Slow Infusion Rate Research Articles

Acute amiodarone toxicity due to an administration error: could excipient be responsible?

Acute amiodarone toxicity due to an administration error: could excipient be responsible?

Facilitation of voluntary swallowing by chemical stimulation of the posterior tongue and pharyngeal region in humans

In this study, we investigated the functional difference between chemical stimulations of the posterior tongue (PT) and pharyngeal region (PR) for facilitation of voluntary swallowing in humans. The PT or PR stimulation consisted of infusion of water (distilled water), 0.3M NaCl solution or olive oil (non-chemical stimulant) into the PT or the PR through a fine tube at a very slow infusion rate (0.2ml/min). Water was used as a stimulant of water receptors. A solution of 0.3M NaCl was used as an inhibitor of the response of water receptors and as a stimulant of salt taste receptors. Excitation of the mucosal receptors would facilitate voluntary swallowing and diminution of sensory inputs from the oral mucosa would induce difficulty in swallowing. Swallowing intervals (SIs) during voluntary swallowing were measured by submental electromyographic activity. Infusion of water into the PR shortened SI (facilitation of swallowing) and infusion of 0.3M NaCl or olive oil into the same region prolonged it (difficulty in swallowing). On the other hand, infusion of water into the PT prolonged SI and infusion of 0.3M NaCl into the same region shortened it. The results suggest that water receptors are localized in the PR and that salt taste receptors are almost absent in the PR and present in the PT. With diminution of sensory inputs from the oral mucosa, central inputs would play a dominant role in initiating swallowing voluntarily, and SI would be prolonged. With weak stimulation (infusion of 0.3M NaCl into the PR or infusion of water into the PT), SI was prolonged and inter-individual variation in SI was pronounced, suggesting that the ability of the central regulation of swallowing to perform repetitive voluntary swallowing varies among subjects. With stimulation of water receptors or salt taste receptors, SI was shortened and inter-individual variation in SI was moderate, suggesting that sensory inputs are important for performing voluntary swallowing smoothly and that the sensory inputs compensate for the difficulty in performing swallowing caused by the central mechanism.

Nutrición por sonda nasogástrica en la pancreatitis aguda grave

To establish the nasogastric enteral nutrition tolerance in patients with severe acute pancreatitis. A total of 12 patients with severe acute pancreatitis (> or = 3 Ranson criteria; C-reactive protein > 210 mg/dl) and adverse clinical course were included during 2006. When we verified the disease severity, nasogastric (10 F) enteral nutrition was initiated. We used a low fat semi-elemental feed (Dietgrif) in a slow infusion rate. We evaluated the enteral nutrition tolerance and the adverse events. The patient (4 women and 8 men) mean age (standard deviation) was 70 (11) years and the mean hospital stay was 86 days (range: 14-405 days). The etiology of pancreatitis was: gallstones 8, alcohol abuse one and unknown 3. All patients had medical and/or pancreatic complications. Seven had significant pancreatic necrosis detected in the abdominal computed tomography. Three patients were admitted in the critical care unit and 2 died. The nasogastric enteral nutrition was well tolerated in 8 out of 12 patients (67%) regardless of their medical or pancreatic complications. Only in 3 patients we had initially to discontinue the feeding because of ileus and total parenteral nutrition was provisionally necessary. Enteral nutrition was impossible in one patient because of duodenal stenosis. Nasogastric enteral nutrition is well tolerated in patients with severe acute pancreatitis and it is an alternative to others nutritional routes.

Rapid Infusion of Rituximab (RIR) Is Well Tolerated and Can Safely Be Delivered in Patients with Lymphoproliferative Diseases.

