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Biomedical subjects

F Wappler

Publications and source records attributed to F Wappler.

At least 19 recordsLinked to original sources

The 'heparin lock': cause for iatrogenic coagulopathy.

BACKGROUND AND OBJECTIVE: The reasons for coagulopathy may be multiple and the identification of the underlying cause is often difficult. Recently, we identified two patients showing characteristics of heparin overdose during surgery. We hypothesised that filling a Shaldon dialysis catheter with heparin prior to closure, so-called heparin lock, might have triggered this coagulation disorder. Therefore, the aim of this in vitro study was to show whether this procedure can lead to an iatrogenic administration of heparin. METHODS: A Shaldon catheter (GamCath; Joka Kathetertechnik, Hechingen, Germany) was hung up in a container filled with NaCl solution 0.9% 5 mL and a heparin lock was simulated. Instead of using heparin solution we injected 1 mL of a KCl solution (1 mol L(-1)) into the Shaldon catheter, because the measurement of the potassium concentration is faster and more reliable than that of heparin. Ten measurements were taken after fast (0.5 s) and slow (3 s) injection speeds. RESULTS: Although the catheter volume is specified as 1.07 mL, an amount up to 0.51 mL KCl solution on average was detectable in the solution after locking the catheter with 1 mL KCl solution. CONCLUSIONS: Following a heparin lock a considerable amount of the injected solution is accidentally administered to the patient. Only 49.1% of the injected volume may remain in the Shaldon catheter. This could lead to an increased risk of coagulopathy.

Algorithms↗

[Respiratory sinus arrhythmia as predictor of blood pressure stability during anaesthetic induction in diabetics].

OBJECTIVE: Diabetics with cardiovascular autonomous neuropathy (CAN) can show severe hypotension during the course of anaesthesia. To improve the safety of anaesthesia, pre-operative evaluation of this concomitant disorder is recommended. The conventional test battery described by Ewing and Clarke to diagnose CAN is relatively time-consuming and complex. The aim of this study was to evaluate whether patients at risk could be reliably identified with less diagnostic effort. METHODS: Fifty patients with diabetes mellitus undergoing an ophthalmosurgical procedure were investigated. To evaluate their cardiovascular reflex status, the following tests were performed one day before surgery: determination of heart rate variation (HRV) under deep respiration (6 breaths/min), and the response of heart rate (max/min 30:15 ratio) and blood pressure after getting up from a supine position. Anaesthesia was induced with thiopental and fentanyl and maintained with enflurane/N (2)0; vecuronium was administered for tracheal intubation. Patients whose systolic blood pressure fell below 90 mm Hg during the induction phase were assigned to Group H (hypotensive), the remaining patients to Group N (non-hypotensive). The groups were compared regarding the pre-operatively collected variables. RESULTS: The demographic data were comparable in the two groups with exception of the length of diabetes. Regarding blood pressure reaction during orthostatic load, there was no significant difference between the groups. In contrast, the parameters of HRV under deep respiration (with exception of the "mean circular resultant") and the max/min 30 : 15 ratio were significantly lower in patients of Group H than in Group N. The best differentiation between the groups offered the E/I ratio (= quotient resulting from the longest R-R interval during expiration (E) and the shortest R-R interval during inspiration (I) under deep breathing) as a measure of respiratory sinus arrhythmia. The incidence of hypotension during anaesthetic induction in patients with a normal E/I ratio was 8.7 %, but in patients with a pathologically reduced E/I ratio 51.9 % ( P = 0.0019). The sensitivity of this test concerning hypotension that occurred was 87.5 %, the specificity 61.7 %. CONCLUSION: The available results prove the close connection between the pre-operatively measured breadth of respiratory sinus arrhythmia and blood pressure response during anaesthetic induction. Patients at risk of hypotension can be identified reliably and quickly during pre-operative screening with the help of a single, simple test procedure.

Adult↗

[Pre-operative measurement of heart rate variability in diabetics: a method to estimate blood pressure stability during anaesthesia induction].

BACKGROUND: In diabetics severe hyopotension can occur during anaesthesia as a consequence of cardiovascular autonomic neuropathy (CAN). A simple approach to recognize CAN is heart rate variability (HRV) measured at rest. The aim of this study was to determine the relationship between pre-operatively measured HRV and blood pressure stability during induction phase of anaesthesia. PATIENTS AND METHODS: A total of 35 diabetics undergoing an ophthalmosurgical procedure under general anaesthesia were investigated. HRV was examined one day before surgery by the following parameters: coefficient of variation (CV), root mean squared successive difference (RMSSD), and power spectrum. Anaesthesia was induced with thiopental and fentanyl and maintained with enflurane/N(2)O; tracheal intubation was performed after relaxation with vecuronium. Patients who developed a drop in systolic blood pressure below 90 mmHg during anaesthesia induction were assigned to group H (hypotensive), the other patients to group N (normotensive). The groups were compared regarding HRV and other variables. RESULTS: Of all patients 13 developed hypotension during anaesthesia induction (group H). The groups were comparable regarding the demographic data. Parameters of HRV, with the exception of spectral power in low frequency (LF) band of power spectrum, were significantly lower in group H. The groups differed mainly in relation to spectral power in the mid-frequency (MF) band of the power spectrum, and especially regarding CV. In patients with normal CV incidence of hypotension after anaesthesia induction was 11%, but in patients with abnormally reduced CV, 65% (p=0.002). CONCLUSION: The results confirm a significant relationship between HRV pre-operatively measured at rest and blood pressure stability during anaesthesia induction in diabetics. Particularly examination of CV, a simple test feasible within few minutes, may be useful in pre-operative risk stratification of these patients. Application of the time consuming traditional test combination to identify CAN seems to be unnecessary.

Aged↗

Phosphodiesterase-III-inhibition with amrinone leads to contracture development in skeletal muscle preparations of malignant hyperthermia susceptible swine.

BACKGROUND AND OBJECTIVE: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated. METHODS: MH-trigger-free general anaesthesia was performed in eight MHS and eight MHN swine. The MH status of the swine was determined by detection of the Arg615-Cys point mutation on chromosome 6 indicating MH susceptibility. Skeletal muscle specimens were excised for the in vitro contracture tests with amrinone. Amrinone was added cumulatively every 5 min to muscle specimens in order to obtain organ bath concentrations between 20 and 400 micromol L(-1). The in vitro effects of amrinone on muscle contractures and twitches were measured. RESULTS: Amrinone-induced contractures in all skeletal muscle preparations. MHS muscles developed contractures at significantly lower bath concentrations of amrinone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 80, 100, 150, 200 and 400 micromol L(-1) amrinone. Muscle twitches remained unchanged up to and including 200 micromol L(-1) amrinone. CONCLUSIONS: Inhibition of PDE-III in general elicited higher contractures in MHS than in MHN muscles. Therefore, a contribution of PDE-III and the cyclic adenosine monophosphate (cAMP) system in the pathophysiology of MH must be suspected.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia].

OBJECTIVE: Theophylline, a methylxanthine, leads to an increase of the cytoplasmic Ca(2+)-concentration in the muscle cell. Since the in-vitro contracture test (IVCT) with halothane and caffeine does not distinguish a 100% between malignant hyperthermia susceptible (MHS) and non-susceptible (MHN), we examined the in-vitro effects of theophylline in porcine skeletal muscle preparations. METHODS: After approval by the local animal care committee ten MHS- and nine MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administrations of theophylline in concentrations of 3.0 respectively 5.0 mmol/l. Muscle contracture development and twitch amplitudes were recorded over a period of 30 minutes. Data are expressed as medians and ranges. RESULTS: After both theophylline bolus administrations MHS-muscles developed significantly higher contractures compared to the MHN-specimens. The MHS-muscles reached a maximum contracture of 17.0 mN (7.2-59.6 mN) after administration of 3.0 mmol/l theophylline. In comparison, two MHN-specimens showed weak contractures with a maximum of 1.4 mN. The 5.0 mmol/l theophylline IVCT resulted in maximum contractures of 19.1 mN (2.1-39.2 mN) for the MHS-preparations. Just in three MHN-muscles weak contractures of 0.0 mN (0.0-0.8 mN) were recorded. Thus, a significant difference without overlap was revealed for the maximum contracture. CONCLUSION: Theophylline in concentrations of 3.0 and 5.0 mmol/l revealed a clear difference between MHS- and MHN-porcine muscle preparations. Further examinations on human skeletal muscles are needed to demonstrate the value of theophylline in the IVCT MH-diagnosis.

Animals↗

[Is a presymptomatic malignant hyperthermia in-vitro diagnosis with 4-chloro-3-ethyl phenol possible? A study using porcine skeletal preparations].

OBJECTIVE: The diagnosis of malignant hyperthermia is currently performed with the in-vitro contracture test (IVCT) with halothane and caffeine. This test has a sensitivity of 99.0 % but only a specificity of 93.6 %. A cumulative IVCT with 4-chloro-3-ethyl-phenole (CEP) has recently been shown to differentiate between MH susceptible (MHS) and MH normal (MHN) swine. The pur-pose of this study was to investigate the ability of bolus CEP-applications to distinguish between porcine MHS- and MHN-muscle specimens using the IVCT. METHODS: After approval by the local animal care committee 8 MHS- and 8 MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administration of CEP in concentrations of 75 resp. 100 micro mol l (-1). Predefined parameters were: (1) onset time of the contracture development, (2) time to the achievement of the 2, 5 and 10 mN contracture level and (3) maximum contracture level. Data are expressed as medians and ranges. RESULTS: After 75 micro mol l (-1) CEP administration all MHS-muscles showed contractures after 0.5 min (0.2 min/0.9 min). The 2 mN contracture level was reached by all MHS-, the 5 mN level by four MHS- and the 10 mN level by one MHS-specimen. The maximum contracture was 5.3 mN (2.4 mN/12.9 mN). The onset time after 100 micro mol l (-1) CEP was registered as 0.3 min (0.1 min/0.7 min) in the MHS-preparations. Again, the 2 mN level was achieved by all MHS-specimens, the 5 mN level by 5 and the 10 mN level by one MHS-bundle. The maximum contracture was measured as 5.9 mN (2.8 mN/13.9 mN). In 7 MHN-specimens no contracture development was measured. After 75 micro mol l (-1) CEP one MHN-muscle showed a maximum contracture of 1.0 mN, after 100 micro mol l (-1) CEP one MHN-bundle demonstrated a maximum contracture of 1.1 mN. Hence, a significant difference between MHS and MHN without overlap was revealed with both CEP-concentrations in the onset time of contracture, in the 2 mN contracture level and the maximum contracture. CONCLUSION: Since a clear differentiation between MHS and MHN porcine specimens was achieved after bolus application of 75 and 100 micro mol l (-1) CEP, MH-diagnosis might be possible with a CEP-IVCT. It seems worthwhile to examine this hypothesis in men.

Animals↗

Dantrolene--a review of its pharmacology, therapeutic use and new developments.

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.

Dantrolene↗

Branching fractions of tau leptons to three charged hadrons.

From electron-positron collision data collected with the CLEO detector operating at Cornell Electron Storage Ring near sqrt[s]=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as B(tau(-)-->pi(-)pi(+)pi(-)nu(tau))=(9.13+/-0.05+/-0.46)%, B(tau(-)-->K-pi(+)pi(-)nu(tau))=(3.84+/-0.14+/-0.38) x 10(-3), B(tau(-)-->K-K+pi(-)nu(tau))=(1.55+/-0.06+/-0.09) x 10(-3), and B(tau(-)-->K-K+K-nu(tau))<3.7 x 10(-5) at 90% C.L., where the uncertainties are statistical and systematic, respectively.

Journal Article↗

[Dantrolene. Pharmacological and therapeutic aspects].

Malignant hyperthermia (MH) is a genetic, potentially life-threatening disorder of the skeletal muscle presenting during or following general anaesthesia. Trigger agents are volatile anaesthetics and depolarising muscle relaxants. Dantrolene is the only available drug for effective and specific MH therapy, which reduces significantly the mortality rate. Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown. Recent studies identified the ryanodine receptor, the calcium release channel of the sarcoplasmic reticulum, as the direct molecular target of dantrolene. In addition to its use for MH, dantrolene is used in other disorders such as neuroleptic malignant syndrome and spasticity. Since dantrolene is weakly water soluble, the clinical preparation is time and manpower consuming. New agents have been synthesized, but because of economic considerations no registration for clinical usage has been realised.

Dantrolene↗

Cardiac and thoracic vascular surgery.

The number of aged individuals is growing, and consequently the demands on resources for cardiac surgery will increase in the elderly. Even in the absence of obvious coexisting diseases, advanced age is always accompanied by a general decline in organ functions, and specifically by changes in structure and function of the heart and vasculature that will ultimately affect cardiovascular performance (e.g. hypertension, ischaemic heart disease, etc.). These alterations have to be taken into account when older patients require anaesthesia for cardiac surgery. Pre-operative examination must be performed carefully to estimate cardiac function as well as dysfunction of other organ systems. Benzodiazepines as well as alpha2-adrenoceptor agonists can be used for pre-medication; induction and maintenance of anaesthesia can be performed as balanced anaesthesia or total intravenous anaesthesia. Essential monitoring should include pulmonary artery catheterization and/or transoesophageal echocardiography. During cardiac surgery the risk for elderly individuals is increased; in particular, the central nervous system is more often compromised in the elderly than in younger patients. However, elderly patients without significant co-morbidity have a mortality rate comparable to that of younger patients.

Aged↗

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH. METHODS: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 micromol L(-1) in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min. RESULTS: After bolus administration of 4-chloro-m-cresol, 75 micromol L(-1), 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 micromol L(-1). Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH. CONCLUSIONS: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

Biopsy↗

Inhalational induction of anaesthesia with 8% sevoflurane in children: conditions for endotracheal intubation and side-effects.

BACKGROUND AND OBJECTIVE: This study was designed to assess the conditions for endotracheal intubation or insertion of a laryngeal mask airway following an inhalational induction using 8% sevoflurane and nitrous oxide without the use of muscle relaxants or opioids. METHODS: There were two groups: 30 children had endotracheal intubation and 30 children had a laryngeal mask airway inserted. Induction of anaesthesia was accomplished using an inspiratory concentration of sevoflurane 8% in a nitrous oxide and oxygen mixture. After an end-expiratory concentration of sevoflurane of at least 4% had been reached, when the pupils were miotic and centred, the trachea was intubated or a laryngeal mask inserted. The time to loss of consciousness and successful airway management was recorded. Jaw relaxation, movements, visibility, and position of the vocal cords and vital parameters were monitored. RESULTS: Jaw relaxation was complete in all children. The vocal cords were completely visible in all patients of the tracheal intubation group, whereas vocal cord relaxation was incomplete in five children. Nevertheless, all children had an atraumatic intubation or insertion of the laryngeal mask without the use of a muscle relaxant. Vital signs were stable in both groups. There were no cases of restlessness and/or postoperative shivering. Four patients in the endotracheal group (13.3%) were nauseous and three (10%) vomited, while two children (6.6%) in the laryngeal mask group experienced nausea and vomiting. CONCLUSIONS: Induction with sevoflurane in nitrous oxide and oxygen leads to fast loss of consciousness and provides ideal conditions for managing the airway without supplemental opioids or muscle relaxants. Furthermore, sevoflurane using this technique was very well tolerated, indicated by high haemodynamic stability and a reduced rate of postoperative restlessness, shivering, nausea and vomiting.

Anesthesia, Inhalation↗