-labelled antibodies. Electric mobility shift assay served for evaluation of activator protein 1 nuclear binding in HL-60 cells. RESULTS: Incubation of whole blood with morphine and subsequent stimulation with lipopolysaccharide decreased activator protein 1 nuclear content. Exposure to naloxone before morphine treatment abolished morphine-induced inhibition of activator protein 1 activity in human blood monocytes and neutrophils. Nitric oxide synthase inhibitors also reversed morphine's effects. CD14 expression on neutrophils was reduced after morphine treatment. These effects were antagonized by nitric oxide synthase inhibitors and naloxone. CONCLUSION: Morphine inhibits activator protein 1 activation by a mu opioid receptor pathway coupled to nitric oxide as second messenger. The decrease in CD14 expression caused by morphine may play a role in inhibition of activator protein 1 activation following lipopolysaccharide treatment of phagocytes.

[Activation of granulocytes and antiproteases in open heart surgery]. / Aktivierung von Granulozyten und Antiproteasen bei herzchirurgischen Eingriffen mit extrakorporaler Zirkulation.

OBJECTIVE: Cardiovascular surgical procedures with extracorporeal circulation (ECC) lead to neutrophil activation followed by the release of proteases such as neutrophil elastase (NE) and oxidants. The mis-balance between proteases and their physiological inhibitors may contribute to morbidity in the postoperative period. In this study, the effects of cardiac surgery on neutrophil mediators were evaluated. Release of neutrophil elastase and plasma levels of the natural NE antagonists alpha (1)-proteinase inhibitor (API) and secretory leukocyte proteinase inhibitor (SLPI) were measured. The oxidative burst and the phagocytic activity were also evaluated. Tissue destruction was quantified by measuring the serum concentration of fibronectin. METHODS: Blood samples were obtained from 30 patients undergoing elective coronary artery bypass grafting (n = 30). NE and SLPI concentrations were measured by ELISA, API and fibronectin plasma levels were determined by nephelometry. Neutrophil phagocytic activity and oxidative burst were evaluated by flow cytometry. RESULTS: Neutrophil elastase plasma concentrations rose during ECC (245 +/- 107 microg/ml versus 44 +/- 14 microg/ml after induction, p < 0.001), whereas SLPI and API were decreased after onset of ECC. 24 h after ECC SLPI (54 +/- 17 ng/ml versus 41 +/- 10 ng/ml, p < 0.05) and API (3 +/- 0.5 g/l versus 1.6 +/- 0.3 g/l, p < 0.05) increased significantly compared to baseline values. A minor increase in phagocytic activity was observed after the onset of ECC. There were no significant changes in the oxidative burst. CONCLUSION: Cardiac surgery with ECC leads to neutrophil activation and elastase release. The imbalance between NE and the NE inhibitors API and SLPI may increase the risk for tissue damage due to granulocyte activation after cardiac surgery.

[Morphine inhibits complement receptor expression, phagocytosis and oxidative burst by a nitric oxide dependent mechanism]. / Morphin hemmt die Expression von Komplementrezeptoren sowie Phagozytose und Oxidativen Burst in Monozyten über einen NO-abhängigen Mechanismus.

OBJECTIVE: Monocytes play a crucial role in the immune response by recognition, ingestion, and intracellular killing of microorganisms. We investigated whether morphine and fentanyl influence CD 11b and CD35 surface receptor expression, phagocytic activity and superoxide anion generation of monocytes in a whole blood flow cytometric assay. METHODS: Whole blood of 13 healthy volunteers was incubated with different morphine and fentanyl concentrations. Expression of surface receptors CD 11b and CD35 was determined by fluorochrome-labelled antibodies. Phagocytic activity was assessed by ingestion of fluorescent bacteria. Conversion of dihydrorhodamin served for oxidative burst measurements. RESULTS: Morphine inhibited monocyte function in a concentration and time dependent manner. Morphine-induced changes were abolished by preincubation with the NO synthase inhibitor N-nitro-l-arginine as well as naloxone. Fentanyl failed to inhibit receptor expression, phagocytosis and reactive oxygen production by monocytes in clinically relevant as well as supraclinical concentrations. CONCLUSION: Our results suggest that these monocyte functions are inhibited by a morphine-stimulated NO release mediated by a mu opiate receptor subtype expressed on the surface of monocytes. In contrast, fentanyl did not share morphine's inhibitory effects on monocyte activity.

Strategies to reduce perioperative blood loss related to non-surgical bleeding.

