Intravenous medication administrations have a high incidence of error but there is limited evidence of associated factors or error severity.
To measure the frequency, type and severity of intravenous administration errors in hospitals and the associations between errors, procedural failures and nurse experience.
Prospective observational study of 107 nurses preparing and administering 568 intravenous medications on six wards across two teaching hospitals. Procedural failures (eg, checking patient identification) and clinical intravenous errors (eg, wrong intravenous administration rate) were identified and categorised by severity.
Of 568 intravenous administrations, 69.7% (n=396; 95% CI 65.9 to 73.5) had at least one clinical error and 25.5% (95% CI 21.2 to 29.8) of these were serious. Four error types (wrong intravenous rate, mixture, volume, and drug incompatibility) accounted for 91.7% of errors. Wrong rate was the most frequent and accounted for 95 of 101 serious errors. Error rates and severity decreased with clinical experience. Each year of experience, up to 6 years, reduced the risk of error by 10.9% and serious error by 18.5%. Administration by bolus was associated with a 312% increased risk of error. Patient identification was only checked in 47.9% of administrations but was associated with a 56% reduction in intravenous error risk.
Intravenous administrations have a higher risk and severity of error than other medication administrations. A significant proportion of errors suggest skill and knowledge deficiencies, with errors and severity reducing as clinical experience increases. A proportion of errors are also associated with routine violations which are likely to be learnt workplace behaviours. Both areas suggest specific targets for intervention.
Medication errors; intravenous medications; nurses; patient safety; information technology; quality of care; healthcare quality; health services research; medication safety
Status epilepticus (SE) is a serious neurological condition and requires prompt treatment. Sodium valproate has been used to treat SE successfully but its role as the first-line antiepileptic drug (AED) is still controversial. This study evaluated the efficacy of intravenous sodium valproate to determine if it is non-inferior to intravenous phenytoin in SE treatment.
Patients diagnosed as SE during 2003–2010 who were of an age of more than 15 years and received either intravenous sodium valproate or intravenous phenytoin as the first-line treatment were enrolled. Clinical characteristics and outcomes of SE were recorded and analyzed. The differences of outcomes between sodium valproate and phenytoin group were determined by descriptive statistics.
During the study period, there were 37 and 17 SE patients who received intravenous phenytoin and intravenous sodium valproate as the first-line treatment, respectively. All patients received diazepam 10 mg intravenously as a rescue medication before starting the antiepileptic agents if uncontrolled except one patient in the sodium valproate group. There were no significant differences between the phenytoin and sodium valproate groups in all outcome variables including numbers of patients with clinically-controlled seizures, non-dependent patients, time to seizure control, and duration of hospitalization, and death. No serious cardiovasculars event such as hypotension occurred in either group.
Intravenous sodium valproate is non-inferior to intravenous phenytoin as the first-line treatment in SE with no significant cardiovascular compromises.
Phenytoin; Sodium valproate; Efficacy; Status epilepticus; Comparison
Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months' treatment with the weekly intramuscular preparation and six months' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.
Serum human growth hormone (HGH), serum immunoreactive insulin (IRI), plasma free fatty acids, and blood glucose were measured during intravenous glucose and intravenous tolbutamide tolerance tests in 13 normal and 13 prediabetic (offspring of two diabetic parents) males, closely matched for weight and age. Only prediabetics with normal glucose tolerance during oral, intravenous, and cortisone-primed glucose tolerance tests were evaluated.
Mean serum HGH levels were significantly higher in prediabetics in response to intravenous tolbutamide and at the end of the 3-hr intravenous glucose tolerance tests (IVGTT). This is interpreted as a hyperresponsiveness of the growth hormone-releasing mechanisms in prediabetic subjects.
The insulin response during the first 10 min of an IVGTT was significantly reduced in prediabetic males as compared to normal controls, whereas the insulin response to intravenous tolbutamide was not significantly different at the same time intervals in the same subjects.