It has been proved that Rituximab is a useful drug for the treatment of patients with lymphoma. Being a humanized antibody, it presents high specificity. Rituximab is a well tolerated medicine, although a slow infusion rate given in many hours is recommended to avoid reactions derived from the liberation of cytokines. As a consequence, patients need admissions for a treatment that can take hours. The recent demostration of its usefulness in the maintenance of the response of patients with follicular lymphomas has concluded in the revision of hospitalization time, proposing a faster infusion. We are presenting our experience with RIR, on a group of patients with lymphoproliferative diseases. We used RIR with the aim to observe the toxicity and to reduce the time of hospitalization in patients with lymphoma. We evaluated the adverse events and tested the feasibility of a 90 minutes infusion schedule for rituximab (20% of the dose administered in the first 30 minutes, remaining administered over 60 minutes). Premedication included oral paracetamol and intravenous hidrocortisone and diphenhydramine. Sixty seven RIR were used to treated 31 patients (27 non-Hodgkin Lymphoma and 4 Chronic Lymphocitic Leukemia). All of them had previously received one or more rituximab conventional infusion without grade 3 or 4 toxicity. Twenty nine patients received also CHOP or CHOP-like chemotherapy and the other two Rituximab alone as maintenance therapy. Overall RIR was well tolerated. There were 5 adverse events. Four patients developed grade one adverse events: one patient had an hypotension episode, one presented chest pain and the other two had abdominal pain. Only one patient developed a grade 3 adverse event (abdominal pain) and withdrew the RIR schedule. We conclude that rapid infusion rituximab is safe and well tolerated. The adoption of this schedule in clinical practice reduces in many hours the time of hospitalization for patients with lymphoma and may be a cost-effective strategy.

Acute ST Elevation Myocardial Infarction during Intravenous Immunoglobulin Infusion

Intravenous immunoglobulin (IVIG) preparations are increasingly being used in the treatment of autoimmune disorders. This treatment is regarded as generally safe, and most of the adverse effects associated with IVIG administration are mild and transient. This paper reports a 72-year-old patient with known ischemic heart disease admitted for a Guillain-Barré syndrome variant, who developed acute ST elevation myocardial infarction (MI) during the first hours of IVIG infusion. The literature on acute MI during IVIG treatment is reviewed. Evaluation of each patient for cardiovascular risk prior to IVIG treatment is recommended as is the assessment of risk versus benefit. If IVIG is prescribed, we propose close monitoring and slow infusion rate.

Acute stroke with high-dose intravenous immune globulin

A case of acute stroke in a patient who was receiving high-dose intravenous immune globulin (IVIG) for dermatomyositis is reported. A 43-year-old woman presented with overwhelming proximal weakness and myalgias, swelling in her hands, facial and knee rash, generalized fatigue, numbness in her left arm, and lower-back pain. Physical examination revealed that she had symptoms consistent with dermatomyositis. The patient was initially treated with prednisone but developed a severe adverse drug reaction to the medication. The prednisone was discontinued, and the patient was admitted to the hospital for a first-time dose of IVIG therapy. During the infusion, the patient was found to have a facial droop, left-sided hemiplegia, and an increase in restlessness. A large, significant right internal carotid artery occlusion was discovered and initially treated mechanically and then with drugs in an attempt to establish revascularization. A subsequent computed tomography scan of the brain demonstrated a large right-middle cerebral distribution infarct with slight hemorrhage into the basal ganglia. IVIG is increasingly being used for many approved and non-approved indications. Although rare, stroke associated with thrombosis caused by the administration of IVIG has been reported in the literature. On the basis of the Naranjo probability scale, this adverse drug event was calculated as a probable reaction due to the administration of IVIG. A patient had an acute stroke after receiving a high dose of IVIG for dermatomyositis. Patients should be given a slower rate of infusion and smaller dosages of IVIG, and they should be closely monitored for potential stroke associated with thrombosis during IVIG therapy.

Phase II study of the clinical and biological activity of cetuximab and celecoxib in patients (pts) with refractory colorectal cancer (CRC)