The treatment of critically ill patients has advanced markedly over the last decade. However, non-surgical bleeding of a diffuse nature from numerous tiny capillaries still remains a challenge. Once initiated, this type of bleeding may be troublesome and a vicious circle develops since it is not a single vessel contributing to this blood loss. The description 'non-surgical blood loss' is often given to this. This review describes a step-by-step approach for the treatment of non-surgical bleeding and includes various measures, such as desmopressin, blood components, antifibrinolytics, antithrombin III, prothrombin complex concentrates and factor XIII. While most non-surgical bleedings can be managed using the approach described here, a number of patients still continue to bleed. In these cases, the surgeon should re-evaluate the bleeding in terms of its surgical origin. If this can positively be excluded and if all of measures described fail to reduce or stop the bleeding, further treatment of such uncontrolled bleeding remains symptomatic.

Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro.

BACKGROUND: Opioid peptides released from immunocytes during inflammation and stress in critically ill patients are associated with an altered immune response. Moreover, concentrations of opioid peptides are increased in peripheral blood and at the sites of inflammatory reactions. METHODS: Using flow cytometric assay of whole human blood, we investigated direct effects of endogenous and synthetic opioid peptides on surface expression of complement receptors CD35 and CD11b/CD18 and Fcã receptor III CD16, and superoxide anion generation of neutrophils. RESULTS: The endogenous opioid peptides beta-endorphin(1-31) and met-enkephalin, representing the N-terminal fragment of beta-endorphin(1-31), and the synthetic delta opioid receptor agonists D-Ala(2)-D-Leu(5)-enkephalin and D-Pen(2)-enkephalin produced concentration-dependent stimulation of neutrophil activity. Incubation with met-enkephalin 10(-7) M or beta-endorphin(1-31) 10(-7) M led to an increase in receptor expression of up to 10% (met-enkephalin) and 15% (beta-endorphin(1-31)). After incubation with D-Ala(2)-D-Leu(5)-enkephalin or D-Pen(2/5)-enkephalin, receptor expression was increased by up to 30%. This correlated with concentration-dependent stimulation of the production of reactive oxygen intermediates, as shown by an increase of up to 40% in oxidative burst activity. All effects were abolished after preincubation with naloxone or with the selective delta opioid antagonist naltrindole, whereas the selective micro receptor antagonist d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) showed only partial inhibitory effects. CONCLUSIONS: Our data suggest a delta opioid receptor-mediated stimulatory effect on neutrophil function. beta-Endorphin(27-31), the C-terminal fragment of beta-endorphin(1-31), did not alter neutrophil function, indicating that beta-endorphin(1-31) mediates its effect on neutrophils via the N-terminal fragment. This study may contribute to a better understanding of neuroimmune interaction.

Temperature course and distribution during plasma heating with a microwave device.

In spite of the much shorter thawing times, the use of microwave devices for heating units of fresh frozen plasma is still being discussed. Concerns about general and localised overheating are the main arguments against the use of microwave devices. We evaluated the warming of fresh frozen plasma using the recently introduced Transfusio-therm 2000(R) microwave blood warmer. Units of fresh frozen plasma were weighed and the heating times were recorded. The surface temperature of the fresh frozen plasma bags during heating was recorded every 10 s. Temperature variation on the surface was examined by measuring the difference between peripheral and centrally placed temperature sensors. After heating, plasma temperature was determined using a calibrated thermometer. There were no signs of overheating during the heating process. The surface temperature of three units of fresh frozen plasma heated simultaneously (n = 45) was 34.0 degrees C (SD, 1.5 degrees C) after a mean heating time of 23.2 min (SD, 1.1 min). The mean (SD) temperature difference was -0.6 (0.5) degrees C and the mean (SD) plasma temperature was 33.6 (0.8) degrees C. Heating one fresh frozen plasma unit at a time (n = 20), the mean (SD) heating time was 6.3 (0.4) min. The surface temperature after heating was 34.3 (0.2) degrees C, the mean (SD) temperature difference was -0.6 (0.4) degrees C and the mean (SD) plasma temperature after heating 33.1 (0.6) degrees C. We conclude that no general or localised overheating of fresh frozen plasma occurs during or after heating with the microwave blood warmer.

Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function.

