U. Grundmann

The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy.

In this prospective, double-blind, randomized, placebo-controlled study we compared the efficacy of three IV non-opioid analgesics for postoperative pain relief after lumbar microdiscectomy. Eighty healthy patients were randomly divided into 4 treatment groups (n = 20 each) to receive either parecoxib 40 mg, paracetamol 1 g, metamizol 1 g, or placebo IV 45 min before the end of surgery. In the postanesthesia care unit (PACU) patients were treated using patient-controlled analgesia (PCA) with piritramide. In the metamizol group the pain score at arrival in the PACU was significantly lower compared with the paracetamol, parecoxib, and placebo groups. In addition, in the metamizol group significantly fewer patients required additional PCA compared with the other groups studied. However, in those patients who required additional pain therapy in the four treatment groups, there was no significant difference in time to first request for piritramide and cumulative consumption of piritramide as assessed by the PCA data in the PACU. The incidence of adverse side effects was infrequent in all groups. These results suggest that in patients undergoing lumbar microdiscectomy, metamizol is superior to parecoxib, paracetamol, and placebo for immediate postoperative pain relief with minimal side effects.

Narcotrend index versus bispectral index as electroencephalogram measures of anesthetic drug effect during propofol anesthesia.

The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) performs an automatic analysis of the electroencephalogram (EEG) during anesthesia based on a visual assessment of the raw EEG. Its newest software version 4.0 includes a dimensionless index that, similar to the bispectral index (BIS), ranges from 100 (awake) to 0. We compared the performance of Narcotrend index and BIS as EEG measures of anesthetic drug effect during propofol anesthesia. Eighteen adult patients scheduled for radical prostatectomy were investigated. An epidural catheter was placed in the lumbar space and electrodes for BIS (version XP; Aspect Medical Systems, Natick, MA) and Narcotrend were positioned as recommended by the manufacturers. Narcotrend index, BIS values, and propofol plasma and effect site concentrations as parallelly simulated by Rugloop software (Department of Anesthesia, Ghent University, Belgium) were automatically recorded in intervals of 5 s. Induction of anesthesia consisted of a fentanyl bolus and a propofol infusion. After endotracheal intubation, patients received 15 mL bupivacaine 0.5% epidurally, and 45 min later propofol dosages were subsequently increased and decreased twice. Simulated propofol effect site concentrations ranged from 2.0 ± 0.4 &mgr;g/mL (smallest) to 6.3 ± 1.3 &mgr;g/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (PK) the performance of the Narcotrend index (PK = 0.88 ± 0.03) to predict propofol effect site concentrations was comparable to the BIS (PK = 0.85 ± 0.04). Using the respective EEG index as a measure of drug effect the mean ke0 was calculated as 0.20 ± 0.05 min−1 for Narcotrend index and 0.16 ± 0.07 min−1 for BIS. In the observed propofol concentration range Narcotrend index detected differences in EEG dynamics as well as BIS.

Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors.

Background The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide. Methods Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor &agr; (TNF-&agr;) and interleukin (IL)-1&bgr; and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose–response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-&agr; release were studied. Results Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th–75th percentile 9–42; IL-1ra: median 1,528 pg/ml, 25th–75th percentile 1,075–17,047;P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-&agr;: median 0 pg/ml, 25th–75th percentile 0–6; IL-1&bgr;: median 1 pg/ml, 25th–75th percentile 0–81; nonsignificant). Removal of plasma at T2 increased TNF-&agr; response to lipopolysaccharide (+83.8%;P < 0.05), whereas it suppressed IL-10 (−36.8%;P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-&agr; and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti–IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-&agr; response in vitro, their addition post-treatment failed to restore the monocytic TNF-&agr; response. Conclusions Plasma contains interacting factors that inhibit the release of TNF-&agr; and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-&agr; response.

Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass.

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-&agr; response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-&agr; upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-&agr; responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-&agr; response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.

Thoracic but not lumbar epidural anaesthesia increases liver blood flow after major abdominal surgery.