14516 Background: The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways play key roles in colon carcinogenesis. EGFR and COX-2 signaling can be mutually reinforcing. Celecoxib, a selective COX-2 inhibitor, inhibits the EGFR pathway through inhibition of PI3/Akt and NF-κB pathways. This study explores the clinical and biological effects of blockade of complementary pathways of the EGFR by combining cetuximab with celecoxib. Methods: Cetuximab-naive pts with refractory CRC were treated with cetuximab (400 mg/m2 loading dose followed by weekly cetuximab at 250 mg/m2) and celecoxib (200 mg orally twice daily). Patients were assessed for response every 8 weeks. Urinary PGE-M, a metabolite of PGE-2 which correlates with in vivo COX-2 activity, and serum TGF-a, a ligand that binds to EGFR, were measured to assess the biological effect of COX-2 and EGFR blockade. Results: Seventeen of a planned 40 pts accrued to this study. Currently, data is available on 12 of these patients. Three pts had to stop treatment on 1st infusion due to a grade 3 cetuximab infusion reaction. One pt had a mild infusion reaction and was successfully rechallenged after pre-medication and a slower infusion rate. By RECIST criteria, 1 pt (8.3%) achieved a partial response (PR) and 4 pts (33%) had a best response of stable disease (SD). The mean time on study for the 9 pts without grade 3 infusion reaction was 95.7 days (range 28- 175). Pts with SD or PR were on study for a mean of 135 days (range 107–175 days) and pts with progressive disease (PD) were on study for a mean of 47 days (range 28–56 days). Baseline urinary PGE-M levels in pts with SD or PR were higher than in pts with PD (30.5+17.6 vs 18.1+9.4 ng/mg Cr). Baseline serum TGF-a levels were similar between the two groups (27.1+9.6 vs 25.4+10.3 pg/ml respectively). Conclusions: In preliminary analysis, this regimen resulted in response rates similar to published response rates for single agent cetuximab. Pts with at least SD had higher baseline urinary PGE-M levels, which may serve as a marker for efficacy of this combined therapy. Data on serial TGF-a and PGE-M levels will be presented. Response data on all 17 pts will be presented. Supported by P50 CA95103 and Bristol-Myers Squibb. Celecoxib provided by Pfizer. [Table: see text]

Is There a Role for Bisphosphonates in Chronic Kidney Disease?

Patients with stage 5 chronic kidney disease (CKD) including those on dialysis can and do develop osteoporosis. They also develop a wide range of other metabolic bone diseases that may look like osteoporosis when it is defined by either the World Health Organization bone mineral density (BMD) criteria or by the development of fragility fractures. Those dialysis patients with osteoporosis that is due to gonadal hormone deficiency such as postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, or male osteoporosis may benefit from the administration of bisphosphonates (BPs). The challenges lie in the diagnosis of osteoporosis in this population where adynamic, osteomalacic, hyperparathyroid, or aluminum bone disease are also prevalent, with concommitant low BMD and low trauma fractures, but where BPs may be contraindicated. The only secure means to diagnose osteoporosis in this patient population is by quantitative bone histomorphometry demonstrating low trabecular bone volume and disrupted microarchitecture. Once the diagnosis of osteoporosis is established, BPs should be considered for a well-defined brief period of time (e.g., 2-3 years), even though there is no evidence for a fracture reduction benefit in this population. If a BP is chosen there may be a need for dose adjustment or slower infusion rates (for the intravenous formulations), as a greater bone retention may occur for these renally cleared agents. While it is unknown what consequences could develop from increased bone retention in patients with little renal function, data are needed if more bone retention of BP might lead to a greater risk of the development of adynamic bone disease and lower bone strength. More data are needed to define the risks and benefits of BPs in patients with stage 5 CKD.

Phase 1 Clinical Experience Using Intravenous Administration of PV701, an Oncolytic Newcastle Disease Virus

PV701 is a naturally-attenuated, non-recombinant, oncolytic strain of Newcastle disease virus that displays preclinical intravenous (IV) efficacy. PV701 is selective at killing human cancer cells versus normal human cells based on tumor specific defects in the interferon (IFN)-mediated antiviral response. This oncolytic virus displays a broad spectrum of antitumor activity in vitro and in vivo. Preclinical models successfully predicted key clinical parameters including the mechanism of toxicity, two complementary strategies (desensitization and slow infusion) to reduce toxicity, and the starting dose for phase 1 trials. In three phase 1 trials of 114 patients using IV administration of PV701, Wellstat Biologics Corporation has evaluated the effects of dose, schedule, and infusion rate for PV701. Three general classes of side effects were seen: flu-like symptoms; tumor-site-specific adverse events (AEs); and infusion reactions. The first PV701 dose desensitized the patient to the side effects of further doses, allowing a marked increase in the maximum tolerated dose for subsequent doses compared to the first dose. Tumor responses were first noted at the higher doses achieved using desensitization. In the most recent phase 1 trial of 19 patients at Hamilton, Ontario, that employed desensitization, high repeat doses, and a slower infusion rate (Hamilton Regimen), there were six responses (4 major; 2 minor) and a total of six patients with survival for at least 2 years. In addition, patient tolerability improved using the Hamilton Regimen compared to IV bolus dosing used previously. Phase 2 studies of this novel biologic agent are about to begin.

Cerebrospinal Fluid and Spinal Cord Distribution of Baclofen and Bupivacaine during Slow Intrathecal Infusion in Pigs

Increasing numbers of patients are receiving chronic intrathecal infusions of local anesthetics, baclofen, opioids, and other analgesics via implanted pumps. These infusions typically deliver drugs at rates measured in microliters per hour. However, to date, there have been no studies aimed at characterizing drug distribution within cerebrospinal fluid (CSF) and spinal cord during these slow infusion rates. Therefore, this study was designed to address this knowledge gap. Anesthetized pigs were instrumented with eight intrathecal microdialysis probes placed at multiple points along the neuroaxis in both the anterior and posterior intrathecal space to permit continuous CSF sampling for measurement of bupivacaine and baclofen concentrations. Animals were divided into three groups and received bupivacaine and baclofen infusions at 20 or 1,000 microl/h or as a 1,000-microl bolus over 5 min every hour. Drug administration continued for 8 h, at which time the animals were killed, and the spinal cord was removed and divided into 1-cm-long sections that were further divided into anterior and posterior portions for measurement of bupivacaine and baclofen concentrations. In all groups, drug concentration in CSF and spinal cord decreased rapidly as a function of distance from the site of administration, with most drug found within a few centimeters. In addition, there were significant anterior-posterior differences in both CSF and spinal cord drug concentrations. During slow intrathecal infusion, drug distribution in CSF and spinal cord is severely limited in all groups, although significantly more so in the 20-microl/h infusion group.

Comparison of two thiopental infusion rates for the induction of anaesthesia in dogs

ObjectiveTo compare the induction dose requirements of thiopental using two different infusion rates for induction of anaesthesia in dogs. Study designProspective, randomized study. AnimalsFifty, healthy (ASA I or II) client-owned dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective surgery. Materials and methodsAnimals were randomly assigned to receive an infusion of 2.5% thiopental at a rate of either 0.1 ml kg−1 minute−1 or 0.4 ml kg−1minute−1, 30–40 minutes after pre-anaesthetic medication with intramuscular acepromazine (0.025 mg kg−1) and pethidine (3.5 mg kg−1). Thiopental administration was controlled by a precision syringe driver. Statistical analyses of the results, using the outcome ‘mg kg−1 required for induction’ (log-transformed) included unpaired t-tests for all categorical data (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable linear regression for continuous variables (mass, age). All variables were then considered in a multivariable linear regression model. The quality of induction with the two different infusion rates was also assessed. ResultsAfter controlling for quality of sedation, the thiopental induction dose requirement was significantly less (p < 0.001) with the slower infusion rate (median = 7.5 mg kg−1; range 4.9–13.7) compared with the faster infusion rate (median =11.0 mg kg−1; range 6.6–18.0). The quality of sedation also affected the dose required (p = 0.03). The slower infusion rate was associated with a significantly poorer induction quality (p = 0.3). ConclusionsSlow thiopental infusion (0.1 ml kg−1 minute−1) for anaesthesia induction after acepromazine/pethidine pre-anaesthetic medication reduced the induction dose requirement, although the quality of induction was inferior. Clinical relevanceThe induction dose of thiopental was reduced with a slower administration rate and so slow administration is recommended in thiopental-sensitive animals.

Review: intravenous immunoglobulin therapy and thromboembolic complications

Intravenous immunglobulin (IVIg) is used to treat a number of immune-deficiences and autoimmune diseases. Safety concerns related to a number of reported thromboembolic complications prompted us to review the literature. These complications happened mainly in individuals that had risk factors for thromboembolism, like advanced age, previous thromboembolic diseases, bed-ridden, and in individuals in which high doses or high infusion rates of IVIg were administered. The mechanism responsible for these events seems to be a rise in plasma viscosity that can trigger a thromboembolic event, especially in cases in which there is an underlying circulation impairment. Complications can be minimized by using IVIg only in clear-cut indications, weighting risk versus benefit in patients who are at high risk for thromboembolism and by sticking to carefully monitored slow infusion rates. IVIg for the treatment of autoimmune disorders should be administered as a five-day course of 2 g/kg of body weight. Each daily dose of 400 mg/kg should be given in not less than eight hours.

