Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study).

OBJECTIVES: Dyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV-1-infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naïve HIV-1-infected patients) study compared prospectively ritonavir-boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed-dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV-naïve HIV-1-infected patients. Lipid profiles and CR from baseline to week 48 are reported. METHODS: Changes from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), TC:HDL-c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention-to-treat (ITT) with last observation carried forward (LOCF) for missing data. RESULTS: At week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P=0.038), HDL-c (9.7 vs. 3.9 mg/dL; P<0.0001), LDL-c (15.0 vs. 10.4 mg/dL; P=0.011) and ApoA1 (0.18 vs. 0.08 g/L; P<0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P=0.0001). Significantly greater mean decreases in TC:HDL-c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P=0.0001 and P=0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference -0.069; 95% confidence interval (CI) -0.61 to 0.46; P=0.80]. CONCLUSIONS: In ARV-naïve patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r.

[Pulmonary artery catheter in anaesthesiology and intensive care medicine]. / Pulmonalarterienkatheter: Einsatz in Anästhesie und Intensivmedizin.

The indication for the use of the pulmonary artery catheter (PAC) in high-risk patients is still a matter of discussion. Observational studies suggested that the use of the PAC did not result in decreased mortality but may even lead to increased mortality and morbidity. Therefore, a number of randomized controlled trials have been performed throughout recent years in patients suffering from sepsis/ARDS, congestive heart failure, multi-organ failure and those undergoing high-risk non-cardiac surgery. The majority of recent randomized studies failed to demonstrate any benefit of the PAC with respect to mortality and morbidity. However, the use of the PAC was also regularly not associated with an increase in morbidity and/or mortality. This review gives an overview of measurement parameters obtained by the current generation of PACs, alternatives to the PAC and recent studies on the use of the PAC in clinical practice.

[Preoperative long-term therapy]. / Präoperative Dauertherapie.

A large number of patients undergoing elective surgical procedures already take routine medication preoperatively. The majority of these patients use drugs for therapy of preexisting cardiovascular, pulmonary or endocrinological diseases which are independent of the planned surgical procedure. The number and type of preoperative drug therapy are correlated to age, gender and co-morbidity of the patients. Furthermore, patients with higher ASA-classes usually take more drugs, as they suffer from several medical diseases. Information about the perioperative handling of routine drug therapy is important for the planning of anaesthesia and surgery. A close cooperation of all medical specialities involved is necessary, in particular when patients take anticoagulants or other substances which should be withdrawn or replaced. This review focuses on the handling of routine preoperative medication by the anaesthesiologist in the light of available literature.

[The transillumination technique. An alternative to conventional intubation?]. / Die Transilluminationstechnik. Eine Alternative zur konventionellen Intubation?

The technique of light-guided intubation is based on the principle that a source of light brought into the trachea results in clearly visible and defined transcutaneous illumination, while no illumination can be observed with the light source in the oesophagus (Fig. 1-7). The Trachlight is a reintroduced instrument for this alternative intubation technique. The essential developments are: a length-adjustable stylet with a removable internal metal wire, a brighter light source, a stable handle with tight fixation of the endotracheal tube, and a time-dependent warning device to avoid extended intubations. One hundred twenty patients (Mallampati I. ASA I-III) were included in the study (conventional intubation [group KL, n = 60]. Trachlight intubation [group TT, n = 60]. The goals of the investigation were to examine the handling, application, problems, limitations, and possible indications of the method. The recorded parameters were: number of intubation attempts: course and duration of intubation; complications; and difficulties. In 40 patients (20 in each group) the indication for invasive blood pressure measurement was given due to the surgical procedure, and circulatory parameters were recorded at defined moments during the intubation course. In group KL 55 patients were intubated in the attempt, 4 on the second, and 1 on the third (mean duration 23.6 +/- 10.4 s, range 12-60 s). Complications were: unilateral intubation (3 patients), bradycardia (2), asystole (1) and soft-tissue injury (1). Of the 60 patients in group TT. 54 were intubated successfully, the mean time needed being 29.9 +/- 14.8 s (range: 6-61 s). The remaining 6 were then intubated by the conventional method. Positive results in group TT included: easy handling and application, no injury to soft tissues or teeth, and invariably correct placement of the tube. Problems included: sufficient transillumination was achieved only after (entire) dimming of the room, insufficient control over the distal end of the tube due to an unfixed metal wire, unintentional switching off of the light while with-drawing the metal wire, difficulties in withdrawing the metal wire (too strong fixation), as well as disturbing effects of the warning device (blinking of the light 30 s after switching on). Reasons for the 6 intubation failures were introduction of the instrument into the oesophagus despite a supposed correct position, impossibility of correct placement in a patient with an extremely large goiter, and insufficiently clear transillumination in 3 extremely obese patients. The cardiovascular parameters showed no changes during laryngeal manipulation; a clear rise in heart rate and blood pressure was recorded, however, when the tube was inserted into the trachea. The cardiovascular parameters during conventional intubations were similar. The light-guided intubation technique can be regarded as a further alternative for airway management, due to the described improvement of the instrument. The indication for the technique is given in patients in whom no difficulty with intubation is expected, to avoid soft tissue damage and traumatising temporomandibular joint movements. Preclinical use may be limited due to environmental brightness. In patients with expected difficult airway management, fiberoptic intubation will remain the method of choice.

