C Diefenbach

University of Cologne, Köln, North Rhine-Westphalia, Germany

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Publications (62)116.35 Total impact

  • European Journal of Anaesthesiology 01/2001; 18. DOI:10.1097/00003643-200100001-00093 · 3.01 Impact Factor
  • Hermann Mellinghoff, Mahir Uslu, Christoph Diefenbach, Thomas Meuser
    Anesthesiology 01/2000; 93(Supplement):A-1022. DOI:10.1097/00000542-200009001-01022 · 6.17 Impact Factor
  • Anesthesiology 01/2000; 93(Supplement):A-60. DOI:10.1097/00000542-200009001-00060 · 6.17 Impact Factor
  • M Uslu, H Mellinghoff, C Diefenbach
    Anesthesia & Analgesia 09/1999; 89(2):340-1. · 3.42 Impact Factor
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    Mahir Uslu, Hermann Mellinghoff, Christoph Diefenbach
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    ABSTRACT: n a 5-yr-old boy with Duchenne's muscular dystro- phy (DMD), the repeated administration of miva- curium 0.13 mg/kg was associated with a normal dose-response relationship and time from end of in- jection to twitch recovery to 25% of control (DUR25%) and a twofold normal recovery index (time from 25% to 75% recovery). There was no difference between electromyogram (EMG) and mechanical twitch ten- sion recording. Thus, the characteristics of mivacu- rium neuromuscular block in patients with DMD may be more favorable than those of atracurium and vecu- ronium previously reported in the literature. In patients with Duchenne's muscular dystrophy (DMD), after atracurium and vecuronium, the recovery from neuromuscular block is 3-6 times longer than that in healthy individuals (1,2). Similar results in patients with dystrophia myotonica led to the recommendation to use the shortest acting nondepolarizing muscle relax- ant available (3). Mivacurium is the shortest acting non- depolarizing muscle relaxant in current clinical use. There has been no account in the literature of its use in patients with DMD. We describe a patient with DMD in whom mivacurium was used for muscle relaxation mon- itored by simultaneous recording of the evoked twitch tension and the evoked compound EMG.
    Anesthesia & Analgesia 08/1999; 89(2):340-341. DOI:10.1097/00000539-199908000-00017 · 3.42 Impact Factor
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    ABSTRACT: 1. Pseudocholinesterase (ChE) activity is a determinant of the elimination kinetics of several drugs used in anesthesia. The time course of ChE activity was investigated in 16 patients undergoing cardiosurgery for a cardiopulmonary bypass (CPB) in normothermia or hypothermia. 2. The onset of the CPB was accompanied by a decrease in ChE activity (-37%) (P<0.05) and protein concentration (-24%) (P<0.05). The quotient ChE activity/protein concentration was numerically reduced to a smaller extent (-15%) (P>0.05). After the CPB was finished, ChE activity and the protein concentration remained low for the remaining operation time. 3. There was no difference in ChE activity, measured in vitro at 37 degrees C, between the normothermic and hypothermic group (P>0.05). 4. There was no correlation between heparin concentration in serum and reduction of ChE activity in vitro (P>0.05). In vitro, the ChE activity was not affected by either heparin in doses as high as 10,000 U/ml or aprotinin in doses as high as 10,000 U/ml (P>0.05). 5. CONCLUSIONS: (1) ChE activity is reduced by CPB mainly by hemodilution and (2) the pharmacological agents used in the present anesthetic technique (heparin, aprotinin, midazolam, fentanyl, propofol and mivacurium) do not inhibit ChE activity at therapeutic serum concentrations.
    General Pharmacology 01/1999; 32(1):65-9.
  • Anesthesia & Analgesia 01/1999; 88. DOI:10.1097/00000539-199902001-00359 · 3.42 Impact Factor
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    ABSTRACT: 1.Pseudocholinesterase (ChE) activity is a determinant of the elimination kinetics of several drugs used in anesthesia. The time course of ChE activity was investigated in 16 patients under-going cardiosurgery for a cardiopulmonary bypass (CPB) in normothermia or hypothermia.2.The onset of the CPB was accompanied by a decrease in ChE activity (−37%) (P0.05).4.There was no correlation between heparin concentration in serum and reduction of ChE activity in vitro (P>0.05). In vitro, the ChE activity was not affected by either heparin in doses as high as 10,000 U/ml or aprotinin in doses as high as 10,000 U/ml (P>0.05).5.Conclusions: (1) ChE activity is reduced by CPB mainly by hemodilution and (2) the pharmacological agents used in the present anesthetic technique (heparin, aprotinin, midazolam, fentanyl, propofol and mivacurium) do not inhibit ChE activity at therapeutic serum concentrations.
    General Pharmacology 01/1999; 32(1). DOI:10.1016/S0306-3623(98)00072-X
  • C Diefenbach
    Der Anaesthesist 10/1997; 46(9):807. · 0.74 Impact Factor
  • Hermann Mellinghoff, Christoph Diefenbach, Ulf Börner
    Seminars in Anesthesia Perioperative Medicine and Pain 09/1997; 16(3):197-205. DOI:10.1016/S0277-0326(97)80032-3
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    ABSTRACT: The colloid osmotic pressure (COP) is not routinely assessed during pediatric heart surgery. Two cases of unrecognized hyperoncotic states associated with renal failure have been observed after pediatric heart surgery. We studied the hypothesis that the COP cannot be estimated from the total plasma protein (TPP) or albumin level. The course of COP and its correlation to the TPP and albumin level were investigated in 25 children undergoing elective heart surgery. Infusion therapy was performed solely on the basis of clinical parameters and TPP/albumin levels. COP values were determined in a blinded fashion at the end of the study. No correlation between TPP/albumin and the COP could be determined preoperatively. On arrival at the ICU correlation was strong. A weak correlation was observed at 24 hours and 48 hours after surgery. However, the observed wide range of the confidential bands indicates that the COP cannot be estimated correctly, neither from the TPP, nor from the albumin level. Due to colloidal oversubstitution COP was significantly increased compared to preoperative level at 48 hrs following surgery. As estimation of COP from TPP or albumin level is inaccurate, oncometry should be performed during pediatric heart surgery.
    The Journal of cardiovascular surgery 07/1997; 38(3):249-55. · 1.37 Impact Factor
  • H. Mellinghoff, C. Diefenbach
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    ABSTRACT: Atracurium ist ein Razemat aus zehn Stereoisomeren, von denen Cisatracurium (51W89) 15% ausmacht. Für Cisatracurium (Kation, MG 929) wurde eine ED95 von 50 μg/kg ermittelt. Die ED95 von Atracurium (Besylat, MG 1245) ist 250 μg/kg. Damit hat Cisatracurium auf der Basis molarer Äquivalenz bei erwachsenen Patienten eine etwa 3,5mal stärkere neuromuskulär blockierende Wirkung als Atracurium. Wir verglichen Atracurium mit Cisatracurium und konnten keinen wesentlichen Unterschied in der Pharmakodynamik beider Substanzen feststellen. Altersunterschiede und Vorerkrankungen: Bei Kindern beträgt die ED95 von Cisatracurium 40 μg/kg. Bei älteren Patienten wurde eine gegenüber jüngeren gering verzögerte Anschlagszeit von Cisatracurium gemessen. Chronisches Nierenversagen verlängerte die Wirkung von Cisatracurium nicht. Die Erholung der neuromuskulären Übertragung nach einer Cisatracurium-Infusion von bis zu 145 h bei Intensivpatienten war nur etwa 70% länger als nach etwa 2 h Infusionsdauer bei gesunden chirurgischen Patienten. Nebenwirkungen: Nach Bolusinjektion bis zur 8fachen ED95 Cisatracurium wurden weder kardiovaskuläre Nebenwirkungen noch ein klinisch relevanter oder dosisabhängiger Anstieg des Plasmahistaminspiegels gemessen noch wurde ein Flush beobachtet. Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 μg/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 μg/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 μg/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio >0.7 (68±18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.
    Der Anaesthesist 06/1997; 46(6):481-485. DOI:10.1007/s001010050427 · 0.74 Impact Factor
  • H Mellinghoff, C Diefenbach
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    ABSTRACT: Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.
    Der Anaesthesist 06/1997; 46(6):481-5. · 0.74 Impact Factor
  • C Diefenbach, H Mellinghoff
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    ABSTRACT: Mivacurium is a short-acting, nondepolarising muscle relaxant of the benzylisoquinoline type that undergoes rapid breakdown by plasma cholinesterase. After 2.5 times the ED95 (0.2 mg/kg), tracheal intubation can be accomplished within 2-3 min following injection. The ensuing DUR 25% (i.e., time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to moderate histamine release following doses 3-4 times the ED95. In patients with end-stage liver or renal disease as well as those with atypical plasma cholinesterase, the duration of action of mivacurium is prolonged.
    Der Anaesthesist 06/1997; 46(5):385-8. · 0.74 Impact Factor
  • V Nigrovic, C Diefenbach, H Mellinghoff
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    ABSTRACT: This review discusses concepts of isomers, stereoisomers, chirality, and enantiomers as applied to drugs used in anaesthesia. The inhalational anaesthetics enflurane and isoflurane are examples of stereoisomers. A chiral centre is formed when a carbon or quaternary nitrogen atom is connected to four different atoms. A molecule with one chiral centre is then present in one of two possible configurations termed enantiomers. A racemate is a mixture of both enantiomers in equal proportions. Many of the drugs used in anaesthesia are racemic mixtures (the inhalation anaesthetics, local anaesthetics, ketamine, and others). The shape of the atracurium molecule is comparable to that of a dumb-bell:the two isoquinoline groups representing the two bulky ends connected by an aliphatic chain. In each isoquinoline group there are two chiral centres, one formed by a carbon and the other by a quaternary nitrogen atom. From a geometric point of view, the connections from the carbon atom to a substituted benzene ring and from the quaternary nitrogen to the aliphatic chain may point in the same direction (cis configuration) or in opposite directions (trans configuration). The two isoquinoline groups in atracurium are paired in three geometric configurations: cis-cis, trans-trans, or cis-trans. However, the two chiral centres allow each isoquinoline group to exist in one of four stereoisometric configurations. In the symmetrical atracurium molecule, the number of possible stereoisomers is limited to ten. Among these, 1 R-cis, 1'R-cis atracurium was isolated and its pharmacologic properties studied. This isomer, named cis-atracurium, offers clinical advantages over the atracurium mixture, principally due to the lack of histamine-releasing propensity and the higher neuromuscular blocking potency. The ester groups appear in one of two steric configurations true and reverse esters. In the true esters, oxygen is positioned between the nitrogen atom and the carbonyl group, while in the reverse esters in its positioned on the other side of the carbonyl group. True esters, suxamethonium and mivacurium, are hydrolysed by the enzyme plasma cholinesterase (butyrylcholinesterase), albeit at different rates. The more rapid degradation of suxamethonium is responsible for its fast onset and short duration of action in comparison with mivacurium. The reverse esters, atracurium, cisatracurium, and remifentanil, are hydrolysed by nonspecific esterases in plasma (carboxyesterases). Remifentanil is hydrolysed rapidly; the degradation leads to its inactivation and short duration of action. Cis-atracurium is preferentially degraded and inactivated by a process known as Hofmann elimination. In a second step, one of the degradation products, the monoester acrylate, is hydrolysed by a nonspecific esterase.
    Der Anaesthesist 05/1997; 46(4):282-6. · 0.74 Impact Factor
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    ABSTRACT: INTRODUCTION: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards. MUSCLE RELAXANTS: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90 s. Slight vagolytic effects were reported following injection of 0.6 mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid break-down by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.
    Der Anaesthesist 02/1997; 46(1):3-13. · 0.74 Impact Factor
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    ABSTRACT: The aim of this study was to develop a pharmacodynamic model for nondepolarizing muscle relaxants (neuromuscular blocking agents, NMBAs) based on anatomical, physiological, and pharmacological considerations and analyse whether the time to onset of the submaximal neuromuscular block (NMB) depends on the affinities of the NMBAs for the postsynaptic receptors or on the pharmacokinetic properties of the NMBAs. A quantitative description of the development of neuromuscular block was achieved by formulating a pharmacodynamic model based on anatomical, physiological and pharmacological considerations. The principal characteristics of the model are: (1) Diffusion of the NMBAs out of the capillaries into the interstitial space of muscle and from there into the synaptic space of the motor end plates (2) Receptor concentration in the synaptic space of 300 microM and the total amount of receptors in 100 g muscle of between 1.43 x (10(-11) to 10(-10) mol. (3) Interaction of NMBAs with the receptors defined by the association (k(assoc) = 4 x 10(8) min-1 x M-1) and dissociation (k(dissoc) one of 4, 40, or 400 min-1) rate constants. The simulations demonstrated that different affinities of the NMBAs for the postsynaptic receptors (defined by k(assoc)/k(dissoc)) do not influence the onset of the submaximal NMB. On the other hand, the time to the peak submaximal NMB is dependent on the pharmacokinetic properties of the drugs: Those NMBAs that leave plasma rapidly produce the block faster but the fraction of the dose that contributes to the block is small. This fraction is larger for those NMBAs that produce NMB later and, hence, these NMBAs require smaller equieffective doses. We conclude that those muscle relaxants that produce neuromuscular block rapidly require larger equieffective doses due to their more rapid initial disappearance from plasma.
    British Journal of Clinical Pharmacology 02/1997; 43(1):55-63. DOI:10.1111/j.1365-2125.1997.tb00033.x · 3.69 Impact Factor
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    ABSTRACT: Zusammenfassung Einführung: In einer Übersicht werden die aktuellen Entwicklungen in der Messung der neuromuskulären Blockade sowie die neuen Muskelrelaxanzien dargestellt. Muskelrelaxanzien: Von den seit 1995/96 in Deutschland neu zugelassenen Muskelrelaxanzien Rocuronium, Cisatracurium und Mivacurium, bietet Rocuronium die kürzeste Anschlagszeit bei ansonsten gleichem neuromuskulär blockierenden Wirkprofil wie Vecuronium. Die 2fache ED95 führt innerhalb von 60 bis 90 s zu guten bis sehr guten Intubationsbedingungen. Cisatracurium ist eines der zehn Isomere von Atracurium mit etwa der fünffachen neuromuskulär blockierenden Potenz. Unter Bewahrung der atracuriumtypischen mittellangen Wirkdauer und der Metabolisierung durch den Hofmann-Abbau, zeichnet sich Cisatracurium durch eine sehr viel geringere unspezifische Histaminfreisetzung aus. Mivacurium ist ein kurzwirkendes Benzylisochinolin-Muskelrelaxans, das einer raschen enzymatischen Inaktivierung durch die Plasmacholinesterase unterliegt. Es füllt die pharmakodynamische Lücke zwischen Succinylcholin und den mittellang wirkenden Muskelrelaxanzien, ohne jedoch den kurzen Wirkungseintritt von Rocuronium oder Succinylcholin zu erreichen. Nachteilig sind die mögliche Histaminfreisetzung und die Wirkungsverlängerung bei verminderter bzw. atypischer Plasmacholinesterase.