BENEFIT OF SLOW INFUSION OF HYPERTONIC SALINE/DEXTRAN IN SWINE WITH UNCONTROLLED AORTOTOMY HEMORRHAGE

In laboratory models of uncontrolled hemorrhage, immediate resuscitation from hemorrhage is associated with high mortality. However, in clinical practice, resuscitation is often delayed and the rate of fluid administration is limited. We hypothesized that a slow rate of infusion after delayed resuscitation, reflecting the clinical environment, might improve survival in the presence of uncontrolled hemorrhage. To investigate the rate of administration in the presence of delayed resuscitation, we subjected anesthetized swine weighing 35 to 45 kg to wire suture abdominal aortotomy that resulted in an uncontrolled hemorrhage. After a 30-min delay, hemorrhaged swine were infused i.v. with 4 mL/kg hypertonic saline/Dextran solution (7.5% saline in 6% Dextran 70) administered as a bolus over 1 min or as a slow infusion over 12 min (the time period to administer a similar volume to a human with a gravity feed i.v. and an 18-gauge needle) and were then monitored for another 90 min. Survival increased to 78% (seven of nine) in the slow infusion group compared with a survival rate of 56% (five of nine) in the bolus group and 50% (7/14) in the untreated controls. Blood loss was significantly higher in the bolus group (926 +/- 77 mL) compared with the slow infusion (714 +/- 83 mL) and control groups (604 +/- 46 mL). Hypertonic saline/Dextran administered slowly significantly increased cardiac output and blood pressure. Taken together, these results are consistent with the hypothesis that resuscitation solutions can be effective for treatment of uncontrolled hemorrhage when administered at a slow infusion rate 30 min after the insult.

153 Quality of life in typical atrial flutter patients before and after radiofrequency catheter ablation using irrigational and conventional techniques

Purpose: to evaluate quality of life (QoL) before and after radiofrequency catheter ablation (RFA) of isthmus-depended atrial flutter (AF) patients. Material and Methods: the study included 69 consecutive pts (8 female), 55,64-12.3 years of age, referred for electrophysiological study (EPS) and radiofrequency ablation (RFA) due to paroxysmal typical AE The tachyarhythmia history was 7.24-6.0 years. Incidences of AF were 10.84-4.9 per month regardless of antiarrhythmic drug (AAD) therapy pursued. Conventional catheters were used in 49 pts (group one). Irrigated tip catheters with slow infusion rate (10 cc/min) were used in 20 pts (group the second). Bi-directional cavatricuspid isthmus block was verified using local criteria. QoL was evaluated by SF-36 questionnaire and symptom checklist-frequency and Severity Scale specific for cardiac arrhythmias during follow up period by the month the 2nd, 6th and the 12 after RFA. Results: the recurrences of the arrhythmia were observed in 7 cases (14.3%) of group one and in 2 cases (10%) of group two during first two-month of follow-up period. Repeated RFA were successful in all these cases. Improvement of QoL parameters, symptom-frequency score and symptom-severity score was observed by the 2nd months after RFA in both groups (p<0.05). Follow-up questioning (6, 12 mo. after RFA) showed comparable gradual increasing of QoL parameters in both groups. Conclusion: successful RFA of AF by means of either irrigational or conventional technique significantly improves QoL parameters by the month the 2nd after the procedure with subsequent improvement of the parameters of interest during 12 months of follow up period.

