43 resultados para Infusions

em BORIS: Bern Open Repository and Information System - Berna - Suiça


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We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

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To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers.

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Foetal alloimmune thrombocytopenia (FNAIT) is often treated transplacentally with maternally administered i.v. immunoglobulins, but not all foetuses show a consistent platelet increase during such treatment.

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The capability of goats to maintain milk production during water deprivation is remarkable and not yet fully understood. The aim of the present study was to investigate whether intravenous infusions of hypertonic NaCl cause release of both vasopressin and oxytocin and whether the peptides, in combination with the hyperosmolality, affect milk flow and milk composition. Six Swedish domestic landrace goats in their first to third lactation were milked every 30 min during experiments. Hypertonic NaCl (HNaCl) or isotonic NaCl (IsoNaCl) were infused for 90 min. Goats were not allowed to drink during infusions. Plasma vasopressin concentration increased during HNaCl infusions, and did not change in response to IsoNaCl infusions. Plasma oxytocin concentration did not change during either infusion. Milk flow was maintained during the infusions. Milk fat concentration decreased in the three samples taken before onset of the infusions, but then increased gradually during HNaCl infusions, while it continued to fall during the IsoNaCl infusions. Milk osmolality followed the rise in plasma osmolality during the HNaCl infusions and did not change in IsoNaCl experiments. Milk lactose concentration increased throughout both series of experiments, the concentration being higher during HNaCl infusions. Milk protein concentration did not change during HNaCl infusions, but fell in the IsoNaCl experiments. It is concluded that the hyperosmolality in combination with elevated plasma vasopressin levels did not disturb the secretory activity of the mammary cells, but rather facilitated emptying of the alveolar milk. Such a mechanism may help to explain the sustained milk production in water deprived goats.

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BACKGROUND: To overcome the ototoxicity of cisplatin, single bolus infusions were replaced by repeated prolonged infusions of lower doses or by continuous infusions at still lower infusion rates. However, considering ototoxicity little is, in fact, known about the tolerance of repeated prolonged or continuous infusion in children. PROCEDURE: Auditory function was monitored along with plasma concentrations of free and total platinum (Pt), and with standard serum parameters (sodium, potassium, calcium, magnesium, phosphate, chloride, and creatinine) in 24 children receiving cisplatin by continuous infusion for the treatment of neuroblastoma and osteosarcoma or by repeated 1 or 6 hr infusions for the treatment of germ cell tumors. RESULTS: Hearing deteriorated in 10/15 osteosarcoma patients, 2/3 neuroblastoma patients, and 1/6 patients with germ cell tumors. Ototoxicity occurred after cumulative doses between 120 and 360 mg/m(2) cisplatin. In osteosarcoma patients, ototoxicity was associated with a comparatively higher mean plasma concentration of free Pt. However, Pt plasma concentrations did not discriminate between patients with or without ototoxicity. In patients experiencing ototoxicity serum creatinine increased by 45% compared to pre-treatment levels (mean). Serum creatinine increased by 26% in patients without ototoxicity (P < 0.05, Mann-Whitney Rank sum test). Despite standardized hydration, discrete but significant changes of potassium, sodium, magnesium, and phosphate were observed during and/or after cisplatin infusion, which, however, did not discriminate between patients with and without ototoxicity. CONCLUSIONS: While continuous cisplatin infusions are less nephrotoxic than repeated prolonged infusions, we observed considerable ototoxicity in patients treated with continuous cisplatin infusions, which necessitates further evaluations on the tolerance of continuous cisplatin infusions in children.

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OBJECTIVE: To compare anesthesia recovery quality after racemic (R-/S-) or S-ketamine infusions during isoflurane anesthesia in horses. ANIMALS: 10 horses undergoing arthroscopy. PROCEDURES: After administration of xylazine for sedation, horses (n = 5/group) received R-/S-ketamine (2.2 mg/kg) or S-ketamine (1.1 mg/kg), IV, for anesthesia induction. Anesthesia was maintained with isoflurane in oxygen and R-/S-ketamine (1 mg/kg/h) or S-ketamine (0.5 mg/kg/h). Heart rate, invasive mean arterial pressure, and end-tidal isoflurane concentration were recorded before and during surgical stimulation. Arterial blood gases were evaluated every 30 minutes. Arterial ketamine and norketamine enantiomer plasma concentrations were quantified at 60 and 120 minutes. After surgery, horses were kept in a padded recovery box, sedated with xylazine, and video-recorded for evaluation of recovery quality by use of a visual analogue scale (VAS) and a numeric rating scale. RESULTS: Horses in the S-ketamine group had better numeric rating scale and VAS values than those in the R-/S-ketamine group. In the R-/S-ketamine group, duration of infusion was positively correlated with VAS value. Both groups had significant increases in heart rate and mean arterial pressure during surgical stimulation; values in the R-/S-ketamine group were significantly higher than those of the S-ketamine group. Horses in the R-/S-ketamine group required slightly higher end-tidal isoflurane concentration to maintain a surgical plane of anesthesia. Moderate respiratory acidosis and reduced oxygenation were evident. The R-norketamine concentrations were significantly lower than S-norketamine concentrations in the R-/S-ketamine group. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with R-/S-ketamine, anesthesia recovery was better with S-ketamine infusions in horses.

