PubMed Health⌕ Search

Biomedical subjects

P M Lauven

Publications and source records attributed to P M Lauven.

At least 19 recordsLinked to original sources

[Postoperative cognition disorders in elderly patients. The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1)].

OBJECTIVE: Cognitive dysfunction is a known problem after operations and may be especially relevant in the elderly. The aim of this international multicentre study was to investigate short- and long-term cognitive dysfunction in elderly patients and to elucidate the relevance of hypoxaemia and hypotension as causative factors. METHODS: 1218 patients aged 60 years and older and scheduled for major non-cardiac surgery under general anaesthesia were investigated. Oxygen saturation was measured by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. Blood pressure was recorded every 3 minutes during the operation and every 15-30 min for the rest of that day and night. Cognitive testing was performed before and 1 week and 3 months after the operation. Cognitive dysfunction was identified with neuropsychological tests compared with controls recruited from the UK (n = 176) and the same countries as study centres (n = 145). RESULTS: Postoperative cognitive dysfunction was present in 25.8% of patients 1 week after surgery and in 9.9% 3 months after surgery, compared with 3.4% and 2.8%, respectively, of the UK controls. Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were the risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for long-term postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. CONCLUSION: With this investigation long-term cognitive dysfunction could be proven definitively for elderly patients after major operations under general anaesthesia. No factors with prophylactic or therapeutic influence were detectable so that aetiology and pathophysiology of POCD could not be further determined.

Aged↗

[Pharmacokinetics in newborns and infants].

Physiologic changes influence the pharmacokinetics of drugs relevant to anesthesia in neonates and infants. The neonatal phase is the phase of life with the most rapid and dramatic changes of organ-functions responsible for pharmacokinetics of most anesthetics. Changes in body composition and the content of plasma proteins influence volume of distribution, the drug distribution to different compartments and the amount of free fraction in plasma. Due to the immaturity of hepatic microsomal enzyme systems there is a decreased metabolism particular of agents which undergo low hepatic extraction like Diazepam, Morphine or some local anesthetics. In the first year of life capacity of the enzymatic systems increases and also clearance increases. Until puberty the clearance of some drugs is greater than the adult level. There are also pharmacodynamic changes like modified sensitivity to some drugs like volatile anesthetics or neuromuscular blocking agents. In summary neonates and infants are a highly heterogenous group with large interindividual differences. Therefore the dosage of anesthetic agents must be individualized to achieve optimal pharmacodynamic effects without toxicity in this age group.

Anesthesia↗

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

Abdomen↗

[Pharmacokinetics from the viewpoint of the clinical anesthetist].

Pharmacokinetics describes the time-depend course of plasma concentration of a drug. Pharmacodynamics describes the pharmacological effect of the substance. Both together form the pharmacological model used in clinical practice. The global descriptors total clearance Cltot, volume of distribution Vd, and half-life t1/2 allow for a first good approximation of drug delivery and a characterisation of drugs. Unwanted side-effects such as inadequate anaesthesia or prolonged recovery periods may be explained. The main clinical use of pharmacokinetics is to sustain dosing schemes based on scientific data. It also may be helpful in creating new administration schemes especially for continuous infusion of intravenous hypnotics or analgetics. New developments such as Target-Controlled Infusion (TCI) are based on pharmacokinetic data and computations and may be an improvement for the clinically working anaesthetist.

Anesthesia Recovery Period↗

[Antagonists in anesthesia].