Comparison of cisatracurium-induced neuromuscular block at the masseter and adductor pollicis muscle.

Adequate relaxation of the masseter muscle is important during endotracheal intubation and for the patency of a patient's airway during recovery from anaesthesia. We evaluated onset and recovery from cisatracurium-induced neuromuscular block at the masseter and adductor pollicis muscles. Thirty patients were randomly allocated to receive either 0.1 or 0.15 mg kg(-1) cisatracurium. The evoked response was measured at both muscles using acceleromyography. Onset time was significantly shorter at the masseter muscle than at the adductor pollicis (0.1 mg kg(-1) cisatracurium: 155+/-52 vs. 229+/-44 s; 0.15 mg kg(-1) cisatracurium: 105+/-24 vs. 174+/-35 s). Following 0.1 mg kg(-1) cisatracurium, recovery to a TOF-ratio of 0.7 was faster at the masseter compared to the adductor pollicis (P < 0.05). In the 0.15 mg kg(-1) cisatracurium group recovery of T1 to 75% of control and to a TOF-ratio of 0.7 occurred sooner at the masseter (P < 0.05). We conclude that onset and recovery from cisatracurium neuromuscular block occurs more rapidly at the masseter than at the adductor pollicis. It appears unlikely that residual paralysis is present at the masseter once neuromuscular function at the adductor pollicis has completely recovered.

[Cisatricurium in the orbicularis oculi muscle. Comparisn of the neuromuscular action of cisatracurium and atracurium in the orbicularis oculi muscle and the adductor pollicis muscle]. / Cisatracurium am M. orbicularis oculi. Vergleich der neuromuskulären Wirkung von Cisatracurium und Atracurium am M. orbicularis oculi und M. adductor pollicis.

OBJECTIVES: Muscle relaxants have different pharmacodynamic profiles in various muscles. Therefore, results obtained for one muscle cannot be extrapolated to other muscles. In the adductor pollicis muscle cisatracurium exerts a pharmacodynamic profile comparable to atracurium, despite the known difference in onset time. However, studies evaluating the neuromuscular effect of cisatracurium in different muscles are lacking. Accordingly, this study compares the pharmacodynamic profile of cisatracurium and atracurium in the orbicularis oculi muscle (OO) - which shows a neuromuscular course similar to the diaphragm and the laryngeal muscles - and the adductor pollicis muscle (AP). METHODS: Forty-five patients (ASA I-II), scheduled for elective spinal surgery were anaesthetized with propofol and fentanyl. Endotracheal intubation was performed without using a muscle relaxant. Neuromuscular transmission was monitored using acceleromyography in both muscles. Patients received 0.1 mg/kg (2x ED(95)) or 0.15 mg/kg (3x ED(95)) cisatracurium, or 0.5 mg/kg atracurium (2x ED(95)) at random. Onset and recovery times were measured according to the recommendation of the Copenhagen Consensus Conference. RESULTS: Onset time was significantly shorter in the OO than in the AP following 0.15 mg/kg cisatracurium and 0.5 mg/kg atracurium (P<0.05). No differences in onset time between the two muscles were found after 0.1 mg/kg cisatracurium. The recovery of T(1) to 10% of its control was completed sooner in the OO than in the AP in all three groups (P<0.05). CONCLUSIONS: Cisatracurium shows a dose-dependent shorter onset time in the OO than in the AP. This is consistent with the current view that the onset of non-depolarizing neuromuscular blockers is more rapid in the OO than in the AP. However, at least a dose of 3x ED(95) of cisatracurium was necessary to show a difference in onset time between both muscles. In contrast, atracurium is reported to lead to a significantly shorter onset of neuromuscular block in the OO following 2x the ED(95). The more rapid recovery of T(1) to 10% of its control in all three groups in the OO is due to the relative resistance of this muscle to muscle relaxants.