Background and objective Epidural blockade in major abdominal surgery bears the potential to increase gastrointestinal perfusion and thus to improve patient outcome. The aim of this study was to assess the differential influence of thoracic and lumbar epidural anaesthesia and analgesia (EAA) on blood lactate levels and central venous oxygen saturation (ScvO2) as parameters of global oxygen supply/demand ratio, as well as on the plasma disappearance rate of indocyanine green (PDRICG), a noninvasive method to evaluate liver perfusion. Methods We enrolled 17 patients receiving thoracic and 17 patients receiving lumbar EAA in addition to general anaesthesia for major abdominal surgery. Lactate, ScvO2 and PDRICG were measured postoperatively on the ICU. Subsequently, epidural application of local anaesthetics was started with a bolus of bupivacaine 0.25% (thoracic 10 ml, lumbar 12 ml) followed by continuous infusion of bupivacaine (thoracic 8 ml h−1 0.175%, lumbar 10 ml h−1 0.125%) and fentanyl (2 μg ml−1). Central venous pressure was maintained by titrated volume replacement. Lactate, ScvO2 and PDRICG were measured again after 2 h. Results In both the groups, the mean arterial pressure and heart rate as well as lactate levels and ScvO2 did not change significantly. Although there was a slight but not significant decrease of PDRICG in patients with lumbar EAA (from 25.9 ± 7.68 to 23.2 ± 5.90; NS), thoracic EAA resulted in a significant increase of PDRICG (from 21.3 ± 5.13 to 24.0 ± 6.66; P < 0.05) for the group mean, but with substantial variability in individual patients in the lumbar EAA group. Conclusion Liver perfusion was increased with thoracic but not lumbar EAA after major abdominal surgery in most patients. PDRICG allows assessment of individual changes of liver blood flow due to therapeutic intervention, for example, EAA.

Einfluss des Geschlechts auf den Verlauf der neuromuskulären Blockade nach Rocuronium

ZusammenfassungFragestellung. Die pharmakodynamische Wirkung zahlreicher Anästhetika und Adjuvanzien wird auch durch das Geschlecht der Patienten beeinflusst. Ziel der vorliegenden Studie war es zu untersuchen ob es zwischen männlichen und weiblichen Patienten Unterschiede im Verlauf der neuromuskulären Blockade von 0,45 mg/kg Rocuronium (1,5 × ED95) gibt. Methodik. Mittels Elektromyographie wurde an jeweils 20 weiblichen (Gruppe A) und 20 männlichen Patienten (Gruppe B) der zeitliche Verlauf der neuromuskulären Blockade und die maximale Muskelblockade nach 0,45 mg/kg Rocuronium untersucht. Ergebnisse. Die Patientinnen waren 38 (±8) Jahre, die Patienten 37 (±10) Jahre alt (n.s.). In Gruppe A betrug der body mass index (BMI) 24,2 (±2,9)kg/m2, in Gruppe B 25,2 (1,7) kg/m2; n.s. Die männlichen Patienten waren signifikant schwerer und größer als die weiblichen Patienten: 77,5 (±5,5) kg vs. 65,7 (±9,3) kg; p<0,01 und 178 (±6,8) cm vs. 164 (±6,7) cm; p<0,01. Verglichen mit den männlichen Patienten war die Anschlagzeit von Rocuronium bei den weiblichen Patienten im Mittel 43 s kürzer (211 (±56) s vs. 168 (±65) s, p<0,05). Das Ausmaß der maximalen Blockade nach 0,45 mg/kg Rocuronium betrug in Gruppe A 94 (±3)% (Spannbreite: 89%–100%); in Gruppe B hingegen war die maximale neuromuskuläre Blockade signifikant geringer ausgeprägt: 89 (±6)% (Spannbreite 74%–97%); (p<0,01). Die Wirkdauer war bei Frauen signifikant länger als bei Männer (23 (±5) min vs. 17 (±5) min, p<0,05); der Erholungsindex war hingegen in beiden Gruppen vergleichbar: 9 (±4) min vs. 9 (±3) min (n.s.); Tabelle 2. Schlussfolgerung. In der vorliegenden Untersuchung kam es nach 0,45 mg/kg Rocuronium bei Frauen zu einer deutlich ausgeprägteren neuromuskulären Blockade als bei Männern. Dies zeigte sich sowohl in einer größeren maximalen Muskelblockade als auch in einer kürzeren Anschlagzeit und einer längeren Wirkdauer.AbstractBackground. We studied 40 patients (20 female and 20 male) undergoing elective surgery under general anaesthesia to evaluate the effect of gender on the pharmacodynamics of rocuronium. Methods. Using electromyography (EMG) we determined the maximal neuromuscular block and time course of action of 0.45 mg/kg rocuronium (1.5×ED95). Results. Age and body mass index were comparable between females and males (38 (±8) vs. 37 (±10) years and 24.2 (±2.9) vs. 25.2 (±1.7) kg/m2. However, significant differences in weight and height were found between females and males (65.7±9.3 kg vs. 77.5±5.5 kg; p<0.01 and 178±6.8 cm vs. 164±6.7 cm; p<0,01). Onset time was shorter in females (168±65 s vs. 211±56 s; p<0.05). Maximal neuromuscular blockade after 0.45 mg/kg rocuronium was 94 (±3) % in females and 89 (±6) % in males; p<0.01. Clinical duration was increased in females (23±5 min vs. 17±5 min; p<0.05), while the recovery index was comparable between both groups (9±4 min in females and 9±3 min in males; n.s.). Conclusion. Compared to men neuromuscular blockade after 0.45 mg/kg rocuronium was more pronounced in women. The onset time was shortened and the clinical duration increased in female patients.