Immunomodulatory Effects of Intravenous Immunoglobulins as a Treatment for Autoimmune Diseases, Cancer, and Recurrent Pregnancy Loss

Intravenous immunoglobulin (IVIG) is a safe preparation, made of human plasma of thousands of healthy donors. The fascinating history of gamma globulin therapy begins in 1930 when Finland treated pneumococcal pneumonia patients with equine serum, which prolonged their survival from pneumonia. Since then, significant breakthroughs were achieved by Cohn, Bruton, Imbach, and others, whose clinical contribution to the world of medicine was of great importance. Originally IVIG was used to treat immunodeficiencies. Later on the use of IVIG extended to autoimmune diseases as well. The efficacy of IVIG has been established only in several autoimmune diseases; clinical reports of trials, series, and case reports indicate significant improvement in many more autoimmune diseases. IVIG have also showed antimetastatic effects in a variety of cancer cell lines, as well as in a few case reports. The efficiency of IVIG has also been observed in recurrent pregnancy loss (RPL), either as a result of an autoimmune disease or spontaneous. Several attempts were made to discover the immunomodulatory effects of IVIG, but it is still not fully understood. Clearly IVIG has multiple mechanisms of actions, which are thought to cooperate synergistically. One of the main mechanisms of actions of IVIG is its ability to neutralize pathogenic autoantibodies via anti-idiotypic antibodies within IVIG preparation. The ability of IVIG to neutralize pathogenic autoantibodies is of great importance in many autoimmune diseases, as well as in RPL. In cancer cell lines, IVIG modulates the immune system in a few ways, including the induction of IL-12 secretion, which consequently activates natural killer cells, and the induction of expression of proapoptotic genes only in cancer cells. Side effects from IVIG are rare and mostly mild and transient. More importantly adverse effects can be minimized by administration to a selective patient population in a proper way: slow infusion rate of 0.4 g/Kg body weight IVIG for 5 consecutive days, given in monthly cycles. The only downside of IVIG therapy is its high price. Therefore, clinicians should balance efficiency versus cost in deciding whether or not to treat certain conditions with IVIG.

Carboplatin Hypersensitivity Reactions: A Single Institution Experience

Carboplatin-related hypersensitivity reactions, frequently encountered in the heavily pretreated subpopulation of patients with gynecologic malignancies, can be severe and even potentially lethal—precluding these patients from an effective salvage treatment. We describe our experience in the management of such reactions and the application of a pretreatment protocol with corticosteroids, antihistamines and a slow infusion rate in order to safely re-administer carboplatin to the above patients.From 1998 to 2004, twenty patients developed an allergic reaction to carboplatin. Sixteen of them (80%) suffered from ovarian cancer. Upon resolution of the acute reaction, thirteen patients were pretreated according to our protocol and were re-exposed to carboplatin.Fifteen patients experienced the reaction during second-line carboplatin-based treatment and 5 patients after 3 or more regimens. Fifteen of the reactions (75%) were severe. Thirteen patients were re-treated with carboplatin after the application of our protocol, all of them successfully, even though 10 patients (77%) experienced minor symptoms during subsequent courses. On the contrary, only one of the 6 patients who were re-treated without the application of the protocol was able to receive further platinum-based treatment.In conclusion, pretreatment with corticosteroids, antihistamines and a slower infusion rate may make re-treatment possible in patients having experienced hypersensitivity to carboplatin.

Intravenous Immunoglobulin Therapy and Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Intravenous Immunoglobulin: Adverse Effects and Safe Administration

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Infusion rates and drug distribution in brain tumor models in rats

The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy. The authors used two brain tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps were used to deliver chemotherapy--carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively. In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin. After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.

Insensitivity of the microdialysis zero-net-flux method to nonlinear uptake and release processes

In the microdialysis zero-net-flux (ZNF) method the extraction efficiency is conventionally obtained by linear regression. The linear analysis may become invalid for certain analytes that have nonlinear uptake/release processes in the tissue. To examine this hypothesis, a nonlinear model was used to numerically investigate the nonlinearity of the ZNF plot caused by nonlinear uptake and release processes. Three findings from this analysis are: (i) the ZNF method is markedly insensitive to the nonlinear active processes; (ii) a slow infusion rate or a long probe membrane can suppress the nonlinearity; (iii) the release under autoreceptor control does not affect the slope and linearity of the concentration difference plot. It is concluded that in the nM infusion range, the ZNF method is unable to distinguish whether or not the tissue clearance process is nonlinear. During electrical stimulation, neurotransmitter overflow may cause the microdialysis ZNF method to exhibit nonlinearity.