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Biomedical subjects

C Diefenbach

Publications and source records attributed to C Diefenbach.

At least 37 records · Page 2Linked to original sources

[Coronary stent implantation without preliminary dilatation].

BACKGROUND: Extensive coronary dissections are rare but represent serious complications of percutaneous transluminal coronary angioplasty (PTCA). In order to prevent dissections in large coronary vessels (> or = 2.5 mm), we evaluated stent implantation without predilatation in 98 selected patients with favorable coronary anatomy and lesion morphology. METHODS: Coronary stenting without predilatation was performed 41 times in the LAD, 41 times in the RCA, 11 times in the RCx, and 5 times in a vein graft. Mean diameter stenosis was 83 +/- 3%. Thirty-six patients had type A lesions and 62 patients type B lesions. Patients with type C lesions were excluded. Only premounted stents were used. RESULTS: The clinical situation was stable angina in 68 patients, unstable angina in 18, and acute myocardial infarction in 12. Stenting without predilatation was successful in 92 patients (94%). In 6 cases (6%) it was not possible to cross the lesion with the premounted stent, and predilatation was necessary prior to successful stent implantation. Two out of 11 RCx-related lesions (18%) could not be stented without predilatation. However, ultimate success of PTCA was 100%. No stent was lost. Mean remaining stenosis amounted to 3 +/- 6%. Minor angiographically detectable dissections after stent deployment were noted in 8 patients (8%). Inflation time (30 +/- 22 s) and fluoroscopic time (4.5 +/- 2.1 min) compared favorably to standard procedures. During 30 d follow-up no subacute stent thrombosis, but 2 non-Q-wave myocardial infarctions due to lost side branches were reported. CONCLUSIONS: Coronary stenting with premounted stents without predilation is feasible and safe in selected patients in order to reduce fluoroscopic and procedural time and to save costs. Furthermore, this procedure might reduce the risk of hazardous coronary dissections.

Adult↗

The significance of oncometry for infusion therapy during pediatric heart surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: As estimation of COP from TPP or albumin level is inaccurate, oncometry should be performed during pediatric heart surgery.

Blood Proteins↗

[Muscle relaxants. New substances and neuromuscular monitoring].

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.

Anesthesia↗

[Esters and stereoisomers].

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.

Anesthetics↗

[The clinical pharmacology of mivacurium].

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.

Anesthesia↗

[The clinical pharmacology of cisatracurium].

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.

Adult↗

Onset of the neuromuscular block simulated in an anatomical model.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: We conclude that those muscle relaxants that produce neuromuscular block rapidly require larger equieffective doses due to their more rapid initial disappearance from plasma.

Dose-Response Relationship, Drug↗

The significance of oncometry for infusion therapy during pediatric heart surgery.

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.

Age Factors↗

Stereoselective high-performance liquid chromatographic assay with fluorometric detection of the three isomers of mivacurium and their cis- and trans-alcohol and ester metabolites in human plasma.

An improved high-performance liquid chromatography assay for the three stereoisomers of the muscle relaxant mivacurium and its metabolites in plasma is presented. The principal steps in the assay are precipitation of plasma proteins by acetonitrile, lyophilization of the supernatant and ion-exchange chromatography on Spherisorb 5-SCX column, with gradient elution (acetonitrile from 32 to 68% v/v and ionic gradient from 7 to 56 nmol l-1 Na2SO4), a flow-rate of 2.0 ml min-1, D-tubocurarine as internal standard and fluorometric detection (excitation wavelength = 280 nm, emission wavelength = 320 nm). Quantitation limit of cis-cis, cis-trans, trans-trans isomers were 0.003, 0.002 and 0.005 mumol l-1, respectively. Quantitation limits for the monoestercis metabolite were 0.011 mumol l-1, for the monoestertrans metabolite 0.017 mumol l-1, for the amino-alcoholtrans 0.020 mumol l-1 and for the amino-alcoholcis 0.021 mumol l-1. None of eight drugs used during anaesthesia interfered with the assay in vitro. Satisfactory performance was demonstrated by the measurement of the isomers and their metabolites in plasma of two patients over a 6-h period after repeated injections of mivacurium.