In modern anaesthesia various antagonists are used. They provide efficient tools to facilitate better control of pharmacological effects and side effects of drugs routinely used in anaesthesia. Naloxone is a competitive antagonist of opioids without any intrinsic activity. It counteracts respiratory depression, pruritus, sedation and analgesia caused by opioids. It is fast-acting with a duration of action of 45 to 90 min. Several investigators have reported severe side effects of naloxone including hypertension, tachyarrhythmias, left heart failure and cardiac arrest, and hence the use of naloxone must be carefully considered in every single patient. Flumazenil is a competitive antagonist of benzodiazepines. It is a remarkably safe drug and very effective to terminate all benzodiazepine effects in anaesthesia and intensive-care patients. Serious complications caused by flumazenil have been reported in patients receiving benzodiazepines in the treatment of seizure disorders and in patients with mixed intoxications. Neostigmine is one of several antagonists of neuromuscular blocking agents. Its side effects include bradycardia, increased bronchial secretions and increased peristalsis. Indication depends on the results of neuromuscular monitoring. Physostigmine is an unspecific antagonist of the central anticholinergic syndrome, an acute psychosis that may be caused by numerous drugs used in anaesthesia. Generally, antagonists should be carefully titrated. In emergency medicine the use of these antagonists is not recommended; the primary goal is to restore vital functions.

Anesthesia, General↗

[The cardiotoxicity of bupivacaine during pacemaker stimulation is dependent on the stimulation frequency. Results of an experimental study].

The cardiotoxic effects of bupivacaine are related to the temporal dispersion of effective refractory periods in different parts of the cardiac conduction system. This effect facilitates the occurrence of re-entry arrhythmias under burst stimulation [4, 8]. In this study physiological increments in heart rate were simulated by cardiac pacing, and the electrophysiological and haemodynamic effects under the influence of cardiotoxic concentrations of bupivacaine were measured. METHODS. After institutional approval we generated cardiotoxic arterial plasma concentrations of bupivacaine (6.9 +/- 1.6 micrograms/ml) in pigs (n = 8; 15-22 kg) by i.v. injection of 4 mg bupivacaine/kg, followed by a constant rate infusion of 0.2 mg/kg per min [8]. The pigs were anaesthetized with midazolam, fentanyl and pancuronium and normoventilated with a FiO2 of 0.4. Internal right atrial and right ventricular pacing was performed with increasing frequencies of 20, 40, 60, 80 and 100 stimulations/min above individual spontaneous heart rates (AL) before (control) and after the administration of bupivacaine. ECG, MAP, LVSP, dp/dtmax and stimulation thresholds were recorded. Student's t-test, and the U-test of Wilcoxon, Mann and Whitney were used for statistical testing with a significance level of 0.05. RESULTS. By inducing a frequency-dependent increase in stimulation threshold, bupivacaine prevented regular atrial pacing with frequencies higher than AL + 60. Ventricular pacing with a frequency of AL+40 induced a lethal arrhythmia in 1 animal. In the remaining 7 pigs ventricular pacing showed a frequency-dependent increase in stimulation thresholds (Fig. 1) and stimulus-QRS intervals (Fig. 5). MAP (Fig. 2), LVSP (Fig. 3) and cardiac inotropy (Fig. 4) showed frequency-dependent decreases under ventricular pacing. CONCLUSIONS. The toxic effects of bupivacaine on pacing thresholds, av conduction, intraventricular conduction, cardiac inotropy, and blood pressure are modulated by the stimulation frequency of a cardiac pacemaker. The cardiotoxic effects of bupivacaine seem to be use dependent. Even minor increments in heart rate can induce malignant arrhythmias. Cardiac pacing can be difficult in the presence of toxic bupivacaine concentrations, and high-frequency pacing should be avoided. It has to be verified whether higher heart rates generated by the physiological pacemakers of the heart do also increase the cardio-circulatory toxicity of bupivacaine. If that holds true, drugs that can induce tachycardias should be avoided in the treatment of bupivacaine toxicity.

Animals↗

Anaesthesia techniques for midazolam and flumazenil--an overview.