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Intravenous bisphosphonates reduce fracture risk but have been associated in rare cases with deteriorating renal-function in cancer patients. The renal effects of zoledronic acid were assessed in osteoporotic postmenopausal women from 27 countries who received three annual infusions of zoledronic acid or a placebo in a randomized, double-blind trial. Serum creatinine, estimated creatinine clearance and urinary protein were measured before and after at least one infusion in a predefined renal safety cohort of 5035 equally divided patients. This group was compared to 7714 patients whose parameters were measured annually. Significantly more transient pre- to post-infusion increases in serum creatinine occurred in zoledronic acid than placebo-treated patients with significant elevations, relative to pre-infusion, only in the second year. All 31 zoledronic acid and 8 of 10 patients on placebo recovered their pre-infusion serum creatinine value within 12 months. No differences in mean changes in serum creatinine, estimated creatinine clearance or adverse renal events were found. We found that transient changes in renal function can occur following an annual zoledronic acid infusion but, in the long term, renal function was not different from control patients.

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Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

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OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 mug kg(-1) hour(-1), reducing after 50 minutes to 2.75 mug kg(-1) hour(-1), and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 mug kg(-1) ) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4-1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups. CONCLUSION AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.

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Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal aspergillosis after successful medical treatment using intranasal infusions of 1% or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment protocols were good, with half of the dogs being asymptomatic throughout the follow-up period. The remaining dogs showed mild clinical signs compatible with chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic lymphoplasmacytic rhinitis/sinusitis and episodes of bacterial rather than fungal infection. Three dogs had confirmed reinfection or relapse 2 to 36 months after clinical resolution.

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Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.

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OBJECTIVE To compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses. STUDY DESIGN Prospective, randomized, blinded clinical trial. ANIMALS Forty horses (ASA I-III) undergoing elective surgery. METHODS Horses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI group received lidocaine (1.5 mg kg(-1) over 10 minutes, followed by 40 microg kg(-1) minute(-1)) and ketamine (60 microg kg(-1) minute(-1)), both reduced to 65% of the initial dose after 50 minutes, and stopped 15 minutes before the end of anaesthesia. Standard clinical cardiovascular and respiratory parameters were monitored. Recovery quality was scored from one (very good) to five (very poor). Differences between ISO and LKI groups were analysed with a two-sample t-test for parametric data or a Fischer's exact test for proportions (p < 0.05 for significance). Results are mean +/- SD. RESULTS Heart rate was lower (p = 0.001) for LKI (29 +/- 4) than for ISO (34 +/- 6). End-tidal concentrations of isoflurane (ISO: 1.57% +/- 0.22; LKI: 0.97% +/- 0.33), the number of horses requiring thiopental (ISO: 10; LKI: 2) or dobutamine (ISO:8; LKI:3), and dobutamine infusion rates (ISO:0.26 +/- 0.09; LKI:0.18 +/- 0.06 microg kg(-1) minute(-1)) were significantly lower in LKI compared to the ISO group (p < 0.001). No other significant differences were found, including recovery scores. CONCLUSIONS AND CLINICAL RELEVANCE These results support the use of lidocaine and ketamine to improve anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to 2 hours in mechanically ventilated horses, with comparable quality of recovery.

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Deep vein thrombosis (DVT) and its complication, pulmonary embolism, are frequent causes of disability and mortality. Although blood flow disturbance is considered an important triggering factor, the mechanism of DVT initiation remains elusive. Here we show that 48-hour flow restriction in the inferior vena cava (IVC) results in the development of thrombi structurally similar to human deep vein thrombi. von Willebrand factor (VWF)-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the IVC. Mice with half normal VWF levels were also protected in the stenosis model. Besides promoting platelet adhesion, VWF carries Factor VIII. Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF(-/-) mice, indicating that impaired coagulation was not the primary reason for the absence of DVT in VWF(-/-) mice. Infusion of GPG-290, a mutant glycoprotein Ib?-immunoglobulin chimera that specifically inhibits interaction of the VWF A1 domain with platelets, prevented thrombosis in wild-type mice. Intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was dramatically higher in wild-type than in VWF(-/-) IVC. Our results demonstrate a pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis.

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OBJECTIVE: To evaluate the effect of IL-6 blockade using tocilizumab in inducing remission of arterial large vessel vasculitides (LVV). METHODS: Five consecutive patients with giant-cell arteritis (GCA) and two with Takayasu’s arteritis (TA) were treated by tocilizumab infusions (8 mg/kg). Tocilizumab was given every other week for the first month and once monthly thereafter. Clinical symptoms of disease activity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and glucocorticoid (GC) dosage necessary to maintain remission were prospectively assessed. MR angiography was performed to monitor local inflammation. RESULTS: Of the seven patients three were newly diagnosed and four showed GC resistance, i.e. GC could not be lowered to less than 7.5 mg/day. The mean follow-up time was 4.3 months (range 3–7 months). All patients achieved a rapid and complete clinical response and normalisation of the acute phase proteins. Remarkably, prednisone dosage could be reduced within 12 weeks to a mean of 2.5 mg/day (range 0–10 mg/day). No relapse and no drug-related side effects were noted. CONCLUSION: Collectively the data suggest that IL-6 blockade using tocilizumab qualifies as a therapeutic option to induce rapid remission in large vessel vasculitides.

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Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia.