Search PubMed⌕ Search

Biomedical subjects

M Georgieff

Publications and source records attributed to M Georgieff.

At least 163 records · Page 9Linked to original sources
PubMed1996

The effects of ketamine-isomers on neuronal injury and regeneration in rat hippocampal neurons.

There is a difference in the relative anesthetic potency of the isomers of ketamine. Neuroprotective differences may therefore also exist. After an 8-min exposure to 500 microM glutamate or axonal transection, cultured rat hippocampal neurons were maintained untreated or in the presence of ketamine-racemate, S(+)-ketamine, or R(-)-ketamine (10(-4) M, 10(-5) M, 10(-6) M). Cell survival was examined by dye inclusion/esterase activity, morphology by phase contrast and immunofluorescence microscopy, and [3H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [3H]ARA increased fivefold. Dendritic length and branching decreased to a quarter and axonal extensions to the half. Ketamine-racemate 10(-4) M increased survival to 65%, and induced longer dendrites (P < or = 0.05). S(+)-Ketamine 10(-4) M increased survival to 80%, reduced [3H]ARA threefold, and preserved cytoskeletal arborizations (P < or = 0.05). Axotomy decreased survival to 60% and caused a minor increase in [3H]ARA after 7 days. Survival was 80% after 10(-4) M ketamine-racemate and 90% after 10(-4) M S(+)-ketamine (P < or = 0.05). Only S(+)-ketamine supported axonal reoutgrowth and decreased [3H]ARA (P < or = 0.05). R(-)-Ketamine was ineffective after both types of injury. Ketamine-racemate and S(+)-ketamine attenuated injury after glutamate exposure or axonal transection in hippocampal neurons in vitro. Neuroregenerative effects were uniquely demonstrated by S(+)-ketamine.

Anesthetics, Dissociative↗
PubMed1996

Influence of vaginal versus abdominal hysterectomy on perioperative glucose metabolism.

The aim of this study was to investigate the metabolic effects of abdominal versus vaginal hysterectomy with specific regard to perioperative glucose metabolism. Fourteen patients received either abdominal (AH, n = 7) or vaginal hysterectomy (VH, n = 7). Hepatic glucose production was measured before and 2.5 h after the operation by stable isotope technique ([6,6-2H2]-glucose). Metabolic substrates (glucose, lactate, nonesterified fatty acids [NEFA], beta-hydroxybutyrate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra-, and postoperatively. VH induced a higher postoperative glucose concentration than the abdominal approach (VH, 148 +/- 25 mg/dL; AH, 111 +/- 16 mg/dL; P < 0.05). Since postoperative enhancement of hepatic glucose production was comparable in both groups, glucose clearance was lower after the vaginal procedure (VH, 1.7 +/- 0.3 mL.kg-1.min-1; AH, 2.1 +/- 0.3 mL.kg-1.min-1; P < 0.05). NEFA, beta-hydroxybutyrate, and catecholamines similarily increased after surgery. Cortisol levels were more increased after VH (VH, 80 +/- 26 micrograms/dL; AH, 37 +/- 14 micrograms/dL; P < 0.001). Lactate, glucagon, and insulin concentrations did not change perioperatively. The more pronounced hyperglycemic response to VH was due to lower peripheral glucose use caused by higher postoperative cortisol values. The mechanisms responsible for this marked cortisol enhancement after the vaginal operation as well as the clinical significance for patients with preexisting impaired carbohydrate tolerance, however, remained unclear and warrant further investigation.

3-Hydroxybutyric Acid↗
PubMed1996

Effects of ventilation on hemodynamics and myocardial blood flow during active compression-decompression resuscitation in pigs.

