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Concept: Bolus


Case The objective of this case report is to report the development of tardive dyskinesia in an African-American adolescent male after short-term treatment with metoclopramide 10 mg orally three times daily secondary to delayed gastric emptying. The patient developed symptoms of tardive dyskinesia after 2 days of therapy with metoclopramide. Metoclopramide was discontinued and diphenhydramine 50 mg was initially administered intravenously followed with 25 mg orally every 4 hours as needed. While there are case reports of drug-induced tardive dyskinesia after intravenous administration of metoclopramide, this is to our knowledge the first report of tardive dyskinesia after short-term treatment with oral metoclopramide in an adolescent. Conclusion Awareness of the risk of development of this adverse effect even with short-term treatment with metoclopramide and in younger patients is important.

Concepts: Medical terms, Patient, Intravenous therapy, Report, Tardive dyskinesia, Bolus, Metoclopramide, Case report


The objective of this study was to investigate the effect of polymeric microcarriers on the in-vivo intranasal uptake of an anti-migraine drug for brain targeting. Mucoadhesive powder formulations consisted of antimigraine drug, zolmitriptan, and chitosans (various molecular weights and types) or hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration was evaluated by in-vitro and ex-vivo mucoadhesion and permeation tests. The formulations based on chitosan glutamate (CG) or HPMC were tested in-vivo because they showed good mucoadhesive properties and altered the permeation rate of the drug. The in-vivo results from intravenous infusion and nasal aqueous suspension of the drug or nasal particulate powders were compared. The plasmatic AUC values obtained within 8 h following intravenous administration appeared about three times higher than those obtained by nasal administration, independent of the formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained from nasal and intravenous administrations were respectively 30 and 90 times lower than the concentrations of the drug in the blood. Thus, nasal administration potentiated the central zolmitriptan activity allowing a reduction of the drug peripheral levels, with respect to the intravenous administration. Among nasally administered formulations, CG microparticles showed the highest efficacy in promoting the central uptake of zolmitriptan within 1 h.

Concepts: Chemistry, Intravenous therapy, Cerebrospinal fluid, Route of administration, Methyl cellulose, Psychoactive drug, Hypromellose, Bolus


STUDY OBJECTIVE: To determine whether a bolus technique provides enhanced analgesia compared with a continuous infusion for femoral nerve block. DESIGN: Prospective, single-blinded, randomized controlled trial ( Identifier: NCT01226927). SETTING: Perioperative areas and orthopedic surgical ward of a university hospital. PATIENTS: 45 ASA physical status 1, 2, and 3 patients undergoing unilateral primary total knee arthroplasty. INTERVENTIONS: All patients received single-injection sciatic and femoral nerve blocks plus a femoral nerve catheter placement for postoperative analgesia. Patients were randomly assigned to an automated intermittent bolus (5 mL every 30 min with 0.1 mL/hr basal rate) or a continuous infusion (10.1 mL/hr) delivery method of 0.2% ropivacaine. MEASUREMENTS: Consumption of intravenous patient-controlled analgesia (IV-PCA) and visual analog scale (VAS) pain scores were assessed postoperatively at set intervals until the morning of postoperative day (POD) 2. MAIN RESULTS: The mean (SEM) cumulative IV-PCA dose (mg of hydromorphone) for the 36-hour postoperative interval measured was 12.9 ± 2.32 in the continuous infusion rate group (n = 20) and 7.8 ± 1.02 in the intermittent bolus group [n = 21, t(39) = 2.04, P = 0.048; a 39 ± 14% difference in total usage]. Pain scores were statistically significantly lower in the intermittent bolus group in the afternoon of POD 1 (t(39) = 2.47, P = 0.018), but were otherwise similar. CONCLUSIONS: An automated intermittent bolus infusion technique for femoral nerve catheters is associated with clinically and statistically significantly less IV-PCA use (ie, an opioid-sparing effect) than a continuous infusion technique.