BACKGROUND: Local anesthetics inhibit migration, enzyme release and superoxide anion generation of polymorphonuclear leukocytes (PMN). Due to their ability to phagocytose and kill bacteria PMN represent a major defense mechanism in the circulating blood. In this study we determined the influence of racemic bupivacaine and its enantiomers on neutrophil phagocytic activity, oxidative burst as well as surface expression of complement and Fcgamma receptors. METHODS: Venous blood was pre-incubated with different concentrations of either racemic bupivacaine, R-(+) or S-(-) bupivacaine. Fluoresceine isothiocyanate (FITC)-labeled antibodies against Fcgamma receptor III (CD16), complement receptor 1 (CD35) and complement receptor 3 (CD11b) were used to determine surface receptor expression. Phagocytic activity was measured by ingestion of FITC-labeled vital Staphylococcus aureus. Oxidative burst was determined by conversion of nonfluorescent dihydrorhodamine 123 into fluorescent rhodamine 123. Fluorescent intensity of each sample was determined by flow cytometry. RESULTS: Racemic bupivacaine inhibited surface receptor expression, phagocytosis, and oxidative burst in a time- and concentration-dependent manner. Although the S-(-) enantiomer exerted significantly less inhibitory action on neutrophil function compared to R-(+) and racemic bupivacaine, these effects were small compared to the overall changes. CONCLUSION: These findings suggest that bupivacaine impairs surface receptor expression and may thereby contribute to reduced phagocytic activity and oxidative burst. Enantiomer-specific effects of bupivacaine may play a minor role in the inhibition of these leukocyte functions.

Morphine suppresses complement receptor expression, phagocytosis, and respiratory burst in neutrophils by a nitric oxide and mu(3) opiate receptor-dependent mechanism.

We investigated whether morphine and fentanyl influence surface receptor expression, phagocytic activity and superoxide anion generation of neutrophils in a whole blood flow cytometric assay. Morphine suppressed complement and Fcgamma receptor expression and neutrophil function in a concentration- and time-dependent manner. Morphine-induced changes were similar to those caused by the nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine and were abolished by preincubation with the NO synthase inhibitor N-nitro-L-arginine as well as naloxone. Fentanyl had no immunosuppressive effects. These results suggest that these neutrophil functions are inhibited by morphine-stimulated NO release mediated by the mu(3) opiate receptor subtype found on immunocytes.

Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism.

BACKGROUND: The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils. METHODS: The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used. RESULTS: Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release. CONCLUSION: Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.

[The effect of different volume expanders on neutrophil granulocyte function in vitro]. / Der Einfluss verschiedener Volumenersatzmittel auf die Funktion von neutrophilen Granulozyten in vitro.

INTRODUCTION: The influence of kolloids on the immune system is not well documented. In this study we investigated the effects of gelatine, hydroxyethylstarch (HES), human albumine, and dextrane on neutrophil function and receptor expression by flow cytometry. METHODS: Whole blood of healthy volunteers was incubated for 30 minutes with either gelatine, HES (6% and 10%), dextrane 40 and 60, or human albumin 20%. Phagocytic capacity was determined by uptake of fluorescein-isothiocyanate labeled bacteria, the conversion of dihydrorhodamine 123 into fluorescent rhodamine 123 was used for oxidative burst measurements. Expression of complement receptors CD 11b and CD35 was investigated using fluorescein-isothiocyanate labeled antibodies. RESULTS: Incubation with gelatine significantly increased expression of complement receptors and oxidative burst. Dextranes and HES had no influence on neutrophil function. Human albumin reduced the oxidative burst, whereas CD 35 expression was increased. CONCLUSION: The physiological significance of these changes in a range of 10% has to be clarified in further investigations.

Reduction of postoperative nausea and vomiting by dimenhydrinate suppositories after strabismus surgery in children.

UNLABELLED: Although dimenhydrinate has been used for treatment and prevention of postoperative nausea and vomiting (PONV) since the fifties, there have been few controlled studies about its efficacy. We performed a double-blinded study of 301 children aged 4 to 10 yr who underwent strabismus surgery. Preanesthetic medication with midazolam (0.5 mg/kg) as well as application of either dimenhydrinate suppositories or a placebo preparation was performed 30 min before the induction of anesthesia. Anesthesia was induced with thiopentone (5-10 mg/kg) and vecuronium (0.1 mg/kg) and maintained with halothane (1%-2%) in N(2)O/O(2) (65%/35%). The incidence of PONV, requirements for rescue dimenhydrinate, and time to recovery were recorded. The overall incidence of PONV was 60.1% in the placebo group and 30.7% in the dimenhydrinate group. In the dimenhydrinate group, children had to be observed in the recovery room significantly longer than those in the placebo group. Children having received dimenhydrinate were discharged from the recovery room with lower arousal scores. We conclude that the rectal administration of dimenhydrinate is effective for the prevention of PONV, although the sedative effect may require longer postoperative monitoring. IMPLICATIONS: We performed a double-blinded, randomized study to investigate the effects of prophylactic rectal dimenhydrinate application on postoperative nausea and vomiting in children undergoing strabismus surgery. In comparison with placebo, dimenhydrinate reduced the incidence of postoperative vomiting from 60.1% to 30.7%.