The effects of norepinephrine on hemodynamics and renal function in severe septic shock states

Objective To investigate the effect of norepinephrine (NE) on hemodynamics, oxygen metabolism and renal function in patients with severe septic shock.Design Prospective study.Setting Post-operative ICU in a municipal general hospital.Patients The study included 56 patients with extreme low resistance states due to abdominal sepsis, who remained hypotensive (MAP<60 mmHg) despite optimal fluid therapy and dopamine>20g/kg/min and cumulative doses of dopamine and dobutamine>30g/kg/min, respectively.Interventions After registration of baseline values dopamine was reduced to 2.5g/kg/min, and norepinephrine was administered starting at a dose of 0.05 g/kg/min until a mean arterial pressure of more than 60 mmHg could be maintained.Measurements and results During norepinephrine infusion (dosage ranging between 0.1–2g/kg/min, mean dose rate: 0.4g/kg/min) mean arterial pressure and systemic vascular resistance index increased significantly (p<0.001). After 8h a significant increase in stroke volume (p<0.05) and decrease in heart rate (P<0.05) could be observed. There was no significant change in cardiac index (CI), oxygen delivery (O₂AVI) and oxygen consumption (VO₂I). Creatinine clearance increased significantly (p<0.005) from a control value of 75±37 ml/min to 102±43 ml/min after 48 h NE-trearment.Conclusion Our results suggest that norepinephrine can be used safely in the treatment of severe septic shock states. Mean arterial pressure and glomerular filtration rate improved markedly without deleterious effects on CI, O₂AVI and VO₂I.     

Effects of thiopental on resistance vessels in cat skeletal muscle

Barbiturates are used clinically as anaesthetics and to reduce raised intracranial pressure. One side effect is hypotension, usually ascribed to a depression of cardiac contractility, while their effects on the resistance vessels are more controversial: both vasodilation and vasoconstriction have been described. This study analyzes the effects of thiopental on basal vascular tone in the cat skeletal muscle. We found that total resistance increased by almost 20% at low (50mol/l) and decreased down to about 50% of control at high (350 mol/l) plasma concentrations of thiopental. The vasoconstriction dominated in the large arterioles (i.d. >25 m) and the vasodilation in the small arterioles (i.d. <25 m). A dosedependent inhibition of myogenic vascular reactivity (here defined as the maximum resistance increase to a transient rise in transmural pressure) coincided with the vasodilation. Autoregulation of blood flow was depressed by thiopental. During vasoconstriction there was a net transcapillary fluid absorption and during vasodilation a net fluid filtration. The fluid movements could be ascribed to variations in capillary hydrostatic pressure. If applicable to the cerebral circulation these results suggest that thiopental at high plasma concentrations might induce, instead of reduce, interstitial brain oedema.     

Plasma lipid peroxides and antioxidants in human septic shock

In order to assess if an oxidant/antioxidant imaalance is involved in human septic shock and its outcome, we measured plasma levels of the lipid peroxides malondialdehyde—as thiobarbituric acid reactive substance—conjugated dienes and fluorescent products, together with the antioxidants alpha-tocopherol, glutathione peroxidase activity and selenium in 12 patients with septic shock and compared them with values of normal controls. At first measurements, malondialdehyde (median 3.9 mol/l; range 2–38.8) and fluorescent products (median 21.2%; range 9.4–134) were elevated (p<0.05), alpha-tocopherol (median 15 mol/l; range 7–25) and selenium (median 0.76 g/ml; range 0.49–1.09) were depressed (p<0.05). Conjugated dienes and glutathione peroxidase activity were in the normal range. In non-survivors (n=5) initial levels of malondialdehyde and fluorescent products (median 11 versus 3.1 mol/l; 74 versus 135 respectively) were higher than in survivors (p<0.05) and initial selenium levels were lower (median 0.58 versus 0.92 g/l;p<0.05). These results are consistent with the concept that an oxidant/antioxidant imbalance—as indicated by elevated plasma lipid peroxides and depressed antioxidants—is involved in human septic shock and a fatal outcome.     

