Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

The hand in systemic diseases other than rheumatoid arthritis

This review outlines the skin, vascular and musculoskeletal symptoms affecting the hand during systemic inflammatory diseases other than rheumatoid arthritis. Skin lesions are diagnosed clinically and their symptomatology is documented through an extensive series of photographs. These conditions may require specific care before a surgical procedure can be performed. Vascular lesions are also diagnosed clinically and their symptomatology is described in detail. It is important to recognize that acrocyanosis is always benign. The surgeon should be able to distinguish between primary, but benign Raynaud's disease and secondary Raynaud's syndrome, which has a high risk of finger necrosis. Current preventative and curative treatments for finger necrosis are described. The clinical, radiological, progressive and therapeutic features of musculoskeletal lesions are reviewed, namely those associated with psoriatic arthritis, systemic sclerosis and lupus.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Subchronic Centrifugal Mechanical Assist in an Unheparinized Calf Model

Abstract. The purpose of this study was to determine whether the major centrifugal pumps currently in use in the United States (Medtronic, BioMedicus BioPump and Carmeda-coated BioPump, Sams 3M centrifugal pump, and St. Jude Medical Lifestream) could function as left mechanical assist devices in the subchronic (72 h) unheparinized calf model. Calves were instrumented for left atrial to aorta ex vivo assist, and the pump flow was set at 3.5 ± 0.4 L/min. Two calves (Sarns 3M and St. Jude) survived 72 h of pumping without clinical complications. The other 2 calves died at 62 and 66 h (Medtronic Bio-Pump and Carmeda-coated BioPump, respectively); both had pelvic limb paralysis. The seal of the Sarns 3M pump head ruptured after approximately 36 h of pumping and required replacement. On postmortem examination, pump-associated thromboembolic lesions were detected in 3 of the 4 calves in one or more of the following organs: kidney, pancreas, abomasum, duodenum, ileum, spleen, and lumbar spinal cord. The calf with the Sarns 3M pump had no discernable lesions. Because of the clinical abnormalities and postmortem lesions in the unheparinized calf model, it was suggested that anticoagulation is necessary for conducting centrifugal mechanical assist studies in calves using presently available technology.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

The influence of age and administration rate on the brain sensitivity to propofol in rats

Background: It is well established that the dose of propofol for induction of anaesthesia is influenced by patient age. This may be explained by differences in pharmacokinetics or pharmaco-dynamics. To evaluate the effect of age on propofol pharmaco-dynamics, the brain concentration of propofol at the time of an EEG end-point was used as a measure of CNS sensitivity.
Methods: Ninety-five rats were assigned to 4 groups. Anaesthesia was induced by continuous propofol infusion at different rates. The dose of propofol and duration of anaesthesia were determined from 23 up to 776 days of age. The rats were killed at 23,287 or 776 days of age at the EEG end-point and samples of cerebral cortex, midbrain, cerebellum, serum and fat tissue were submitted to HPLC analysis of propofol concentrations.
Results: The induction dose of propofol varied with age and administration rate. Young animals needed a higher dose of propofol. Old animals had higher brain concentrations of propofol at the EEG end-point than young animals. However, propofol concentrations in serum were higher in young animals. The propofol concentration in the brain was influenced by the administration rate.
Conclusion: The dose of propofol for induction of anaesthesia in rats is influenced by animal age and administration rate. Young animals need a larger induction dose than old rats, but are more sensitive as measured by the brain concentration of propofol. The larger induction dose in young rats when compared with adults is explained by pharmacokinetic differences rather than by pharmacodynamic changes.     

