Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves.

PURPOSE: Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China. METHODS: The Diprifusor™ TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C(p)) of propofol for the two groups was set at 1 µg·mL(-1) and increased by 1 µg·mL(-1) every minute to gradually reach 5 µg·mL(-1) after 5 min. The BIS values were fitted against the estimated C(p) and the predicted effect-site concentration (C(e)) in a sigmoid E(max) model. RESULTS: The sigmoid E(max) curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C(p) at loss of consciousness (LOC), predicted C(e) at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 µg·mL(-1), 1.6 ± 0.4 µg·mL(-1), 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 µg·mL(-1), 2.4 ± 1.5 µg·mL(-1), 3.9 ± 0.5 min, respectively; P < 0.0001). CONCLUSION: When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.

BIS-vista occipital montage in patients undergoing neurosurgical procedures during propofol-remifentanil anesthesia.

BACKGROUND: Neurosurgical procedures that require a frontal approach could be an impediment for a successful Bispectral Index (BIS) frontal sensor placement. The aim of this study was to explore the utility of using the new BIS-Vista monitor (Aspect Medical Systems, Newton, MA) for occipital sensor placement in the patients undergoing brain neurosurgical procedures during propofol-remifentanil anesthesia. METHODS: Two BIS Quatro sensors (Aspect Medical Systems, Newton, MA) mounted on the occipital and frontal regions were connected to two BIS-Vista monitors at three anesthesia states: before induction, during anesthesia maintenance, and recovery. RESULTS: There were significant differences before induction (P = 0.0002) and at anesthesia maintenance (P = 0.0014) between mean +/- SD occipital (83.4 +/- 4.8, 66.7 +/- 7.2) and frontal (93.1 +/- 3.4, 56.9 +/- 9.1) BIS-Vista values. During anesthesia recovery, there was no difference (P = 0.7421) between occipital (54.6 +/- 9.3) and frontal (53.1 +/- 7.3) BIS-Vista values. Bland and Altman analysis revealed a BIS-Vista negative-bias (limits of agreement) of -9.7 (+1.1, -20.5) before anesthesia induction, +9.8 positive-bias (+22.8, -1.7) during anesthesia maintenance, and -0.9 bias (+10.9, -12.8) during anesthesia recovery. CONCLUSION: We demonstrated that not only the regional limits of agreement are too wide to allow data of the two montages to be used interchangeably but also the variation is a function of anesthetic depth. However, keeping in mind a relatively consistent BIS-Vista -10 bias before induction and +10 bias during anesthesia maintenance with limits of agreement of approximately +/-11 BIS units, approximately double the clinically acceptable less than 10 BIS units level of agreement, BIS-Vista off-label occipital montage might be helpful in following a trend of propofol-remifentanil anesthesia in individual cases where frontal access is particularly difficult.

The patient with coronary stents and antiplatelet agents: what to do and how to deal?

The management of patients with recent coronary artery stents presenting for noncardiac surgery has become a major topic of interest and concern for all perioperative care givers. The present review will update recent reports and particularly new guidelines as well as recommendations. Based on the available literature, all experts recommend avoiding premature discontinuation of antiplatelet drug therapy if possible except for a few surgical procedures. Drug-eluting stents obviously carry more risks than bare-metal stents.

Premature preoperative discontinuation of antiplatelet drug therapy in cardiovascular risk patients: a preliminary study on the role of P2Y12 receptor monitoring.

BACKGROUND AND OBJECTIVE: In high-bleeding risk procedures, discontinuation of antiplatelet drug therapy with clopidogrel may be requested by surgeons, usually 7-10 days before the surgical procedure. New platelet function tests, such as the vasodilator-stimulated phosphoprotein phosphorylation assay, may help to assess the perioperative status of the clopidogrel-specific P2Y12 receptor. METHODS: Using vasodilator-stimulated phosphoprotein phosphorylation assay, the platelet reactivity index (PRI) was measured in 80 individuals, including 20 healthy volunteers, 20 cardiologic patients under full antiplatelet drug therapy with clopidogrel and aspirin, 20 surgical patients without any antiplatelet drugs and 20 patients under clopidogrel, discontinued 7 days before the surgical procedure. RESULTS: The mean PRI (95% confidence interval) in healthy volunteers was 86 (82-89%) and that in the surgical control group was 77% (72-81%). In cardiologic patients under full antiplatelet therapy, mean PRI was 51% (42-60%). In the clopidogrel discontinuation group, PRI increased from 51% (40-62%) on day 0 to 65% (57-74%) on day 3 and to 76% (69-84%) on day 5. On the morning of surgery, mean PRI was 85% (80-91%). The PRI values on the 5th day were equivalent to those of the surgical control group (mean difference -0.4%, 95% confidence interval -8.6% to 7.8%, P = 0.9). Fifty-five percent of the patients in the discontinuation group had a PRI of more than 50% on day 0. CONCLUSION: The study using vasodilator-stimulated phosphoprotein phosphorylation assay, one of the new platelet function assays for the assessment of inhibition of platelet P2Y12 receptor, demonstrates that the PRI on day 5 after discontinuation of clopidogrel is equivalent to a surgical control group and it questions the rigid practice of delaying surgery for 7-10 days, particularly in patients without a clopidogrel effect.