BACKGROUND: Active compression-decompression (ACD) improves hemodynamics and vital organ blood flow during cardiopulmonary resuscitation. The effects of intermittent positive pressure ventilation (IPPV) on ACD have not been studied. This study was designed to compare the effects of ACD with and without IPPV on gas exchange, hemodynamics, and myocardial blood flow. METHODS: After 30 s ventricular fibrillation, 14 tracheally intubated pigs were allocated to receive either ACD combined with IPPV (ACD-IPPV) or ACD alone. In animals treated with ACD-IPPV, the lungs were ventilated using a servo ventilator. Animals treated with ACD received 100% oxygen by a reservoir but ventilation was not assisted. RESULTS: Minute ventilation (median) was 6.5 and 6.1 l/min after 1 and 7 min of ACD-IPPV, and was 4.2 and 1.6 l/min after 1 and 7 min of ACD. In contrast to ACD-IPPV, PaO2 was less and PaCO2 was greater with ACD. Mean arterial (53 and 40 mmHg; P < 0.05) and mean central venous pressure (25 and 14 mmHg; P < 0.01) were greater during ACD-IPPV as compared with ACD. After administration of epinephrine 0.2 mg/kg, myocardial blood flow increased only in ACD-IPPV treated animals, and 5 min after epinephrine administration, myocardial blood flow was greater during ACD-IPPV (33 ml.min-1.100 g-1) as compared with ACD (15 ml.min-1.100 g-1; P < 0.05). Restoration of spontaneous circulation could be achieved only in animals subjected to ACD-IPPV. CONCLUSIONS: Gas exchange was critically impaired during the late phase of ACD. Compared with ACD-IPPV, myocardial blood flow was less preserved with ACD and was too low to achieve restoration of spontaneous circulation.

Animals↗
PubMed1996

Prophylactic use of epidural mepivacaine/morphine, systemic diclofenac, and metamizole reduces postoperative morphine consumption after major abdominal surgery.

BACKGROUND: Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. While preemptive analgesic treatment with numerous agents has been successful in experimental animals, results of human studies remain conflicting. The authors used a multimodal approach for preemptive analgesia before abdominal surgery: diclofenac and metamizole inhibit prostaglandin synthesis, thus influencing peripheral sensitization; epidural local anesthetics induce conduction block, epidural opioids inhibit nociceptive synaptic transmission, and metamizole induces descending inhibition. The interaction of these drugs might suppress spinal nociceptive sensitization and postoperative analgesic demand. METHODS: One hundred forty-two patients scheduled for major abdominal surgery were randomly assigned to one of three groups and studied prospectively. Epidural catheters in groups 1 and 2 were placed at interspaces T8-T10, the position of the catheter was confirmed by epidurography, and sensory testing after administration of 5 ml mepivacaine 1%. Group 1 received 75 mg intramuscular diclofenac, 1000 mg intravenous metamizole, 5.3 +/- 1 mg epidural morphine, and 15-20 ml mepivacaine 1% 85 +/- 41 min before skin incision. Epidural analgesia was maintained by injections of 0.1 ml.kg-1.h-1 mepivacaine 1%. Group 2 patients received the balanced analgesia regimen before wound closure (221 +/- 86 min after skin incision). Group 3 patients did not receive any study substances. General anesthesia was induced with 5 mg/kg thiopental and 2 micrograms/kg fentanyl and maintained with enflurane and nitrous oxide. Postoperative analgesia consisted of patient-controlled intravenous morphine over 5 days. RESULTS: Median visual analog scale pain intensities were < 3 cm and did not differ among the groups. Morphine consumption per hour on postoperative day 2 was 0.8 +/- 0.1 mg/h (group 1) < 1.2 +/- 0.1 mg/h (group 2) = 1.1 +/- 0.1 mg/h (group 3) and cumulative morphine consumption (in mg) on the morning of day 5 was 95 +/- 9 (group 1) < 111 +/- 11 (group 2) < 137 +/- 10 (group 3). CONCLUSIONS: A significant reduction of patient controlled analgesia requirements could be achieved by our preincisional balanced analgesia regimen compared to application before wound closure. The more distinct difference between patients receiving balanced analgesia and those in the control group is based on the analgesic action of the study substances, which lasted about 14 h.

Abdomen↗
PubMed1996

Perioperative endotoxemia and bacterial translocation during major abdominal surgery: evidence for the protective effect of endogenous prostacyclin?

OBJECTIVE: To investigate the potential role of endogenous prostacyclin (PGI2) released after mesenteric traction during major abdominal surgery on perioperative endotoxemia and bacterial translocation. DESIGN: Prospective, randomized, double-blind clinical study. SETTING: Operating room and surgical intensive care unit in a university hospital. PATIENTS: Fifty consecutive patients scheduled for major abdominal surgery (pancreas resection, abdominal aortic surgery). INTERVENTIONS: Fifteen minutes before skin incision, either 400 mg of ibuprofen or a placebo equivalent were administered intravenously. Immediately after peritoneal incision, eventration and action of the small bowel was intentionally performed in a uniform fashion. MEASUREMENTS AND MAIN RESULTS: Baseline values were obtained before induction of anesthesia. Additional measurements, along with assessments of hemodynamics and gas exchange, were performed before incision of the peritoneum and at 5, 30, and 45 mins and 3, 6, and 24 hrs after mesenteric traction. Arterial plasma concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2) were determined by radioimmunoassay. Endotoxin was measured by limulus amebocyte lysate test. Mesenteric lymph nodes were sampled in 31 patients (ibuprofen n = 14, placebo n = 17) and sent for culture under sterile conditions. Transient hypotension and a marked increase of plasma 6-keto-prostaglandin F1 alpha concentrations occurred up to 6 hrs after mesenteric traction in untreated patients with median peak concentrations (2243 vs. 72 ng/L [p < .0001, placebo vs. ibuprofen], observed 5 mins after mesenteric traction). Endotoxemia occurred in both study groups. However, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group. Median peak concentrations (0.12 vs. 0.27 EU/mL [p < .001, placebo vs. ibuprofen]) were observed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenteric lymph nodes were detected exclusively in the ibuprofen group (n = 5, p < .01). CONCLUSIONS: In ibuprofen-pretreated patients, significantly higher endotoxin concentrations as well as bacterial translocation to mesenteric lymph nodes occurred, despite the absence of a transient decrease in mean arterial pressure that had been associated with PGI2 release. Therefore, we hypothesized that during major abdominal surgery, endogenous PGI2 released in response to mesenteric traction may play a crucial role in maintaining splanchnic microcirculation and thus preserving gut mucosal barrier function.

APACHE↗
PubMed1996

Diffusion of anaesthetic gases through different polymers.

BACKGROUND: Improvement of working conditions and anaesthesia with closed systems includes reduction of gas leaks during anaesthesia. One source of contamination is the permeation of gases through plastic materials. The volume of gas permeating through a polymer depends on its molecular structure, the solubility and the diffusion coefficient. METHODS: We designed an experimental set-up to measure the permeation rates of nitrous oxide, enflurane and isoflurane through components of the anaesthetic ventilator made of silicone, latex, rubber and polyvinylchloride (PVC). Reservoir bags, ventilation tubes and endotracheal tubes were investigated. RESULTS: The highest permeation rates of anaesthetic gases were observed with silicone materials. Permeation through silicone exceeded that of the least permeable material by more than 10.000 times. By summarizing the permeation rates of the single items, the use of silicone increases the anaesthetic system's leakage rate by 4 ml/min, which means an increase of 18% in a modern anaesthetic ventilator and of 31% in a closed system. CONCLUSIONS: The highest permeation rates were found for nitrous oxide through silicone, although nitrous oxide has a known low solubility in plastic materials. The result demonstrates the dependency of the leakage rate on the diffusibility. The leakage of anaesthetic gases caused by silicone items does not alone lead to unacceptable pollution of operating theatres. To minimize the total leakage rates of minimal-flow-systems, however, plastic materials with low solubility and low diffusion coefficients have to be used.

Anesthesia, Inhalation↗
PubMed1996

Effects of selective phosphodiesterase 3 inhibition in the perfused liver of the rat after endotoxin treatment.

1. This study was designed to investigate the role of rat phosphodiesterase 3 (RPDE3) in regulation of liver metabolism in sepsis. We studied the effects of the phosphodiesterase 3 inhibitor (PDI), enoximone, alone and in combination with regulating factors of hepatic carbohydrate metabolism and bile secretion in the perfused liver of rats treated 4 h earlier with endotoxin. In addition, cyclic AMP and cyclic GMP levels were determined in the effluate and bile by radio immunoassay methods. 2. After endotoxin treatment, infusion of enoximone at three concentrations (1 microM, 10 microM) resulted in an increased glucose output from -1.4 +/- 0.9 to 7.8 +/- 2.5 mumol l-1 20 min-1. Bile acid-independent bile flow increased also, in a dose-dependent manner. 3. In untreated livers, cyclic AMP release increased in the effluate from 1000 +/- 73 fmol g-1 min-1 to 1710 +/- 143 fmol g-1 min-1 when enoximone (10 microM) was administered. In bile from untreated livers, the level of cyclic AMP was also significantly increased by enoximone. After endotoxin treatment, the enoximone (10 microM) effect on cyclic AMP levels in effluate and bile was greatly reduced. Levels of cyclic GMP in the effluate and bile appeared unchanged in the presence of enoximone. 4. During co-infusion of glucagon (1 nM) and enoximone (10 microM), cyclic nucleotide levels in the effluate and bile of livers after endotoxin treatment were determined. In the effluate, cyclic AMP release increased from 827 +/- 144 fmol g-1 min-1 to 17802 +/- 2821 fmol g-1 min-1 when glucagon was administered. The presence of enoximone enhanced cyclic AMP further to 41696 +/- 920 fmol g-1 min-1. The same changes in cyclic AMP release were found in bile. Levels of cyclic GMP in the effluate and bile were not significantly affected by the administration of glucagon and the PDI. 5. Glucose release was determined during glucagon, sympathetic nerves stimulation and phenylephrine administration in the presence and absence of enoximone. The addition of enoximone to glucagon increased glucose release by 8.2 +/- 2.8 mumol g-1 20 min-1, without alteration of lactate balance. The PDI enhanced the glycogenolytic effects of nerve stimulation and of phenylephrine, accompanied by a reduction in lactate production. 6. Enoximone significantly enhanced the bile acid independent bile flow after glucagon, nerves stimulation and after administration of phenylephrine. Bile acid secretion was unaffected by the PDI. The vasoconstrictor effect of nerve stimulation was reduced by the PDI. 7. We conclude that endotoxin treatment reduces the ability of the PDI, enoximone, to increase cyclic AMP release in the perfused liver. The significant increase in cyclic AMP release after stimulation with glucagon and enoximone favours the view that RPDE3 is involved in the degradation of cyclic AMP in the liver after exposure to endotoxin. Additionally, the inhibition of the RPDE3 results in glucose release, vasodilatation and choleresis in endotoxin pretreated livers.

Animals↗
PubMed1995

Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs.

BACKGROUND: This study was designed to compare the effects of epinephrine with those of vasopressin on vital organ blood flow during closed-chest cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation. METHODS AND RESULTS: Vasopressin was compared with epinephrine by randomly allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or 0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood flow, determined by use of radiolabeled microspheres during CPR, before and then 90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22 +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/- 6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52 +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18 +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose vasopressin). At the same times, calculated coronary systolic perfusion pressures were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1, 39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/- 6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/- 5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin); and calculated coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low-dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose vasopressin). Total cerebral blood flow was significantly higher after high-dose vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5 minutes between groups). Five animals in the epinephrine, 5 in the low-dose vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin groups were successfully resuscitated and survived the 1-hour observation period. CONCLUSIONS: We conclude that administration of vasopressin leads to a significantly higher coronary perfusion pressure and myocardial blood flow than epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.

Animals↗
PubMed1995

Adjustment of metabolism, catecholamines and beta-adrenoceptors to 90 min of cycle ergometry.