Distribution, tolerability and tissue compatibility of intrathecal tizanidine in the sheep

Background : Tizanidine (TZD) is an alpha-2-adrenergic drug with potential spinal analgesic action and could be a substitute or additive for intrathecal (i.t.) opiates in chronic pain treatment. However, long-term tolerability and tissue compatibility are not yet established.
Methods : Three sheep were infused intrathecally with TZD up to 4000 μg/d over a time period of up to 440 d using implantable drug administration devices; one control animal was infused with vehicle only; standard values were collected from untreated sheep. CSF samples and blood samples were analyzed to determine pharmacokinetics and systemic redistribution. Behavioral effects were studied. The spinal cord tissue was investigated using standard laboratory histology.
Results : Bolus kinetics after i.t. injection of TZD are best described by a two-phase model. Elimination half-lives of TZD in CSF were 15 min and 152 min, respectively. Clearance of TZD from lumbar CSF was 0.48 ml/min. Doses higher than 500 μg i.t. caused dose-dependent motor inactivity and sleepiness. Continuous i.t. TZD up to 4 mg/d was well tolerated regarding behavior, physical activity, heart rate, muscle strength, and coordination. Minor elevations of CSF cell counts and total protein were detected both in saline and TZD-treated animals, presumably due to local irritation by the catheter and repeated sampling procedures. Histological evaluation of the spinal cord and adjacent tissues showed no abnormalities.
Conclusion : The long-term intrathecal infusion of TZD is well tolerated and non-toxic in the sheep. The data favor clinical trials in patients with chronic pain.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Inhibited hypothalamic histamine metabolism during isoflurane and sevoflurane anesthesia in rats

Background : Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism.
Methods : Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test.
Results : Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation.
Conclusions : Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.     

Péridurale obstétricale : qualité de l’information médicale en français sur Internet en 2009 et 2010

Objective

The variability of the medical information available on the Internet (MedInfoWeb) raises concern about its quality. There is no data about the quality of MedInfoWeb concerning epidural analgesia for labour (EAL). Our aims were to assess the quality of MedInfoWeb concerning EAL and to study the stability of MedInfoWeb and the ranking of website into search engine (SE) during 1 year.

Study design

Observational study.

Materials and methods

We created our own data form to analyse the firsts 40 Google^®, Alta Vista^® and Yahoo^® websites. In 2009 and 2010, two independent assessors assessed the quality of the website structure (structure score noted out of 25) and the quality of medical information (medical score noted out of 30). The global score (noted on 55) was the addition of structure and medical scores. A HONcode labelling was noted.

Results

Between 2009 and 2010, the average global (23 vs. 22), structure (11 vs. 11) and medical (12 vs. 12) Scores were stable. The SE's quality was comparable. A SE website's rank was not related to its global score. The labelling HONcode websites were the best (26 vs. 21, P = 0.048). The best website in 2009 and 2010 was doctissimo.fr. In 2010, only 58% of the websites were still presents.

Conclusion

The quality of MedInfoWeb concerning EAL is poor and did not improve between 2009 and 2010. The MedInfoWeb is unstable: 42% of the websites disappeared in 1 year. No website or SE is currently able to give reliable medical information concerning EAL.     

Constrictive pericarditis: Clinical profile and management

One-hundred and sixteen patients were surgically treated for constrictive pericarditis over a period of 18 years. Twenty-eight patients were less than 15 years old. All patients had exertional dyspnoea and elevated jugular venous pressure. Eighty-eight patients had NYHA class III or IV functional disability. Only 2 cases had atrial fibrillation. Seventeen patients had roentgenographic evidence of pericardial calcification. Fluoroscopy showed diminished cardiac movements in 110 cases. Cardiac catheterisation in 77 patients demonstrated classical haemodynamic pattern of constrictive pericarditis. All our patients underwent subtotal pericardiectomy through a left anterolateral approach. Seventy-one patients had histological evidence of tuberculous pericarditis. Nearly 88 per cent of the followed up cases reported good to excellent relief. The hospital mortality was 6.9 per cent. Our observations and inferences are compared with those of other published reports.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

Risque allergique en anesthésie pédiatrique

Objectives

To propose the different modalities of management of the allergic risk occurring during paediatric anaesthesia.

Study design

Literature analysis.

Methods

Literature research using the Medline^® database and MeSH format according to keywords, including publications in French and English since 1982.