It appears, therefore, that measuring IRI during an IVGTT can be valuable in detecting the earliest signs of diabetes even before any disturbance of blood glucose homeostasis is seen.
The possibility that growth hormone hypersecretion in prediabetics might play a role in the pathogenesis of human diabetes mellitus is discussed.
The authors examined charts for evidence of the use of intravenous fluids in all patients who died from malignant disease occurring in a tertiary care teaching hospital during a one-year period. Of 106 patients who were identified, 86 received intravenous fluids within their last 30 days of life, and 73 died with an intravenous line running.
Intravenous fluid use appeared to be independent of age, sex, language, presence of family members, primary tumour site, presence of metastases, duration of illness, and presence of a “no cardiopulmonary resuscitation” order. Total lengths of stay and survival time after obtaining “do not resuscitate” orders were longer in those who died without intravenous fluids. More than two-thirds of patients with cancer who died in hospital did so with an intravenous line.
“do not resuscitate” orders; family medicine; intravenous fluid administration; oncology; palliative care
Acute ischemic stroke is a major cause of morbidity and mortality in Europe, North America, and Asia. Its treatment has completely changed over the past decade with different interventional approaches, such as intravenous trials, intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries. Intravenous thrombolysis with tissue plaminogen activator (tPA) within 4.5 hours of symptoms onset significantly improved clinical outcomes in patients with acute ischemic stroke. Pharmacological intra-arterial thrombolysis has been shown effective until 6 hours after middle cerebral artery occlusion and offers a higher rate of recanalization compared with intravenous thrombolysis, whereas combined intravenous/ intra-arterial thrombolysis seems to be as safe as isolated intravenous thrombolysis. The more recent advances in reperfusion therapies have been done in mechanical embolus disruption or removal. Merci Retriever and Penumbra System have been approved for clot removal in brain arteries, but not as a therapeutic modality for acute ischemic stroke since it is no clear whether mechanical thrombectomy improves clinical outcome in acute stroke. However, mechanical devices are being used in clinical practice for patients who are ineligible for tPA or who have failed to respond to intravenous tPA. We summarize the results of the major thrombolytic trials and the latest neurointerventional approaches to ischemic stroke.
Thrombolysis; intra-arterial thrombolysis; mechanical thrombectomy; cardioembolic stroke; stroke subtype.
Pediatric peripheral venipuncture and intravenous cannulation are difficult. However, successful venipuncture and intravenous cannulation are absolutely required for pediatric clinical risk management. This study assessed the success rate of venipuncture and intravenous cannulation when transmitted light was applied to the pediatric dorsum manus. The subjects included 100 young children who were scheduled for dental treatment or oral surgery under general anesthesia. Anesthesia was induced, and insertion of an intravenous catheter into the dorsum manus was attempted with or without using transmitted light. The patients were evaluated to determine whether the venipuncture was successful, and whether the intravenous cannulation of the external catheter was successful. The success rate of venipuncture was 100% when transmitted light was used, and 83% when the transmitted light was not used (P = 0.000016). In addition, the success rate of intravenous cannulation was 88% when transmitted light was used, and 55% when the transmitted light was not used (P = 0.0000002). The shape of the vein in the dorsum manus can be clearly recognized when transmitted light is used. The use of light significantly increased the success rate of intravenous cannulation, because it allowed direct confirmation of the direction to push the intravenous catheter forward. The use of transmitted light allows for more successful venipuncture and intravenous cannulation in young children.
transmitted light; pediatric peripheral venipuncture; pediatric peripheral intravenous cannulation
Dental fear may be the most common reason for referral for intravenous sedation. Intravenous sedation offers many patients an opportunity to obtain needed dental care. However, intravenous sedation also has costs and may not help patients overcome their fear. Given a sample of 518 dentally-fearful patients in the USA presenting for dental care, this study examined the variables which predicted receiving intravenous sedation or not. About one-fifth of the patients received intravenous sedation, while the others received only cognitive behavioural therapy. Having more carious teeth, higher dental fear, more negative beliefs about dentists, lifetime diagnoses of panic disorder and/or generalized anxiety disorder, fewer existing coping skills, and a lower desire to cope with the dental situation were each predictive of having intravenous sedation. When the variables were considered simultaneously, only lower desire to cope contributed uniquely to the prediction. In a setting where psychological treatment for dental fear is available, patients’ desire to cope with their fear was the most important factor in determining whether they received intravenous sedation or not.