Effect of flumazenil on bispectral index monitoring in unpremedicated patients.

BACKGROUND: Flumazenil is an imidazobenzodiazepine that promptly reverses via competitive inhibition the hypnotic/sedative effects of benzodiazepines on gamma-aminobutyric acid receptors. Endogenous benzodiazepine ligands (endozepines) were isolated in urine, cerebrospinal fluid, and breast milk of women who had not received benzodiazepines. The bispectral index (BIS), an electroencephalographically derived parameter widely used for monitoring the effects of anesthetic/hypnotic drugs, was shown to correlate to various conditions that could influence electroencephalography. The authors examined the hypothesis that 0.5 mg of flumazenil administered to healthy unpremedicated patients during deep surgical remifentanil/propofol anesthesia would increase the BIS value and might expedite recovery from anesthesia. METHODS: Sixty healthy unpremedicated patients were randomly allocated to the flumazenil or control groups. After study drug administration, the authors compared BIS values and various recovery parameters in the flumazenil and control groups. RESULTS: BIS baseline values in the flumazenil group (38.7 +/- 3.8) increased 15 min after flumazenil administration (53.2 +/- 4.7), with a significant difference over time (P < 0.0001) between the two groups. Mean recovery parameters time, comprising time to spontaneous breathing, eye opening/hand squeezing on verbal command, extubation, and date of birth recollection, was significantly shorter (P = 0.0002) in the flumazenil group (6.9 +/- 2.6 min) compared with the control group (9.8 +/- 2.9 min). CONCLUSIONS: This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.

Bispectral index monitoring of a narcolepsy-cataplexy episode during regional anesthesia.

Narcolepsy or Gélineau syndrome is an extremely incapacitating chronic sleep disorder of unknown etiology that is characterized by uncontrollable attacks of deep sleep and is typically associated with cataplexy sudden loss of muscle tone. The Bispectral Index (BIS), an electroencephalographic-derived cerebral monitor, used for monitoring the effects of anesthetic/hypnotic drugs was shown to correlate to various conditions that could influence the eletroencephalogram. We assessed the utility of using BIS for monitoring a possible narcolepsy-cataplexy episode and whether a distinctive BIS profile might offer an early warning of an impending narcoleptic/cataplectic spell. We recorded both hemispheres, using two synchronized BIS-XP monitors, during a narcolepsy-cataplexy episode in a 57-yr-old male patient undergoing lower limb surgery under femoral nerve block regional anesthesia. The patient went through three stages: first a prodromal "intermittent low-vigilance" phase interrupted by high electromyographic activity. This was followed by a second "continuous low-vigilance" phase of BIS around 75 with low electromyographic activity, ending with a third "nonresponsive vigilance" phase of a full-blown narcolepsy-cataplexy episode of BIS around 45 with complete loss of muscle power. The purpose of presenting this report is to emphasize the fact that narcoleptic patients can still run the risk of loss of consciousness with atonia under regional anesthesia, and such an undesirable complication cannot be under-estimated. BIS monitoring is a simple method that could offer an early warning of an imminent episode, with its associated hazards, in patients with narcolepsy-cataplexy undergoing surgery under regional anesthesia.

The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia.

BACKGROUND: The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM. METHODS: Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 x 10(3) mm(-3), 50 x 10(3) mm(-3), and 100 x 10(3) mm(-3) and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted. RESULTS: Clot strength (MCE) decreased at a platelet count below 100 x 10(3) mm(-3), whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10(3) mm(-3). Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10(3) mm(-3)). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients. CONCLUSIONS: These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.

Gastrointestinal motility in acute illness.

Critical illness affects gastrointestinal motility - not only as a primary problem, which brings the patient to the intensive care unit (ICU), but also as a complication consecutive to the ICU stay. Motility disturbances may result from impaired function of gastrointestinal muscle, pacemaker cell function and nerve activity. The most important neural control system is the enteric nervous system that contains the largest collection of neurons (10(8) cells) outside the central nervous system. Through its organization it can operate independently of the brain and generate motility patterns according to need: a postprandial motility pattern starting after food intake, and an interdigestive motility pattern starting several hours after a meal. Undisturbed intestinal motility depends critically on a balanced interaction between inhibition and excitation, and a disturbance in this balance leads to severe derangements of intestinal motility. These motility disturbances differ in clinical appearance and location but can affect all parts of the gastrointestinal tract. This review focuses on select motility disturbances such as gastroparesis, postoperative ileus, and Ogilvie's syndrome. Generally effective methods to treat these conditions are given. Finally, we focus on special management options to prevent such motility disturbances or to reduce their severity.

Platelet Inhibition and Bleeding in Patients Undergoing Non-Cardiac Surgery-The BIANCA Observational Study.

Nearly 20% of patients will need non-cardiac surgery within 1 year of coronary stenting and their management is complicated by concomitant antiplatelet therapy. Platelet function testing may optimize the timing of surgery in these patients. In this prospective observational study, we explored the association between platelet reactivity and bleeding in patients undergoing non-cardiac surgery treated with clopidogrel with or without aspirin within 7 days before surgery. The timing of surgery was at the surgeon's discretion. Blood was drawn at induction of anaesthesia and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator stimulated phosphoprotein (VASP) assay, Multiplate Analyzer and Innovance PFA-200. The primary endpoint was surgery-related thrombolysis in myocardial infarction (TIMI) bleeding. Among 197 patients enrolled, 72 and 12% underwent surgery within 24 and 48 hours of the last dose of clopidogrel, respectively. The median (interquartile range [IQR]) for pre-operative maximal adenosine diphosphate (ADP)-induced aggregation was 33.0% (21.0-57.5%), for VASP-platelet reactivity index was 61.5% (40.1-75.4%), for Multiplate was 22.0 (14.5-36.0) U*min and for Innovance PFA-200 was 224 (101.0-300.0) seconds. TIMI bleeding, observed in 25% of patients, decreased with increasing tertiles of platelet reactivity to ADP assessed by LTA (p = 0.031). Additionally, in a multivariable logistic regression analysis, platelet reactivity to ADP assessed by LTA was significantly associated with TIMI bleeding, as were age and urgency of surgery. These results demonstrate that in clopidogrel-treated patients, pre-operative platelet reactivity to ADP is associated with surgical bleeding risk. An objective assessment of pre-operative platelet function may optimize the timing of non-cardiac surgery in these patients.

Intestinal motility disturbances in intensive care patients pathogenesis and clinical impact.

BACKGROUND: Gastrointestinal motility disturbances in critically ill patients are frequent in the ICU setting, causing considerable discomfort and are associated with increased rates of morbidity and mortality. This review focuses on the pathophysiological basis of intestinal motility, the major patterns of pathological motility alterations, the impact on patient outcome, and current therapeutic options. DISCUSSION: Intestinal motility is controlled by the enteric nervous system, modulated by hormones and extrinsic afferent and efferent neurons. Pathological motility disturbances can affect the stomach, small bowel, and colon separately or in combination. Changes in esophageal motor activity contribute to the aspiration of gastric juice, whereas early enteral feeding most frequently fails due to gastric intolerance. Disturbances in digestive and interdigestive motility patterns and the inability to switch motor activity from the interdigestive to the digestive pattern also contribute to feeding disability and thus to increased morbidity and mortality as well. CONCLUSIONS: The therapeutic options for motility disturbances in critically ill patients include the adjustment of electrolyte imbalances, tailored fluid management, early enteral feeding, appropriate management of catecholamines and drugs used for analgosedation, and prokinetic drugs. Unfortunately, the therapeutic options for treating motility disturbances in ICU patients are still limited. This situation requires careful assessment of ICU patients with respect to gut motility disturbances and their pathophysiological mechanisms and an individually tailored treatment to prevent further aggravation of existing motility disturbances.

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy.

INTRODUCTION: The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. MATERIALS AND METHODS: Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. RESULTS: No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 - 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. CONCLUSIONS: Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced.

Bispectral-index-guided versus clinically guided remifentanil/propofol analgesia/sedation for interventional radiological procedures: an observer-blinded randomized study.

Patients undergoing potentially painful interventional radiological procedures generally require a combination of analgesia and sedation. This sedation/analgesia should allow the patient to communicate while also remaining calm. Bispectral index (BIS) monitoring could be useful in achieving this. The primary end-point of our study was to compare the percentage time with optimal sedation, defined as Sedation Agitation Scale (SAS) grade 4, between a BIS-guided remifentanil/propofol regimen and a clinically guided regimen in 54 randomly allocated patients. The mean +/- sd percentage time with optimal sedation was significantly longer (P = 0.004) in the BIS group (76.6% +/- 14.7%) than in the SAS group (63.8% +/- 16.4%). There was a significant difference in the weighted mean infusion rates of remifentanil (P = 0.0067) and propofol (P = 0.0075) in the BIS group (0.066 +/- 0.027 microg.kg(-1) . min(-1) 1.59 +/- 0.44 mg.kg(-1) . h(-1)) compared with the SAS group (0.091 +/- 0.036 microg.kg(-1).min(-1) 1.92 +/- 0.43 mg.kg(-1).h(-1)), respectively. BIS values exhibited a temporal correlation to SAS scores (r2 = 0.72). In conclusion, a BIS-guided regimen was more effective than a SAS-guided regimen. The use of BIS resulted in fewer remifentanil and propofol doses. The targeted BIS range of 80-85 provided a sufficient functional level of sedation.

Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability.

Plaque destabilization leading to myocardial infarction is observed after surgery even if the intervention is of noncardiovascular nature. Mediators of peri- or postoperative stress responsible for such events could include catecholamines and lipopolysaccharide (LPS). Monocytes may be involved in destabilization of atherosclerotic plaques by production of matrix metalloproteinases (MMP). We examined whether catecholamines could affect the expression of MMPs in human monocytes/macrophages and whether catecholamines could modulate LPS-stimulated expression of particular MMPs in these cells. Epinephrine and norepinephrine up-regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral blood monocytes and monocyte-derived macrophages. We further characterized this effect employing the monocytic cell line U937 and showed that catecholamines potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA levels of the respective MMPs also increased. These effects did not result from higher mRNA stability but rather from increased transcription possibly induced by enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2-receptors. If this mechanism is also effective in vivo, our findings might, at least in part, help to explain the observation that cardiac events are important causes of morbidity and mortality after noncardiac surgery and support the findings that peri-operative beta-blockade has been shown to reduce postoperative mortality from cardiac events.

Contractile action of levosimendan and epinephrine during acidosis.

We evaluated the inotropic actions of levosimendan and epinephrine, both singly and in combination, under isohydric (pH 7.4) and acidotic (pH 7.0) conditions in isolated guinea-pig hearts. Acidosis depressed contractility and myocardial relaxation by 25-30%, and both inotropes were less efficacious at pH 7.0, while their potencies were unaffected. In combination experiments, the presence of levosimendan increased the potency of epinephrine approximately 17-fold (pH 7.4) and 11-fold (pH 7.0), and the presence of epinephrine increased the potency of levosimendan approximately 12-fold (pH 7.4) and approximately 21-fold (pH 7.0). At pH 7.0, both inotropes augmented papillary muscle contraction to a similar extent, but in contrast to epinephrine, levosimendan non-significantly [corrected] raised cAMP levels. In conclusion, combining levosimendan with epinephrine helps to overcome the depressed inotropic actions of epinephrine during acidosis, suggesting that additional studies which might justify clinical evaluation of the concurrent use of the two agents should be performed.

