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Biomedical subjects

H A Adams

Publications and source records attributed to H A Adams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors.

BACKGROUND: The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide. METHODS: Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-alpha release were studied. RESULTS: Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0-6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-alpha response in vitro, their addition post-treatment failed to restore the monocytic TNF-alpha response. CONCLUSIONS: Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.

Adult↗
PubMed1999

[Effect of anesthetics on the function of the gastrointestinal tract].

In spite of numerous interactions between the gut and the entire organism, today's knowledge in this field is still limited. In intensive care patients, reduced gastrointestinal perfusion and motility result in sequestration of fluids and translocation of bacteria and endotoxins, and the immunological function of the gut is depressed. To prevent gastrointestinal organ failure, early restitution of enteral nutrition is a main goal in intensive care medicine. Thus, the influence of anaesthetics on gut function is of special importance in analgosedation of intensive care patients. Pharmacological data of common anaesthetics allow judgement of their global effects on the gut. Interactions with opioid receptors of the enteral nerve system and systemic effects on the vegetative nerve system are of special interest. The results of in vitro and clinical studies show profound negative effects of opiods on gastrointestinal motility. Piritramide seems to be excluded from this judgement, but further studies with equipotent analgetic doses, when compared with fentanyl, are necessary. Ketamine is an analgetic alternative without relevant negative effects on gastrointestinal motility. Among the sedative components of analgosedation, midazolam, gamma-hydroxy butyric acid and probably propofol are useful, whereas barbiturates seem to have negative effects. Epidural anaesthesia with local anaesthetics is of additional benefit.

Anesthetics↗
PubMed1998

[Volume replacement solutions--pharmacology and clinical use].

PHYSIOLOGY AND PATHOPHYSIOLOGY: Total body water represents 60% of body weight (BW), consisting of 40% BW intra- and 20% BW extracellular fluid. Extracellular fluid is divided into 16% BW interstitial fluid and 4% BW plasma volume (Fig. 1). The colloid oncotic pressure (COP) of the plasma proteins, which is about 25 mmHg (Fig. 2), is the main factor for the retention of intravascular volume and the prevention of interstitial edema. Within a defined range, oxygen transport capacity can be improved by normovolaemic haemodilution. Under strictly normovolaemic conditions ("controlled haemodilution"), the critical haemoglobin concentration for intensive care patients is about 10.0 g/dl, and 8-6 g/dl in patients with satisfactory compensatory mechanisms under stable clinical conditions. Larger blood volume deficits are replaced step by step with volume replacement solutions (crystalloids and synthetic colloids), packed red cells, fresh-frozen plasma, and platelets (Fig. 3). VOLUME REPLACEMENT WITH CRYSTALLOID AND COLLOID SOLUTIONS: Crystalloid solutions do not contain any macromolecules. Due to their lack of intrinsic COP, they spread rapidly over the intravascular and interstitial space. To achieve a comparable volume effect like colloid solutions, a fourfold infusion volume is necessary. Thus, crystalloids should be used in addition to colloid solutions to compensate the interstitial fluid deficit. Hyperosmotic-hyperoncotic solutions have not yet been established, and their benefit seems doubtful. Synthetic colloid solutions contain gelatin, dextran, or hydroxyethyl starch (HES) molecules. Due to their intrinsic COP, fluid is fixated in the intravascular space (Fig. 4). Solutions with high COP increase the intravascular volume due to resorption of interstitial fluid (plasma expanders). Pharmacological characterisation of synthetic colloids includes concentration [%], mean molecular weight [x1,000 Dalton] and degree and position of substitution (HES only). Main clinical features are the maximal volume effect and the duration of a 100% and a 50% volume effect (Fig. 5). For economic reasons, 5% albumin should not be used for volume replacement. The use of 20% albumin in intensive care patients is also limited and recommended only if a capillary leck is unlikely and the dose limits of synthetic colloids are reached. Gelatin is a polypeptide of bovine origin and achieves a shortlasting isovolaemic volume effect. When compared with dextran or HES, negative effects on haemostatis are less, and the renal function is not impaired. Thus, gelatin is first of all indicated in patients with limited volume demand, and secondly in situations with massive blood losses, when the dose limits of HES are reached. Dextran has no specific benefits. HES is a polysaccharide of maize or potato origin. By substitution of glucose molecules with hydroxyethyl groups, starch molecules are protected against fast amylase degradation. Metabolism depends on the degree and position of substitution and mean molecular weight. Smaller molecules are eliminated via the kidneys, but a certain amount of larger molecules is stored in the reticulo-endothelial system. HES is available in very different preparations (concentration 3-10%, mean molecular weight 70,000-450,000 Dalton, substitution 50-70%). Special indications of 10% HES 200/0.5 are rapid hypervolaemic replacement of massive blood losses and increase of COP in intensive care patients without capillary leak. Synthetic colloids as well as albumin may lead to adverse reactions, which are generally very rare. In large-scala studies, no significant differences have been found with regard to incidence and severity.

Animals↗
PubMed1998

Stability of local anesthetics in heparinized blood, plasma and sulfuric acid.

BACKGROUND: This study was undertaken to investigate the stability of local anesthetics in different media. METHODS: 60 patients with axillary plexus block, using prilocaine, mepivacaine or lidocaine 1%, or with lumbar epidural catheter-anesthesia, using bupivacaine 0.5%, were investigated. Stability was evaluated in heparinized whole blood for 24 h at +4 degrees C, in plasma for 8 week at -25 degrees C and in sulfuric acid for 6 months at -25 degrees C. RESULTS: Mean recovery rates were between 96.4% and 102.6% in all local anesthetics and media. No statistical significance became obvious for differences between recovery rates and initial values. CONCLUSION: Stability of prilocaine, mepivacaine, lidocaine and bupivacaine can be expected when samples are stored as heparinized whole blood for 24 h at +4 degrees C, plasma for 8 weeks at -25 degrees C, and after preparation into sulfuric acid for 6 months at -25 degrees C.

Anesthesia, Epidural↗
PubMed1998

[Mechanisms of action of ketamine].

Racemic ketamine is a mixture of equal amounts of the two enantiomers (S)-ketamine and (R)-ketamine. The analgesic and anaesthetic potency of (S)-ketamine is about threefold superior to (R)-ketamine. Along with faster elimination, improved control of the anaesthetic state with reduced drug load is achieved. Pharmacokinetic properties of (S)-ketamine are generally comparable with the racemic mixture. The pharmacological profile of ketamine is characterized by the so-called "dissociative anaesthesic state" with profound analgesic and moderate hypnotic properties and by marked sympathomimetic reactions. Important adverse effects are hallucinations and hypersalivation. This pharmacological profile cannot be explained by a single mechanism. Analgesic, anaesthetic and sympathomimetic effects are mediated by different sites of action. N-methyl-D-aspartate (NMDA)-receptor antagonism is the most important neuropharmacological mechanism for the analgesic effects of ketamine. The same mechanism may be involved in the supposed neuroprotective potency of the substance. Effects on opiate receptors may contribute to the analgesic state as well as to dysphoric reactions. Sympathomimetic properties are mediated by enhanced central peripheral monoaminergic transmission. Inhibition of central and peripheral cholinergic transmission may contribute to the induction of anaesthetic state and hallucinations. Effects on neuromuscular transmission are unimportant. Local anaesthetic qualities are obvious as well, but are not responsible for systemic effects. At the different sites of action, qualitatively comparable effects of (S)- and (R)-ketamine were found, but significant quantitative differences are obvious as well.

Anesthesia, Intravenous↗
PubMed1997

[Endocrine reactions following S-(+)-ketamine].

ANAESTHETICS, ENDOCRINE SYSTEM, AND STRESS: The effects of anaesthetics on the nervous system are invariably associated with endocrine reactions, which are of great importance for the general characterization of anaesthetics or anaesthetic regimens. In this context, the endocrine stress response is mainly represented by adrenaline (A), noradrenaline (NA), antidiuretic hormone/vasopressin (ADH), adrenocorticotropic hormone (ACTH), and cortisol. PHARMACOLOGICAL PROFILE AND ANAESTHETIC ACTION OF KETAMINE: The pharmacological profile of ketamine is characterized by the term "dissociative anaesthesia." At the present time, the anaesthetic action of ketamine cannot be explained by a single mechanism. Its overall action might be due to different central and peripheral factors, and stereospecific effects are obvious. ENDOCRINE RESPONSES TO RACEMIC KETAMINE AND S(+)-KETAMINE: In contrast to stereospecific differences in the anaesthetic action of racemic ketamine and S-(+)-ketamine, the endocrine reactions to the S-(+) isomer and the racemic mixture are very similar. When S(+)-ketamine is used as the sole anaesthetic, significant activation of the sympathoadrenergic system with increases in plasma levels of A and NA can be observed. This effect is mitigated by midazolam. In combination with propofol, sympathoadrenergic responsiveness is preserved without overwhelming effects. In contrast to monoanaesthesia with S(+)-ketamine, during combination with midazolam and propofol significant increases in plasma ADH levels are observed, which might be due to suppressed sympathoadrenergic reactivity. In addition, surgical stress activates the pituitary-adrenocortical system with increases in ACTH and cortisol. Effects of midazolam and propofol on this effect are similar. SYNOPSIS AND CLINICAL ASPECTS: S-(+)-ketamine as a monoanaesthetic has significant sympathomimetic properties, which are beneficial during induction of patients in shock and patients with asthma. The combination of S-(+)-ketamine and midazolam has weaker sympathomimetic and general endocrine-stimulating properties, and can be used for analgosedation in patients with cardiovascular instability and exogenous catecholamine requirements. In combination with propofol, the sympathomimetic and general endocrine-stimulating effects of S-(+)-ketamine are less pronounced because of contrasting properties of both drugs. This combination might be useful in patients with endocrine deficits and for analgosedation, when rapid recovery is necessary and negative circulatory effects should be avoided.

Anesthetics, General↗
PubMed1997

[From the racemate to the eutomer: (S)-ketamine. Renaissance of a substance?].

The pharmacological profile of ketamine: Until recently, clinically available ketamine was a racemic mixture containing equal amounts of two enantiomers, (S)- and (R)-ketamine. The pharmacological profile of racemic ketamine is characterized by the so called dissociative anesthetic state and profound sympathomimetic properties. Among the different sites of action, N-methyl-D-aspartate (NMDA)-receptor antagonism is considered to be the most important neuropharmacological mechanism of ketamine. Effects on opiate receptors, monoaminergic and cholinergic transmitters, and local anesthetic effects are obvious as well. Following intravenous administration, a rapid onset of action is seen within 1 min, lasting for about 10 min. The anaesthetic state is terminated due to redistribution, followed by hepatic and renal elimination with a half-life period of 2-3 h. For alternative administration, the intramuscular and oral route is also appropriate. The most important adverse effects are hallucinations and excessive increases in blood pressure and heart rate. These reactions can be attenuated or avoided by combining of ketamine with sedative or hypnotic drugs like midazolam and/or propofol. During controlled ventilation, increases in intracranial pressure are unlikely to occur. The special pharmacological profile of (S)-ketamine: In general, the pharmacological properties of (S)-ketamine are comparable to the racemic compound. On the different sites of action, qualitatively comparable effects were found, but significant quantitative differences also became obvious. When compared with (R)-ketamine and the racmic mixture, the analgesic and anesthetic potency of (S)-ketamine is threefold or twofold higher. Thus, a 50% reduction of dosage is possible to achieve comparable clinical results. Because of the faster elimination of (S)-ketamine, better control of anesthesia will be provided. In summary, the pharmacokinetic improvements of (S)-ketamine are characterized by a reduced drug load, along with more rapid recovery. The clinical use of (S)-ketamine: The clinical use of (S)-ketamine depends on its analgesic and sympathomimetic properties, whereas the anaesthetic potency remains in the background. In clinical anesthesiology, (S)-ketamine, especially in combination with midazolam and/or propofol, can be used for short procedures with preserved spontaneous ventilation, for induction of anesthesia in patients with shock or asthmatic disorders, and for induction and maintenance of anesthesia in caesarean sections. Additional indications are repeated anesthesia, for example, in burn patients, analgesia during delivery and diagnostic procedures and intramuscular administration in uncooperative patients. The value of (S)-ketamine as an analgesic component for total intravenous anesthesia has not been defined yet. In comparison with opioides, the advantages are related to improved hemodynamic stability and reduced postoperative respiratory depression. When (S)-ketamine, especially in combination with midazolam, is used for analgosedation in intensive care medicine, a reduction of exogenous catecholamine demand can be expected. Moreover, the effects on intestinal motility are superior to opioids. In combination with midazolam and propofol, excellent control of analgosedation was found, making both combinations suitable for situations in which repeated neurological assessment of patients is necessary. In emergency and disaster medicine, (S)-ketamine is of outstanding importance because of its minimal logistic requirements, the chance for intramuscular administration and the broad range of use for analgesia, anaesthesia and analgosedation as well. Further perspectives of (S)-ketamine may be the treatment of chronic pain and the assumed neuroprotective action of the substance.

Anesthesia, General↗
PubMed1997

[Endocrine reactions, circulatory and resuscitation behavior in ketamine-midazolam anesthesia. A comparative study of ketamine racemate vs. (S)-ketamine in knee surgery].

UNLABELLED: Clinically used ketamine is a racemic mixture of two isomers, (S)- and (R)-ketamine, in equal amounts. Previous investigations showed the anaesthetic potency of (S)-ketamine to be three times higher than that of (R)-ketamine. The aim of this study was to compare the effects of (S)-ketamine/midazolam and racemic ketamine/midazolam on endocrine and cardiovascular parameters, recovery, and side effects in unpremedicated patients during knee surgery. METHODS: 41 patients scheduled for elective knee surgery were investigated in a prospective, double-blind, and randomised design. For induction of intravenous anesthesia, patients received 0.1 mg/kg midazolam, 0.003 mg/kg atropine, 1 mg/kg (S)-ketamine or 2 mg/kg racemic ketamine, respectively. For tracheal intubation, 1 mg vecuronium and 1.5 mg/kg suxamethonium were injected. After intubation and relaxation with a total dose of 0.1 mg/kg vecuronium, a continuous infusion of 0.5 mg/kg/h (S)- or 1 mg/kg/h racemic ketamine was administered throughout the surgery. In addition, 0.05 mg/kg/h midazolam was infused continuously in both groups throughout surgery. Ventilation was performed with N2O/O2 (FiO2 0.3). Blood samples were taken using a central venous line five times before induction as well as during and after surgery for analysis of adrenaline, noradrenaline (by high-pressure liquid chromatography with electrochemical detection), anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by radioimmunoassay). In addition, systolic and diastolic arterial pressure (SAP, DAP), heart rate (HR), and arterial oxygen saturation were measured. The time intervals between the end of ketamine and midazolam infusion and the return of consciousness and orientation were recorded. The incidence and quality of dreams and other side effects were reported by the patients. RESULTS: Biometric data of the groups were comparable. Plasma adrenaline and noradrenaline did not change significantly during anaesthesia. ADH increased significantly (p < 0.05) after skin incision in both groups.

Adolescent↗
PubMed1997

[S-(+)-ketamine. Circulatory interactions during total intravenous anesthesia and analgesia-sedation].

UNLABELLED: General cardiovascular properties of ketamine: "In vitro", ketamine has moderate negative inotropic effects. "In vivo", a significant central sympathomimetic action with consecutive hemodynamic effects is dominant. The sympathomimetic potency of ketamine is one of the most significant pharmacological features of the substance with direct clinical implications. Monoanaesthesia with S-(+)-ketamine: After application of racemic ketamine or S(+)-ketamine as well, identic and significant increases in plasma catecholamines, arterial pressure and heart rate are observed. This outstanding sympathomimetic action is beneficial in induction of patients with shock or asthmatic state. TIVA and analgosedation with S-(+)-ketamine and midazolam: The sympathomimetic effect of S(+)-ketamine, and racemic ketamine as well, is mitigated by midazolam. Nevertheless, significant increases in heart rate and arteriel pressure might be observed. Clinical use of the combination is common in short procedures like reposition maneuvers. Of greater importance is the use for analgosedation in patients with cardiovascular instability, particularly in patients with exogenous catecholamine demand. TIVA and analgosedation with S-(+)-ketamine and propofol: When S(+)-ketamine is combined with propofol, the sympatholytic effects of propofol are counteracted by S(+)-ketamine, and stable hemodynamic conditions are presented. This combination seems useful for TIVA in patients with hypotonic dysregulation or endocrine deficits like hypothyreosis and adrenal insufficiency. Furthermore, analgosedation with S(+)-ketamine and propofol is advantageous, when rapid recovery is necessary and negative circulatory effects should be avoided. CONCLUSION: Sympathoadrenergic and hemodynamic effects of S(+)-ketamine and racemic ketamine are generally identical. The distinctest action is observed, when S(+)-ketamine is used as a monoanaesthetic. In combination with midazolam, a significant reduction is achieved. In combination with propofol, the sympatholytic effects of this hypnotic agent are compensated by S(+)-ketamine. With respect to sympathoadrenergic and hemodynamic reactions, the clinical position of S(+)-ketamine is unchanged. Nevertheless, a significant clinical progress can be expected due to improved recovery and reduced substance load, when racemic ketamine is replaced by S(+)-ketamine.

Analgesia↗
PubMed1997

[Results of autologous blood donation in orthopedic hip and knee joint replacement].

OBJECTIVE: This study was undertaken to investigate the efficiency of autologous blood donation (ABD) with regard to saving of homologous transfusion, to determine the reasons for exclusion from donations and the rate of incidents during the procedure, and to investigate the quality of autologous fresh frozen plasma (AFFP). METHODS: During an observation period of 4.5 years, all patients scheduled for elective orthopaedic hip and knee replacement were included. A period of 4 years was evaluated retrospectively, and the last half year was evaluated prospectively. RESULTS: Among a collective of 710 patients, 55 (8%) non-donors and 655 (92%) donors with a total number of 1592 ABD were found. Mean age of non-donors with hip surgery was significantly higher than that of donors (72 vs. 64 years), the same was observed in patients with knee surgery (71 vs. 68 years). In the hip surgery group, 11 of 338 patients were non-donors (3%), compared with 44 of 372 patients with knee surgery (12%). In the prospective part of the study, 7% of 121 patients were non-donors. Reasons for exclusion from donation were 5 times of medical and 4 times of organisational nature. In donors for hip surgery, a mean of 3.0 units was collected, compared with 1.9 units in donors for knee surgery. On the day before operation, mean haemoglobin concentrations were similar in donors and non-donors. During ABD, 11 incidents were observed, representing 0.69% of all ABD, 83.5% of 327 donors with hip surgery left the hospital without any transfusion of homologous blood, 16.5 of donors with hip surgery received one or more homologous transfusions, compared with 100% of non-donors (p < 0.001). In knee surgery, 93.3% of donors and 63.6% of non-donors required no homologous blood, whereas 6.7% of donors and 36.4% of non-donors received one or more homologous transfusions (p < 0.001). 529 of 2850 autologous blood units (19%) were not transfused, and 19 of these units were rejected due to technical or organisational problems. In 97 patients with 240 ABD and 240 AFFP, prothrombine time, fibrinogen concentration and AT III in defrosted AFFP exceeded 70% of the values determined before ABD. CONCLUSION: ABD is a safe procedure in almost all, even elderly, patients scheduled for elective orthopaedic hip or knee replacement in both types of operations, ABD reduces the risk of homologous transfusion significantly. A number of 3-4 units is necessary for total hip replacement, whereas 2 units are sufficient for partial or total knee replacement. Haemostatic quality of AFFP meets the requirements of fresh frozen homologous plasma.

Adult↗
PubMed1996

[Specific risks of active compression-decompression in cardiopulmonary resuscitation: a case report].

Circulatory effects of cardiopulmonary resuscitation with active compression-decompression (CPR-ACD) are superior to the conventional technique. Decompression, thoracic expansion and a corresponding suction effect obviously improves cardiac preload. Due to significant or unphysiological thoracic expansion, thorax, diaphragma, and epigastrium are exposed to considerable traction powers. In a patient with fulminant pulmonary embolism, conventional cardiac massage and ACD were maintained during 65 minutes with simultaneous systemic thrombolytic therapy. After CPR, the patient developed a massive haemorrhagic shock. During emergency laparotomy, significant adhesions of upper abdominal organs with serious injuries of spleen and liver were found. Traction powers during CPR-ACD in combination with abdominal adhesions are considered responsible. Until improved outcome of CPR-ACD is demonstrated in larger clinical investigations, at least initially conventional cardiac massage should be preferred before the ACD-technique is used. Special attention to patients with a history of upper abdominal operations or chronic inflammatory lung diseases is mandatory.

Cardiopulmonary Resuscitation↗
PubMed1995

Ketamine and strychnine treatment of an infant with nonketotic hyperglycinaemia.

UNLABELLED: Non-ketotic hyperglycinaemia (NKH) is a severe seizure disorder associated with high glycine levels. Glycine is a major inhibitory neurotransmitter in the CNS, but has also modulating effects at one of the glutamate receptors, the N-methyl-D-aspartate-(NMDA) receptor. Based on this knowledge we treated a female newborn suffering from severe NKH with the NMDA receptor blocker ketamine in association with strychnine and magnesium supplementation. This treatment led to cessation of seizures, reappearance of swallowing and sucking and improved the neurological status. Some pharmacokinetic data of strychnine and ketamine in the infant are given. CONCLUSION: Ketamine in combination with strychnine may be beneficial in non-ketotic hyperglycinaemia.

Amino Acid Metabolism, Inborn Errors↗