Effect of isoflurane on monocyte adhesion molecule expression in human whole blood.

BACKGROUND: Recruitment of monocytes to inflamed tissue is a crucial step in the acute inflammatory reaction. Adherence of monocytes to endothelial cells followed by transmigration depends on monocyte surface adhesion molecules, inflammatory cytokines and chemoattractant chemokines. In the present study, we determined the effect of isoflurane on monocyte adhesion receptor expression in vitro. METHODS: Citrated whole blood was incubated for 60 min with either 0.5 or 1 MAC isoflurane. In unstimulated blood samples and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) monocyte cell-surface expression of the selectins PSGL-1 and L-selectin, and the beta2-integrins CD11a and CD11b were evaluated by flow cytometry. RESULTS: Isoflurane reduced significantly the expression of PSGL-1 on unstimulated monocytes, whereas the remaining selectins and beta2-integrins were not affected. At both concentrations, the FMLP-induced removal of PSGL-1 from the monocyte surface was increased. Furthermore, at 1 MAC isoflurane the FMLP-induced increase in CD11a expression was significantly inhibited. The surface expression of L-selectin and CD11b was not affected following exposure to isoflurane. CONCLUSION: Isoflurane increases the removal of the selectin PSGL-1 from the monocyte surface. Since PSGL-1 is important during the initial step of monocyte adhesion to endothelial P-selectin, the decrease in monocyte surface PSGL-1 may have profound effects on monocyte-endothelial interactions. Furthermore, the effects of isoflurane on monocyte adhesion molecule expression are different from those reported for neutrophils.

Onset of neuromuscular block at the masseter and adductor pollicis muscles following rocuronium or succinylcholine.

PURPOSE: To compare the onset time of two different rocuronium doses (0.6 and 0.9 mg x kg(-1)) and succinylcholine (1.5 mg x kg(-1), preceeded by 0.06 mg x kg(-1) rocuronium) at the masseter and the adductor pollicis muscle. METHODS: In a randomized study, 60 ASA I or II adult women, 18-65 yr of age, were anesthetized with propofol and fentanyl and nitrous oxide in oxygen. Neuromuscular monitoring was performed using acceleromyography simultaneously on the masseter and adductor pollicis. Onset time was measured at both muscles using supramaximal 0.1 Hz single twitch stimulation (square-wave pulse 0.2 msec duration). RESULTS: In all patients, complete neuromuscular block occurred at the masseter and adductor pollicis muscles. Lag-time and onset time were faster at the masseter that at the adductor pollicis muscle in both rocuronium-groups (P < 0.01) and in the succinylcholine-group (P < 0.01). Furthermore, onset time was more rapid after 0.9 mg x kg(-1) rocuronium (65 +/- 7 s) than after succinylcholine (83 +/- 19 sec) at the AP (P < 0.05), but did not differ at the masseter (33 +/- 6 vs 36 +/- 7 sec). CONCLUSIONS: Following rocuronium and succinylcholine, onset time is faster at the masseter than at the adductor pollicis muscle.

The effects of sevoflurane and desflurane in vitro on platelet-leukocyte adhesion in whole blood.

The interaction between platelets and leukocytes plays an important role in inflammatory and thrombotic processes. We investigated whether the volatile anaesthetics sevoflurane and desflurane alter the formation of platelet-leukocyte aggregates and the expression of P-selectin on platelets. Whole blood was incubated with 1 and 2 minimum alveolar concentration (MAC) sevoflurane or desflurane. Unstimulated and adenosine diphosphate, or thrombin receptor agonist peptide-6-stimulated samples were stained with fluorochrome-conjugated antibodies. The formation of platelet-leukocyte conjugates and the expression of P-selectin on platelets were measured using flow cytometry. Sevoflurane was found to enhance the binding of platelets to lymphocytes, neutrophils and monocytes, it also increased the expression of P-selectin on platelets especially in the stimulated samples. Desflurane decreased the percentage of lymphocyte-platelet, neutrophil-platelet and monocyte-platelet conjugates principally in unstimulated samples. The results show that these two volatile anaesthetics have differing effects on the formation of platelet-leukocyte conjugates in vitro. Sevoflurane also enhanced the expression of P-selectin on platelets.

Xenon modulates neutrophil adhesion molecule expression in vitro.

BACKGROUND AND OBJECTIVE: Xenon reduces the infarct size after regional ischaemia in the rabbit heart in vivo, but the underlying mechanisms are unknown. Since adhesion molecules on neutrophils are closely involved in the pathophysiology of ischaemia/reperfusion injury and modulation of neutrophil function, we investigated the effect of xenon on neutrophil adhesion molecule expression in vitro. METHODS: Freshly isolated neutrophils were incubated with 30% or 60% xenon for 60 min. In unstimulated and after stimulation with either N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate neutrophil surface expression of PSGL-1, L-selectin, CD11a and CD11b were measured by flow cytometry. RESULTS: At both concentrations, xenon reduced the surface expression of PSGL-1 by 10% (P < 0.05), and of L-selectin by 15% (P < 0.05) in the 60% xenon group. Furthermore, N-formyl-methionyl-leucyl-phenylalanine activated neutrophils showed an increased removal of L-selectin from the neutrophil surface following incubation with xenon (30% compared to controls, P < 0.05). Neutrophil beta2-integrin expression was not altered by xenon. CONCLUSIONS: Xenon increases the removal of the selectins PSGL-1 and L-selectin from the neutrophil surface in vitro. Since both selectins are involved in the initial contact between neutrophils and endothelial cells, xenon may affect neutrophil adhesion to endothelium during ischaemia/reperfusion injury. However, because the beta2-integrin expression was unaffected by xenon, further investigations are required to clarify whether xenon may modulate neutrophil transmigration through endothelial cells in vivo.

Xenon does not affect human platelet function in vitro.

We sought to determine whether xenon affects platelet glycoprotein expression and platelet-related hemostasis in vitro at a clinically relevant concentration. Human whole blood was stimulated with either adenosine diphosphate or the thrombin receptor agonist peptide (TRAP)-6 after incubation with 65% xenon. Halothane at 2 minimum alveolar anesthetic concentration was used as a positive control. Platelet function and activation were evaluated with two-color flow cytometry. The expression of the platelet glycoproteins GPIIb/IIIa, GPIb, and P selectin were detected with fluorochrome-conjugated monoclonal antibodies. In vitro measurement of platelet-related hemostasis under conditions of high shear stress was performed in citrated whole blood with a platelet function analyzer (PFA-100((R))) by using collagen/epinephrine and collagen/adenosine diphosphate cartridges. Xenon did not affect basal or agonist-induced expression of platelet membrane glycoproteins, activation-dependent conformational changes of the GPIIb/IIIa receptor, expression of P selectin, or PFA closure times. In contrast, halothane reduced TRAP-6-induced activation of the GPIIb/IIIa complex. Furthermore, collagen/epinephrine-induced PFA closure time was significantly prolonged. These results demonstrate that xenon does not affect the unstimulated or agonist-induced platelet glycoprotein expression, activation of GPIIb/IIIa, or platelet-related hemostasis.

Sevoflurane inhibits unstimulated and agonist-induced platelet antigen expression and platelet function in whole blood in vitro.

BACKGROUND: Previous studies have reported conflicting results about the effect of sevoflurane on platelet aggregation. To clarify this point, we investigated the effects of sevoflurane on platelet antigen expression and function in vitro. METHODS: Human whole blood was incubated for 1 h with 0.5 and 1 minimum alveolar concentration sevoflurane, 21% O(2), and 5% CO(2). A control sample was kept at the same conditions without sevoflurane. After stimulation with adenosine diphosphate or thrombin receptor agonist peptide 6, samples were stained with fluorochrome conjugated antibodies, and the expression of platelet glycoproteins GPIIb/IIIa, GPIb, and P-selectin, as well as activated GPIIb/IIIa, were measured with two-color flow cytometry. In addition, platelet function was assessed by means of thromboelastography and using the platelet function analyzer 100. RESULTS: Already in subanesthetic concentrations, sevoflurane inhibits unstimulated and agonist-induced GPIIb/IIIa surface expression and activated GPIIb/IIIa expression on platelets in whole blood. The agonist-induced redistribution of GPIb into the open canalicular system was also impaired by sevoflurane, whereas no effect on P-selectin expression in activated platelets could be found. Sevoflurane significantly reduced the maximum thromboelastographic amplitude. Furthermore, platelet function analyzer 100 closure times were significantly prolonged. CONCLUSION: The results show that sevoflurane significantly impairs platelet antigen expression in vitro. It is especially the inhibition of GPIIb/IIIa expression and activation that impairs bleeding time as reflected in thromboelastographic measurements and platelet function analyzer 100 closure times. The exact inhibitory mechanism remains unclear.