Results

The overall incidence for anaphylactic reactions was estimated at one in 7741 anaesthetic procedures during paediatric anaesthesia. Latex anaphylaxis was mostly involved with an incidence at one in 10,159 anesthetic procedures. The risk factors of latex sensitization are known. Primary latex prophylaxis is efficient in patients at risk of latex sensitization. In contrast to adults, neuromuscular blocking agents (NMBAs) are rarely involved in children, with an incidence at 1 in 81,275 anaesthetic procedures. The Ring and Messmer clinical scale allows quantifying the severity and helps managing the care of immediate hypersensitivity reactions. Clinical symptoms associate cardiovascular, respiratory and cutaneous-mucous signs according to different severity grades. Epinephrine associated to fluid loading, remains the first-line agent in case of severe reactions. The allergological assessment is key to the management of these reactions and is required in order to identify the mechanism of the reaction and the culprit drug or substance involved.

Conclusions

Allergic reactions to NMBAs occurring during paediatric anaesthesia are rare whereas those with latex are more frequent. Therefore, the reduction of the allergic risk during paediatric anaesthesia essentially requires a latex-free environment.     

Pharmacokinetic aspects of fluid therapy

Volume kinetics could be a useful tool to better understand fluid distribution and its implications for fluid therapy. By using non-linear regression, it is possible to fit dilution data to an equation that describes fluid distribution in one- and two-volume models reasonably well. These models could be adapted to fit different clinical situations. In the future, it would be useful to design models similar to target control infusion models in pharmacokinetics. Such models should probably use dilution of Hb or other endogenous tracers in combination with blood pressure as endpoints.

• peri-operative fluid therapy continues to be an exercise in empiricism, with nagging questions about efficacy and complications

• in 1997, several authors introduced kinetic modeling (volume kinetics) describing the peak effects and clearance of intravenously infused fluids in terms similar to those used in pharmacokinetics

• this chapter briefly summarizes currently accepted principles of fluid therapy, discusses the general approach to kinetic analysis of fluid therapy, reviews currently available data defining kinetic responses to fluid therapy, and speculates about future applications of this approach

• further research is warranted where anaesthetic drugs in combination with haemorrhage are studied kinetically in humans

• it is important to implement a non-invasive analysis of an endogenous tracer such as Hb to facilitate future use of kinetic models for fluids

• an outcome study comparing fluid administration according to kinetic principles vs standard of care is warranted

Myocardial hydatid cyst

A 40 year old male presented with supraventricular tachycardia and localised calcified bulge of the left heart border. Thoracotomy revealed a hard, calcified and spherical cyst arising from the antero lateral wall of the left ventricle. The pericardium was normal. The cyst was deroofed and left open. It contained thick, amorphous, yellowish material. The postoperative course was uneventful. The patient is asymptomatic 12 months after surgery. Based on paper presented in the V Asian Congress of Thoracic & Cardiovascular Surgery, Madras, India in February 1981.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Cutaneous Plasmacytosis Associated with Ehrlichiosis in an African-American Patient

Cutaneous plasmacytosis is a rare disease that presents clinically with multiple red-brown papules and plaques with minimal to no epidermal change. Histopathologic findings include a perivascular dermal infiltration of polyclonal plasma cells. The etiology of cutaneous plasmacytosis is unknown, but hypothesized to be due to persistent or repeated antigenic stimulation. Ehrlichia represents a family of obligate intracellular bacteria that have been associated with the development of plasma cell dyscrasias in the veterinary literature. We present a case of a 67-year-old male patient with the development of progressively worsening cutaneous plasmacytosis following prolonged hospitalization secondary to ehrlichiosis sepsis. The patient initially presented with isolated cutaneous involvement and normal laboratory findings that eventually progressed to include multiple laboratory abnormalities, including anemia, hyperproteinemia, and elevated serum creatinine. Further diagnostic workup was declined by the patient despite evidence of progression to systemic plasmacytosis or multiple myeloma.