Our group is attempting to construct an artificial pancreas based on intravenous glucose monitoring and intravenous insulin delivery. To do so, the pharmacology of intravenous insulin administration must be studied. We used a pig model to determine the inherent lag time in the insulin/blood glucose system. The goal was to suggest a method that reduces the blood glucose level in a rapid and yet predictable manner.
Six pigs received continuous intravenous insulin infusions at 0.04, 0.08, or 0.4 IU/kg/h for 60 min. Two pigs received short-term intravenous infusions at 0.4 IU/kg/h for 2 min, repeated five times at 60-min intervals. Four animals received five intravenous insulin bolus injections at 60-min intervals, two at 0.01 IU/kg and two 0.02 IU/kg, with a final dose of 0.04 IU/kg. The blood glucose level was measured every 1–5 min.
A high rate of intravenous insulin infusion led to rapid declines in blood glucose levels. The same rapid decline was achieved when the infusion was halted after 2 min. Using the latter method and with intravenous insulin boluses, blood glucose levels started to rise again after approximately 15–20 min. Insulin boluses led to a first detectable decrease in blood glucose level after 2–6 min and to a maximum rate of decrease shortly thereafter.
We found that intravenous bolus injections of insulin lowered blood glucose levels rapidly and predictably. Repetitive small intravenous insulin boluses together with an accurate and fast-responding intravascular continuous glucose monitor should be studied as a method of closed-loop glycemic control.
The pharmacokinetics of once-daily oral levofloxacin (study A) or intravenous levofloxacin (study B) in 40 healthy male volunteers were investigated in two separate randomized, double-blind, parallel-design, placebo-controlled studies. Levofloxacin at 500 mg or placebo was administered orally or intravenously as a single dose on day 1; daily oral or intravenous dosing resumed on days 4 to 10. In a third study (study C), the comparability of the bioavailabilities of two oral and one intravenous levofloxacin formulations were investigated with 24 healthy male subjects in an open-label, randomized, three-way crossover study. Levofloxacin at 500 mg as a single tablet or an intravenous infusion was administered on day 1; following a 1-week washout period, subjects received the second regimen (i.e., the other oral formulation or the intravenous infusion); the third and final regimen was administered following a 1-week washout period. The concentrations of drug in plasma and urine were measured by validated high-pressure liquid chromatography methods. Pharmacokinetic parameters were estimated by noncompartmental methods. In both study A (oral levofloxacin) and study B (intravenous levofloxacin), steady state was attained within 48 h after the start of the multiple dosing on day 4. Levofloxacin pharmacokinetics were linear and predictable for the single and multiple 500-mg, once-daily oral and intravenous dosing regimens, and the values of the pharmacokinetic parameters for the oral and intravenous administrations were similar. Study C indicated that levofloxacin was rapidly and completely absorbed from the oral tablets, with mean times to the maximum concentration of drug in serum of approximately 1.5 h and mean absolute bioavailability of > or =99%. These results support the interchangeability of the oral and intravenous routes of levofloxacin administration.
Audits of medication and intravenous fluid orders and of return to the pharmacy of unused intravenous solutions were conducted in 1980 at a university teaching hospital in response to a prevailing impression among pharmacists that physicians' orders were often written in an incomplete, nonstandardized fashion and that intravenous fluid wastage was common. A disturbing number of order were incomplete and judged to be ambiguous. Less than 25% of orders for intravenously given solutions contained adequate instructions for subsequent administration of fluids. Intravenous fluid return amounted to an estimated loss of $137,695 per year in wasted material and labor.