Concepts: Pharmacology, Randomized controlled trial, Intravenous therapy, Knee replacement, Catheter, Bolus, Infusion pump, Basal


The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated. Biocompatible poly(ethylene glycol) (PEG)-coated poly(DL-lactide-co-glycolide) (PLGA) as wall material, solid and perfluorodecalin (PFD)-filled PEG-PLGA microcapsules (1.5 µm diameter) were manufactured by using a modified solvent evaporation method with either 1% poly(vinyl alcohol) (PVA) or 1.5% cholate as emulsifying agents. Compared to microcapsules manufactured with cholate, the protein adsorption (albumin and IgG) was clearly decreased and agglomeration of capsules was prevented, when PVA was used. The intravenous administration of these microcapsules, both solid and PFD-filled, in rats was successful and exhibited a circulatory half-life of about 1 h. Our data clearly demonstrate that PEG-PLGA microcapsules, manufactured by using PVA, are suitable biocompatible, long-circulating drug carriers, applicable for intravenous administration.

Concepts: Blood, Nanoparticle, Drug, Intravenous therapy, Liquid, Ibn al-Nafis, Bolus, Drug carrier


Purpose: In a prospective study, we compared the different perfusion kinetics of HCC and ICC using dynamic contrast-enhanced ultrasound (DCE-US). Materials and Methods: Patients with proven HCC and ICC were included. Three-minute video clips of CEUS examinations (CPS - low MI mode) after a bolus injection of 1.2 ml SonoVue(®) were recorded and analyzed with quantification software (VueBox(®)). Parameters for the arterial contrast enhancement [rise time (RT), time-to-peak (TTP)] towards portal venous contrast enhancement [mean transit time (local) (mTTl) and fall time (FT)] were quantified. Furthermore, contrast wash-out after peak enhancement (PE) (40 s, 80 s, 100 s and 120 s after PE) was compared between HCC and ICC. Results: 43 patients with proven HCC (n = 23 HCC; cirrhosis n = 16) and ICC (n = 20 ICC; Cirrhosis n = 6) were examined. No statistical difference of the arterial DCEUS parameters was found between HCC and ICC. Contrast enhancement of the portal venous and late phases showed significantly lower values in the ICC group indicating early wash-out of the contrast agent: mTTl (p = 0.0209): HCC 118.4 s (SD± 88.4); ICC 64.8 s (SD± 49.7). FT (p = 0.0433): HCC 42.5 s (SD± 27.7); ICC 27.7 s (SD± 16.2). The percental loss of intensity at a definite time point after PE was significantly higher in ICC than in HCC lesions. Conclusion: DCE-US is able to detect and quantify differences in perfusion kinetics between HCC and ICC. Whereas arterial contrast enhancement patterns may overlap between HCC and ICC, a timed characterization of wash-out kinetics may offer an additional tool to characterize HCC and ICC. The presence of a rapid loss of signal intensity in the early portal venous phase is significantly higher in ICC than in HCC lesions.

Concepts: Blood, Medical imaging, Magnetic resonance imaging, Vein, Contrast medium, Bolus, Quantification


Emulsified isoflurane is a novel intravenous anesthetic, which is a lipid emulsion of isoflurane. As some drugs have a QTc-prolongation effect which can increase a risk of arrhythmia, this study was to evaluate the effects of emulsified isoflurane on the QTc interval. This was a single-center, randomized, single-blind, non-comparative study. Subjects were randomly allocated to receive an intravenous bolus injection of 22.63, 38.26, or 49.73 mg/kg emulsified isoflurane, respectively. Standard 12-lead electrocardiograms were recorded before administration and at 28 timepoints after administration. Blood samples and the end-tidal isoflurane concentrations were collected for pharmacokinetic analysis. The primary target variable was the QTcF change from baseline at each time point. A two-sided 90% confidence interval (CI) was calculated for a QTcF change from baseline at each timepoint. The maximal 90% CIs of the mean QTcF from the baseline for 22.63, 38.26 and 49.73mg/kg emulsified isoflurane were 2.52-21.18 ms, 15.66-35.90 ms, and 17.65-40.71 ms, respectively. Non-significant relationship was observed between QTcF and the plasma concentration (or the end-tidal isoflurane concentration). Single intravenous dose of emulsified isoflurane of the anticipated therapeutic dose or supra-therapeutic doses was associated with a potential dose-dependent and non-concentration-related QTc-prolongation effect.