Urapidil reduces elevated pulmonary vascular resistance in patients before heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance is a major limitation for heart transplantation. Urapidil is a centrally and peripherally acting anti-hypertensive drug, able to decrease elevated pulmonary vascular resistance in patients with either chronic obstructive pulmonary disease or heart failure. Urapidil is available as an oral or intravenous drug. In this study, we evaluated the possible beneficial effects of intravenous urapidil in patients with reversible, elevated pulmonary vascular resistance who were scheduled for heart transplantation. METHODS: After approval by the Ethics Committee and written consent, 22 consecutive patients with end-stage heart failure and history of pulmonary vascular resistance >3 Wood units were enrolled into an open, prospective study. Using a (right ventricular ejection fraction) REF-Swan-Ganz catheter, hemodynamics were determined during administration of nitric oxide, and before and after 3 repeated intravenous applications of 10 mg urapidil. The treatment goal was reduction of pulmonary vascular resistance by at least 30%. RESULTS: Twenty-two patients were included to obtain complete data for 14 patients. Eight patients were not treated with urapidil: 7 patients had normal pulmonary vascular resistance at baseline, and 1 patient experienced moderate pulmonary edema before the study began. Two patients did not reach the treatment goal. In patients who responded to urapidil, the following hemodynamic changes were observed: decreased pulmonary vascular resistance (-48%), decreased transpulmonary gradient (20.0 to 13.7 mm Hg), decreased mean pulmonary arterial pressure (40 to 31 mm Hg), decreased systemic vascular resistance (-27%), mean arterial pressure (80 to 72 mm Hg), and increased right heart ejection fraction (21% to 27%). Heart rate remained unchanged. CONCLUSIONS: Intravenous urapidil lowered elevated pulmonary vascular resistance in patients before heart transplantation. In comparison with other vasodilative drugs, the major benefit of urapidil is its oral formulation.

Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine.

OBJECTIVE: Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis. DESIGN: In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory. INTERVENTIONS: Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine; inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath. MEASUREMENTS AND RESULTS: Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03-100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03-0.1 micro M), whereas concentrations >0.3 micro M inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1-0.3 micro M neostigmine. CONCLUSIONS: Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation.

[Periprocedual management of vitamin K antagonist's with low molecular weight heparins during invasive procedures--Consensus of experts]. / Niedermolekulare Heparine zur Überbrückung der Pause von Vitamin-K-Antagonisten während interventioneller Eingriffe ­ Expertenkonsensus.

Interruption of an ongoing therapy with vitamin K antagonists (VKAs) is necessary in almost all patients undergoing major surgery. The purpose of the following expert recommendations is to provide easy to use guidance for the periprocedural management of patients on VKAs based on current evidence from the literature. Management of anticoagulation during the time of interruption of VKAs is based on balancing the thromboembolic (TE) risk of underlying conditions against the bleeding risk of the surgical procedure. VKAs should be stopped 3­7days prior to surgery. Low molecular weight heparin (LMWH) is used to cover ("bridge") the progressive pre-operative loss of anticoagulation and the slow post-operative onset of anticoagulant activity of VKAs. Patients with high risk of TE should receive a therapeutic dose of LMWH, patients with a moderate risk of TE should receive half of this dose. Patients with a low risk of TE do not need bridging therapy with LMWH. In case of an uneventful postoperative course, patients with a therapeutic pre-operative dose should be treated post-operatively with the same dose, starting on day 4 in case of major surgery and on day 2 in case of minor procedures. Patients with a half-therapeutic preoperative dose should be treated post-operatively with the same dose, starting on day 3 in case of major surgery and on day 1 in case of minor procedures. Therapy with VKAs should be re-instituted on the second post-operative day based on the preoperative dosage. Procedure-related post-operative thromboprophylaxis should be given irrespective of these recommendations on days without "bridging" anticoagulation.

Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study.

BACKGROUND: Aspirin and clopidogrel therapy is associated with a variable bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the role of platelet function testing in clopidogrel-treated patients undergoing CABG. METHODS AND RESULTS: One hundred eighty patients on background aspirin with/without clopidogrel therapy undergoing elective first time isolated on-pump CABG were enrolled in a prospective single-center, nonrandomized, unblinded investigation (Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG] study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP-induced platelet-fibrin clot strength [MA(ADP)]) was determined by thrombelastography; CABG was done within 1 day, 3-5 days, and >5 days in patients with an MA(ADP) >50 mm, 35-50 mm, and <35 mm, respectively. The primary end point was 24-hour chest tube drainage and key secondary end point was total number of transfused red blood cells. Equivalence was defined as ≤25% difference between groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81-107%) of the amount observed in clopidogrel-naive patients, and the total amount of red blood cells transfused did not differ between groups (1.80 U versus 2.08 U, respectively, P=0.540). The total waiting period in clopidogrel-treated patients was 233 days (mean, 2.7 days per patient). CONCLUSIONS: A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and ≈50% shorter waiting time than recommended in the current guidelines. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00857155.