The results of the audits were disseminated among the staff. In addition, the pharmacy changed its operations to detect more quickly and correct the problems caused by ambiguous orders. Later studies showed a reduction in the return of unused intravenous fluids and some improvement in order writing. Inadequate and ambiguous orders were still judged to be a problem, however, especially intravenous fluid orders that omitted instructions for subsequent fluid requirements and “open-ended” intravenous fluid orders. Such orders were eight times more likely to be associated with return of unused intravenous fluids than orders with adequate instructions for giving fluids subsequently.
Swine dysentery was induced in 18 swine exposed by intravenous injection of a filtrate which contained Treponema hyodysenteriae and was obtained from macerated colonic scrapings of swine dysentery. However, swine dysentery did not develop in swine injected intravenously with a pure culture of T. hyodysenteriae or when combined with a colonic filtrate from normal swine. Diarrheal feces from the swine injected intravenously with the filtered T. hyodysenteriae contained more mucus, and fecal smears contained more T. hyodysenteriae and fewer other bacteria than did swine exposed orally to colon infected with swine dysentery or filtered T. hyodysenteriae. In the colons of the 12 swine injected intravenously with filtered T. hyodysenteriae that died, there was a minimum amount of croupous membrane and, microscopically, the T. hyodysenteriae were located deep in the colonic crypts. Five of the six surviving swine injected intravenously with filtered T. hyodysenteriae developed serum anti-T. hyodysenteriae antibodies using the indirect fluorescent antibody test and four of these swine developed diarrhea when reexposed with swine dysentery infected colon six weeks after initial exposure. None of the swine injected intravenously with cultured T. hyodysenteriae developed serum anti-T. hyodysenteriae antibodies and all were highly susceptible to swine dysentery.
Chloramphenicol was given intravenously and intramuscularly to calves and the blood levels determined over 27 hours. At a dosage of 11 mg/kg chloramphenicol was detected in the blood for 25 hours after intravenous and 27 hours after intramuscular administration. The blood levels after intravenous administration indicate that chloramphenicol in animals moves in a two compartment model. Kinetic parameters were determined for intravenous but not intramuscular chloramphenicol treatment. The blood levels of chloramphenicol were higher following intramuscular than intravenous administration from five hours onward. Chloramphenicol distributed quickly and widely throughout the animal's body.
It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously ½ hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions.
The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII. In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide. Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.
A rare case of Eikenella corrodens endocarditis in an intravenous drug user is reported. Repeated blood cultures from the patient established the diagnosis of this infection. However, evaluation of the cardiac function using two-dimensional echocardiography with Doppler flow demonstrated a large pedunculated tricuspid vegetation. Also evident on this study was a dilated right ventricle with diminished contractility and regurgitation. Complete sterilization of the blood was achieved after a 2-week course of intravenous penicillin and gentamicin followed by an additional 4-week course of intravenous penicillin alone. Clinicians treating suspected IV drug users should be aware of the potential pathogenicity of this rare, facultative, anaerobic gram-negative bacillus (E corrodens). A combination of intravenous penicillin and aminoglycoside should be considered as the initial treatment followed by an additional course of intravenous penicillin for such patients with valvular vegetation.
We have previously shown that Picolax® bowel preparation causes a significant dehydrating effect, which can be minimised by administering a calculated volume of intravenous fluid. The aim of this prospective study was to assess whether peri-operative outcome is affected by administering a calculated volume of intravenous fluid during bowel preparation.
PATIENTS AND METHODS
Patients having bowel preparation (Picolax®: Ferring Pharmaceuticals Ltd, Middlesex, UK) prior to colonic surgery were prospectively randomised to receive no intravenous fluid (group 1) or calculated intravenous crystalloid based on their body weight (group 2), during preparation. In both groups, transfusion was protocol-driven. Outcome variables measured included intra-operative and postoperative intravenous fluid requirement, hourly recorded urine output for 24 h, number of patients transfused, number of units of blood transfused, time to the passage of flatus, time to having their bowels open, time until tolerating a full diet, complications and length of stay in hospital.