Adrenaline infusion of 0.1 microgram.kg-1.min-1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied beta-adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity beta-adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (-)125 Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg.kg-1.min-1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg.kg-1.min-1 and from 0.40 (SD 0.05) to 0.32 (SD 0.04) mg.kg-1.min-1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol.l-1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol.l-1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol.l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ultrastructure and mucociliary transport of bronchial respiratory epithelium in intubated patients.

OBJECTIVE: The objective of this study was to investigate whether reduced bronchial mucus transport velocity (BTV) is associated with a loss of cilia or ultrastructural abnormalities of cilia in intubated patients. DESIGN: The patients were studied prospectively in a convenience sample trial. SETTING: The study took place in a university hospital. PATIENTS AND PARTICIPANTS: 29 orally intubated patients in a surgical ICU. INTERVENTIONS: BTV was measured with radiolabeled microspheres in the right and left primary bronchus. Following these measurements, biopsy samples were taken from the bronchi for scanning (SEM) and transmission (TEM) electron-microscopic investigations. MEASUREMENTS AND RESULTS: SEM: Patients with normal or slight impaired BTV (group 1, n = 14: BTV: 8.5 mm/min (3.8-11.5); median with range) showed more cilia on the luminal surface than patients with markedly depressed BTV (p < 0.05) (group 2, n = 15: BTV: 0 (0-2.1)). The difference was statistically significant. The BTV values correlated moderately with the number of cilia on the luminal surface (r = 0.46; p = 0.02). TEM: In group 1, 6.5% (3.9-14.9) of cilia were abnormal (median with range) vs 9.3% (4.9-13.7) in group 2; these differences were not statistically significant. Neither was there any significant correlation between BTV and the frequency of abnormal cilia. CONCLUSIONS: Impaired mucociliary transport in intubated patients is associated with a loss of cilia rather than ultrastructural abnormalities of cilia, which are less relevant.

Adult↗
PubMed1995

Are the effects of noradrenaline, adrenaline and dopamine infusions on VO2 and metabolism transient?

OBJECTIVE: To determine whether noradrenaline, adrenaline and dopamine have persistent actions on VO2 and metabolism. DESIGN: Descriptive laboratory investigation. SETTING: Laboratory of the Department of Anaesthesiology at a University Hospital. SUBJECTS: 9 volunteers. INTERVENTION: VO2 and the plasma concentration of glucose and free fatty acids were measured prior to and during a 4 h infusion of saline (control), noradrenaline (0.14 microgram/kg min) adrenaline (0.08 microgram/kg min) or dopamine (7 micrograms/kg min), n = 9 each. VO2 was measured using an open circuit gas exchange system. MEASUREMENTS AND MAIN RESULTS: VO2 increased from 250 +/- 22 ml/min to 280 +/- 38 ml/min during noradrenaline, to 298 +/- 30 ml/min during adrenaline and to 292 +/- 39 ml/min during dopamine infusion. The plasma glucose concentration increased from 6.2 +/- 0.6 mmol/l to 8.8 +/- 0.8 mmol/l, 13.2 +/- 1.4 and 7.3 +/- 0.4 mmol/l during infusion of noradrenaline, adrenaline or dopamine, respectively. The plasma free fatty acid concentration increased from 0.28 +/- 0.10 mmol/l to 0.79 +/- 0.21 mmol/l during noradrenaline and to 0.52 +/- 0.09 mmol/l during dopamine. In contrast, free fatty acid values averaged baseline values at the end of the adrenaline infusion after an initial increase to 0.72 +/- 0.31 mmol/l. CONCLUSIONS: Administration of noradrenaline, adrenaline or dopamine resulted in persistent increases in VO2 in volunteers. With the exception of the transient adrenaline effect on fatty acids the metabolic actions were steady during 4 h of adrenergic stimulation. Since the adrenergic effect on VO2 is persistent over time a similar action in patients (e.g. septic shock) during treatment with adrenoceptor agonists may be important. Thus, an increase in VO2 during therapy may not only reflect an oxygen debt but also a pharmacodynamic action of adrenoceptor mediated calorigenic and metabolic induction.