Alcohols↗

[New muscle relaxants].

Mivacurium is a short-acting nondepolarising muscle relaxant of the benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With 2.5 fold ED95, 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 and about half as long as with equipotent doses of atracurium and vecuronium. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to a moderate histamine release following doses of 3-4 times the ED95. In patients with end stage liver or renal disease as well as in patients with atypical plasma cholinesterase the duration of action of mivacurium is prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking agent chemically related to vecuronium. Compared with the latter, rocuronium is less potent, has a shorter onset of action, and no cumulative effects. Adequate intubating conditions are achieved within 60 to 90 s after i.v. injection of twice the ED95. Its elimination from the blood occurs primarily via liver uptake, while renal elimination is about 10 to 30%. Slight vagolytic effects are reported following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis-atracurium, is five times as potent as the chiral mixture while having a similar pharmacodynamic and kinetic profile. It does not cause significant histamine release or clinically relevant cardiovascular effects at doses up to 8 times the ED95. Laudanosine release seems to be less with cis-atracurium than with atracurium.

Androstanols↗

A comparison of cisatracurium and atracurium: onset of neuromuscular block after bolus injection and recovery after subsequent infusion.

Cisatracurium is a new nondepolarizing muscle relaxant. In patients randomized to receive either cisatracurium (n = 40) or atracurium (n = 20) we compared the time course of neuromuscular block. The initial bolus dose of cisatracurium was 0.1 mg/kg, that of atracurium 0.5 mg/kg. Neuromuscular block, maintained with an infusion of either drug, was reversed with neostigmine 45 micrograms/kg and atropine 20 micrograms/kg in one half of the patients. Neuromuscular transmission was assessed by recording the mechanical twitch response to train-of-four nerve stimulation. Onset times were 3.1 +/- 1.0 min with cisatracurium and 2.3 +/- 1.1 min with atracurium (P = 0.008). The infusion rates for a 95% +/- 4% neuromuscular block were 1.5 +/- 0.4 micrograms.kg-1.min-1 for cisatracurium and 6.6 +/- 1.7 micrograms.kg-1.min-1 for atracurium, 3.3 times those of cisatracurium when referenced to the active cations. After the infusion, the spontaneous recovery intervals 25%-75% of 18 +/- 11 min and 18 +/- 8 min for cisatracurium and atracurium (P = 0.896) were shortened to 5 +/- 2 min and 4 +/- 3 min (P = 0.921) after neostigmine. While attributing different onset times also to differences in the initial doses, we conclude that time profiles for neuromuscular block of both muscle relaxants, when given in equipotent doses, are not different.

Adolescent↗

Muscle relaxants: a clinical update.

The new nondepolarizing muscle relaxant rocuronium belongs to the chemical group of aminosteroidal muscle relaxants and is similar to vecuronium in its chemical structure and pharmacologic action. The principal clinical advantage of rocuronium over vecuronium is the short time to onset of the neuromuscular block. The two other new muscle relaxants, mivacurium and cis-atracurium, belong to the group of benzylisoquinoline muscle relaxants. Mivacurium is rapidly degraded in plasma and its principal characteristic is, hence, a short duration of action. Cis-atracurium is one of the 10 stereoisomers of atracurium. While its action is similar to that of atracurium, it does not release histamine and its administration is not accompanied by marked changes in blood pressure or heart rate. Even the simple tactile monitoring of the neuromuscular transmission enables the clinician to adjust the doses of these and other muscle relaxants to the needs of individual patients. Precise adjustment of the doses of muscle relaxants contributes to their safer clinical use by avoiding an excessively deep and unnecessarily prolonged neuromuscular block.