Comparative pharmacodynamic modeling using bispectral and narcotrend-index with and without a pharmacodynamic plateau during sevoflurane anesthesia.

BACKGROUND: We compared two pharmacodynamic models, one with and one without a plateau effect. Bispectral indices (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as an electroencephalographic measure of sevoflurane drug effect. In addition, we tried to analyze the origin of the plateau. METHODS: We investigated 26 adult patients scheduled for radical prostatectomy. At least 45 min after induction of general anesthesia, end-tidal sevoflurane concentrations were varied between 1 vol% and 4 vol%. To evaluate the relationship between concentrations and electroencephalographic indices, two different pharmacodynamic models were applied: a conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. RESULTS: The end-tidal sevoflurane concentration ranged from 1.04 ± 0.17 vol% to 4.43 ± 0.43 vol%. The difference between the log likelihood values of the new pharmacokinetic/pharmacodynamic model with two connected sigmoidal curves and the classical Emax model with one sigmoidal curve is 396 (P < 0.001) for the BIS monitor and 1121 (P < 0.001) for the NCT. The plateau is positioned at the change between the maximum &dgr; power and the increase of burst suppression ratio. CONCLUSION: A pharmacokinetic/pharmacodynamic model consisting of two sigmoid curves with an intervening plateau describes the effect of sevoflurane on BIS and NCT indices better than a model with a single sigmoid curve.

The Performance of Six Pulse Oximeters in the Environment of Neuronavigation

BACKGROUND: Although the use of pulse oximeters may be regarded a standard of care for monitoring anesthesia procedures, these monitors may be susceptible to various kinds of disturbances. Recently, it was suggested that neuronavigation equipment may interfere with pulse oximeter accuracy. In this study, we evaluated the effect of a neurosurgical image guidance system on the performance of six different pulse oximeters. Two simple shielding methods were evaluated. METHODS: Twenty healthy, adult, nonsmoking volunteers were equipped with six different pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen saturation, and signal quality were assessed. After activation of the Brain Lab VectorVision Neuronavigation System, the effects on signal quality and saturation recognition were evaluated. Measurements were repeated using two different shielding techniques, a cotton blanket and aluminum sheets. RESULTS: Activation of the image guidance system resulted in a significant disturbance of signal quality and saturation detection, which was partially reversible by both shielding techniques. Significant differences were noted among the six brands of pulse oximeters for signal quality (P < 0.001) and saturation recognition (P < 0.001), and for the response to shielding methods (P < 0.001). Coverage of the probes with aluminum foil resulted an in undisturbed saturation recognition in all subjects with almost all monitors. CONCLUSIONS: Infrared pulse waves from neurosurgical navigation equipment may interfere with pulse oximeter measurements. Shielding the probe with aluminum foil sufficiently eliminated the infrared interference.