Adult↗
PubMed1995

[Quality control in anesthesiology. Results of a prospective study following the recommendations of the German Society of Anesthesiology and Intensive Care].

The German Social Law has required quality assurance (QA) procedures since 1989. The measures must be suitable to allow "comparing investigations". In 1992 the German Society of Anaesthesiology and Intensive Care Medicine published recommendations for QA in anaesthesia: most problems during an anaesthetic should be documented in a standardised manner, and thus, a list of 63 pitfalls, events, and complications (PECs) and five degrees of severity were defined. The goal of this study was to determine the frequency of PECs in anaesthesia and to correlate PECs with procedures and preoperative health status. MATERIALS AND METHODS. Demographic data, preoperative findings, type and duration of anaesthesia and operation, and kind and severity of PECs were integrated in an automatically readable anaesthetic data record (ARADR). During 12 months all anaesthetics in our department were documented by the ARADR; the records were read by a reading device and the data stored in a modern SQL database (Informix). Degrees of severity: I. PEC leads to reaction of anaesthetist, no impact for recovery room (RR); II. impact for RR, no impact on transfer to ward; III. significant prolongation of RR stay or additional monitoring on ward; IV. PEC leads to intensive care unit admission; V. disabling damage or death. RESULTS. In all, 18350 anaesthetics were recorded (9055 male, 9295 female); the median age was 41 years (1 day-99 years). In 4251 (23.2%) anaesthetics 5927 PECs occurred, 3412 of them involving the cardiovascular and 949 the respiratory system, the latter with a tendency to higher degrees of severity. PECs caused by technical equipment (126) or lesions caused by anaesthesists (342) had no fatal outcomes and were less severe. Patients in ASA class I had 12.3% anaesthetics with PECs, ASA II 23.3%, ASA III 33.8%, ASA IV 34.9%, and ASA V 58.5%. PECs of degrees IV and V showed a higher incidence in the higher ASA classes. There was no fatal PEC in an ASA class I patient and only one (of 13615) in an elective procedure. Emergency cases had more frequent and more severe PECs: 16 of 19 PECs of degree V were in ASA class IV and V patients and 15 in emergency situations, all of them in surgical patients. Patients with cardiovascular disease had a more frequent incidence of PECs by a factor of 1.39 to 5.93 than those without such disease. CONCLUSIONS. Standardised incident reporting by defined PECs seems a good way to describe problems in anaesthesia. The types of PECs in our study had a similar distribution to those in other investigations, but there was a tendency to less frequent fatal PECs in ASA classes I to IV and more frequent ones in ASA class V. We expect better comparability when multicenter studies are done using identical methods in the next few years. Perhaps different patients collectives with special risks will be detected; efforts in quality improvement could focus on these patients.

Adolescent↗
PubMed1995

[The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study].

Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in the BAL (Figs. 1, 2). Plasma concentrations of malondialdehyde were similar (Fig. 3). Only the levels of conjugated dienes were significantly higher on the 5th treatment day in the placebo group (Fig. 4). The organ function of the lung (FiO2, PEEP, PaO2), liver (SGOT, bilirubin), and kidney (creatinine) and coagulation parameters (PTT, prothrombin time, platelet count) were similar in the two groups during the time of investigation. We observed no clinically relevant differences in the tracheobronchial mucus (Table 2). CONCLUSION. The present data do not support routine use of NAC in ventilated patients, either as an antioxidant or as a mucolytic agent. Intravenous administration of 3 g NAC/day had no clinically relevant effect on glutathione levels, lipid peroxidation products, tracheobronchial mucus, and clinical condition.

APACHE↗
PubMed1995

Enhancement of hepatic glucose release and bile flow by the phosphodiesterase-III-inhibitor enoximone in the perfused rat liver.

The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the treatment of cardiac failure can be associated with hyperglycaemia. This phenomenon could be caused by hepatic events induced by PDI. The purpose of our study was to investigate the effects of the PDI enoximone on hepatic carbohydrate metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and lactate production, portal flow and bile flow were determined. Administration of enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid-independent bile flow in a dose-dependent manner. The PDI enhanced the glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from 9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol glucose/g/20 min). Furthermore, lactate production was significantly reduced by enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked or diminished by enoximone administration. In summary, it was shown that the PDI enoximone is able to enhance hepatic glucose production. Bile acid-independent bile flow was increased by the inhibition of phosphodiesterase-III. The effects of enoximone and glycogenolytic hormones on glucose release were synergistic. The vasoconstrictive action of catecholamines was reduced or completely prevented by enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and choleretic properties in the liver.

Animals↗
PubMed1995

Glycerol metabolism in patients with alcohol-induced liver cirrhosis.

The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.

Journal Article↗
PubMed1995

Right ventricular function after coronary artery bypass grafting in patients with and without revascularization of the right coronary artery.

OBJECTIVES: To evaluate the influence of revascularization of a stenosis of the right coronary artery on right ventricular function. DESIGN: Prospective study. SETTING: Single institutional study in a university hospital. PARTICIPANTS: 20 patients with different degrees of stenosis of the right coronary artery undergoing elective coronary artery bypass grafting. INTERVENTIONS: In 10 patients, bypass surgery included revascularization of a significant stenosis of the right coronary artery (group 1). In 10 other patients, the pathology of the right coronary artery was judged to be not significant, without indication for revascularization (group 2). MEASUREMENTS AND MAIN RESULTS: Using the fast-response thermodilution pulmonary artery catheter, right ventricular function was estimated perioperatively. After termination of extracorporeal circulation, there was an increase in right ventricular volumes in group 2 (p < 0.05) and an initial decrease in group 1 (p < 0.05), with higher volumes in group 2 compared with group 1 (p < 0.05). The ejection fraction increased in group 1 (p < 0.05) and decreased in group 2 after operation (p < 0.05), with higher values in group 1 compared with group 2 (p < 0.05). In addition to these findings, the pressure-volume relationship showed a leftward and upward shift in group 1 and a rightward shift in group 2 postoperatively. CONCLUSIONS: These results indicate that right ventricular depression can occur after bypass grafting in patients with a moderate stenosis of the right coronary artery that is not revascularized. Revascularization of more severe stenosis of the right coronary artery appears to preserve postoperative right ventricular function.

Cardiac Volume↗
PubMed1995

Pre- and postoperative investigations of hepatic glucose production and leucine turnover in Cushing's disease utilizing stable isotope techniques.

Impairment of glucose tolerance and muscle wasting indicating a disorder of glucose metabolism are characteristic features of Cushing's syndrome. We have examined glucose and amino acid metabolism in eleven patients with pituitary dependent Cushing's disease in comparison to nine healthy controls. Furthermore, the therapeutic effect of selective pituitary microsurgery was studied by repeated stable isotope measurements of hepatic glucose production and leucine turnover rates. Eight patients remitted after surgery and 3 had persistent disease. All patients were investigated prior to surgery and again 1 week and 3 months after the operation with (6,6-2H2)-glucose and (5,5,5-2H3)-leucine by means of a primed (4 mg/kg.min and 0.27 mg/kg.min), continuous (0.05 mg/kg.min and 0.005 mg/kg.min) infusion. In Cushing's disease, both the preoperatively elevated mean glucose production rate (2.34 +/- 0.63 mg/kg.min) and the reduced mean leucine turnover (0.213 +/- 0.025 mg/kg.min) were found to be linked with hepatic insulin resistance and an insulin-induced reduction in protein breakdown combined with a reduced protein synthesis. Mean glucose production and leucine flux both normalized after surgery in the remitting patients (2.18 +/- 0.15 mg/kg.min and 0.244 +/- 0.047 mg/kg.min 3 months after the operation). The metabolic disorders thus were reversible following successful correction of hormonal oversecretion by transsphenoidal surgery.

Adult↗