Midazolam, the latest benzodiazepine agonist, may be used in doses of 0.15 to 0.2 mg.kg-1 for induction of anaesthesia. It provides good correlation between plasma concentration and anaesthetic effect with an interindividual variability of only 20-25%. On this basis, dosage recommendations for midazolam in total intravenous anaesthesia techniques are possible, aiming at hypnotic plasma concentrations of at least 250 ng.ml-1. Due to its biological half-life of 150-180 min and interindividual differences in drug susceptibility, prolonged recovery periods have been observed that can safely and reliably be antagonised by flumazenil, if necessary. It is recommended that flumazenil be administered carefully by titration in increments of 0.1 mg.min-1 to avoid emergence reactions by awakening too fast (tachycardia, hypertension). Usually a mean total dose of 0.4-0.5 mg will lead to prompt awakening.

Anesthesia, Intravenous↗

Methohexital vs midazolam/flumazenil anaesthesia during laryngoscopy under jet ventilation.

In a randomised clinical study, two total intravenous anaesthesia techniques for microlaryngoscopic laser surgery were compared. After an induction dose of 100 mg methohexital, Group I received a maintenance infusion of 10 mg.min-1. In Group II anaesthesia was obtained by 15 mg midazolam followed by 0.1 mg.min-1 continuously and terminated by the injection of flumazenil. For analgesia 5 mg alfentanil were administered. Opiate-induced respiratory depression was antagonised by 0.08 to 0.12 mg naloxone. Prior to, during, and after surgery, adrenergic response was assessed by HPLC-analysis of blood taken from a peripheral vein. Haemodynamic responses to the operation and during the post-operative period were almost identical in both groups. In Group I, the mean recovery period of 14 min was significantly longer than in Group II (9 min), where patients received a mean dose of 0.53 mg (+/- 0.15) flumazenil. Resedation could be observed in all patients receiving flumazenil within 60 min after antagonisation, which was associated with a mean decrease in O2-saturation from 95% to 88%. There was no difference in epinephrine and norepinephrine blood levels between the two groups prior to and during anaesthesia. In all patients, arousal was associated with a significant increase in the epinephrine plasma concentration. While blood levels in Group I decreased during the post-operative period to levels prior to surgery, the concentrations in Group II remained elevated. In one patient who received no naloxone, the reversal of midazolam action induced a 16-fold increase in catecholamine levels (from 50 to 800 ng.l-1) associated with a tachycardia of 170 b.min-1 and hypertension of 160 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacology of drugs for conscious sedation.

In endoscopic monitoring and treatment of gastrointestinal disease, it is important that patients will accept repeated examination. They are less likely to do so if the procedure is remembered as distressing or uncomfortable, as is likely when it is performed under topical anaesthesia alone. The aim of conscious sedation is a lightly sedated patient, who is awake, cooperative on demand, amnesic, and free from anxiety and fear. Various drugs in low doses can be used to meet these criteria. Among these are phenothiazines, butyrophenones, barbiturate and non-barbiturate hypnotics, benzodiazepines, and the hypno-analgesic, ketamine. As benzodiazepines offer both sedative and profound amnesic and anxiolytic effects, these drugs are used for conscious sedation worldwide. Diazepam has been the 'gold standard' of sedation, but the more modern benzodiazepines, particularly midazolam, are now more commonly used. In general, benzodiazepines demonstrate a broad therapeutic range. In accordance with dose, however, sedative drugs may induce side-effects, such as drowsiness, lowering of blood pressure, and respiratory depression. In addition, some may induce more wide-ranging side-effects, such as histamine liberation and anaphylactic reactions, thrombophlebitis, and pain on injection. They may have severe drug interactions when used in combination with local anaesthetics, hypnotics and opioids. In older patients, lower doses are necessary for sedation. Sedative drugs should be administered slowly, to avoid haemodynamic and respiratory side-effects.

Adult↗

[Interdisciplinary computerized evaluation of perioperative risk factors].

The identification and assessment of perioperative risk factors combined with interdisciplinary management may lead to minimized risk for the patient. The numerous medical and administrative data should be collected by a computer. This was done in a preliminary study at the university of Bonn, where 9772 anaesthesias given for general surgery were evaluated. The necessary outcome studies should be based on statistical evaluation of the data (factor analysis) and their interpretation should be an interdisciplinary concern.

Adolescent↗