Thirty-three patients were recruited – group 1 (n = 18) and group 2 (n = 15). There were 24 men and 9 women, median age 69 years (range, 29–86 years). There was no significant difference between the groups with respect to age, sex, weight, ASA grade, preoperative haemoglobin concentration, duration or type of operation. The total number of patients receiving a transfusion (P = 0.026) and the number of units of blood transfused (P = 0.017) was significantly greater in group 1. The number of units of blood transfused intra-operatively was significantly greater in group 1 (P = 0.029). Significantly fewer patients had a urine output <30 ml/h in the first 24-h after operation (P = 0.046) in group 2. There was no difference between groups in other outcomes measures.
This study indicates that a calculated volume of intravenous fluid administered during bowel preparation improves patient outcomes with respect to blood transfusion and postoperative oliguria. We advocate calculated intravenous fluid administration in all patients undergoing bowel preparation prior to colonic surgery.
Picolax®; Colorectal surgery; Fluid therapy; Transfusion
A group general practice in Dublin's inner city has had extensive experience of intravenous drug users since the late 1970s. Since 1985 a total of 54 human immunodeficiency virus (HIV) seropositive patients have attended the practice, of whom 48 are intravenous drug users, four are the children of drug users and two have been infected through sexual contacts. Three patients have developed the acquired immune deficiency syndrome and at least eight have symptomatic HIV disease. Sixty per cent of Ireland's seropositive population have been infected through intravenous drug abuse but nationally only 16% of all intravenous drug users tested are seropositive; in the study practice, however, at least 35% (48/137) of known intravenous drug users are seropositive.
To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA).
RESEARCH DESIGN AND METHODS
In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34).
There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03).
Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA.
Osteoporosis is a disease characterized by low bone mineral density and poor bone quality resulting in reduced bone strength and increased risk of fracture. Oral bisphosphonates, first-line therapy for most patients with osteoporosis, are associated with suboptimal adherence to therapy due to factors that include a complex dosing regimen and gastrointestinal intolerance in some patients. Intravenous bisphosphonates address these limitations through infrequent injectable dosing that assures 100% bioavailability. Intravenous zoledronic acid is the newest bisphosphonate to be approved for the treatment of osteoporosis.
This review assesses the evidence for the therapeutic effects of intravenous zoledronic acid for the treatment of osteoporosis.
Zoledronic acid 5 mg administered as an annual 15-min intravenous infusion has been shown to reduce the risk of vertebral fractures, hip fractures, and other fractures in a three-year randomized, double-blind, placebo-controlled trial in women with postmenopausal osteoporosis. In a randomized, double-blind, placebo-controlled trial in women and men with a recent surgical repair of low-trauma hip fracture, it reduced the risk of new clinical fractures and improved survival. In both studies, zoledronic acid was associated with a good safety profile and was generally well tolerated. Zoledronic acid has the potential to improve clinical outcomes by reducing the risk of fracture in patients with osteoporosis.
Intravenous zoledronic acid 5 mg every 12 months reduces fracture risk in women with postmenopausal osteoporosis and in women and men with recent low-trauma hip fracture.
osteoporosis; zoledronic acid; treatment; management; fracture; bisphosphonates
To estimate the effect of intravenous and nebulised magnesium sulphate upon hospital admissions and pulmonary function in adults and children with acute asthma.
We undertook a systematic review and meta‐analysis of randomised and quasi‐randomised trials of intravenous or nebulised magnesium sulphate in acute asthma. Trials were identified by searches of the electronic literature, relevant journal websites and conference proceedings, and contact with authors and experts. Data were pooled using random effects meta‐analysis of the relative risk (RR) of hospital admission and the standardised mean difference (SMD) in pulmonary function.