Concepts: Pharmacology, Cardiology, Cardiac electrophysiology, QT interval, Interval finite element, Pharmacokinetics, Bolus, Dosage forms


Poppy seed tea (PST) has a long history of use for its medicinal (analgesic, anti-diarrhoeal, anxiolytic) effects. It is also commonly used as a recreational drug in its oral form throughout the world, but reports of intravenous use are very rare. We present two cases of intravenously injected PST with dramatic effects in order to create awareness among health professionals of this method of drug use and its potential complications, as well as to help clinicians dealing with opiate-dependent patients to warn them of the risk.

Concepts: Illness, Opioid, Caffeine, Recreational drug use, Bolus, Opium, Poppy seed, Poppy tea


The aim of this work was to evaluate the potential of INVITE based nanomicelles, an amphiphilic polymer constituted by Inulin (INU) and vitamin E (VITE), as a platform for improving the biopharmaceutical properties of hydrophobic drugs. For this purpose, curcumin was selected as a model and curcumin-INVITE nanomicelles were prepared. This drug delivery system was characterized both in vitro for what concerns the physicochemical properties, blood compatibility and cellular uptake, and in vivo for the evaluation of the pharmacokinetic profile. It was found that these nanomicelles release curcumin in a controlled manner and they are able to penetrate cellular membrane. Moreover, they showed an improved pharmacokinetic profile after intravenous administration. In conclusion, INVITE micelles might constitute promising nanocarriers for improving the biopharmaceutical performance of hydrophobic drugs.

Concepts: Pharmacology, Improve, In vivo, Intravenous therapy, Drugs, In vitro, ADME, Bolus


Intravenous fluid resuscitation is ubiquitous throughout medicine and is often considered a benign procedure. Yet, there is now clear recognition of the potential harms of fluid overload after initial resuscitation. In recent years, there has also been an increasing focus on comparing various resuscitation fluids with respect to both benefits and risks. Studies have examined colloids, such as albumin and starches, against the clinical standard of crystalloids. In addition, evidence has emerged to suggest that outcomes may be different between resuscitation with chloride-rich vs balanced crystalloid solutions. In this article, we review the current literature regarding choice of intravenous fluids for resuscitation in the intensive care setting and describe the dangers associated with fluid overload in critically ill patients.

Concepts: Health care, Intravenous therapy, Illness, Liquid, Non-Newtonian fluid, Bolus


This study characterized the pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous bolus administration to cats. Seven 6- to-year-old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK-467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK-467 [75, 150, 300 or 600 μg/kg-only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two-compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half-life (min) were 342 (131-660), 829 (496-1243), 14.6 (9.6-22.7) and 48 (40-69) for D12.5; 296 (179-982), 1111 (908-2175), 18.2 (12.4-22.9) and 52 (40-76) for D25; 653 (392-927), 1595 (1094-1887), 22.7 (18.5-36.4) and 48 (35-60) for dexmedetomidine in D25M600; 117 (112-163), 491 (379-604), 3.0 (2.0-4.5) and 122 (99-139) for M300; and 147 (112-173), 462 (403-714), 2.8 (2.1-4.8) and 118 (97-172) for MK-467 in D25M600. MK-467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK-467.

Concepts: Pharmacology, Intravenous therapy, Thermodynamics, Distribution, Pharmacokinetics, Cat, Bolus, Neutering