Studies on the ultrastructure of blood cells and the microaggregate fraction in stored human blood

Electron microscopy of citrate-phosphatedextrose (CPD) buffered bank blood performed over 21 days shows that the normal architecture of erythrocytes, platelets and leucocytes disappears and that deformed organelles, leucocyte ghosts, cell fragments and microaggregates accumulate. Leucocytes and platelets emerge as the most sensitive indicators of blood deterioration showing profound morphological changes from the first day. Microaggregates which passed through a 20-m high capacity transfusion filter were identified as platelet conglomerates, leucocyte ghost and platelet-leucocyte ghost coaggregates with diameters of 6–20, 20–30 and 30–40 m respectively. of these aggregates present in the filtrate, 62% fell into the size range of 20–40 m. The composition of microaggregates varies with storage time, the platelet conglomerates appear first during or after Day 1, leucocyte ghosts after Day 5 followed by platelet-leucocyte ghost coaggregate formation. At this stage the number of intact leucocytes and platelets is reduced and the filtrate shows an abundance of leucocyte debris. Microfiltration would thus appear to reduce but not eliminate the danger of microembolism and damage to capillary endothelium.     

Multicenter,randomized trial of ramosetron plus dexamethasone versus ramosetron alone in controlling cisplatin-induced emesis

Goals To establish whether the combination of a corticosteroid (dexamethasone) and the newer serotonin-3 (5-HT₃) receptor antagonist ramosetron is superior to ramosetron alone in controlling cisplatin-induced emesis.Patients and methods A total of 283 patients aged 18–75 years with confirmed malignant disease who were scheduled to receive cisplatin 50 mg/m² with or without other antineoplastic agents were randomized to intravenous treatment with either ramosetron 300 g plus dexamethasone 20 mg (n=149) or ramosetron 300 g alone (n=134) given 30 min prior to cisplatin infusion. If vomiting occurred in the following 24 h, patients in both groups received an intravenous rescue dose of ramosetron 300 g. Subsequently, on days 2 and 3, treatment was continued orally with either ramosetron 100 g once daily plus dexamethasone 8 mg twice daily, or ramosetron 100 g once daily.Main results During the first 24 h after cisplatin infusion, significantly more patients receiving combination therapy had a complete response (no nausea or vomiting or requirement for rescue therapy) than those receiving ramosetron alone (68% vs 54%, respectively; P=0.034), and significantly fewer patients needed a rescue dose of ramosetron (22% vs 34%, respectively; P=0.032). In addition, the percentages of patients with no nausea and no vomiting were significantly greater in the ramosetron plus dexamethasone group than in the ramosetron-alone group at both 24 h and 72 h after cisplatin administration.Conclusions The antiemetic efficacy of ramosetron in cancer patients receiving highly emetogenic cisplatin chemotherapy is significantly enhanced by its use in combination with dexamethasone.This work is presented on behalf of the Philippines Nasea Study Group whose members are listed in the Appendix.     

A comparison of dopamine,dobutamine and isoproterenol in the treatment of shock

Twelve patients in shock, defined as being present if the mean arterial blood pressure was less than 60 mm Hg, pulmonary arterial occlusion pressure was 15 mm Hg or greater, urine output was 20 ml or less for 2 consecutive hours, and there was clinical evidence of poor peripheral perfusion, underwent a comparative therapeutic trial with dopamine at 200 g · min^-1 and 400 g · min^-1 (2.5–5.5 g · kg^-1 · min^-1), dobutamine 250 g · min^-1 and 500 g · min^-1 (3.5–7 g · kg^-1 · min^-1) and isoproterenol 2 g · min^-1 and 4 g · min^-1 (0.025–0.055 g · kg^-1 · min^-1). Isoproterenol at 2 g · min^-1, produced a significant increase in pulse rate, cardiac output, left ventricular stroke work index and decrease in mean pulmonary blood pressure and pulmonary arterial occlusion pressure and at 4 g · min^-1 a significant increase in stroke volume, mixed venous oxygen tension and decrease in right atrial pressure and systemic vascular resistance was also observed. Dopamine at 200 g · min^-1 produced a significant increase in cardiac output, pulmonary arterial occlusion pressure and mixed venous oxygen tension and at 400 g · min^-1 a significant increase in pulse rate, mean arterial blood pressure mean pulmonary blood pressure, right ventricular stroke work index, right atrial pressure and pulmonary arterial occlusion pressure and decrease in arterial oxygen tension was also observed. Dobutamine at 250 g · min^-1 produced a significant increase in cardiac output, and at 500 g · min^-1 a significant increase in pulse rate, mixed venous oxgen tension and decrease in pulmonary arterial occlusion pressure.All agents increased pulse rate and cardiac output, although in the dosages chosen dopamine was the only agent do so with an increase in pulmonary arterial occlusion pressure and decrease in arterial oxygen tension. In patients in shock if an inotropic agent is considered necessary its pulmonary effect should be considered along with its effect on coronary and peripheral perfusion since dopamine may reduce arterial oxygenation.     

Cortisol and catecholamine kinetics during continuous hemodiafiltration in patients with multiple organ dysfunction syndrome

Objective To assess the influence of continuous hemodiafiltration (CHDF) on cortisol and catecholamine kinetics in multiple organ dysfunction syndrome.Design Consecutive clinical study.Setting General intensive care unit of a university hospital.Patients Ten adult patients with multiple organ dysfunction syndrome requiring CHDF.Measurements and results A total of 40 samples were collected during CHDF for cortisol and catecholamine assays. The clearances for cortisol, epinephrine, norepinephrine and dopamine were 2.5±1.7 ml/min, 26.3±2.7 ml/min, 16.7±4.2 ml/min and 26.3±2.6 ml/min (Mean±SE), and their daily extractions were 1.8±0.2 mg/day, 11.4±4.8 g/day, 1.0±0.1 g and 2.3±0.3 g/day, respectively. There were no significant changes in blood cortisol and catecholamine levels during CHDF conducted for 48 h.Conclusions The cortisol and catecholamine losses during CHDF were small and unlikely to lead to hemodynamic disturbances.     

Transthoracic electrical impedance during extracorporeal hemodialysis in acute respiratory failure (“Shocked lung syndrome”)

The alteration (Z ₀ ) of transthoracic electrical impedance (TEI) during extracorporeal hemodialysis (EHD) was investigated in two Groups of patients with acute renal and acute respiratory failure, that differed with respect to the severity of respiratory insufficiency. Group I had moderate respiratory failure (Fi _{O 2} 0.31±0.10, Pa _{0 2} 84±14 mmHg), and Group II had severe respiratory failure (Fi _{0 2} 0.75±0.17, Pa _{O O} 77±14 mmHg). There was a significant correlation between increase in TEI (Z₀) and decrease in body weight (BW) in each individual patient, but the slope of regression lines was remarkably flattened in Group II. In Group I, TEI was 1.9±0.9 , the calculated TEI for 500 gr decrease in BW (Z_{0–500 gr}) was 0.59±0.21 , and a significant correlation existed between pooled data of Z₀ and BW. In Group II TEI increased less significantly, TEI was 0.6±0.3 (P<0.001), Z_{0–500 gr} was 0.26±0.27 (P<0.01), and there was no correlation between pooled data of Z₀ and BW. Increase of TEI in Group II could be completely attributed to increase in hematocrit. It is concluded that patients of Group I with acute renal failure and moderate respiratory failure lost intrathoracic fluid during EHD, whereas patients of Group II with severe respiratory failure did not. TEI during EHD may serve as a test for detection of fixed fluid within the pulmonary interstitium indicating a poor prognosis of the acute respiratory failure.     

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation

Objective Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA.Design Prospective trial.Setting University laboratory.Subjects A total of 78 guinea pigs (498.9±10.6 g).Interventions Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 l/kg) injection.Measurement and results Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time-and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not.Conclusions It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.     

Impaired gastric emptying in mechanically ventilated,critically ill patients

Objective To measure gastric emptying in critically ill patients using an acetaminophen absorption model and determine which variables are associated with impaired gastric emptying.Design A prospective, cohort study.Setting A medical/surgical ICU at a tertiary care hospital: Hamilton General Hospital, Hamilton, Ontario.Patients and participants We recruited 72 mechanically ventilated patients expected to remain in the ICU for more than 48h. Our results were compared to those in healthy volunteers.Intervention Within 48 h of admission to the ICU, 1.6 g acetaminophen suspension were administered via a nasogastric tube into the stomach. Blood samples were drawn at=0, 30, 60, 90, and 120 min for measurement of plasma acetaminophen levels determined by the enzymatic degradation method.Measurements and results Maximal concentration of acetaminophen was 94.1 (75.3) mol/l compared to 208.4 (33.1) mol/l in a control population (p<0.0001). The time to reach the maximal concentration was 105 min (60–180) compared to 30 min (15–90) in controls (p<0.0001). The area under the time-acetaminophen concentration curvet=120 was 9301 (7343) mol/min per 1 compared to 11644 (1336) mol/min per 1 in the controls (p=0.28). The variables associated with delayed gastric emptying were age, sex and use of opioids for analgesia and sedation.Conclusions Gastric emptying is delayed in critically ill patients. The important consequences of this phenomenon include intolerance to enteral nutrition and gastric colonization. Strategies to minimize the use of narcotics may improve gastric emptying. Studies to examine the effect of gastrointestinal prokinetic agents on gastric emptying are needed.     

A dose-finding study of granisetron,a novel antiemetic,in patients receiving high-dose cisplatin

In this double-blind study, the efficacy and safety of a single intravenous dose of a novel antiemetic, granisetron, was assessed at two dose levels (40 g/kg and 160 g/kg). A group of 355 patients were given prophylactic granisetron prior to receiving highdose cisplatin chemotherapy. In the first 24 h, 57% and 59% of patients, respectively, experienced no vomiting and no more than mild nausea. Two further doses of granisetron (40 g/kg) were permitted in the first 24 h to treat any emergent symptoms of nausea and vomiting; 66 patients (39%) in the 40-g/kg treatment group and 56 patients (34%) in the 160-g/kg group received at least one additional dose. Additional treatment with granisetron resulted in resolution or improvement of symptoms in at least 73% of these patients. Over the 7-day study period, 52% of patients in the lower-dose group and 48% in the higher required no further conventional antiemetic therapy. The two different dose levels were equal both in terms in efficacy and safety. Granisetron was well tolerated throughout the dose range of the study [40–240 g kg^-1 (24 h)^-1]. The commonest adverse event was headache, seen in 14%–16% of patients. In all but one case this resolved spontaneously or responded to simple treatment.on behalf of the Granisetron Study Group     

Development of a lipoprotein based molecular imaging MR contrast agent for the noninvasive detection of early atherosclerotic disease

Introduction: Currently there are no clinically available means of noninvasively detecting early atherosclerotic disease because these lesions are characterized by an accumulation of extracellular lipid and foam cells, but a lack of significant wall thickening or architectural distortion. Objective: We hypothesize that a paramagnetically labeled low density lipoprotein (LDL) could serve as a functional probe to detect sites of abnormal lipid metabolism in the vessel wall that represent sites of early disease. Methods: Isolated LDL was first incubated with manganese–mesoporphyrin, a hydrophobic MR contrast agent (MnMeso). Size exclusion chromatography and absorption mass spectroscopy were performed on the resulting samples to prove that an association between the two occurred. Subsequently, foam cell cultures (n=7) were incubated (10–30g/ml for 48h) with these labeled lipoproteins and the T1 relaxivity of centrifuged pellets of these cells was determined by using an inversion recovery sequence on a 1.5T scanner. These results were compared to control measurements made from foam cell cultures fed unlabeled lipoproteins (n=7). Results: Measured T1 relaxation times of the cells fed the MnMeso–LDL (443.3±51.8ms) was significantly different from the T1 relaxivity obtained from cells fed unlabeled lipoproteins (661.3±60.9ms). These findings indicate that the amount of contrast bound to the constructed lipoproteins is sufficient to produce measurable MR signal changes noninvasively. Conclusions: The study results support the feasibility of future in vivo MR experiments with labeled lipoproteins to assess lipoprotein kinetics in the vessel wall, which will hopefully provide a means of detecting early atherosclerotic disease.     

Prolonged gramulocyte activation,as well as hypoxanthine and free radical production after open heart surgery in children

Objective To investigate granulocyte activation, as well as hypoxanthine and free radical production in children during the first day after cardiopulmonary bypass.Design: A prospective study of pediatric patients undergoing either cardiac surgery with a cardiopulmonary bypass or thoracotomy and extracardiac vascular surgery not requiring a cardiopulmonary bypass.Setting Operative and intensive care units, Children's Hospital, University of Helsinki, Finland.Patients Seven consecutive patients undergoing elective correaction of a ventricular septal defect and six patients undergoing extracardiac surgery for ligation of a patent ductus arteriousus or repair a coarctation of the aorta.Measurements and main results Plasma concentrations of myeloperoxidase (140–334 g/l preoperatively, 460–1692 g/l at 0.2 h after declamping, 471–1386 g/l at 0.5 h after declamping) and lactoferrin (77–258 g/l preoperatively, 533–1783 at 0.2 h 404–1482 g/l at 0.5 h) as markers of granulocyte activation, and hypoxanthine (0–5.7 mol/l preoperatively, 4.3–17.0 mol/l at 0.2 h, 6.5–17.9 mol/l at 0.5 h) increased in a biphasic manner at 0.2–0.5 h and 6–10 h postoperatively (allp<0.05). Expired ethane, as an index of free radical activity, increased at 10 h postoperatively (36–119 pmol/kg per min preoperatively, 72–152 pmol/kg per min,p<0.05).Conclusion Granulocyte activation, and hypoxanthine and free radical production occur at least 10 h after cardiopulmonary bypass. In children undergoing open heart surgery, attempts to reduce free radical activity should be extended to the postoperative period.This study was supported by the Foundation for Pediatric Research, Academy of Finland, and the Sigrid Jusélius Foundation     

Two Bankrobbers With “Antisocial” and “Schizoid/Avoidant” Personality Disorders, Comorbid With Partial Seizures: Temporal Lobe Epilepsy and Limbic Psychotic Trigger Reaction, Respectively

Diagnostic overshadowing is illustrated by two cases of unplanned, motiveless bank robbery, initially merely attributed to antisocoial or schizoid/avoidant (loner) personality disorder, respectively. Both disorders, however, were comorbid with their potentially unobservable counterparts, with brief partial seizures, supported by both men's abnormal scalp-EEG's, their symptomatology with psychosis, and their histories of closed head injury in childhood. Such injuries are known to render particularly the temporo-limbic brain system susceptible to later partial seizure: Mr. A. had temporal lobe epilepsy (TLE) with stereotypic auditory command hallucinations and clouding of consciousness. (His past antisocial aggressive behavior might also have reflected TLE-related inter-ictal events.) Mr. B. had the symptomatology proposed as limbic psychotic trigger reaction (LPTR). Mr. B., a social loner, typically ruminated on past intermittent moderate stresses, a specific precondition of seizure kindling, ultimately elicited by a specific stimulus, resembling his past hurts. As is typical for LPTR, Mr. B. had no clouding of consciousness and no amnesia for his atavistically regressive acts, committed with flat affect, nausea, and fleeting delusions of grandeur (being gifted, like Rembrandt).     

Pharmacokinetics of panipenem/betamipron in patients with end-stage renal disease

Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of panipenem/betamipron. In this study, the pharmacokinetics of panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of panipenem/betamipron (500mg/500mg). The in vitro extraction ratios of panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of panipenem in patients were 9.53 ± 1.26l/h with hemodialysis, and 2.92 ± 0.238l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643l/h and 0.615 ± 0.511l/h, respectively. The clearance of panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500mg/500mg of panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.     

Impact of Kendall,Hollon, Beck,Hammen, and Ingram (1987) on treatment of the continuity issue in “depression” research

The article, Issues and Recommendations Regarding Use of the Beck Depression Inventory (Kendall, Hollon, Beck, Hammen, & Ingram, 1987), has had a major impact on depression research. A majority of studies using only the BDI in nonclinical samples now refer to the construct measured as dysphoria rather than depression. This word change, however, is not always accompanied by other changes in research design and interpretation that would seem warranted by the concerns that initially prompted the dysphoria recommendation, such as the nonspecificity of high BDI scores to major depression. Researchers typically continue to derive hypotheses from depression theory, use only the BDI to measure dysphoria rather than purer markers of negative affectivity, cite as a limitation of their findings the danger of assuming continuity between subclinical and clinical depression, and sometimes lapse into depression terminology. Alternative suggestions are made for considering how the particular goals of a study might lead to various ways of handling the continuity issue.We are grateful to Tony Ahrens, Diane Arnkoff, and anonymous reviewers for feedback on earlier drafts.     

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles

Background Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles.Methods For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mgkg^–1 per day,n=14) cobalt chloride hexahydrate (12 mg kg^–1 per day,n=14) or saline (n=10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect.Results During the study period, no significant increase in body weight was noted in the cobalttreated group (–4±1%), which was in contrast to the hydroxocobalamin-treated group (+21±2%) and the saline-treated group (22±2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90±16.30 vs 0.70±0.40 mol g^–1 in the control group,P<0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10±16.50 mol g^–1,P<0.001 vs cobalt-treated group) and the myocardium (4.50±1.20 mol g,P<0.001 vs cobalt-treated group).Conclusion These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.N. Péry and C. Coirault were the recipients of a fellowship grant from the Fondation pour la Recherche Médicale     

Prostacyclin counteracts the increase in capillary permeability induced by tumour necrosis factor-α

Objective To analyse how prostacyclin interferes with the short-term local circulatory effects of tumour necrosis factor- (TNF) in a skeletal muscle.Design An autoperfused sympathectomised cat gastrocnemius muscle enclosed in a plethysmograph.Interventions Arterial blood flow, total and segmental vascular resistances (large-bore arterial vessels, arterioles and veins), hydrostatic capillary pressure, tissue volume and capillary filtration coefficient were followed during local intraarterial infusion of TNF at various rates (2.5, 5.0 and 7.5 g/kg per min) and during intra-arterial infusion of prostacyclin simultaneously with the highest dose of TNF. The capillary filtration coefficient reflects the capillary surface for fluid exchange.Results Arterial infusion of TNF had no influence on vascular resistance up to 5.0 g/kg per min but induced vasodilation at 7.5 g/kg per min. No effects on the recorded hydrostatic capillary pressure were observed. The capillary filtration coefficient and the capillary filtration increased with the infusion rate of TNF the former by 55%. Simultaneous arterial infusion of prostacyclin (350 ng/kg per min) caused further vasodilation and an increase in hydrostatic capillary pressure and completely restored the capillary filtration coefficient to control. The TNF-induced filtration was partly restored.Conclusions The local circulatory effect of TNF is small apart from a graded increase in the capillary filtration coefficient, most likely reflecting an increase in capillary permeability. The prostacyclininduced decrease in capillary filtration coefficient most likely reflects a restoration of capillary permeability. The TNF-induced transcapillary filtration is not fully reduced by prostacyclin due to a simultaneous increase in hydrostatic capillary pressure.     

Learning about new anesthetics using a model driven,full human simulator

Objective.New pharmacological agents are introduced into medical practice at an ever-increasing pace. Teaching how to use new medications in the clinical setting presents educational challenges and puts patients at risk. Methods.Patients and clinical settings in which remifentanil might provide clinical advantages over existing anesthetics were identified. A simulator curriculum was developed to demonstrate the use of remifentanil in the sample cases. The simulation was designed to highlight the clinical advantages and potential side effects of remifentanil. A screen displaying the concentrations of remifentanil in plasma and in the hypothetical effector site was developed. A simulator was modified (addition of an infusion pump and a pharmacokinetic screen display) and transported to several cities in the U.S.A. An instructor guided small groups of anesthesiologists and anesthetists through a structured program that enabled participants to observe drug effects in simulated patients. Results.There were 836 participants in the remifentanil program, which was offered in 58 cities in the U.S.A. Surveys were completed by 574 anesthesiologists. There was a significant difference in comfort level for using remifentanil after the session compared to before (Chi-square, p< 0.001.) The statement: Clinical simulation experience is a means to learn about new agents like remifentanilwas rated as excellent by 81% and as good by 19% of participants. No participant found the experience to be not useful. Conclusions.Patient simulation is a novel method of introducing new drugs to the medical community and is perceived by anesthesia providers as a valuable addition to available teaching methods.     

Transbronchial regional electroplethysmography of the lungs

Objective. The objective of this study was to describe a method of transbronchial regional electroplethysmography of the lungs.Methods. The electrical resistance of a division of a lung, such as a segment or subsegment, as well as its pulsatile oscillation, were measured using a two-part process: A catheter-transducer was wedged into a small bronchus and the electrical resistance of a blood sample obtained from the same patient was measured. The electroplethysmograph (EPG) was developed for this purpose. The theory behind our method is based on a model of the lung as a three-component structure (blood-tissue-air). We performed experiments on isolated lung lobes of animals, using simultaneous electrometric and direct determination of physiologic indices for regional lung function.Results. Equations have been proposed to calculate blood volume, V_b (±10%); air volume, V_a (±11%); pulsatile increment of the blood volume, V (±10%); and regional stroke volume, RSV (±20%) per 100 cm³ of the lung. The proposed formulas yield an accuracy that is adequate for the clinical range of variations in V_b and V_a, as well as V and RSV. Experiments on lung lobes indicate that the conductivity of lung tissue (_t) is not large. This allows one to calculate the above indices without our having obtained accurate values for conductivity.Conclusions. The method of Transbronchial regional electroplethysmography of the lungs is described and cases in which this method was used for clinical investigation are presented.Glossary Resistivity of suspension - ₁ Resistivity of conducting medium - ₂ Resistivity of conducting spheres - Electroconductivity of the lung at diastole - ₁ Electroconductivity of the lung at systole - _b Electroconductivity of blood - _t Electroconductivity of tissue - _bt Electroconductivity of conducting medium (blood+tissue) - Pulsatile electroconductivity increment in the lung - _e Electrical equivalent of regional stroke volume - V Volume of lung - V_B Blood volume of lung - V_T Tissue volume of lung - V_A Air volume of lung - V_b Regional blood volume per lung volume unit - V_a Regional air volume per lung volume unit - V Regional pulsatile blood increment in the lungs - Ratio of the conducting medium (blood+tissue) volume to the lung volume unit - Ratio of the blood volume to the volume unit of the conducting medium - R Electrical resistance - R Electrical resistance increment - RSV Regional stroke volume per the organ volume unit - F Form-factor - l Cell length - S Cell cross-section area - K Empirical correction coefficient - K₁ Coefficient of electrode installation