Einfluss des Geschlechts auf die Intubationsbedingungen nach Rocuronium

PURPOSE There is increasing evidence for gender differences in the pharmacokinetics and pharmacodynamics of anaesthetic drugs and neuromuscular blocking agents, e.g. rocuronium (Roc). Females require 30% less Roc than males to achieve the same degree of neuromuscular block and onset times are shorter. However, whether this leads to an improvement of the intubation conditions in females is unclear. METHODS After approval of the ethics committee 60 female and 60 male patients were each randomised into 2 groups to receive 0.6 mg/kg body weight Roc or 1.0 mg/kg succinylcholine (Sux; control group). Induction: thiopentone (5 mg/kg), fentanyl (3 microg/kg) then Roc (Roc groups) or Sux (Sux groups) and tracheal intubation after 60 s. Time to intubation, glottic exposure and intubating conditions were assessed. RESULTS Men were significantly larger and heavier (p<0.001) than women, but the body mass index was comparable (ns). Number of attempts, time to intubation, and Cormack grades were comparable (ns). However, the rate of clinically acceptable intubation conditions was significantly higher in the female compared to the male Roc group: 80% vs 47%, p<0.05. The incidence of clinically acceptable intubation conditions in the female Roc and Sux groups were similar (80%). CONCLUSION The intubation conditions after Roc were significantly better in women than in men. The differences were Roc-related and did not occur in the control groups.

Procalcitonin nach extrakorporaler Zirkulation Synthese im Hepatosplanchnikusgebiet

Zusammenfassung Der Syntheseort für das inflammatorische Peptid Procalcitonin (PCT) ist bisher nicht bekannt. In der vorliegenden Studie wurde bei kardiochirurgischen Patienten nach Hinweisen für einen Syntheseort nach extrakorporaler Zirkulation (EKZ) gesucht. Methodik: Bei 20 Patienten, die sich einer operativen kardialen Revaskularisation mit EKZ unterzogen, wurde perioperativ zeitgleich PCT im arteriellen, lebervenösen und gemischtvenösen Blut bestimmt. Ergebnisse: PCT stieg bereits 4 Stunden postoperativ signifikant gegenüber den Ausgangswerten an (arteriell: 0,74±0,45 vs. 0,16±0,04 ng/ml), 18 Stunden postoperativ wurden die höchsten Serumkonzentrationen gemessen (arteriell: 1,44±1,01 ng/ml). Die lebervenösen PCT-Konzentrationen waren hierbei signifikant höher als die arteriellen (lebervenös: 1,67±1,29 ng/ml). Schlußfolgerung: Diese Studie gibt Hinweise auf einen Syntheseort für PCT im Hepatosplanchnikusgebiet. Ob eine gestörte Mukosabarriere mit konsekutiver Endotoxineinschwemmung oder die Zytokinantwort im Rahmen der inflammatorischen Reaktion nach EKZ zur PCT Induktion beitragen bleibt letztendlich ungeklärt.SummaryProcalcitonin (PCT) is an inflammatory peptide of still unknown origin. In this study we investigated a potential source for circulating PCT in patients undergoing coronary artery bypass grafting. Methods: To determine PCT concentrations, arterial, liver-venous and mixed-venous blood samples were collected time matched perioperatively in 20 patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB). Results: PCT concentrations significantly increased 4 hours postoperatively compared to baseline values (0,74±0,45 vs. 0,16±0,04 ng/ml). The highest concentrations were measured 18 hours postoperatively (1,44±1,01 ng/ml). PCT concentrations in liver venous samples were significantly higher (1,67±1,29 ng/ml) than in time matched collected arterial samples (1,44±1,01 ng/ml). Conclusion: These results provide evidence, that hepatosplanchnicus is a source for PCT synthesis in patients following CPB. The mechanism of PCT induction remains unclear. A loss of gut mucosal barrier function with translocation of endotoxins and the inflammatory response with release of cytokines following cardiopulmonary bypass has to be discussed.