24 studies (15 intravenous, 9 nebulised) incorporating 1669 patients were included. Intravenous treatment was associated in adults with weak evidence of an effect upon respiratory function (SMD 0.25, 95% confidence interval (CI) −0.01 to 0.51; p = 0.05), but no significant effect upon hospital admission (RR 0.87, 95% CI 0.70 to 1.08; p = 0.22), and in children with a significant effect upon respiratory function (SMD 1.94, 95% CI 0.80 to 3.08; p<0.001) and hospital admission (RR 0.70, 95% CI 0.54 to 0.90; p = 0.005). Nebulised treatment was associated in adults with weak evidence of an effect upon respiratory function (SMD 0.17, 95% CI −0.02 to 0.36; p = 0.09), and hospital admission (RR 0.68, 95% CI 0.46 to 1.02; p = 0.06), and in children with no significant effect upon respiratory function (SMD −0.26, 95% CI –1.49 to 0.98; p = 0.69) or hospital admission (RR 2.0, 95% CI 0.19 to 20.93; p = 0.56).
Intravenous magnesium sulphate appears to be an effective treatment in children. Further trials are needed of intravenous and nebulised magnesium sulphate in adults and nebulised magnesium sulphate in children.
This report provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. Aminoacid L-histidine (His) containing no thiol functionality was tested intravenously to compare in vivo efficacy of the aminothiol (GSH, Cys) chelators with that of aminoimidazole (His) chelator. In these studies, 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of the chelator. The intravenous route of administration of GSH or Cys was most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. The oral administration of liposomal GSH reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.
decorporation; 60Cobalt; aminothiol receptors; cysteine; glutathione
Effects of amphotericin B on production of endogenous tumour necrosis factor alpha (TNF-alpha) and anti-tumour activity in mice was examined. Intravenous administration of Fungizone, an amphotericin B preparation complexed with deoxycholate, augmented the induction of endogenous TNF in response to a second stimulus with intravenous doses of FK23 (heat-killed Enterococcus faecalis). This augmentation was observed when more than 1.8 microg of Fungizone was injected intravenously before intravenous dosing of FK23. The time interval between priming injection of Fungizone and secondary injection of FK23 for the maximal effect was 3 h. Similar augmentation of TNF production was also observed in amphotericin B-primed and FK23-injected mice. Correspondingly, anti-tumour activity of the combined, intravenous injection of Fungizone and FK23 with a 3-h interval was examined. Growth of Meth A fibrosarcoma was clearly inhibited by this combination but not by administration of either one alone. These results suggest that amphotericin B is able to elicit anti-tumour activity, perhaps through activation of the immune system, and in particular augmentation of the induction of endogenous TNF.
Intravenous iron therapy is pivotal in the treatment of anemia of chronic kidney disease to optimize the response of hemoglobin to erythropoiesis-stimulating agents. Intravenous iron use in patients with chronic kidney disease is on the rise. Recent clinical trial data prompting safety concerns regarding the use of erythropoiesis-stimulating agents has stimulated new US Food and Drug Administration label changes and restrictions for these agents, and has encouraged more aggressive use of intravenous iron. The currently available intravenous iron products differ with regard to the stability of the iron-carbohydrate complex and potential to induce hypersensitivity reactions. Ferumoxytol is a newer large molecular weight intravenous iron formulation that is a colloidal iron oxide nanoparticle suspension coated with polyglucose sorbitol carboxymethyl ether. Ferumoxytol has robust iron-carbohydrate complex stability with minimal dissociation or appearance of free iron in the serum, allowing the drug to be given in relatively large doses with a rapid rate of administration. Clinical trials have demonstrated the superior efficacy of ferumoxytol versus oral iron with minimal adverse effects. However, recent postmarketing data have demonstrated a risk of hypersensitivity that has prompted new changes to the product information mandated by the Food and Drug Administration. Additionally, the long-term safety of this agent has not been evaluated, and its place in the treatment of anemia of chronic kidney disease has not been fully elucidated.
iron; ferumoxytol; oxidative stress; safety; kidney disease