    Der Anaesthesist 01/1997; 46(1):3-13. DOI:10.1007/s001010050364 · 0.74 Impact Factor
  • C. Diefenbach, H. Mellinghoff
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    ABSTRACT: Mivacurium ist das erste für die klinische Anwendung zugelassene kurzwirkende nicht depolarisierende Muskelrelaxans. Seine Benzylisochinolinstruktur wird durch die Plasmacholinesterase gespalten und die neuromuskulär blockierende Wirkung der Substanz beendet. Pharmakologie: Die klinische Wirkdauer einer Intubationsdosis von 0,2 mg/kg Mivacurium (2,5fache ED95) ist mit 15 bis 20 min etwa dreimal so lang wie die von Succinylcholin. Der Erholungsindex (Zeit von 25% bis 75% Erholung) von Mivacurium ist mit 5 bis 7 min sehr kurz und unabhängig von der verwendeten Gesamtdosis. Bei rascher Injektion von Mivacurium wurden Hautrötungen und Blutdrucksenkungen um ca. 10 bis 20% des Ausgangswerts als Zeichen einer Histaminfreisetzung beobachtet. Bei verminderter Aktivität der Plasmacholinesterase ist die Wirkung von Mivacurium verlängert. Anwendungsschwerpunkte von Mivacurium sind Eingriffe von ca. 15 bis 60 min Dauer. Mivacurium is a short-acting, nondepolarising muscle relaxant of the benzylisoquinoline type that undergoes rapid breakdown by plasma cholinesterase. After 2.5 times the ED95 (0.2 mg/kg), tracheal intubation can be accomplished within 2–3 min following injection. The ensuing DUR 25% (i.e., time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to moderate histamine release following doses 3–4 times the ED95. In patients with end-stage liver or renal disease as well as those with atypical plasma cholinesterase, the duration of action of mivacurium is prolonged
    Der Anaesthesist 01/1997; 46(5):385-388. DOI:10.1007/s001010050414 · 0.74 Impact Factor
  • V. Nigrovic, C. Diefenbach, H. Mellinghoff
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    ABSTRACT: Zusammenfassung Isomere: Die Grundbegriffe Isomere, Strukturisomere, Chiralität und Enantiomere werden am Beispiel verschiedener Medikamente erläutert. Die Inhalationsanästhetika Enfluran und Isofluran sind Beispiele für Strukturisomere. Sie enthalten wie auch Halothan ein Kohlenstoffatom, an dessen vier Bindungsstellen vier verschiedene Atome gebunden sind. Solche Atome bilden ein chirales Zentrum und ermöglichen zwei räumliche Konfigurationen eines Moleküls, die Enantiomere genannt werden. Eine Mischung, die die beiden Enantiomere zu gleichen Anteilen enthält, wird als Razemat bezeichnet. Halothan, Enfluran, Isofluran und andere Medikamente liegen als Razemate vor. Ein quaternäres Stickstoffatom kann in analoger Weise ebenfalls ein chirales Zentrum bilden. Die beiden Isochinolingruppen des Atracurium enthalten jeweils zwei chirale Zentren, ein Kohlenstoffatom und ein quaternäres Stickstoffatom. Jede dieser Isochinolingruppen kann in vier verschiedenen räumlichen Konfigurationen (Stereoisomere) vorliegen. Infolge der Symmetrie des Atracuriummoleküls beschränkt sich die Zahl der möglichen Stereoisomere auf 10. Eines dieser Stereoisomere mit dem Namen Cisatracurium weist günstigere pharmakologische Eigenschaften auf als das Isomerengemisch Atracurium. Ester: Moleküle mit Esterbindungen liegen in der Form „wahrer” oder „verkehrter” Ester als Stereoisomere vor. Wahre Ester werden von der Plasmacholinesterase hydrolytisch gespalten. Succinylcholin und Mivacurium sind wahre Ester mit unterschiedlichen Abbauraten. Die schnellere Abbaurate von Succinylcholin erklärt dessen kürzere Anschlagzeit und kürzere Wirkdauer. Verkehrte Ester werden von nichtspezifischen Esterasen (Carboxyesterasen) hydrolytisch abgebaut. Manche der „verkehrten” Ester, wie Remifentanil, werden sehr schnell, andere, wie Cisatracurium, dagegen nur langsam, oder überhaupt nicht, hydrolysiert.
    Der Anaesthesist 01/1997; 46(4):282-286. DOI:10.1007/s001010050402 · 0.74 Impact Factor