Androstanols↗

Alcuronium: a pharmacodynamic and pharmacokinetic update.

Alcuronium may be considered a muscle relaxant of historical rather than clinical significance. However, recent information from the manufacturer revealed its persisting clinical use in 26 countries worldwide. Thus, a pharmacodynamic-pharmacokinetic update appears mandatory. An intravenous (IV) single-bolus injection of alcuronium (0.25 mg/kg = ED95) was administered to 10 patients undergoing maxillofacial surgery during nitrous-oxide opioid anesthesia. Alcuronium neuromuscular block (evoked twitch tension), plasma concentration, and renal elimination (high-performance liquid chromatography [HPLC] assay) were measured during the 12-h after its administration. The time of onset, the time from end of injection to recovery to 25% of control twitch tension (DUR25%), and the recovery index were 2.2 +/- 1.2, 54 +/- 14, and 37 +/- 11 min, respectively (mean +/- SD). Two hours after the injection of alcuronium, partial recovery from the neuromuscular block had occurred from 100% to 26% +/- 24% depression of twitch tension, although less than 25% of the injected dose was recovered from the urine. The 12-h plasma concentration and urinary recovery were 0.1 +/- 0.08 mg/L (one-sixth of the 50% inhibitory concentration) and 61% +/- 20%, respectively. Recovery from neuromuscular block was dominated by intercompartmental distribution rather than by renal elimination. Since alcuronium does not undergo biodegradation, our data may serv as a reference for the complex pharmacokinetics of readily metabolized modern muscle relaxants. The long plasma half-life with slow excretion merits attention with respect to the erroneous original perception that alcuronium was an intermediate-acting muscle relaxant.

Adult↗

Changes in plasma cholinesterase activity and mivacurium neuromuscular block in response to normothermic cardiopulmonary bypass.

The effect of reduced plasma cholinesterase (ChE) activity in response to normothermic cardiopulmonary bypass (CPB) on mivacurium neuromuscular block was studied in nine patients anesthetized with propofol/fentanyl. Mivacurium was injected intravenously as an initial bolus of 150 micrograms/kg; repeat doses of 75 micrograms/kg were given when the evoked twitch tension attained 75% of control. With the institution of CPB, the previously normal ChE activity was reduced by 42% and remained low until the end of the procedure. The times of onset (time from the end of injection to maximum neuromuscular block) of the maintenance doses of mivacurium were 26% longer during than before or after CPB (P < 0.05). Their DUR25% (time from end of injection to recovery of neuromuscular transmission to 25% of control) were 13 +/- 3 min (means +/- SD) before, 14 +/- 4 min during, and 16 +/- 4 min (P < 0.05) after CPB. It is concluded, that, although markedly reducing the patient's previously normal ChE activity, normothermic CPB had little effect on the time characteristics of mivacurium neuromuscular block.

Aged↗

Comparison of ondansetron and droperidol in the prevention of nausea and vomiting after inpatient minor gynecologic surgery.

Ondansetron and droperidol are both effective in the prevention of postoperative nausea and vomiting (PONV). In this randomized, double-blind study, 80 inpatients scheduled for minor gynecologic surgery received either ondansetron 8 mg intravenously (i.v.) or droperidol 2.5 mg i.v. 5 min prior to induction of isoflurane-narcotic anesthesia. PONV was absent in 68% of the patients after ondansetron and in 88% after droperidol (P < 0.05). The respective times of complete arousal from anesthesia were 171 min and 229 min (P < 0.001). After ondansetron and droperidol, the incidence of severe drowsiness, restlessness, anxiety, or dizziness was 5% and 28%, respectively (P < 0.01). Thus after minor gynecologic surgery, droperidol 2.5 mg i.v. was superior to ondansetron 8 mg i.v. in the prevention of PONV. However, relative to ondansetron, droperidol entailed an average 1-h delay in recovery from anesthesia.

Adult↗